UB2R1_HUMAN
ID UB2R1_HUMAN Reviewed; 236 AA.
AC P49427; A8K689;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Ubiquitin-conjugating enzyme E2 R1;
DE EC=2.3.2.23 {ECO:0000269|PubMed:12037680, ECO:0000269|PubMed:17698585, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:20347421};
DE AltName: Full=(E3-independent) E2 ubiquitin-conjugating enzyme R1;
DE EC=2.3.2.24 {ECO:0000269|PubMed:17588522};
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 project:
RT 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., Yamanaka K.,
RA Pagano M., Iwai K., Ciechanover A.;
RT "Identification of the ubiquitin carrier proteins, E2s, involved in signal-
RT induced conjugation and subsequent degradation of IkappaBalpha.";
RL J. Biol. Chem. 274:14823-14830(1999).
RN [8]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=10373550; DOI=10.1128/mcb.19.7.5001;
RA Pati D., Meistrich M.L., Plon S.E.;
RT "Human Cdc34 and Rad6B ubiquitin-conjugating enzymes target repressors of
RT cyclic AMP-induced transcription for proteolysis.";
RL Mol. Cell. Biol. 19:5001-5013(1999).
RN [9]
RP SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=10769200; DOI=10.1242/jcs.113.10.1687;
RA Reymond F., Wirbelauer C., Krek W.;
RT "Association of human ubiquitin-conjugating enzyme CDC34 with the mitotic
RT 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 of the
RT 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 kappa B
RT 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 AND
RP 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 WITH THE
RP 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 ubiquitin-
RT conjugating enzyme, and possesses in vitro E3 ubiquitin ligase activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:8815-8820(2001).
RN [14]
RP INTERACTION WITH SCF COMPLEX, FUNCTION, AND ACTIVITY 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 CATALYTIC 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 UBC3B
RT 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 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 ubiquitin
RT ligase sites specific for different E2 ubiquitin-conjugating 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 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 of
RT 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 (SCF)-
RT mediated ubiquitination and cell cycle progression.";
RL Biochem. J. 405:569-581(2007).
RN [20]
RP CATALYTIC ACTIVITY AS E3-INDEPENDENT E2 UBIQUITIN-CONJUGATING ENZYME.
RX PubMed=17588522; DOI=10.1016/j.molcel.2007.05.014;
RA Hoeller D., Hecker C.M., Wagner S., Rogov V., Doetsch V., Dikic I.;
RT "E3-independent monoubiquitination of ubiquitin-binding proteins.";
RL Mol. Cell 26:891-898(2007).
RN [21]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASN-85; TYR-87; SER-95;
RP ASP-102; ASP-103; GLU-108; GLU-112; SER-138; ASP-143; MET-147; ARG-149;
RP LYS-150 AND 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 ubiquitin
RT to a substrate and assembly of polyubiquitin chains.";
RL Mol. Cell. Biol. 27:7041-7052(2007).
RN [22]
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 conjugation.";
RL Mol. Cell 32:21-31(2008).
RN [23]
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 of
RT cullin-RING ubiquitin ligase substrates.";
RL Cell 139:957-968(2009).
RN [24]
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 levels
RT of p27KIP1 by targeting ScfSKP2 ubiquitin ligase and Src.";
RL J. Biol. Chem. 284:5265-5276(2009).
RN [25]
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 [26]
RP FUNCTION, AND CATALYTIC ACTIVITY.
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 [27]
RP FUNCTION, AND CATALYTIC ACTIVITY.
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 [28]
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., Buerckstuemmer T.,
RA 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 [29]
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.
RN [30] {ECO:0007744|PDB:3RZ3}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 7-184 IN COMPLEX WITH
RP INHIBITOR 4,5-DIDEOXY-5-(3',5'-DICHLOROBIPHENYL-4-YL)-4-
RP [(METHOXYACETYL)AMINO]-L-ARABINONIC ACID.
RX PubMed=21683433; DOI=10.1016/j.cell.2011.05.039;
RA Ceccarelli D.F., Tang X., Pelletier B., Orlicky S., Xie W., Plantevin V.,
RA Neculai D., Chou Y.C., Ogunjimi A., Al-Hakim A., Varelas X., Koszela J.,
RA Wasney G.A., Vedadi M., Dhe-Paganon S., Cox S., Xu S., Lopez-Girona A.,
RA Mercurio F., Wrana J., Durocher D., Meloche S., Webb D.R., Tyers M.,
RA Sicheri F.;
RT "An allosteric inhibitor of the human Cdc34 ubiquitin-conjugating enzyme.";
RL Cell 145:1075-1087(2011).
