UniProt Accession

 UB2R1_HUMAN; P49427; A8K689 

Genbank Protein ID

 L22005; BT006659; AY650399; AK291554; CH471242; BC009850; BC018143; BC023979 

Genbank Nucleotide ID

 AAC37534.1; AAP35305.1; AAT46688.1; BAF84243.1; EAW61190.1; AAH09850.1; AAH18143.1; AAH23979.1 

Protein Name

 Ubiquitin-conjugating enzyme E2 R1 

Protein Synonyms/Alias

 Ubiquitin-conjugating enzyme E2-32 kDa complementing; Ubiquitin-conjugating enzyme E2-CDC34; Ubiquitin-protein ligase R1 

Gene Name

 CDC34 

Gene Synonyms/Alias

 UBCH3; UBE2R1 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
11	PLVPSSQKALLLELK	ubiquitination	[1, 2, 3, 4]
18	KALLLELKGLQEEPV	ubiquitination	[1, 5, 6, 7, 8]
63	GYFKARLKFPIDYPY	ubiquitination	[1, 2, 3, 4, 6, 7, 8, 9]
80	PAFRFLTKMWHPNIY	ubiquitination	[6]
193	TLAEYCVKTKAPAPD	ubiquitination	[6]

Reference

 [1] 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]
 [2] 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]
 [3] 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]
 [4] 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]
 [5] 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]
 [6] 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]
 [7] 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]
 [8] 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]
 [9] 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

 Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys- 48'-linked polyubiquitination. Cooperates with the E2 UBCH5C and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation. Performs ubiquitin chain elongation building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin. UBE2D3 acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with a monoubiquitin. Cooperates with the SCF(SKP2) E3 ligase complex to regulate cell proliferation through ubiquitination and degradation of MYBL2 and KIP1. Involved in ubiquitin conjugation and degradation of CREM isoform ICERIIgamma and ATF15 resulting in abrogation of ICERIIgamma- and ATF5- mediated repression of cAMP-induced transcription during both meiotic and mitotic cell cycles. Involved in the regulation of the cell cycle G2/M phase through its targeting of the WEE1 kinase for ubiquitination and degradation. Also involved in the degradation of beta-catenin. Is target of human herpes virus 1 protein ICP0, leading to ICP0-dependent dynamic interaction with proteasomes. 

Sequence Annotation

 REGION 190 236 SCF-binding.
 ACT_SITE 93 93 Glycyl thioester intermediate.
 MOD_RES 203 203 Phosphoserine; by CK2.
 MOD_RES 222 222 Phosphoserine; by CK2.
 MOD_RES 231 231 Phosphoserine; by CK2.
 MOD_RES 233 233 Phosphothreonine; by CK2.
 MOD_RES 236 236 Phosphoserine; by CK2.  

Keyword

 3D-structure; ATP-binding; Cell cycle; Complete proteome; Cytoplasm; Ligase; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Ubl conjugation; Ubl conjugation pathway. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 236 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; IDA:HPA.
 GO:0005634; C:nucleus; NAS:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
 GO:0006270; P:DNA replication initiation; NAS:UniProtKB.
 GO:0000082; P:G1/S transition of mitotic cell cycle; NAS:UniProtKB.
 GO:0043951; P:negative regulation of cAMP-mediated signaling; IDA:UniProtKB.
 GO:0043161; P:proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
 GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB. 

Interpro

 IPR000608; UBQ-conjugat_E2.
 IPR023313; UBQ-conjugating_AS.
 IPR016135; UBQ-conjugating_enzyme/RWD. 

Pfam

 PF00179; UQ_con 

SMART

  

PROSITE

 PS00183; UBIQUITIN_CONJUGAT_1
 PS50127; UBIQUITIN_CONJUGAT_2 

PRINTS