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Protein

Dihydrofolate reductase

Gene

DHFR

Organism
Sus scrofa (Pig)
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: tetrahydrofolate biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate.
Proteins known to be involved in this subpathway in this organism are:
  1. Dihydrofolate reductase (DHFR)
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 keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei9NADP; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei70SubstrateBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi15 – 21NADPBy similarity7
Nucleotide bindingi54 – 56NADPBy similarity3
Nucleotide bindingi76 – 78NADPBy similarity3
Nucleotide bindingi116 – 123NADPBy similarity8

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Methotrexate resistance, One-carbon metabolism

Keywords - Ligandi

NADP, RNA-binding

Enzyme and pathway databases

UniPathwayiUPA00077; UER00158.

Names & Taxonomyi

Protein namesi
Recommended name:
Dihydrofolate reductase (EC:1.5.1.3)
Gene namesi
Name:DHFR
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
Proteomesi
  • UP000008227 Componenti: Unplaced

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001863651 – 186Dihydrofolate reductaseAdd BLAST186

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei32N6-acetyllysine; alternateBy similarity1
Modified residuei32N6-succinyllysine; alternateBy similarity1
Modified residuei162Cysteine derivative; partial1

Keywords - PTMi

Acetylation

Proteomic databases

PaxDbiP00377.
PeptideAtlasiP00377.
PRIDEiP00377.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000015020.

Structurei

3D structure databases

ProteinModelPortaliP00377.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini3 – 184DHFRPROSITE-ProRule annotationAdd BLAST182

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni30 – 35Substrate bindingBy similarity6

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG1324. Eukaryota.
COG0262. LUCA.
HOGENOMiHOG000040235.
HOVERGENiHBG000773.
InParanoidiP00377.

Family and domain databases

CDDicd00209. DHFR. 1 hit.
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.

P00377-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
VRPLNCIVAV SQNMGIGKNG DLPWPPLRNE YKYFQRMTTT SSVEGKQNLV
60 70 80 90 100
IMGRKTWFSI PEKNRPLKDR INIVLSRELK EPPQGAHFLA KSLDDALKLT
110 120 130 140 150
EQPELKDKVD MVWIVGGSSV YKEAMNKPGH IRLFVTRIMK EFESDTFFPE
160 170 180
IDLEKYKLLS ECSGVPSDVQ EEKGIKYKFE VYEKNN
Length:186
Mass (Da):21,455
Last modified:July 21, 1986 - v1
Checksum:iD05DB526FE5C12CE
GO

Sequence databases

PIRiA00389. RDPGD.
UniGeneiSsc.7139.

Cross-referencesi

Sequence databases

PIRiA00389. RDPGD.
UniGeneiSsc.7139.

3D structure databases

ProteinModelPortaliP00377.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000015020.

Proteomic databases

PaxDbiP00377.
PeptideAtlasiP00377.
PRIDEiP00377.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

eggNOGiKOG1324. Eukaryota.
COG0262. LUCA.
HOGENOMiHOG000040235.
HOVERGENiHBG000773.
InParanoidiP00377.

Enzyme and pathway databases

UniPathwayiUPA00077; UER00158.

Family and domain databases

CDDicd00209. DHFR. 1 hit.
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...

Entry informationi

Entry nameiDYR_PIG
AccessioniPrimary (citable) accession number: P00377
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: October 5, 2016
This is version 90 of the entry and version 1 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

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.