RN [31] {ECO:0007744|PDB:2OB4}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 7-184, FUNCTION, AND
RP AUTOUBIQUITINATION.
RX PubMed=22496338; DOI=10.1074/mcp.o111.013706;
RA Sheng Y., Hong J.H., Doherty R., Srikumar T., Shloush J., Avvakumov G.V.,
RA Walker J.R., Xue S., Neculai D., Wan J.W., Kim S.K., Arrowsmith C.H.,
RA Raught B., Dhe-Paganon S.;
RT "A human ubiquitin conjugating enzyme (E2)-HECT E3 ligase structure-
RT function screen.";
RL Mol. Cell. Proteomics 11:329-341(2012).
RN [32] {ECO:0007744|PDB:4MDK}
RP X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS) OF 7-184 IN COMPLEX WITH
RP INHIBITOR 4,5-DIDEOXY-5-(3',5'-DICHLOROBIPHENYL-4-YL)-4-
RP [(METHOXYACETYL)AMINO]-L-ARABINONIC ACID, INTERACTION WITH RBX1, AND
RP MUTAGENESIS OF TYR-70; THR-117; SER-129 AND GLU-133.
RX PubMed=24316736; DOI=10.1038/nchembio.1412;
RA Huang H., Ceccarelli D.F., Orlicky S., St-Cyr D.J., Ziemba A., Garg P.,
RA Plamondon S., Auer M., Sidhu S., Marinier A., Kleiger G., Tyers M.,
RA Sicheri F.;
RT "E2 enzyme inhibition by stabilization of a low-affinity interface with
RT ubiquitin.";
RL Nat. Chem. Biol. 10:156-163(2014).
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 (PubMed:22496338). Cooperates with the E2
CC UBCH5C and the SCF(FBXW11) E3 ligase complex for the polyubiquitination
CC of NFKBIA leading to its subsequent proteasomal degradation. Performs
CC ubiquitin chain elongation building ubiquitin chains from the UBE2D3-
CC primed NFKBIA-linked ubiquitin. UBE2D3 acts as an initiator E2, priming
CC the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22'
CC with a monoubiquitin. Cooperates with the SCF(SKP2) E3 ligase complex
CC to regulate cell proliferation through ubiquitination and degradation
CC of 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. Is target of human herpes virus 1 protein ICP0, leading
CC to ICP0-dependent dynamic interaction with proteasomes
CC (PubMed:10329681, PubMed:10373550, PubMed:10871850, PubMed:11675391,
CC PubMed:12037680, PubMed:15652359, PubMed:17461777, PubMed:17698585,
CC PubMed:19112177, PubMed:19126550, PubMed:19945379, PubMed:20061386,
CC PubMed:20347421). {ECO:0000269|PubMed:10329681,
CC ECO:0000269|PubMed:10373550, ECO:0000269|PubMed:10871850,
CC ECO:0000269|PubMed:11675391, ECO:0000269|PubMed:12037680,
CC ECO:0000269|PubMed:15652359, ECO:0000269|PubMed:17461777,
CC ECO:0000269|PubMed:17698585, ECO:0000269|PubMed:19112177,
CC ECO:0000269|PubMed:19126550, ECO:0000269|PubMed:19945379,
CC ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:20347421,
CC ECO:0000269|PubMed:22496338}.
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:0000255|PROSITE-ProRule:PRU00388, ECO:0000255|PROSITE-
CC ProRule:PRU10133, ECO:0000269|PubMed:12037680,
CC ECO:0000269|PubMed:17698585, ECO:0000269|PubMed:20061386,
CC ECO:0000269|PubMed:20347421};
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:0000269|PubMed:17588522};
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:0000269|PubMed:11675391}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.11 uM for beta-catenin-monoubiquin
CC {ECO:0000269|PubMed:19945379};
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 (PubMed:10918611, PubMed:11675391, PubMed:18851830,
CC PubMed:19945379, PubMed:19112177, PubMed:24316736). When
CC phosphorylated, interacts with beta-TrCP (BTRC) (PubMed:12037680).
CC Interacts with human herpes virus 1 protein ICP0 and associates with
CC the proteasome for degradation (PubMed:11447293, PubMed:11805320,
CC PubMed:12060736). Interacts with casein kinase subunit CSNK2B
CC (PubMed:11546811). Interacts with CNTD1; this interaction regulates the
CC cell-cycle progression (By similarity). {ECO:0000250|UniProtKB:Q8CFI2,
CC ECO:0000269|PubMed:10918611, ECO:0000269|PubMed:11447293,
CC ECO:0000269|PubMed:11546811, ECO:0000269|PubMed:11675391,
CC ECO:0000269|PubMed:11805320, ECO:0000269|PubMed:12037680,
CC ECO:0000269|PubMed:12060736, ECO:0000269|PubMed:18851830,
CC ECO:0000269|PubMed:19112177, ECO:0000269|PubMed:19945379,
CC ECO:0000269|PubMed:24316736}.
