UniProt Accession

 DYR_MOUSE; P00375; P70693; Q61485; Q61487; Q61579 

Genbank Protein ID

 V00734; X56066; BC005796; M10071; L26316; J00387; J00382; J00383; J00384; J00385; J00386; V00731; M10722; M10811; V00733 

Genbank Nucleotide ID

 CAA24112.1; CAA39544.1; AAH05796.1; AAA37637.1; AAA37523.1; AAA37638.1; AAA37638.1; AAA37638.1; AAA37638.1; AAA37638.1; AAA37638.1; CAB43539.2; AAA37524.1; AAA37525.1; CAA24111.1 

Protein Name

 Dihydrofolate reductase 

Protein Synonyms/Alias

  

Gene Name

 Dhfr 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Mus musculus (Mouse) 

NCBI Taxa ID

 10090 

Lysine Modification

Position	Peptide	Type	References
33	PPLRNEFKYFQRMTT	acetylation	[1, 2]
33	PPLRNEFKYFQRMTT	succinylation	[2]
92	RGAHFLAKSLDDALR	acetylation	[1]
174	LSEVQEEKGIKYKFE	acetylation	[2, 3, 4]
174	LSEVQEEKGIKYKFE	ubiquitination	[5]

Reference

 [1] Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.
 Chen Y, Zhao W, Yang JS, Cheng Z, Luo H, Lu Z, Tan M, Gu W, Zhao Y.
 Mol Cell Proteomics. 2012 Oct;11(10):1048-62. [PMID: 22826441]
 [2] SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways.
 Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, Xie Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, Zhao Y.
 Mol Cell. 2013 Jun 27;50(6):919-30. [PMID: 23806337]
 [3] Quantitative assessment of the impact of the gut microbiota on lysine epsilon-acetylation of host proteins using gnotobiotic mice.
 Simon GM, Cheng J, Gordon JI.
 Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11133-8. [PMID: 22733758]
 [4] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [5] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 4 185 DHFR.
 NP_BIND 16 22 NADP.
 NP_BIND 55 57 NADP.
 NP_BIND 77 79 NADP.
 NP_BIND 117 124 NADP.
 REGION 31 36 Substrate binding.
 BINDING 10 10 NADP; via amide nitrogen and carbonyl
 BINDING 71 71 Substrate.  

Keyword

 3D-structure; Complete proteome; Direct protein sequencing; Methotrexate resistance; NADP; One-carbon metabolism; Oxidoreductase; Reference proteome; RNA-binding. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 187 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0004146; F:dihydrofolate reductase activity; ISS:UniProtKB.
 GO:0051871; F:dihydrofolic acid binding; IEA:Compara.
 GO:0008144; F:drug binding; ISS:UniProtKB.
 GO:0003729; F:mRNA binding; ISS:UniProtKB.
 GO:0050661; F:NADP binding; IEA:Compara.
 GO:0046452; P:dihydrofolate metabolic process; IEA:Compara.
 GO:0006545; P:glycine biosynthetic process; IEA:InterPro.
 GO:0009165; P:nucleotide biosynthetic process; IEA:InterPro.
 GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
 GO:0031427; P:response to methotrexate; IEA:UniProtKB-KW.
 GO:0035094; P:response to nicotine; IEA:Compara.
 GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:UniProtKB-UniPathway.
 GO:0046653; P:tetrahydrofolate metabolic process; ISS:UniProtKB. 

Interpro

 IPR012259; DHFR.
 IPR024072; DHFR-like_dom.
 IPR017925; DHFR_CS.
 IPR001796; DHFR_dom. 

Pfam

 PF00186; DHFR_1 

SMART

  

PROSITE

 PS00075; DHFR_1
 PS51330; DHFR_2 

PRINTS

 PR00070; DHFR.