GLYM_HUMAN
ID GLYM_HUMAN Reviewed; 504 AA.
AC P34897; B7Z9F1; E7EQ19; E7EU43; O00740; Q8N1A5;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 3.
DT 03-AUG-2022, entry version 223.
DE RecName: Full=Serine hydroxymethyltransferase, mitochondrial;
DE Short=SHMT;
DE EC=2.1.2.1 {ECO:0000269|PubMed:24075985, ECO:0000269|PubMed:25619277, ECO:0000269|PubMed:29364879, ECO:0000269|PubMed:33015733};
DE AltName: Full=Glycine hydroxymethyltransferase;
DE AltName: Full=Serine methylase;
DE Flags: Precursor;
GN Name=SHMT2 {ECO:0000312|HGNC:HGNC:10852};
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 [LARGE SCALE MRNA] (ISOFORM 3).
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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Lymph, Muscle, Ovary, and Uterus;
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-35.
RX PubMed=10828359; DOI=10.1016/s0065-2571(99)00035-7;
RA Snell K., Baumann U., Byrne P.C., Chave K.J., Renwick S.B., Sanders P.G.,
RA Whitehouse S.K.;
RT "The genetic organization and protein crystallographic structure of human
RT serine hydroxymethyltransferase.";
RL Adv. Enzyme Regul. 40:353-403(2000).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 22-504.
RX PubMed=8999870; DOI=10.1074/jbc.272.3.1842;
RA Stover P.J., Chen L.H., Suh J.R., Stover D.M., Keyomarsi K., Shane B.;
RT "Molecular cloning, characterization, and regulation of the human
RT mitochondrial serine hydroxymethyltransferase gene.";
RL J. Biol. Chem. 272:1842-1848(1997).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 31-504 (ISOFORM 1).
RX PubMed=8505317; DOI=10.1016/s0021-9258(19)50286-1;
RA Garrow T.A., Brenner A.A., Whitehead M.V., Chen X.-N., Duncan R.G.,
RA Korenberg J.R., Shane B.;
RT "Cloning of human cDNAs encoding mitochondrial and cytosolic serine
RT hydroxymethyltransferases and chromosomal localization.";
RL J. Biol. Chem. 268:11910-11916(1993).
RN [9]
RP SUBCELLULAR LOCATION, FUNCTION IN ASSOCIATION WITH MITOCHONDRIAL DNA, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=18063578; DOI=10.1074/jbc.m708444200;
RA Bogenhagen D.F., Rousseau D., Burke S.;
RT "The layered structure of human mitochondrial DNA nucleoids.";
RL J. Biol. Chem. 283:3665-3675(2008).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-103; LYS-181; LYS-196; LYS-297;
RP LYS-356; LYS-464; LYS-469 AND LYS-474, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
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 [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21876188; DOI=10.1073/pnas.1103623108;
RA Anderson D.D., Quintero C.M., Stover P.J.;
RT "Identification of a de novo thymidylate biosynthesis pathway in mammalian
RT mitochondria.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:15163-15168(2011).
RN [13]
RP IDENTIFICATION IN THE BRISC COMPLEX, IDENTIFICATION BY MASS SPECTROMETRY,
RP INTERACTION WITH ABRAXAS2, CATALYTIC ACTIVITY, IDENTIFICATION IN A COMPLEX
RP WITH ABRAXAS2 AND IFNAR1, AND SUBCELLULAR LOCATION.
RX PubMed=24075985; DOI=10.1016/j.celrep.2013.08.025;
RA Zheng H., Gupta V., Patterson-Fortin J., Bhattacharya S., Katlinski K.,
RA Wu J., Varghese B., Carbone C.J., Aressy B., Fuchs S.Y., Greenberg R.A.;
RT "A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates interferon
RT responses.";
RL Cell Rep. 5:180-193(2013).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-470, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [15]
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 [16]
RP INTERACTION WITH KIRREL3.
