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    SHMT2 serine hydroxymethyltransferase 2 [ Homo sapiens (human) ]

    Gene ID: 6472, updated on 27-Nov-2024

    Summary

    Official Symbol
    SHMT2provided by HGNC
    Official Full Name
    serine hydroxymethyltransferase 2provided by HGNC
    Primary source
    HGNC:HGNC:10852
    See related
    Ensembl:ENSG00000182199 MIM:138450; AllianceGenome:HGNC:10852
    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
    GLYA; SHMT; mSHMT; NEDCASB; HEL-S-51e
    Summary
    This gene encodes the mitochondrial form of a pyridoxal phosphate-dependent enzyme that catalyzes the reversible reaction of serine and tetrahydrofolate to glycine and 5,10-methylene tetrahydrofolate. The encoded product is primarily responsible for glycine synthesis. The activity of the encoded protein has been suggested to be the primary source of intracellular glycine. The gene which encodes the cytosolic form of this enzyme is located on chromosome 17. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
    Expression
    Ubiquitous expression in liver (RPKM 35.4), lymph node (RPKM 21.8) and 25 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See SHMT2 in Genome Data Viewer
    Location:
    12q13.3
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (57229711..57234935)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (57197949..57203173)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (57623494..57628718)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene LDL receptor related protein 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4576 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:57608455-57608977 Neighboring gene microRNA 1228 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:57609975-57610474 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:57610622-57611230 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:57611231-57611837 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:57617093-57617999 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4578 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6528 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6529 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6530 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:57624967-57625547 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:57625548-57626129 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:57626711-57627291 Neighboring gene Sharpr-MPRA regulatory region 225 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6532 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:57631624-57632226 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4579 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:57633295-57634200 Neighboring gene OCT4-H3K4me1 hESC enhancer GRCh37_chr12:57636011-57636914 Neighboring gene neurexophilin 4 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6534 Neighboring gene NDUFA4 mitochondrial complex associated like 2 Neighboring gene Sharpr-MPRA regulatory region 5413 Neighboring gene SH3 and cysteine rich domain 3 Neighboring gene R3H domain containing 2 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr12:57673563-57674762 Neighboring gene Sharpr-MPRA regulatory region 11351 Neighboring gene Sharpr-MPRA regulatory region 7317 Neighboring gene RNA, U6 small nuclear 879, pseudogene

    Genomic regions, transcripts, and products

    Expression

    • Project title: 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

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities
    MedGen: C5436848 OMIM: 619121 GeneReviews: Not available
    not available

    EBI GWAS Catalog

    Description
    Biological insights from 108 schizophrenia-associated genetic loci.
    EBI GWAS Catalog

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables L-allo-threonine aldolase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables amino acid binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables chromatin binding IDA
    Inferred from Direct Assay
    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 glycine hydroxymethyltransferase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    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 
    Process Evidence Code Pubs
    involved_in L-serine biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in L-serine metabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in L-serine metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    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 glycine metabolic process IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    involved_in glycine metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in one-carbon metabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in one-carbon metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of cell population proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in protein K63-linked deubiquitination IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in protein homotetramerization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in protein tetramerization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of aerobic respiration IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of mitochondrial translation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of oxidative phosphorylation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in response to type I interferon 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
    part_of BRISC complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in extracellular exosome HDA PubMed 
    located_in microtubule cytoskeleton IDA
    Inferred from Direct Assay
    more info
     
    located_in mitochondrial inner membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in mitochondrial inner membrane TAS
    Traceable Author Statement
    more info
     
    located_in mitochondrial matrix IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in mitochondrial nucleoid IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in mitochondrion HTP PubMed 
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 

    General protein information

    Preferred Names
    serine hydroxymethyltransferase, mitochondrial
    Names
    GLY A+
    epididymis secretory sperm binding protein Li 51e
    glycine auxotroph A, human complement for hamster
    glycine hydroxymethyltransferase
    mitochondrial serine hydroxymethyltransferase
    serine aldolase
    serine hydroxymethylase
    serine hydroxymethyltransferase 2 (mitochondrial)
    serine methylase
    threonine aldolase
    NP_001159828.1
    NP_001159829.1
    NP_001159830.1
    NP_001159831.1
    NP_005403.2
    XP_011536977.1
    XP_054228880.1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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_029163.1 RefSeqGene

      Range
      5139..10363
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001166356.2NP_001159828.1  serine hydroxymethyltransferase, mitochondrial isoform 2 precursor

      See identical proteins and their annotated locations for NP_001159828.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the central coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.
      Source sequence(s)
      BC032584, BC091501
      Consensus CDS
      CCDS55837.1
      UniProtKB/TrEMBL
      Q53ET4
      Related
      ENSP00000452315.1, ENST00000557487.5
      Conserved Domains (2) summary
      PLN03226
      Location:45492
      PLN03226; serine hydroxymethyltransferase; Provisional
      pfam00464
      Location:49438
      SHMT; Serine hydroxymethyltransferase
    2. NM_001166357.1NP_001159829.1  serine hydroxymethyltransferase, mitochondrial isoform 3

