Full text data of SHMT1
SHMT1
[Confidence: low (only semi-automatic identification from reviews)]
Serine hydroxymethyltransferase, cytosolic; SHMT; 2.1.2.1 (Glycine hydroxymethyltransferase; Serine methylase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Serine hydroxymethyltransferase, cytosolic; SHMT; 2.1.2.1 (Glycine hydroxymethyltransferase; Serine methylase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P34896
ID GLYC_HUMAN Reviewed; 483 AA.
AC P34896; D3DXD0; Q96HY0; Q9UMD1; Q9UMD2;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1994, sequence version 1.
DT 22-JAN-2014, entry version 145.
DE RecName: Full=Serine hydroxymethyltransferase, cytosolic;
DE Short=SHMT;
DE EC=2.1.2.1;
DE AltName: Full=Glycine hydroxymethyltransferase;
DE AltName: Full=Serine methylase;
GN Name=SHMT1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8505317;
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Xu L., Mangum J.H., Robertson D.L.;
RL Submitted (JAN-1994) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Mammary gland;
RX PubMed=9056951;
RA Chave K.J., Snell K., Sanders P.G.;
RT "Isolation and characterisation of human genomic sequences encoding
RT cytosolic serine hydroxymethyltransferase.";
RL Biochem. Soc. Trans. 25:53-53(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT PHE-474.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP PHE-474.
RC TISSUE=Bone marrow, Lymph, and Testis;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-271 (ISOFORM 2), AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [7]
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.,
RA Buerckstuemmer T., 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 [8]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 11-480.
RX PubMed=9753690; DOI=10.1016/S0969-2126(98)00112-9;
RA Renwick S.B., Snell K., Baumann U.;
RT "The crystal structure of human cytosolic serine
RT hydroxymethyltransferase: a target for cancer chemotherapy.";
RL Structure 6:1105-1116(1998).
CC -!- FUNCTION: Interconversion of serine and glycine.
CC -!- CATALYTIC ACTIVITY: 5,10-methylenetetrahydrofolate + glycine +
CC H(2)O = tetrahydrofolate + L-serine.
CC -!- COFACTOR: Pyridoxal phosphate.
CC -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC -!- SUBUNIT: Homotetramer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P34896-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P34896-2; Sequence=VSP_006095;
CC Note=Contains a N6-acetyllysine at position 271;
CC Name=3;
CC IsoId=P34896-3; Sequence=VSP_006096;
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.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; L11931; AAA63257.1; -; mRNA.
DR EMBL; L23928; AAA36020.1; -; mRNA.
DR EMBL; L23928; AAA36019.1; -; mRNA.
DR EMBL; L23928; AAA36018.1; -; mRNA.
DR EMBL; Y14485; CAB54838.1; -; mRNA.
DR EMBL; Y14486; CAB54839.1; -; mRNA.
DR EMBL; Y14487; CAB54840.1; -; mRNA.
DR EMBL; CH471196; EAW55637.1; -; Genomic_DNA.
DR EMBL; CH471196; EAW55640.1; -; Genomic_DNA.
DR EMBL; CH471196; EAW55641.1; -; Genomic_DNA.
DR EMBL; BC007979; AAH07979.1; -; mRNA.
DR EMBL; BC022874; AAH22874.1; -; mRNA.
DR EMBL; BC038598; AAH38598.1; -; mRNA.
DR PIR; A46746; A46746.
DR RefSeq; NP_004160.3; NM_004169.4.
DR RefSeq; NP_683718.1; NM_148918.2.
DR RefSeq; XP_005256824.1; XM_005256767.1.
DR UniGene; Hs.513987; -.
DR UniGene; Hs.636044; -.
DR PDB; 1BJ4; X-ray; 2.65 A; A=11-480.
DR PDBsum; 1BJ4; -.
DR ProteinModelPortal; P34896; -.
DR SMR; P34896; 11-480.
DR IntAct; P34896; 5.
DR STRING; 9606.ENSP00000318868; -.
DR BindingDB; P34896; -.