RX PubMed=25902260; DOI=10.1371/journal.pone.0123106;
RA Liu Y.F., Sowell S.M., Luo Y., Chaubey A., Cameron R.S., Kim H.G.,
RA Srivastava A.K.;
RT "Autism and intellectual disability-associated KIRREL3 interacts with
RT neuronal proteins MAP1B and MYO16 with potential roles in
RT neurodevelopment.";
RL PLoS ONE 10:E0123106-E0123106(2015).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [18]
RP SUCCINYLATION AT LYS-280, ACTIVITY REGULATION, SUBUNIT, AND MUTAGENESIS OF
RP LYS-103; LYS-280; LYS-302; LYS-356; LYS-464; LYS-469 AND LYS-474.
RX PubMed=29180469; DOI=10.1158/0008-5472.can-17-1912;
RA Yang X., Wang Z., Li X., Liu B., Liu M., Liu L., Chen S., Ren M., Wang Y.,
RA Yu M., Wang B., Zou J., Zhu W.G., Yin Y., Gu W., Luo J.;
RT "SHMT2 desuccinylation by SIRT5 drives cancer cell proliferation.";
RL Cancer Res. 78:372-386(2018).
RN [19]
RP FUNCTION.
RX PubMed=29452640; DOI=10.1016/j.molcel.2018.01.024;
RA Minton D.R., Nam M., McLaughlin D.J., Shin J., Bayraktar E.C.,
RA Alvarez S.W., Sviderskiy V.O., Papagiannakopoulos T., Sabatini D.M.,
RA Birsoy K., Possemato R.;
RT "Serine catabolism by SHMT2 is required for proper mitochondrial
RT translation initiation and maintenance of formylmethionyl-tRNAs.";
RL Mol. Cell 69:610-621(2018).
RN [20]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF GLU-98; TYR-106 AND
RP LYS-280.
RX PubMed=29364879; DOI=10.1038/nature25460;
RA Morscher R.J., Ducker G.S., Li S.H., Mayer J.A., Gitai Z., Sperl W.,
RA Rabinowitz J.D.;
RT "Mitochondrial translation requires folate-dependent tRNA methylation.";
RL Nature 554:128-132(2018).
RN [21]
RP INVOLVEMENT IN NEDCASB, VARIANTS NEDCASB SER-157; ARG-186; ASP-379;
RP SER-423; PRO-435 AND ALA-499, CHARACTERIZATION OF VARIANT NEDCASB ALA-499,
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=33015733; DOI=10.1007/s00401-020-02223-w;
RG SHMT2 Working Group;
RA Garcia-Cazorla A., Verdura E., Julia-Palacios N., Anderson E.N.,
RA Goicoechea L., Planas-Serra L., Tsogtbaatar E., Dsouza N.R., Schlueter A.,
RA Urreizti R., Tarnowski J.M., Gavrilova R.H., Ruiz M., Rodriguez-Palmero A.,
RA Fourcade S., Cogne B., Besnard T., Vincent M., Bezieau S., Folmes C.D.,
RA Zimmermann M.T., Klee E.W., Pandey U.B., Artuch R., Cousin M.A., Pujol A.;
RT "Impairment of the mitochondrial one-carbon metabolism enzyme SHMT2 causes
RT a novel brain and heart developmental syndrome.";
RL Acta Neuropathol. 140:971-975(2020).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.04 ANGSTROMS) OF 17-504.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human mitochondrial serine hydroxymethyltransferase
RT 2.";
RL Submitted (OCT-2010) to the PDB data bank.
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 22-504, FUNCTION, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND COFACTOR.
RX PubMed=25619277; DOI=10.1111/febs.13211;
RA Giardina G., Brunotti P., Fiascarelli A., Cicalini A., Costa M.G.,
RA Buckle A.M., di Salvo M.L., Giorgi A., Marani M., Paone A., Rinaldo S.,
RA Paiardini A., Contestabile R., Cutruzzola F.;
RT "How pyridoxal 5'-phosphate differentially regulates human cytosolic and
RT mitochondrial serine hydroxymethyltransferase oligomeric state.";
RL FEBS J. 282:1225-1241(2015).
CC -!- FUNCTION: Catalyzes the cleavage of serine to glycine accompanied with
CC the production of 5,10-methylenetetrahydrofolate, an essential
CC intermediate for purine biosynthesis (PubMed:24075985, PubMed:29364879,
CC PubMed:33015733 PubMed:25619277, PubMed:33015733). Serine provides the
CC major source of folate one-carbon in cells by catalyzing the transfer
CC of one carbon from serine to tetrahydrofolate (PubMed:25619277).
