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SHMT1 serine hydroxymethyltransferase 1 [ Homo sapiens (human) ]

Gene ID: 6470, updated on 2-Nov-2024

Summary

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Official Symbol
SHMT1provided by HGNC
Official Full Name
serine hydroxymethyltransferase 1provided by HGNC
Primary source
HGNC:HGNC:10850
See related
Ensembl:ENSG00000176974 MIM:182144; AllianceGenome:HGNC:10850
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
SHMT; CSHMT
Summary
This gene encodes the cytosolic form of serine hydroxymethyltransferase, a pyridoxal phosphate-containing enzyme that catalyzes the reversible conversion of serine and tetrahydrofolate to glycine and 5,10-methylene tetrahydrofolate. This reaction provides one-carbon units for synthesis of methionine, thymidylate, and purines in the cytoplasm. This gene is located within the Smith-Magenis syndrome region on chromosome 17. A pseudogene of this gene is located on the short arm of chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
Expression
Biased expression in kidney (RPKM 121.9), liver (RPKM 84.9) and 13 other tissues See more
Orthologs
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Genomic context

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See SHMT1 in Genome Data Viewer
Location:
17p11.2
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (18327873..18363550, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (18274679..18310356, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (18231187..18266864, complement)

Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene DNA topoisomerase III alpha Neighboring gene H3K27ac hESC enhancer GRCh37_chr17:18217357-18217880 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11836 Neighboring gene H3K27ac hESC enhancer GRCh37_chr17:18218405-18218928 Neighboring gene ribosomal protein L21 pseudogene 121 Neighboring gene ribosomal protein L7a pseudogene 65 Neighboring gene ReSE screen-validated silencer GRCh37_chr17:18224803-18224995 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:18225507-18226008 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:18226009-18226508 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8275 Neighboring gene SMCR8-C9orf72 complex subunit Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:18233711-18234211 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:18235020-18235826 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:18235827-18236631 Neighboring gene microRNA 6778 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8276 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:18276669-18277169 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:18283393-18283894 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:18285838-18286409 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:18286410-18286980 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:18292166-18292878 Neighboring gene envoplakin like Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:18302365-18302865 Neighboring gene H3K27ac hESC enhancer GRCh37_chr17:18303020-18303520 Neighboring gene H3K27ac hESC enhancer GRCh37_chr17:18303521-18304021 Neighboring gene TBC1 domain family member 3 pseudogene 4

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Role of Cytosolic Serine Hydroxymethyl Transferase 1 (SHMT1) in Phosphate-Induced Vascular Smooth Muscle Cell Calcification. Boehme B, et al. Kidney Blood Press Res, 2018. PMID 30071536
  2. Carnitine biosynthesis in mammals. Vaz FM, et al. Biochem J, 2002 Feb 1. PMID 11802770, Free PMC Article
  3. Polymorphism C1420T of Serine hydroxymethyltransferase gene on maternal risk for Down syndrome. Marucci GH, et al. Mol Biol Rep, 2012 Mar. PMID 21687976
  4. [Correlations between serine hydroxymethyltransferase1 C1420T polymorphisms and susceptibilities to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma]. Wang YM, et al. Ai Zheng, 2006 Mar. PMID 16536979
  5. Impact of SHMT1 polymorphism on the clinical outcome of patients with metastatic colorectal cancer treated with first-line FOLFIRI+bevacizumab. Budai B, et al. Pharmacogenet Genomics, 2012 Jan. PMID 22044939

