P34896 (GLYC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine hydroxymethyltransferase, cytosolic
Short name=SHMT
EC=2.1.2.1

Alternative name(s):
Glycine hydroxymethyltransferase
Serine methylase

Gene names

Name:

SHMT1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	483 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Interconversion of serine and glycine.
Catalytic activity	5,10-methylenetetrahydrofolate + glycine + H2O = tetrahydrofolate + L-serine.
Cofactor	Pyridoxal phosphate.
Pathway	One-carbon metabolism; tetrahydrofolate interconversion.
Subunit structure	Homotetramer.
Subcellular location	Cytoplasm.
Miscellaneous	In eukaryotes there are two forms of the enzymes: a cytosolic one and a mitochondrial one.
Sequence similarities	Belongs to the SHMT family.

Ontologies

Keywords
Biological process	One-carbon metabolism
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Pyridoxal phosphate
Molecular function	Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	L-serine catabolic process Inferred from direct assay PubMed 17482557. Source: UniProtKB carnitine biosynthetic process Traceable author statement. Source: Reactome folic acid metabolic process Inferred from direct assay PubMed 11278996. Source: UniProtKB glycine biosynthetic process from serine Inferred from electronic annotation. Source: Compara protein homotetramerization Inferred from electronic annotation. Source: Compara protein tetramerization Inferred from direct assay Ref.8. Source: UniProtKB purine nucleobase biosynthetic process Inferred from direct assay PubMed 11516159. Source: UniProtKB tetrahydrofolate interconversion Inferred from electronic annotation. Source: UniProtKB-UniPathway
Cellular_component	cytosol Inferred from direct assay PubMed 17482557. Source: UniProtKB mitochondrion Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay. Source: HPA
Molecular_function	L-allo-threonine aldolase activity Inferred from electronic annotation. Source: Compara amino acid binding Inferred from electronic annotation. Source: Compara glycine hydroxymethyltransferase activity Inferred from direct assay PubMed 17482557Ref.1. Source: UniProtKB protein homodimerization activity Inferred from direct assay Ref.8. Source: UniProtKB pyridoxal phosphate binding Inferred from direct assay PubMed 17482557. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P34896-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P34896-2)

The sequence of this isoform differs from the canonical sequence as follows:
     274-312: Missing.

Note: Contains a N6-acetyllysine at position 271.

Isoform 3 (identifier: P34896-3)

The sequence of this isoform differs from the canonical sequence as follows:
     273-352: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 483

482

Serine hydroxymethyltransferase, cytosolic

PRO_0000113504

Amino acid modifications

Modified residue

34

1

Phosphotyrosine By similarity

Modified residue

257

1

N6-(pyridoxal phosphate)lysine

Natural variations

Alternative sequence

273 – 352

80

Missing in isoform 3.

VSP_006096

Alternative sequence

274 – 312

39

Missing in isoform 2.

VSP_006095

Natural variant

340

1

E → Q.
Corresponds to variant rs7215148 [ dbSNP | Ensembl ].

VAR_059795

Natural variant

474

1

L → F. Ref.4 Ref.5
Corresponds to variant rs1979277 [ dbSNP | Ensembl ].

VAR_022010

Secondary structure

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483

Helix Strand Turn

Details...