CC Contributes to the de novo mitochondrial thymidylate biosynthesis
CC pathway via its role in glycine and tetrahydrofolate metabolism:
CC thymidylate biosynthesis is required to prevent uracil accumulation in
CC mtDNA (PubMed:21876188). Also required for mitochondrial translation by
CC producing 5,10-methylenetetrahydrofolate; 5,10-
CC methylenetetrahydrofolate providing methyl donors to produce the
CC taurinomethyluridine base at the wobble position of some mitochondrial
CC tRNAs (PubMed:29452640, PubMed:29364879). Associates with mitochondrial
CC DNA (PubMed:18063578). In addition to its role in mitochondria, also
CC plays a role in the deubiquitination of target proteins as component of
CC the BRISC complex: required for IFNAR1 deubiquitination by the BRISC
CC complex (PubMed:24075985). {ECO:0000269|PubMed:18063578,
CC ECO:0000269|PubMed:21876188, ECO:0000269|PubMed:24075985,
CC ECO:0000269|PubMed:25619277, ECO:0000269|PubMed:29364879,
CC ECO:0000269|PubMed:29452640, ECO:0000269|PubMed:33015733}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + glycine + H2O =
CC (6S)-5,6,7,8-tetrahydrofolate + L-serine; Xref=Rhea:RHEA:15481,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15636, ChEBI:CHEBI:33384,
CC ChEBI:CHEBI:57305, ChEBI:CHEBI:57453; EC=2.1.2.1;
CC Evidence={ECO:0000269|PubMed:24075985, ECO:0000269|PubMed:25619277,
CC ECO:0000269|PubMed:29364879, ECO:0000269|PubMed:33015733};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:15483;
CC Evidence={ECO:0000305|PubMed:33015733};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|PubMed:25619277, ECO:0000305|PubMed:29364879};
CC -!- ACTIVITY REGULATION: Hydroxymethyltransferase is inhibited by
CC succinylation at Lys-280. {ECO:0000269|PubMed:29180469}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=278 uM for L-serine {ECO:0000269|PubMed:25619277};
CC KM=23 uM for tetrahydrofolate {ECO:0000269|PubMed:25619277};
CC -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC {ECO:0000305|PubMed:25619277, ECO:0000305|PubMed:33015733}.
CC -!- SUBUNIT: Homotetramer; in the presence of bound pyridoxal 5'-phosphate
CC (PubMed:29180469, PubMed:25619277). Homodimer; in the absence of bound
CC pyridoxal 5'-phosphate (PubMed:29180469, PubMed:25619277). Pyridoxal
CC 5'-phosphate binding mediates an important conformation change that is
CC required for tetramerization (PubMed:25619277). Interacts with
CC ABRAXAS2; the interaction is direct. Identified in a complex with
CC ABRAXAS2 and the other subunits of the BRISC complex, at least composed
CC of the ABRAXAS2, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Identified in a
CC complex with ABRAXAS2 and IFNAR1 (PubMed:24075985). Interacts with
CC KIRREL3 (PubMed:25902260). {ECO:0000269|PubMed:24075985,
CC ECO:0000269|PubMed:25619277, ECO:0000269|PubMed:25902260,
CC ECO:0000269|PubMed:29180469}.
CC -!- INTERACTION:
CC P34897; Q15041: ARL6IP1; NbExp=6; IntAct=EBI-352908, EBI-714543;
CC P34897; Q9Y376: CAB39; NbExp=3; IntAct=EBI-352908, EBI-306905;
CC P34897; Q96DZ9: CMTM5; NbExp=4; IntAct=EBI-352908, EBI-2548702;
CC P34897; Q96DZ9-2: CMTM5; NbExp=3; IntAct=EBI-352908, EBI-11522780;
CC P34897; Q8IZU9: KIRREL3; NbExp=4; IntAct=EBI-352908, EBI-16427312;
CC P34897; Q969L2: MAL2; NbExp=3; IntAct=EBI-352908, EBI-944295;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:21876188,
CC ECO:0000269|PubMed:24075985}. Mitochondrion matrix, mitochondrion
CC nucleoid {ECO:0000269|PubMed:18063578}. Mitochondrion inner membrane
CC {ECO:0000269|PubMed:21876188}. Cytoplasm {ECO:0000269|PubMed:24075985}.
