CBS_MOUSE
ID CBS_MOUSE Reviewed; 561 AA.
AC Q91WT9; Q91WU3;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Cystathionine beta-synthase {ECO:0000305};
DE EC=4.2.1.22 {ECO:0000250|UniProtKB:P35520};
DE AltName: Full=Beta-thionase;
DE AltName: Full=Serine sulfhydrase;
GN Name=Cbs;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Kidney;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Liver, Pancreas, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 (By
CC similarity). Also involved in the production of hydrogen sulfide, a
CC gasotransmitter with signaling and cytoprotective effects on neurons
CC (By similarity). {ECO:0000250|UniProtKB:P32232,
CC ECO:0000250|UniProtKB:P35520}.
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:0000250|UniProtKB:P35520};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250|UniProtKB:P35520};
CC -!- ACTIVITY REGULATION: Allosterically activated by S-adenosyl-
CC methionine/AdoMet. Activated by S-adenosylhomocysteine/AdoHcy. Binds
CC non-covalently to a heme group that may control the redox sensitivity
CC of the enzyme. {ECO:0000250|UniProtKB:P35520}.
CC -!- PATHWAY: Amino-acid biosynthesis; L-cysteine biosynthesis; L-cysteine
CC from L-homocysteine and L-serine: step 1/2.
CC {ECO:0000250|UniProtKB:P35520}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P35520}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P35520}. Nucleus
CC {ECO:0000250|UniProtKB:P35520}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q91WT9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q91WT9-2; Sequence=VSP_021790;
CC -!- SIMILARITY: Belongs to the cysteine synthase/cystathionine beta-
CC synthase family. {ECO:0000305}.
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DR EMBL; AK077669; BAC36943.1; -; mRNA.
DR EMBL; BC013472; AAH13472.1; -; mRNA.
DR EMBL; BC013480; AAH13480.1; -; mRNA.
DR EMBL; BC026595; AAH26595.1; -; mRNA.
DR CCDS; CCDS28609.1; -. [Q91WT9-1]
DR CCDS; CCDS28610.1; -. [Q91WT9-2]
DR RefSeq; NP_001258282.1; NM_001271353.1. [Q91WT9-2]
DR RefSeq; NP_659104.1; NM_144855.3. [Q91WT9-1]
DR RefSeq; NP_835742.1; NM_178224.3. [Q91WT9-2]
DR RefSeq; XP_006523612.1; XM_006523549.3. [Q91WT9-1]
DR RefSeq; XP_006523613.1; XM_006523550.3. [Q91WT9-1]
DR RefSeq; XP_006523614.1; XM_006523551.3. [Q91WT9-1]
DR AlphaFoldDB; Q91WT9; -.
DR SMR; Q91WT9; -.
DR BioGRID; 198533; 8.
DR DIP; DIP-60823N; -.
DR IntAct; Q91WT9; 1.
DR STRING; 10090.ENSMUSP00000066878; -.
DR iPTMnet; Q91WT9; -.
DR PhosphoSitePlus; Q91WT9; -.
DR SwissPalm; Q91WT9; -.
DR jPOST; Q91WT9; -.
DR MaxQB; Q91WT9; -.
DR PaxDb; Q91WT9; -.
DR PeptideAtlas; Q91WT9; -.
DR PRIDE; Q91WT9; -.
DR ProteomicsDB; 281411; -. [Q91WT9-1]
DR ProteomicsDB; 281412; -. [Q91WT9-2]
DR DNASU; 12411; -.
DR Ensembl; ENSMUST00000067801; ENSMUSP00000066878; ENSMUSG00000024039. [Q91WT9-1]
DR Ensembl; ENSMUST00000078509; ENSMUSP00000077597; ENSMUSG00000024039. [Q91WT9-2]
DR Ensembl; ENSMUST00000118504; ENSMUSP00000113209; ENSMUSG00000024039. [Q91WT9-2]
DR Ensembl; ENSMUST00000236853; ENSMUSP00000158269; ENSMUSG00000024039. [Q91WT9-1]
DR GeneID; 12411; -.
DR KEGG; mmu:12411; -.
DR UCSC; uc008bvl.2; mouse. [Q91WT9-1]
DR UCSC; uc008bvm.2; mouse. [Q91WT9-2]
DR CTD; 875; -.
DR MGI; MGI:88285; Cbs.
DR VEuPathDB; HostDB:ENSMUSG00000024039; -.
DR eggNOG; KOG1252; Eukaryota.
DR GeneTree; ENSGT00510000047027; -.
DR HOGENOM; CLU_021018_0_0_1; -.
DR InParanoid; Q91WT9; -.
DR OMA; KFADDEW; -.
DR OrthoDB; 1016546at2759; -.
DR PhylomeDB; Q91WT9; -.
DR TreeFam; TF300784; -.
DR BRENDA; 4.2.1.22; 3474.
DR Reactome; R-MMU-1614603; Cysteine formation from homocysteine.
DR UniPathway; UPA00136; UER00201.
