Full text data of UBE4B
UBE4B
(HDNB1, KIAA0684, UFD2)
[Confidence: low (only semi-automatic identification from reviews)]
Ubiquitin conjugation factor E4 B (Homozygously deleted in neuroblastoma 1; Ubiquitin fusion degradation protein 2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Ubiquitin conjugation factor E4 B (Homozygously deleted in neuroblastoma 1; Ubiquitin fusion degradation protein 2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
O95155
ID UBE4B_HUMAN Reviewed; 1302 AA.
AC O95155; A8K8S9; G0ZJH6; O75169; O95338; Q5SZ12; Q5SZ16; Q96QD4;
read moreAC Q9BYI7;
DT 01-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 22-JAN-2014, entry version 117.
DE RecName: Full=Ubiquitin conjugation factor E4 B;
DE AltName: Full=Homozygously deleted in neuroblastoma 1;
DE AltName: Full=Ubiquitin fusion degradation protein 2;
GN Name=UBE4B; Synonyms=HDNB1, KIAA0684, UFD2;
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] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9653645; DOI=10.1006/geno.1997.5186;
RA Onyango P., Lubyova B., Gardellin P., Kurzbauer R., Weith A.;
RT "Molecular cloning and expression analysis of five novel genes in
RT chromosome 1p36.";
RL Genomics 50:187-198(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Substantia nigra;
RX PubMed=10980605; DOI=10.1038/sj.onc.1203786;
RA Ohira M., Kageyama H., Mihara M., Furuta S., Machida T.,
RA Shishikura T., Takayasu H., Islam A., Nakamura Y., Takahashi M.,
RA Tomioka N., Sakiyama S., Kaneko Y., Toyoda A., Hattori M., Sakaki Y.,
RA Ohki M., Horii A., Soeda E., Inazawa J., Seki N., Kuma H., Nozawa I.,
RA Nakagawara A.;
RT "Identification and characterization of a 500-kb homozygously deleted
RT region at 1p36.2-p36.3 in a neuroblastoma cell line.";
RL Oncogene 19:4302-4307(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY,
RP MUTAGENESIS OF ASP-109; ASP-121 AND ASP-123, AND CLEAVAGE BY CASPASES.
RX PubMed=11802788; DOI=10.1042/0264-6021:3610587;
RA Mahoney J.A., Odin J.A., White S.M., Shaffer D., Koff A.,
RA Casciola-Rosen L., Rosen A.;
RT "The human homologue of the yeast polyubiquitination factor Ufd2p is
RT cleaved by caspase 6 and granzyme B during apoptosis.";
RL Biochem. J. 361:587-595(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), AND ALTERNATIVE SPLICING.
RC TISSUE=Skeletal muscle;
RX PubMed=22174917; DOI=10.1371/journal.pone.0028861;
RA Mammen A.L., Mahoney J.A., St Germain A., Badders N., Taylor J.P.,
RA Rosen A., Spinette S.;
RT "A novel conserved isoform of the ubiquitin ligase UFD2a/UBE4B is
RT expressed exclusively in mature striated muscle cells.";
RL PLoS ONE 6:E28861-E28861(2011).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. X.
RT The complete sequences of 100 new cDNA clones from brain which can
RT code for large proteins in vitro.";
RL DNA Res. 5:169-176(1998).
RN [6]
RP SEQUENCE REVISION.
RA Ohara O., Suyama M., Nagase T., Ishikawa K.;
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Cerebellum;
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1112-1302.
RA Barrow I.K.-P., Boguski M.S., Touchman J.W., Spencer F.;
RT "Full-insert sequence of mapped XREF EST.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-803, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-31, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-803, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-31; SER-88; SER-90;
RP SER-101 AND SER-803, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-84; SER-88; SER-90 AND
RP SER-101, AND MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-803 AND SER-1265, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [19]
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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-103 AND SER-803, AND
RP MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Binds to the ubiquitin moieties of preformed conjugates
CC and catalyzes ubiquitin chain assembly in conjunction with E1, E2,
CC and E3 (By similarity).
CC -!- SUBUNIT: Interacts with VCP (By similarity).
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=O95155-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95155-2; Sequence=VSP_007102;
CC Name=3;
CC IsoId=O95155-3; Sequence=VSP_007101, VSP_007102, VSP_007103;
CC Note=No experimental confirmation available;
CC Name=4; Synonyms=UFD2a-7/7a, UFD2A-III;
CC IsoId=O95155-4; Sequence=VSP_053372;
CC Note=Expressed exclusively in mature striated muscle cells;
CC -!- TISSUE SPECIFICITY: Highest expression in ovary, testis, heart and
CC skeletal muscle. Expression is low in colon, thymus and peripheral
CC blood leukocytes. Almost undetectable in lung and spleen.
CC -!- PTM: Proteolytically cleaved by caspases during apoptosis. Cleaved
CC efficiently at Asp-123 by caspase-6 and granzyme B. Cleaved with
CC approximately 10-fold less efficiency at Asp-109 by caspase-3 and
CC caspase-7.
