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UniProtKB - Q86XF0 (DYR2_HUMAN)
Protein
Dihydrofolate reductase 2, mitochondrial
Gene
DHFR2
Organism
Homo sapiens (Human)
Status
Functioni
Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Required to prevent uracil accumulation in mtDNA. Binds its own mRNA and that of DHFR.
2 PublicationsMiscellaneous
Humans have acquired two dihydrofolate reductase enzymes during their evolution, DHFR and DHFR2. In contrast to human, mice and brown rats have just one.1 Publication
Catalytic activityi
- (6S)-5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + H+ + NADPHPROSITE-ProRule annotation1 PublicationEC:1.5.1.3PROSITE-ProRule annotation1 Publication
Kineticsi
- KM=209 µM for dihydrofolate1 Publication
- KM=20 µM for NADPH1 Publication
: tetrahydrofolate biosynthesis Pathwayi
This protein is involved in step 1 of the subpathway that synthesizes 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate. This subpathway is part of the pathway tetrahydrofolate biosynthesis, which is itself part of Cofactor biosynthesis.View all proteins of this organism that are known to be involved in the subpathway that synthesizes 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate, the pathway tetrahydrofolate biosynthesis and in Cofactor biosynthesis.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 10 | NADP; via amide nitrogen and carbonyl oxygenBy similarity | 1 | |
Binding sitei | 71 | SubstrateBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 16 – 22 | NADPBy similarity | 7 | |
Nucleotide bindingi | 55 – 57 | NADPBy similarity | 3 | |
Nucleotide bindingi | 77 – 79 | NADPBy similarity | 3 | |
Nucleotide bindingi | 117 – 124 | NADPBy similarity | 8 |
GO - Molecular functioni
- dihydrofolate reductase activity Source: UniProtKB
- folate reductase activity Source: Reactome
- mRNA binding Source: UniProtKB
- NADP binding Source: GO_Central
GO - Biological processi
- dihydrofolate metabolic process Source: GO_Central
- folic acid metabolic process Source: GO_Central
- glycine biosynthetic process Source: InterPro
- one-carbon metabolic process Source: UniProtKB-KW
- tetrahydrofolate biosynthetic process Source: GO_Central
- tetrahydrofolate metabolic process Source: UniProtKB
- thymidine biosynthetic process Source: UniProtKB
Keywordsi
Molecular function | Oxidoreductase |
Biological process | One-carbon metabolism |
Ligand | NADP |
Enzyme and pathway databases
BRENDAi | 1.5.1.3, 2681 |
PathwayCommonsi | Q86XF0 |
Reactomei | R-HSA-196757, Metabolism of folate and pterines |
SignaLinki | Q86XF0 |
UniPathwayi | UPA00077;UER00158 |
Names & Taxonomyi
Protein namesi | Recommended name: Dihydrofolate reductase 2, mitochondrialAlternative name(s): Dihydrofolate reductase, mitochondrial (EC:1.5.1.3) Dihydrofolate reductase-like protein 1 |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:27309, DHFR2 |
MIMi | 616588, gene |
neXtProti | NX_Q86XF0 |
VEuPathDBi | HostDB:ENSG00000178700 |
Subcellular locationi
Mitochondrion
- Mitochondrion 2 Publications
- Mitochondrion matrix 1 Publication
- Mitochondrion inner membrane 1 Publication
Cytosol
- cytosol Source: Reactome
Mitochondrion
- mitochondrial inner membrane Source: UniProtKB
- mitochondrial matrix Source: UniProtKB
- mitochondrion Source: UniProtKB
Keywords - Cellular componenti
Membrane, Mitochondrion, Mitochondrion inner membranePathology & Biotechi
Organism-specific databases
DisGeNETi | 200895 |
OpenTargetsi | ENSG00000178700 |
PharmGKBi | PA134889916 |
Miscellaneous databases
Pharosi | Q86XF0, Tbio |
Chemistry databases
