MTRR 5-methyltetrahydrofolate-homocysteine methyltransferase reductase [Homo sapiens (human)] - Gene

Summary

Official Symbol: MTRRprovided by HGNC
Official Full Name: 5-methyltetrahydrofolate-homocysteine methyltransferase reductaseprovided by HGNC
Primary source: HGNC:HGNC:7473
See related: Ensembl:ENSG00000124275 MIM:602568; AllianceGenome:HGNC:7473
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: MSR; cblE
Summary: This gene encodes a member of the ferredoxin-NADP(+) reductase (FNR) family of electron transferases. This protein functions in the synthesis of methionine by regenerating methionine synthase to a functional state. Because methionine synthesis requires methyl-group transfer by a folate donor, activity of the encoded enzyme is important for folate metabolism and cellular methylation. Mutations in this gene can cause homocystinuria-megaloblastic anemia, cbl E type. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2015]
Expression: Ubiquitous expression in lung (RPKM 14.2), kidney (RPKM 10.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 5p15.31

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
110	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (7850859..7901113)
110	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (7808272..7840236)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (7869261..7901226)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

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?

Investigation of the relationship between MTRR A66G, MTR A2756G gene variations and cell anomalies in early diagnosis and progression of bladder cancer.
Title: Investigation of the relationship between MTRR A66G, MTR A2756G gene variations and cell anomalies in early diagnosis and progression of bladder cancer.
MTRR rs1532268 polymorphism and gastric cancer risk: evidence from a meta-analysis.
Title: MTRR rs1532268 polymorphism and gastric cancer risk: evidence from a meta-analysis.
Evidence of Association between MTRR and TNF-alpha Gene Polymorphisms and Oral Health-Related Quality of Life in Children with Anterior Open Bite.
Title: Evidence of Association between MTRR and TNF-α Gene Polymorphisms and Oral Health-Related Quality of Life in Children with Anterior Open Bite.
Analysis of the frequency distribution of five single-nucleotide polymorphisms of the MTRRgene in a Chinese pediatric population with acute lymphoblastic leukemia.
Title: Analysis of the frequency distribution of five single-nucleotide polymorphisms of the MTRRgene in a Chinese pediatric population with acute lymphoblastic leukemia.
Contribution of 5-Methyltetrahydrofolate-Homocysteine Methyltransferase Reductase Genotypes to Colorectal Cancer in Taiwan.
Title: Contribution of <i>5-Methyltetrahydrofolate-Homocysteine Methyltransferase Reductase</i> Genotypes to Colorectal Cancer in Taiwan.
Folate metabolism abnormalities in infertile patients with endometriosis.
Title: Folate metabolism abnormalities in infertile patients with endometriosis.
Association of methionine synthase (rs1805087), methionine synthase reductase (rs1801394), and methylenetetrahydrofolate dehydrogenase 1 (rs2236225) genetic polymorphisms with recurrent implantation failure.
Title: Association of methionine synthase (rs1805087), methionine synthase reductase (rs1801394), and methylenetetrahydrofolate dehydrogenase 1 (rs2236225) genetic polymorphisms with recurrent implantation failure.
Genetic variants in S-adenosyl-methionine synthesis pathway and nonsyndromic cleft lip with or without cleft palate in Chile.
Title: Genetic variants in S-adenosyl-methionine synthesis pathway and nonsyndromic cleft lip with or without cleft palate in Chile.
Association of three missense mutations in the homocysteine-related MTHFR and MTRR gene with risk of polycystic ovary syndrome in Southern Chinese women.
Title: Association of three missense mutations in the homocysteine-related MTHFR and MTRR gene with risk of polycystic ovary syndrome in Southern Chinese women.
Unconventional Biocatalytic Approaches to the Synthesis of Chiral Sulfoxides.
Title: Unconventional Biocatalytic Approaches to the Synthesis of Chiral Sulfoxides.