CC Nucleus {ECO:0000269|PubMed:24075985}. Note=Mainly localizes in the
CC mitochondrion. Also found in the cytoplasm and nucleus as part of the
CC BRISC complex (PubMed:24075985). {ECO:0000269|PubMed:24075985}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P34897-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P34897-2; Sequence=VSP_043088;
CC Name=3;
CC IsoId=P34897-3; Sequence=VSP_043844;
CC -!- PTM: Succinylation at Lys-280 inhibits the hydroxymethyltransferase
CC activity. Desuccinylation by SIRT5 restores the activity, leading to
CC promote cell proliferation. {ECO:0000269|PubMed:29180469}.
CC -!- DISEASE: Neurodevelopmental disorder with cardiomyopathy, spasticity,
CC and brain abnormalities (NEDCASB) [MIM:619121]: An autosomal recessive
CC neurodevelopmental disorder characterized by global developmental
CC delay, moderate to severe intellectual disability, spastic paraparesis,
CC ataxia, and/or peripheral neuropathy. Patients also exhibit dysmorphic
CC features and congenital microcephaly. Most affected individuals develop
CC progressive hypertrophic cardiomyopathy in childhood or have cardiac
CC developmental anomalies. Brain imaging shows corpus callosum
CC abnormalities in all patients, and perisylvian polymicrogyria-like
CC pattern in some individuals. {ECO:0000269|PubMed:33015733}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: In eukaryotes there are two forms of the enzymes: a
CC cytosolic one and a mitochondrial one.
CC -!- SIMILARITY: Belongs to the SHMT family. {ECO:0000305}.
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DR EMBL; AK315916; BAH14287.1; -; mRNA.
DR EMBL; BT006866; AAP35512.1; -; mRNA.
DR EMBL; AC137834; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471054; EAW96994.1; -; Genomic_DNA.
DR EMBL; CH471054; EAW96998.1; -; Genomic_DNA.
DR EMBL; BC011911; AAH11911.1; -; mRNA.
DR EMBL; BC013677; AAH13677.1; -; mRNA.
DR EMBL; BC032584; AAH32584.1; -; mRNA.
DR EMBL; BC044211; AAH44211.1; -; mRNA.
DR EMBL; Y12331; CAA72999.1; -; Genomic_DNA.
DR EMBL; U23143; AAA64572.1; -; Genomic_DNA.
DR EMBL; L11932; AAA63258.1; -; mRNA.
DR CCDS; CCDS53805.1; -. [P34897-3]
DR CCDS; CCDS55837.1; -. [P34897-2]
DR CCDS; CCDS8934.1; -. [P34897-1]
DR PIR; B46746; B46746.
DR RefSeq; NP_001159828.1; NM_001166356.1. [P34897-2]
DR RefSeq; NP_001159829.1; NM_001166357.1. [P34897-3]
DR RefSeq; NP_001159830.1; NM_001166358.1. [P34897-3]
DR RefSeq; NP_001159831.1; NM_001166359.1. [P34897-3]
DR RefSeq; NP_005403.2; NM_005412.5. [P34897-1]
DR PDB; 4PVF; X-ray; 2.60 A; A/B=22-504.
DR PDB; 5V7I; X-ray; 2.47 A; A/B=29-504.
DR PDB; 5X3V; X-ray; 2.85 A; A/B=22-504.
DR PDB; 6DK3; X-ray; 2.04 A; A=17-504.
DR PDB; 6H3C; EM; 3.90 A; E/J=17-504.
DR PDB; 6M5O; X-ray; 2.30 A; A/B=17-504.
DR PDB; 6QVG; X-ray; 2.32 A; A/B=1-504.
DR PDB; 6QVL; X-ray; 2.28 A; A/B=1-504.
DR PDB; 6R8F; EM; 3.80 A; K/L=1-504.
DR PDB; 7BYI; X-ray; 2.76 A; A/B=22-504.
DR PDBsum; 4PVF; -.
DR PDBsum; 5V7I; -.
