CBS_HUMAN
ID CBS_HUMAN Reviewed; 551 AA.
AC P35520; B2R993; D3DSK4; Q99425; Q9BWC5;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 237.
DE RecName: Full=Cystathionine beta-synthase {ECO:0000305};
DE EC=4.2.1.22 {ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:23974653, ECO:0000269|PubMed:23981774, ECO:0000269|PubMed:25044645};
DE AltName: Full=Beta-thionase;
DE AltName: Full=Serine sulfhydrase;
GN Name=CBS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=7903580; DOI=10.1093/hmg/2.10.1633;
RA Kraus J.P., Le K., Swaroop M., Ohura T., Tahara T., Rosenberg L.E.,
RA Roper M.D., Kozich V.;
RT "Human cystathionine beta-synthase cDNA: sequence, alternative splicing and
RT expression in cultured cells.";
RL Hum. Mol. Genet. 2:1633-1638(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=7598711; DOI=10.1006/bbrc.1995.1886;
RA Chasse J.-F., Paly E., Paris D., Paul V., Sinet P.-M., Kamoun P.,
RA London J.;
RT "Genomic organization of the human cystathionine beta-synthase gene:
RT evidence for various cDNAs.";
RL Biochem. Biophys. Res. Commun. 211:826-832(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8022826; DOI=10.1073/pnas.91.14.6614;
RA Kruger W.D., Cox D.R.;
RT "A yeast system for expression of human cystathionine beta-synthase:
RT structural and functional conservation of the human and yeast genes.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:6614-6618(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9383285; DOI=10.1007/s003359900611;
RA Chasse J.-F., Paul V., Escanez R., Kamoun P., London J.;
RT "Human cystathionine beta-synthase: gene organization and expression of
RT different 5' alternative splicing.";
RL Mamm. Genome 8:917-921(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING.
RX PubMed=9790750; DOI=10.1006/geno.1998.5437;
RA Kraus J.P., Oliveriusova J., Sokolova J., Kraus E., Vlcek C.,
RA de Franchis R., Maclean K.N., Bao L., Bukovska G., Patterson D., Paces V.,
RA Ansorge W., Kozich V.;
RT "The human cystathionine beta-synthase (CBS) gene: complete sequence,
RT alternative splicing, and polymorphisms.";
RL Genomics 52:312-324(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10830953; DOI=10.1038/35012518;
RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-69.
RC TISSUE=Brain, Eye, Lung, and Muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP CHARACTERIZATION.
RX PubMed=681363; DOI=10.1016/s0021-9258(19)46963-9;
RA Kraus J.P., Packman S., Fowler B., Rosenberg L.E.;
RT "Purification and properties of cystathionine beta-synthase from human
RT liver. Evidence for identical subunits.";
RL J. Biol. Chem. 253:6523-6528(1978).
RN [12]
RP SUMOYLATION AT LYS-211, AND SUBCELLULAR LOCATION.
RX PubMed=17087506; DOI=10.1021/bi0615644;
RA Kabil O., Zhou Y., Banerjee R.;
RT "Human cystathionine beta-synthase is a target for sumoylation.";
RL Biochemistry 45:13528-13536(2006).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-199, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [18]
RP CHARACTERIZATION OF VARIANTS CBSD LEU-49; ARG-65; ARG-78; ASN-102; VAL-114;
RP GLN-125; LYS-144; ARG-148; TYR-165; LYS-176; ALA-180; MET-191; LYS-228;
RP ARG-262; LYS-266; THR-278; LYS-302; ARG-305; SER-307; CYS-369; LEU-422;
RP THR-435; GLN-439; ASN-444; LEU-466 AND SER-539, FUNCTION, CATALYTIC
RP ACTIVITY, PATHWAY, ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=20506325; DOI=10.1002/humu.21273;
RA Kozich V., Sokolova J., Klatovska V., Krijt J., Janosik M., Jelinek K.,
RA Kraus J.P.;
RT "Cystathionine beta-synthase mutations: effect of mutation topology on
RT folding and activity.";
RL Hum. Mutat. 31:809-819(2010).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1-413 IN COMPLEX WITH PYRIDOXAL
RP PHOSPHATE AND IRON, SUBUNIT, ACTIVITY REGULATION, AND REGION.
RX PubMed=11483494; DOI=10.1093/emboj/20.15.3910;
RA Meier M., Janosik M., Kery V., Kraus J.P., Burkhard P.;
RT "Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-
RT phosphate-dependent heme protein.";
RL EMBO J. 20:3910-3916(2001).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 45-406 IN COMPLEX WITH PYRIDOXAL
RP PHOSPHATE AND IRON, ALLOSTERIC ACTIVATOR ADOMET, MUTAGENESIS OF CYS-272 AND
RP CYS-275, AND REGION.
RX PubMed=12173932; DOI=10.1021/bi026052d;
RA Taoka S., Lepore B.W., Kabil O., Ojha S., Ringe D., Banerjee R.;
RT "Human cystathionine beta-synthase is a heme sensor protein. Evidence that
RT the redox sensor is heme and not the vicinal cysteines in the CXXC motif
RT seen in the crystal structure of the truncated enzyme.";
RL Biochemistry 41:10454-10461(2002).
RN [21]
RP REVIEW ON CBSD VARIANTS.
RX PubMed=10338090;
RX DOI=10.1002/(sici)1098-1004(1999)13:5<362::aid-humu4>3.0.co;2-k;
RA Kraus J.P., Janosik M., Kozich V., Mandell R., Shih V.E., Sperandeo M.P.,
RA Sebastio G., de Franchis R., Andria G., Kluijtmans L.A.J., Blom H.J.,
RA Boers G.H.J., Gordon R.B., Kamoun P., Tsai M.Y., Kruger W.D., Koch H.G.,
RA Ohura T., Gaustadnes M.;
RT "Cystathionine beta-synthase mutations in homocystinuria.";
RL Hum. Mutat. 13:362-375(1999).
RN [22]
RP VARIANT CBSD THR-278.
RX PubMed=1301198; DOI=10.1002/humu.1380010206;
RA Kozich V., Kraus J.P.;
RT "Screening for mutations by expressing patient cDNA segments in E. coli:
RT homocystinuria due to cystathionine beta-synthase deficiency.";
RL Hum. Mutat. 1:113-123(1992).
RN [23]
RP VARIANTS CBSD VAL-114 AND LEU-145.
RX PubMed=8353501; DOI=10.1093/hmg/2.6.815;
RA Kozich V., de Franchis R., Kraus J.P.;
RT "Molecular defect in a patient with pyridoxine-responsive homocystinuria.";
RL Hum. Mol. Genet. 2:815-816(1993).
RN [24]
RP VARIANTS CBSD THR-278 AND SER-307.
RX PubMed=7506602; DOI=10.1093/hmg/2.11.1857;
RA Hu F.L., Gu Z., Kozich V., Kraus J.P., Ramesh V., Shih V.E.;
RT "Molecular basis of cystathionine beta-synthase deficiency in pyridoxine
RT responsive and nonresponsive homocystinuria.";
RL Hum. Mol. Genet. 2:1857-1860(1993).
RN [25]
RP VARIANTS CBSD ARG-78 AND ASN-102.
RX PubMed=7981678; DOI=10.1093/hmg/3.7.1103;
RA de Franchis R., Kozich V., McInnes R., Kraus J.P.;
RT "Identical genotypes in siblings with different homocystinuric phenotypes:
RT identification of three mutations in cystathionine beta-synthase using an
RT improved bacterial expression system.";
RL Hum. Mol. Genet. 3:1103-1108(1994).
RN [26]
RP VARIANTS CBSD GLN-125 AND ASP-131.
RX PubMed=7849717; DOI=10.1093/hmg/3.10.1883;
RA Marble M., Geraghty M.T., de Franchis R., Kraus J.P., Valle D.;
RT "Characterization of a cystathionine beta-synthase allele with three
RT mutations in cis in a patient with B6 nonresponsive homocystinuria.";
RL Hum. Mol. Genet. 3:1883-1886(1994).
RN [27]
RP VARIANTS CBSD.
RX PubMed=7967489; DOI=10.1007/bf00711354;
RA Kraus J.P.;
RT "Komrower Lecture. Molecular basis of phenotype expression in
RT homocystinuria.";
RL J. Inherit. Metab. Dis. 17:383-390(1994).
RN [28]
RP VARIANTS CBSD ARG-139; LYS-144 AND THR-278.
RX PubMed=7611293;
RA Shih V.E., Fringer J.M., Mandell R., Kraus J.P., Berry G.T.,
RA Heidenreich R.A., Korson M.S., Levy H.L., Ramesh V.;
RT "A missense mutation (I278T) in the cystathionine beta-synthase gene
RT prevalent in pyridoxine-responsive homocystinuria and associated with mild
RT clinical phenotype.";
RL Am. J. Hum. Genet. 57:34-39(1995).
RN [29]
RP VARIANTS CBSD SER-88; GLN-125 AND MET-257.
RX PubMed=7762555;
RA Sebastio G., Sperandeo M.P., Panico M., de Franchis R., Kraus J.P.,
RA Andria G.;
RT "The molecular basis of homocystinuria due to cystathionine beta-synthase
RT deficiency in Italian families, and report of four novel mutations.";
RL Am. J. Hum. Genet. 56:1324-1333(1995).
RN [30]
RP VARIANTS CBSD TYR-165 AND MET-371.
RX PubMed=7635485; DOI=10.1007/bf00207394;
RA Kluijtmans L.A.J., Blom H.J., Boers G.H.J., van Oost B.A., Trijbels F.J.M.,
RA van den Heuvel L.P.W.J.;
RT "Two novel missense mutations in the cystathionine beta-synthase gene in
RT homocystinuric patients.";
RL Hum. Genet. 96:249-250(1995).
RN [31]
RP VARIANTS CBSD MET-168; HIS-224; THR-278; SER-307; VAL-331 AND GLU-454.
RX PubMed=8528202; DOI=10.1093/hmg/4.7.1155;
RA Kruger W.D., Cox D.R.;
RT "A yeast assay for functional detection of mutations in the human
RT cystathionine beta-synthase gene.";
RL Hum. Mol. Genet. 4:1155-1161(1995).
RN [32]
RP VARIANT CBSD LEU-290.
RX PubMed=7564249; DOI=10.1007/bf00711769;
RA Sperandeo M.P., Panico M., Pepe A., Candito M., de Franchis R., Kraus J.P.,
RA Andria G., Sebastio G.;
RT "Molecular analysis of patients affected by homocystinuria due to
RT cystathionine beta-synthase deficiency: report of a new mutation in exon 8
RT and a deletion in intron 11.";
RL J. Inherit. Metab. Dis. 18:211-214(1995).
RN [33]
RP VARIANT CBSD ASN-444, AND CHARACTERIZATION OF VARIANT CBSD ASN-444.
