UBE4B_HUMAN
ID UBE4B_HUMAN Reviewed; 1302 AA.
AC O95155; A8K8S9; G0ZJH6; O75169; O95338; Q5SZ12; Q5SZ16; Q96QD4; Q9BYI7;
DT 01-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Ubiquitin conjugation factor E4 B {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q9ES00};
DE AltName: Full=Homozygously deleted in neuroblastoma 1 {ECO:0000312|EMBL:BAB40446.1};
DE AltName: Full=RING-type E3 ubiquitin transferase E4 B;
DE AltName: Full=Ubiquitin fusion degradation protein 2 {ECO:0000312|EMBL:AAD02233.1};
GN Name=UBE4B {ECO:0000312|HGNC:HGNC:12500};
GN Synonyms=HDNB1 {ECO:0000312|EMBL:BAB40446.1},
GN KIAA0684 {ECO:0000312|EMBL:BAA31659.3}, UFD2 {ECO:0000312|EMBL:AAD02233.1};
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] (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., Shishikura T.,
RA Takayasu H., Islam A., Nakamura Y., Takahashi M., Tomioka N., Sakiyama S.,
RA Kaneko Y., Toyoda A., Hattori M., Sakaki Y., Ohki M., Horii A., Soeda E.,
RA Inazawa J., Seki N., Kuma H., Nozawa I., 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, MUTAGENESIS OF
RP 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 expressed
RT 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. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT 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., 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 [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., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., 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., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., 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., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., 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 project:
RT 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 IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-31, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [13]
RP FUNCTION, INTERACTION WITH VCP; STUB1 AND UNC45B, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=17369820; DOI=10.1038/ncb1554;
RA Janiesch P.C., Kim J., Mouysset J., Barikbin R., Lochmueller H.,
RA Cassata G., Krause S., Hoppe T.;
RT "The ubiquitin-selective chaperone CDC-48/p97 links myosin assembly to
RT human myopathy.";
RL Nat. Cell Biol. 9:379-390(2007).
RN [14]
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., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-803, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-31; SER-88; SER-90; SER-101
RP AND SER-803, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
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 [17]
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., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-84; SER-88; SER-90 AND
RP SER-101, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-803 AND SER-1265, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [20]
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 [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-103 AND SER-803, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [23]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
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., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23; SER-31; SER-101; SER-105;
RP SER-124; SER-238; SER-383; SER-803 AND SER-1265, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Ubiquitin-protein ligase that probably functions as an E3
CC ligase in conjunction with specific E1 and E2 ligases (By similarity).
CC May also function as an E4 ligase mediating the assembly of
CC polyubiquitin chains on substrates ubiquitinated by another E3
CC ubiquitin ligase (By similarity). May regulate myosin assembly in
CC striated muscles together with STUB1 and VCP/p97 by targeting myosin
CC chaperone UNC45B for proteasomal degradation (PubMed:17369820).
CC {ECO:0000250|UniProtKB:P54860, ECO:0000250|UniProtKB:Q9ES00,
CC ECO:0000269|PubMed:17369820}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000250|UniProtKB:Q9ES00};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q9ES00}.
CC -!- SUBUNIT: Interacts with VCP/p97. Interacts with STUB1/CHIP and UNC45B.
CC {ECO:0000269|PubMed:17369820}.
CC -!- INTERACTION:
CC O95155-1; P62837: UBE2D2; NbExp=2; IntAct=EBI-15869194, EBI-347677;
CC O95155-1; P61077-1: UBE2D3; NbExp=3; IntAct=EBI-15869194, EBI-15567256;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17369820}. Nucleus
CC {ECO:0000250|UniProtKB:Q9ES00}.
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 Name=4; Synonyms=UFD2a-7/7a, UFD2A-III;
CC IsoId=O95155-4; Sequence=VSP_053372;
CC -!- TISSUE SPECIFICITY: Expressed in differentiated myotubes (at protein
CC level) (PubMed:17369820). Highest expression in ovary, testis, heart
CC and skeletal muscle (PubMed:11802788). Expression is low in colon,
CC thymus and peripheral blood leukocytes (PubMed:11802788). Almost
CC undetectable in lung and spleen (PubMed:11802788).
