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Protein

Probable bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2

Gene

MTHFD2L

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

Catalytic activityi

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

Cofactori

Mg2+By similarity

Pathwayi: tetrahydrofolate interconversion

This protein is involved in the pathway tetrahydrofolate interconversion, which is part of One-carbon metabolism.
View all proteins of this organism that are known to be involved in the pathway tetrahydrofolate interconversion and in One-carbon metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei247NADBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi214 – 216NADBy similarity3

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Multifunctional enzyme, Oxidoreductase
Biological processAmino-acid biosynthesis, Histidine biosynthesis, Methionine biosynthesis, One-carbon metabolism, Purine biosynthesis
LigandMagnesium, NAD

Enzyme and pathway databases

ReactomeiR-HSA-196757 Metabolism of folate and pterines
UniPathwayiUPA00193

Names & Taxonomyi

Protein namesi
Recommended name:
Probable bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2
Alternative name(s):
NADP-dependent methylenetetrahydrofolate dehydrogenase 2-like protein
Short name:
MTHFD2-like
Including the following 2 domains:
NAD-dependent methylenetetrahydrofolate dehydrogenase (EC:1.5.1.15)
Methenyltetrahydrofolate cyclohydrolase (EC:3.5.4.9)
Gene namesi
Name:MTHFD2L
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000163738.18
HGNCiHGNC:31865 MTHFD2L
MIMi614047 gene
neXtProtiNX_Q9H903

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & Biotechi

Organism-specific databases

OpenTargetsiENSG00000163738
PharmGKBiPA134943916

Polymorphism and mutation databases

BioMutaiMTHFD2L
DMDMi353526325

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003370971 – 347Probable bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2Add BLAST347

Proteomic databases

EPDiQ9H903
PaxDbiQ9H903
PeptideAtlasiQ9H903
PRIDEiQ9H903
ProteomicsDBi81265
81266 [Q9H903-1]
81267 [Q9H903-2]
81268 [Q9H903-3]
81269 [Q9H903-5]

PTM databases

iPTMnetiQ9H903
PhosphoSitePlusiQ9H903

Expressioni

Tissue specificityi

Isoform 1, isoform 4 and isoform 5 are expressed in brain and placenta.1 Publication

Gene expression databases

BgeeiENSG00000163738
CleanExiHS_MTHFD2L
ExpressionAtlasiQ9H903 baseline and differential
GenevisibleiQ9H903 HS

Organism-specific databases

HPAiHPA035434

Interactioni

Protein-protein interaction databases

BioGridi137092, 9 interactors
IntActiQ9H903, 1 interactor
STRINGi9606.ENSP00000379108

Structurei

3D structure databases

ProteinModelPortaliQ9H903
SMRiQ9H903
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni98 – 102Substrate bindingBy similarity5
Regioni145 – 147Substrate bindingBy similarity3
Regioni323 – 327Substrate bindingBy similarity5

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0089 Eukaryota
COG0190 LUCA
GeneTreeiENSGT00920000149057
HOGENOMiHOG000218242
HOVERGENiHBG006411
InParanoidiQ9H903
KOiK13403
OMAiGIPKLIT
OrthoDBiEOG091G0VB7
PhylomeDBiQ9H903
TreeFamiTF323998

Family and domain databases

HAMAPiMF_01576 THF_DHG_CYH, 1 hit
InterProiView protein in InterPro
IPR036291 NAD(P)-bd_dom_sf
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
PS00767 THF_DHG_CYH_2, 1 hit

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 4 (identifier: Q9H903-4) [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
MTVPVRGFSL LRGRLGRAPA LGRSTAPSVR APGEPGSAFR GFRSSGVRHE
60 70 80 90 100
AIIISGTEMA KHIQKEIQRG VESWVSLGNR RPHLSIILVG DNPASHTYVR
110 120 130 140 150
NKIRAASAVG ICSELILKPK DVSQEELLDV TDQLNMDPRV SGILVQLPLP
160 170 180 190 200
DHVDERTICN GIAPEKDVDG FHIINIGRLC LDQHSLIPAT ASAVWEIIKR
210 220 230 240 250
TGIQTFGKNV VVAGRSKNVG MPIAMLLHTD GEHERPGGDA TVTIAHRYTP
260 270 280 290 300
KEQLKIHTQL ADIIIVAAGI PKLITSDMVK EGAAVIDVGI NYVHDPVTGK
310 320 330 340
TKLVGDVDFE AVKKKAGFIT PVPGGVGPMT VAMLLKNTLL AAKKIIY
Length:347
Mass (Da):37,315
Last modified:October 19, 2011 - v3
Checksum:i2A2C787BF7C89C2E
GO
Isoform 1 (identifier: Q9H903-1) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-58: Missing.

Show »
Length:289
Mass (Da):31,285
Checksum:i7AF37065528EA88A
GO
Isoform 2 (identifier: Q9H903-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-277: Missing.

Note: No experimental confirmation available.
Show »
Length:70
Mass (Da):7,340
Checksum:i2F10655C298DA41F
GO
Isoform 3 (identifier: Q9H903-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-58: Missing.
     269-281: GIPKLITSDMVKE → ERFHHFAQDLSNS
     282-347: Missing.

Note: No experimental confirmation available.
Show »
Length:223
Mass (Da):24,608
Checksum:i0AE4A0AD8E097705
GO
Isoform 5 (identifier: Q9H903-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     269-310: Missing.

Show »
Length:305
Mass (Da):32,891
Checksum:i2C88E9615943EE91
GO

Sequence cautioni

The sequence AAH32771 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB14441 differs from that shown. Contaminating sequence. Sequence of unknown origin in the N-terminal part.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0418771 – 277Missing in isoform 2. 1 PublicationAdd BLAST277
Alternative sequenceiVSP_0418781 – 58Missing in isoform 1 and isoform 3. 2 PublicationsAdd BLAST58
Alternative sequenceiVSP_041879269 – 310Missing in isoform 5. CuratedAdd BLAST42
Alternative sequenceiVSP_041880269 – 281GIPKL…DMVKE → ERFHHFAQDLSNS in isoform 3. 1 PublicationAdd BLAST13
Alternative sequenceiVSP_041881282 – 347Missing in isoform 3. 1 PublicationAdd BLAST66

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC093677 Genomic DNA No translation available.
AC097470 Genomic DNA No translation available.
CH471057 Genomic DNA Translation: EAX05705.1
AX794779 mRNA No translation available.
BC032771 mRNA Translation: AAH32771.1 Different initiation.
BC065771 mRNA Translation: AAH65771.1
AK023167 mRNA Translation: BAB14441.1 Sequence problems.
CCDSiCCDS47075.1 [Q9H903-4]
RefSeqiNP_001138450.1, NM_001144978.1 [Q9H903-4]
UniGeneiHs.721011
Hs.740700
Hs.740707

Genome annotation databases

EnsembliENST00000325278; ENSP00000321984; ENSG00000163738 [Q9H903-1]
ENST00000395759; ENSP00000379108; ENSG00000163738 [Q9H903-4]
ENST00000429519; ENSP00000391327; ENSG00000163738 [Q9H903-3]
GeneIDi441024
KEGGihsa:441024
UCSCiuc011cbj.3 human [Q9H903-4]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiMTD2L_HUMAN
AccessioniPrimary (citable) accession number: Q9H903
Secondary accession number(s): Q6P079, Q8N560
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: October 19, 2011
Last modified: July 18, 2018
This is version 131 of the entry and version 3 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. SIMILARITY comments
    Index of protein domains and families

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