UniProt Accession

 DYR_HUMAN; P00374; Q14130; Q6IRW8 

Genbank Protein ID

 J00140; V00507; J00139; K01612; K01613; J00138; K01614; X00855; X00856; X00857; X00858; X00859; AC008434; BC000192; BC003584; BC070280; BC071996 

Genbank Nucleotide ID

 AAA58485.1; CAA23765.1; AAA58484.1; AAA58484.1; AAA58484.1; AAA58484.1; AAA58484.1; CAA25409.1; CAA25409.1; CAA25409.1; CAA25409.1; CAA25409.1; AAH00192.1; AAH03584.2; AAH70280.1; AAH71996.1 

Protein Name

 Dihydrofolate reductase 

Protein Synonyms/Alias

  

Gene Name

 DHFR 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
19	SQNMGIGKNGDLPWP	ubiquitination	[1, 2]
47	TTSSVEGKQNLVIMG	ubiquitination	[1, 3]
55	QNLVIMGKKTWFSIP	ubiquitination	[1]
56	NLVIMGKKTWFSIPE	ubiquitination	[1]
64	TWFSIPEKNRPLKGR	ubiquitination	[1]
69	PEKNRPLKGRINLVL	ubiquitination	[3]
81	LVLSRELKEPPQGAH	ubiquitination	[1, 3]
99	RSLDDALKLTEQPEL	ubiquitination	[1, 2, 3]
109	EQPELANKVDMVWIV	ubiquitination	[1, 2, 3]
123	VGGSSVYKEAMNHPG	ubiquitination	[1]
133	MNHPGHLKLFVTRIM	ubiquitination	[1, 3, 4]
156	FPEIDLEKYKLLPEY	ubiquitination	[1, 2, 3, 5]
158	EIDLEKYKLLPEYPG	ubiquitination	[1, 2, 3, 4, 6]
174	LSDVQEEKGIKYKFE	ubiquitination	[1, 3, 6]
177	VQEEKGIKYKFEVYE	ubiquitination	[1]
179	EEKGIKYKFEVYEKN	ubiquitination	[1, 2, 3]
185	YKFEVYEKND*****	ubiquitination	[1, 3, 5]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [5] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [6] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
 Xu G, Paige JS, Jaffrey SR.
 Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865] 

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 65 65 Substrate.
 BINDING 71 71 Substrate.  

Keyword

 3D-structure; Complete proteome; Disease mutation; 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:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0004146; F:dihydrofolate reductase activity; IDA:UniProtKB.
 GO:0008144; F:drug binding; IDA:UniProtKB.
 GO:0003729; F:mRNA binding; IDA:UniProtKB.
 GO:0050661; F:NADP binding; IEA:InterPro.
 GO:0046655; P:folic acid metabolic process; TAS:Reactome.
 GO:0006545; P:glycine biosynthetic process; NAS:UniProtKB.
 GO:0046209; P:nitric oxide metabolic process; TAS:Reactome.
 GO:0009165; P:nucleotide biosynthetic process; NAS:UniProtKB.
 GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
 GO:0050999; P:regulation of nitric-oxide synthase activity; TAS:Reactome.
 GO:0000083; P:regulation of transcription involved in G1/S phase of mitotic cell cycle; TAS:Reactome.
 GO:0031427; P:response to methotrexate; IEA:UniProtKB-KW.
 GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:UniProtKB-UniPathway.
 GO:0046653; P:tetrahydrofolate metabolic process; IDA: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.