Full text data of CDC34
CDC34
(UBCH3, UBE2R1)
[Confidence: low (only semi-automatic identification from reviews)]
Ubiquitin-conjugating enzyme E2 R1; 6.3.2.19 (Ubiquitin-conjugating enzyme E2-32 kDa complementing; Ubiquitin-conjugating enzyme E2-CDC34; Ubiquitin-protein ligase R1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Ubiquitin-conjugating enzyme E2 R1; 6.3.2.19 (Ubiquitin-conjugating enzyme E2-32 kDa complementing; Ubiquitin-conjugating enzyme E2-CDC34; Ubiquitin-protein ligase R1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P49427
ID UB2R1_HUMAN Reviewed; 236 AA.
AC P49427; A8K689;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1997, sequence version 2.
DT 22-JAN-2014, entry version 133.
DE RecName: Full=Ubiquitin-conjugating enzyme E2 R1;
DE EC=6.3.2.19;
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8248134; DOI=10.1073/pnas.90.22.10484;
RA Plon S.E., Leppig K.A., Do H.N., Groudine M.;
RT "Cloning of the human homolog of the CDC34 cell cycle gene by
RT complementation in yeast.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:10484-10488(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT HIS-227.
RG NIEHS SNPs program;
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Lung;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, AND MUTAGENESIS OF CYS-93.
RX PubMed=10329681; DOI=10.1074/jbc.274.21.14823;
RA Gonen H., Bercovich B., Orian A., Carrano A., Takizawa C.,
RA Yamanaka K., Pagano M., Iwai K., Ciechanover A.;
RT "Identification of the ubiquitin carrier proteins, E2s, involved in
RT signal-induced conjugation and subsequent degradation of
RT IkappaBalpha.";
RL J. Biol. Chem. 274:14823-14830(1999).
RN [8]
RP INTERACTION WITH ATF5 AND CREM, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=10373550;
RA Pati D., Meistrich M.L., Plon S.E.;
RT "Human Cdc34 and Rad6B ubiquitin-conjugating enzymes target repressors
RT of cyclic AMP-induced transcription for proteolysis.";
RL Mol. Cell. Biol. 19:5001-5013(1999).
RN [9]
RP SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=10769200;
RA Reymond F., Wirbelauer C., Krek W.;
RT "Association of human ubiquitin-conjugating enzyme CDC34 with the
RT mitotic spindle in anaphase.";
RL J. Cell Sci. 113:1687-1694(2000).
RN [10]
RP FUNCTION.
RX PubMed=10871850; DOI=10.1038/sj.onc.1203618;
RA Charrasse S., Carena I., Brondani V., Klempnauer K.H., Ferrari S.;
RT "Degradation of B-Myb by ubiquitin-mediated proteolysis: involvement
RT of the Cdc34-SCF(p45Skp2) pathway.";
RL Oncogene 19:2986-2995(2000).
RN [11]
RP INTERACTION WITH SCF COMPLEX.
RX PubMed=10918611; DOI=10.1038/sj.onc.1203647;
RA Strack P., Caligiuri M., Pelletier M., Boisclair M., Theodoras A.,
RA Beer-Romero P., Glass S., Parsons T., Copeland R.A., Auger K.R.,
RA Benfield P., Brizuela L., Rolfe M.;
RT "SCF(beta-TRCP) and phosphorylation dependent ubiquitination of I
RT kappa B alpha catalyzed by Ubc3 and Ubc4.";
RL Oncogene 19:3529-3536(2000).
RN [12]
RP INTERACTION WITH CSNK2B, PHOSPHORYLATION AT SER-203; SER-222; SER-231;
RP THR-233 AND SER-236, MUTAGENESIS OF SER-203; SER-222; SER-231; THR-233
RP AND SER-236, AND SUBCELLULAR LOCATION.
RX PubMed=11546811; DOI=10.1074/jbc.M106453200;
RA Block K., Boyer T.G., Yew P.R.;
RT "Phosphorylation of the human ubiquitin-conjugating enzyme, CDC34, by
RT casein kinase 2.";
RL J. Biol. Chem. 276:41049-41058(2001).
RN [13]
RP INTERACTION WITH HUMAN HERPESVIRUS 1 PROTEIN ICP0, AND ASSOCIATION
RP WITH THE PROTEASOME.
RX PubMed=11447293; DOI=10.1073/pnas.161283098;
RA Van Sant C., Hagglund R., Lopez P., Roizman B.;
RT "The infected cell protein 0 of herpes simplex virus 1 dynamically
RT interacts with proteasomes, binds and activates the cdc34 E2
RT ubiquitin-conjugating enzyme, and possesses in vitro E3 ubiquitin
RT ligase activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:8815-8820(2001).
RN [14]
RP INTERACTION WITH SCF COMPLEX, FUNCTION, AND ENZYME REGULATION.
RX PubMed=11675391; DOI=10.1074/jbc.M108008200;
RA Wu K., Chen A., Tan P., Pan Z.Q.;
RT "The Nedd8-conjugated ROC1-CUL1 core ubiquitin ligase utilizes Nedd8
RT charged surface residues for efficient polyubiquitin chain assembly
RT catalyzed by Cdc34.";
RL J. Biol. Chem. 277:516-527(2002).
RN [15]
RP ENZYME ACTIVITY, FUNCTION, INTERACTION WITH BTRC, PHOSPHORYLATION AT
RP SER-231, AND MUTAGENESIS OF CYS-93; LEU-97 AND SER-231.
RX PubMed=12037680; DOI=10.1038/sj.onc.1205574;
RA Semplici F., Meggio F., Pinna L.A., Oliviero S.;
RT "CK2-dependent phosphorylation of the E2 ubiquitin conjugating enzyme
RT UBC3B induces its interaction with beta-TrCP and enhances beta-catenin
RT degradation.";
RL Oncogene 21:3978-3987(2002).
RN [16]
RP INTERACTION WITH HUMAN HERPES VIRUS 1 PROTEIN ICP0, AND
RP AUTOUBIQUITINATION.
RX PubMed=11805320; DOI=10.1073/pnas.022531599;
RA Hagglund R., Van Sant C., Lopez P., Roizman B.;
RT "Herpes simplex virus 1-infected cell protein 0 contains two E3
RT ubiquitin ligase sites specific for different E2 ubiquitin-conjugating
RT enzymes.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:631-636(2002).
RN [17]
RP INTERACTION WITH HUMAN HERPES VIRUS 1 PROTEIN ICP0, AND
RP AUTOUBIQUITINATION.