RX PubMed=8755636; DOI=10.1172/jci118791;
RA Kluijtmans L.A.J., Boers G.H.J., Stevens E.M.B., Renier W.O., Kraus J.P.,
RA Trijbels F.J.M., van den Heuvel L.P.W.J., Blom H.J.;
RT "Defective cystathionine beta-synthase regulation by S-adenosylmethionine
RT in a partially pyridoxine responsive homocystinuria patient.";
RL J. Clin. Invest. 98:285-289(1996).
RN [34]
RP VARIANTS CBSD ARG-116; THR-278 AND LEU-290.
RX PubMed=8803779; DOI=10.1007/bf01799266;
RA Sperandeo M.P., Candito M., Sebastio G., Rolland M.O., Turc-Carel C.,
RA Giudicelli H., Dellamonica P., Andria G.;
RT "Homocysteine response to methionine challenge in four obligate
RT heterozygotes for homocystinuria and relationship with cystathionine beta-
RT synthase mutations.";
RL J. Inherit. Metab. Dis. 19:351-356(1996).
RN [35]
RP VARIANTS CBSD LYS-144; THR-278; GLU-331; MET-353 AND GLN-439.
RX PubMed=9156316;
RA Dawson P.A., Cox A.J., Emmerson B.T., Dudman N.P.B., Kraus J.P.,
RA Gordon R.B.;
RT "Characterisation of five missense mutations in the cystathionine beta-
RT synthase gene from three patients with B6-nonresponsive homocystinuria.";
RL Eur. J. Hum. Genet. 5:15-21(1997).
RN [36]
RP VARIANTS CBSD MET-262; LYS-266; THR-278; SER-307; ALA-320 AND CYS-369.
RX PubMed=9361025; DOI=10.1093/hmg/6.13.2213;
RA Kim C.E., Gallagher P.M., Guttormsen A.B., Refsum H., Ueland P.M., Ose L.,
RA Foelling I., Whitehead A.S., Tsai M.Y., Kruger W.D.;
RT "Functional modeling of vitamin responsiveness in yeast: a common
RT pyridoxine-responsive cystathionine beta-synthase mutation in
RT homocystinuria.";
RL Hum. Mol. Genet. 6:2213-2221(1997).
RN [37]
RP VARIANTS CBSD GLU-384 AND SER-539.
RX PubMed=8990018;
RX DOI=10.1002/(sici)1098-1004(1997)9:1<81::aid-humu18>3.0.co;2-l;
RA Aral B., Coude M., London J., Aupetit J., Chasse J.-F., Zabot M.-T.,
RA Chadefaux-Vekemans B., Kamoun P.;
RT "Two novel mutations (K384E and L539S) in the C-terminal moiety of the
RT cystathionine beta-synthase protein in two French pyridoxine-responsive
RT homocystinuria patients.";
RL Hum. Mutat. 9:81-82(1997).
RN [38]
RP VARIANTS CBSD LYS-176; THR-278 AND SER-307.
RX PubMed=9266356; DOI=10.1023/a:1005325911665;
RA Kozich V., Janosik M., Sokolova J., Oliveriusova J., Orendac M.,
RA Kraus J.P., Elleder D.;
RT "Analysis of CBS alleles in Czech and Slovak patients with homocystinuria:
RT report on three novel mutations E176K, W409X and 1223 + 37 del99.";
RL J. Inherit. Metab. Dis. 20:363-366(1997).
RN [39]
RP VARIANTS CBSD TYR-370 AND GLN-439.
RX PubMed=10462600; DOI=10.1054/modi00200129;
RA Tsai M.Y., Wong P.W.K., Garg U., Hanson N.Q., Schwichtenberg K.;
RT "Two novel mutations in the cystathionine beta-synthase gene of
RT homocystinuric patients.";
RL Mol. Diagn. 2:129-133(1997).
RN [40]
RP VARIANTS CBSD LYS-144 AND TYR-165.
RX PubMed=10215408;
RX DOI=10.1002/(sici)1098-1004(1998)11:4<332::aid-humu16>3.0.co;2-p;
RA Gordon R.B., Cox A.J., Dawson P.A., Emmerson B.T., Kraus J.P., Dudman N.P.;
RT "Mutational analysis of the cystathionine beta-synthase gene: a splicing
RT mutation, two missense mutations and an insertion in patients with
RT homocystinuria.";
RL Hum. Mutat. 11:332-332(1998).
RN [41]
RP VARIANTS CBSD PRO-101; LYS-228; MET-262; THR-278; SER-307 AND PRO-355.
RX PubMed=9889017; DOI=10.1006/mgme.1998.2771;
RA Gallagher P.M., Naughten E., Hanson N.Q., Schwichtenberg K., Bignell M.,
RA Yuan M., Ward P., Yap S., Whitehead A.S., Tsai M.Y.;
RT "Characterization of mutations in the cystathionine beta-synthase gene in
RT Irish patients with homocystinuria.";
RL Mol. Genet. Metab. 65:298-302(1998).
RN [42]
RP VARIANTS CBSD TRP-58; VAL-126; LYS-302 AND CYS-336.
RX PubMed=10408774;
RX DOI=10.1002/(sici)1098-1004(1999)13:6<453::aid-humu4>3.0.co;2-k;
RA de Franchis R., Kraus E., Kozich V., Sebastio G., Kraus J.P.;
RT "Four novel mutations in the cystathionine beta-synthase gene: effect of a
RT second linked mutation on the severity of the homocystinuric phenotype.";
RL Hum. Mutat. 13:453-457(1999).
RN [43]
RP VARIANTS CBSD ARG-262 AND THR-278, AND VARIANT GLN-102.
RX PubMed=11013450;
RX DOI=10.1002/1098-1004(200010)16:4<372::aid-humu12>3.0.co;2-j;
RA Gat-Yablonski G., Mandel H., Fowler B., Taleb O., Sela B.-A.;
RT "Homocystinuria in the Arab population of Israel: identification of two
RT novel mutations using DGGE analysis.";
RL Hum. Mutat. 16:372-372(2000).
RN [44]
RP VARIANTS CBSD ARG-65; VAL-114; LYS-144; THR-155; TYR-165; LYS-176 AND
RP THR-278, AND CHARACTERIZATION OF VARIANTS CBSD VAL-114; LYS-144; THR-155;
RP TYR-165; LYS-176 AND THR-278.
RX PubMed=11359213; DOI=10.1086/320597;
RA Janosik M., Oliveriusova J., Janosikova B., Sokolova J., Kraus E.,
RA Kraus J.P., Kozich V.;
RT "Impaired heme binding and aggregation of mutant cystathionine beta-
RT synthase subunits in homocystinuria.";
RL Am. J. Hum. Genet. 68:1506-1513(2001).
RN [45]
RP VARIANTS CBSD PRO-125 AND THR-361.
RX PubMed=11553052; DOI=10.1034/j.1399-0004.2001.600212.x;
RA Castro R., Heil S.G., Rivera I., Jakobs C., de Almeida I.T., Blom H.J.;
RT "Molecular genetic analysis of the cystathionine beta-synthase gene in
RT Portuguese homocystinuria patients: three novel mutations.";
RL Clin. Genet. 60:161-163(2001).
RN [46]
RP VARIANTS CBSD ARG-85; THR-278; LEU-422; THR-435; ASN-444 AND LEU-466, AND
RP CHARACTERIZATION OF VARIANTS CBSD ARG-85; LEU-422; THR-435 AND LEU-466.
RX PubMed=12007221; DOI=10.1002/humu.10089;
RA Maclean K.N., Gaustadnes M., Oliveriusova J., Janosik M., Kraus E.,
RA Kozich V., Kery V., Skovby F., Ruediger N., Ingerslev J., Stabler S.P.,
RA Allen R.H., Kraus J.P.;
RT "High homocysteine and thrombosis without connective tissue disorders are
RT associated with a novel class of cystathionine beta-synthase (CBS)
RT mutations.";
RL Hum. Mutat. 19:641-655(2002).
RN [47]
RP VARIANTS CBSD LEU-49; PRO-101; ARG-109; GLN-125; LYS-144; TYR-165; LYS-228;
RP THR-278; LYS-302; SER-307; GLU-331; CYS-336; SER-347; MET-353; CYS-369;
RP MET-371 AND GLN-439, AND CHARACTERIZATION OF VARIANTS CBSD PRO-101;
RP ARG-109; LYS-228 AND SER-347.
RX PubMed=12124992; DOI=10.1002/humu.10104;
RA Gaustadnes M., Wilcken B., Oliveriusova J., McGill J., Fletcher J.,
RA Kraus J.P., Wilcken D.E.;
RT "The molecular basis of cystathionine beta-synthase deficiency in
RT Australian patients: genotype-phenotype correlations and response to
RT treatment.";
RL Hum. Mutat. 20:117-126(2002).
RN [48]
RP VARIANTS CBSD TRP-125; MET-191; TYR-275; CYS-336; PRO-338; ASN-349; GLN-379
RP AND PRO-456.
RX PubMed=12815602; DOI=10.1002/humu.9153;
RA Urreizti R., Balcells S., Rodes M., Vilarinho L., Baldellou A., Couce M.L.,
RA Munoz C., Campistol J., Pinto X., Vilaseca M.A., Grinberg D.;
RT "Spectrum of CBS mutations in 16 homocystinuric patients from the iberian
RT peninsula: high prevalence of T191M and absence of I278T or G307S.";
RL Hum. Mutat. 22:103-103(2003).
RN [49]
RP VARIANTS CBSD PRO-101; THR-226; SER-228; PRO-231; THR-278; SER-307;
RP ALA-320; MET-353; ASN-376 AND LYS-526, AND CHARACTERIZATION OF VARIANTS
RP CBSD PRO-101; THR-226; SER-228; PRO-231; THR-278; SER-307; ALA-320;
RP MET-353; ASN-376 AND LYS-526.
RX PubMed=14635102; DOI=10.1002/humu.10290;
RA Kruger W.D., Wang L., Jhee K.H., Singh R.H., Elsas L.J. II;
RT "Cystathionine beta-synthase deficiency in Georgia (USA): correlation of
RT clinical and biochemical phenotype with genotype.";
RL Hum. Mutat. 22:434-441(2003).
RN [50]
RP VARIANTS CBSD MET-143; ARG-148; LYS-228 AND THR-278, AND CHARACTERIZATION
RP OF VARIANTS CBSD MET-143 AND ARG-148.
RX PubMed=15146473; DOI=10.1002/humu.9249;
RA Orendac M., Pronicka E., Kubalska J., Janosik M., Sokolova J.,
RA Linnebank M., Koch H.G., Kozich V.;
RT "Identification and functional analysis of two novel mutations in the CBS
RT gene in Polish patients with homocystinuria.";
RL Hum. Mutat. 23:631-631(2004).