DR BioGRID-ORCS; 12411; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Cbs; mouse.
DR PRO; PR:Q91WT9; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q91WT9; protein.
DR Bgee; ENSMUSG00000024039; Expressed in left lobe of liver and 175 other tissues.
DR ExpressionAtlas; Q91WT9; baseline and differential.
DR Genevisible; Q91WT9; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0070025; F:carbon monoxide binding; ISO:MGI.
DR GO; GO:0004122; F:cystathionine beta-synthase activity; IMP:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0020037; F:heme binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0072341; F:modified amino acid binding; ISO:MGI.
DR GO; GO:0070026; F:nitric oxide binding; ISO:MGI.
DR GO; GO:0050421; F:nitrite reductase (NO-forming) activity; ISO:MGI.
DR GO; GO:0019825; F:oxygen binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; ISS:UniProtKB.
DR GO; GO:1904047; F:S-adenosyl-L-methionine binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0097746; P:blood vessel diameter maintenance; IMP:MGI.
DR GO; GO:0001974; P:blood vessel remodeling; IMP:MGI.
DR GO; GO:0060351; P:cartilage development involved in endochondral bone morphogenesis; IMP:MGI.
DR GO; GO:0071456; P:cellular response to hypoxia; ISO:MGI.
DR GO; GO:0021587; P:cerebellum morphogenesis; IMP:MGI.
DR GO; GO:0019344; P:cysteine biosynthetic process; IMP:MGI.
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; ISO:MGI.
DR GO; GO:0001958; P:endochondral ossification; IMP:MGI.
DR GO; GO:0043418; P:homocysteine catabolic process; ISS:UniProtKB.
DR GO; GO:0050667; P:homocysteine metabolic process; IMP:MGI.
DR GO; GO:0070814; P:hydrogen sulfide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0019448; P:L-cysteine catabolic process; ISO:MGI.
DR GO; GO:0006565; P:L-serine catabolic process; ISO:MGI.
DR GO; GO:0006563; P:L-serine metabolic process; ISS:UniProtKB.
DR GO; GO:0060135; P:maternal process involved in female pregnancy; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0043506; P:regulation of JUN kinase activity; IMP:MGI.
DR GO; GO:0010749; P:regulation of nitric oxide mediated signal transduction; IMP:MGI.
DR GO; GO:0051593; P:response to folic acid; IMP:MGI.
DR GO; GO:0006801; P:superoxide metabolic process; IMP:MGI.
DR GO; GO:0019346; P:transsulfuration; ISO:MGI.
DR CDD; cd04608; CBS_pair_CBS; 1.
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 Alternative splicing; Amino-acid biosynthesis; CBS domain;
KW Cysteine biosynthesis; Cytoplasm; Heme; Iron; Isopeptide bond; Lyase;
KW Metal-binding; Nucleus; Phosphoprotein; Pyridoxal phosphate;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..561
FT /note="Cystathionine beta-synthase"
FT /id="PRO_0000262592"
FT DOMAIN 414..474
FT /note="CBS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT BINDING 49
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:0000250|UniProtKB:P35520"
FT BINDING 62
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:0000250|UniProtKB:P35520"
FT BINDING 146
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P35520"
FT BINDING 253..257
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P35520"
FT BINDING 346
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P35520"
FT MOD_RES 116
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:P35520"
FT MOD_RES 196
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35520"
FT CROSSLNK 208
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:P35520"
FT VAR_SEQ 514..528
FT /note="SRDQAWSGVVGGPTD -> Y (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_021790"
SQ SEQUENCE 561 AA; 61544 MW; 072CF81AFE10372E CRC64;
MPSGTSQCED GSAGGFQHLD MHSEKRQLEK GPSGDKDRVW IRPDTPSRCT WQLGRAMADS
PHYHTVLTKS PKILPDILRK IGNTPMVRIN KISKNAGLKC ELLAKCEFFN AGGSVKDRIS
LRMIEDAERA GNLKPGDTII EPTSGNTGIG LALAAAVKGY RCIIVMPEKM SMEKVDVLRA
LGAEIVRTPT NARFDSPESH VGVAWRLKNE IPNSHILDQY RNASNPLAHY DDTAEEILQQ
CDGKLDMLVA SAGTGGTITG IARKLKEKCP GCKIIGVDPE GSILAEPEEL NQTEQTAYEV
EGIGYDFIPT VLDRAVVDKW FKSNDEDSFA FARMLIAQEG LLCGGSSGSA MAVAVKAARE
LQEGQRCVVI LPDSVRNYMS KFLSDKWMLQ KGFMKEELSV KRPWWWRLRV QELSLSAPLT
VLPTVTCEDT IAILREKGFD QAPVVNESGA ILGMVTLGNM LSSLLAGKVR PSDEVCKVLY
KQFKPIHLTD TLGTLSHILE MDHFALVVHE QIQSRDQAWS GVVGGPTDCS NGMSSKQQMV
FGVVTAIDLL NFVAAREQTQ T