RX PubMed=12060736; DOI=10.1073/pnas.122246999;
RA Hagglund R., Roizman B.;
RT "Characterization of the novel E3 ubiquitin ligase encoded in exon 3
RT of herpes simplex virus-1-infected cell protein 0.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:7889-7894(2002).
RN [18]
RP FUNCTION.
RX PubMed=15652359; DOI=10.1016/j.yexcr.2004.10.008;
RA Butz N., Ruetz S., Natt F., Hall J., Weiler J., Mestan J., Ducarre M.,
RA Grossenbacher R., Hauser P., Kempf D., Hofmann F.;
RT "The human ubiquitin-conjugating enzyme Cdc34 controls cellular
RT proliferation through regulation of p27Kip1 protein levels.";
RL Exp. Cell Res. 303:482-493(2005).
RN [19]
RP PHOSPHORYLATION AT SER-203; SER-222 AND SER-231, AND FUNCTION.
RX PubMed=17461777; DOI=10.1042/BJ20061812;
RA Sadowski M., Mawson A., Baker R., Sarcevic B.;
RT "Cdc34 C-terminal tail phosphorylation regulates Skp1/cullin/F-box
RT (SCF)-mediated ubiquitination and cell cycle progression.";
RL Biochem. J. 405:569-581(2007).
RN [20]
RP FUNCTION, AND MUTAGENESIS OF ASN-85; TYR-87; SER-95; ASP-102; ASP-103;
RP GLU-108; GLU-112; SER-138; ASP-143; MET-147; ARG-149; LYS-150 AND
RP GLU-153.
RX PubMed=17698585; DOI=10.1128/MCB.00812-07;
RA Gazdoiu S., Yamoah K., Wu K., Pan Z.Q.;
RT "Human Cdc34 employs distinct sites to coordinate attachment of
RT ubiquitin to a substrate and assembly of polyubiquitin chains.";
RL Mol. Cell. Biol. 27:7041-7052(2007).
RN [21]
RP INTERACTION WITH SCF COMPLEX.
RX PubMed=18851830; DOI=10.1016/j.molcel.2008.08.021;
RA Saha A., Deshaies R.J.;
RT "Multimodal activation of the ubiquitin ligase SCF by Nedd8
RT conjugation.";
RL Mol. Cell 32:21-31(2008).
RN [22]
RP FUNCTION, INTERACTION WITH SCF COMPLEX, DOMAIN, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=19945379; DOI=10.1016/j.cell.2009.10.030;
RA Kleiger G., Saha A., Lewis S., Kuhlman B., Deshaies R.J.;
RT "Rapid E2-E3 assembly and disassembly enable processive ubiquitylation
RT of cullin-RING ubiquitin ligase substrates.";
RL Cell 139:957-968(2009).
RN [23]
RP IDENTIFICATION IN A UBIQUITIN LIGASE COMPLEX WITH HINT1 AND RBX1, AND
RP FUNCTION.
RX PubMed=19112177; DOI=10.1074/jbc.M804531200;
RA Cen B., Li H., Weinstein I.B.;
RT "Histidine triad nucleotide-binding protein 1 up-regulates cellular
RT levels of p27KIP1 by targeting ScfSKP2 ubiquitin ligase and Src.";
RL J. Biol. Chem. 284:5265-5276(2009).
RN [24]
RP INDUCTION, AND FUNCTION.
RX PubMed=19126550; DOI=10.1074/jbc.C900002200;
RA Legesse-Miller A., Elemento O., Pfau S.J., Forman J.J., Tavazoie S.,
RA Coller H.A.;
RT "let-7 Overexpression leads to an increased fraction of cells in G2/M,
RT direct down-regulation of Cdc34, and stabilization of Wee1 kinase in
RT primary fibroblasts.";
RL J. Biol. Chem. 284:6605-6609(2009).
RN [25]
RP FUNCTION.
RX PubMed=20061386; DOI=10.1074/jbc.M109.089003;
RA David Y., Ziv T., Admon A., Navon A.;
RT "The E2 ubiquitin-conjugating enzymes direct polyubiquitination to
RT preferred lysines.";
RL J. Biol. Chem. 285:8595-8604(2010).
RN [26]
RP FUNCTION.
RX PubMed=20347421; DOI=10.1016/j.molcel.2010.02.025;
RA Wu K., Kovacev J., Pan Z.Q.;
RT "Priming and extending: a UbcH5/Cdc34 E2 handoff mechanism for
RT polyubiquitination on a SCF substrate.";
RL Mol. Cell 37:784-796(2010).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 7-184.
RG Structural genomics consortium (SGC);
RT "Human ubiquitin-conjugating enzyme cdc34.";
RL Submitted (FEB-2009) to the PDB data bank.
CC -!- FUNCTION: Accepts ubiquitin from the E1 complex and catalyzes its
CC covalent attachment to other proteins. In vitro catalyzes 'Lys-
CC 48'-linked polyubiquitination. Cooperates with the E2 UBCH5C and
CC the SCF(FBXW11) E3 ligase complex for the polyubiquitination of
CC NFKBIA leading to its subsequent proteasomal degradation. Performs
CC ubiquitin chain elongation building ubiquitin chains from the
CC UBE2D3-primed NFKBIA-linked ubiquitin. UBE2D3 acts as an initiator
CC E2, priming the phosphorylated NFKBIA target at positions 'Lys-21'
CC and/or 'Lys-22' with a monoubiquitin. Cooperates with the
CC SCF(SKP2) E3 ligase complex to regulate cell proliferation through
CC ubiquitination and degradation of MYBL2 and KIP1. Involved in
CC ubiquitin conjugation and degradation of CREM isoform ICERIIgamma
CC and ATF15 resulting in abrogation of ICERIIgamma- and ATF5-
CC mediated repression of cAMP-induced transcription during both
CC meiotic and mitotic cell cycles. Involved in the regulation of the
CC cell cycle G2/M phase through its targeting of the WEE1 kinase for
CC ubiquitination and degradation. Also involved in the degradation
CC of beta-catenin. Is target of human herpes virus 1 protein ICP0,
CC leading to ICP0-dependent dynamic interaction with proteasomes.
CC -!- CATALYTIC ACTIVITY: ATP + ubiquitin + protein lysine = AMP +
CC diphosphate + protein N-ubiquityllysine.