RN [51]
RP VARIANTS CBSD 247-LYS--GLY-256 DEL; PRO-288 AND TRP-379.
RX PubMed=15365998; DOI=10.1002/humu.9280;
RA Linnebank M., Janosik M., Kozich V., Pronicka E., Kubalska J., Sokolova J.,
RA Linnebank A., Schmidt E., Leyendecker C., Klockgether T., Kraus J.P.,
RA Koch H.G.;
RT "The cystathionine beta-synthase (CBS) mutation c.1224-2A>C in Central
RT Europe: vitamin B6 nonresponsiveness and a common ancestral haplotype.";
RL Hum. Mutat. 24:352-353(2004).
RN [52]
RP VARIANTS CBSD ALA-168; MET-191 AND THR-278.
RX PubMed=15993874; DOI=10.1016/j.cccn.2005.05.030;
RA Porto M.P.R., Galdieri L.C., Pereira V.G., Vergani N., da Rocha J.C.C.,
RA Micheletti C., Martins A.M., Perez A.B.A., Almeida V.D.;
RT "Molecular analysis of homocystinuria in Brazilian patients.";
RL Clin. Chim. Acta 362:71-78(2005).
RN [53]
RP VARIANTS CBSD GLN-154; VAL-155; ASP-234 DEL; MET-257; THR-288; CYS-336;
RP SER-347 AND MET-353, VARIANT CYS-18, CHARACTERIZATION OF VARIANTS CBSD
RP GLN-154; VAL-155; ASP-234 DEL; MET-257; THR-288; CYS-336; SER-347 AND
RP MET-353, AND CHARACTERIZATION OF VARIANT CYS-18.
RX PubMed=16205833; DOI=10.1007/s10038-005-0312-2;
RA Lee S.-J., Lee D.H., Yoo H.-W., Koo S.K., Park E.-S., Park J.-W., Lim H.G.,
RA Jung S.-C.;
RT "Identification and functional analysis of cystathionine beta-synthase gene
RT mutations in patients with homocystinuria.";
RL J. Hum. Genet. 50:648-654(2005).
RN [54]
RP CHARACTERIZATION OF VARIANTS CBSD TRP-125; ARG-148; VAL-173; MET-191;
RP THR-226; TYR-275; CYS-336; HIS-336; PRO-338; ASN-349; GLN-379 AND PRO-456,
RP AND CHARACTERIZATION OF VARIANT GLN-548.
RX PubMed=16429402; DOI=10.1002/humu.9395;
RA Urreizti R., Asteggiano C., Cozar M., Frank N., Vilaseca M.A., Grinberg D.,
RA Balcells S.;
RT "Functional assays testing pathogenicity of 14 cystathionine-beta synthase
RT mutations.";
RL Hum. Mutat. 27:211-211(2006).
RN [55]
RP VARIANTS CBSD MET-173 DEL; LEU-200; SER-278; ASN-281; VAL-321 AND SER-446,
RP AND CHARACTERIZATION OF VARIANTS CBSD MET-173 DEL; SER-278; ASN-281 AND
RP VAL-321.
RX PubMed=21520339; DOI=10.1002/humu.21514;
RA Cozar M., Urreizti R., Vilarinho L., Grosso C., Dodelson de Kremer R.,
RA Asteggiano C.G., Dalmau J., Garcia A.M., Vilaseca M.A., Grinberg D.,
RA Balcells S.;
RT "Identification and functional analyses of CBS alleles in Spanish and
RT Argentinian homocystinuric patients.";
RL Hum. Mutat. 32:835-842(2011).
RN [56]
RP VARIANTS CBSD THR-278 AND CYS-336.
RX PubMed=21240075; DOI=10.1097/pat.0b013e3283419dbb;
RA Kwok J.S., Fung S.L., Lui G.C., Law E.L., Chan M.H., Leung C.B., Tang N.L.;
RT "CBS gene mutations found in a Chinese pyridoxine-responsive homocystinuria
RT patient.";
RL Pathology 43:81-83(2011).
RN [57]
RP VARIANT CBSD LYS-266, CHARACTERIZATION OF VARIANT CBSD LYS-266, AND
RP ACTIVITY REGULATION.
RX PubMed=22738154; DOI=10.1021/bi300421z;
RA Smith A.T., Su Y., Stevens D.J., Majtan T., Kraus J.P., Burstyn J.N.;
RT "Effect of the disease-causing R266K mutation on the heme and PLP
RT environments of human cystathionine beta-synthase.";
RL Biochemistry 51:6360-6370(2012).
RN [58]
RP VARIANTS CBSD ARG-85; ASN-87 AND ASN-234, CHARACTERIZATION OF VARIANTS CBSD
RP ASN-87 AND ASN-234, FUNCTION, CATALYTIC ACTIVITY, PATHWAY, COFACTOR,
RP SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=23981774; DOI=10.1016/j.gene.2013.08.021;
RA Casique L., Kabil O., Banerjee R., Martinez J.C., De Lucca M.;
RT "Characterization of two pathogenic mutations in cystathionine beta-
RT synthase: different intracellular locations for wild-type and mutant
RT proteins.";
RL Gene 531:117-124(2013).
RN [59]
RP VARIANT CBSD GLY-449, CHARACTERIZATION OF VARIANTS CBSD LEU-427; ASN-444;
RP GLY-449; LEU-500 AND GLN-540, AND CATALYTIC ACTIVITY.
RX PubMed=25044645; DOI=10.1002/humu.22616;
RA Mendes M.I., Santos A.S., Smith D.E., Lino P.R., Colaco H.G.,
RA de Almeida I.T., Vicente J.B., Salomons G.S., Rivera I., Blom H.J.,
RA Leandro P.;
RT "Insights into the regulatory domain of cystathionine Beta-synthase:
RT characterization of six variant proteins.";
RL Hum. Mutat. 35:1195-1202(2014).
RN [60]
RP VARIANTS CBSD LEU-49; LYS-269 DEL; THR-278; HIS-336; LEU-427; ASN-444;
RP LEU-500 AND GLN-540, CHARACTERIZATION OF VARIANTS CBSD LEU-49; LYS-269 DEL;
RP THR-278; HIS-336; LEU-427; ASN-444; LEU-500 AND GLN-540, FUNCTION,
RP CATALYTIC ACTIVITY, PATHWAY, AND ACTIVITY REGULATION.
RX PubMed=23974653; DOI=10.1007/s10545-013-9647-6;
RA Mendes M.I., Colaco H.G., Smith D.E., Ramos R.J., Pop A., van Dooren S.J.,
RA Tavares de Almeida I., Kluijtmans L.A., Janssen M.C., Rivera I.,
RA Salomons G.S., Leandro P., Blom H.J.;
RT "Reduced response of Cystathionine Beta-Synthase (CBS) to S-
RT Adenosylmethionine (SAM): Identification and functional analysis of CBS
RT gene mutations in Homocystinuria patients.";
RL J. Inherit. Metab. Dis. 37:245-254(2014).
CC -!- FUNCTION: Hydro-lyase catalyzing the first step of the transsulfuration
CC pathway, where the hydroxyl group of L-serine is displaced by L-
CC homocysteine in a beta-replacement reaction to form L-cystathionine,
CC the precursor of L-cysteine. This catabolic route allows the
CC elimination of L-methionine and the toxic metabolite L-homocysteine
CC (PubMed:23981774, PubMed:20506325, PubMed:23974653). Also involved in
CC the production of hydrogen sulfide, a gasotransmitter with signaling
CC and cytoprotective effects on neurons (By similarity).
CC {ECO:0000250|UniProtKB:P32232, ECO:0000269|PubMed:20506325,
CC ECO:0000269|PubMed:23974653, ECO:0000269|PubMed:23981774}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-homocysteine + L-serine = H2O + L,L-cystathionine;
CC Xref=Rhea:RHEA:10112, ChEBI:CHEBI:15377, ChEBI:CHEBI:33384,
CC ChEBI:CHEBI:58161, ChEBI:CHEBI:58199; EC=4.2.1.22;
CC Evidence={ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:23974653,
CC ECO:0000269|PubMed:23981774, ECO:0000269|PubMed:25044645};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|PubMed:23981774};
CC -!- ACTIVITY REGULATION: Allosterically activated by S-adenosyl-
CC methionine/AdoMet. Activated by S-adenosylhomocysteine/AdoHcy
CC (PubMed:20506325). Binds non-covalently to a heme group that may
CC control the redox sensitivity of the enzyme (PubMed:11483494,
CC PubMed:12173932, PubMed:22738154). {ECO:0000269|PubMed:11483494,
CC ECO:0000269|PubMed:12173932, ECO:0000269|PubMed:20506325,
CC ECO:0000269|PubMed:22738154, ECO:0000269|PubMed:23974653}.
CC -!- PATHWAY: Amino-acid biosynthesis; L-cysteine biosynthesis; L-cysteine
CC from L-homocysteine and L-serine: step 1/2.
CC {ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:23974653,
CC ECO:0000269|PubMed:23981774}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:11483494,
CC ECO:0000269|PubMed:12173932, ECO:0000269|PubMed:20506325,
CC ECO:0000269|PubMed:23981774}.
CC -!- INTERACTION:
CC P35520; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-740135, EBI-1383687;
CC P35520; P35520: CBS; NbExp=6; IntAct=EBI-740135, EBI-740135;
CC P35520; P35222: CTNNB1; NbExp=3; IntAct=EBI-740135, EBI-491549;
CC P35520; Q15438: CYTH1; NbExp=3; IntAct=EBI-740135, EBI-997830;
CC P35520; Q08426: EHHADH; NbExp=4; IntAct=EBI-740135, EBI-2339219;
CC P35520; O75344: FKBP6; NbExp=3; IntAct=EBI-740135, EBI-744771;
CC P35520; P51116: FXR2; NbExp=3; IntAct=EBI-740135, EBI-740459;
CC P35520; P06241: FYN; NbExp=3; IntAct=EBI-740135, EBI-515315;
CC P35520; P22466: GAL; NbExp=3; IntAct=EBI-740135, EBI-6624768;
CC P35520; P42858: HTT; NbExp=12; IntAct=EBI-740135, EBI-466029;
CC P35520; Q92993-2: KAT5; NbExp=3; IntAct=EBI-740135, EBI-20795332;
CC P35520; O75928-2: PIAS2; NbExp=3; IntAct=EBI-740135, EBI-348567;
CC P35520; Q13526: PIN1; NbExp=4; IntAct=EBI-740135, EBI-714158;
CC P35520; P17612: PRKACA; NbExp=3; IntAct=EBI-740135, EBI-476586;
CC P35520; P54619: PRKAG1; NbExp=3; IntAct=EBI-740135, EBI-1181439;
CC P35520; P25786: PSMA1; NbExp=4; IntAct=EBI-740135, EBI-359352;
CC P35520; P57075: UBASH3A; NbExp=4; IntAct=EBI-740135, EBI-2105393;
CC P35520; Q7KZS0: UBE2I; NbExp=6; IntAct=EBI-740135, EBI-10180829;
CC P35520; Q9UJ78-2: ZMYM5; NbExp=3; IntAct=EBI-740135, EBI-17634549;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17087506,
CC ECO:0000269|PubMed:23981774}. Nucleus {ECO:0000269|PubMed:17087506}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Major;
CC IsoId=P35520-1; Sequence=Displayed;
CC Name=2; Synonyms=Minor;
CC IsoId=P35520-2; Sequence=VSP_001217;
CC -!- TISSUE SPECIFICITY: In the adult strongly expressed in liver and
CC pancreas, some expression in heart and brain, weak expression in lung
CC and kidney. In the fetus, expressed in brain, liver and kidney.