CC -!- INTERACTION:
CC P49427; Q13616: CUL1; NbExp=3; IntAct=EBI-975634, EBI-359390;
CC P49427; P50221: MEOX1; NbExp=3; IntAct=EBI-975634, EBI-2864512;
CC P49427; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-975634, EBI-16439278;
CC P49427; O00560: SDCBP; NbExp=6; IntAct=EBI-975634, EBI-727004;
CC P49427; Q8IUQ4: SIAH1; NbExp=3; IntAct=EBI-975634, EBI-747107;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=The phosphorylation of
CC the C-terminal tail plays an important role in mediating nuclear
CC localization. Colocalizes with beta-tubulin on mitotic spindles in
CC anaphase.
CC -!- TISSUE SPECIFICITY: Expressed in testes during spermatogenesis to
CC regulate repression of cAMP-induced transcription.
CC {ECO:0000269|PubMed:10373550}.
CC -!- INDUCTION: Negatively regulated by the let-7 microRNA.
CC {ECO:0000269|PubMed:19126550}.
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:0000269|PubMed:10769200,
CC ECO:0000269|PubMed:19945379}.
CC -!- PTM: Autoubiquitinated (PubMed:22496338, PubMed:11805320,
CC PubMed:12060736). Autoubiquitination is promoted by the human herpes
CC virus 1 protein ICP0 and leads to degradation by the Ubiquitin-
CC proteasomal pathway (PubMed:11805320, PubMed:12060736).
CC {ECO:0000269|PubMed:11805320, ECO:0000269|PubMed:12060736,
CC ECO:0000269|PubMed:22496338}.
CC -!- PTM: Phosphorylated by CK2. Phosphorylation of the C-terminal tail by
CC CK2 controles the nuclear localization. {ECO:0000269|PubMed:11546811,
CC ECO:0000269|PubMed:12037680, ECO:0000269|PubMed:17461777}.
CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family.
CC {ECO:0000255|PROSITE-ProRule:PRU00388}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC37534.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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 CCDS; CCDS12030.1; -.
DR PIR; A49630; A49630.
DR RefSeq; NP_004350.1; NM_004359.1.
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 PDB; 4MDK; X-ray; 2.61 A; A/B/C/D=7-184.
DR PDB; 7M2K; X-ray; 2.47 A; A/C/E/G=7-184.
DR PDBsum; 2OB4; -.
DR PDBsum; 3RZ3; -.
DR PDBsum; 4MDK; -.
DR PDBsum; 7M2K; -.
DR AlphaFoldDB; P49427; -.
DR SMR; P49427; -.
DR BioGRID; 107432; 321.
DR CORUM; P49427; -.
DR DIP; DIP-37783N; -.
DR IntAct; P49427; 19.
DR MINT; P49427; -.
DR STRING; 9606.ENSP00000215574; -.
DR GlyGen; P49427; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P49427; -.
DR PhosphoSitePlus; P49427; -.
DR BioMuta; CDC34; -.
DR DMDM; 2507505; -.
DR EPD; P49427; -.
DR jPOST; P49427; -.
DR MassIVE; P49427; -.
DR MaxQB; P49427; -.
DR PaxDb; P49427; -.
DR PeptideAtlas; P49427; -.
DR PRIDE; P49427; -.
DR ProteomicsDB; 56009; -.
DR Antibodypedia; 1040; 376 antibodies from 36 providers.
DR CPTC; P49427; 2 antibodies.
DR DNASU; 997; -.
DR Ensembl; ENST00000215574.9; ENSP00000215574.2; ENSG00000099804.9.
DR GeneID; 997; -.
DR KEGG; hsa:997; -.
DR MANE-Select; ENST00000215574.9; ENSP00000215574.2; NM_004359.2; NP_004350.1.
DR UCSC; uc002lov.4; human.
DR CTD; 997; -.
DR DisGeNET; 997; -.
DR GeneCards; CDC34; -.
DR HGNC; HGNC:1734; CDC34.
DR HPA; ENSG00000099804; Low tissue specificity.
DR MIM; 116948; gene.
DR neXtProt; NX_P49427; -.
DR OpenTargets; ENSG00000099804; -.