CC -!- ENZYME REGULATION: CDC34-catalyzed polyubiquitin chain assembly
CC activity is stimulated by the conjugation of NEDD8 to the CUL1 SCF
CC E3 ligase complex subunit.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.11 uM for beta-catenin-monoubiquin;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
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
CC is neddylated, the interaction between the E2 and the SCF complex
CC is strengthened. When phosphorylated, interacts with beta-TrCP
CC (BTRC). Interacts with human herpes virus 1 protein ICP0 and
CC associates with the proteasome for degradation. Interacts with
CC casein kinase subunit CSNK2B.
CC -!- INTERACTION:
CC Q13616:CUL1; NbExp=3; IntAct=EBI-975634, EBI-359390;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=The phosphorylation
CC of the C-terminal tail plays an important role in mediating
CC nuclear localization. Colocalizes with beta-tubulin on mitotic
CC spindles in anaphase.
CC -!- TISSUE SPECIFICITY: Expressed in testes during spermatogenesis to
CC regulate repression of cAMP-induced transcription.
CC -!- INDUCTION: Negatively regulated by the let-7 microRNA.
CC -!- DOMAIN: The C-terminal acidic tail is required for nuclear
CC localization and is involved in the binding to SCF E3 ligase
CC complexes, and more specifically with the CUL1 subunit.
CC -!- PTM: Autoubiquitinated. Autoubiquitination is promoted by the
CC human herpes virus 1 protein ICP0 and leads to degradation by the
CC Ubiquitin-proteasomal pathway.
CC -!- PTM: Phosphorylated by CK2. Phosphorylation of the C-terminal tail
CC by CK2 controles the nuclear localization.
CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC37534.1; Type=Erroneous initiation;
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cdc34/";
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DR EMBL; L22005; AAC37534.1; ALT_INIT; mRNA.
DR EMBL; BT006659; AAP35305.1; -; mRNA.
DR EMBL; AY650399; AAT46688.1; -; Genomic_DNA.
DR EMBL; AK291554; BAF84243.1; -; mRNA.
DR EMBL; CH471242; EAW61190.1; -; Genomic_DNA.
DR EMBL; BC009850; AAH09850.1; -; mRNA.
DR EMBL; BC018143; AAH18143.1; -; mRNA.
DR EMBL; BC023979; AAH23979.1; -; mRNA.
DR PIR; A49630; A49630.
DR RefSeq; NP_004350.1; NM_004359.1.
DR UniGene; Hs.514997; -.
DR PDB; 2OB4; X-ray; 2.40 A; A=7-184.
DR PDB; 3RZ3; X-ray; 2.30 A; A/B/C/D=7-184.
DR PDBsum; 2OB4; -.
DR PDBsum; 3RZ3; -.
DR ProteinModelPortal; P49427; -.
DR SMR; P49427; 7-183.
DR DIP; DIP-37783N; -.
DR IntAct; P49427; 12.
DR MINT; MINT-238910; -.
DR STRING; 9606.ENSP00000215574; -.
DR PhosphoSite; P49427; -.
DR DMDM; 2507505; -.
DR PaxDb; P49427; -.
DR PeptideAtlas; P49427; -.
DR PRIDE; P49427; -.
DR DNASU; 997; -.
DR Ensembl; ENST00000215574; ENSP00000215574; ENSG00000099804.
DR GeneID; 997; -.
DR KEGG; hsa:997; -.
DR UCSC; uc002lov.3; human.
DR CTD; 997; -.
DR GeneCards; GC19P000532; -.
DR HGNC; HGNC:1734; CDC34.
DR HPA; CAB005109; -.
DR HPA; CAB047311; -.
DR HPA; HPA002382; -.
DR MIM; 116948; gene.
DR neXtProt; NX_P49427; -.
DR PharmGKB; PA26265; -.
DR eggNOG; COG5078; -.
DR HOGENOM; HOG000233454; -.
DR HOVERGEN; HBG063308; -.
DR InParanoid; P49427; -.
DR KO; K02207; -.
DR OMA; RVNLVDE; -.
DR OrthoDB; EOG7VB2HT; -.
DR PhylomeDB; P49427; -.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P49427; -.
DR UniPathway; UPA00143; -.
DR EvolutionaryTrace; P49427; -.
DR GeneWiki; CDC34; -.
DR GenomeRNAi; 997; -.
DR NextBio; 4188; -.
DR PRO; PR:P49427; -.
DR Bgee; P49427; -.
DR CleanEx; HS_CDC34; -.
DR Genevestigator; P49427; -.
DR GO; GO:0005737; C:cytoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; NAS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
DR GO; GO:0006270; P:DNA replication initiation; NAS:UniProtKB.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; NAS:UniProtKB.
DR GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; IDA:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
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; UBIQUITIN_CONJUGAT_1; 1.
DR PROSITE; PS50127; UBIQUITIN_CONJUGAT_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell cycle; Complete proteome; Cytoplasm;
KW Ligase; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1 236 Ubiquitin-conjugating enzyme E2 R1.
FT /FTId=PRO_0000082451.
FT REGION 190 236 SCF-binding.
FT COMPBIAS 200 236 Asp/Glu-rich (acidic).
FT ACT_SITE 93 93 Glycyl thioester intermediate.
FT MOD_RES 203 203 Phosphoserine; by CK2.
FT MOD_RES 222 222 Phosphoserine; by CK2.
FT MOD_RES 231 231 Phosphoserine; by CK2.
FT MOD_RES 233 233 Phosphothreonine; by CK2.
FT MOD_RES 236 236 Phosphoserine; by CK2.
FT VARIANT 227 227 D -> H (in dbSNP:rs16990650).
FT /FTId=VAR_021277.
FT MUTAGEN 85 85 N->Q: Inhibits both mono and
FT polyubiquitination of NFKBIA.
FT MUTAGEN 87 87 Y->A: Decreases polyubiquitination of
FT NFKBIA.
FT MUTAGEN 93 93 C->S,A: Loss of function.
FT MUTAGEN 95 95 S->D: Inhibits both mono and
FT polyubiquitination of NFKBIA.
FT MUTAGEN 97 97 L->S: Loss of function.
FT MUTAGEN 102 102 D->A: Inhibits polyubiquitination of
FT NFKBIA; when associated with A-103.
FT MUTAGEN 103 103 D->A: Inhibits polyubiquitination of
FT NFKBIA; when associated with A-102.
FT MUTAGEN 108 108 E->A: Inhibits both mono and
FT polyubiquitination of NFKBIA; when
FT associated with A-112.