DrugBanki | DB02402, 5-(4-Methoxyphenoxy)-2,4-Quinazolinediamine DB02001, 5-(4-Morpholin-4-Yl-Phenylsulfanyl)-2,4-Quinazolinediamine DB04306, 5-[(4-Methylphenyl)Sulfanyl]-2,4-Quinazolinediamine DB01958, 5-[4-Tert-Butylphenylsulfanyl]-2,4-Quinazolinediamine DB01929, 5-Chloryl-2,4,6-quinazolinetriamine DB04163, 5-Phenylsulfanyl-2,4-Quinazolinediamine DB07862, 7-(1-ETHYL-PROPYL)-7H-PYRROLO-[3,2-F]QUINAZOLINE-1,3-DIAMINE DB08203, 7-[2-METHOXY-1-(METHOXYMETHYL)ETHYL]-7H-PYRROLO[3,2-F] QUINAZOLINE-1,3-DIAMINE DB12116, Epigallocatechin gallate |
Genetic variation databases
BioMutai | DHFR2 |
DMDMi | 74727819 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000186368 | 1 – 187 | Dihydrofolate reductase 2, mitochondrialAdd BLAST | 187 |
Proteomic databases
jPOSTi | Q86XF0 |
MassIVEi | Q86XF0 |
MaxQBi | Q86XF0 |
PaxDbi | Q86XF0 |
PeptideAtlasi | Q86XF0 |
PRIDEi | Q86XF0 |
ProteomicsDBi | 70273 |
TopDownProteomicsi | Q86XF0 |
PTM databases
iPTMneti | Q86XF0 |
PhosphoSitePlusi | Q86XF0 |
Expressioni
Tissue specificityi
Expressed in numerous cell lines.1 Publication
Gene expression databases
Bgeei | ENSG00000178700, Expressed in buccal mucosa cell and 223 other tissues |
ExpressionAtlasi | Q86XF0, baseline and differential |
Genevisiblei | Q86XF0, HS |
Organism-specific databases
HPAi | ENSG00000178700, Low tissue specificity |
Interactioni
Protein-protein interaction databases
BioGRIDi | 128354, 291 interactors |
IntActi | Q86XF0, 25 interactors |
STRINGi | 9606.ENSP00000377768 |
Miscellaneous databases
RNActi | Q86XF0, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 4 – 185 | DHFRPROSITE-ProRule annotationAdd BLAST | 182 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 31 – 36 | Substrate bindingBy similarity | 6 |
Sequence similaritiesi
Belongs to the dihydrofolate reductase family.Curated
Phylogenomic databases
eggNOGi | KOG1324, Eukaryota |
GeneTreei | ENSGT00390000010283 |
InParanoidi | Q86XF0 |
OMAi | AMSQNMG |
OrthoDBi | 1489621at2759 |
PhylomeDBi | Q86XF0 |
TreeFami | TF317636 |
Family and domain databases
CDDi | cd00209, DHFR, 1 hit |
Gene3Di | 3.40.430.10, 1 hit |
InterProi | View protein in InterPro IPR012259, DHFR IPR024072, DHFR-like_dom_sf IPR001796, DHFR_dom |
PANTHERi | PTHR48069, PTHR48069, 1 hit |
Pfami | View protein in Pfam PF00186, DHFR_1, 1 hit |
SUPFAMi | SSF53597, SSF53597, 1 hit |
PROSITEi | View protein in PROSITE PS51330, DHFR_2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
Q86XF0-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MFLLLNCIVA VSQNMGIGKN GDLPRPPLRN EFRYFQRMTT TSSVEGKQNL
60 70 80 90 100
VIMGRKTWFS IPEKNRPLKD RINLVLSREL KEPPQGAHFL ARSLDDALKL
110 120 130 140 150
TERPELANKV DMIWIVGGSS VYKEAMNHLG HLKLFVTRIM QDFESDTFFS
160 170 180
EIDLEKYKLL PEYPGVLSDV QEGKHIKYKF EVCEKDD
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketC9JJ68 | C9JJ68_HUMAN | Dihydrofolate reductase | DHFR2 | 114 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_061135 | 166 | V → I1 PublicationCorresponds to variant dbSNP:rs17855824Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AL832912 mRNA Translation: CAH10617.1 AC130896 Genomic DNA No translation available. CH471052 Genomic DNA Translation: EAW79895.1 CH471052 Genomic DNA Translation: EAW79896.1 BC045541 mRNA Translation: AAH45541.1 BC063379 mRNA Translation: AAH63379.1 |
CCDSi | CCDS2926.1 |
RefSeqi | NP_001182572.1, NM_001195643.1 NP_789785.1, NM_176815.4 XP_011510839.1, XM_011512537.2 |
Genome annotation databases
Ensembli | ENST00000314636.3; ENSP00000319170.2; ENSG00000178700.9 ENST00000394221.3; ENSP00000377768.2; ENSG00000178700.9 ENST00000461173.5; ENSP00000418415.1; ENSG00000178700.9 ENST00000619045.1; ENSP00000480823.1; ENSG00000178700.9 |
GeneIDi | 200895 |
KEGGi | hsa:200895 |
MANE-Selecti | ENST00000314636.3; ENSP00000319170.2; NM_176815.5; NP_789785.1 |
UCSCi | uc003dri.3, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AL832912 mRNA Translation: CAH10617.1 AC130896 Genomic DNA No translation available. CH471052 Genomic DNA Translation: EAW79895.1 CH471052 Genomic DNA Translation: EAW79896.1 BC045541 mRNA Translation: AAH45541.1 BC063379 mRNA Translation: AAH63379.1 |