CC -!- DISEASE: Cystathionine beta-synthase deficiency (CBSD) [MIM:236200]: An
CC enzymatic deficiency resulting in altered sulfur metabolism and
CC homocystinuria. The clinical features of untreated homocystinuria due
CC to CBS deficiency include myopia, ectopia lentis, intellectual
CC disability, skeletal anomalies resembling Marfan syndrome, and
CC thromboembolic events. Light skin and hair can also be present.
CC Biochemical features include increased urinary homocystine and
CC methionine. {ECO:0000269|PubMed:10215408, ECO:0000269|PubMed:10408774,
CC ECO:0000269|PubMed:10462600, ECO:0000269|PubMed:11013450,
CC ECO:0000269|PubMed:11359213, ECO:0000269|PubMed:11553052,
CC ECO:0000269|PubMed:12007221, ECO:0000269|PubMed:12124992,
CC ECO:0000269|PubMed:12815602, ECO:0000269|PubMed:1301198,
CC ECO:0000269|PubMed:14635102, ECO:0000269|PubMed:15146473,
CC ECO:0000269|PubMed:15365998, ECO:0000269|PubMed:15993874,
CC ECO:0000269|PubMed:16205833, ECO:0000269|PubMed:16429402,
CC ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:21240075,
CC ECO:0000269|PubMed:21520339, ECO:0000269|PubMed:22738154,
CC ECO:0000269|PubMed:23974653, ECO:0000269|PubMed:23981774,
CC ECO:0000269|PubMed:25044645, ECO:0000269|PubMed:7506602,
CC ECO:0000269|PubMed:7564249, ECO:0000269|PubMed:7611293,
CC ECO:0000269|PubMed:7635485, ECO:0000269|PubMed:7762555,
CC ECO:0000269|PubMed:7849717, ECO:0000269|PubMed:7967489,
CC ECO:0000269|PubMed:7981678, ECO:0000269|PubMed:8353501,
CC ECO:0000269|PubMed:8528202, ECO:0000269|PubMed:8755636,
CC ECO:0000269|PubMed:8803779, ECO:0000269|PubMed:8990018,
CC ECO:0000269|PubMed:9156316, ECO:0000269|PubMed:9266356,
CC ECO:0000269|PubMed:9361025, ECO:0000269|PubMed:9889017}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the cysteine synthase/cystathionine beta-
CC synthase family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=CBS mutation database;
CC URL="http://cbs.lf1.cuni.cz/index.php";
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DR EMBL; L19501; AAA19874.1; -; mRNA.
DR EMBL; X82166; CAA57656.1; -; mRNA.
DR EMBL; L14577; AAA98524.1; -; mRNA.
DR EMBL; X88562; CAA61252.1; -; Genomic_DNA.
DR EMBL; X91910; CAA61252.1; JOINED; Genomic_DNA.
DR EMBL; X98811; CAA61252.1; JOINED; Genomic_DNA.
DR EMBL; X98812; CAA61252.1; JOINED; Genomic_DNA.
DR EMBL; X98813; CAA61252.1; JOINED; Genomic_DNA.
DR EMBL; X98814; CAA61252.1; JOINED; Genomic_DNA.
DR EMBL; X98815; CAA61252.1; JOINED; Genomic_DNA.
DR EMBL; X98816; CAA61252.1; JOINED; Genomic_DNA.
DR EMBL; X98817; CAA61252.1; JOINED; Genomic_DNA.
DR EMBL; X98818; CAA61252.1; JOINED; Genomic_DNA.
DR EMBL; X98819; CAA61252.1; JOINED; Genomic_DNA.
DR EMBL; X98820; CAA61252.1; JOINED; Genomic_DNA.
DR EMBL; X98821; CAA61252.1; JOINED; Genomic_DNA.
DR EMBL; X98822; CAA61252.1; JOINED; Genomic_DNA.
DR EMBL; X98823; CAA61252.1; JOINED; Genomic_DNA.
DR EMBL; AF042836; AAC64684.1; -; Genomic_DNA.
DR EMBL; AF042836; AAC64683.1; -; Genomic_DNA.
DR EMBL; BT007154; AAP35818.1; -; mRNA.
DR EMBL; AK313691; BAG36440.1; -; mRNA.
DR EMBL; AP001630; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471079; EAX09508.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09509.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09510.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09511.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09515.1; -; Genomic_DNA.
DR EMBL; BC000440; AAH00440.1; -; mRNA.
DR EMBL; BC007257; AAH07257.1; -; mRNA.
DR EMBL; BC010242; AAH10242.1; -; mRNA.
DR EMBL; BC011381; AAH11381.1; -; mRNA.
DR CCDS; CCDS13693.1; -. [P35520-1]
DR CCDS; CCDS82646.1; -. [P35520-1]
DR CCDS; CCDS86979.1; -. [P35520-2]
DR PIR; A55760; A55760.
DR RefSeq; NP_000062.1; NM_000071.2. [P35520-1]
DR RefSeq; NP_001171479.1; NM_001178008.2. [P35520-1]
DR RefSeq; NP_001171480.1; NM_001178009.2. [P35520-1]
DR RefSeq; NP_001307227.1; NM_001320298.1. [P35520-1]
DR RefSeq; NP_001308002.1; NM_001321073.1. [P35520-1]
DR RefSeq; XP_011528079.1; XM_011529777.1. [P35520-2]
DR RefSeq; XP_011528083.1; XM_011529781.1.
DR RefSeq; XP_011528084.1; XM_011529782.1.
DR RefSeq; XP_011544396.1; XM_011546094.1.
DR RefSeq; XP_011544397.1; XM_011546095.2.
DR RefSeq; XP_011544399.1; XM_011546097.2.
DR RefSeq; XP_011544400.1; XM_011546098.1.
DR RefSeq; XP_011544401.1; XM_011546099.1.
DR RefSeq; XP_016883700.1; XM_017028211.1.
DR RefSeq; XP_016883701.1; XM_017028212.1.
DR RefSeq; XP_016883702.1; XM_017028213.1.
DR RefSeq; XP_016883703.1; XM_017028214.1.
DR RefSeq; XP_016883704.1; XM_017028215.1.
DR RefSeq; XP_016883705.1; XM_017028216.1.
DR RefSeq; XP_016883706.1; XM_017028217.1.
DR RefSeq; XP_016883707.1; XM_017028218.1.
DR RefSeq; XP_016883978.1; XM_017028489.1.
DR RefSeq; XP_016883979.1; XM_017028490.1.
DR RefSeq; XP_016883980.1; XM_017028491.1. [P35520-1]
DR RefSeq; XP_016883981.1; XM_017028492.1.
DR PDB; 1JBQ; X-ray; 2.60 A; A/B/C/D/E/F=2-413.
DR PDB; 1M54; X-ray; 2.90 A; A/B/C/D/E/F=44-406.
DR PDB; 4COO; X-ray; 2.00 A; A/B=1-551.
DR PDB; 4L0D; X-ray; 2.97 A; A/B=1-551.
DR PDB; 4L27; X-ray; 3.39 A; A/B/C/D=2-551.
DR PDB; 4L28; X-ray; 2.63 A; A/B/C/D=2-551.
DR PDB; 4L3V; X-ray; 3.63 A; A/B/C=2-551.
DR PDB; 4PCU; X-ray; 3.58 A; A/B=1-551.
DR PDB; 4UUU; X-ray; 1.71 A; A/B=406-547.
DR PDB; 5MMS; X-ray; 2.80 A; A/B/C/D/E/F=1-408.
DR PDBsum; 1JBQ; -.
DR PDBsum; 1M54; -.
DR PDBsum; 4COO; -.
DR PDBsum; 4L0D; -.
DR PDBsum; 4L27; -.
DR PDBsum; 4L28; -.
DR PDBsum; 4L3V; -.
DR PDBsum; 4PCU; -.
DR PDBsum; 4UUU; -.
DR PDBsum; 5MMS; -.
DR AlphaFoldDB; P35520; -.
DR SMR; P35520; -.
DR BioGRID; 107321; 129.
DR BioGRID; 3195666; 10.
DR IntAct; P35520; 42.
DR MINT; P35520; -.
DR BindingDB; P35520; -.
DR ChEMBL; CHEMBL3399911; -.
DR DrugBank; DB00118; Ademetionine.
DR DrugBank; DB00151; Cysteine.
DR DrugBank; DB00114; Pyridoxal phosphate.
DR DrugBank; DB00133; Serine.
DR DrugCentral; P35520; -.
DR GuidetoPHARMACOLOGY; 1443; -.
DR GlyGen; P35520; 2 sites, 2 O-linked glycans (2 sites).
DR iPTMnet; P35520; -.
DR PhosphoSitePlus; P35520; -.
DR SwissPalm; P35520; -.
DR BioMuta; CBS; -.
DR DMDM; 543959; -.
DR EPD; P35520; -.
DR jPOST; P35520; -.
DR MassIVE; P35520; -.
DR MaxQB; P35520; -.
DR PRIDE; P35520; -.
DR ProteomicsDB; 55074; -. [P35520-1]
DR ProteomicsDB; 55075; -. [P35520-2]
DR Antibodypedia; 768; 495 antibodies from 37 providers.
DR DNASU; 875; -.
DR Ensembl; ENST00000352178.9; ENSP00000344460.5; ENSG00000160200.18. [P35520-1]
DR Ensembl; ENST00000359624.7; ENSP00000352643.3; ENSG00000160200.18. [P35520-1]
DR Ensembl; ENST00000398158.5; ENSP00000381225.1; ENSG00000160200.18. [P35520-1]
DR Ensembl; ENST00000398165.8; ENSP00000381231.4; ENSG00000160200.18. [P35520-1]
DR GeneID; 102724560; -.
DR GeneID; 875; -.
DR KEGG; hsa:102724560; -.
DR KEGG; hsa:875; -.
DR MANE-Select; ENST00000398165.8; ENSP00000381231.4; NM_000071.3; NP_000062.1.
DR UCSC; uc002zct.3; human. [P35520-1]
DR CTD; 875; -.
DR DisGeNET; 102724560; -.