DR PDBsum; 5X3V; -.
DR PDBsum; 6DK3; -.
DR PDBsum; 6H3C; -.
DR PDBsum; 6M5O; -.
DR PDBsum; 6QVG; -.
DR PDBsum; 6QVL; -.
DR PDBsum; 6R8F; -.
DR PDBsum; 7BYI; -.
DR AlphaFoldDB; P34897; -.
DR SMR; P34897; -.
DR BioGRID; 112368; 637.
DR CORUM; P34897; -.
DR IntAct; P34897; 123.
DR MINT; P34897; -.
DR STRING; 9606.ENSP00000333667; -.
DR BindingDB; P34897; -.
DR ChEMBL; CHEMBL4295747; -.
DR DrugBank; DB11638; Artenimol.
DR DrugBank; DB00145; Glycine.
DR DrugBank; DB00114; Pyridoxal phosphate.
DR DrugBank; DB00116; Tetrahydrofolic acid.
DR GlyGen; P34897; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P34897; -.
DR MetOSite; P34897; -.
DR PhosphoSitePlus; P34897; -.
DR SwissPalm; P34897; -.
DR BioMuta; SHMT2; -.
DR DMDM; 6226865; -.
DR EPD; P34897; -.
DR jPOST; P34897; -.
DR MassIVE; P34897; -.
DR MaxQB; P34897; -.
DR PaxDb; P34897; -.
DR PeptideAtlas; P34897; -.
DR PRIDE; P34897; -.
DR ProteomicsDB; 54948; -. [P34897-1]
DR ProteomicsDB; 54949; -. [P34897-2]
DR ProteomicsDB; 54950; -. [P34897-3]
DR Antibodypedia; 16145; 259 antibodies from 30 providers.
DR DNASU; 6472; -.
DR Ensembl; ENST00000328923.8; ENSP00000333667.3; ENSG00000182199.11. [P34897-1]
DR Ensembl; ENST00000414700.7; ENSP00000406881.3; ENSG00000182199.11. [P34897-3]
DR Ensembl; ENST00000449049.7; ENSP00000413770.3; ENSG00000182199.11. [P34897-3]
DR Ensembl; ENST00000553474.5; ENSP00000452419.1; ENSG00000182199.11. [P34897-3]
DR Ensembl; ENST00000557487.5; ENSP00000452315.1; ENSG00000182199.11. [P34897-2]
DR GeneID; 6472; -.
DR KEGG; hsa:6472; -.
DR MANE-Select; ENST00000328923.8; ENSP00000333667.3; NM_005412.6; NP_005403.2.
DR UCSC; uc001sni.3; human. [P34897-1]
DR CTD; 6472; -.
DR DisGeNET; 6472; -.
DR GeneCards; SHMT2; -.
DR HGNC; HGNC:10852; SHMT2.
DR HPA; ENSG00000182199; Tissue enhanced (liver).
DR MalaCards; SHMT2; -.
DR MIM; 138450; gene.
DR MIM; 619121; phenotype.
DR neXtProt; NX_P34897; -.
DR OpenTargets; ENSG00000182199; -.
DR PharmGKB; PA35755; -.
DR VEuPathDB; HostDB:ENSG00000182199; -.
DR eggNOG; KOG2467; Eukaryota.
DR GeneTree; ENSGT00390000002762; -.
DR HOGENOM; CLU_022477_0_1_1; -.
DR InParanoid; P34897; -.
DR OMA; RCQHSEV; -.
DR PhylomeDB; P34897; -.
DR TreeFam; TF314667; -.
DR BioCyc; MetaCyc:HS00049-MON; -.
DR BRENDA; 2.1.2.1; 2681.
DR PathwayCommons; P34897; -.
DR Reactome; R-HSA-196757; Metabolism of folate and pterines.
DR Reactome; R-HSA-9013408; RHOG GTPase cycle.
DR SABIO-RK; P34897; -.
DR SignaLink; P34897; -.
DR SIGNOR; P34897; -.
DR UniPathway; UPA00193; -.
DR BioGRID-ORCS; 6472; 36 hits in 1079 CRISPR screens.
DR ChiTaRS; SHMT2; human.
DR EvolutionaryTrace; P34897; -.