CC -!- SIMILARITY: Belongs to the ubiquitin conjugation factor E4 family.
CC -!- SIMILARITY: Contains 1 U-box domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA31659.3; Type=Erroneous initiation;
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DR EMBL; AF043117; AAD02233.1; -; mRNA.
DR EMBL; AB028839; BAB40446.1; -; mRNA.
DR EMBL; AF331520; AAK69622.1; -; mRNA.
DR EMBL; JF289274; AEK06331.1; -; mRNA.
DR EMBL; AB014584; BAA31659.3; ALT_INIT; mRNA.
DR EMBL; AK292444; BAF85133.1; -; mRNA.
DR EMBL; AL590639; CAI14687.1; -; Genomic_DNA.
DR EMBL; AL096841; CAI14687.1; JOINED; Genomic_DNA.
DR EMBL; AL590639; CAI14688.1; -; Genomic_DNA.
DR EMBL; AL096841; CAI14688.1; JOINED; Genomic_DNA.
DR EMBL; AL096841; CAI21859.1; -; Genomic_DNA.
DR EMBL; AL590639; CAI21859.1; JOINED; Genomic_DNA.
DR EMBL; AL096841; CAI21860.1; -; Genomic_DNA.
DR EMBL; AL590639; CAI21860.1; JOINED; Genomic_DNA.
DR EMBL; BC093696; AAH93696.1; -; mRNA.
DR EMBL; AF091093; AAC72962.1; ALT_SEQ; mRNA.
DR PIR; T00358; T00358.
DR RefSeq; NP_001099032.1; NM_001105562.2.
DR RefSeq; NP_006039.2; NM_006048.4.
DR RefSeq; XP_005263479.1; XM_005263422.1.
DR UniGene; Hs.593974; -.
DR PDB; 2KRE; NMR; -; A=1208-1302.
DR PDB; 3L1X; X-ray; 2.60 A; A=1208-1302.
DR PDB; 3L1Z; X-ray; 3.17 A; B=1208-1302.
DR PDBsum; 2KRE; -.
DR PDBsum; 3L1X; -.
DR PDBsum; 3L1Z; -.
DR ProteinModelPortal; O95155; -.
DR SMR; O95155; 1223-1300.
DR DIP; DIP-40309N; -.
DR IntAct; O95155; 6.
DR MINT; MINT-2798575; -.
DR STRING; 9606.ENSP00000343001; -.
DR PhosphoSite; O95155; -.
DR PaxDb; O95155; -.
DR PRIDE; O95155; -.
DR Ensembl; ENST00000253251; ENSP00000253251; ENSG00000130939.
DR Ensembl; ENST00000343090; ENSP00000343001; ENSG00000130939.
DR Ensembl; ENST00000377157; ENSP00000366362; ENSG00000130939.
DR GeneID; 10277; -.
DR KEGG; hsa:10277; -.
DR UCSC; uc021ogc.1; human.
DR CTD; 10277; -.
DR GeneCards; GC01P010092; -.
DR HGNC; HGNC:12500; UBE4B.
DR HPA; HPA019219; -.
DR MIM; 613565; gene.
DR neXtProt; NX_O95155; -.
DR PharmGKB; PA37148; -.
DR eggNOG; COG5113; -.
DR HOGENOM; HOG000294109; -.
DR HOVERGEN; HBG058129; -.
DR InParanoid; O95155; -.
DR KO; K10597; -.
DR OMA; ECSFDSD; -.
DR OrthoDB; EOG7TXKFT; -.
DR ChiTaRS; UBE4B; human.
DR EvolutionaryTrace; O95155; -.
DR GeneWiki; UBE4B; -.
DR GenomeRNAi; 10277; -.
DR NextBio; 35514999; -.
DR PMAP-CutDB; O95155; -.
DR PRO; PR:O95155; -.
DR ArrayExpress; O95155; -.
DR Bgee; O95155; -.
DR CleanEx; HS_UBE4B; -.
DR Genevestigator; O95155; -.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0000151; C:ubiquitin ligase complex; TAS:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; ISS:UniProtKB.
DR GO; GO:0034450; F:ubiquitin-ubiquitin ligase activity; IEA:InterPro.
DR GO; GO:0008626; P:granzyme-mediated apoptotic signaling pathway; IDA:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:MGI.
DR GO; GO:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; TAS:UniProtKB.
DR GO; GO:0009411; P:response to UV; IDA:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR019474; Ub_conjug_fac_E4_core.
DR InterPro; IPR003613; Ubox_domain.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF04564; U-box; 1.
DR Pfam; PF10408; Ufd2P_core; 1.
DR SMART; SM00504; Ubox; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; Phosphoprotein; Polymorphism; Reference proteome;
KW Ubl conjugation pathway.
FT CHAIN 1 1302 Ubiquitin conjugation factor E4 B.
FT /FTId=PRO_0000194993.
FT DOMAIN 1231 1293 U-box.