DR ChEMBL; CHEMBL1772927; -.
DR DrugBank; DB00145; Glycine.
DR DrugBank; DB01055; Mimosine.
DR DrugBank; DB00114; Pyridoxal Phosphate.
DR DrugBank; DB00116; Tetrahydrofolic acid.
DR PhosphoSite; P34896; -.
DR DMDM; 462184; -.
DR PaxDb; P34896; -.
DR PRIDE; P34896; -.
DR DNASU; 6470; -.
DR Ensembl; ENST00000316694; ENSP00000318868; ENSG00000176974.
DR Ensembl; ENST00000352886; ENSP00000345881; ENSG00000176974.
DR Ensembl; ENST00000354098; ENSP00000318805; ENSG00000176974.
DR GeneID; 6470; -.
DR KEGG; hsa:6470; -.
DR UCSC; uc002gsz.3; human.
DR CTD; 6470; -.
DR GeneCards; GC17M018231; -.
DR HGNC; HGNC:10850; SHMT1.
DR HPA; HPA023314; -.
DR MIM; 182144; gene.
DR neXtProt; NX_P34896; -.
DR PharmGKB; PA35753; -.
DR eggNOG; COG0112; -.
DR HOGENOM; HOG000239405; -.
DR HOVERGEN; HBG002807; -.
DR InParanoid; P34896; -.
DR KO; K00600; -.
DR OMA; PEFRLYQ; -.
DR OrthoDB; EOG7327NN; -.
DR BioCyc; MetaCyc:HS11114-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR UniPathway; UPA00193; -.
DR ChiTaRS; SHMT1; human.
DR EvolutionaryTrace; P34896; -.
DR GenomeRNAi; 6470; -.
DR NextBio; 25133; -.
DR PRO; PR:P34896; -.
DR ArrayExpress; P34896; -.
DR Bgee; P34896; -.
DR CleanEx; HS_SHMT1; -.
DR Genevestigator; P34896; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0016597; F:amino acid binding; IEA:Ensembl.
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:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IDA:UniProtKB.
DR GO; GO:0045329; P:carnitine biosynthetic process; TAS:Reactome.
DR GO; GO:0046655; P:folic acid metabolic process; IDA:UniProtKB.
DR GO; GO:0019264; P:glycine biosynthetic process from serine; IEA:Ensembl.
DR GO; GO:0006565; P:L-serine catabolic process; IDA:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; IEA:Ensembl.
DR GO; GO:0051262; P:protein tetramerization; IDA:UniProtKB.
DR GO; GO:0009113; P:purine nucleobase biosynthetic process; IDA:UniProtKB.
DR GO; GO:0035999; P:tetrahydrofolate interconversion; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major_sub1.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_major_sub2.
DR InterPro; IPR001085; Ser_HO-MeTrfase.
DR InterPro; IPR019798; Ser_HO-MeTrfase_PLP_BS.
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; Complete proteome;
KW Cytoplasm; One-carbon metabolism; Polymorphism; Pyridoxal phosphate;
KW Reference proteome; Transferase.
FT INIT_MET 1 1 Removed (By similarity).
FT CHAIN 2 483 Serine hydroxymethyltransferase,
FT cytosolic.
FT /FTId=PRO_0000113504.
FT MOD_RES 257 257 N6-(pyridoxal phosphate)lysine.
FT VAR_SEQ 273 352 Missing (in isoform 3).
FT /FTId=VSP_006096.
FT VAR_SEQ 274 312 Missing (in isoform 2).
FT /FTId=VSP_006095.
FT VARIANT 340 340 E -> Q (in dbSNP:rs7215148).
FT /FTId=VAR_059795.
FT VARIANT 474 474 L -> F (in dbSNP:rs1979277).
FT /FTId=VAR_022010.