Submit: New GeneRIF Correction See all GeneRIFs (221)

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
Methylcobalamin deficiency type cblE MedGen: C1856057 OMIM: 236270 GeneReviews: Disorders of Intracellular Cobalamin Metabolism	Compare labs
Neural tube defects, folate-sensitive MedGen: C1866558 OMIM: 601634 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Identification of novel germline polymorphisms governing capecitabine sensitivity. 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)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-143127 (e-PCR)
- UniSTS:184064

MTRR_214 (e-PCR)
- UniSTS:277513

RH11562 (e-PCR)
- UniSTS:63875

STS-N29717 (e-PCR)
- UniSTS:76471

G19837 (e-PCR)
- UniSTS:17856

A002A03 (e-PCR)
- UniSTS:17857

Homology

Homologs of the MTRR gene: The MTRR gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, C.elegans, and frog.
Orthologs from Annotation Pipeline: 451 organisms have orthologs with human gene MTRR
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables FAD binding	IDA Inferred from Direct Assay more info	PubMed
enables FMN binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables FMN binding	IDA Inferred from Direct Assay more info	PubMed
enables NADPH binding	IDA Inferred from Direct Assay more info	PubMed
enables NADPH-hemoprotein reductase activity	IDA Inferred from Direct Assay more info	PubMed
enables [methionine synthase] reductase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables [methionine synthase] reductase activity	IDA Inferred from Direct Assay more info	PubMed
enables [methionine synthase] reductase activity	TAS Traceable Author Statement more info	PubMed
enables flavin adenine dinucleotide binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables flavin adenine dinucleotide binding	IDA Inferred from Direct Assay more info	PubMed
enables oxidoreductase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables oxidoreductase activity, acting on metal ions, NAD or NADP as acceptor	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA methylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in S-adenosylmethionine cycle	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in folic acid metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in folic acid metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in homocysteine catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in homocysteine metabolic process	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in methionine biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in methionine biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cystathionine beta-synthase activity	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info	PubMed
is_active_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in intermediate filament cytoskeleton	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: methionine synthase reductase

Names: [methionine synthase]-cobalamin methyltransferase (cob(II)alamin reducing); aqCbl reductase; aquacobalamin reductase; methionine synthase reductase, mitochondrial

NP_001351369.1

EC 1.16.1.8

NP_001351370.1

EC 1.16.1.8

NP_001351371.1

EC 1.16.1.8

NP_002445.2

EC 1.16.1.8

NP_076915.3

EC 1.16.1.8

XP_024301832.1

EC 1.16.1.8

XP_047273189.1

EC 1.16.1.8

XP_047273190.1

EC 1.16.1.8

XP_047273191.1

EC 1.16.1.8

XP_047273192.1

EC 1.16.1.8

XP_047273193.1

EC 1.16.1.8

XP_047273194.1

EC 1.16.1.8

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_008856.1 RefSeqGene

Range

5045..37010

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001364440.2 → NP_001351369.1 methionine synthase reductase

Status: REVIEWED

Description

Transcript Variant: This variant (6) represents the longest transcript. Variants 1, 2, 6, 7, and 8 all encode the same protein.

Source sequence(s)

AC010346, AC025174

UniProtKB/Swiss-Prot

Q7Z4M8

Conserved Domains (2) summary

cd06203
Location:277 → 697

methionine_synthase_red; Human methionine synthase reductase (MSR) restores methionine sythase which is responsible for the regeneration of methionine from homocysteine, as well as the coversion of methyltetrahydrofolate to tetrahydrofolate. In MSR, electrons are transferred ...

pfam00258
Location:6 → 142

Flavodoxin_1; Flavodoxin
NM_001364441.2 → NP_001351370.1 methionine synthase reductase

Status: REVIEWED

Description

Transcript Variant: This variant (7) differs in the 5' UTR compared to variant 6. Variants 1, 2, 6, 7, and 8 all encode the same protein.

Source sequence(s)

AC010346, AC025174

UniProtKB/Swiss-Prot

Q7Z4M8

Conserved Domains (2) summary

cd06203
Location:277 → 697

methionine_synthase_red; Human methionine synthase reductase (MSR) restores methionine sythase which is responsible for the regeneration of methionine from homocysteine, as well as the coversion of methyltetrahydrofolate to tetrahydrofolate. In MSR, electrons are transferred ...

pfam00258
Location:6 → 142

Flavodoxin_1; Flavodoxin
NM_001364442.2 → NP_001351371.1 methionine synthase reductase

Status: REVIEWED

Description

Transcript Variant: This variant (8) differs in the 5' UTR compared to variant 6. Variants 1, 2, 6, 7, and 8 all encode the same protein.