DR PharmGKB; PA26265; -.
DR VEuPathDB; HostDB:ENSG00000099804; -.
DR eggNOG; KOG0425; Eukaryota.
DR GeneTree; ENSGT00940000160356; -.
DR HOGENOM; CLU_030988_1_2_1; -.
DR InParanoid; P49427; -.
DR OMA; LFYEDDC; -.
DR OrthoDB; 1116856at2759; -.
DR PhylomeDB; P49427; -.
DR TreeFam; TF101107; -.
DR BRENDA; 2.3.2.23; 2681.
DR BRENDA; 2.3.2.24; 2681.
DR PathwayCommons; P49427; -.
DR Reactome; R-HSA-202424; Downstream TCR signaling.
DR Reactome; R-HSA-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-HSA-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-HSA-8866652; Synthesis of active ubiquitin: roles of E1 and E2 enzymes.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; P49427; -.
DR SIGNOR; P49427; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 997; 22 hits in 1087 CRISPR screens.
DR ChiTaRS; CDC34; human.
DR EvolutionaryTrace; P49427; -.
DR GeneWiki; CDC34; -.
DR GenomeRNAi; 997; -.
DR Pharos; P49427; Tbio.
DR PRO; PR:P49427; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P49427; protein.
DR Bgee; ENSG00000099804; Expressed in left testis and 189 other tissues.
DR ExpressionAtlas; P49427; baseline and differential.
DR Genevisible; P49427; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; NAS:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0035458; P:cellular response to interferon-beta; IMP: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:0090261; P:positive regulation of inclusion body assembly; IEA:Ensembl.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl.
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 GO; GO:0036211; P:protein modification process; NAS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
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 DisProt; DP02094; -.
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 3D-structure; ATP-binding; Cell cycle; Cytoplasm; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Transferase; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..236
FT /note="Ubiquitin-conjugating enzyme E2 R1"
FT /id="PRO_0000082451"
FT DOMAIN 8..174
FT /note="UBC core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388"
FT REGION 190..236
FT /note="SCF-binding"
FT REGION 216..236
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 93
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388"
FT MOD_RES 203
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:11546811,
FT ECO:0000269|PubMed:17461777"
FT MOD_RES 222
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:11546811,
FT ECO:0000269|PubMed:17461777"
FT MOD_RES 231
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:11546811,
FT ECO:0000269|PubMed:12037680, ECO:0000269|PubMed:17461777"
FT MOD_RES 233
FT /note="Phosphothreonine; by CK2"
FT /evidence="ECO:0000269|PubMed:11546811"
FT MOD_RES 236
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:11546811"
FT VARIANT 227
FT /note="D -> H (in dbSNP:rs16990650)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_021277"
FT MUTAGEN 70
FT /note="Y->R: Loss of RBX1-binding."
FT /evidence="ECO:0000269|PubMed:24316736"
FT MUTAGEN 85
FT /note="N->Q: Inhibits both mono and polyubiquitination of
FT NFKBIA."
FT /evidence="ECO:0000269|PubMed:17698585"
FT MUTAGEN 87
FT /note="Y->A: Decreases polyubiquitination of NFKBIA."
FT /evidence="ECO:0000269|PubMed:17698585"
FT MUTAGEN 93
FT /note="C->S,A: Loss of function."
FT /evidence="ECO:0000269|PubMed:10329681,
FT ECO:0000269|PubMed:12037680"
FT MUTAGEN 95
FT /note="S->D: Inhibits both mono and polyubiquitination of
FT NFKBIA."
FT /evidence="ECO:0000269|PubMed:17698585"
FT MUTAGEN 97
FT /note="L->S: Loss of function."
FT /evidence="ECO:0000269|PubMed:12037680"
FT MUTAGEN 102
FT /note="D->A: Inhibits polyubiquitination of NFKBIA; when
FT associated with A-103."
FT /evidence="ECO:0000269|PubMed:17698585"
FT MUTAGEN 103
FT /note="D->A: Inhibits polyubiquitination of NFKBIA; when
FT associated with A-102."
FT /evidence="ECO:0000269|PubMed:17698585"
FT MUTAGEN 108
FT /note="E->A: Inhibits both mono and polyubiquitination of
FT NFKBIA; when associated with A-112."
FT /evidence="ECO:0000269|PubMed:17698585"
FT MUTAGEN 112
FT /note="E->A: Inhibits both mono andpolyubiquitination of
FT NFKBIA; when associated with A-108."
FT /evidence="ECO:0000269|PubMed:17698585"
FT MUTAGEN 117
FT /note="T->E: Loss of RBX1-binding."