DR GenomeRNAi; 6472; -.
DR Pharos; P34897; Tchem.
DR PRO; PR:P34897; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P34897; protein.
DR Bgee; ENSG00000182199; Expressed in tendon of biceps brachii and 207 other tissues.
DR ExpressionAtlas; P34897; baseline and differential.
DR Genevisible; P34897; HS.
DR GO; GO:0070552; C:BRISC complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IEA:Ensembl.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:0042645; C:mitochondrial nucleoid; IDA:BHF-UCL.
DR GO; GO:0005739; C:mitochondrion; IDA:BHF-UCL.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0004372; F:glycine hydroxymethyltransferase activity; IDA:UniProtKB.
DR GO; GO:0008732; F:L-allo-threonine aldolase activity; IEA:Ensembl.
DR GO; GO:0048027; F:mRNA 5'-UTR binding; IBA:GO_Central.
DR GO; GO:0000900; F:mRNA regulatory element binding translation repressor activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IBA:GO_Central.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IDA:UniProtKB.
DR GO; GO:0070905; F:serine binding; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IBA:GO_Central.
DR GO; GO:0046655; P:folic acid metabolic process; IBA:GO_Central.
DR GO; GO:0019264; P:glycine biosynthetic process from serine; IBA:GO_Central.
DR GO; GO:0006544; P:glycine metabolic process; IDA:UniProtKB.
DR GO; GO:0006564; P:L-serine biosynthetic process; IEA:Ensembl.
DR GO; GO:0006565; P:L-serine catabolic process; IBA:GO_Central.
DR GO; GO:0006563; P:L-serine metabolic process; IDA:UniProtKB.
DR GO; GO:0006730; P:one-carbon metabolic process; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; IMP:UniProtKB.
DR GO; GO:0051262; P:protein tetramerization; IDA:UniProtKB.
DR GO; GO:0009113; P:purine nucleobase biosynthetic process; IBA:GO_Central.
DR GO; GO:1903715; P:regulation of aerobic respiration; IMP:UniProtKB.
DR GO; GO:0070129; P:regulation of mitochondrial translation; IMP:UniProtKB.
DR GO; GO:0002082; P:regulation of oxidative phosphorylation; IMP:UniProtKB.
DR GO; GO:0034340; P:response to type I interferon; IDA:UniProtKB.
DR GO; GO:0035999; P:tetrahydrofolate interconversion; IBA:GO_Central.
DR GO; GO:0046653; P:tetrahydrofolate metabolic process; IDA:UniProtKB.
DR CDD; cd00378; SHMT; 1.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR HAMAP; MF_00051; SHMT; 1.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR InterPro; IPR001085; Ser_HO-MeTrfase.
DR InterPro; IPR019798; Ser_HO-MeTrfase_PLP_BS.
DR InterPro; IPR039429; SHMT-like_dom.
DR PANTHER; PTHR11680; PTHR11680; 1.
DR Pfam; PF00464; SHMT; 1.
DR PIRSF; PIRSF000412; SHMT; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
DR PROSITE; PS00096; SHMT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cardiomyopathy; Cytoplasm;
KW Disease variant; Intellectual disability; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Mitochondrion nucleoid; Nucleus;
KW One-carbon metabolism; Phosphoprotein; Pyridoxal phosphate;
KW Reference proteome; Transferase; Transit peptide.