Source sequence(s)

AC010346, AC025174

UniProtKB/Swiss-Prot

Q7Z4M8

Conserved Domains (2) summary

cd06203
Location:277 → 697

methionine_synthase_red; Human methionine synthase reductase (MSR) restores methionine sythase which is responsible for the regeneration of methionine from homocysteine, as well as the coversion of methyltetrahydrofolate to tetrahydrofolate. In MSR, electrons are transferred ...

pfam00258
Location:6 → 142

Flavodoxin_1; Flavodoxin
NM_002454.3 → NP_002445.2 methionine synthase reductase

See identical proteins and their annotated locations for NP_002445.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) differs in the 5' UTR compared to variant 6. Variants 1, 2, 6, 7, and 8 all encode the same protein.

Source sequence(s)

BC054816, BC109216

Consensus CDS

CCDS47190.1

UniProtKB/Swiss-Prot

Q7Z4M8, Q9UBK8

Related

ENSP00000402510.2, ENST00000440940.7

Conserved Domains (2) summary

cd06203
Location:277 → 697

methionine_synthase_red; Human methionine synthase reductase (MSR) restores methionine sythase which is responsible for the regeneration of methionine from homocysteine, as well as the coversion of methyltetrahydrofolate to tetrahydrofolate. In MSR, electrons are transferred ...

pfam00258
Location:6 → 142

Flavodoxin_1; Flavodoxin
NM_024010.4 → NP_076915.3 methionine synthase reductase

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 6. Variants 1, 2, 6, 7, and 8 all encode the same protein.

Source sequence(s)

AC010346, AC025174

UniProtKB/Swiss-Prot

Q7Z4M8

Related

ENSP00000264668.2, ENST00000264668.6

Conserved Domains (2) summary

cd06203
Location:277 → 697

methionine_synthase_red; Human methionine synthase reductase (MSR) restores methionine sythase which is responsible for the regeneration of methionine from homocysteine, as well as the coversion of methyltetrahydrofolate to tetrahydrofolate. In MSR, electrons are transferred ...

pfam00258
Location:6 → 142

Flavodoxin_1; Flavodoxin

RNA

NR_134480.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate splice site in 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)

BC054816, BC109217, DA384356
NR_134481.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) 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)

AF121214, BC035977, BC054816
NR_134482.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (5) 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)

BC054816, BC062577, BC109217
NR_157168.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC010346, AC025174
NR_157169.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC010346, AC025174

Related

ENST00000511461.5
NR_157170.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC010346, AC025174
NR_157171.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC010346, AC025174
NR_157172.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC010346, AC025174
NR_157173.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC010346, AC025174
NR_157174.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC010346, AC025174
NR_157175.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC010346, AC025174
NR_157176.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC010346, AC025174
NR_157177.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC010346, AC025174
NR_157178.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC010346, AC025174

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 110 details...

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000005.10 Reference GRCh38.p14 Primary Assembly

Range

7850859..7901113

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047417233.1 → XP_047273189.1 methionine synthase reductase isoform X1

UniProtKB/Swiss-Prot

Q7Z4M8
XM_024446064.2 → XP_024301832.1 methionine synthase reductase isoform X1

UniProtKB/Swiss-Prot

Q7Z4M8

Conserved Domains (2) summary

cd06203
Location:277 → 697

methionine_synthase_red; Human methionine synthase reductase (MSR) restores methionine sythase which is responsible for the regeneration of methionine from homocysteine, as well as the coversion of methyltetrahydrofolate to tetrahydrofolate. In MSR, electrons are transferred ...

pfam00258
Location:6 → 142

Flavodoxin_1; Flavodoxin
XM_047417234.1 → XP_047273190.1 methionine synthase reductase isoform X1

UniProtKB/Swiss-Prot

Q7Z4M8
XM_047417235.1 → XP_047273191.1 methionine synthase reductase isoform X2
XM_047417236.1 → XP_047273192.1 methionine synthase reductase isoform X3
XM_047417237.1 → XP_047273193.1 methionine synthase reductase isoform X4

Related

ENSP00000421991.1, ENST00000510525.5
XM_047417238.1 → XP_047273194.1 methionine synthase reductase isoform X5