Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial

Gene

MTHFD2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Miscellaneous

This NAD-dependent bifunctional enzyme has very different kinetic properties than the larger NADP-dependent trifunctional enzyme and is unique in that it requires formation of an enzyme-magnesium complex to allow binding of NAD.

Catalytic activityi

5,10-methylenetetrahydrofolate + NAD+ = 5,10-methenyltetrahydrofolate + NADH.
5,10-methenyltetrahydrofolate + H2O = 10-formyltetrahydrofolate.

Cofactori

GO - Molecular functioni

  • magnesium ion binding Source: UniProtKB
  • methenyltetrahydrofolate cyclohydrolase activity Source: UniProtKB
  • methylenetetrahydrofolate dehydrogenase (NAD+) activity Source: UniProtKB
  • methylenetetrahydrofolate dehydrogenase (NADP+) activity Source: UniProtKB
  • phosphate ion binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Oxidoreductase
Biological processOne-carbon metabolism
LigandMagnesium, NAD

Enzyme and pathway databases

BRENDAi1.5.1.15. 2681.
ReactomeiR-HSA-196757. Metabolism of folate and pterines.
SABIO-RKiP13995.

Names & Taxonomyi

Protein namesi
Recommended name:
Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial
Including the following 2 domains:
NAD-dependent methylenetetrahydrofolate dehydrogenase (EC:1.5.1.15)
Methenyltetrahydrofolate cyclohydrolase (EC:3.5.4.9)
Gene namesi
Name:MTHFD2
Synonyms:NMDMC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:7434. MTHFD2.

Subcellular locationi

GO - Cellular componenti

  • extracellular space Source: UniProtKB
  • mitochondrial matrix Source: Reactome
  • mitochondrion Source: UniProtKB

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Organism-specific databases

DisGeNETi10797.
OpenTargetsiENSG00000065911.
PharmGKBiPA31238.

Chemistry databases

ChEMBLiCHEMBL3621036.
DrugBankiDB00157. NADH.
DB00116. Tetrahydrofolic acid.

Polymorphism and mutation databases

BioMutaiMTHFD2.
DMDMi115311607.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 35MitochondrionCombined sourcesAdd BLAST35
ChainiPRO_000003404936 – 350Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrialAdd BLAST315

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei50N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP13995.
MaxQBiP13995.
PaxDbiP13995.
PeptideAtlasiP13995.
PRIDEiP13995.

PTM databases

iPTMnetiP13995.
PhosphoSitePlusiP13995.

Expressioni

Developmental stagei

Expressed only in developing normal tissues.

Gene expression databases

BgeeiENSG00000065911.
CleanExiHS_MTHFD2.
ExpressionAtlasiP13995. baseline and differential.
GenevisibleiP13995. HS.

Organism-specific databases

HPAiCAB003684.
HPA049657.

Interactioni

Subunit structurei

Homodimer.

Protein-protein interaction databases

BioGridi116011. 24 interactors.
IntActiP13995. 8 interactors.
MINTiMINT-4656441.
STRINGi9606.ENSP00000377617.

Chemistry databases

BindingDBiP13995.

Structurei

Secondary structure

1350
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi42 – 62Combined sources21
Beta strandi69 – 76Combined sources8
Helixi79 – 95Combined sources17
Beta strandi98 – 104Combined sources7
Helixi110 – 122Combined sources13
Beta strandi128 – 131Combined sources4
Helixi141 – 147Combined sources7
Helixi150 – 152Combined sources3
Helixi159 – 166Combined sources8
Helixi175 – 187Combined sources13
Beta strandi195 – 199Combined sources5
Turni203 – 205Combined sources3
Helixi206 – 214Combined sources9
Beta strandi219 – 221Combined sources3
Beta strandi227 – 231Combined sources5
Helixi237 – 244Combined sources8
Beta strandi248 – 252Combined sources5
Helixi262 – 264Combined sources3
Beta strandi270 – 273Combined sources4
Beta strandi277 – 279Combined sources3
Beta strandi288 – 290Combined sources3
Helixi295 – 298Combined sources4
Turni299 – 301Combined sources3
Beta strandi303 – 305Combined sources3
Beta strandi308 – 311Combined sources4
Helixi312 – 329Combined sources18

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ZN4model-A/B37-350[»]
5TC4X-ray1.89A36-350[»]
ProteinModelPortaliP13995.
SMRiP13995.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0089. Eukaryota.
COG0190. LUCA.
GeneTreeiENSGT00880000137956.
HOGENOMiHOG000218242.
HOVERGENiHBG006411.
InParanoidiP13995.
KOiK13403.
OMAiAGKLCGD.
OrthoDBiEOG091G0VB7.
PhylomeDBiP13995.
TreeFamiTF323998.