CCDSi | CCDS2926.1 |
RefSeqi | NP_001182572.1, NM_001195643.1 NP_789785.1, NM_176815.4 XP_011510839.1, XM_011512537.2 |
3D structure databases
AlphaFoldDBi | Q86XF0 |
SMRi | Q86XF0 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 128354, 291 interactors |
IntActi | Q86XF0, 25 interactors |
STRINGi | 9606.ENSP00000377768 |
Chemistry databases
DrugBanki | DB02402, 5-(4-Methoxyphenoxy)-2,4-Quinazolinediamine DB02001, 5-(4-Morpholin-4-Yl-Phenylsulfanyl)-2,4-Quinazolinediamine DB04306, 5-[(4-Methylphenyl)Sulfanyl]-2,4-Quinazolinediamine DB01958, 5-[4-Tert-Butylphenylsulfanyl]-2,4-Quinazolinediamine DB01929, 5-Chloryl-2,4,6-quinazolinetriamine DB04163, 5-Phenylsulfanyl-2,4-Quinazolinediamine DB07862, 7-(1-ETHYL-PROPYL)-7H-PYRROLO-[3,2-F]QUINAZOLINE-1,3-DIAMINE DB08203, 7-[2-METHOXY-1-(METHOXYMETHYL)ETHYL]-7H-PYRROLO[3,2-F] QUINAZOLINE-1,3-DIAMINE DB12116, Epigallocatechin gallate |
PTM databases
iPTMneti | Q86XF0 |
PhosphoSitePlusi | Q86XF0 |
Genetic variation databases
BioMutai | DHFR2 |
DMDMi | 74727819 |
Proteomic databases
jPOSTi | Q86XF0 |
MassIVEi | Q86XF0 |
MaxQBi | Q86XF0 |
PaxDbi | Q86XF0 |
PeptideAtlasi | Q86XF0 |
PRIDEi | Q86XF0 |
ProteomicsDBi | 70273 |
TopDownProteomicsi | Q86XF0 |
Protocols and materials databases
Antibodypediai | 32082, 120 antibodies from 19 providers |
DNASUi | 200895 |
Genome annotation databases
Ensembli | ENST00000314636.3; ENSP00000319170.2; ENSG00000178700.9 ENST00000394221.3; ENSP00000377768.2; ENSG00000178700.9 ENST00000461173.5; ENSP00000418415.1; ENSG00000178700.9 ENST00000619045.1; ENSP00000480823.1; ENSG00000178700.9 |
GeneIDi | 200895 |
KEGGi | hsa:200895 |
MANE-Selecti | ENST00000314636.3; ENSP00000319170.2; NM_176815.5; NP_789785.1 |
UCSCi | uc003dri.3, human |
Organism-specific databases
CTDi | 200895 |
DisGeNETi | 200895 |
GeneCardsi | DHFR2 |
HGNCi | HGNC:27309, DHFR2 |
HPAi | ENSG00000178700, Low tissue specificity |
MIMi | 616588, gene |
neXtProti | NX_Q86XF0 |
OpenTargetsi | ENSG00000178700 |
PharmGKBi | PA134889916 |
VEuPathDBi | HostDB:ENSG00000178700 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1324, Eukaryota |
GeneTreei | ENSGT00390000010283 |
InParanoidi | Q86XF0 |
OMAi | AMSQNMG |
OrthoDBi | 1489621at2759 |
PhylomeDBi | Q86XF0 |
TreeFami | TF317636 |
Enzyme and pathway databases
UniPathwayi | UPA00077;UER00158 |
BRENDAi | 1.5.1.3, 2681 |
PathwayCommonsi | Q86XF0 |
Reactomei | R-HSA-196757, Metabolism of folate and pterines |
SignaLinki | Q86XF0 |
Miscellaneous databases
BioGRID-ORCSi | 200895, 379 hits in 1004 CRISPR screens |
ChiTaRSi | DHFR2, human |
GenomeRNAii | 200895 |
Pharosi | Q86XF0, Tbio |
PROi | PR:Q86XF0 |
RNActi | Q86XF0, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000178700, Expressed in buccal mucosa cell and 223 other tissues |
ExpressionAtlasi | Q86XF0, baseline and differential |
Genevisiblei | Q86XF0, HS |
Family and domain databases
CDDi | cd00209, DHFR, 1 hit |
Gene3Di | 3.40.430.10, 1 hit |
InterProi | View protein in InterPro IPR012259, DHFR IPR024072, DHFR-like_dom_sf IPR001796, DHFR_dom |
PANTHERi | PTHR48069, PTHR48069, 1 hit |
Pfami | View protein in Pfam PF00186, DHFR_1, 1 hit |
SUPFAMi | SSF53597, SSF53597, 1 hit |
PROSITEi | View protein in PROSITE PS51330, DHFR_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | DYR2_HUMAN | |
Accessioni | Q86XF0Primary (citable) accession number: Q86XF0 Secondary accession number(s): D3DN30, Q6P4I9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 20, 2005 |
Last sequence update: | June 1, 2003 | |
Last modified: | May 25, 2022 | |
This is version 142 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human chromosome 3
Human chromosome 3: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families