FT HELIX 13 21
FT HELIX 26 29
FT HELIX 31 46
FT STRAND 47 49
FT HELIX 59 65
FT HELIX 68 70
FT STRAND 80 84
FT HELIX 87 103
FT TURN 108 110
FT STRAND 111 114
FT HELIX 120 131
FT STRAND 137 141
FT HELIX 143 145
FT HELIX 149 151
FT HELIX 162 166
FT STRAND 167 172
FT TURN 176 178
FT HELIX 183 193
FT STRAND 196 200
FT HELIX 211 220
FT STRAND 224 228
FT HELIX 230 232
FT HELIX 233 237
FT HELIX 244 246
FT STRAND 249 256
FT HELIX 257 259
FT STRAND 265 270
FT STRAND 272 276
FT TURN 278 280
FT STRAND 283 285
FT HELIX 288 296
FT TURN 297 300
FT HELIX 306 318
FT HELIX 322 344
FT STRAND 355 362
FT HELIX 363 366
FT HELIX 370 379
FT STRAND 385 387
FT STRAND 400 404
FT HELIX 406 410
FT HELIX 415 438
FT HELIX 445 452
FT STRAND 453 455
FT HELIX 458 472
SQ SEQUENCE 483 AA; 53083 MW; 6CDD6CA06D017C19 CRC64;
MTMPVNGAHK DADLWSSHDK MLAQPLKDSD VEVYNIIKKE SNRQRVGLEL IASENFASRA
VLEALGSCLN NKYSEGYPGQ RYYGGTEFID ELETLCQKRA LQAYKLDPQC WGVNVQPYSG
SPANFAVYTA LVEPHGRIMG LDLPDGGHLT HGFMTDKKKI SATSIFFESM PYKVNPDTGY
INYDQLEENA RLFHPKLIIA GTSCYSRNLE YARLRKIADE NGAYLMADMA HISGLVAAGV
VPSPFEHCHV VTTTTHKTLR GCRAGMIFYR KGVKSVDPKT GKEILYNLES LINSAVFPGL
QGGPHNHAIA GVAVALKQAM TLEFKVYQHQ VVANCRALSE ALTELGYKIV TGGSDNHLIL
VDLRSKGTDG GRAEKVLEAC SIACNKNTCP GDRSALRPSG LRLGTPALTS RGLLEKDFQK
VAHFIHRGIE LTLQIQSDTG VRATLKEFKE RLAGDKYQAA VQALREEVES FASLFPLPGL
PDF
//
ID GLYC_HUMAN Reviewed; 483 AA.
AC P34896; D3DXD0; Q96HY0; Q9UMD1; Q9UMD2;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1994, sequence version 1.
DT 22-JAN-2014, entry version 145.
DE RecName: Full=Serine hydroxymethyltransferase, cytosolic;
DE Short=SHMT;
DE EC=2.1.2.1;
DE AltName: Full=Glycine hydroxymethyltransferase;
DE AltName: Full=Serine methylase;
GN Name=SHMT1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8505317;
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Xu L., Mangum J.H., Robertson D.L.;
RL Submitted (JAN-1994) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Mammary gland;
RX PubMed=9056951;
RA Chave K.J., Snell K., Sanders P.G.;
RT "Isolation and characterisation of human genomic sequences encoding
RT cytosolic serine hydroxymethyltransferase.";
RL Biochem. Soc. Trans. 25:53-53(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT PHE-474.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP PHE-474.
RC TISSUE=Bone marrow, Lymph, and Testis;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-271 (ISOFORM 2), AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [7]
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.,
RA Buerckstuemmer T., 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 [8]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 11-480.
RX PubMed=9753690; DOI=10.1016/S0969-2126(98)00112-9;
RA Renwick S.B., Snell K., Baumann U.;
RT "The crystal structure of human cytosolic serine
RT hydroxymethyltransferase: a target for cancer chemotherapy.";
RL Structure 6:1105-1116(1998).
CC -!- FUNCTION: Interconversion of serine and glycine.
CC -!- CATALYTIC ACTIVITY: 5,10-methylenetetrahydrofolate + glycine +
CC H(2)O = tetrahydrofolate + L-serine.
CC -!- COFACTOR: Pyridoxal phosphate.