Helix

13 – 21

9

Helix

26 – 29

4

Helix

31 – 46

16

Beta strand

47 – 49

3

Helix

59 – 65

7

Helix

68 – 70

3

Beta strand

80 – 84

5

Helix

87 – 103

17

Turn

108 – 110

3

Beta strand

111 – 114

4

Helix

120 – 131

12

Beta strand

137 – 141

5

Helix

143 – 145

3

Helix

149 – 151

3

Helix

162 – 166

5

Beta strand

167 – 172

6

Turn

176 – 178

3

Helix

183 – 193

11

Beta strand

196 – 200

5

Helix

211 – 220

10

Beta strand

224 – 228

5

Helix

230 – 232

3

Helix

233 – 237

5

Helix

244 – 246

3

Beta strand

249 – 256

8

Helix

257 – 259

3

Beta strand

265 – 270

6

Beta strand

272 – 276

5

Turn

278 – 280

3

Beta strand

283 – 285

3

Helix

288 – 296

9

Turn

297 – 300

4

Helix

306 – 318

13

Helix

322 – 344

23

Beta strand

355 – 362

8

Helix

363 – 366

4

Helix

370 – 379

10

Beta strand

385 – 387

3

Beta strand

400 – 404

5

Helix

406 – 410

5

Helix

415 – 438

24

Helix

445 – 452

8

Beta strand

453 – 455

3

Helix

458 – 472

15

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 1994. Version 1. Checksum: 6CDD6CA06D017C19	FASTA	483	53,083
	10 20 30 40 50 60 MTMPVNGAHK DADLWSSHDK MLAQPLKDSD VEVYNIIKKE SNRQRVGLEL IASENFASRA 70 80 90 100 110 120 VLEALGSCLN NKYSEGYPGQ RYYGGTEFID ELETLCQKRA LQAYKLDPQC WGVNVQPYSG 130 140 150 160 170 180 SPANFAVYTA LVEPHGRIMG LDLPDGGHLT HGFMTDKKKI SATSIFFESM PYKVNPDTGY 190 200 210 220 230 240 INYDQLEENA RLFHPKLIIA GTSCYSRNLE YARLRKIADE NGAYLMADMA HISGLVAAGV 250 260 270 280 290 300 VPSPFEHCHV VTTTTHKTLR GCRAGMIFYR KGVKSVDPKT GKEILYNLES LINSAVFPGL 310 320 330 340 350 360 QGGPHNHAIA GVAVALKQAM TLEFKVYQHQ VVANCRALSE ALTELGYKIV TGGSDNHLIL 370 380 390 400 410 420 VDLRSKGTDG GRAEKVLEAC SIACNKNTCP GDRSALRPSG LRLGTPALTS RGLLEKDFQK 430 440 450 460 470 480 VAHFIHRGIE LTLQIQSDTG VRATLKEFKE RLAGDKYQAA VQALREEVES FASLFPLPGL PDF
	Isoform 2 [UniParc]. Checksum: 92091DCEB64B65D1	FASTA	444	49,028
	10 20 30 40 50 60 MTMPVNGAHK DADLWSSHDK MLAQPLKDSD VEVYNIIKKE SNRQRVGLEL IASENFASRA 70 80 90 100 110 120 VLEALGSCLN NKYSEGYPGQ RYYGGTEFID ELETLCQKRA LQAYKLDPQC WGVNVQPYSG 130 140 150 160 170 180 SPANFAVYTA LVEPHGRIMG LDLPDGGHLT HGFMTDKKKI SATSIFFESM PYKVNPDTGY 190 200 210 220 230 240 INYDQLEENA RLFHPKLIIA GTSCYSRNLE YARLRKIADE NGAYLMADMA HISGLVAAGV 250 260 270 280 290 300 VPSPFEHCHV VTTTTHKTLR GCRAGMIFYR KGVAVALKQA MTLEFKVYQH QVVANCRALS 310 320 330 340 350 360 EALTELGYKI VTGGSDNHLI LVDLRSKGTD GGRAEKVLEA CSIACNKNTC PGDRSALRPS 370 380 390 400 410 420 GLRLGTPALT SRGLLEKDFQ KVAHFIHRGI ELTLQIQSDT GVRATLKEFK ERLAGDKYQA 430 440 AVQALREEVE SFASLFPLPG LPDF
	Isoform 3 [UniParc]. Checksum: 9CE930DFA6FC1FF7	FASTA	403	44,552
	10 20 30 40 50 60 MTMPVNGAHK DADLWSSHDK MLAQPLKDSD VEVYNIIKKE SNRQRVGLEL IASENFASRA 70 80 90 100 110 120 VLEALGSCLN NKYSEGYPGQ RYYGGTEFID ELETLCQKRA LQAYKLDPQC WGVNVQPYSG 130 140 150 160 170 180 SPANFAVYTA LVEPHGRIMG LDLPDGGHLT HGFMTDKKKI SATSIFFESM PYKVNPDTGY 190 200 210 220 230 240 INYDQLEENA RLFHPKLIIA GTSCYSRNLE YARLRKIADE NGAYLMADMA HISGLVAAGV 250 260 270 280 290 300 VPSPFEHCHV VTTTTHKTLR GCRAGMIFYR KGGSDNHLIL VDLRSKGTDG GRAEKVLEAC 310 320 330 340 350 360 SIACNKNTCP GDRSALRPSG LRLGTPALTS RGLLEKDFQK VAHFIHRGIE LTLQIQSDTG 370 380 390 400 VRATLKEFKE RLAGDKYQAA VQALREEVES FASLFPLPGL PDF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of human cDNAs encoding mitochondrial and cytosolic serine hydroxymethyltransferases and chromosomal localization." Garrow T.A., Brenner A.A., Whitehead M.V., Chen X.-N., Duncan R.G., Korenberg J.R., Shane B. J. Biol. Chem. 268:11910-11916(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Xu L., Mangum J.H., Robertson D.L. Submitted (JAN-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[3]	"Isolation and characterisation of human genomic sequences encoding cytosolic serine hydroxymethyltransferase." Chave K.J., Snell K., Sanders P.G. Biochem. Soc. Trans. 25:53-53(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Mammary gland.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT PHE-474.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT PHE-474. Tissue: Bone marrow, Lymph and Testis.
[6]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-271 (ISOFORM 2), MASS SPECTROMETRY.
[7]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]	"The crystal structure of human cytosolic serine hydroxymethyltransferase: a target for cancer chemotherapy." Renwick S.B., Snell K., Baumann U. Structure 6:1105-1116(1998) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 11-480.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L11931 mRNA. Translation: AAA63257.1.
L23928 mRNA. Translation: AAA36020.1.
L23928 mRNA. Translation: AAA36019.1.
L23928 mRNA. Translation: AAA36018.1.
Y14485 mRNA. Translation: CAB54838.1.
Y14486 mRNA. Translation: CAB54839.1.
Y14487 mRNA. Translation: CAB54840.1.
CH471196 Genomic DNA. Translation: EAW55637.1.
CH471196 Genomic DNA. Translation: EAW55640.1.
CH471196 Genomic DNA. Translation: EAW55641.1.
BC007979 mRNA. Translation: AAH07979.1.
BC022874 mRNA. Translation: AAH22874.1.
BC038598 mRNA. Translation: AAH38598.1.