CC {ECO:0000269|PubMed:11802788, ECO:0000269|PubMed:17369820}.
CC -!- DOMAIN: The U-box domain is required for the ubiquitin protein ligase
CC activity. {ECO:0000250|UniProtKB:Q9ES00}.
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. {ECO:0000269|PubMed:11802788}.
CC -!- MISCELLANEOUS: [Isoform 4]: Expressed exclusively in mature striated
CC muscle cells. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the ubiquitin conjugation factor E4 family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA31659.3; Type=Erroneous initiation; Evidence={ECO:0000305};
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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; AL096841; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL590639; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC093696; AAH93696.1; -; mRNA.
DR EMBL; AF091093; AAC72962.1; ALT_SEQ; mRNA.
DR CCDS; CCDS110.1; -. [O95155-2]
DR CCDS; CCDS41245.1; -. [O95155-1]
DR PIR; T00358; T00358.
DR RefSeq; NP_001099032.1; NM_001105562.2. [O95155-1]
DR RefSeq; NP_006039.2; NM_006048.4. [O95155-2]
DR RefSeq; XP_005263479.1; XM_005263422.1. [O95155-4]
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 PDB; 5O75; X-ray; 1.48 A; A=1226-1302.
DR PDBsum; 2KRE; -.
DR PDBsum; 3L1X; -.
DR PDBsum; 3L1Z; -.
DR PDBsum; 5O75; -.
DR AlphaFoldDB; O95155; -.
DR SMR; O95155; -.
DR BioGRID; 115566; 110.
DR DIP; DIP-40309N; -.
DR IntAct; O95155; 15.
DR MINT; O95155; -.
DR STRING; 9606.ENSP00000343001; -.
DR GlyGen; O95155; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O95155; -.
DR PhosphoSitePlus; O95155; -.
DR BioMuta; UBE4B; -.
DR EPD; O95155; -.
DR jPOST; O95155; -.
DR MassIVE; O95155; -.
DR MaxQB; O95155; -.
DR PaxDb; O95155; -.
DR PeptideAtlas; O95155; -.
DR PRIDE; O95155; -.
DR ProteomicsDB; 50670; -. [O95155-1]
DR ProteomicsDB; 50671; -. [O95155-2]
DR ProteomicsDB; 50672; -. [O95155-3]
DR Antibodypedia; 13520; 186 antibodies from 31 providers.
DR DNASU; 10277; -.
DR Ensembl; ENST00000253251.12; ENSP00000253251.8; ENSG00000130939.20. [O95155-2]
DR Ensembl; ENST00000343090.11; ENSP00000343001.6; ENSG00000130939.20. [O95155-1]
DR Ensembl; ENST00000672724.1; ENSP00000500453.1; ENSG00000130939.20. [O95155-4]
DR GeneID; 10277; -.
DR KEGG; hsa:10277; -.
DR MANE-Select; ENST00000343090.11; ENSP00000343001.6; NM_001105562.3; NP_001099032.1.
DR UCSC; uc001aqr.5; human. [O95155-1]
DR CTD; 10277; -.
DR DisGeNET; 10277; -.
DR GeneCards; UBE4B; -.
DR HGNC; HGNC:12500; UBE4B.
DR HPA; ENSG00000130939; Low tissue specificity.
DR MIM; 613565; gene.
DR neXtProt; NX_O95155; -.
DR OpenTargets; ENSG00000130939; -.
DR Orphanet; 1606; 1p36 deletion syndrome.
DR PharmGKB; PA37148; -.
DR VEuPathDB; HostDB:ENSG00000130939; -.
DR eggNOG; KOG2042; Eukaryota.
DR GeneTree; ENSGT00390000009300; -.
DR HOGENOM; CLU_003224_2_0_1; -.
DR InParanoid; O95155; -.
DR OMA; LRWELHS; -.
DR OrthoDB; 194967at2759; -.
DR PhylomeDB; O95155; -.
DR TreeFam; TF300802; -.
DR BRENDA; 2.3.2.27; 2681.
DR BRENDA; 2.3.2.B12; 2681.
