UB2R1_MOUSE
ID UB2R1_MOUSE Reviewed; 235 AA.
AC Q8CFI2; Q505K8;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Ubiquitin-conjugating enzyme E2 R1;
DE EC=2.3.2.23;
DE AltName: Full=(E3-independent) E2 ubiquitin-conjugating enzyme R1;
DE EC=2.3.2.24;
DE AltName: Full=E2 ubiquitin-conjugating enzyme R1;
DE AltName: Full=Ubiquitin-conjugating enzyme E2-32 kDa complementing;
DE AltName: Full=Ubiquitin-conjugating enzyme E2-CDC34;
DE AltName: Full=Ubiquitin-protein ligase R1;
GN Name=Cdc34; Synonyms=Ubch3, Ube2r1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=129, and C57BL/6J; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP INTERACTION WITH SCF COMPLEX, AND FUNCTION.
RX PubMed=10230406; DOI=10.1016/s1097-2765(00)80481-5;
RA Tan P., Fuchs S.Y., Chen A., Wu K., Gomez C., Ronai Z., Pan Z.-Q.;
RT "Recruitment of a ROC1-CUL1 ubiquitin ligase by Skp1 and HOS to catalyze
RT the ubiquitination of I kappa B alpha.";
RL Mol. Cell 3:527-533(1999).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP INTERACTION WITH CNTD1.
RX PubMed=32640224; DOI=10.1016/j.celrep.2020.107858;
RA Gray S., Santiago E.R., Chappie J.S., Cohen P.E.;
RT "Cyclin N-Terminal Domain-Containing-1 Coordinates Meiotic Crossover
RT Formation with Cell-Cycle Progression in a Cyclin-Independent Manner.";
RL Cell Rep. 32:107858-107858(2020).
CC -!- FUNCTION: Accepts ubiquitin from the E1 complex and catalyzes its
CC covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-
CC linked polyubiquitination. Cooperates with the E2 UBCH5C and the
CC SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA
CC leading to its subsequent proteasomal degradation. Performs ubiquitin
CC chain elongation building ubiquitin chains from the UBE2D3-primed
CC NFKBIA-linked ubiquitin. UBE2D3 acts as an initiator E2, priming the
CC phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with
CC a monoubiquitin. Cooperates with the SCF(SKP2) E3 ligase complex to
CC regulate cell proliferation through ubiquitination and degradation of
CC MYBL2 and KIP1. Involved in ubiquitin conjugation and degradation of
CC CREM isoform ICERIIgamma and ATF15 resulting in abrogation of
CC ICERIIgamma- and ATF5-mediated repression of cAMP-induced transcription
CC during both meiotic and mitotic cell cycles. Involved in the regulation
CC of the cell cycle G2/M phase through its targeting of the WEE1 kinase
CC for ubiquitination and degradation. Also involved in the degradation of
CC beta-catenin. {ECO:0000250|UniProtKB:P49427,
CC ECO:0000269|PubMed:10230406}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine +
CC [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin-
CC activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-
CC conjugating enzyme]-L-cysteine.; EC=2.3.2.23;
CC Evidence={ECO:0000250|UniProtKB:P49427, ECO:0000255|PROSITE-
CC ProRule:PRU00388, ECO:0000255|PROSITE-ProRule:PRU10133};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E1 ubiquitin-activating enzyme]-L-
CC cysteine + N(6)-monoubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.24; Evidence={ECO:0000250|UniProtKB:P49427};
CC -!- ACTIVITY REGULATION: CDC34-catalyzed polyubiquitin chain assembly
CC activity is stimulated by the conjugation of NEDD8 to the CUL1 SCF E3
CC ligase complex subunit. {ECO:0000250|UniProtKB:P49427}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000255|PROSITE-ProRule:PRU00388}.
CC -!- SUBUNIT: Interacts with SCF (SKP1-CUL1-F-box protein) E3 ubiquitin
CC ligase complex. Identified in a SCF (SKP1-CUL1-F-box protein) E3
CC ubiquitin ligase complex together with HINT1 and RBX1. When cullin is
CC neddylated, the interaction between the E2 and the SCF complex is
CC strengthened (By similarity). When phosphorylated, interacts with beta-
CC TrCP (BTRC) (By similarity). Interacts with casein kinase subunit
CC CSNK2B. Interacts with CNTD1; this interaction regulates the cell-cycle
CC progression (PubMed:32640224). {ECO:0000250|UniProtKB:P49427,
CC ECO:0000269|PubMed:32640224}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P49427}. Nucleus
CC {ECO:0000250|UniProtKB:P49427}. Note=The phosphorylation of the C-
CC terminal tail plays an important role in mediating nuclear
CC localization. Colocalizes with beta-tubulin on mitotic spindles in
CC anaphase. {ECO:0000250|UniProtKB:P49427}.
CC -!- DOMAIN: The C-terminal acidic tail is required for nuclear localization
CC and is involved in the binding to SCF E3 ligase complexes, and more
CC specifically with the CUL1 subunit. {ECO:0000250|UniProtKB:P49427}.
CC -!- PTM: Phosphorylated by CK2. Phosphorylation of the C-terminal tail by
CC CK2 controles the nuclear localization. {ECO:0000250|UniProtKB:P49427}.
CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family.
CC {ECO:0000255|PROSITE-ProRule:PRU00388}.
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DR EMBL; BC039160; AAH39160.1; -; mRNA.
DR EMBL; BC094502; AAH94502.1; -; mRNA.
DR CCDS; CCDS23983.1; -.
DR RefSeq; NP_808281.1; NM_177613.2.
DR RefSeq; XP_017169376.1; XM_017313887.1.
DR RefSeq; XP_017169377.1; XM_017313888.1.
DR AlphaFoldDB; Q8CFI2; -.
DR SMR; Q8CFI2; -.
DR BioGRID; 229706; 4.
DR IntAct; Q8CFI2; 3.
DR STRING; 10090.ENSMUSP00000020550; -.
DR iPTMnet; Q8CFI2; -.
DR PhosphoSitePlus; Q8CFI2; -.
DR SwissPalm; Q8CFI2; -.
DR EPD; Q8CFI2; -.
DR MaxQB; Q8CFI2; -.
DR PaxDb; Q8CFI2; -.
DR PeptideAtlas; Q8CFI2; -.
DR PRIDE; Q8CFI2; -.
DR ProteomicsDB; 298350; -.
DR DNASU; 216150; -.
DR Ensembl; ENSMUST00000020550; ENSMUSP00000020550; ENSMUSG00000020307.
DR Ensembl; ENSMUST00000166603; ENSMUSP00000128806; ENSMUSG00000020307.
DR GeneID; 216150; -.
DR KEGG; mmu:216150; -.
DR UCSC; uc007fzi.1; mouse.
DR CTD; 997; -.
DR MGI; MGI:102657; Cdc34.
DR VEuPathDB; HostDB:ENSMUSG00000020307; -.
DR eggNOG; KOG0425; Eukaryota.
DR GeneTree; ENSGT00940000160356; -.
DR HOGENOM; CLU_030988_1_2_1; -.
DR InParanoid; Q8CFI2; -.
DR OMA; LFYEDDC; -.
DR OrthoDB; 1116856at2759; -.
DR PhylomeDB; Q8CFI2; -.
DR TreeFam; TF101107; -.
DR Reactome; R-MMU-202424; Downstream TCR signaling.
DR Reactome; R-MMU-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-MMU-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-MMU-8866652; Synthesis of active ubiquitin: roles of E1 and E2 enzymes.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 216150; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Cdc34; mouse.
DR PRO; PR:Q8CFI2; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q8CFI2; protein.
DR Bgee; ENSMUSG00000020307; Expressed in quadriceps femoris and 67 other tissues.
DR ExpressionAtlas; Q8CFI2; baseline and differential.
DR Genevisible; Q8CFI2; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016607; C:nuclear speck; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0061631; F:ubiquitin conjugating enzyme activity; IDA:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0035458; P:cellular response to interferon-beta; ISO:MGI.
DR GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; ISO:MGI.
DR GO; GO:0090261; P:positive regulation of inclusion body assembly; ISO:MGI.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0006513; P:protein monoubiquitination; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; ISO:MGI.
DR GO; GO:0016567; P:protein ubiquitination; ISO:MGI.
DR GO; GO:0070848; P:response to growth factor; IEA:Ensembl.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR CDD; cd00195; UBCc; 1.
DR Gene3D; 3.10.110.10; -; 1.
DR InterPro; IPR000608; UBQ-conjugat_E2.
DR InterPro; IPR023313; UBQ-conjugating_AS.
DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD.
DR Pfam; PF00179; UQ_con; 1.
DR SUPFAM; SSF54495; SSF54495; 1.
DR PROSITE; PS00183; UBC_1; 1.
DR PROSITE; PS50127; UBC_2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell cycle; Cytoplasm; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Transferase; Ubl conjugation pathway.
FT CHAIN 1..235
FT /note="Ubiquitin-conjugating enzyme E2 R1"
FT /id="PRO_0000082452"
FT DOMAIN 8..174
FT /note="UBC core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388"
FT REGION 190..235
FT /note="SCF-binding"
FT /evidence="ECO:0000250|UniProtKB:P49427"
FT ACT_SITE 93
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388,
FT ECO:0000255|PROSITE-ProRule:PRU10133"
FT MOD_RES 203
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:P49427"
FT MOD_RES 221
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:P49427"
FT MOD_RES 230
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:P49427"
FT MOD_RES 232
FT /note="Phosphothreonine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:P49427"
FT MOD_RES 235
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:P49427"
SQ SEQUENCE 235 AA; 26622 MW; 3259FA0CD407E1E3 CRC64;
MARPLVPSSQ KALLLELKGL QEEPVEGFRV TLVDEGDLYN WEVAIFGPPN TYYEGGYFKA
RLKFPIDYPY SPPAFRFLTK MWHPNIYETG DVCISILHPP VDDPQSGELP SERWNPTQNV
RTILLSVISL LNEPNTFSPA NVDASVMYRK WKESKGKDRE YTDIIRKQVL GTKVDAERDG
VKVPTTLAEY CVKTKAPAPD EGSDLFYDDY YEDGEVEEAD SCFGDEEDDS GTEES