DR DisGeNET; 875; -.
DR GeneCards; CBS; -.
DR GeneReviews; CBS; -.
DR HGNC; HGNC:1550; CBS.
DR HPA; ENSG00000160200; Tissue enhanced (liver, pancreas).
DR MalaCards; CBS; -.
DR MIM; 236200; phenotype.
DR MIM; 613381; gene.
DR neXtProt; NX_P35520; -.
DR OpenTargets; ENSG00000160200; -.
DR OpenTargets; ENSG00000274276; -.
DR Orphanet; 394; Classic homocystinuria.
DR PharmGKB; PA26123; -.
DR VEuPathDB; HostDB:ENSG00000160200; -.
DR GeneTree; ENSGT00510000047027; -.
DR HOGENOM; CLU_021018_0_0_1; -.
DR InParanoid; P35520; -.
DR OMA; IEITMDT; -.
DR OrthoDB; 1016546at2759; -.
DR PhylomeDB; P35520; -.
DR TreeFam; TF300784; -.
DR BioCyc; MetaCyc:HS08461-MON; -.
DR BRENDA; 4.2.1.22; 2681.
DR PathwayCommons; P35520; -.
DR Reactome; R-HSA-1614603; Cysteine formation from homocysteine.
DR Reactome; R-HSA-2408508; Metabolism of ingested SeMet, Sec, MeSec into H2Se.
DR SABIO-RK; P35520; -.
DR SignaLink; P35520; -.
DR SIGNOR; P35520; -.
DR UniPathway; UPA00136; UER00201.
DR BioGRID-ORCS; 102724560; 0 hits in 13 CRISPR screens.
DR BioGRID-ORCS; 875; 11 hits in 1080 CRISPR screens.
DR ChiTaRS; CBS; human.
DR EvolutionaryTrace; P35520; -.
DR GeneWiki; Cystathionine_beta_synthase; -.
DR Pharos; P35520; Tchem.
DR PRO; PR:P35520; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; P35520; protein.
DR Bgee; ENSG00000160200; Expressed in right lobe of liver and 95 other tissues.
DR ExpressionAtlas; P35520; baseline and differential.
DR Genevisible; P35520; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0070025; F:carbon monoxide binding; IDA:BHF-UCL.
DR GO; GO:0004122; F:cystathionine beta-synthase activity; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0072341; F:modified amino acid binding; IDA:UniProtKB.
DR GO; GO:0070026; F:nitric oxide binding; IDA:BHF-UCL.
DR GO; GO:0050421; F:nitrite reductase (NO-forming) activity; IDA:BHF-UCL.
DR GO; GO:0019825; F:oxygen binding; IDA:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IDA:UniProtKB.
DR GO; GO:1904047; F:S-adenosyl-L-methionine binding; IDA:BHF-UCL.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0097746; P:blood vessel diameter maintenance; IEA:Ensembl.
DR GO; GO:0001974; P:blood vessel remodeling; IEA:Ensembl.
DR GO; GO:0060351; P:cartilage development involved in endochondral bone morphogenesis; IEA:Ensembl.
DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR GO; GO:0021587; P:cerebellum morphogenesis; IEA:Ensembl.
DR GO; GO:0019344; P:cysteine biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0006535; P:cysteine biosynthetic process from serine; IEA:InterPro.
DR GO; GO:0019343; P:cysteine biosynthetic process via cystathionine; IEA:InterPro.
DR GO; GO:0042262; P:DNA protection; IMP:BHF-UCL.
DR GO; GO:0001958; P:endochondral ossification; IEA:Ensembl.
DR GO; GO:0043418; P:homocysteine catabolic process; IDA:UniProtKB.
DR GO; GO:0050667; P:homocysteine metabolic process; IDA:UniProtKB.
DR GO; GO:0070814; P:hydrogen sulfide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0019448; P:L-cysteine catabolic process; IDA:UniProtKB.
DR GO; GO:0006565; P:L-serine catabolic process; IDA:UniProtKB.
DR GO; GO:0006563; P:L-serine metabolic process; IDA:UniProtKB.
DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0043506; P:regulation of JUN kinase activity; IEA:Ensembl.
DR GO; GO:0010749; P:regulation of nitric oxide mediated signal transduction; IEA:Ensembl.
DR GO; GO:0051593; P:response to folic acid; IEA:Ensembl.
DR GO; GO:0006801; P:superoxide metabolic process; IEA:Ensembl.
DR GO; GO:0019346; P:transsulfuration; IEA:Ensembl.
DR CDD; cd04608; CBS_pair_CBS; 1.
DR DisProt; DP01976; -.
DR Gene3D; 3.10.580.10; -; 1.
DR Gene3D; 3.40.50.1100; -; 2.
DR InterPro; IPR046353; CBS_C.
DR InterPro; IPR000644; CBS_dom.
DR InterPro; IPR046342; CBS_dom_sf.
DR InterPro; IPR005857; Cysta_beta_synth.
DR InterPro; IPR001216; P-phosphate_BS.
DR InterPro; IPR001926; PLP-dep.
DR InterPro; IPR036052; Trypto_synt_PLP_dependent.
DR Pfam; PF00571; CBS; 1.
DR Pfam; PF00291; PALP; 1.
DR SMART; SM00116; CBS; 1.
DR SUPFAM; SSF53686; SSF53686; 1.
DR SUPFAM; SSF54631; SSF54631; 1.
DR TIGRFAMs; TIGR01137; cysta_beta; 1.
DR PROSITE; PS51371; CBS; 1.
DR PROSITE; PS00901; CYS_SYNTHASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Allosteric enzyme; Alternative splicing;
KW Amino-acid biosynthesis; CBS domain; Cysteine biosynthesis; Cytoplasm;
KW Disease variant; Heme; Iron; Isopeptide bond; Lyase; Metal-binding;
KW Nucleus; Phosphoprotein; Pyridoxal phosphate; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..551
FT /note="Cystathionine beta-synthase"
FT /id="PRO_0000167133"
FT DOMAIN 418..476
FT /note="CBS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT REGION 1..74
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 28..44
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 52
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000269|PubMed:11483494,
FT ECO:0000269|PubMed:12173932"
FT BINDING 65
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000269|PubMed:11483494,
FT ECO:0000269|PubMed:12173932"
FT BINDING 149
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:11483494,
FT ECO:0000269|PubMed:12173932"
FT BINDING 256..260
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:11483494,
FT ECO:0000269|PubMed:12173932"
FT BINDING 349
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:11483494,
FT ECO:0000269|PubMed:12173932"
FT MOD_RES 27
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 119
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000269|PubMed:11483494,
FT ECO:0000269|PubMed:12173932"
FT MOD_RES 199
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 211
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:17087506"
FT VAR_SEQ 518
FT /note="Y -> SQDQAWAGVVGGPAD (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_001217"
FT VARIANT 18
FT /note="R -> C (associated with 1/3 to 2/3 the enzyme
FT activity of the wild-type; dbSNP:rs201827340)"
FT /evidence="ECO:0000269|PubMed:16205833"
FT /id="VAR_046921"
FT VARIANT 49
FT /note="P -> L (in CBSD; decreased expression; no effect on
FT cystathionine beta-synthase activity; increased
FT homotetramer formation; dbSNP:rs148865119)"
FT /evidence="ECO:0000269|PubMed:12124992,
FT ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:23974653"
FT /id="VAR_008049"
FT VARIANT 58
FT /note="R -> W (in CBSD; linked with V-114; 18% of activity;
FT dbSNP:rs555959266)"
FT /evidence="ECO:0000269|PubMed:10408774"
FT /id="VAR_008050"
FT VARIANT 65
FT /note="H -> R (in CBSD; decreased cystathionine beta-
FT synthase activity; inhibited by AdoMet and AdoHcy;
FT decreased homotetramer formation; dbSNP:rs1191141364)"
FT /evidence="ECO:0000269|PubMed:11359213,
FT ECO:0000269|PubMed:20506325"
FT /id="VAR_021790"
FT VARIANT 69
FT /note="A -> P (in dbSNP:rs17849313)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_046922"
FT VARIANT 78
FT /note="P -> R (in CBSD; severe form; associated in cis with
FT N-102; decreased cystathionine beta-synthase activity;
FT decreased homotetramer formation; dbSNP:rs786204608)"
FT /evidence="ECO:0000269|PubMed:20506325,
FT ECO:0000269|PubMed:7981678"
FT /id="VAR_002171"
FT VARIANT 85
FT /note="G -> R (in CBSD; loss of cystathionine beta-synthase
FT activity; dbSNP:rs863223435)"
FT /evidence="ECO:0000269|PubMed:12007221,
FT ECO:0000269|PubMed:23981774"
FT /id="VAR_008051"
FT VARIANT 87
FT /note="T -> N (in CBSD; decreased cystathionine beta-
FT synthase activity; increased aggregation)"
FT /evidence="ECO:0000269|PubMed:23981774"
FT /id="VAR_074590"
FT VARIANT 88
FT /note="P -> S (in CBSD)"
FT /evidence="ECO:0000269|PubMed:7762555"
FT /id="VAR_002172"
FT VARIANT 101
FT /note="L -> P (in CBSD; common mutation in Irish
FT population; loss of activity; dbSNP:rs786204757)"
FT /evidence="ECO:0000269|PubMed:12124992,
FT ECO:0000269|PubMed:14635102, ECO:0000269|PubMed:9889017"
FT /id="VAR_021791"
FT VARIANT 102
FT /note="K -> N (in CBSD; associated in cis with R-78;
FT decreased cystathionine beta-synthase activity; decreased
FT homotetramer formation; dbSNP:rs786204609)"
FT /evidence="ECO:0000269|PubMed:20506325,
FT ECO:0000269|PubMed:7981678"