CC -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC -!- SUBUNIT: Homotetramer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P34896-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P34896-2; Sequence=VSP_006095;
CC Note=Contains a N6-acetyllysine at position 271;
CC Name=3;
CC IsoId=P34896-3; Sequence=VSP_006096;
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.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; L11931; AAA63257.1; -; mRNA.
DR EMBL; L23928; AAA36020.1; -; mRNA.
DR EMBL; L23928; AAA36019.1; -; mRNA.
DR EMBL; L23928; AAA36018.1; -; mRNA.
DR EMBL; Y14485; CAB54838.1; -; mRNA.
DR EMBL; Y14486; CAB54839.1; -; mRNA.
DR EMBL; Y14487; CAB54840.1; -; mRNA.
DR EMBL; CH471196; EAW55637.1; -; Genomic_DNA.
DR EMBL; CH471196; EAW55640.1; -; Genomic_DNA.
DR EMBL; CH471196; EAW55641.1; -; Genomic_DNA.
DR EMBL; BC007979; AAH07979.1; -; mRNA.
DR EMBL; BC022874; AAH22874.1; -; mRNA.
DR EMBL; BC038598; AAH38598.1; -; mRNA.
DR PIR; A46746; A46746.
DR RefSeq; NP_004160.3; NM_004169.4.
DR RefSeq; NP_683718.1; NM_148918.2.
DR RefSeq; XP_005256824.1; XM_005256767.1.
DR UniGene; Hs.513987; -.
DR UniGene; Hs.636044; -.
DR PDB; 1BJ4; X-ray; 2.65 A; A=11-480.
DR PDBsum; 1BJ4; -.
DR ProteinModelPortal; P34896; -.
DR SMR; P34896; 11-480.
DR IntAct; P34896; 5.
DR STRING; 9606.ENSP00000318868; -.
DR BindingDB; P34896; -.
DR ChEMBL; CHEMBL1772927; -.
DR DrugBank; DB00145; Glycine.
DR DrugBank; DB01055; Mimosine.
DR DrugBank; DB00114; Pyridoxal Phosphate.
DR DrugBank; DB00116; Tetrahydrofolic acid.
DR PhosphoSite; P34896; -.
DR DMDM; 462184; -.
DR PaxDb; P34896; -.
DR PRIDE; P34896; -.
DR DNASU; 6470; -.
DR Ensembl; ENST00000316694; ENSP00000318868; ENSG00000176974.
DR Ensembl; ENST00000352886; ENSP00000345881; ENSG00000176974.
DR Ensembl; ENST00000354098; ENSP00000318805; ENSG00000176974.
DR GeneID; 6470; -.
DR KEGG; hsa:6470; -.
DR UCSC; uc002gsz.3; human.
DR CTD; 6470; -.
DR GeneCards; GC17M018231; -.
DR HGNC; HGNC:10850; SHMT1.
DR HPA; HPA023314; -.
DR MIM; 182144; gene.
DR neXtProt; NX_P34896; -.
DR PharmGKB; PA35753; -.
DR eggNOG; COG0112; -.
DR HOGENOM; HOG000239405; -.
DR HOVERGEN; HBG002807; -.
DR InParanoid; P34896; -.
DR KO; K00600; -.
DR OMA; PEFRLYQ; -.
DR OrthoDB; EOG7327NN; -.
DR BioCyc; MetaCyc:HS11114-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR UniPathway; UPA00193; -.
DR ChiTaRS; SHMT1; human.
DR EvolutionaryTrace; P34896; -.
DR GenomeRNAi; 6470; -.
DR NextBio; 25133; -.
DR PRO; PR:P34896; -.
DR ArrayExpress; P34896; -.
DR Bgee; P34896; -.
DR CleanEx; HS_SHMT1; -.
DR Genevestigator; P34896; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0016597; F:amino acid binding; IEA:Ensembl.
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:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IDA:UniProtKB.
DR GO; GO:0045329; P:carnitine biosynthetic process; TAS:Reactome.
