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P00376

- DYR_BOVIN

UniProt

P00376 - DYR_BOVIN

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Protein
Dihydrofolate reductase
Gene
DHFR
Organism
Bos taurus (Bovine)
Status
Reviewed - 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.

Catalytic activityi

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

Pathwayi

Sites

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

Regions

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

GO - Molecular functioni

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

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_201998. E2F mediated regulation of DNA replication.
REACT_217517. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
REACT_222884. Metabolism of folate and pterines.
REACT_225533. G1/S-Specific Transcription.
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: Chromosome 7

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 187186Dihydrofolate reductase
PRO_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.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini4 – 185182DHFR
Add
BLAST

Region

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

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0262.
GeneTreeiENSGT00390000010283.
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

MVRPLNCIVA VSQNMGIGKN GDLPWPPLRN EFQYFQRMTT VSSVEGKQNL    50
VIMGRKTWFS IPEKNRPLKD RINIVLSREL KEPPKGAHFL AKSLDDALEL 100
IEDPELTNKV DVVWIVGGSS VYKEAMNKPG HVRLFVTRIM QEFESDAFFP 150
EIDFEKYKLL PEYPGVPLDV QEEKGIKYKF EVYEKNN 187
Length:187
Mass (Da):21,604
Last modified:January 23, 2007 - v3
Checksum:i0727DD855C8A7CD8
GO

Sequence conflict

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

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
BC114162 mRNA. Translation: AAI14163.1.
PIRiA00388. RDBOD.
RefSeqiNP_001071351.1. NM_001077883.1.
UniGeneiBt.18730.

Genome annotation databases

EnsembliENSBTAT00000010103; ENSBTAP00000010103; ENSBTAG00000007681.
GeneIDi508809.
KEGGibta:508809.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
BC114162 mRNA. Translation: AAI14163.1 .
PIRi A00388. RDBOD.
RefSeqi NP_001071351.1. NM_001077883.1.
UniGenei Bt.18730.

3D structure databases

ProteinModelPortali P00376.
SMRi P00376. Positions 2-187.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9913.ENSBTAP00000010103.

Chemistry

BindingDBi P00376.
ChEMBLi CHEMBL1075051.

Proteomic databases

PaxDbi P00376.
PRIDEi P00376.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSBTAT00000010103 ; ENSBTAP00000010103 ; ENSBTAG00000007681 .
GeneIDi 508809.
KEGGi bta:508809.

Organism-specific databases

CTDi 1719.

Phylogenomic databases

eggNOGi COG0262.
GeneTreei ENSGT00390000010283.
HOGENOMi HOG000040235.
HOVERGENi HBG000773.
InParanoidi P00376.
KOi K00287.
OrthoDBi EOG7V1FS3.
TreeFami TF317636.

Enzyme and pathway databases

UniPathwayi UPA00077 ; UER00158 .
Reactomei REACT_201998. E2F mediated regulation of DNA replication.
REACT_217517. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
REACT_222884. Metabolism of folate and pterines.
REACT_225533. G1/S-Specific Transcription.
SABIO-RK P00376.

Miscellaneous databases

NextBioi 20868689.

Family and domain databases

Gene3Di 3.40.430.10. 1 hit.
InterProi IPR012259. DHFR.
IPR024072. DHFR-like_dom.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
[Graphical view ]
Pfami PF00186. DHFR_1. 1 hit.
[Graphical view ]
PRINTSi PR00070. DHFR.
SUPFAMi SSF53597. SSF53597. 1 hit.
PROSITEi PS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. NIH - Mammalian Gene Collection (MGC) project
    Submitted (FEB-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(1982) [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: September 3, 2014
This is version 95 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

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