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MTHFD2 methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase [ Homo sapiens (human) ]

Gene ID: 10797, updated on 17-Jun-2024

Summary

Official Symbol
MTHFD2provided by HGNC
Official Full Name
methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolaseprovided by HGNC
Primary source
HGNC:HGNC:7434
See related
Ensembl:ENSG00000065911 MIM:604887; AllianceGenome:HGNC:7434
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
NMDMC
Summary
This gene encodes a nuclear-encoded mitochondrial bifunctional enzyme with methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase activities. The enzyme functions as a homodimer and is unique in its absolute requirement for magnesium and inorganic phosphate. Formation of the enzyme-magnesium complex allows binding of NAD. Alternative splicing results in two different transcripts, one protein-coding and the other not protein-coding. This gene has a pseudogene on chromosome 7. [provided by RefSeq, Mar 2009]
Expression
Ubiquitous expression in appendix (RPKM 27.6), lymph node (RPKM 27.0) and 25 other tissues See more
Orthologs
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Genomic context

See MTHFD2 in Genome Data Viewer
Location:
2p13.1
Exon count:
9
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (74198615..74217565)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (74207390..74226316)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (74425742..74444692)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:74374793-74375452 Neighboring gene BOLA3 divergent transcript Neighboring gene MOB kinase activator 1A Neighboring gene ReSE screen-validated silencer GRCh37_chr2:74403666-74403858 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:74405031-74405714 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16046 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16047 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:74414816-74415489 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:74415490-74416162 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr2:74419240-74419966 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:74419967-74420694 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:74425404-74425962 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11655 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11656 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:74433385-74433964 Neighboring gene Sharpr-MPRA regulatory region 13618 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:74455229-74455729 Neighboring gene solute carrier family 4 member 5 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16049 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16050 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16051 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:74513902-74514036 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:74516904-74517404 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:74517405-74517905 Neighboring gene keratin 18 pseudogene 26 Neighboring gene RNA, U6 small nuclear 542, 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?

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Nef nef HIV-1 Nef is identified to have a physical interaction with methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2 (MTHFD2) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed

Go to the HIV-1, Human Interaction Database

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 magnesium ion binding IDA
Inferred from Direct Assay
more info
PubMed 
enables magnesium ion binding IMP
Inferred from Mutant Phenotype
more info
PubMed 
enables methenyltetrahydrofolate cyclohydrolase activity IBA
Inferred from Biological aspect of Ancestor
more info
 
enables methenyltetrahydrofolate cyclohydrolase activity IDA
Inferred from Direct Assay
more info
PubMed 
enables methenyltetrahydrofolate cyclohydrolase activity ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
enables methenyltetrahydrofolate cyclohydrolase activity TAS
Traceable Author Statement
more info
 
enables methylenetetrahydrofolate dehydrogenase (NAD+) activity IBA
Inferred from Biological aspect of Ancestor
more info
 
enables methylenetetrahydrofolate dehydrogenase (NAD+) activity IDA
Inferred from Direct Assay
more info
PubMed 
enables methylenetetrahydrofolate dehydrogenase (NAD+) activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
enables methylenetetrahydrofolate dehydrogenase (NAD+) activity TAS
Traceable Author Statement
more info
 
enables methylenetetrahydrofolate dehydrogenase (NADP+) activity IBA
Inferred from Biological aspect of Ancestor
more info
 
enables methylenetetrahydrofolate dehydrogenase (NADP+) activity IDA
Inferred from Direct Assay
more info
PubMed 
enables methylenetetrahydrofolate dehydrogenase (NADP+) activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
enables phosphate ion binding IDA
Inferred from Direct Assay
more info
PubMed 
enables phosphate ion binding IMP
Inferred from Mutant Phenotype
more info
PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
involved_in folic acid metabolic process TAS
Traceable Author Statement
more info
 
involved_in tetrahydrofolate interconversion 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
located_in extracellular space HDA PubMed 
located_in mitochondrial matrix TAS
Traceable Author Statement
more info
 
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
 
located_in mitochondrion IDA
Inferred from Direct Assay
more info
 
located_in mitochondrion ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 

General protein information

Preferred Names
bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial
Names
NAD-dependent methylene tetrahydrofolate dehydrogenase cyclohydrolase
NP_001397121.1
NP_006627.2
XP_006711987.1
XP_054196197.1

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_029162.2 RefSeqGene

    Range
    5002..23952
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001410192.1NP_001397121.1  bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial isoform B

    Status: REVIEWED

    Source sequence(s)
    AC073263
    UniProtKB/TrEMBL
    A0A7I2V482
    Related
    ENSP00000503701.1, ENST00000679055.1
  2. NM_006636.4NP_006627.2  bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial isoform A precursor

    See identical proteins and their annotated locations for NP_006627.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the shorter transcript and is the protein-coding transcript.
    Source sequence(s)
    AC073263, BC017054, BX475613, CB124593
    Consensus CDS
    CCDS1935.2
    UniProtKB/Swiss-Prot
    P13995, Q53G90, Q53GV5, Q53S36, Q7Z650
    UniProtKB/TrEMBL
    B2R7W0
    Related
    ENSP00000377617.2, ENST00000394053.7
    Conserved Domains (3) summary
    cd01080
    Location:150329
    NAD_bind_m-THF_DH_Cyclohyd; NADP binding domain of methylene-tetrahydrofolate dehydrogenase/cyclohydrolase
    COG0190
    Location:39334
    FolD; 5,10-methylene-tetrahydrofolate dehydrogenase/Methenyl tetrahydrofolate cyclohydrolase [Coenzyme transport and metabolism]
    pfam00763
    Location:39155
    THF_DHG_CYH; Tetrahydrofolate dehydrogenase/cyclohydrolase, catalytic domain

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

  1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    74198615..74217565
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006711924.3XP_006711987.1  bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial isoform X1

    See identical proteins and their annotated locations for XP_006711987.1

    UniProtKB/TrEMBL
    A0A7I2V482
    Related
    ENSP00000503927.1, ENST00000678731.1
    Conserved Domains (1) summary
    COG0190
    Location:3232
    FolD; 5,10-methylene-tetrahydrofolate dehydrogenase/Methenyl tetrahydrofolate cyclohydrolase [Coenzyme transport and metabolism]

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    74207390..74226316
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054340222.1XP_054196197.1  bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial isoform X1

    UniProtKB/TrEMBL
    A0A7I2V482