FT MUTAGEN 112 112 E->A: Inhibits both mono
FT andpolyubiquitination of NFKBIA; when
FT associated with A-108.
FT MUTAGEN 138 138 S->A: Decreases monoubiquitination of
FT NFKBIA and inhibits polyubiquitination of
FT NFKBIA.
FT MUTAGEN 143 143 D->A: Inhibits polyubiquitination of
FT NFKBIA; when associated with A-147; A-
FT 149; A-150 and A-153.
FT MUTAGEN 147 147 M->A: Inhibits polyubiquitination of
FT NFKBIA; when associated with A-143; A-
FT 149; A-150 and A-153.
FT MUTAGEN 149 149 R->A: Inhibits polyubiquitination of
FT NFKBIA; when associated with A-147; A-
FT 147; A-150 and A-153.
FT MUTAGEN 150 150 K->A: Inhibits polyubiquitination of
FT NFKBIA; when associated with A-143; A-
FT 147; A-149 and A-153.
FT MUTAGEN 153 153 E->A: Inhibits polyubiquitination of
FT NFKBIA; when associated with A-143; A-
FT 147; A-149 and A-150.
FT MUTAGEN 203 203 S->A: Abolishes phosphorylation by CK2.
FT Impairs nuclear localization; when
FT associated with A-222; A-231; A-233 and
FT A-236.
FT MUTAGEN 222 222 S->A: Abolishes phosphorylation by CK2.
FT Impairs nuclear localization; when
FT associated with A-203; A-231; A-233 and
FT A-236.
FT MUTAGEN 231 231 S->A: Abolishes phosphorylation by CK2.
FT Impairs nuclear localization; when
FT associated with A-203; A-222; A-233 and
FT A-236.
FT MUTAGEN 233 233 T->A: Abolishes phosphorylation by CK2.
FT Impairs nuclear localization; when
FT associated with A-203; A-222; A-231 and
FT A-236.
FT MUTAGEN 236 236 S->A: Abolishes phosphorylation by CK2.
FT Impairs nuclear localization; when
FT associated with A-203; A-222; A-231 and
FT A-233.
FT HELIX 8 22
FT STRAND 28 32
FT STRAND 40 46
FT TURN 52 55
FT STRAND 57 63
FT TURN 66 69
FT STRAND 74 79
FT STRAND 90 92
FT HELIX 94 97
FT HELIX 120 132
FT HELIX 142 153
FT TURN 154 156
FT HELIX 160 178
SQ SEQUENCE 236 AA; 26737 MW; 258960666B589DB3 CRC64;
MARPLVPSSQ KALLLELKGL QEEPVEGFRV TLVDEGDLYN WEVAIFGPPN TYYEGGYFKA
RLKFPIDYPY SPPAFRFLTK MWHPNIYETG DVCISILHPP VDDPQSGELP SERWNPTQNV
RTILLSVISL LNEPNTFSPA NVDASVMYRK WKESKGKDRE YTDIIRKQVL GTKVDAERDG
VKVPTTLAEY CVKTKAPAPD EGSDLFYDDY YEDGEVEEEA DSCFGDDEDD SGTEES
//
ID UB2R1_HUMAN Reviewed; 236 AA.
AC P49427; A8K689;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1997, sequence version 2.
DT 22-JAN-2014, entry version 133.
DE RecName: Full=Ubiquitin-conjugating enzyme E2 R1;
DE EC=6.3.2.19;
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8248134; DOI=10.1073/pnas.90.22.10484;
RA Plon S.E., Leppig K.A., Do H.N., Groudine M.;
RT "Cloning of the human homolog of the CDC34 cell cycle gene by
RT complementation in yeast.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:10484-10488(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT HIS-227.
RG NIEHS SNPs program;
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Lung;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, AND MUTAGENESIS OF CYS-93.
RX PubMed=10329681; DOI=10.1074/jbc.274.21.14823;
RA Gonen H., Bercovich B., Orian A., Carrano A., Takizawa C.,
RA Yamanaka K., Pagano M., Iwai K., Ciechanover A.;
RT "Identification of the ubiquitin carrier proteins, E2s, involved in
RT signal-induced conjugation and subsequent degradation of
RT IkappaBalpha.";
RL J. Biol. Chem. 274:14823-14830(1999).
RN [8]
RP INTERACTION WITH ATF5 AND CREM, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=10373550;
RA Pati D., Meistrich M.L., Plon S.E.;
RT "Human Cdc34 and Rad6B ubiquitin-conjugating enzymes target repressors
RT of cyclic AMP-induced transcription for proteolysis.";
RL Mol. Cell. Biol. 19:5001-5013(1999).
RN [9]
RP SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=10769200;
RA Reymond F., Wirbelauer C., Krek W.;
RT "Association of human ubiquitin-conjugating enzyme CDC34 with the
RT mitotic spindle in anaphase.";
RL J. Cell Sci. 113:1687-1694(2000).
RN [10]
RP FUNCTION.
RX PubMed=10871850; DOI=10.1038/sj.onc.1203618;
RA Charrasse S., Carena I., Brondani V., Klempnauer K.H., Ferrari S.;
RT "Degradation of B-Myb by ubiquitin-mediated proteolysis: involvement
RT of the Cdc34-SCF(p45Skp2) pathway.";
RL Oncogene 19:2986-2995(2000).
RN [11]
RP INTERACTION WITH SCF COMPLEX.
RX PubMed=10918611; DOI=10.1038/sj.onc.1203647;
RA Strack P., Caligiuri M., Pelletier M., Boisclair M., Theodoras A.,
RA Beer-Romero P., Glass S., Parsons T., Copeland R.A., Auger K.R.,
RA Benfield P., Brizuela L., Rolfe M.;
RT "SCF(beta-TRCP) and phosphorylation dependent ubiquitination of I
RT kappa B alpha catalyzed by Ubc3 and Ubc4.";
RL Oncogene 19:3529-3536(2000).
RN [12]
RP INTERACTION WITH CSNK2B, PHOSPHORYLATION AT SER-203; SER-222; SER-231;
RP THR-233 AND SER-236, MUTAGENESIS OF SER-203; SER-222; SER-231; THR-233
RP AND SER-236, AND SUBCELLULAR LOCATION.
RX PubMed=11546811; DOI=10.1074/jbc.M106453200;
RA Block K., Boyer T.G., Yew P.R.;
RT "Phosphorylation of the human ubiquitin-conjugating enzyme, CDC34, by
RT casein kinase 2.";
RL J. Biol. Chem. 276:41049-41058(2001).