See all (186) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Structure-based mechanism of riboregulation of the metabolic enzyme SHMT1.
    Title: Structure-based mechanism of riboregulation of the metabolic enzyme SHMT1.
  2. Serine hydroxymethyltransferase 1 promotes low-grade glioma progression by activating mTORC1 signaling.
    Title: Serine hydroxymethyltransferase 1 promotes low-grade glioma progression by activating mTORC1 signaling.
  3. Association Between SHMT1 rs1979277 Polymorphism and Risk of Acute Lymphoblastic Leukemia: A Systematic Review and Meta-analysis.
    Title: Association Between SHMT1 rs1979277 Polymorphism and Risk of Acute Lymphoblastic Leukemia: A Systematic Review and Meta-analysis.
  4. Targeting serine hydroxymethyltransferases 1 and 2 for T-cell acute lymphoblastic leukemia therapy.
    Title: Targeting serine hydroxymethyltransferases 1 and 2 for T-cell acute lymphoblastic leukemia therapy.
  5. The association between serine hydroxymethyl transferase 1 gene hypermethylation and ischemic stroke.
    Title: The association between serine hydroxymethyl transferase 1 gene hypermethylation and ischemic stroke.
  6. Tumor Reliance on Cytosolic versus Mitochondrial One-Carbon Flux Depends on Folate Availability.
    Title: Tumor Reliance on Cytosolic versus Mitochondrial One-Carbon Flux Depends on Folate Availability.
  7. The human cytosolic serine hydroxymethyltransferase /Deltaflap variant exhibited different catalytic properties in (6S)-tetrahydrofolate (THF)-dependent reactions compared with the WT but had similar activity in THF-independent aldol cleavage of beta-hydroxyamino acid.
    Title: A flap motif in human serine hydroxymethyltransferase is important for structural stabilization, ligand binding, and control of product release.
  8. association of the variant rs1979277 (G > A) and nonsyndromic cleft lip with or without cleft palate in a Chilean population
    Title: A SHMT1 variant decreases the risk of nonsyndromic cleft lip with or without cleft palate in Chile.
  9. The moonlighting RNA-binding activity of cytosolic SHMT contributes to control compartmentalization of serine metabolism.
    Title: The moonlighting RNA-binding activity of cytosolic serine hydroxymethyltransferase contributes to control compartmentalization of serine metabolism.
  10. Characterized the serine hydroxymethyltransferase reaction catalyzed by SHMT1 and SHMT2, with a focus on pH dependence and substrate inhibition. SHMT2 maintains a pronounced tetrahydrofolate substrate inhibition even at the alkaline pH characteristic of the mitochondrial matrix, whereas with SHMT1 this is almost abolished. At this pH, SHMT2 also shows a catalytic efficiency that is much higher than that of SHMT1.
    Title: Human Cytosolic and Mitochondrial Serine Hydroxymethyltransferase Isoforms in Comparison: Full Kinetic Characterization and Substrate Inhibition Properties.
Submit: New GeneRIF Correction See all GeneRIFs (73)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC15229, MGC24556

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables aldehyde-lyase activity EXP
Inferred from Experiment
more info
 PubMed 
enables glycine hydroxymethyltransferase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables glycine hydroxymethyltransferase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables mRNA 5'-UTR binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables mRNA regulatory element binding translation repressor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables pyridoxal phosphate binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables pyridoxal phosphate binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables serine binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables small molecule binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in L-serine catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in L-serine metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in carnitine biosynthetic process TAS
Traceable Author Statement
more info
  
involved_in cellular response to leukemia inhibitory factor IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to tetrahydrofolate IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in dTMP biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in folic acid metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in folic acid metabolic process TAS
Traceable Author Statement
more info
  
involved_in glycine biosynthetic process from serine IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in glycine metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of translation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein homotetramerization IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in purine nucleobase biosynthetic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in tetrahydrofolate interconversion IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in tetrahydrofolate interconversion IEA
Inferred from Electronic Annotation
more info
  
involved_in tetrahydrofolate metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in tetrahydrofolate metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
serine hydroxymethyltransferase, cytosolic
Names
cytoplasmic serine hydroxymethyltransferase
glycine hydroxymethyltransferase
serine hydroxymethyltransferase 1 (soluble)
serine methylase
NP_001268715.1
NP_004160.3
NP_683718.1
XP_005256824.1
XP_011522294.1
XP_016880446.1
XP_016880447.1
XP_024306655.1
XP_047292501.1
XP_054172909.1
XP_054172910.1
XP_054172911.1
XP_054172912.1
XP_054172913.1
XP_054172914.1
XP_054188074.1
XP_054188075.1
XP_054188076.1
XP_054188077.1
XP_054188078.1
XP_054188079.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_017111.1 RefSeqGene

