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Protein

Probable bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2

Gene

MTHFD2L

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Oxidoreductase

Keywords - Biological processi

Amino-acid biosynthesis, Histidine biosynthesis, Methionine biosynthesis, One-carbon metabolism, Purine biosynthesis

Keywords - Ligandi

Magnesium, 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

HGNCiHGNC:31865. MTHFD2L.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134943916.

Polymorphism and mutation databases

BioMutaiMTHFD2L.
DMDMi353526325.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 347347Probable bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2PRO_0000337097Add
BLAST

Proteomic databases

EPDiQ9H903.
MaxQBiQ9H903.
PaxDbiQ9H903.
PeptideAtlasiQ9H903.
PRIDEiQ9H903.

PTM databases

iPTMnetiQ9H903.
PhosphoSiteiQ9H903.

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. 6 interactions.
STRINGi9606.ENSP00000379108.

Structurei

3D structure databases

ProteinModelPortaliQ9H903.
SMRiQ9H903. Positions 52-345.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0089. Eukaryota.
COG0190. LUCA.
GeneTreeiENSGT00840000129764.
HOGENOMiHOG000218242.
HOVERGENiHBG006411.
InParanoidiQ9H903.
KOiK13403.
OMAiTEMAKHI.
OrthoDBiEOG091G0VB7.
PhylomeDBiQ9H903.
TreeFamiTF323998.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
HAMAPiMF_01576. THF_DHG_CYH. 1 hit.
InterProiIPR016040. 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.
[Graphical view]
PfamiPF00763. THF_DHG_CYH. 1 hit.
PF02882. THF_DHG_CYH_C. 1 hit.
[Graphical view]
PRINTSiPR00085. THFDHDRGNASE.
SUPFAMiSSF51735. SSF51735. 1 hit.
PROSITEiPS00767. THF_DHG_CYH_2. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 277277Missing in isoform 2. 1 PublicationVSP_041877Add
BLAST
Alternative sequencei1 – 5858Missing in isoform 1 and isoform 3. 2 PublicationsVSP_041878Add
BLAST
Alternative sequencei269 – 31042Missing in isoform 5. CuratedVSP_041879Add
BLAST
Alternative sequencei269 – 28113GIPKL…DMVKE → ERFHHFAQDLSNS in isoform 3. 1 PublicationVSP_041880Add
BLAST
Alternative sequencei282 – 34766Missing in isoform 3. 1 PublicationVSP_041881Add
BLAST

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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ9H903.
SMRiQ9H903. Positions 52-345.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi137092. 6 interactions.
STRINGi9606.ENSP00000379108.

PTM databases

iPTMnetiQ9H903.
PhosphoSiteiQ9H903.

Polymorphism and mutation databases

BioMutaiMTHFD2L.
DMDMi353526325.

Proteomic databases

EPDiQ9H903.
MaxQBiQ9H903.
PaxDbiQ9H903.
PeptideAtlasiQ9H903.
PRIDEiQ9H903.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi441024.
GeneCardsiMTHFD2L.
HGNCiHGNC:31865. MTHFD2L.
HPAiHPA035434.
MIMi614047. gene.
neXtProtiNX_Q9H903.
PharmGKBiPA134943916.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0089. Eukaryota.
COG0190. LUCA.
GeneTreeiENSGT00840000129764.
HOGENOMiHOG000218242.
HOVERGENiHBG006411.
InParanoidiQ9H903.
KOiK13403.
OMAiTEMAKHI.
OrthoDBiEOG091G0VB7.
PhylomeDBiQ9H903.
TreeFamiTF323998.

Enzyme and pathway databases

UniPathwayiUPA00193.
ReactomeiR-HSA-196757. Metabolism of folate and pterines.

Miscellaneous databases

ChiTaRSiMTHFD2L. human.
GenomeRNAii441024.
PROiQ9H903.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163738.
CleanExiHS_MTHFD2L.
ExpressionAtlasiQ9H903. baseline and differential.
GenevisibleiQ9H903. HS.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
HAMAPiMF_01576. THF_DHG_CYH. 1 hit.
InterProiIPR016040. 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.
[Graphical view]
PfamiPF00763. THF_DHG_CYH. 1 hit.
PF02882. THF_DHG_CYH_C. 1 hit.
[Graphical view]
PRINTSiPR00085. THFDHDRGNASE.
SUPFAMiSSF51735. SSF51735. 1 hit.
PROSITEiPS00767. THF_DHG_CYH_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMTD2L_HUMAN
AccessioniPrimary (citable) accession number: Q9H903
Secondary accession number(s): Q6P079, Q8N560
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: October 19, 2011
Last modified: September 7, 2016
This is version 115 of the entry and version 3 of the sequence. [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, Multifunctional enzyme, 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

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.