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Protein

Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial

Gene

Mthfd2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Although its dehydrogenase activity is NAD-specific, it can also utilize NADP at a reduced efficiency.By similarity

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei233NADBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi200 – 202NADBy similarity3

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

BRENDAi1.5.1.15. 3474.
ReactomeiR-MMU-196757. Metabolism of folate and pterines.
SABIO-RKiP18155.

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1338850. Mthfd2.

Subcellular locationi

GO - Cellular componenti

  • extracellular space Source: MGI
  • mitochondrion Source: MGI

Keywords - Cellular componenti

Mitochondrion

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 35Mitochondrion1 PublicationAdd BLAST35
ChainiPRO_000003405036 – 350Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrialAdd BLAST315

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei50N6-acetyllysine; alternateBy similarity1
Cross-linki50Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Ubl conjugation

Proteomic databases

EPDiP18155.
MaxQBiP18155.
PaxDbiP18155.
PeptideAtlasiP18155.
PRIDEiP18155.

PTM databases

iPTMnetiP18155.
PhosphoSitePlusiP18155.

Expressioni

Gene expression databases

BgeeiENSMUSG00000005667.
ExpressionAtlasiP18155. baseline and differential.
GenevisibleiP18155. MM.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000005810.

Structurei

3D structure databases

ProteinModelPortaliP18155.
SMRiP18155.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni84 – 88Substrate bindingBy similarity5
Regioni131 – 133Substrate bindingBy similarity3
Regioni309 – 313Substrate bindingBy similarity5

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0089. Eukaryota.
COG0190. LUCA.
GeneTreeiENSGT00880000137956.
HOGENOMiHOG000218242.
HOVERGENiHBG006411.
InParanoidiP18155.
KOiK13403.
OMAiAGKLCGD.
OrthoDBiEOG091G0VB7.
PhylomeDBiP18155.
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.

Sequencei

Sequence statusi: Complete.

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

P18155-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASVSLLSAL AVRLLRPTHG CHPRLQPFHL AAVRNEAVVI SGRKLAQQIK
60 70 80 90 100
QEVQQEVEEW VASGNKRPHL SVILVGDNPA SHSYVLNKTR AAAEVGINSE
110 120 130 140 150
TIVKPASVSE EELLNSIRKL NNDENVDGLL VQLPLPEHID ERKVCNAVSP
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 VIDVGINRVQ DPVTAKPKLV GDVDFEGVKK
310 320 330 340 350
KAGYITPVPG GVGPMTVAML MKNTIIAAKK VLRPEELEVF KSKQRGVATN
Length:350
Mass (Da):37,863
Last modified:November 1, 1990 - v1
Checksum:i896AD40D9154E9D7
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J04627 mRNA. Translation: AAA39827.1.
M63445
, M63415, M63439, M63440, M63441, M63442, M63443, M63444 Genomic DNA. Translation: AAA39828.1.
AK076019 mRNA. Translation: BAC36124.1.
AK159680 mRNA. Translation: BAE35283.1.
AK165840 mRNA. Translation: BAE38407.1.
BC019511 mRNA. Translation: AAH19511.1.
S52980 Genomic DNA. No translation available.
CCDSiCCDS20277.1.
PIRiA33267.
RefSeqiNP_032664.1. NM_008638.2.
UniGeneiMm.443.
Mm.475021.

Genome annotation databases

EnsembliENSMUST00000005810; ENSMUSP00000005810; ENSMUSG00000005667.
GeneIDi17768.
KEGGimmu:17768.
UCSCiuc009cne.2. mouse.

Similar proteinsi

Entry informationi

Entry nameiMTDC_MOUSE
AccessioniPrimary (citable) accession number: P18155
Secondary accession number(s): Q3TMN4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: November 1, 1990
Last modified: August 30, 2017
This is version 158 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Multifunctional enzyme, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families