RN [13]
RP INTERACTION WITH HUMAN HERPESVIRUS 1 PROTEIN ICP0, AND ASSOCIATION
RP WITH THE PROTEASOME.
RX PubMed=11447293; DOI=10.1073/pnas.161283098;
RA Van Sant C., Hagglund R., Lopez P., Roizman B.;
RT "The infected cell protein 0 of herpes simplex virus 1 dynamically
RT interacts with proteasomes, binds and activates the cdc34 E2
RT ubiquitin-conjugating enzyme, and possesses in vitro E3 ubiquitin
RT ligase activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:8815-8820(2001).
RN [14]
RP INTERACTION WITH SCF COMPLEX, FUNCTION, AND ENZYME REGULATION.
RX PubMed=11675391; DOI=10.1074/jbc.M108008200;
RA Wu K., Chen A., Tan P., Pan Z.Q.;
RT "The Nedd8-conjugated ROC1-CUL1 core ubiquitin ligase utilizes Nedd8
RT charged surface residues for efficient polyubiquitin chain assembly
RT catalyzed by Cdc34.";
RL J. Biol. Chem. 277:516-527(2002).
RN [15]
RP ENZYME ACTIVITY, FUNCTION, INTERACTION WITH BTRC, PHOSPHORYLATION AT
RP SER-231, AND MUTAGENESIS OF CYS-93; LEU-97 AND SER-231.
RX PubMed=12037680; DOI=10.1038/sj.onc.1205574;
RA Semplici F., Meggio F., Pinna L.A., Oliviero S.;
RT "CK2-dependent phosphorylation of the E2 ubiquitin conjugating enzyme
RT UBC3B induces its interaction with beta-TrCP and enhances beta-catenin
RT degradation.";
RL Oncogene 21:3978-3987(2002).
RN [16]
RP INTERACTION WITH HUMAN HERPES VIRUS 1 PROTEIN ICP0, AND
RP AUTOUBIQUITINATION.
RX PubMed=11805320; DOI=10.1073/pnas.022531599;
RA Hagglund R., Van Sant C., Lopez P., Roizman B.;
RT "Herpes simplex virus 1-infected cell protein 0 contains two E3
RT ubiquitin ligase sites specific for different E2 ubiquitin-conjugating
RT enzymes.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:631-636(2002).
RN [17]
RP INTERACTION WITH HUMAN HERPES VIRUS 1 PROTEIN ICP0, AND
RP AUTOUBIQUITINATION.
RX PubMed=12060736; DOI=10.1073/pnas.122246999;
RA Hagglund R., Roizman B.;
RT "Characterization of the novel E3 ubiquitin ligase encoded in exon 3
RT of herpes simplex virus-1-infected cell protein 0.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:7889-7894(2002).
RN [18]
RP FUNCTION.
RX PubMed=15652359; DOI=10.1016/j.yexcr.2004.10.008;
RA Butz N., Ruetz S., Natt F., Hall J., Weiler J., Mestan J., Ducarre M.,
RA Grossenbacher R., Hauser P., Kempf D., Hofmann F.;
RT "The human ubiquitin-conjugating enzyme Cdc34 controls cellular
RT proliferation through regulation of p27Kip1 protein levels.";
RL Exp. Cell Res. 303:482-493(2005).
RN [19]
RP PHOSPHORYLATION AT SER-203; SER-222 AND SER-231, AND FUNCTION.
RX PubMed=17461777; DOI=10.1042/BJ20061812;
RA Sadowski M., Mawson A., Baker R., Sarcevic B.;
RT "Cdc34 C-terminal tail phosphorylation regulates Skp1/cullin/F-box
RT (SCF)-mediated ubiquitination and cell cycle progression.";
RL Biochem. J. 405:569-581(2007).
RN [20]
RP FUNCTION, AND MUTAGENESIS OF ASN-85; TYR-87; SER-95; ASP-102; ASP-103;
RP GLU-108; GLU-112; SER-138; ASP-143; MET-147; ARG-149; LYS-150 AND
RP GLU-153.
RX PubMed=17698585; DOI=10.1128/MCB.00812-07;
RA Gazdoiu S., Yamoah K., Wu K., Pan Z.Q.;
RT "Human Cdc34 employs distinct sites to coordinate attachment of
RT ubiquitin to a substrate and assembly of polyubiquitin chains.";
RL Mol. Cell. Biol. 27:7041-7052(2007).
RN [21]
RP INTERACTION WITH SCF COMPLEX.
RX PubMed=18851830; DOI=10.1016/j.molcel.2008.08.021;
RA Saha A., Deshaies R.J.;
RT "Multimodal activation of the ubiquitin ligase SCF by Nedd8
RT conjugation.";
RL Mol. Cell 32:21-31(2008).
RN [22]
RP FUNCTION, INTERACTION WITH SCF COMPLEX, DOMAIN, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=19945379; DOI=10.1016/j.cell.2009.10.030;
RA Kleiger G., Saha A., Lewis S., Kuhlman B., Deshaies R.J.;
RT "Rapid E2-E3 assembly and disassembly enable processive ubiquitylation
RT of cullin-RING ubiquitin ligase substrates.";
RL Cell 139:957-968(2009).
RN [23]
RP IDENTIFICATION IN A UBIQUITIN LIGASE COMPLEX WITH HINT1 AND RBX1, AND
RP FUNCTION.
RX PubMed=19112177; DOI=10.1074/jbc.M804531200;
RA Cen B., Li H., Weinstein I.B.;
RT "Histidine triad nucleotide-binding protein 1 up-regulates cellular
RT levels of p27KIP1 by targeting ScfSKP2 ubiquitin ligase and Src.";
RL J. Biol. Chem. 284:5265-5276(2009).
RN [24]
RP INDUCTION, AND FUNCTION.
RX PubMed=19126550; DOI=10.1074/jbc.C900002200;
RA Legesse-Miller A., Elemento O., Pfau S.J., Forman J.J., Tavazoie S.,
RA Coller H.A.;
RT "let-7 Overexpression leads to an increased fraction of cells in G2/M,
RT direct down-regulation of Cdc34, and stabilization of Wee1 kinase in
RT primary fibroblasts.";
RL J. Biol. Chem. 284:6605-6609(2009).
RN [25]
RP FUNCTION.