      See identical proteins and their annotated locations for NP_001159829.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) is the longest transcript. It differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (3) has a shorter N-terminus, compared to isoform 1. Variants 3, 4, and 5 encode the same isoform 3. Translation efficiency is uncertain from this alternative start codon, and there is rapid turnover of the mitochondrial protein in the cytoplasm prior to mitochondrial import due to its shortened import presequence (PMID 8999870).
      Source sequence(s)
      AK315916, BC091501, DC339924
      Consensus CDS
      CCDS53805.1
      UniProtKB/TrEMBL
      Q5HYG8
      Related
      ENSP00000413770.3, ENST00000449049.7
      Conserved Domains (2) summary
      PLN03226
      Location:24481
      PLN03226; serine hydroxymethyltransferase; Provisional
      pfam00464
      Location:28427
      SHMT; Serine hydroxymethyltransferase
    3. NM_001166358.2NP_001159830.1  serine hydroxymethyltransferase, mitochondrial isoform 3

      See identical proteins and their annotated locations for NP_001159830.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (3) has a shorter N-terminus, compared to isoform 1. Variants 3, 4, and 5 encode the same isoform 3. Translation efficiency is uncertain from this alternative start codon, and there is rapid turnover of the mitochondrial protein in the cytoplasm prior to mitochondrial import due to its shortened import presequence (PMID 8999870).
      Source sequence(s)
      AC137834, BC091501, BX647711
      Consensus CDS
      CCDS53805.1
      UniProtKB/TrEMBL
      Q5HYG8
      Related
      ENSP00000406881.3, ENST00000414700.7
      Conserved Domains (2) summary
      PLN03226
      Location:24481
      PLN03226; serine hydroxymethyltransferase; Provisional
      pfam00464
      Location:28427
      SHMT; Serine hydroxymethyltransferase
    4. NM_001166359.1NP_001159831.1  serine hydroxymethyltransferase, mitochondrial isoform 3

      See identical proteins and their annotated locations for NP_001159831.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (3) has a shorter N-terminus, compared to isoform 1. Variants 3, 4, and 5 encode the same isoform 3. Translation efficiency is uncertain from this alternative start codon, and there is rapid turnover of the mitochondrial protein in the cytoplasm prior to mitochondrial import due to its shortened import presequence (PMID 8999870).
      Source sequence(s)
      AC137834, AK296183, BC091501, CN395976
      Consensus CDS
      CCDS53805.1
      UniProtKB/TrEMBL
      Q5HYG8
      Related
      ENSP00000452419.1, ENST00000553474.5
      Conserved Domains (2) summary
      PLN03226
      Location:24481
      PLN03226; serine hydroxymethyltransferase; Provisional
      pfam00464
      Location:28427
      SHMT; Serine hydroxymethyltransferase
    5. NM_005412.6NP_005403.2  serine hydroxymethyltransferase, mitochondrial isoform 1 precursor

      See identical proteins and their annotated locations for NP_005403.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      BC011911, BC091501, DC386590
      Consensus CDS
      CCDS8934.1
      UniProtKB/Swiss-Prot
      B7Z9F1, E7EQ19, E7EU43, O00740, P34897, Q8N1A5
      UniProtKB/TrEMBL
      Q53ET4, V9HW06
      Related
      ENSP00000333667.3, ENST00000328923.8
      Conserved Domains (1) summary
      PLN03226
      Location:45502
      PLN03226; serine hydroxymethyltransferase; Provisional

    RNA

    1. NR_029415.1 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) contains an alternate 5' exon and lacks an internal exon, compared to variant 1. This variant is represented as non-coding because it lacks a large portion of the coding region and is likely a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC137834, AK297173, BC091501, CN395976
      Related
      ENST00000555116.5
    2. NR_029416.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) contains an alternate 5' exon and lacks an internal exon, compared to variant 1. This variant is represented as non-coding because it lacks a large portion of the coding region and is likely a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC137834, AK301443, BC091501
    3. NR_029417.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8) lacks an internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      BC091501, DC386590
      Related
      ENST00000556825.5
    4. NR_048562.1 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (9) contains an alternate 5' exon, lacks an internal exon, and uses an alternate splice site in an internal exon, compared to variant 1. This variant is represented as non-coding due to the presence of an upstream ORF that is predicted to interfere with translation of the longest ORF; translation of the upstream ORF renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      BC008711
      Related
      ENST00000555774.5

    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_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      57229711..57234935
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011538675.4XP_011536977.1  serine hydroxymethyltransferase, mitochondrial isoform X1

      See identical proteins and their annotated locations for XP_011536977.1

      UniProtKB/TrEMBL
      B4DLV4
      Conserved Domains (1) summary
      cl18945
      Location:101352
      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 ...

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      57197949..57203173
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054372905.1XP_054228880.1  serine hydroxymethyltransferase, mitochondrial isoform X1

      UniProtKB/TrEMBL
      B4DLV4