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Protein

Serine hydroxymethyltransferase, cytosolic

Gene

SHMT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Interconversion of serine and glycine (PubMed:8505317, PubMed:24698160).2 Publications

Miscellaneous

In eukaryotes there are two forms of the enzymes: a cytosolic one and a mitochondrial one.Curated

Catalytic activityi

5,10-methylenetetrahydrofolate + glycine + H2O = tetrahydrofolate + L-serine.2 Publications

Cofactori

pyridoxal 5'-phosphate3 Publications

Enzyme regulationi

Inhibited by tetrahydrofolate concentrations above 40 µM.1 Publication

Kineticsi

  1. KM=0.18 mM for L-serine1 Publication
  2. KM=5.2 µM for tetrahydrofolate1 Publication

    Pathwayi: tetrahydrofolate interconversion

    This protein is involved in the pathway tetrahydrofolate interconversion, which is part of One-carbon metabolism.1 Publication
    View all proteins of this organism that are known to be involved in the pathway tetrahydrofolate interconversion and in One-carbon metabolism.

    GO - Molecular functioni

    • glycine hydroxymethyltransferase activity Source: UniProtKB
    • identical protein binding Source: IntAct
    • L-allo-threonine aldolase activity Source: Ensembl
    • mRNA 5'-UTR binding Source: CAFA
    • protein homodimerization activity Source: UniProtKB
    • pyridoxal phosphate binding Source: UniProtKB
    • serine binding Source: BHF-UCL
    • translation repressor activity, mRNA regulatory element binding Source: CAFA

    GO - Biological processi

    • carnitine biosynthetic process Source: Reactome
    • cellular response to leukemia inhibitory factor Source: Ensembl
    • cellular response to tetrahydrofolate Source: BHF-UCL
    • dTMP biosynthetic process Source: Ensembl
    • folic acid metabolic process Source: UniProtKB
    • glycine biosynthetic process from serine Source: Ensembl
    • glycine metabolic process Source: UniProtKB
    • L-serine catabolic process Source: UniProtKB
    • L-serine metabolic process Source: UniProtKB
    • negative regulation of translation Source: CAFA
    • protein homotetramerization Source: UniProtKB
    • protein tetramerization Source: UniProtKB
    • purine nucleobase biosynthetic process Source: UniProtKB
    • tetrahydrofolate interconversion Source: BHF-UCL
    • tetrahydrofolate metabolic process Source: UniProtKB

    Keywordsi

    Molecular functionTransferase
    Biological processOne-carbon metabolism
    LigandPyridoxal phosphate

    Enzyme and pathway databases

    BioCyciMetaCyc:HS11114-MONOMER
    BRENDAi2.1.2.1 2681
    ReactomeiR-HSA-196757 Metabolism of folate and pterines
    R-HSA-71262 Carnitine synthesis
    UniPathwayiUPA00193

    Protein family/group databases

    MoonProtiP34896

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Serine hydroxymethyltransferase, cytosolic (EC:2.1.2.12 Publications)
    Short name:
    SHMT
    Alternative name(s):
    Glycine hydroxymethyltransferase
    Serine methylase
    Gene namesi
    Name:SHMT1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 17

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000176974.17
    HGNCiHGNC:10850 SHMT1
    MIMi182144 gene
    neXtProtiNX_P34896

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi6470
    OpenTargetsiENSG00000176974
    PharmGKBiPA35753

    Chemistry databases

    ChEMBLiCHEMBL1772927
    DrugBankiDB02800 5-Hydroxymethylene-6-Hydrofolic Acid
    DB00145 Glycine
    DB01055 Mimosine
    DB02824 N-Pyridoxyl-Glycine-5-Monophosphate
    DB00114 Pyridoxal Phosphate
    DB00116 Tetrahydrofolic acid
    DB02067 Triglu-5-Formyl-Tetrahydrofolate

    Polymorphism and mutation databases

    BioMutaiSHMT1
    DMDMi462184

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001135041 – 483Serine hydroxymethyltransferase, cytosolicAdd BLAST483

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei257N6-(pyridoxal phosphate)lysineCombined sources1 Publication1
    Isoform 2 (identifier: P34896-2)
    Modified residuei271N6-acetyllysineCombined sources1

    Keywords - PTMi

    Acetylation

    Proteomic databases

    EPDiP34896
    MaxQBiP34896
    PaxDbiP34896
    PeptideAtlasiP34896
    PRIDEiP34896