DR GO; GO:0046655; P:folic acid metabolic process; IDA:UniProtKB.
DR GO; GO:0019264; P:glycine biosynthetic process from serine; IEA:Ensembl.
DR GO; GO:0006565; P:L-serine catabolic process; IDA:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; IEA:Ensembl.
DR GO; GO:0051262; P:protein tetramerization; IDA:UniProtKB.
DR GO; GO:0009113; P:purine nucleobase biosynthetic process; IDA:UniProtKB.
DR GO; GO:0035999; P:tetrahydrofolate interconversion; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major_sub1.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_major_sub2.
DR InterPro; IPR001085; Ser_HO-MeTrfase.
DR InterPro; IPR019798; Ser_HO-MeTrfase_PLP_BS.
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; Complete proteome;
KW Cytoplasm; One-carbon metabolism; Polymorphism; Pyridoxal phosphate;
KW Reference proteome; Transferase.
FT INIT_MET 1 1 Removed (By similarity).
FT CHAIN 2 483 Serine hydroxymethyltransferase,
FT cytosolic.
FT /FTId=PRO_0000113504.
FT MOD_RES 257 257 N6-(pyridoxal phosphate)lysine.
FT VAR_SEQ 273 352 Missing (in isoform 3).
FT /FTId=VSP_006096.
FT VAR_SEQ 274 312 Missing (in isoform 2).
FT /FTId=VSP_006095.
FT VARIANT 340 340 E -> Q (in dbSNP:rs7215148).
FT /FTId=VAR_059795.
FT VARIANT 474 474 L -> F (in dbSNP:rs1979277).
FT /FTId=VAR_022010.
FT HELIX 13 21
FT HELIX 26 29
FT HELIX 31 46
FT STRAND 47 49
FT HELIX 59 65
FT HELIX 68 70
FT STRAND 80 84
FT HELIX 87 103
FT TURN 108 110
FT STRAND 111 114
FT HELIX 120 131
FT STRAND 137 141
FT HELIX 143 145
FT HELIX 149 151
FT HELIX 162 166
FT STRAND 167 172
FT TURN 176 178
FT HELIX 183 193
FT STRAND 196 200
FT HELIX 211 220
FT STRAND 224 228
FT HELIX 230 232
FT HELIX 233 237
FT HELIX 244 246
FT STRAND 249 256
FT HELIX 257 259
FT STRAND 265 270
FT STRAND 272 276
FT TURN 278 280
FT STRAND 283 285
FT HELIX 288 296
FT TURN 297 300
FT HELIX 306 318
FT HELIX 322 344
FT STRAND 355 362
FT HELIX 363 366
FT HELIX 370 379
FT STRAND 385 387
FT STRAND 400 404
FT HELIX 406 410
FT HELIX 415 438
FT HELIX 445 452
FT STRAND 453 455
FT HELIX 458 472
SQ SEQUENCE 483 AA; 53083 MW; 6CDD6CA06D017C19 CRC64;
MTMPVNGAHK DADLWSSHDK MLAQPLKDSD VEVYNIIKKE SNRQRVGLEL IASENFASRA
VLEALGSCLN NKYSEGYPGQ RYYGGTEFID ELETLCQKRA LQAYKLDPQC WGVNVQPYSG
SPANFAVYTA LVEPHGRIMG LDLPDGGHLT HGFMTDKKKI SATSIFFESM PYKVNPDTGY
INYDQLEENA RLFHPKLIIA GTSCYSRNLE YARLRKIADE NGAYLMADMA HISGLVAAGV
VPSPFEHCHV VTTTTHKTLR GCRAGMIFYR KGVKSVDPKT GKEILYNLES LINSAVFPGL
QGGPHNHAIA GVAVALKQAM TLEFKVYQHQ VVANCRALSE ALTELGYKIV TGGSDNHLIL
VDLRSKGTDG GRAEKVLEAC SIACNKNTCP GDRSALRPSG LRLGTPALTS RGLLEKDFQK
VAHFIHRGIE LTLQIQSDTG VRATLKEFKE RLAGDKYQAA VQALREEVES FASLFPLPGL
//
MIM
182144
*RECORD*
*FIELD* NO
182144
*FIELD* TI
*182144 SERINE HYDROXYMETHYLTRANSFERASE, CYTOSOLIC; SHMT1
*FIELD* TX
Serine hydroxymethyltransferase (SHMT), a pyridoxal phosphate-containing
read moreenzyme, catalyzes the reversible conversion of serine and
tetrahydrofolate to glycine and 5,10-methylene tetrahydrofolate. Some
eukaryotic cells, including human cells, contain both cytosolic and
mitochondrial forms of SHMT. Mammalian cells that lack mitochondrial
SHMT activity are auxotrophic for glycine (SHMT2; 138450). It has been
suggested that glycine synthesis from serine occurs in the mitochondria,
whereas cytosolic SHMT may catalyze the conversion of glycine to serine,
although direct evidence for this proposal is lacking. Garrow et al.