FT /id="VAR_002173"
FT VARIANT 102
FT /note="K -> Q (in dbSNP:rs34040148)"
FT /evidence="ECO:0000269|PubMed:11013450"
FT /id="VAR_008052"
FT VARIANT 109
FT /note="C -> R (in CBSD; loss of activity;
FT dbSNP:rs778220779)"
FT /evidence="ECO:0000269|PubMed:12124992"
FT /id="VAR_021792"
FT VARIANT 114
FT /note="A -> V (in CBSD; mild form; when linked with W-58
FT severe form; decreased cystathionine beta-synthase
FT activity; decreases homotetramer formation by promoting
FT formation of larger aggregates; dbSNP:rs121964964)"
FT /evidence="ECO:0000269|PubMed:11359213,
FT ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:8353501"
FT /id="VAR_002174"
FT VARIANT 116
FT /note="G -> R (in CBSD; dbSNP:rs760214620)"
FT /evidence="ECO:0000269|PubMed:8803779"
FT /id="VAR_008053"
FT VARIANT 121
FT /note="R -> C (in CBSD; dbSNP:rs775992753)"
FT /id="VAR_008054"
FT VARIANT 121
FT /note="R -> H (in CBSD; dbSNP:rs770095972)"
FT /id="VAR_008055"
FT VARIANT 121
FT /note="R -> L (in CBSD; mild form; dbSNP:rs770095972)"
FT /id="VAR_008056"
FT VARIANT 125
FT /note="R -> P (in CBSD)"
FT /evidence="ECO:0000269|PubMed:11553052"
FT /id="VAR_046923"
FT VARIANT 125
FT /note="R -> Q (in CBSD; severe form; when linked with D-131
FT moderate form; loss of cystathionine beta-synthase
FT activity; decreased homotetramer formation;
FT dbSNP:rs781444670)"
FT /evidence="ECO:0000269|PubMed:12124992,
FT ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:7762555,
FT ECO:0000269|PubMed:7849717"
FT /id="VAR_002175"
FT VARIANT 125
FT /note="R -> W (in CBSD; exhibits an activity lower than 4%
FT of the wild-type enzyme; absent capacity to form multimeric
FT quaternary structure; dbSNP:rs886057100)"
FT /evidence="ECO:0000269|PubMed:12815602,
FT ECO:0000269|PubMed:16429402"
FT /id="VAR_008057"
FT VARIANT 126
FT /note="M -> V (in CBSD; loss of activity)"
FT /evidence="ECO:0000269|PubMed:10408774"
FT /id="VAR_008058"
FT VARIANT 128
FT /note="E -> D (in CBSD; dbSNP:rs374593242)"
FT /id="VAR_008059"
FT VARIANT 131
FT /note="E -> D (in CBSD; linked with Q-125; loss of
FT activity; dbSNP:rs1555875351)"
FT /evidence="ECO:0000269|PubMed:7849717"
FT /id="VAR_002176"
FT VARIANT 139
FT /note="G -> R (in CBSD; mild form; dbSNP:rs121964965)"
FT /evidence="ECO:0000269|PubMed:7611293"
FT /id="VAR_008060"
FT VARIANT 143
FT /note="I -> M (in CBSD; 4% of activity; stable;
FT dbSNP:rs370167302)"
FT /evidence="ECO:0000269|PubMed:15146473"
FT /id="VAR_021793"
FT VARIANT 144
FT /note="E -> K (in CBSD; loss of cystathionine beta-synthase
FT activity; impaired stimulation by AdoMet and AdoHcy;
FT decreased homotetramer formation; dbSNP:rs121964966)"
FT /evidence="ECO:0000269|PubMed:10215408,
FT ECO:0000269|PubMed:11359213, ECO:0000269|PubMed:12124992,
FT ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:7611293,
FT ECO:0000269|PubMed:9156316"
FT /id="VAR_002177"
FT VARIANT 145
FT /note="P -> L (in CBSD; dbSNP:rs121964963)"
FT /evidence="ECO:0000269|PubMed:8353501"
FT /id="VAR_002178"
FT VARIANT 148
FT /note="G -> R (in CBSD; loss of cystathionine beta-synthase
FT activity; impaired stimulation by AdoMet and AdoHcy; loss
FT of homotetramer formation; dbSNP:rs755952006)"
FT /evidence="ECO:0000269|PubMed:15146473,
FT ECO:0000269|PubMed:16429402, ECO:0000269|PubMed:20506325"
FT /id="VAR_008061"
FT VARIANT 151..159
FT /note="Missing (in CBSD)"
FT /id="VAR_008063"
FT VARIANT 151
FT /note="G -> R (in CBSD; dbSNP:rs373782713)"
FT /id="VAR_008062"
FT VARIANT 152
FT /note="I -> M (in CBSD; severe form)"
FT /id="VAR_008064"
FT VARIANT 154
FT /note="L -> Q (in CBSD; protein expression is comparable to
FT wild-type; significant decrease of enzyme activity)"
FT /evidence="ECO:0000269|PubMed:16205833"
FT /id="VAR_046924"
FT VARIANT 155
FT /note="A -> T (in CBSD; complete loss of activity; severely
FT affects homotetramer formation by promoting formation of
FT larger aggregates; dbSNP:rs1429138569)"
FT /evidence="ECO:0000269|PubMed:11359213"
FT /id="VAR_008065"
FT VARIANT 155
FT /note="A -> V (in CBSD; protein expression is comparable to
FT wild-type; significant decrease of enzyme activity)"
FT /evidence="ECO:0000269|PubMed:16205833"
FT /id="VAR_046925"
FT VARIANT 165
FT /note="C -> Y (in CBSD; severe form; protein expression is
FT comparable to wild-type; loss of cystathionine beta-
FT synthase activity; no effect on homotetramer formation;
FT dbSNP:rs1347651454)"
FT /evidence="ECO:0000269|PubMed:10215408,
FT ECO:0000269|PubMed:11359213, ECO:0000269|PubMed:12124992,
FT ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:7635485"
FT /id="VAR_002179"
FT VARIANT 168
FT /note="V -> A (in CBSD)"
FT /evidence="ECO:0000269|PubMed:15993874"
FT /id="VAR_046926"
FT VARIANT 168
FT /note="V -> M (in CBSD; dbSNP:rs121964970)"
FT /evidence="ECO:0000269|PubMed:8528202"
FT /id="VAR_002180"
FT VARIANT 173
FT /note="M -> V (in CBSD; presents 40% of the wild-type
FT activity; highly reduced capacity to form multimeric
FT quaternary structure)"
FT /evidence="ECO:0000269|PubMed:16429402"
FT /id="VAR_046927"
FT VARIANT 173
FT /note="Missing (in CBSD; loss of activity)"
FT /evidence="ECO:0000269|PubMed:21520339"
FT /id="VAR_066098"
FT VARIANT 176
FT /note="E -> K (in CBSD; severe form; loss of cystathionine
FT beta-synthase activity; inhibited by AdoMet; severely
FT decreases homotetramer formation by promoting formation of
FT larger aggregates; dbSNP:rs762065361)"
FT /evidence="ECO:0000269|PubMed:11359213,
FT ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:9266356"
FT /id="VAR_008066"
FT VARIANT 180
FT /note="V -> A (in CBSD; decreased cystathionine beta-
FT synthase activity; decreases homotetramer formation;
FT dbSNP:rs1555875010)"
FT /evidence="ECO:0000269|PubMed:20506325"
FT /id="VAR_008067"
FT VARIANT 191
FT /note="T -> M (in CBSD; moderate and severe forms; loss of
FT cystathionine beta-synthase activity; absent capacity to
FT form multimeric quaternary structure; dbSNP:rs121964973)"
FT /evidence="ECO:0000269|PubMed:12815602,
FT ECO:0000269|PubMed:15993874, ECO:0000269|PubMed:16429402,
FT ECO:0000269|PubMed:20506325"
FT /id="VAR_008068"
FT VARIANT 198
FT /note="D -> V (in CBSD)"
FT /id="VAR_008069"
FT VARIANT 200
FT /note="P -> L (in CBSD; dbSNP:rs758712880)"
FT /evidence="ECO:0000269|PubMed:21520339"
FT /id="VAR_066099"
FT VARIANT 224
FT /note="R -> H (in CBSD; dbSNP:rs761647392)"
FT /evidence="ECO:0000269|PubMed:8528202"
FT /id="VAR_002181"
FT VARIANT 226
FT /note="A -> T (in CBSD; presents 20% of the wild-type
FT activity; dramatically reduced capacity to form multimeric
FT quaternary structure; dbSNP:rs763835246)"
FT /evidence="ECO:0000269|PubMed:14635102,
FT ECO:0000269|PubMed:16429402"
FT /id="VAR_008070"
FT VARIANT 228
FT /note="N -> K (in CBSD; loss of cystathionine beta-synthase
FT activity; decreased homotetramer formation;
FT dbSNP:rs1464223176)"
FT /evidence="ECO:0000269|PubMed:12124992,
FT ECO:0000269|PubMed:15146473, ECO:0000269|PubMed:20506325,
FT ECO:0000269|PubMed:9889017"
FT /id="VAR_021794"
FT VARIANT 228
FT /note="N -> S (in CBSD; has significantly decreased levels
FT of enzyme activity; dbSNP:rs1555874803)"
FT /evidence="ECO:0000269|PubMed:14635102"
FT /id="VAR_046928"
FT VARIANT 231
FT /note="A -> P (in CBSD; has significantly decreased levels
FT of enzyme activity)"
FT /evidence="ECO:0000269|PubMed:14635102"
FT /id="VAR_046929"
FT VARIANT 234
FT /note="D -> N (in CBSD; decreased cystathionine beta-
FT synthase activity; changed localization; decreased
FT interaction with pyridoxal 5'-phosphate; no effect on
FT homotetramer formation; dbSNP:rs773734233)"
FT /evidence="ECO:0000269|PubMed:23981774"
FT /id="VAR_008071"
FT VARIANT 234
FT /note="Missing (in CBSD; protein expression is comparable
FT to wild-type; significant decrease of enzyme activity)"
FT /evidence="ECO:0000269|PubMed:16205833"
FT /id="VAR_046930"
FT VARIANT 239
FT /note="E -> K (in CBSD)"
FT /id="VAR_002182"
FT VARIANT 247..256
FT /note="Missing (in CBSD)"
FT /evidence="ECO:0000269|PubMed:15365998"
FT /id="VAR_046931"
FT VARIANT 257
FT /note="T -> M (in CBSD; moderate to severe form; protein
FT expression is comparable to wild-type; significant decrease