FT SITE 109 110 Cleavage; by caspase-3 and caspase-7.
FT SITE 123 124 Cleavage; by caspase-6 and granzyme B.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 31 31 Phosphoserine.
FT MOD_RES 84 84 Phosphoserine.
FT MOD_RES 88 88 Phosphoserine.
FT MOD_RES 90 90 Phosphoserine.
FT MOD_RES 101 101 Phosphoserine.
FT MOD_RES 103 103 Phosphoserine.
FT MOD_RES 803 803 Phosphoserine.
FT MOD_RES 1265 1265 Phosphoserine.
FT VAR_SEQ 1 116 Missing (in isoform 3).
FT /FTId=VSP_007101.
FT VAR_SEQ 270 398 Missing (in isoform 2 and isoform 3).
FT /FTId=VSP_007102.
FT VAR_SEQ 398 398 P -> PSMYDNPFSFLFLALSGDSSDEEDEEEDDDDGDGDD
FT EGGGGGDDFSCVQFGS (in isoform 4).
FT /FTId=VSP_053372.
FT VAR_SEQ 1234 1234 D -> GKWTH (in isoform 3).
FT /FTId=VSP_007103.
FT VARIANT 605 605 V -> I (in dbSNP:rs17034499).
FT /FTId=VAR_052437.
FT MUTAGEN 109 109 D->A: Abolishes cleavage by caspase-3 and
FT caspase-7.
FT MUTAGEN 121 121 D->A: Abolishes cleavage by caspase-6. No
FT effect on cleavage by granzyme B.
FT MUTAGEN 123 123 D->A: Abolishes cleavage by caspase-6 and
FT granzyme B.
FT HELIX 1230 1232
FT TURN 1235 1237
FT STRAND 1242 1246
FT TURN 1248 1250
FT STRAND 1252 1254
FT HELIX 1255 1264
FT TURN 1269 1271
FT HELIX 1277 1279
FT HELIX 1284 1298
SQ SEQUENCE 1302 AA; 146185 MW; 6BAA80984B03E43B CRC64;
MEELSADEIR RRRLARLAGG QTSQPTTPLT SPQRENPPGP PIAASAPGPS QSLGLNVHNM
TPATSPIGAS GVAHRSQSSE GVSSLSSSPS NSLETQSQSL SRSQSMDIDG VSCEKSMSQV
DVDSGIENME VDENDRREKR SLSDKEPSSG PEVSEEQALQ LVCKIFRVSW KDRDRDVIFL
SSLSAQFKQN PKEVFSDFKD LIGQILMEVL MMSTQTRDEN PFASLTATSQ PIAAAARSPD
RNLLLNTGSN PGTSPMFCSV ASFGASSLSS LYESSPAPTP SFWSSVPVMG PSLASPSRAA
SQLAVPSTPL SPHSAASGTA AGSQPSSPRY RPYTVTHPWA SSGVSILSSS PSPPALASSP
QAVPASSSRQ RPSSTGPPLP PASPSATSRR PSSLRISPSL GASGGASNWD SYSDHFTIET
CKETDMLNYL IECFDRVGIE EKKAPKMCSQ PAVSQLLSNI RSQCISHTAL VLQGSLTQPR
SLQQPSFLVP YMLCRNLPYG FIQELVRTTH QDEEVFKQIF IPILQGLALA AKECSLDSDY
FKYPLMALGE LCETKFGKTH PVCNLVASLR LWLPKSLSPG CGRELQRLSY LGAFFSFSVF
AEDDVKVVEK YFSGPAITLE NTRVVSQSLQ HYLELGRQEL FKILHSILLN GETREAALSY
MAAVVNANMK KAQMQTDDRL VSTDGFMLNF LWVLQQLSTK IKLETVDPTY IFHPRCRITL
PNDETRVNAT MEDVNDWLTE LYGDQPPFSE PKFPTECFFL TLHAHHLSIL PSCRRYIRRL
RAIRELNRTV EDLKNNESQW KDSPLATRHR EMLKRCKTQL KKLVRCKACA DAGLLDESFL
RRCLNFYGLL IQLLLRILDP AYPDITLPLN SDVPKVFAAL PEFYVEDVAE FLFFIVQYSP
QALYEPCTQD IVMFLVVMLC NQNYIRNPYL VAKLVEVMFM TNPAVQPRTQ KFFEMIENHP
LSTKLLVPSL MKFYTDVEHT GATSEFYDKF TIRYHISTIF KSLWQNIAHH GTFMEEFNSG
KQFVRYINML INDTTFLLDE SLESLKRIHE VQEEMKNKEQ WDQLPRDQQQ ARQSQLAQDE
RVSRSYLALA TETVDMFHIL TKQVQKPFLR PELGPRLAAM LNFNLQQLCG PKCRDLKVEN
PEKYGFEPKK LLDQLTDIYL QLDCARFAKA IADDQRSYSK ELFEEVISKM RKAGIKSTIA
IEKFKLLAEK VEEIVAKNAR AEIDYSDAPD EFRDPLMDTL MTDPVRLPSG TIMDRSIILR
HLLNSPTDPF NRQTLTESML EPVPELKEQI QAWMREKQNS DH
//
ID UBE4B_HUMAN Reviewed; 1302 AA.