DR PathwayCommons; O95155; -.
DR SignaLink; O95155; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 10277; 95 hits in 1125 CRISPR screens.
DR ChiTaRS; UBE4B; human.
DR EvolutionaryTrace; O95155; -.
DR GeneWiki; UBE4B; -.
DR GenomeRNAi; 10277; -.
DR Pharos; O95155; Tbio.
DR PRO; PR:O95155; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O95155; protein.
DR Bgee; ENSG00000130939; Expressed in buccal mucosa cell and 210 other tissues.
DR ExpressionAtlas; O95155; baseline and differential.
DR Genevisible; O95155; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
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; IBA:GO_Central.
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:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0009411; P:response to UV; IDA:UniProtKB.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IBA:GO_Central.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; TAS:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR019474; Ub_conjug_fac_E4_core.
DR InterPro; IPR045132; UBE4.
DR InterPro; IPR003613; Ubox_domain.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR13931; PTHR13931; 1.
DR Pfam; PF04564; U-box; 1.
DR Pfam; PF10408; Ufd2P_core; 1.
DR SMART; SM00504; Ubox; 1.
DR PROSITE; PS51698; U_BOX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; Nucleus;
KW Phosphoprotein; Reference proteome; Transferase; Ubl conjugation pathway.
FT CHAIN 1..1302
FT /note="Ubiquitin conjugation factor E4 B"
FT /id="PRO_0000194993"
FT DOMAIN 1227..1300
FT /note="U-box"
FT REGION 1..155
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 299..406
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1057..1077
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..15
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 31..45
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..123
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 129..151
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 299..331
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 338..373
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 386..406
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 109..110
FT /note="Cleavage; by caspase-3 and caspase-7"
FT SITE 123..124
FT /note="Cleavage; by caspase-6 and granzyme B"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 23
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 31
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"
FT MOD_RES 84
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 88
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:24275569"
FT MOD_RES 90
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 101
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 103
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 105
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 124
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 238
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 383
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 803
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 969
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ES00"
FT MOD_RES 1265
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..116
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_007101"
FT VAR_SEQ 270..398
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:10980605,
FT ECO:0000303|PubMed:11802788, ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9734811"
FT /id="VSP_007102"
FT VAR_SEQ 398
FT /note="P -> PSMYDNPFSFLFLALSGDSSDEEDEEEDDDDGDGDDEGGGGGDDFSC
FT VQFGS (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:22174917"
FT /id="VSP_053372"
FT VAR_SEQ 1234
FT /note="D -> GKWTH (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_007103"
FT VARIANT 605
FT /note="V -> I (in dbSNP:rs17034499)"
FT /id="VAR_052437"
FT MUTAGEN 109
FT /note="D->A: Abolishes cleavage by caspase-3 and caspase-
FT 7."
FT /evidence="ECO:0000269|PubMed:11802788"
FT MUTAGEN 121
FT /note="D->A: Abolishes cleavage by caspase-6. No effect on
FT cleavage by granzyme B."
FT /evidence="ECO:0000269|PubMed:11802788"
FT MUTAGEN 123
FT /note="D->A: Abolishes cleavage by caspase-6 and granzyme
FT B."
FT /evidence="ECO:0000269|PubMed:11802788"
FT HELIX 1230..1232
FT /evidence="ECO:0007829|PDB:5O75"
FT TURN 1235..1237
FT /evidence="ECO:0007829|PDB:3L1X"
FT STRAND 1242..1246
FT /evidence="ECO:0007829|PDB:5O75"
FT TURN 1248..1250
FT /evidence="ECO:0007829|PDB:2KRE"
FT STRAND 1252..1254
FT /evidence="ECO:0007829|PDB:5O75"
FT HELIX 1255..1264
FT /evidence="ECO:0007829|PDB:5O75"
FT TURN 1269..1271
FT /evidence="ECO:0007829|PDB:5O75"
FT HELIX 1277..1279
FT /evidence="ECO:0007829|PDB:5O75"
FT HELIX 1284..1294
FT /evidence="ECO:0007829|PDB:5O75"
FT TURN 1296..1298
FT /evidence="ECO:0007829|PDB:2KRE"
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