(1993) cloned human cDNAs for cytosolic and mitochondrial SHMT by
functional complementation of an Escherichia coli glyA mutant with a
human cDNA library. The cDNA for the cytosolic enzyme encoded a
483-residue protein of M(r) 53,020. The deduced protein sequence shared
63% identity with that of the SHMT2 protein. By isotopic in situ
hybridization, Garrow et al. (1993) assigned the cytosolic and
mitochondrial SHMT genes to 17p11.2 and 12q13, respectively. The high
degree of nucleotide sequence identity between the 2 isozymes as well as
the presence of keratin genes in both chromosomal regions was consistent
with these regions of chromosomes 12 and 17 having arisen by a
duplication event.
Folate-dependent one-carbon metabolism is critical for the synthesis of
numerous cellular constituents required for cell growth, and SHMT is
central to this process. Elsea et al. (1995) found that the SHMT1 gene
maps to the critical interval for Smith-Magenis syndrome (SMS; 182290)
on 17p11.2. They found that the gene spans approximately 40 kb. It was
found to be deleted in all 26 SMS patients examined by PCR, fluorescence
in situ hybridization, and/or Southern analysis. Furthermore,
haploinsufficiency was indicated by the fact that SHMT enzyme activity
in patient lymphoblasts was approximately 50% that of unaffected parent
lymphoblasts. They suggested that haploinsufficiency may play a role in
the SMS phenotype and that this finding may point to possible
therapeutic interventions.
Byrne et al. (1996) described an SHMT pseudogene with 90% identity to
SHMT cDNA. By fluorescence in situ hybridization, they mapped the
pseudogene to 1p33-p32.3.
*FIELD* RF
1. Byrne, P. C.; Shipley, J. M.; Chave, K. J.; Sanders, P. G.; Snell,
K.: Characterisation of a human serine hydroxymethyltransferase pseudogene
and its localisation of 1p32.3-33. Hum. Genet. 97: 340-344, 1996.
2. Elsea, S. H.; Juyal, R. C.; Jiralerspong, S.; Finucane, B. M.;
Pandolfo, M.; Greenberg, F.; Baldini, A.; Stover, P.; Patel, P. I.
: Haploinsufficiency of cytosolic serine hydroxymethyltransferase
in the Smith-Magenis syndrome. Am. J. Hum. Genet. 57: 1342-1350,
1995.
3. Garrow, T. A.; Brenner, A. A.; Whitehead, V. M.; Chen, X.-N.; Duncan,
R. G.; Korenberg, J. R.; Shane, B.: Cloning of human cDNAs encoding
mitochondrial and cytosolic serine hydroxymethyltransferases and chromosomal
localization. J. Biol. Chem. 268: 11910-11916, 1993.