FT of enzyme activity; dbSNP:rs758236584)"
FT /evidence="ECO:0000269|PubMed:16205833,
FT ECO:0000269|PubMed:7762555"
FT /id="VAR_002183"
FT VARIANT 262
FT /note="T -> M (in CBSD; moderate form; dbSNP:rs149119723)"
FT /evidence="ECO:0000269|PubMed:9361025,
FT ECO:0000269|PubMed:9889017"
FT /id="VAR_008072"
FT VARIANT 262
FT /note="T -> R (in CBSD; severe form; loss of cystathionine
FT beta-synthase activity; loss of homotetramer formation)"
FT /evidence="ECO:0000269|PubMed:11013450,
FT ECO:0000269|PubMed:20506325"
FT /id="VAR_021795"
FT VARIANT 266
FT /note="R -> G (in CBSD)"
FT /id="VAR_008073"
FT VARIANT 266
FT /note="R -> K (in CBSD; mild form; decreased cystathionine
FT beta-synthase activity; decreased homotetramer formation;
FT no effect on heme-binding; decreased stability;
FT dbSNP:rs121964969)"
FT /evidence="ECO:0000269|PubMed:20506325,
FT ECO:0000269|PubMed:22738154, ECO:0000269|PubMed:9361025"
FT /id="VAR_008074"
FT VARIANT 269
FT /note="Missing (in CBSD; loss of expression)"
FT /evidence="ECO:0000269|PubMed:23974653"
FT /id="VAR_074591"
FT VARIANT 270
FT /note="Missing (in CBSD)"
FT /id="VAR_008075"
FT VARIANT 275
FT /note="C -> Y (in CBSD; severe form; exhibits an activity
FT lower than 4% of the wild-type enzyme; absent capacity to
FT form multimeric quaternary structure)"
FT /evidence="ECO:0000269|PubMed:12815602,
FT ECO:0000269|PubMed:16429402"
FT /id="VAR_021796"
FT VARIANT 278
FT /note="I -> S (in CBSD; loss of activity)"
FT /evidence="ECO:0000269|PubMed:21520339"
FT /id="VAR_066100"
FT VARIANT 278
FT /note="I -> T (in CBSD; mild to severe form; common
FT mutation; decreased expression; loss of cystathionine beta-
FT synthase activity; impaired stimulation by AdoMet and
FT AdoHcy; severely affects homotetramer formation by
FT promoting formation of larger aggregates; dbSNP:rs5742905)"
FT /evidence="ECO:0000269|PubMed:11013450,
FT ECO:0000269|PubMed:11359213, ECO:0000269|PubMed:12007221,
FT ECO:0000269|PubMed:12124992, ECO:0000269|PubMed:1301198,
FT ECO:0000269|PubMed:14635102, ECO:0000269|PubMed:15146473,
FT ECO:0000269|PubMed:15993874, ECO:0000269|PubMed:20506325,
FT ECO:0000269|PubMed:21240075, ECO:0000269|PubMed:23974653,
FT ECO:0000269|PubMed:7506602, ECO:0000269|PubMed:7611293,
FT ECO:0000269|PubMed:8528202, ECO:0000269|PubMed:8803779,
FT ECO:0000269|PubMed:9156316, ECO:0000269|PubMed:9266356,
FT ECO:0000269|PubMed:9361025, ECO:0000269|PubMed:9889017"
FT /id="VAR_002184"
FT VARIANT 281
FT /note="D -> N (in CBSD; loss of activity)"
FT /evidence="ECO:0000269|PubMed:21520339"
FT /id="VAR_066101"
FT VARIANT 288
FT /note="A -> P (in CBSD)"
FT /evidence="ECO:0000269|PubMed:15365998"
FT /id="VAR_046932"
FT VARIANT 288
FT /note="A -> T (in CBSD; protein expression is comparable to
FT wild-type; significant decrease of enzyme activity;
FT dbSNP:rs141502207)"
FT /evidence="ECO:0000269|PubMed:16205833"
FT /id="VAR_046933"
FT VARIANT 290
FT /note="P -> L (in CBSD; dbSNP:rs760912339)"
FT /evidence="ECO:0000269|PubMed:7564249,
FT ECO:0000269|PubMed:8803779"
FT /id="VAR_002185"
FT VARIANT 302
FT /note="E -> K (in CBSD; no effect on cystathionine beta-
FT synthase activity; inhibited by AdoHcy and impaired
FT activation by AdoMet; no effect on homotetramer formation;
FT dbSNP:rs779270933)"
FT /evidence="ECO:0000269|PubMed:10408774,
FT ECO:0000269|PubMed:12124992, ECO:0000269|PubMed:20506325"
FT /id="VAR_008076"
FT VARIANT 305
FT /note="G -> R (in CBSD; loss of cystathionine beta-synthase
FT activity; no effect on homotetramer formation)"
FT /evidence="ECO:0000269|PubMed:20506325"
FT /id="VAR_008077"
FT VARIANT 307
FT /note="G -> S (in CBSD; moderate to severe form; linked
FT with D-534; common mutation; loss of cystathionine beta-
FT synthase activity; impaired stimulation by AdoMet and
FT AdoHcy; no effect on homotetramer formation;
FT dbSNP:rs121964962)"
FT /evidence="ECO:0000269|PubMed:12124992,
FT ECO:0000269|PubMed:14635102, ECO:0000269|PubMed:20506325,
FT ECO:0000269|PubMed:7506602, ECO:0000269|PubMed:8528202,
FT ECO:0000269|PubMed:9266356, ECO:0000269|PubMed:9361025,
FT ECO:0000269|PubMed:9889017"
FT /id="VAR_002186"
FT VARIANT 320
FT /note="V -> A (in CBSD; has 36% of wild-type enzyme
FT activity; dbSNP:rs781567152)"
FT /evidence="ECO:0000269|PubMed:14635102,
FT ECO:0000269|PubMed:9361025"
FT /id="VAR_008078"
FT VARIANT 321
FT /note="D -> V (in CBSD; loss of activity)"
FT /evidence="ECO:0000269|PubMed:21520339"
FT /id="VAR_066102"
FT VARIANT 331
FT /note="A -> E (in CBSD; dbSNP:rs777919630)"
FT /evidence="ECO:0000269|PubMed:12124992,
FT ECO:0000269|PubMed:9156316"
FT /id="VAR_008079"
FT VARIANT 331
FT /note="A -> V (in CBSD; dbSNP:rs777919630)"
FT /evidence="ECO:0000269|PubMed:8528202"
FT /id="VAR_002187"
FT VARIANT 336
FT /note="R -> C (in CBSD; protein expression is comparable to
FT wild-type; loss of activity; absent capacity to form
FT multimeric quaternary structure; dbSNP:rs398123151)"
FT /evidence="ECO:0000269|PubMed:10408774,
FT ECO:0000269|PubMed:12124992, ECO:0000269|PubMed:12815602,
FT ECO:0000269|PubMed:16205833, ECO:0000269|PubMed:16429402,
FT ECO:0000269|PubMed:21240075"
FT /id="VAR_002188"
FT VARIANT 336
FT /note="R -> H (in CBSD; mild form; no effect on expression;
FT exhibits an activity lower than 4% of the wild-type enzyme;
FT altered stimulation by AdoMet; absent capacity to form
FT multimeric quaternary structure; dbSNP:rs760417941)"
FT /evidence="ECO:0000269|PubMed:16429402,
FT ECO:0000269|PubMed:23974653"
FT /id="VAR_008080"
FT VARIANT 338
FT /note="L -> P (in CBSD; severe form; exhibits an activity
FT lower than 4% of the wild-type enzyme; absent capacity to
FT form multimeric quaternary structure)"
FT /evidence="ECO:0000269|PubMed:12815602,
FT ECO:0000269|PubMed:16429402"
FT /id="VAR_021797"
FT VARIANT 347
FT /note="G -> S (in CBSD; protein expression is comparable to
FT wild-type; loss of activity; dbSNP:rs771298943)"
FT /evidence="ECO:0000269|PubMed:12124992,
FT ECO:0000269|PubMed:16205833"
FT /id="VAR_021798"
FT VARIANT 349
FT /note="S -> N (in CBSD; severe form; exhibits an activity
FT lower than 4% of the wild-type enzyme; absent capacity to
FT form multimeric quaternary structure)"
FT /evidence="ECO:0000269|PubMed:12815602,
FT ECO:0000269|PubMed:16429402"
FT /id="VAR_021799"
FT VARIANT 352
FT /note="S -> N (in CBSD)"
FT /id="VAR_008081"
FT VARIANT 353
FT /note="T -> M (in CBSD; protein expression is comparable to
FT wild-type; significant decrease of enzyme activity;
FT dbSNP:rs121964972)"
FT /evidence="ECO:0000269|PubMed:12124992,
FT ECO:0000269|PubMed:14635102, ECO:0000269|PubMed:16205833,
FT ECO:0000269|PubMed:9156316"
FT /id="VAR_008082"
FT VARIANT 354
FT /note="V -> M (in CBSD; dbSNP:rs267606146)"
FT /id="VAR_008083"
FT VARIANT 355
FT /note="A -> P (in CBSD; dbSNP:rs1192581453)"
FT /evidence="ECO:0000269|PubMed:9889017"
FT /id="VAR_021800"
FT VARIANT 361
FT /note="A -> T (in CBSD; dbSNP:rs745764562)"
FT /evidence="ECO:0000269|PubMed:11553052"
FT /id="VAR_046934"
FT VARIANT 369
FT /note="R -> C (in CBSD; when linked with C-491 severe form;
FT decreased cystathionine beta-synthase activity; decreased
FT homotetramer formation; dbSNP:rs117687681)"
FT /evidence="ECO:0000269|PubMed:12124992,
FT ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:9361025"
FT /id="VAR_008084"
FT VARIANT 369
FT /note="R -> H (in CBSD; dbSNP:rs11700812)"
FT /id="VAR_002189"
FT VARIANT 370
FT /note="C -> Y (in CBSD; dbSNP:rs757920190)"
FT /evidence="ECO:0000269|PubMed:10462600"
FT /id="VAR_008085"
FT VARIANT 371
FT /note="V -> M (in CBSD; dbSNP:rs372010465)"
FT /evidence="ECO:0000269|PubMed:12124992,
FT ECO:0000269|PubMed:7635485"
FT /id="VAR_002190"
FT VARIANT 376
FT /note="D -> N (in CBSD; has significantly decreased levels
FT of enzyme activity; dbSNP:rs1170128038)"
FT /evidence="ECO:0000269|PubMed:14635102"
FT /id="VAR_046935"
FT VARIANT 379
FT /note="R -> Q (in CBSD; exhibits an activity lower than 4%
FT of the wild-type enzyme; absent capacity to form multimeric
FT quaternary structure; dbSNP:rs763036586)"
FT /evidence="ECO:0000269|PubMed:12815602,
FT ECO:0000269|PubMed:16429402"
FT /id="VAR_021801"
FT VARIANT 379