    PTM databases

    iPTMnetiP34896
    PhosphoSitePlusiP34896
    SwissPalmiP34896

    Expressioni

    Gene expression databases

    BgeeiENSG00000176974
    CleanExiHS_SHMT1
    ExpressionAtlasiP34896 baseline and differential
    GenevisibleiP34896 HS

    Organism-specific databases

    HPAiHPA023314

    Interactioni

    Subunit structurei

    Homotetramer (PubMed:24698160, PubMed:25619277, PubMed:9753690). Identified in complex with ABRAXAS2 and the other subunits of the BRISC complex, at least composed of ABRAXAS2, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1 (PubMed:24075985).4 Publications

    Binary interactionsi

    Show more details

    GO - Molecular functioni

    • identical protein binding Source: IntAct
    • protein homodimerization activity Source: UniProtKB

    Protein-protein interaction databases

    BioGridi112366, 47 interactors
    IntActiP34896, 12 interactors
    MINTiP34896
    STRINGi9606.ENSP00000318868

    Chemistry databases

    BindingDBiP34896

    Structurei

    Secondary structure

    1483
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi13 – 21Combined sources9
    Helixi26 – 29Combined sources4
    Helixi31 – 46Combined sources16
    Beta strandi47 – 49Combined sources3
    Helixi59 – 65Combined sources7
    Helixi68 – 70Combined sources3
    Beta strandi80 – 84Combined sources5
    Helixi87 – 103Combined sources17
    Turni108 – 110Combined sources3
    Beta strandi111 – 114Combined sources4
    Helixi120 – 131Combined sources12
    Beta strandi137 – 141Combined sources5
    Helixi143 – 145Combined sources3
    Helixi149 – 151Combined sources3
    Helixi162 – 166Combined sources5
    Beta strandi167 – 172Combined sources6
    Turni176 – 178Combined sources3
    Helixi183 – 193Combined sources11
    Beta strandi196 – 200Combined sources5
    Helixi211 – 220Combined sources10
    Beta strandi224 – 228Combined sources5
    Helixi230 – 232Combined sources3
    Helixi233 – 237Combined sources5
    Helixi244 – 246Combined sources3
    Beta strandi249 – 256Combined sources8
    Helixi257 – 259Combined sources3
    Beta strandi265 – 270Combined sources6
    Beta strandi272 – 276Combined sources5
    Turni278 – 280Combined sources3
    Beta strandi283 – 285Combined sources3
    Helixi288 – 296Combined sources9
    Turni297 – 300Combined sources4
    Helixi306 – 318Combined sources13
    Helixi322 – 344Combined sources23
    Beta strandi355 – 362Combined sources8
    Helixi363 – 366Combined sources4
    Helixi370 – 379Combined sources10
    Beta strandi385 – 387Combined sources3
    Beta strandi400 – 404Combined sources5
    Helixi406 – 410Combined sources5
    Helixi415 – 438Combined sources24
    Helixi445 – 452Combined sources8
    Beta strandi453 – 455Combined sources3
    Helixi458 – 472Combined sources15

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1BJ4X-ray2.65A11-480[»]
    ProteinModelPortaliP34896
    SMRiP34896
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP34896

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the SHMT family.Curated

    Phylogenomic databases

    eggNOGiKOG2467 Eukaryota
    COG0112 LUCA
    GeneTreeiENSGT00390000002762
    HOGENOMiHOG000239405
    HOVERGENiHBG002807
    InParanoidiP34896
    KOiK00600
    OMAiPLEHIIA
    OrthoDBiEOG091G05AU
    PhylomeDBiP34896
    TreeFamiTF314667

    Family and domain databases

    CDDicd00378 SHMT, 1 hit
    Gene3Di3.40.640.10, 1 hit
    3.90.1150.10, 2 hits
    HAMAPiMF_00051 SHMT, 1 hit
    InterProiView protein in InterPro
    IPR015424 PyrdxlP-dep_Trfase
    IPR015422 PyrdxlP-dep_Trfase_dom1
    IPR015421 PyrdxlP-dep_Trfase_major
    IPR001085 Ser_HO-MeTrfase
    IPR019798 Ser_HO-MeTrfase_PLP_BS
    PIRSFiPIRSF000412 SHMT, 1 hit
    SUPFAMiSSF53383 SSF53383, 1 hit
    PROSITEiView protein in PROSITE
    PS00096 SHMT, 1 hit

    Sequences (4)i

    Sequence statusi: Complete.