    Range
    4993..40670
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001281786.2 → NP_001268715.1  serine hydroxymethyltransferase, cytosolic isoform 3

    See identical proteins and their annotated locations for NP_001268715.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses an alternate 5' exon structure, and thus differs in the 5' UTR and 5' coding region, compared to variant 1. These differences cause translation initiation at a downstream AUG and result in an isoform (3) with a shorter N-terminus, compared to isoform 1.
    Source sequence(s)
    AK298415, AU185281, BM792235, DB451683
    Consensus CDS
    CCDS62112.1
    UniProtKB/Swiss-Prot
    P34896
    Conserved Domains (1) summary
    cl28184
    Location:1 → 342
    PLN03226; serine hydroxymethyltransferase; Provisional

  2. NM_004169.5 → NP_004160.3  serine hydroxymethyltransferase, cytosolic isoform 1

    See identical proteins and their annotated locations for NP_004160.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    BC007979, BC038598, DB451683
    Consensus CDS
    CCDS11196.1
    UniProtKB/Swiss-Prot
    B4DPM9, D3DXD0, P34896, Q96HY0, Q9UMD1, Q9UMD2
    UniProtKB/TrEMBL
    Q53ET7
    Related
    ENSP00000318868.3, ENST00000316694.8
    Conserved Domains (2) summary
    PLN03226
    Location:24 → 480
    PLN03226; serine hydroxymethyltransferase; Provisional
    pfam00464
    Location:26 → 425
    SHMT; Serine hydroxymethyltransferase

  3. NM_148918.3 → NP_683718.1  serine hydroxymethyltransferase, cytosolic isoform 2

    See identical proteins and their annotated locations for NP_683718.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon in the coding region compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.
    Source sequence(s)
    AU185281, BC022874, BM792235, DB451683
    Consensus CDS
    CCDS11197.1
    UniProtKB/TrEMBL
    Q53ET7
    Related
    ENSP00000318805.3, ENST00000354098.7
    Conserved Domains (2) summary
    PLN03226
    Location:24 → 441
    PLN03226; serine hydroxymethyltransferase; Provisional
    cl18945
    Location:26 → 386
    AAT_I; Aspartate aminotransferase (AAT) superfamily (fold type I) of pyridoxal phosphate (PLP)-dependent enzymes. PLP combines with an alpha-amino acid to form a compound called a Schiff base or aldimine intermediate, which depending on the reaction, is the ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

    Range
    18327873..18363550 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011523992.4 → XP_011522294.1  serine hydroxymethyltransferase, cytosolic isoform X3

    See identical proteins and their annotated locations for XP_011522294.1

    UniProtKB/TrEMBL
    Q53ET7
    Conserved Domains (1) summary
    cl28184
    Location:24 → 400
    PLN03226; serine hydroxymethyltransferase; Provisional

  2. XM_024450887.2 → XP_024306655.1  serine hydroxymethyltransferase, cytosolic isoform X3

    UniProtKB/TrEMBL
    Q53ET7
    Conserved Domains (1) summary
    cl28184
    Location:24 → 400
    PLN03226; serine hydroxymethyltransferase; Provisional

  3. XM_017024958.2 → XP_016880447.1  serine hydroxymethyltransferase, cytosolic isoform X2

    UniProtKB/TrEMBL
    Q53ET7
    Conserved Domains (2) summary
    PLN03226
    Location:24 → 441
    PLN03226; serine hydroxymethyltransferase; Provisional
    cl18945
    Location:26 → 386
    AAT_I; Aspartate aminotransferase (AAT) superfamily (fold type I) of pyridoxal phosphate (PLP)-dependent enzymes. PLP combines with an alpha-amino acid to form a compound called a Schiff base or aldimine intermediate, which depending on the reaction, is the ...