RX PubMed=20061386; DOI=10.1074/jbc.M109.089003;
RA David Y., Ziv T., Admon A., Navon A.;
RT "The E2 ubiquitin-conjugating enzymes direct polyubiquitination to
RT preferred lysines.";
RL J. Biol. Chem. 285:8595-8604(2010).
RN [26]
RP FUNCTION.
RX PubMed=20347421; DOI=10.1016/j.molcel.2010.02.025;
RA Wu K., Kovacev J., Pan Z.Q.;
RT "Priming and extending: a UbcH5/Cdc34 E2 handoff mechanism for
RT polyubiquitination on a SCF substrate.";
RL Mol. Cell 37:784-796(2010).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 7-184.
RG Structural genomics consortium (SGC);
RT "Human ubiquitin-conjugating enzyme cdc34.";
RL Submitted (FEB-2009) to the PDB data bank.
CC -!- FUNCTION: Accepts ubiquitin from the E1 complex and catalyzes its
CC covalent attachment to other proteins. In vitro catalyzes 'Lys-
CC 48'-linked polyubiquitination. Cooperates with the E2 UBCH5C and
CC the SCF(FBXW11) E3 ligase complex for the polyubiquitination of
CC NFKBIA leading to its subsequent proteasomal degradation. Performs
CC ubiquitin chain elongation building ubiquitin chains from the
CC UBE2D3-primed NFKBIA-linked ubiquitin. UBE2D3 acts as an initiator
CC E2, priming the phosphorylated NFKBIA target at positions 'Lys-21'
CC and/or 'Lys-22' with a monoubiquitin. Cooperates with the
CC SCF(SKP2) E3 ligase complex to regulate cell proliferation through
CC ubiquitination and degradation of MYBL2 and KIP1. Involved in
CC ubiquitin conjugation and degradation of CREM isoform ICERIIgamma
CC and ATF15 resulting in abrogation of ICERIIgamma- and ATF5-
CC mediated repression of cAMP-induced transcription during both
CC meiotic and mitotic cell cycles. Involved in the regulation of the
CC cell cycle G2/M phase through its targeting of the WEE1 kinase for
CC ubiquitination and degradation. Also involved in the degradation
CC of beta-catenin. Is target of human herpes virus 1 protein ICP0,
CC leading to ICP0-dependent dynamic interaction with proteasomes.
CC -!- CATALYTIC ACTIVITY: ATP + ubiquitin + protein lysine = AMP +
CC diphosphate + protein N-ubiquityllysine.
CC -!- ENZYME REGULATION: CDC34-catalyzed polyubiquitin chain assembly
CC activity is stimulated by the conjugation of NEDD8 to the CUL1 SCF
CC E3 ligase complex subunit.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.11 uM for beta-catenin-monoubiquin;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
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
CC is neddylated, the interaction between the E2 and the SCF complex
CC is strengthened. When phosphorylated, interacts with beta-TrCP
CC (BTRC). Interacts with human herpes virus 1 protein ICP0 and
CC associates with the proteasome for degradation. Interacts with
CC casein kinase subunit CSNK2B.
CC -!- INTERACTION:
CC Q13616:CUL1; NbExp=3; IntAct=EBI-975634, EBI-359390;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=The phosphorylation
CC of the C-terminal tail plays an important role in mediating
CC nuclear localization. Colocalizes with beta-tubulin on mitotic
CC spindles in anaphase.
CC -!- TISSUE SPECIFICITY: Expressed in testes during spermatogenesis to
CC regulate repression of cAMP-induced transcription.
CC -!- INDUCTION: Negatively regulated by the let-7 microRNA.
CC -!- DOMAIN: The C-terminal acidic tail is required for nuclear
CC localization and is involved in the binding to SCF E3 ligase
CC complexes, and more specifically with the CUL1 subunit.
CC -!- PTM: Autoubiquitinated. Autoubiquitination is promoted by the
CC human herpes virus 1 protein ICP0 and leads to degradation by the
CC Ubiquitin-proteasomal pathway.
CC -!- PTM: Phosphorylated by CK2. Phosphorylation of the C-terminal tail
CC by CK2 controles the nuclear localization.
CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC37534.1; Type=Erroneous initiation;
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cdc34/";
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DR EMBL; L22005; AAC37534.1; ALT_INIT; mRNA.
DR EMBL; BT006659; AAP35305.1; -; mRNA.
DR EMBL; AY650399; AAT46688.1; -; Genomic_DNA.
DR EMBL; AK291554; BAF84243.1; -; mRNA.
DR EMBL; CH471242; EAW61190.1; -; Genomic_DNA.
DR EMBL; BC009850; AAH09850.1; -; mRNA.
DR EMBL; BC018143; AAH18143.1; -; mRNA.
DR EMBL; BC023979; AAH23979.1; -; mRNA.
DR PIR; A49630; A49630.
DR RefSeq; NP_004350.1; NM_004359.1.
DR UniGene; Hs.514997; -.
DR PDB; 2OB4; X-ray; 2.40 A; A=7-184.
DR PDB; 3RZ3; X-ray; 2.30 A; A/B/C/D=7-184.
DR PDBsum; 2OB4; -.
DR PDBsum; 3RZ3; -.
DR ProteinModelPortal; P49427; -.
DR SMR; P49427; 7-183.
DR DIP; DIP-37783N; -.
DR IntAct; P49427; 12.
DR MINT; MINT-238910; -.
DR STRING; 9606.ENSP00000215574; -.
DR PhosphoSite; P49427; -.
DR DMDM; 2507505; -.
DR PaxDb; P49427; -.
DR PeptideAtlas; P49427; -.
DR PRIDE; P49427; -.
DR DNASU; 997; -.
DR Ensembl; ENST00000215574; ENSP00000215574; ENSG00000099804.
DR GeneID; 997; -.
DR KEGG; hsa:997; -.
DR UCSC; uc002lov.3; human.
DR CTD; 997; -.
DR GeneCards; GC19P000532; -.
DR HGNC; HGNC:1734; CDC34.
DR HPA; CAB005109; -.
DR HPA; CAB047311; -.
DR HPA; HPA002382; -.
DR MIM; 116948; gene.
DR neXtProt; NX_P49427; -.
DR PharmGKB; PA26265; -.
DR eggNOG; COG5078; -.
DR HOGENOM; HOG000233454; -.
DR HOVERGEN; HBG063308; -.
DR InParanoid; P49427; -.
DR KO; K02207; -.
DR OMA; RVNLVDE; -.