FT /evidence="ECO:0000269|PubMed:24316736"
FT MUTAGEN 129
FT /note="S->L: No effect on activity, when assayed in a Sic1-
FT SCF-cdc4 ubiquitination assay."
FT /evidence="ECO:0000269|PubMed:24316736"
FT MUTAGEN 129
FT /note="S->R: Complete loss of activity, when assayed in a
FT Sic1-SCF-cdc4 ubiquitination assay."
FT /evidence="ECO:0000269|PubMed:24316736"
FT MUTAGEN 133
FT /note="E->R: No effect on activity, when assayed in a Sic1-
FT SCF-cdc4 ubiquitination assay."
FT /evidence="ECO:0000269|PubMed:24316736"
FT MUTAGEN 138
FT /note="S->A: Decreases monoubiquitination of NFKBIA and
FT inhibits polyubiquitination of NFKBIA."
FT /evidence="ECO:0000269|PubMed:17698585"
FT MUTAGEN 143
FT /note="D->A: Inhibits polyubiquitination of NFKBIA; when
FT associated with A-147; A-149; A-150 and A-153."
FT /evidence="ECO:0000269|PubMed:17698585"
FT MUTAGEN 147
FT /note="M->A: Inhibits polyubiquitination of NFKBIA; when
FT associated with A-143; A-149; A-150 and A-153."
FT /evidence="ECO:0000269|PubMed:17698585"
FT MUTAGEN 149
FT /note="R->A: Inhibits polyubiquitination of NFKBIA; when
FT associated with A-147; A-147; A-150 and A-153."
FT /evidence="ECO:0000269|PubMed:17698585"
FT MUTAGEN 150
FT /note="K->A: Inhibits polyubiquitination of NFKBIA; when
FT associated with A-143; A-147; A-149 and A-153."
FT /evidence="ECO:0000269|PubMed:17698585"
FT MUTAGEN 153
FT /note="E->A: Inhibits polyubiquitination of NFKBIA; when
FT associated with A-143; A-147; A-149 and A-150."
FT /evidence="ECO:0000269|PubMed:17698585"
FT MUTAGEN 203
FT /note="S->A: Abolishes phosphorylation by CK2. Impairs
FT nuclear localization; when associated with A-222; A-231; A-
FT 233 and A-236."
FT /evidence="ECO:0000269|PubMed:11546811"
FT MUTAGEN 222
FT /note="S->A: Abolishes phosphorylation by CK2. Impairs
FT nuclear localization; when associated with A-203; A-231; A-
FT 233 and A-236."
FT /evidence="ECO:0000269|PubMed:11546811"
FT MUTAGEN 231
FT /note="S->A: Abolishes phosphorylation by CK2. Impairs
FT nuclear localization; when associated with A-203; A-222; A-
FT 233 and A-236."
FT /evidence="ECO:0000269|PubMed:11546811,
FT ECO:0000269|PubMed:12037680"
FT MUTAGEN 233
FT /note="T->A: Abolishes phosphorylation by CK2. Impairs
FT nuclear localization; when associated with A-203; A-222; A-
FT 231 and A-236."
FT /evidence="ECO:0000269|PubMed:11546811"
FT MUTAGEN 236
FT /note="S->A: Abolishes phosphorylation by CK2. Impairs
FT nuclear localization; when associated with A-203; A-222; A-
FT 231 and A-233."
FT /evidence="ECO:0000269|PubMed:11546811"
FT HELIX 8..22
FT /evidence="ECO:0007829|PDB:3RZ3"
FT STRAND 28..32
FT /evidence="ECO:0007829|PDB:3RZ3"
FT STRAND 40..46
FT /evidence="ECO:0007829|PDB:3RZ3"
FT TURN 52..55
FT /evidence="ECO:0007829|PDB:3RZ3"
FT STRAND 57..63
FT /evidence="ECO:0007829|PDB:3RZ3"
FT TURN 66..69
FT /evidence="ECO:0007829|PDB:3RZ3"
FT STRAND 74..79
FT /evidence="ECO:0007829|PDB:3RZ3"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:3RZ3"
FT HELIX 94..97
FT /evidence="ECO:0007829|PDB:2OB4"
FT HELIX 120..132
FT /evidence="ECO:0007829|PDB:3RZ3"
FT HELIX 142..153
FT /evidence="ECO:0007829|PDB:3RZ3"
FT TURN 154..156
FT /evidence="ECO:0007829|PDB:3RZ3"
FT HELIX 160..178
FT /evidence="ECO:0007829|PDB:3RZ3"
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