*FIELD* CD
Victor A. McKusick: 7/6/1993
*FIELD* ED
psherman: 04/07/1998
alopez: 7/29/1997
terry: 7/7/1997
mark: 2/22/1996
terry: 2/20/1996
mark: 12/15/1995
terry: 12/14/1995
carol: 7/13/1993
carol: 7/6/1993
*RECORD*
*FIELD* NO
182144
*FIELD* TI
*182144 SERINE HYDROXYMETHYLTRANSFERASE, CYTOSOLIC; SHMT1
*FIELD* TX
Serine hydroxymethyltransferase (SHMT), a pyridoxal phosphate-containing
read moreenzyme, catalyzes the reversible conversion of serine and
tetrahydrofolate to glycine and 5,10-methylene tetrahydrofolate. Some
eukaryotic cells, including human cells, contain both cytosolic and
mitochondrial forms of SHMT. Mammalian cells that lack mitochondrial
SHMT activity are auxotrophic for glycine (SHMT2; 138450). It has been
suggested that glycine synthesis from serine occurs in the mitochondria,
whereas cytosolic SHMT may catalyze the conversion of glycine to serine,
although direct evidence for this proposal is lacking. Garrow et al.
(1993) cloned human cDNAs for cytosolic and mitochondrial SHMT by
functional complementation of an Escherichia coli glyA mutant with a
human cDNA library. The cDNA for the cytosolic enzyme encoded a
483-residue protein of M(r) 53,020. The deduced protein sequence shared
63% identity with that of the SHMT2 protein. By isotopic in situ
hybridization, Garrow et al. (1993) assigned the cytosolic and
mitochondrial SHMT genes to 17p11.2 and 12q13, respectively. The high
degree of nucleotide sequence identity between the 2 isozymes as well as
the presence of keratin genes in both chromosomal regions was consistent
with these regions of chromosomes 12 and 17 having arisen by a
duplication event.
Folate-dependent one-carbon metabolism is critical for the synthesis of
numerous cellular constituents required for cell growth, and SHMT is
central to this process. Elsea et al. (1995) found that the SHMT1 gene
maps to the critical interval for Smith-Magenis syndrome (SMS; 182290)
on 17p11.2. They found that the gene spans approximately 40 kb. It was
found to be deleted in all 26 SMS patients examined by PCR, fluorescence
in situ hybridization, and/or Southern analysis. Furthermore,
haploinsufficiency was indicated by the fact that SHMT enzyme activity
in patient lymphoblasts was approximately 50% that of unaffected parent
lymphoblasts. They suggested that haploinsufficiency may play a role in
the SMS phenotype and that this finding may point to possible
therapeutic interventions.
Byrne et al. (1996) described an SHMT pseudogene with 90% identity to
SHMT cDNA. By fluorescence in situ hybridization, they mapped the
pseudogene to 1p33-p32.3.
*FIELD* RF
1. Byrne, P. C.; Shipley, J. M.; Chave, K. J.; Sanders, P. G.; Snell,
K.: Characterisation of a human serine hydroxymethyltransferase pseudogene
and its localisation of 1p32.3-33. Hum. Genet. 97: 340-344, 1996.
2. Elsea, S. H.; Juyal, R. C.; Jiralerspong, S.; Finucane, B. M.;
Pandolfo, M.; Greenberg, F.; Baldini, A.; Stover, P.; Patel, P. I.
: Haploinsufficiency of cytosolic serine hydroxymethyltransferase
in the Smith-Magenis syndrome. Am. J. Hum. Genet. 57: 1342-1350,
1995.
3. Garrow, T. A.; Brenner, A. A.; Whitehead, V. M.; Chen, X.-N.; Duncan,
R. G.; Korenberg, J. R.; Shane, B.: Cloning of human cDNAs encoding
mitochondrial and cytosolic serine hydroxymethyltransferases and chromosomal
localization. J. Biol. Chem. 268: 11910-11916, 1993.
*FIELD* CD
Victor A. McKusick: 7/6/1993
*FIELD* ED
psherman: 04/07/1998
alopez: 7/29/1997
terry: 7/7/1997
mark: 2/22/1996
terry: 2/20/1996
mark: 12/15/1995
terry: 12/14/1995
carol: 7/13/1993
carol: 7/6/1993