DR OrthoDB; EOG7VB2HT; -.
DR PhylomeDB; P49427; -.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P49427; -.
DR UniPathway; UPA00143; -.
DR EvolutionaryTrace; P49427; -.
DR GeneWiki; CDC34; -.
DR GenomeRNAi; 997; -.
DR NextBio; 4188; -.
DR PRO; PR:P49427; -.
DR Bgee; P49427; -.
DR CleanEx; HS_CDC34; -.
DR Genevestigator; P49427; -.
DR GO; GO:0005737; C:cytoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; NAS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
DR GO; GO:0006270; P:DNA replication initiation; NAS:UniProtKB.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; NAS:UniProtKB.
DR GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; IDA:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
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; UBIQUITIN_CONJUGAT_1; 1.
DR PROSITE; PS50127; UBIQUITIN_CONJUGAT_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell cycle; Complete proteome; Cytoplasm;
KW Ligase; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1 236 Ubiquitin-conjugating enzyme E2 R1.
FT /FTId=PRO_0000082451.
FT REGION 190 236 SCF-binding.
FT COMPBIAS 200 236 Asp/Glu-rich (acidic).
FT ACT_SITE 93 93 Glycyl thioester intermediate.
FT MOD_RES 203 203 Phosphoserine; by CK2.
FT MOD_RES 222 222 Phosphoserine; by CK2.
FT MOD_RES 231 231 Phosphoserine; by CK2.
FT MOD_RES 233 233 Phosphothreonine; by CK2.
FT MOD_RES 236 236 Phosphoserine; by CK2.
FT VARIANT 227 227 D -> H (in dbSNP:rs16990650).
FT /FTId=VAR_021277.
FT MUTAGEN 85 85 N->Q: Inhibits both mono and
FT polyubiquitination of NFKBIA.
FT MUTAGEN 87 87 Y->A: Decreases polyubiquitination of
FT NFKBIA.
FT MUTAGEN 93 93 C->S,A: Loss of function.
FT MUTAGEN 95 95 S->D: Inhibits both mono and
FT polyubiquitination of NFKBIA.
FT MUTAGEN 97 97 L->S: Loss of function.
FT MUTAGEN 102 102 D->A: Inhibits polyubiquitination of
FT NFKBIA; when associated with A-103.
FT MUTAGEN 103 103 D->A: Inhibits polyubiquitination of
FT NFKBIA; when associated with A-102.
FT MUTAGEN 108 108 E->A: Inhibits both mono and
FT polyubiquitination of NFKBIA; when
FT associated with A-112.
FT MUTAGEN 112 112 E->A: Inhibits both mono
FT andpolyubiquitination of NFKBIA; when
FT associated with A-108.
FT MUTAGEN 138 138 S->A: Decreases monoubiquitination of
FT NFKBIA and inhibits polyubiquitination of
FT NFKBIA.
FT MUTAGEN 143 143 D->A: Inhibits polyubiquitination of
FT NFKBIA; when associated with A-147; A-
FT 149; A-150 and A-153.
FT MUTAGEN 147 147 M->A: Inhibits polyubiquitination of
FT NFKBIA; when associated with A-143; A-
FT 149; A-150 and A-153.
FT MUTAGEN 149 149 R->A: Inhibits polyubiquitination of
FT NFKBIA; when associated with A-147; A-
FT 147; A-150 and A-153.
FT MUTAGEN 150 150 K->A: Inhibits polyubiquitination of
FT NFKBIA; when associated with A-143; A-
FT 147; A-149 and A-153.
FT MUTAGEN 153 153 E->A: Inhibits polyubiquitination of
FT NFKBIA; when associated with A-143; A-
FT 147; A-149 and A-150.
FT MUTAGEN 203 203 S->A: Abolishes phosphorylation by CK2.
FT Impairs nuclear localization; when
FT associated with A-222; A-231; A-233 and
FT A-236.
FT MUTAGEN 222 222 S->A: Abolishes phosphorylation by CK2.
FT Impairs nuclear localization; when
FT associated with A-203; A-231; A-233 and
FT A-236.
FT MUTAGEN 231 231 S->A: Abolishes phosphorylation by CK2.
FT Impairs nuclear localization; when
FT associated with A-203; A-222; A-233 and
FT A-236.
FT MUTAGEN 233 233 T->A: Abolishes phosphorylation by CK2.
FT Impairs nuclear localization; when
FT associated with A-203; A-222; A-231 and
FT A-236.
FT MUTAGEN 236 236 S->A: Abolishes phosphorylation by CK2.
FT Impairs nuclear localization; when
FT associated with A-203; A-222; A-231 and
FT A-233.
FT HELIX 8 22
FT STRAND 28 32
FT STRAND 40 46
FT TURN 52 55
FT STRAND 57 63
FT TURN 66 69
FT STRAND 74 79
FT STRAND 90 92
FT HELIX 94 97
FT HELIX 120 132
FT HELIX 142 153
FT TURN 154 156
FT HELIX 160 178
SQ SEQUENCE 236 AA; 26737 MW; 258960666B589DB3 CRC64;
MARPLVPSSQ KALLLELKGL QEEPVEGFRV TLVDEGDLYN WEVAIFGPPN TYYEGGYFKA
RLKFPIDYPY SPPAFRFLTK MWHPNIYETG DVCISILHPP VDDPQSGELP SERWNPTQNV
RTILLSVISL LNEPNTFSPA NVDASVMYRK WKESKGKDRE YTDIIRKQVL GTKVDAERDG
VKVPTTLAEY CVKTKAPAPD EGSDLFYDDY YEDGEVEEEA DSCFGDDEDD SGTEES
//
MIM
116948
*RECORD*
*FIELD* NO
116948
*FIELD* TI
*116948 CELL DIVISION CYCLE 34, S. CEREVISIAE, HOMOLOG OF; CDC34
;;UBIQUITIN-CONJUGATING ENZYME CDC34;;
read moreUBC3; UBCH3;;
UBIQUITIN-CONJUGATING ENZYME E2R 1; UBE2R1
*FIELD* TX
CLONING
Normal eukaryotes from yeasts to humans have a conserved checkpoint
mechanism in cell division for maintenance of genomic stability. After
DNA strand breaks, checkpoint genes induce rest in the G1 and G2 phases
of the cell cycle until the damage is repaired. Plon et al. (1993)
isolated a putative human G2 checkpoint gene, a homolog of the CDC34
gene of Saccharomyces cerevisiae. Human CDC34 could substitute
efficiently for yeast CDC34.