FT /note="R -> W (in CBSD; dbSNP:rs769080151)"
FT /evidence="ECO:0000269|PubMed:15365998"
FT /id="VAR_046936"
FT VARIANT 384
FT /note="K -> E (in CBSD; severe form; dbSNP:rs121964967)"
FT /evidence="ECO:0000269|PubMed:8990018"
FT /id="VAR_002191"
FT VARIANT 384
FT /note="K -> N (in CBSD; moderate form)"
FT /id="VAR_008086"
FT VARIANT 391
FT /note="M -> I (in CBSD)"
FT /id="VAR_008087"
FT VARIANT 422
FT /note="P -> L (in CBSD; changed cystathionine beta-synthase
FT activity; impaired stimulation by AdoMet; does not affect
FT homotetramer formation; dbSNP:rs28934892)"
FT /evidence="ECO:0000269|PubMed:12007221,
FT ECO:0000269|PubMed:20506325"
FT /id="VAR_021802"
FT VARIANT 427
FT /note="P -> L (in CBSD; no effect on cystathionine beta-
FT synthase activity; altered stimulation by AdoMet;
FT dbSNP:rs863223434)"
FT /evidence="ECO:0000269|PubMed:23974653,
FT ECO:0000269|PubMed:25044645"
FT /id="VAR_074592"
FT VARIANT 434
FT /note="T -> N (in CBSD; dbSNP:rs1555872506)"
FT /id="VAR_008088"
FT VARIANT 435
FT /note="I -> T (in CBSD; no effect on cystathionine beta-
FT synthase activity; impaired stimulation by AdoMet and
FT AdoHcy; does not affect homotetramer formation)"
FT /evidence="ECO:0000269|PubMed:12007221,
FT ECO:0000269|PubMed:20506325"
FT /id="VAR_008089"
FT VARIANT 439
FT /note="R -> Q (in CBSD; no effect on cystathionine beta-
FT synthase activity; increased homotetramer formation;
FT dbSNP:rs756467921)"
FT /evidence="ECO:0000269|PubMed:10462600,
FT ECO:0000269|PubMed:12124992, ECO:0000269|PubMed:20506325,
FT ECO:0000269|PubMed:9156316"
FT /id="VAR_008090"
FT VARIANT 444
FT /note="D -> N (in CBSD; decreased expression; no effect on
FT cystathionine beta-synthase activity; altered stimulation
FT by AdoMet; increased homotetramer formation;
FT dbSNP:rs28934891)"
FT /evidence="ECO:0000269|PubMed:12007221,
FT ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:23974653,
FT ECO:0000269|PubMed:25044645, ECO:0000269|PubMed:8755636"
FT /id="VAR_002192"
FT VARIANT 446
FT /note="A -> S (in CBSD)"
FT /evidence="ECO:0000269|PubMed:21520339"
FT /id="VAR_066103"
FT VARIANT 449
FT /note="V -> G (in CBSD; no effect on cystathionine beta-
FT synthase activity; altered stimulation by AdoMet)"
FT /evidence="ECO:0000269|PubMed:25044645"
FT /id="VAR_074593"
FT VARIANT 454
FT /note="V -> E (in CBSD)"
FT /evidence="ECO:0000269|PubMed:8528202"
FT /id="VAR_002193"
FT VARIANT 456
FT /note="L -> P (in CBSD; severe; exhibits an activity lower
FT than 4% of the wild-type enzyme; absent capacity to form
FT multimeric quaternary structure)"
FT /evidence="ECO:0000269|PubMed:12815602,
FT ECO:0000269|PubMed:16429402"
FT /id="VAR_021803"
FT VARIANT 466
FT /note="S -> L (in CBSD; increased cystathionine beta-
FT synthase activity; impaired stimulation by AdoMet and
FT AdoHcy; decreased homotetramer formation;
FT dbSNP:rs121964971)"
FT /evidence="ECO:0000269|PubMed:12007221,
FT ECO:0000269|PubMed:20506325"
FT /id="VAR_008091"
FT VARIANT 491
FT /note="R -> C (in CBSD; linked with C-369;
FT dbSNP:rs1339830457)"
FT /id="VAR_008092"
FT VARIANT 500
FT /note="S -> L (in CBSD; no effect on cystathionine beta-
FT synthase activity; altered stimulation by AdoMet;
FT dbSNP:rs755106884)"
FT /evidence="ECO:0000269|PubMed:23974653,
FT ECO:0000269|PubMed:25044645"
FT /id="VAR_074594"
FT VARIANT 526
FT /note="Q -> K (in CBSD; has significantly decreased levels
FT of enzyme activity)"
FT /evidence="ECO:0000269|PubMed:14635102"
FT /id="VAR_046937"
FT VARIANT 534
FT /note="V -> D (in CBSD; linked with S-307)"
FT /id="VAR_008093"
FT VARIANT 539
FT /note="L -> S (in CBSD; loss of cystathionine beta-synthase
FT activity; impaired stimulation by AdoMet and AdoHcy; loss
FT of homotetramer formation; dbSNP:rs121964968)"
FT /evidence="ECO:0000269|PubMed:20506325,
FT ECO:0000269|PubMed:8990018"
FT /id="VAR_002194"
FT VARIANT 540
FT /note="L -> Q (in CBSD; no effect on cystathionine beta-
FT synthase activity; altered stimulation by AdoMet)"
FT /evidence="ECO:0000269|PubMed:23974653,
FT ECO:0000269|PubMed:25044645"
FT /id="VAR_074595"
FT VARIANT 548
FT /note="R -> Q (presents 60% of the wild-type activity;
FT highly reduced capacity to form multimeric quaternary
FT structure; dbSNP:rs150828989)"
FT /evidence="ECO:0000269|PubMed:16429402"
FT /id="VAR_046938"
FT MUTAGEN 272
FT /note="C->A: Reduced heme content and cystathionine beta-
FT synthase activity."
FT /evidence="ECO:0000269|PubMed:12173932"
FT MUTAGEN 275
FT /note="C->S: Reduced heme content and cystathionine beta-
FT synthase activity."
FT /evidence="ECO:0000269|PubMed:12173932"
FT CONFLICT 58
FT /note="R -> P (in Ref. 4; CAA61252)"
FT /evidence="ECO:0000305"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:4COO"
FT STRAND 75..79
FT /evidence="ECO:0007829|PDB:4COO"
FT HELIX 80..82
FT /evidence="ECO:0007829|PDB:4COO"
FT STRAND 83..85
FT /evidence="ECO:0007829|PDB:4COO"
FT STRAND 89..91
FT /evidence="ECO:0007829|PDB:4COO"
FT HELIX 95..98
FT /evidence="ECO:0007829|PDB:4COO"
FT STRAND 103..109
FT /evidence="ECO:0007829|PDB:4COO"
FT HELIX 110..112
FT /evidence="ECO:0007829|PDB:4COO"
FT STRAND 113..117
FT /evidence="ECO:0007829|PDB:4L0D"
FT HELIX 119..132
FT /evidence="ECO:0007829|PDB:4COO"
FT STRAND 141..145
FT /evidence="ECO:0007829|PDB:4COO"
FT HELIX 149..161
FT /evidence="ECO:0007829|PDB:4COO"
FT STRAND 164..170
FT /evidence="ECO:0007829|PDB:4COO"
FT HELIX 175..183
FT /evidence="ECO:0007829|PDB:4COO"
FT STRAND 187..191
FT /evidence="ECO:0007829|PDB:4COO"
FT STRAND 193..195
FT /evidence="ECO:0007829|PDB:5MMS"
FT STRAND 197..199
FT /evidence="ECO:0007829|PDB:4L27"
FT HELIX 203..213
FT /evidence="ECO:0007829|PDB:4COO"
FT STRAND 217..219
FT /evidence="ECO:0007829|PDB:4L28"
FT TURN 222..224
FT /evidence="ECO:0007829|PDB:4COO"
FT HELIX 227..234
FT /evidence="ECO:0007829|PDB:4COO"
FT HELIX 236..243
FT /evidence="ECO:0007829|PDB:4COO"
FT TURN 244..246
FT /evidence="ECO:0007829|PDB:4COO"
FT STRAND 249..254
FT /evidence="ECO:0007829|PDB:4COO"
FT STRAND 256..258
FT /evidence="ECO:0007829|PDB:4COO"
FT HELIX 259..271
FT /evidence="ECO:0007829|PDB:4COO"
FT STRAND 272..274
FT /evidence="ECO:0007829|PDB:1M54"
FT STRAND 276..282
FT /evidence="ECO:0007829|PDB:4COO"
FT STRAND 288..290
FT /evidence="ECO:0007829|PDB:4COO"
FT HELIX 291..294
FT /evidence="ECO:0007829|PDB:4COO"
FT HELIX 317..319
FT /evidence="ECO:0007829|PDB:4COO"
FT STRAND 322..326
FT /evidence="ECO:0007829|PDB:4COO"
FT HELIX 328..342
FT /evidence="ECO:0007829|PDB:4COO"
FT HELIX 348..360
FT /evidence="ECO:0007829|PDB:4COO"
FT HELIX 361..363
FT /evidence="ECO:0007829|PDB:4COO"
FT STRAND 369..374
FT /evidence="ECO:0007829|PDB:4COO"
FT HELIX 378..381
FT /evidence="ECO:0007829|PDB:4COO"
FT TURN 382..386
FT /evidence="ECO:0007829|PDB:4COO"
FT HELIX 388..393
FT /evidence="ECO:0007829|PDB:4COO"
FT HELIX 399..404
FT /evidence="ECO:0007829|PDB:4COO"
FT TURN 408..411
FT /evidence="ECO:0007829|PDB:4UUU"
FT HELIX 414..417
FT /evidence="ECO:0007829|PDB:4UUU"
FT HELIX 431..441
FT /evidence="ECO:0007829|PDB:4UUU"
FT STRAND 444..449
FT /evidence="ECO:0007829|PDB:4UUU"
FT STRAND 455..460
FT /evidence="ECO:0007829|PDB:4UUU"
FT HELIX 461..469
FT /evidence="ECO:0007829|PDB:4UUU"
FT HELIX 479..482
FT /evidence="ECO:0007829|PDB:4UUU"
FT STRAND 489..491
FT /evidence="ECO:0007829|PDB:4UUU"
FT HELIX 496..505
FT /evidence="ECO:0007829|PDB:4UUU"
FT STRAND 509..515
FT /evidence="ECO:0007829|PDB:4UUU"
FT STRAND 526..534
FT /evidence="ECO:0007829|PDB:4UUU"
FT HELIX 536..544
FT /evidence="ECO:0007829|PDB:4UUU"
SQ SEQUENCE 551 AA; 60587 MW; F89E69C67BDE6701 CRC64;
MPSETPQAEV GPTGCPHRSG PHSAKGSLEK GSPEDKEAKE PLWIRPDAPS RCTWQLGRPA
SESPHHHTAP AKSPKILPDI LKKIGDTPMV RINKIGKKFG LKCELLAKCE FFNAGGSVKD
RISLRMIEDA ERDGTLKPGD TIIEPTSGNT GIGLALAAAV RGYRCIIVMP EKMSSEKVDV
LRALGAEIVR TPTNARFDSP ESHVGVAWRL KNEIPNSHIL DQYRNASNPL AHYDTTADEI
LQQCDGKLDM LVASVGTGGT ITGIARKLKE KCPGCRIIGV DPEGSILAEP EELNQTEQTT
YEVEGIGYDF IPTVLDRTVV DKWFKSNDEE AFTFARMLIA QEGLLCGGSA GSTVAVAVKA
AQELQEGQRC VVILPDSVRN YMTKFLSDRW MLQKGFLKEE DLTEKKPWWW HLRVQELGLS
APLTVLPTIT CGHTIEILRE KGFDQAPVVD EAGVILGMVT LGNMLSSLLA GKVQPSDQVG
KVIYKQFKQI RLTDTLGRLS HILEMDHFAL VVHEQIQYHS TGKSSQRQMV FGVVTAIDLL
NFVAAQERDQ K