IPI

IPI00002519.
IPI00220668.
IPI00220669.

PIR

A46746.

RefSeq

NP_004160.3. NM_004169.3.
NP_683718.1. NM_148918.1.

UniGene

Hs.513987.
Hs.636044.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BJ4	X-ray	2.65	A	11-480	[»]

ProteinModelPortal

P34896.

ModBase

Search...

Protein-protein interaction databases

IntAct

P34896. 5 interactions.

STRING

9606.ENSP00000318868.

PTM databases

PhosphoSite

P34896.

Polymorphism databases

DMDM

462184.

Proteomic databases

PaxDb

P34896.

PRIDE

P34896.

Protocols and materials databases

DNASU

6470.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000316694; ENSP00000318868; ENSG00000176974.
ENST00000352886; ENSP00000345881; ENSG00000176974.
ENST00000354098; ENSP00000318805; ENSG00000176974.

GeneID

6470.

KEGG

hsa:6470.

UCSC

uc002gsz.3. human.
uc002gtb.3. human.

Organism-specific databases

CTD

6470.

GeneCards

GC17M018231.

HGNC

HGNC:10850. SHMT1.

HPA

HPA023314.

MIM

182144. gene.

neXtProt

NX_P34896.

PharmGKB

PA35753.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0112.

HOGENOM

HOG000239405.

HOVERGEN

HBG002807.

InParanoid

P34896.

KO

K00600.

OMA

VDLRESH.

OrthoDB

EOG42Z4Q2.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

UniPathway

UPA00193.

Gene expression databases

ArrayExpress

P34896.

Bgee

P34896.

CleanEx

HS_SHMT1.

Genevestigator

P34896.

GermOnline

ENSG00000176974. Homo sapiens.

Family and domain databases

Gene3D

3.40.640.10. 1 hit.
3.90.1150.10. 1 hit.

InterPro

IPR015424. PyrdxlP-dep_Trfase.
IPR015421. PyrdxlP-dep_Trfase_major_sub1.
IPR015422. PyrdxlP-dep_Trfase_major_sub2.
IPR001085. Ser_HO-MeTrfase.
IPR019798. Ser_HO-MeTrfase_PLP_BS.
[Graphical view]

PANTHER

PTHR11680. PTHR11680. 1 hit.

Pfam

PF00464. SHMT. 1 hit.
[Graphical view]

PIRSF

PIRSF000412. SHMT. 1 hit.

SUPFAM

SSF53383. PyrdxlP-dep_Trfase_major. 1 hit.

PROSITE

PS00096. SHMT. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P34896.

ChEMBL

CHEMBL1772927.

ChiTaRS

SHMT1. human.

DrugBank

DB00145. Glycine.
DB01055. Mimosine.
DB00114. Pyridoxal Phosphate.
DB00116. Tetrahydrofolic acid.

EvolutionaryTrace

P34896.

GenomeRNAi

6470.

NextBio

25133.

SOURCE

Search...

Entry information

Entry name

GLYC_HUMAN

Accession

Primary (citable) accession number: P34896
Secondary accession number(s): D3DXD0 , Q96HY0, Q9UMD1, Q9UMD2

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	February 1, 1994
Last modified:	May 1, 2013
This is version 140 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.