FT TRANSIT 1..29
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:P14519"
FT CHAIN 30..504
FT /note="Serine hydroxymethyltransferase, mitochondrial"
FT /id="PRO_0000032562"
FT REGION 30..51
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 103
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 181
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 196
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 280
FT /note="N6-(pyridoxal phosphate)lysine; alternate"
FT /evidence="ECO:0000305|PubMed:29364879"
FT MOD_RES 280
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:29180469"
FT MOD_RES 297
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 356
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 464
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 469
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 470
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 474
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 1..21
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043844"
FT VAR_SEQ 199..208
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_043088"
FT VARIANT 157
FT /note="P -> S (in NEDCASB; unknown pathological
FT significance; dbSNP:rs1426413125)"
FT /evidence="ECO:0000269|PubMed:33015733"
FT /id="VAR_085466"
FT VARIANT 186
FT /note="T -> R (in NEDCASB; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:33015733"
FT /id="VAR_085467"
FT VARIANT 379
FT /note="N -> D (in NEDCASB; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:33015733"
FT /id="VAR_085468"
FT VARIANT 423
FT /note="G -> S (in NEDCASB; unknown pathological
FT significance; dbSNP:rs751223752)"
FT /evidence="ECO:0000269|PubMed:33015733"
FT /id="VAR_085469"
FT VARIANT 435
FT /note="Q -> P (in NEDCASB; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:33015733"
FT /id="VAR_085470"
FT VARIANT 499
FT /note="P -> A (in NEDCASB; no effect on protein abundance;
FT decreased glycine hydroxymethyltransferase activity;
FT associated with altered mitochondrial redox metabolism)"
FT /evidence="ECO:0000269|PubMed:33015733"
FT /id="VAR_085471"
FT MUTAGEN 98
FT /note="E->L: Abolishes serine hydroxymethyltransferase
FT activity, leading to oxidative phosphorylation deficiency;
FT when associated with F-106."
FT /evidence="ECO:0000269|PubMed:29364879"
FT MUTAGEN 103
FT /note="K->R,E: Does not affect succinylation level or
FT hydroxymethyltransferase activity."
FT /evidence="ECO:0000269|PubMed:29180469"
FT MUTAGEN 106
FT /note="Y->F: Abolishes serine hydroxymethyltransferase
FT activity, leading to oxidative phosphorylation deficiency;
FT when associated with L-98."
FT /evidence="ECO:0000269|PubMed:29364879"
FT MUTAGEN 280
FT /note="K->Q: Abolishes pyridoxal phosphate-binding, leading
FT to oxidative phosphorylation deficiency."
FT /evidence="ECO:0000269|PubMed:29364879"
FT MUTAGEN 280
FT /note="K->R,E: Decreased succinylation level and
FT hydroxymethyltransferase activity."
FT /evidence="ECO:0000269|PubMed:29180469"
FT MUTAGEN 302
FT /note="K->R,E: Does not affect succinylation level or
FT hydroxymethyltransferase activity."
FT /evidence="ECO:0000269|PubMed:29180469"
FT MUTAGEN 356
FT /note="K->R,E: Does not affect succinylation level or
FT hydroxymethyltransferase activity."
FT /evidence="ECO:0000269|PubMed:29180469"
FT MUTAGEN 464
FT /note="K->R,E: Does not affect succinylation level or
FT hydroxymethyltransferase activity."