AC O95155; A8K8S9; G0ZJH6; O75169; O95338; Q5SZ12; Q5SZ16; Q96QD4;
read moreAC Q9BYI7;
DT 01-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 22-JAN-2014, entry version 117.
DE RecName: Full=Ubiquitin conjugation factor E4 B;
DE AltName: Full=Homozygously deleted in neuroblastoma 1;
DE AltName: Full=Ubiquitin fusion degradation protein 2;
GN Name=UBE4B; Synonyms=HDNB1, KIAA0684, UFD2;
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] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9653645; DOI=10.1006/geno.1997.5186;
RA Onyango P., Lubyova B., Gardellin P., Kurzbauer R., Weith A.;
RT "Molecular cloning and expression analysis of five novel genes in
RT chromosome 1p36.";
RL Genomics 50:187-198(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Substantia nigra;
RX PubMed=10980605; DOI=10.1038/sj.onc.1203786;
RA Ohira M., Kageyama H., Mihara M., Furuta S., Machida T.,
RA Shishikura T., Takayasu H., Islam A., Nakamura Y., Takahashi M.,
RA Tomioka N., Sakiyama S., Kaneko Y., Toyoda A., Hattori M., Sakaki Y.,
RA Ohki M., Horii A., Soeda E., Inazawa J., Seki N., Kuma H., Nozawa I.,
RA Nakagawara A.;
RT "Identification and characterization of a 500-kb homozygously deleted
RT region at 1p36.2-p36.3 in a neuroblastoma cell line.";
RL Oncogene 19:4302-4307(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY,
RP MUTAGENESIS OF ASP-109; ASP-121 AND ASP-123, AND CLEAVAGE BY CASPASES.
RX PubMed=11802788; DOI=10.1042/0264-6021:3610587;
RA Mahoney J.A., Odin J.A., White S.M., Shaffer D., Koff A.,
RA Casciola-Rosen L., Rosen A.;
RT "The human homologue of the yeast polyubiquitination factor Ufd2p is
RT cleaved by caspase 6 and granzyme B during apoptosis.";
RL Biochem. J. 361:587-595(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), AND ALTERNATIVE SPLICING.
RC TISSUE=Skeletal muscle;
RX PubMed=22174917; DOI=10.1371/journal.pone.0028861;
RA Mammen A.L., Mahoney J.A., St Germain A., Badders N., Taylor J.P.,
RA Rosen A., Spinette S.;
RT "A novel conserved isoform of the ubiquitin ligase UFD2a/UBE4B is
RT expressed exclusively in mature striated muscle cells.";
RL PLoS ONE 6:E28861-E28861(2011).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. X.
RT The complete sequences of 100 new cDNA clones from brain which can
RT code for large proteins in vitro.";
RL DNA Res. 5:169-176(1998).
RN [6]
RP SEQUENCE REVISION.
RA Ohara O., Suyama M., Nagase T., Ishikawa K.;
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Cerebellum;
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1112-1302.
RA Barrow I.K.-P., Boguski M.S., Touchman J.W., Spencer F.;
RT "Full-insert sequence of mapped XREF EST.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-803, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-31, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-803, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-31; SER-88; SER-90;
RP SER-101 AND SER-803, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-84; SER-88; SER-90 AND
RP SER-101, AND MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-803 AND SER-1265, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [19]
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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-103 AND SER-803, AND
RP MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Binds to the ubiquitin moieties of preformed conjugates
CC and catalyzes ubiquitin chain assembly in conjunction with E1, E2,
CC and E3 (By similarity).
CC -!- SUBUNIT: Interacts with VCP (By similarity).
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=O95155-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95155-2; Sequence=VSP_007102;
CC Name=3;
CC IsoId=O95155-3; Sequence=VSP_007101, VSP_007102, VSP_007103;
CC Note=No experimental confirmation available;
CC Name=4; Synonyms=UFD2a-7/7a, UFD2A-III;
CC IsoId=O95155-4; Sequence=VSP_053372;
CC Note=Expressed exclusively in mature striated muscle cells;
CC -!- TISSUE SPECIFICITY: Highest expression in ovary, testis, heart and
CC skeletal muscle. Expression is low in colon, thymus and peripheral
CC blood leukocytes. Almost undetectable in lung and spleen.
CC -!- PTM: Proteolytically cleaved by caspases during apoptosis. Cleaved
CC efficiently at Asp-123 by caspase-6 and granzyme B. Cleaved with
CC approximately 10-fold less efficiency at Asp-109 by caspase-3 and
CC caspase-7.
CC -!- SIMILARITY: Belongs to the ubiquitin conjugation factor E4 family.