  4. XM_005256767.4 → XP_005256824.1  serine hydroxymethyltransferase, cytosolic isoform X1

    See identical proteins and their annotated locations for XP_005256824.1

    UniProtKB/Swiss-Prot
    B4DPM9, D3DXD0, P34896, Q96HY0, Q9UMD1, Q9UMD2
    UniProtKB/TrEMBL
    Q53ET7
    Related
    ENSP00000462041.2, ENST00000583780.2
    Conserved Domains (2) summary
    PLN03226
    Location:24 → 480
    PLN03226; serine hydroxymethyltransferase; Provisional
    pfam00464
    Location:26 → 425
    SHMT; Serine hydroxymethyltransferase

  5. XM_047436545.1 → XP_047292501.1  serine hydroxymethyltransferase, cytosolic isoform X2

  6. XM_017024957.2 → XP_016880446.1  serine hydroxymethyltransferase, cytosolic isoform X1

    UniProtKB/Swiss-Prot
    B4DPM9, D3DXD0, P34896, Q96HY0, Q9UMD1, Q9UMD2
    UniProtKB/TrEMBL
    Q53ET7
    Conserved Domains (2) summary
    PLN03226
    Location:24 → 480
    PLN03226; serine hydroxymethyltransferase; Provisional
    pfam00464
    Location:26 → 425
    SHMT; Serine hydroxymethyltransferase

Reference GRCh38.p14 PATCHES

Genomic

  1. NW_017363819.1 Reference GRCh38.p14 PATCHES

    Range
    88247..123941 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054332103.1 → XP_054188078.1  serine hydroxymethyltransferase, cytosolic isoform X3

  2. XM_054332104.1 → XP_054188079.1  serine hydroxymethyltransferase, cytosolic isoform X3

  3. XM_054332101.1 → XP_054188076.1  serine hydroxymethyltransferase, cytosolic isoform X2

  4. XM_054332099.1 → XP_054188074.1  serine hydroxymethyltransferase, cytosolic isoform X1

    UniProtKB/Swiss-Prot
    B4DPM9, D3DXD0, P34896, Q96HY0, Q9UMD1, Q9UMD2

  5. XM_054332100.1 → XP_054188075.1  serine hydroxymethyltransferase, cytosolic isoform X1

    UniProtKB/Swiss-Prot
    B4DPM9, D3DXD0, P34896, Q96HY0, Q9UMD1, Q9UMD2

  6. XM_054332102.1 → XP_054188077.1  serine hydroxymethyltransferase, cytosolic isoform X2

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060941.1 Alternate T2T-CHM13v2.0

    Range
    18274679..18310356 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054316938.1 → XP_054172913.1  serine hydroxymethyltransferase, cytosolic isoform X3

  2. XM_054316939.1 → XP_054172914.1  serine hydroxymethyltransferase, cytosolic isoform X3

  3. XM_054316936.1 → XP_054172911.1  serine hydroxymethyltransferase, cytosolic isoform X2

  4. XM_054316934.1 → XP_054172909.1  serine hydroxymethyltransferase, cytosolic isoform X1

    UniProtKB/Swiss-Prot
    B4DPM9, D3DXD0, P34896, Q96HY0, Q9UMD1, Q9UMD2

  5. XM_054316935.1 → XP_054172910.1  serine hydroxymethyltransferase, cytosolic isoform X1

    UniProtKB/Swiss-Prot
    B4DPM9, D3DXD0, P34896, Q96HY0, Q9UMD1, Q9UMD2

  6. XM_054316937.1 → XP_054172912.1  serine hydroxymethyltransferase, cytosolic isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P34896.1 GenPept UniProtKB/Swiss-Prot:P34896

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