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Protein

Serine hydroxymethyltransferase, cytosolic

Gene

SHMT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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

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

    • amino acid binding Source: Ensembl
    • glycine hydroxymethyltransferase activity Source: UniProtKB
    • L-allo-threonine aldolase activity Source: Ensembl
    • protein homodimerization activity Source: UniProtKB
    • pyridoxal phosphate binding Source: UniProtKB
    • serine binding Source: BHF-UCL

    GO - Biological processi

    • carnitine biosynthetic process Source: Reactome
    • 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
    • protein homotetramerization Source: UniProtKB
    • protein tetramerization Source: UniProtKB
    • purine nucleobase biosynthetic process Source: UniProtKB
    • tetrahydrofolate interconversion Source: BHF-UCL
    • tetrahydrofolate metabolic process Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Transferase

    Keywords - Biological processi

    One-carbon metabolism

    Keywords - Ligandi

    Pyridoxal phosphate

    Enzyme and pathway databases

    BioCyciMetaCyc:HS11114-MONOMER.
    ZFISH: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

    HGNCiHGNC:10850. SHMT1.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: HPA
    • cytosol Source: UniProtKB
    • extracellular exosome Source: UniProtKB
    • mitochondrion Source: Ensembl
    • nucleus Source: HPA
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi6470.
    OpenTargetsiENSG00000176974.
    PharmGKBiPA35753.

    Chemistry databases

    ChEMBLiCHEMBL1772927.
    DrugBankiDB00145. Glycine.
    DB01055. Mimosine.
    DB00116. Tetrahydrofolic acid.

    Polymorphism and mutation databases

    BioMutaiSHMT1.
    DMDMi462184.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemovedBy similarity
    ChainiPRO_00001135042 – 483Serine hydroxymethyltransferase, cytosolicAdd BLAST482

    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 FAM175B and the other subunits of the BRISC complex, at least composed of FAM175B/ABRO1, BRCC3/BRCC36, BRE/BRCC45 and BABAM1/NBA1 (PubMed:24075985).4 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself3EBI-715117,EBI-715117
    MAPK9P459845EBI-715117,EBI-713568
    SULT1A3P0DMM93EBI-715117,EBI-10196922

    GO - Molecular functioni

    • protein homodimerization activity Source: UniProtKB

    Protein-protein interaction databases

    BioGridi112366. 45 interactors.
    IntActiP34896. 10 interactors.
    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.
    OMAiDANNPAV.
    OrthoDBiEOG091G05AU.
    PhylomeDBiP34896.
    TreeFamiTF314667.

    Family and domain databases

    CDDicd00378. SHMT. 1 hit.
    Gene3Di3.40.640.10. 1 hit.
    3.90.1150.10. 1 hit.
    HAMAPiMF_00051. SHMT. 1 hit.
    InterProiIPR015424. 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]
    PANTHERiPTHR11680. PTHR11680. 1 hit.
    PfamiPF00464. SHMT. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000412. SHMT. 1 hit.
    SUPFAMiSSF53383. SSF53383. 1 hit.
    PROSITEiPS00096. SHMT. 1 hit.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    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 rs7215148dbSNPEnsembl.1
    Natural variantiVAR_022010474L → F.2 PublicationsCorresponds to variant rs1979277dbSNPEnsembl.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

    Cross-referencesi

    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.

    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...

    Protein-protein interaction databases

    BioGridi112366. 45 interactors.
    IntActiP34896. 10 interactors.
    STRINGi9606.ENSP00000318868.

    Chemistry databases

    BindingDBiP34896.
    ChEMBLiCHEMBL1772927.
    DrugBankiDB00145. Glycine.
    DB01055. Mimosine.
    DB00116. Tetrahydrofolic acid.

    Protein family/group databases

    MoonProtiP34896.

    PTM databases

    iPTMnetiP34896.
    PhosphoSitePlusiP34896.
    SwissPalmiP34896.

    Polymorphism and mutation databases

    BioMutaiSHMT1.
    DMDMi462184.

    Proteomic databases

    EPDiP34896.
    MaxQBiP34896.
    PaxDbiP34896.
    PeptideAtlasiP34896.
    PRIDEiP34896.

    Protocols and materials databases

    DNASUi6470.
    Structural Biology KnowledgebaseSearch...

    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]

    Organism-specific databases

    CTDi6470.
    DisGeNETi6470.
    GeneCardsiSHMT1.
    HGNCiHGNC:10850. SHMT1.
    HPAiHPA023314.
    MIMi182144. gene.
    neXtProtiNX_P34896.
    OpenTargetsiENSG00000176974.
    PharmGKBiPA35753.
    GenAtlasiSearch...

    Phylogenomic databases

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

    Enzyme and pathway databases

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

    Miscellaneous databases

    ChiTaRSiSHMT1. human.
    EvolutionaryTraceiP34896.
    GenomeRNAii6470.
    PROiP34896.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000176974.
    CleanExiHS_SHMT1.
    ExpressionAtlasiP34896. baseline and differential.
    GenevisibleiP34896. HS.

    Family and domain databases

    CDDicd00378. SHMT. 1 hit.
    Gene3Di3.40.640.10. 1 hit.
    3.90.1150.10. 1 hit.
    HAMAPiMF_00051. SHMT. 1 hit.
    InterProiIPR015424. 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]
    PANTHERiPTHR11680. PTHR11680. 1 hit.
    PfamiPF00464. SHMT. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000412. SHMT. 1 hit.
    SUPFAMiSSF53383. SSF53383. 1 hit.
    PROSITEiPS00096. SHMT. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiGLYC_HUMAN
    AccessioniPrimary (citable) accession number: P34896
    Secondary accession number(s): B4DPM9
    , D3DXD0, Q96HY0, Q9UMD1, Q9UMD2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1994
    Last sequence update: February 1, 1994
    Last modified: November 30, 2016
    This is version 176 of the entry and version 1 of the sequence. [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

    Miscellaneous

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

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 17
      Human chromosome 17: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.