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Protein

Dihydrofolate reductase

Gene

DHFR

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1 (By similarity).By similarity

Catalytic activityi

5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH.PROSITE-ProRule annotation

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei10 – 101NADP; via amide nitrogen and carbonyl oxygenBy similarity
Binding sitei71 – 711SubstrateBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi16 – 227NADPBy similarity
Nucleotide bindingi55 – 573NADPBy similarity
Nucleotide bindingi77 – 793NADPBy similarity
Nucleotide bindingi117 – 1248NADPBy similarity

GO - Molecular functioni

  1. dihydrofolate reductase activity Source: UniProtKB
  2. drug binding Source: UniProtKB
  3. mRNA binding Source: UniProtKB
  4. NADP binding Source: InterPro

GO - Biological processi

  1. glycine biosynthetic process Source: InterPro
  2. nucleotide biosynthetic process Source: InterPro
  3. one-carbon metabolic process Source: UniProtKB-KW
  4. response to methotrexate Source: UniProtKB-KW
  5. tetrahydrofolate biosynthetic process Source: UniProtKB-UniPathway
  6. tetrahydrofolate metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Methotrexate resistance, One-carbon metabolism

Keywords - Ligandi

NADP, RNA-binding

Enzyme and pathway databases

ReactomeiREACT_273892. E2F mediated regulation of DNA replication.
REACT_279156. G1/S-Specific Transcription.
REACT_333703. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
REACT_349423. Metabolism of folate and pterines.
SABIO-RKP00376.
UniPathwayiUPA00077; UER00158.

Names & Taxonomyi

Protein namesi
Recommended name:
Dihydrofolate reductase (EC:1.5.1.3)
Gene namesi
Name:DHFR
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
ProteomesiUP000009136 Componenti: Chromosome 7

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 187186Dihydrofolate reductasePRO_0000186361Add
BLAST

Proteomic databases

PaxDbiP00376.
PRIDEiP00376.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000010103.

Structurei

3D structure databases

ProteinModelPortaliP00376.
SMRiP00376. Positions 2-187.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini4 – 185182DHFRPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni31 – 366Substrate bindingBy similarity

Sequence similaritiesi

Belongs to the dihydrofolate reductase family.Curated
Contains 1 DHFR (dihydrofolate reductase) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0262.
HOGENOMiHOG000040235.
HOVERGENiHBG000773.
InParanoidiP00376.
KOiK00287.
OrthoDBiEOG7V1FS3.
TreeFamiTF317636.

Family and domain databases

Gene3Di3.40.430.10. 1 hit.
InterProiIPR012259. DHFR.
IPR024072. DHFR-like_dom.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
[Graphical view]
PfamiPF00186. DHFR_1. 1 hit.
[Graphical view]
PRINTSiPR00070. DHFR.
SUPFAMiSSF53597. SSF53597. 1 hit.
PROSITEiPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P00376-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVRPLNCIVA VSQNMGIGKN GDLPWPPLRN EFQYFQRMTT VSSVEGKQNL
60 70 80 90 100
VIMGRKTWFS IPEKNRPLKD RINIVLSREL KEPPKGAHFL AKSLDDALEL
110 120 130 140 150
IEDPELTNKV DVVWIVGGSS VYKEAMNKPG HVRLFVTRIM QEFESDAFFP
160 170 180
EIDFEKYKLL PEYPGVPLDV QEEKGIKYKF EVYEKNN
Length:187
Mass (Da):21,604
Last modified:January 23, 2007 - v3
Checksum:i0727DD855C8A7CD8
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti22 – 221D → N in AAI14163 (Ref. 1) Curated
Sequence conflicti102 – 1021E → Q AA sequence (PubMed:7115669).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC114162 mRNA. Translation: AAI14163.1.
PIRiA00388. RDBOD.
RefSeqiNP_001071351.1. NM_001077883.1.
UniGeneiBt.18730.

Genome annotation databases

GeneIDi508809.
KEGGibta:508809.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC114162 mRNA. Translation: AAI14163.1.
PIRiA00388. RDBOD.
RefSeqiNP_001071351.1. NM_001077883.1.
UniGeneiBt.18730.

3D structure databases

ProteinModelPortaliP00376.
SMRiP00376. Positions 2-187.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000010103.

Chemistry

BindingDBiP00376.
ChEMBLiCHEMBL1075051.

Proteomic databases

PaxDbiP00376.
PRIDEiP00376.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi508809.
KEGGibta:508809.

Organism-specific databases

CTDi1719.

Phylogenomic databases

eggNOGiCOG0262.
HOGENOMiHOG000040235.
HOVERGENiHBG000773.
InParanoidiP00376.
KOiK00287.
OrthoDBiEOG7V1FS3.
TreeFamiTF317636.

Enzyme and pathway databases

UniPathwayiUPA00077; UER00158.
ReactomeiREACT_273892. E2F mediated regulation of DNA replication.
REACT_279156. G1/S-Specific Transcription.
REACT_333703. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
REACT_349423. Metabolism of folate and pterines.
SABIO-RKP00376.

Miscellaneous databases

NextBioi20868689.

Family and domain databases

Gene3Di3.40.430.10. 1 hit.
InterProiIPR012259. DHFR.
IPR024072. DHFR-like_dom.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
[Graphical view]
PfamiPF00186. DHFR_1. 1 hit.
[Graphical view]
PRINTSiPR00070. DHFR.
SUPFAMiSSF53597. SSF53597. 1 hit.
PROSITEiPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. NIH - Mammalian Gene Collection (MGC) project
    Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Hereford.
    Tissue: Heart ventricle.
  2. "Structure of dihydrofolate reductase: primary sequence of the bovine liver enzyme."
    Lai P.-H., Pan Y.-C.E., Gleisner J.M., Peterson D.L., Williams K.R., Blakley R.L.
    Biochemistry 21:3284-3294(1981) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 2-187.
    Tissue: Liver.

Entry informationi

Entry nameiDYR_BOVIN
AccessioniPrimary (citable) accession number: P00376
Secondary accession number(s): Q29RI1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 23, 2007
Last modified: April 1, 2015
This is version 99 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.