SHMT2 serine hydroxymethyltransferase 2 [Homo sapiens (human)] - Gene

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: mouse all
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Genomic context

Location:: 12q13.3

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (57229711..57234935)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (57197949..57203173)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (57623494..57628718)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

YTHDF1 enhances stemness and chemoresistance in triple-negative breast cancer cells by upregulating SIAH2.
Title: YTHDF1 enhances stemness and chemoresistance in triple-negative breast cancer cells by upregulating SIAH2.
The expression and clinical significance of serine hydroxymethyltransferase2 in gastric cancer.
Title: The expression and clinical significance of serine hydroxymethyltransferase2 in gastric cancer.
NFYB increases chemosensitivity in glioblastoma by promoting HDAC5-mediated transcriptional inhibition of SHMT2.
Title: NFYB increases chemosensitivity in glioblastoma by promoting HDAC5-mediated transcriptional inhibition of SHMT2.
MiR-24-1-5p Hinders Malignant Phenotypes of Clear Cell Renal Cell Carcinoma by Targeting SHOX2.
Title: MiR-24-1-5p Hinders Malignant Phenotypes of Clear Cell Renal Cell Carcinoma by Targeting SHOX2.
SHMT2 Promotes Gastric Cancer Development through Regulation of HIF1alpha/VEGF/STAT3 Signaling.
Title: SHMT2 Promotes Gastric Cancer Development through Regulation of HIF1α/VEGF/STAT3 Signaling.
Serine hydroxymethyltransferase 2 knockdown induces apoptosis in ccRCC by causing lysosomal membrane permeabilization via metabolic reprogramming.
Title: Serine hydroxymethyltransferase 2 knockdown induces apoptosis in ccRCC by causing lysosomal membrane permeabilization via metabolic reprogramming.
Exosome-mediated transfer of circ_0063526 enhances cisplatin resistance in gastric cancer cells via regulating miR-449a/SHMT2 axis.
Title: Exosome-mediated transfer of circ_0063526 enhances cisplatin resistance in gastric cancer cells via regulating miR-449a/SHMT2 axis.
Induction of serine hydroxymethyltransferase 2 promotes tumorigenesis and metastasis in neuroblastoma.
Title: Induction of serine hydroxymethyltransferase 2 promotes tumorigenesis and metastasis in neuroblastoma.
SHMT2 promotes the tumorigenesis of renal cell carcinoma by regulating the m6A modification of PPAT.
Title: SHMT2 promotes the tumorigenesis of renal cell carcinoma by regulating the m6A modification of PPAT.
The serine hydroxymethyltransferase-2 (SHMT2) initiates lymphoma development through epigenetic tumor suppressor silencing.
Title: The serine hydroxymethyltransferase-2 (SHMT2) initiates lymphoma development through epigenetic tumor suppressor silencing.

Submit: New GeneRIF Correction See all GeneRIFs (50)

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

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 EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH15808 (e-PCR)
- UniSTS:87611

RH98752 (e-PCR)
- UniSTS:84546

STS-W84778 (e-PCR)
- UniSTS:69470

L11932 (e-PCR)
- UniSTS:39779

RH71214 (e-PCR)
- UniSTS:13268

RH47705 (e-PCR)
- UniSTS:68574

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	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 more info	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
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

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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

EC 2.1.2.1

NP_001159829.1

EC 2.1.2.1

NP_001159830.1

EC 2.1.2.1

NP_001159831.1

EC 2.1.2.1

NP_005403.2

EC 2.1.2.1

XP_011536977.1

EC 2.1.2.1

XP_054228880.1

EC 2.1.2.1

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

NG_029163.1 RefSeqGene

Range

5139..10363

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001166356.2 → NP_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:45 → 492

PLN03226; serine hydroxymethyltransferase; Provisional

pfam00464
Location:49 → 438

SHMT; Serine hydroxymethyltransferase
NM_001166357.1 → NP_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:24 → 481

PLN03226; serine hydroxymethyltransferase; Provisional

pfam00464
Location:28 → 427

SHMT; Serine hydroxymethyltransferase
NM_001166358.2 → NP_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:24 → 481

PLN03226; serine hydroxymethyltransferase; Provisional

pfam00464
Location:28 → 427

SHMT; Serine hydroxymethyltransferase
NM_001166359.1 → NP_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:24 → 481

PLN03226; serine hydroxymethyltransferase; Provisional

pfam00464
Location:28 → 427

SHMT; Serine hydroxymethyltransferase
NM_005412.6 → NP_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:45 → 502

PLN03226; serine hydroxymethyltransferase; Provisional

RNA

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
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
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
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_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

57229711..57234935

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011538675.4 → XP_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:101 → 352

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 ...