CC -!- SIMILARITY: Contains 1 U-box domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA31659.3; Type=Erroneous initiation;
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DR EMBL; AF043117; AAD02233.1; -; mRNA.
DR EMBL; AB028839; BAB40446.1; -; mRNA.
DR EMBL; AF331520; AAK69622.1; -; mRNA.
DR EMBL; JF289274; AEK06331.1; -; mRNA.
DR EMBL; AB014584; BAA31659.3; ALT_INIT; mRNA.
DR EMBL; AK292444; BAF85133.1; -; mRNA.
DR EMBL; AL590639; CAI14687.1; -; Genomic_DNA.
DR EMBL; AL096841; CAI14687.1; JOINED; Genomic_DNA.
DR EMBL; AL590639; CAI14688.1; -; Genomic_DNA.
DR EMBL; AL096841; CAI14688.1; JOINED; Genomic_DNA.
DR EMBL; AL096841; CAI21859.1; -; Genomic_DNA.
DR EMBL; AL590639; CAI21859.1; JOINED; Genomic_DNA.
DR EMBL; AL096841; CAI21860.1; -; Genomic_DNA.
DR EMBL; AL590639; CAI21860.1; JOINED; Genomic_DNA.
DR EMBL; BC093696; AAH93696.1; -; mRNA.
DR EMBL; AF091093; AAC72962.1; ALT_SEQ; mRNA.
DR PIR; T00358; T00358.
DR RefSeq; NP_001099032.1; NM_001105562.2.
DR RefSeq; NP_006039.2; NM_006048.4.
DR RefSeq; XP_005263479.1; XM_005263422.1.
DR UniGene; Hs.593974; -.
DR PDB; 2KRE; NMR; -; A=1208-1302.
DR PDB; 3L1X; X-ray; 2.60 A; A=1208-1302.
DR PDB; 3L1Z; X-ray; 3.17 A; B=1208-1302.
DR PDBsum; 2KRE; -.
DR PDBsum; 3L1X; -.
DR PDBsum; 3L1Z; -.
DR ProteinModelPortal; O95155; -.
DR SMR; O95155; 1223-1300.
DR DIP; DIP-40309N; -.
DR IntAct; O95155; 6.
DR MINT; MINT-2798575; -.
DR STRING; 9606.ENSP00000343001; -.
DR PhosphoSite; O95155; -.
DR PaxDb; O95155; -.
DR PRIDE; O95155; -.
DR Ensembl; ENST00000253251; ENSP00000253251; ENSG00000130939.
DR Ensembl; ENST00000343090; ENSP00000343001; ENSG00000130939.
DR Ensembl; ENST00000377157; ENSP00000366362; ENSG00000130939.
DR GeneID; 10277; -.
DR KEGG; hsa:10277; -.
DR UCSC; uc021ogc.1; human.
DR CTD; 10277; -.
DR GeneCards; GC01P010092; -.
DR HGNC; HGNC:12500; UBE4B.
DR HPA; HPA019219; -.
DR MIM; 613565; gene.
DR neXtProt; NX_O95155; -.
DR PharmGKB; PA37148; -.
DR eggNOG; COG5113; -.
DR HOGENOM; HOG000294109; -.
DR HOVERGEN; HBG058129; -.
DR InParanoid; O95155; -.
DR KO; K10597; -.
DR OMA; ECSFDSD; -.
DR OrthoDB; EOG7TXKFT; -.
DR ChiTaRS; UBE4B; human.
DR EvolutionaryTrace; O95155; -.
DR GeneWiki; UBE4B; -.
DR GenomeRNAi; 10277; -.
DR NextBio; 35514999; -.
DR PMAP-CutDB; O95155; -.
DR PRO; PR:O95155; -.
DR ArrayExpress; O95155; -.
DR Bgee; O95155; -.
DR CleanEx; HS_UBE4B; -.
DR Genevestigator; O95155; -.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0000151; C:ubiquitin ligase complex; TAS:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; ISS:UniProtKB.
DR GO; GO:0034450; F:ubiquitin-ubiquitin ligase activity; IEA:InterPro.
DR GO; GO:0008626; P:granzyme-mediated apoptotic signaling pathway; IDA:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:MGI.
DR GO; GO:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; TAS:UniProtKB.
DR GO; GO:0009411; P:response to UV; IDA:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR019474; Ub_conjug_fac_E4_core.
DR InterPro; IPR003613; Ubox_domain.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF04564; U-box; 1.
DR Pfam; PF10408; Ufd2P_core; 1.
DR SMART; SM00504; Ubox; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; Phosphoprotein; Polymorphism; Reference proteome;
KW Ubl conjugation pathway.
FT CHAIN 1 1302 Ubiquitin conjugation factor E4 B.
FT /FTId=PRO_0000194993.
FT DOMAIN 1231 1293 U-box.
FT SITE 109 110 Cleavage; by caspase-3 and caspase-7.
FT SITE 123 124 Cleavage; by caspase-6 and granzyme B.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 31 31 Phosphoserine.
FT MOD_RES 84 84 Phosphoserine.
