ubiquitin-conjugating enzyme E2 R1; ubiquitin-conjugating enzyme E2-32 kD complementing; ubiquitin-conjugating enzyme E2-CDC34; ubiquitin-protein ligase R1 (CDC34, UBCH3, UBE2R1)

Function

• accepts ubiquitin from the E1 complex & catalyzes its covalent attachment to other proteins
• in vitro catalyzes Lys-48-linked polyubiquitination
• cooperates with the E2 UBCH5C & the SCF(FBXW11) E3 ligase complex for 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 &/or Lys-22 with a monoubiquitin
• cooperates with the SCF(SKP2) E3 ligase complex to regulate cell proliferation through ubiquitination & degradation of MYBL2 & KIP1
• role in ubiquitin conjugation & degradation of CREM isoform ICERIIgamma & ATF15 resulting in abrogation of ICERIIgamma- & ATF5-mediated repression of cAMP-induced transcription during both meiotic & mitotic cell cycles
• role in regulation of the cell cycle G2/M phase through its targeting of the WEE1 kinase for ubiquitination & degradation
• also involved in the degradation of beta-catenin
• CDC34-catalyzed polyubiquitin chain assembly activity is stimulated by the conjugation of NEDD8 to the CUL1 SCF E3 ligase complex subunit
• protein modification; protein ubiquitination
• phosphorylated by CK2: phosphorylation of the C-terminal tail by CK2 controls the nuclear localization
• interacts with SCF E3 ubiquitin ligase complex
• when cullin is neddylated, the interaction between the E2 & the SCF complex is strengthened
• when phosphorylated, interacts with beta-TrCP (BTRC)
• interacts with casein kinase subunit CSNK2B
• autoubiquitinated

Kinetic parameters:

• KM=0.11 uM for beta-catenin-monoubiquin

Structure

• C-terminal acidic tail is required for nuclear localization & is involved in the binding to SCF E3 ligase complexes, & more specifically with the CUL1 subunit
• belongs to the ubiquitin-conjugating enzyme family

Compartment

• cytoplasm, nucleus
• phosphorylation of the C-terminal tail plays a role in mediating nuclear localization
• colocalizes with beta-tubulin on mitotic spindles in anaphase

Expression

• expressed in testes during spermatogenesis to regulate repression of cAMP-induced transcription
• negatively regulated by the let-7 microRNA

Pathology

• target of human herpes virus 1 protein ICP0, leading to ICP0-dependent dynamic interaction with proteasomes
• autoubiquitination is promoted by the human herpes virus 1 protein ICP0 & leads to degradation by the ubiquitin-proteasomal pathway

More general terms

• ubiquitin-conjugating protein E2 (ubiquitin carrier protein)
• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=997
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:997
• OMIM: https://mirror.omim.org/entry/116948
• UniProt: http://www.uniprot.org/uniprot/P49427.html