GENE FUNCTION
Using deletion and site-directed mutagenesis experiments, Semplici et
al. (2002) demonstrated that CK2 (see 115440) phosphorylated CDC34 and
UBC3B (UBE2R2; 612506) at a corresponding serine residue in the C
terminus of each protein. In vitro binding experiments demonstrated that
phosphorylated UBC3B and CDC34 bound specifically to the F-box protein
beta-TRCP (BTRC; 603482), which resulted in enhanced degradation of
beta-catenin (116806), a substrate of BTRC. Semplici et al. (2002)
suggested that CK2-dependent phosphorylation of CDC34 and UBC3B
functions by regulating BTRC substrate recognition.
Pierce et al. (2009) developed a quantitative framework based on product
distribution that predicted that the really interesting new gene (RING)
E3 enzymes SCF(Cdc4) (606278) and SCF-beta-TrCP (603482) work with the
E2 Cdc34 to build polyubiquitin chains on substrates by sequential
transfers of single ubiquitins. Measurements with millisecond time
resolution directly demonstrated that substrate polyubiquitylation
proceeds sequentially. Pierce et al. (2009) concluded that their results
presented an unprecedented glimpse into the mechanism of RING ubiquitin
ligases and illuminated the quantitative parameters that underlie the
rate and pattern of ubiquitin chain assembly.
MAPPING
Plon et al. (1993) demonstrated by in situ hybridization that the CDC34
gene is located in the far telomeric region of 19p13.3, in a region of
syntenic homology between human 19p and mouse 11.
*FIELD* RF
1. Pierce, N. W.; Kleiger, G.; Shan, S.; Deshaies, R. J.: Detection
of sequential polyubiquitylation on a millisecond timescale. Nature 462:
615-619, 2009.
2. Plon, S. E.; Leppig, K. A.; Do, H.-N.; Groudine, M.: Cloning of
the human homolog of the CDC34 cell cycle gene by complementation
in yeast. Proc. Nat. Acad. Sci. 90: 10484-10488, 1993.
3. Semplici, F.; Meggio, F.; Pinna, L. A.; Oliviero, S.: CK2-dependent
phosphorylation of the E2 ubiquitin conjugating enzyme UBC3B induces
its interaction with beta-TrCP and enhances beta-catenin degradation. Oncogene 21:
3978-3987, 2002.
*FIELD* CN
Ada Hamosh - updated: 1/6/2010
Carol A. Bocchini - updated: 12/23/2008
*FIELD* CD
Victor A. McKusick: 9/28/1993
*FIELD* ED
mgross: 03/30/2010
alopez: 1/12/2010
terry: 1/6/2010
carol: 12/23/2008
carol: 4/1/1994
carol: 12/9/1993
carol: 10/13/1993
carol: 9/28/1993
*RECORD*
*FIELD* NO
116948
*FIELD* TI
*116948 CELL DIVISION CYCLE 34, S. CEREVISIAE, HOMOLOG OF; CDC34
;;UBIQUITIN-CONJUGATING ENZYME CDC34;;
read moreUBC3; UBCH3;;
UBIQUITIN-CONJUGATING ENZYME E2R 1; UBE2R1
*FIELD* TX
CLONING
Normal eukaryotes from yeasts to humans have a conserved checkpoint
mechanism in cell division for maintenance of genomic stability. After
DNA strand breaks, checkpoint genes induce rest in the G1 and G2 phases
of the cell cycle until the damage is repaired. Plon et al. (1993)
isolated a putative human G2 checkpoint gene, a homolog of the CDC34
gene of Saccharomyces cerevisiae. Human CDC34 could substitute
efficiently for yeast CDC34.
GENE FUNCTION
Using deletion and site-directed mutagenesis experiments, Semplici et
al. (2002) demonstrated that CK2 (see 115440) phosphorylated CDC34 and
UBC3B (UBE2R2; 612506) at a corresponding serine residue in the C
terminus of each protein. In vitro binding experiments demonstrated that
phosphorylated UBC3B and CDC34 bound specifically to the F-box protein
beta-TRCP (BTRC; 603482), which resulted in enhanced degradation of
beta-catenin (116806), a substrate of BTRC. Semplici et al. (2002)
suggested that CK2-dependent phosphorylation of CDC34 and UBC3B
functions by regulating BTRC substrate recognition.
Pierce et al. (2009) developed a quantitative framework based on product
distribution that predicted that the really interesting new gene (RING)
E3 enzymes SCF(Cdc4) (606278) and SCF-beta-TrCP (603482) work with the
E2 Cdc34 to build polyubiquitin chains on substrates by sequential
transfers of single ubiquitins. Measurements with millisecond time
resolution directly demonstrated that substrate polyubiquitylation
proceeds sequentially. Pierce et al. (2009) concluded that their results
presented an unprecedented glimpse into the mechanism of RING ubiquitin
ligases and illuminated the quantitative parameters that underlie the
rate and pattern of ubiquitin chain assembly.
MAPPING
Plon et al. (1993) demonstrated by in situ hybridization that the CDC34
gene is located in the far telomeric region of 19p13.3, in a region of
syntenic homology between human 19p and mouse 11.
*FIELD* RF
1. Pierce, N. W.; Kleiger, G.; Shan, S.; Deshaies, R. J.: Detection
of sequential polyubiquitylation on a millisecond timescale. Nature 462:
615-619, 2009.
2. Plon, S. E.; Leppig, K. A.; Do, H.-N.; Groudine, M.: Cloning of
the human homolog of the CDC34 cell cycle gene by complementation
in yeast. Proc. Nat. Acad. Sci. 90: 10484-10488, 1993.
3. Semplici, F.; Meggio, F.; Pinna, L. A.; Oliviero, S.: CK2-dependent
phosphorylation of the E2 ubiquitin conjugating enzyme UBC3B induces
its interaction with beta-TrCP and enhances beta-catenin degradation. Oncogene 21:
3978-3987, 2002.
*FIELD* CN
Ada Hamosh - updated: 1/6/2010
Carol A. Bocchini - updated: 12/23/2008
*FIELD* CD
Victor A. McKusick: 9/28/1993
*FIELD* ED
mgross: 03/30/2010
alopez: 1/12/2010
terry: 1/6/2010
carol: 12/23/2008
carol: 4/1/1994
carol: 12/9/1993
carol: 10/13/1993
carol: 9/28/1993