UniProt Accession

 RIR1_HUMAN; P23921; Q9UNN2 

Genbank Protein ID

 X59543; X59617; AF107045; BC006498; L10342 

Genbank Nucleotide ID

 CAA42118.1; CAA42180.1; AAD37491.1; AAH06498.1 

Protein Name

 Ribonucleoside-diphosphate reductase large subunit 

Protein Synonyms/Alias

 Ribonucleoside-diphosphate reductase subunit M1; Ribonucleotide reductase large subunit 

Gene Name

 RRM1 

Gene Synonyms/Alias

 RR1 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
5	***MHVIKRDGRQER	ubiquitination	[1]
17	QERVMFDKITSRIQK	acetylation	[2]
17	QERVMFDKITSRIQK	ubiquitination	[1, 3, 4, 5]
24	KITSRIQKLCYGLNM	ubiquitination	[1, 3, 5, 6]
70	TAATLTTKHPDYAIL	ubiquitination	[7]
88	IAVSNLHKETKKVFS	ubiquitination	[1, 6]
92	NLHKETKKVFSDVME	ubiquitination	[1, 3, 4, 5, 6, 7, 8, 9]
111	YINPHNGKHSPMVAK	ubiquitination	[1, 4]
118	KHSPMVAKSTLDIVL	ubiquitination	[1]
128	LDIVLANKDRLNSAI	ubiquitination	[1, 4]
149	SYNYFGFKTLERSYL	ubiquitination	[1, 3, 4, 5, 7, 10]
158	LERSYLLKINGKVAE	ubiquitination	[1, 3, 4, 5, 7, 9, 10, 11]
162	YLLKINGKVAERPQH	ubiquitination	[1]
180	RVSVGIHKEDIDAAI	ubiquitination	[1, 4]
236	EGIYDTLKQCALISK	ubiquitination	[1, 4]
243	KQCALISKSAGGIGV	ubiquitination	[1]
376	KLYASYEKQGRVRKV	acetylation	[2]
376	KLYASYEKQGRVRKV	ubiquitination	[1, 3, 4, 5, 7, 9, 10]
414	YKDSCNRKSNQQNLG	ubiquitination	[1, 4, 9]
465	EHTYDFKKLAEVTKV	ubiquitination	[1, 4, 5, 12]
471	KKLAEVTKVVVRNLN	ubiquitination	[1, 3, 4, 5, 7, 9, 10, 11]
479	VVVRNLNKIIDINYY	ubiquitination	[1]
496	PEACLSNKRHRPIGI	ubiquitination	[1, 4, 9, 11]
587	DWKVLKEKIAKYGIR	ubiquitination	[1]
590	VLKEKIAKYGIRNSL	ubiquitination	[1, 3, 5]
643	IVNPHLLKDLTERGL	ubiquitination	[1, 3, 4, 5, 7, 13]
656	GLWHEEMKNQIIACN	ubiquitination	[1]
677	PEIPDDLKQLYKTVW	ubiquitination	[1]
681	DDLKQLYKTVWEISQ	ubiquitination	[3, 5]
689	TVWEISQKTVLKMAA	ubiquitination	[1, 3, 5, 7]
693	ISQKTVLKMAAERGA	ubiquitination	[1, 3, 5]
729	SMHFYGWKQGLKTGM	ubiquitination	[1]
733	YGWKQGLKTGMYYLR	ubiquitination	[1]
754	PIQFTLNKEKLKDKE	ubiquitination	[1, 3, 4, 5, 7, 13]
756	QFTLNKEKLKDKEKV	ubiquitination	[1]

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] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [3] 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]
 [4] 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]
 [5] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [6] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [7] 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]
 [8] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [9] 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]
 [10] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [11] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [12] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
 [13] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931] 

Functional Description

 Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. 

Sequence Annotation

 DOMAIN 1 92 ATP-cone.
 REGION 11 17 Allosteric activator binding (By
 REGION 217 218 Substrate binding (By similarity).
 REGION 285 288 Allosteric effector binding, determines
 REGION 427 431 Substrate binding (By similarity).
 REGION 603 607 Substrate binding (By similarity).
 ACT_SITE 427 427 Proton acceptor (By similarity).
 ACT_SITE 429 429 Cysteine radical intermediate (By
 ACT_SITE 431 431 Proton acceptor (By similarity).
 BINDING 5 5 Allosteric activator (By similarity).
 BINDING 53 53 Allosteric activator (By similarity).
 BINDING 88 88 Allosteric activator (By similarity).
 BINDING 202 202 Substrate (By similarity).
 BINDING 247 247 Substrate; via amide nitrogen (By
 MOD_RES 17 17 N6-acetyllysine.
 MOD_RES 376 376 N6-acetyllysine.
 DISULFID 218 444 Redox-active (By similarity).  

Keyword

 3D-structure; Acetylation; Allosteric enzyme; ATP-binding; Complete proteome; Cytoplasm; Disulfide bond; DNA replication; Nucleotide-binding; Oxidoreductase; Polymorphism; Reference proteome. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 792 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005971; C:ribonucleoside-diphosphate reductase complex; NAS:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004748; F:ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor; ISS:UniProtKB.
 GO:0009263; P:deoxyribonucleotide biosynthetic process; ISS:UniProtKB.
 GO:0006260; P:DNA replication; NAS:UniProtKB.
 GO:0015949; P:nucleobase-containing small molecule interconversion; TAS:Reactome.
 GO:0051290; P:protein heterotetramerization; IEA:Compara. 

Interpro

 IPR005144; ATP-cone.
 IPR013346; NrdE_NrdA.
 IPR000788; RNR_lg_C.
 IPR013509; RNR_lsu_N.
 IPR008926; RNR_R1-su_N. 

Pfam

 PF03477; ATP-cone
 PF02867; Ribonuc_red_lgC
 PF00317; Ribonuc_red_lgN 

SMART

  

PROSITE

 PS51161; ATP_CONE
 PS00089; RIBORED_LARGE 

PRINTS

 PR01183; RIBORDTASEM1.