    This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: P34896-1) [UniParc]FASTAAdd to basket

    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.

    « Hide

            10         20         30         40         50
    MTMPVNGAHK DADLWSSHDK MLAQPLKDSD VEVYNIIKKE SNRQRVGLEL
    60 70 80 90 100
    IASENFASRA VLEALGSCLN NKYSEGYPGQ RYYGGTEFID ELETLCQKRA
    110 120 130 140 150
    LQAYKLDPQC WGVNVQPYSG SPANFAVYTA LVEPHGRIMG LDLPDGGHLT
    160 170 180 190 200
    HGFMTDKKKI SATSIFFESM PYKVNPDTGY INYDQLEENA RLFHPKLIIA
    210 220 230 240 250
    GTSCYSRNLE YARLRKIADE NGAYLMADMA HISGLVAAGV VPSPFEHCHV
    260 270 280 290 300
    VTTTTHKTLR GCRAGMIFYR KGVKSVDPKT GKEILYNLES LINSAVFPGL
    310 320 330 340 350
    QGGPHNHAIA GVAVALKQAM TLEFKVYQHQ VVANCRALSE ALTELGYKIV
    360 370 380 390 400
    TGGSDNHLIL VDLRSKGTDG GRAEKVLEAC SIACNKNTCP GDRSALRPSG
    410 420 430 440 450
    LRLGTPALTS RGLLEKDFQK VAHFIHRGIE LTLQIQSDTG VRATLKEFKE
    460 470 480
    RLAGDKYQAA VQALREEVES FASLFPLPGL PDF
    Length:483
    Mass (Da):53,083
    Last modified:February 1, 1994 - v1
    Checksum:i6CDD6CA06D017C19
    GO
    Isoform 2 (identifier: P34896-2) [UniParc]FASTAAdd to basket

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

    Show »
    Length:444
    Mass (Da):49,028
    Checksum:i92091DCEB64B65D1
    GO
    Isoform 3 (identifier: P34896-3) [UniParc]FASTAAdd to basket

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

    Show »
    Length:403
    Mass (Da):44,552
    Checksum:i9CE930DFA6FC1FF7
    GO
    Isoform 4 (identifier: P34896-4) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-138: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:345
    Mass (Da):37,672
    Checksum:iDD683D88B3A1D1FA
    GO

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_059795340E → Q. Corresponds to variant dbSNP:rs7215148Ensembl.1
    Natural variantiVAR_022010474L → F2 PublicationsCorresponds to variant dbSNP:rs1979277Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0546101 – 138Missing in isoform 4. 1 PublicationAdd BLAST138
    Alternative sequenceiVSP_006096273 – 352Missing in isoform 3. CuratedAdd BLAST80
    Alternative sequenceiVSP_006095274 – 312Missing in isoform 2. 1 PublicationAdd BLAST39

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    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
    AK298415 mRNA Translation: BAG60641.1
    AC127537 Genomic DNA No translation available.
    AL353997 Genomic DNA No translation available.
    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
    CCDSiCCDS11196.1 [P34896-1]
    CCDS11197.1 [P34896-2]
    CCDS62112.1 [P34896-4]
    PIRiA46746
    RefSeqiNP_001268715.1, NM_001281786.1 [P34896-4]
    NP_004160.3, NM_004169.4 [P34896-1]
    NP_683718.1, NM_148918.2 [P34896-2]
    XP_005256824.1, XM_005256767.3 [P34896-1]
    XP_011522294.1, XM_011523992.2 [P34896-3]
    XP_016880446.1, XM_017024957.1 [P34896-1]
    XP_016880447.1, XM_017024958.1 [P34896-2]
    UniGeneiHs.513987
    Hs.592944
    Hs.636044

    Genome annotation databases

    EnsembliENST00000316694; ENSP00000318868; ENSG00000176974 [P34896-1]
    ENST00000352886; ENSP00000345881; ENSG00000176974 [P34896-4]
    ENST00000354098; ENSP00000318805; ENSG00000176974 [P34896-2]
    GeneIDi6470
    KEGGihsa:6470
    UCSCiuc002gta.5 human [P34896-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiGLYC_HUMAN
    AccessioniPrimary (citable) accession number: P34896
    Secondary accession number(s): B4DPM9
    , D3DXD0, Q96HY0, Q9UMD1, Q9UMD2
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
    Last sequence update: February 1, 1994
    Last modified: April 25, 2018
    This is version 188 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny 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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health