FT MOD_RES 88 88 Phosphoserine.
FT MOD_RES 90 90 Phosphoserine.
FT MOD_RES 101 101 Phosphoserine.
FT MOD_RES 103 103 Phosphoserine.
FT MOD_RES 803 803 Phosphoserine.
FT MOD_RES 1265 1265 Phosphoserine.
FT VAR_SEQ 1 116 Missing (in isoform 3).
FT /FTId=VSP_007101.
FT VAR_SEQ 270 398 Missing (in isoform 2 and isoform 3).
FT /FTId=VSP_007102.
FT VAR_SEQ 398 398 P -> PSMYDNPFSFLFLALSGDSSDEEDEEEDDDDGDGDD
FT EGGGGGDDFSCVQFGS (in isoform 4).
FT /FTId=VSP_053372.
FT VAR_SEQ 1234 1234 D -> GKWTH (in isoform 3).
FT /FTId=VSP_007103.
FT VARIANT 605 605 V -> I (in dbSNP:rs17034499).
FT /FTId=VAR_052437.
FT MUTAGEN 109 109 D->A: Abolishes cleavage by caspase-3 and
FT caspase-7.
FT MUTAGEN 121 121 D->A: Abolishes cleavage by caspase-6. No
FT effect on cleavage by granzyme B.
FT MUTAGEN 123 123 D->A: Abolishes cleavage by caspase-6 and
FT granzyme B.
FT HELIX 1230 1232
FT TURN 1235 1237
FT STRAND 1242 1246
FT TURN 1248 1250
FT STRAND 1252 1254
FT HELIX 1255 1264
FT TURN 1269 1271
FT HELIX 1277 1279
FT HELIX 1284 1298
SQ SEQUENCE 1302 AA; 146185 MW; 6BAA80984B03E43B CRC64;
MEELSADEIR RRRLARLAGG QTSQPTTPLT SPQRENPPGP PIAASAPGPS QSLGLNVHNM
TPATSPIGAS GVAHRSQSSE GVSSLSSSPS NSLETQSQSL SRSQSMDIDG VSCEKSMSQV
DVDSGIENME VDENDRREKR SLSDKEPSSG PEVSEEQALQ LVCKIFRVSW KDRDRDVIFL
SSLSAQFKQN PKEVFSDFKD LIGQILMEVL MMSTQTRDEN PFASLTATSQ PIAAAARSPD
RNLLLNTGSN PGTSPMFCSV ASFGASSLSS LYESSPAPTP SFWSSVPVMG PSLASPSRAA
SQLAVPSTPL SPHSAASGTA AGSQPSSPRY RPYTVTHPWA SSGVSILSSS PSPPALASSP
QAVPASSSRQ RPSSTGPPLP PASPSATSRR PSSLRISPSL GASGGASNWD SYSDHFTIET
CKETDMLNYL IECFDRVGIE EKKAPKMCSQ PAVSQLLSNI RSQCISHTAL VLQGSLTQPR
SLQQPSFLVP YMLCRNLPYG FIQELVRTTH QDEEVFKQIF IPILQGLALA AKECSLDSDY
FKYPLMALGE LCETKFGKTH PVCNLVASLR LWLPKSLSPG CGRELQRLSY LGAFFSFSVF
AEDDVKVVEK YFSGPAITLE NTRVVSQSLQ HYLELGRQEL FKILHSILLN GETREAALSY
MAAVVNANMK KAQMQTDDRL VSTDGFMLNF LWVLQQLSTK IKLETVDPTY IFHPRCRITL
PNDETRVNAT MEDVNDWLTE LYGDQPPFSE PKFPTECFFL TLHAHHLSIL PSCRRYIRRL
RAIRELNRTV EDLKNNESQW KDSPLATRHR EMLKRCKTQL KKLVRCKACA DAGLLDESFL
RRCLNFYGLL IQLLLRILDP AYPDITLPLN SDVPKVFAAL PEFYVEDVAE FLFFIVQYSP
QALYEPCTQD IVMFLVVMLC NQNYIRNPYL VAKLVEVMFM TNPAVQPRTQ KFFEMIENHP
LSTKLLVPSL MKFYTDVEHT GATSEFYDKF TIRYHISTIF KSLWQNIAHH GTFMEEFNSG
KQFVRYINML INDTTFLLDE SLESLKRIHE VQEEMKNKEQ WDQLPRDQQQ ARQSQLAQDE
RVSRSYLALA TETVDMFHIL TKQVQKPFLR PELGPRLAAM LNFNLQQLCG PKCRDLKVEN
PEKYGFEPKK LLDQLTDIYL QLDCARFAKA IADDQRSYSK ELFEEVISKM RKAGIKSTIA
IEKFKLLAEK VEEIVAKNAR AEIDYSDAPD EFRDPLMDTL MTDPVRLPSG TIMDRSIILR
HLLNSPTDPF NRQTLTESML EPVPELKEQI QAWMREKQNS DH
//
MIM
613565
*RECORD*
*FIELD* NO
613565
*FIELD* TI
*613565 UBIQUITINATION FACTOR E4B; UBE4B
;;UFD2, S. CEREVISIAE, HOMOLOG OF, A; UFD2A;;
read moreKIAA0684
*FIELD* TX
CLONING
By sequencing clones obtained from a size-fractionated human brain cDNA
library, Ishikawa et al. (1998) cloned UBE4B, which they designated
KIAA0684. The deduced 903-amino acid protein shares weak similarity with
Dictyostelium NOSA, a developmental regulator involved in proteasomal
degradation of ubiquitinated proteins (Koegl et al., 1999). See also
UBE4A, 603753. Using RT-PCR, Ishikawa et al. (1998) found uniformly high
KIAA0684 expression in all 10 human tissues examined. In vitro
translation resulted in a protein with an apparent molecular mass of 92
kD by SDS-PAGE.
