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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
    mouse all
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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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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    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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