Family and domain databases

HAMAPiMF_01576. THF_DHG_CYH. 1 hit.
InterProiView protein in InterPro
IPR016040. NAD(P)-bd_dom.
IPR000672. THF_DH/CycHdrlase.
IPR020630. THF_DH/CycHdrlase_cat_dom.
IPR020867. THF_DH/CycHdrlase_CS.
IPR020631. THF_DH/CycHdrlase_NAD-bd_dom.
PANTHERiPTHR10025. PTHR10025. 1 hit.
PfamiView protein in Pfam
PF00763. THF_DHG_CYH. 1 hit.
PF02882. THF_DHG_CYH_C. 1 hit.
PRINTSiPR00085. THFDHDRGNASE.
SUPFAMiSSF51735. SSF51735. 1 hit.
PROSITEiView protein in PROSITE
PS00766. THF_DHG_CYH_1. 1 hit.
PS00767. THF_DHG_CYH_2. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P13995-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAATSLMSAL AARLLQPAHS CSLRLRPFHL AAVRNEAVVI SGRKLAQQIK
60 70 80 90 100
QEVRQEVEEW VASGNKRPHL SVILVGENPA SHSYVLNKTR AAAVVGINSE
110 120 130 140 150
TIMKPASISE EELLNLINKL NNDDNVDGLL VQLPLPEHID ERRICNAVSP
160 170 180 190 200
DKDVDGFHVI NVGRMCLDQY SMLPATPWGV WEIIKRTGIP TLGKNVVVAG
210 220 230 240 250
RSKNVGMPIA MLLHTDGAHE RPGGDATVTI SHRYTPKEQL KKHTILADIV
260 270 280 290 300
ISAAGIPNLI TADMIKEGAA VIDVGINRVH DPVTAKPKLV GDVDFEGVRQ
310 320 330 340 350
KAGYITPVPG GVGPMTVAML MKNTIIAAKK VLRLEEREVL KSKELGVATN
Length:350
Mass (Da):37,895
Last modified:September 19, 2006 - v2
Checksum:i4DBD263CF7BE28F4
GO
Isoform 2 (identifier: P13995-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-102: Missing.

Show »
Length:248
Mass (Da):26,849
Checksum:iB879A764146114F6
GO

Sequence cautioni

The sequence AAX93061 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAD96546 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAD96761 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAA34431 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti75V → A in BAD96546 (Ref. 3) Curated1
Sequence conflicti95V → A in BAD96761 (Ref. 3) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0561881 – 102Missing in isoform 2. 2 PublicationsAdd BLAST102

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X16396 mRNA. Translation: CAA34431.1. Different initiation.
AK300035 mRNA. Translation: BAG61846.1.
AK222826 mRNA. Translation: BAD96546.1. Different initiation.
AK223041 mRNA. Translation: BAD96761.1. Different initiation.
AC073263 Genomic DNA. Translation: AAX93061.1. Different initiation.
CH471053 Genomic DNA. Translation: EAW99671.1.
CH471053 Genomic DNA. Translation: EAW99672.1.
BC001548 mRNA. Translation: AAH01548.2.
BC015062 mRNA. Translation: AAH15062.1.
BC017054 mRNA. Translation: AAH17054.2.
CCDSiCCDS1935.2. [P13995-1]
PIRiS14902. DEHUMT.
RefSeqiNP_006627.2. NM_006636.3. [P13995-1]
XP_006711987.1. XM_006711924.2. [P13995-2]
UniGeneiHs.469030.

Genome annotation databases

EnsembliENST00000394053; ENSP00000377617; ENSG00000065911. [P13995-1]
GeneIDi10797.
KEGGihsa:10797.
UCSCiuc002skk.4. human. [P13995-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiMTDC_HUMAN
AccessioniPrimary (citable) accession number: P13995
Secondary accession number(s): Q53G90
, Q53GV5, Q53S36, Q7Z650
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: September 19, 2006
Last modified: July 5, 2017
This is version 186 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families