Kaneko et al. (2003) cloned mouse Ube4b, which they called Ufd2a, from
testis and T cell cDNA libraries. The deduced 1,174-amino acid protein
has a C-terminal U-box domain including a proline residue perfectly
conserved among U-box proteins. Western blot analysis detected Ufd2a at
an apparent molecular mass of 140 kD in most mouse tissues examined,
with highest abundance in cerebrum, cerebellum, and skeletal muscle.
Immunohistochemical analysis revealed localization of Ufd2a in the
cytoplasm of cortical pyramidal cells and cerebellar Purkinje cells.
GENE FUNCTION
By expressing epitope-tagged mouse proteins in human embryonic kidney
cells, Kaneko et al. (2003) showed that Ufd2a interacted with Vcp
(601023), a AAA-family ATPase implicated in protein folding.
Using an in vitro ubiquitination assay with mouse and human UBE4B and
MDM2 (164785), Wu et al. (2011) showed that either UBE4B or MDM2 alone
led to monoubiquitination of the tumor suppressor p53 (TP53; 191170),
while UBE4B in combination with MDM2 promoted p53 polyubiquitination.
Reciprocal immunoprecipitation analysis and protein pull-down assays
revealed that UBE4B interacted directly with MDM2. Overexpression and
knockdown studies in mouse and human cell lines revealed that
interaction of UBE4B with MDM2 reduced the half-life of p53 via
proteasome-mediated degradation and caused repression of p53-dependent
transactivation and apoptosis.
GENE STRUCTURE
Krona et al. (2003) determined that the UBE4B gene contains 28 exons.
Kaneko et al. (2003) found that the mouse Ube4b gene contains 27 coding
exons. The promoter region has a CpG island that contains a functional
cis-acting element, but no TATA or CAAT boxes.
MAPPING
Using radiation hybrid analysis, Ishikawa et al. (1998) mapped the UBE4B
gene to chromosome 1. By genomic sequence analysis, Krona et al. (2003)
mapped the UBE4B gene to chromosome 1p36.3-p36.2.
*FIELD* RF
1. Ishikawa, K.; Nagase, T.; Suyama, M.; Miyajima, N.; Tanaka, A.;
Kotani, H.; Nomura, N.; Ohara, O.: Prediction of the coding sequences
of unidentified human genes. X. The complete sequences of 100 new
cDNA clones from brain which can code for large proteins in vitro. DNA
Res. 5: 169-176, 1998.
2. Kaneko, C.; Hatakeyama, S.; Matsumoto, M.; Yada, M.; Nakayama,
K.; Nakayama, K. I.: Characterization of the mouse gene for the U-box-type
ubiquitin ligase UFD2a. Biochem. Biophys. Res. Commun. 300: 297-304,
2003.
3. Koegl, M.; Hoppe, T.; Schlenker, S.; Ulrich, H. D.; Mayer, T. U.;
Jentsch, S.: A novel ubiquitination factor, E4, is involved in multiubiquitin
chain assembly. Cell 96: 635-644, 1999.
4. Krona, C.; Ejeskar, K.; Abel, F.; Kogner, P.; Bjelke, J.; Bjork,
E.; Sjoberg, R.-M.; Martinsson, T.: Screening for gene mutations
in a 500 kb neuroblastoma tumor suppressor candidate region in chromosome
1p; mutation and stage-specific expression in UBE4B/UFD2. Oncogene 22:
2343-2351, 2003.
5. Wu, H.; Pomeroy, S. L.; Ferreira, M.; Teider, N.; Mariani, J.;
Nakayama, K. I.; Hatakeyama, S.; Tron, V. A.; Saltibus, L. F.; Spyracopoulos,
L.; Leng, R. P.: UBE4B promotes Hdm2-mediated degradation of the
tumor suppressor p53. Nature Med. 17: 347-355, 2011.