FT /evidence="ECO:0000269|PubMed:29180469"
FT MUTAGEN 469
FT /note="K->R,E: Does not affect succinylation level or
FT hydroxymethyltransferase activity."
FT /evidence="ECO:0000269|PubMed:29180469"
FT MUTAGEN 474
FT /note="K->R,E: Does not affect succinylation level or
FT hydroxymethyltransferase activity."
FT /evidence="ECO:0000269|PubMed:29180469"
FT CONFLICT 308
FT /note="P -> L (in Ref. 8; AAA63258)"
FT /evidence="ECO:0000305"
FT HELIX 49..52
FT /evidence="ECO:0007829|PDB:6DK3"
FT HELIX 54..69
FT /evidence="ECO:0007829|PDB:6DK3"
FT STRAND 70..72
FT /evidence="ECO:0007829|PDB:6DK3"
FT HELIX 82..88
FT /evidence="ECO:0007829|PDB:6DK3"
FT HELIX 91..94
FT /evidence="ECO:0007829|PDB:6DK3"
FT STRAND 103..107
FT /evidence="ECO:0007829|PDB:6QVL"
FT HELIX 111..126
FT /evidence="ECO:0007829|PDB:6DK3"
FT TURN 131..133
FT /evidence="ECO:0007829|PDB:6DK3"
FT STRAND 134..137
FT /evidence="ECO:0007829|PDB:6DK3"
FT HELIX 143..154
FT /evidence="ECO:0007829|PDB:6DK3"
FT STRAND 160..164
FT /evidence="ECO:0007829|PDB:6QVL"
FT HELIX 166..168
FT /evidence="ECO:0007829|PDB:6QVL"
FT HELIX 172..174
FT /evidence="ECO:0007829|PDB:6QVL"
FT HELIX 186..189
FT /evidence="ECO:0007829|PDB:6QVL"
FT STRAND 190..195
FT /evidence="ECO:0007829|PDB:6QVL"
FT TURN 199..201
FT /evidence="ECO:0007829|PDB:6DK3"
FT STRAND 202..204
FT /evidence="ECO:0007829|PDB:6QVL"
FT HELIX 206..216
FT /evidence="ECO:0007829|PDB:6DK3"
FT STRAND 219..223
FT /evidence="ECO:0007829|PDB:6DK3"
FT HELIX 234..244
FT /evidence="ECO:0007829|PDB:6DK3"
FT STRAND 247..251
FT /evidence="ECO:0007829|PDB:6DK3"
FT HELIX 253..255
FT /evidence="ECO:0007829|PDB:6DK3"
FT HELIX 256..260
FT /evidence="ECO:0007829|PDB:6DK3"
FT HELIX 267..269
FT /evidence="ECO:0007829|PDB:6DK3"
FT STRAND 272..280
FT /evidence="ECO:0007829|PDB:6DK3"
FT STRAND 288..293
FT /evidence="ECO:0007829|PDB:6DK3"
FT STRAND 295..299
FT /evidence="ECO:0007829|PDB:6DK3"
FT STRAND 301..303
FT /evidence="ECO:0007829|PDB:6M5O"
FT STRAND 306..308
FT /evidence="ECO:0007829|PDB:6DK3"
FT HELIX 312..319
FT /evidence="ECO:0007829|PDB:6DK3"
FT TURN 320..323
FT /evidence="ECO:0007829|PDB:6DK3"
FT HELIX 329..342
FT /evidence="ECO:0007829|PDB:6DK3"
FT HELIX 345..367
FT /evidence="ECO:0007829|PDB:6DK3"
FT HELIX 373..375
FT /evidence="ECO:0007829|PDB:6DK3"
FT STRAND 378..385
FT /evidence="ECO:0007829|PDB:6DK3"
FT HELIX 387..389
FT /evidence="ECO:0007829|PDB:6DK3"
FT HELIX 393..402
FT /evidence="ECO:0007829|PDB:6DK3"
FT STRAND 408..410
FT /evidence="ECO:0007829|PDB:6DK3"
FT STRAND 418..420
FT /evidence="ECO:0007829|PDB:6DK3"
FT STRAND 422..428
FT /evidence="ECO:0007829|PDB:6DK3"
FT HELIX 429..433
FT /evidence="ECO:0007829|PDB:6DK3"
FT HELIX 438..460
FT /evidence="ECO:0007829|PDB:6DK3"
FT HELIX 465..474
FT /evidence="ECO:0007829|PDB:6DK3"
FT HELIX 476..493
FT /evidence="ECO:0007829|PDB:6DK3"
SQ SEQUENCE 504 AA; 55993 MW; 7A13AF741C68FFD6 CRC64;
MLYFSLFWAA RPLQRCGQLV RMAIRAQHSN AAQTQTGEAN RGWTGQESLS DSDPEMWELL
QREKDRQCRG LELIASENFC SRAALEALGS CLNNKYSEGY PGKRYYGGAE VVDEIELLCQ
RRALEAFDLD PAQWGVNVQP YSGSPANLAV YTALLQPHDR IMGLDLPDGG HLTHGYMSDV
KRISATSIFF ESMPYKLNPK TGLIDYNQLA LTARLFRPRL IIAGTSAYAR LIDYARMREV
CDEVKAHLLA DMAHISGLVA AKVIPSPFKH ADIVTTTTHK TLRGARSGLI FYRKGVKAVD
PKTGREIPYT FEDRINFAVF PSLQGGPHNH AIAAVAVALK QACTPMFREY SLQVLKNARA
MADALLERGY SLVSGGTDNH LVLVDLRPKG LDGARAERVL ELVSITANKN TCPGDRSAIT
PGGLRLGAPA LTSRQFREDD FRRVVDFIDE GVNIGLEVKS KTAKLQDFKS FLLKDSETSQ
RLANLRQRVE QFARAFPMPG FDEH