*FIELD* CN
Patricia A. Hartz - updated: 8/22/2011
*FIELD* CD
Patricia A. Hartz: 9/17/2010
*FIELD* ED
mgross: 08/23/2011
terry: 8/22/2011
alopez: 9/17/2010
*RECORD*
*FIELD* NO
613565
*FIELD* TI
*613565 UBIQUITINATION FACTOR E4B; UBE4B
;;UFD2, S. CEREVISIAE, HOMOLOG OF, A; UFD2A;;
read moreKIAA0684
*FIELD* TX
CLONING
By sequencing clones obtained from a size-fractionated human brain cDNA
library, Ishikawa et al. (1998) cloned UBE4B, which they designated
KIAA0684. The deduced 903-amino acid protein shares weak similarity with
Dictyostelium NOSA, a developmental regulator involved in proteasomal
degradation of ubiquitinated proteins (Koegl et al., 1999). See also
UBE4A, 603753. Using RT-PCR, Ishikawa et al. (1998) found uniformly high
KIAA0684 expression in all 10 human tissues examined. In vitro
translation resulted in a protein with an apparent molecular mass of 92
kD by SDS-PAGE.
Kaneko et al. (2003) cloned mouse Ube4b, which they called Ufd2a, from
testis and T cell cDNA libraries. The deduced 1,174-amino acid protein
has a C-terminal U-box domain including a proline residue perfectly
conserved among U-box proteins. Western blot analysis detected Ufd2a at
an apparent molecular mass of 140 kD in most mouse tissues examined,
with highest abundance in cerebrum, cerebellum, and skeletal muscle.
Immunohistochemical analysis revealed localization of Ufd2a in the
cytoplasm of cortical pyramidal cells and cerebellar Purkinje cells.
GENE FUNCTION
By expressing epitope-tagged mouse proteins in human embryonic kidney
cells, Kaneko et al. (2003) showed that Ufd2a interacted with Vcp
(601023), a AAA-family ATPase implicated in protein folding.
Using an in vitro ubiquitination assay with mouse and human UBE4B and
MDM2 (164785), Wu et al. (2011) showed that either UBE4B or MDM2 alone
led to monoubiquitination of the tumor suppressor p53 (TP53; 191170),
while UBE4B in combination with MDM2 promoted p53 polyubiquitination.
Reciprocal immunoprecipitation analysis and protein pull-down assays
revealed that UBE4B interacted directly with MDM2. Overexpression and
knockdown studies in mouse and human cell lines revealed that
interaction of UBE4B with MDM2 reduced the half-life of p53 via
proteasome-mediated degradation and caused repression of p53-dependent
transactivation and apoptosis.
GENE STRUCTURE
Krona et al. (2003) determined that the UBE4B gene contains 28 exons.
Kaneko et al. (2003) found that the mouse Ube4b gene contains 27 coding
exons. The promoter region has a CpG island that contains a functional
cis-acting element, but no TATA or CAAT boxes.
MAPPING
Using radiation hybrid analysis, Ishikawa et al. (1998) mapped the UBE4B
gene to chromosome 1. By genomic sequence analysis, Krona et al. (2003)
mapped the UBE4B gene to chromosome 1p36.3-p36.2.
*FIELD* RF
1. Ishikawa, K.; Nagase, T.; Suyama, M.; Miyajima, N.; Tanaka, A.;
Kotani, H.; Nomura, N.; Ohara, O.: Prediction of the coding sequences
of unidentified human genes. X. The complete sequences of 100 new
cDNA clones from brain which can code for large proteins in vitro. DNA
Res. 5: 169-176, 1998.
2. Kaneko, C.; Hatakeyama, S.; Matsumoto, M.; Yada, M.; Nakayama,
K.; Nakayama, K. I.: Characterization of the mouse gene for the U-box-type
ubiquitin ligase UFD2a. Biochem. Biophys. Res. Commun. 300: 297-304,
2003.
3. Koegl, M.; Hoppe, T.; Schlenker, S.; Ulrich, H. D.; Mayer, T. U.;
Jentsch, S.: A novel ubiquitination factor, E4, is involved in multiubiquitin
chain assembly. Cell 96: 635-644, 1999.
4. Krona, C.; Ejeskar, K.; Abel, F.; Kogner, P.; Bjelke, J.; Bjork,
E.; Sjoberg, R.-M.; Martinsson, T.: Screening for gene mutations
in a 500 kb neuroblastoma tumor suppressor candidate region in chromosome
1p; mutation and stage-specific expression in UBE4B/UFD2. Oncogene 22:
2343-2351, 2003.
5. Wu, H.; Pomeroy, S. L.; Ferreira, M.; Teider, N.; Mariani, J.;
Nakayama, K. I.; Hatakeyama, S.; Tron, V. A.; Saltibus, L. F.; Spyracopoulos,
L.; Leng, R. P.: UBE4B promotes Hdm2-mediated degradation of the
tumor suppressor p53. Nature Med. 17: 347-355, 2011.
*FIELD* CN
Patricia A. Hartz - updated: 8/22/2011
*FIELD* CD
Patricia A. Hartz: 9/17/2010
*FIELD* ED
mgross: 08/23/2011
terry: 8/22/2011
alopez: 9/17/2010