Full text data of UBE3B
UBE3B
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Ubiquitin-protein ligase E3B; 6.3.2.-
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Ubiquitin-protein ligase E3B; 6.3.2.-
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00000552
IPI00000552 UBE3B variant 1 UBE3B variant 1 membrane n/a n/a n/a n/a n/a n/a n/a n/a 5 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a nuclear n/a found at its expected molecular weight found at molecular weight
IPI00000552 UBE3B variant 1 UBE3B variant 1 membrane n/a n/a n/a n/a n/a n/a n/a n/a 5 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a nuclear n/a found at its expected molecular weight found at molecular weight
UniProt
Q7Z3V4
ID UBE3B_HUMAN Reviewed; 1068 AA.
AC Q7Z3V4; A5D8Z3; Q05BX9; Q659F7; Q7Z7Q1; Q9BXZ4;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
read moreDT 18-MAY-2010, sequence version 3.
DT 22-JAN-2014, entry version 87.
DE RecName: Full=Ubiquitin-protein ligase E3B;
DE EC=6.3.2.-;
GN Name=UBE3B;
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] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RX PubMed=12837265; DOI=10.1016/S0888-7543(03)00111-3;
RA Gong T.-W.L., Huang L., Warner S.J., Lomax M.I.;
RT "Characterization of the human UBE3B gene: structure, expression,
RT evolution, and alternative splicing.";
RL Genomics 82:143-152(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP GLN-346.
RC TISSUE=Endometrial adenocarcinoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT
RP GLN-346.
RC TISSUE=Brain, Lung, Prostate, and Skin;
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-419, 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 [6]
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).
RN [7]
RP VARIANT BPIDS PRO-727.
RX PubMed=23200864; DOI=10.1016/j.ajhg.2012.10.011;
RA Basel-Vanagaite L., Dallapiccola B., Ramirez-Solis R., Segref A.,
RA Thiele H., Edwards A., Arends M.J., Miro X., White J.K., Desir J.,
RA Abramowicz M., Dentici M.L., Lepri F., Hofmann K., Har-Zahav A.,
RA Ryder E., Karp N.A., Estabel J., Gerdin A.K., Podrini C., Ingham N.J.,
RA Altmueller J., Nuernberg G., Frommolt P., Abdelhak S.,
RA Pasmanik-Chor M., Konen O., Kelley R.I., Shohat M., Nuernberg P.,
RA Flint J., Steel K.P., Hoppe T., Kubisch C., Adams D.J., Borck G.;
RT "Deficiency for the ubiquitin ligase UBE3B in a blepharophimosis-
RT ptosis-intellectual-disability syndrome.";
RL Am. J. Hum. Genet. 91:998-1010(2012).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from
CC an E2 ubiquitin-conjugating enzyme in the form of a thioester and
CC then directly transfers the ubiquitin to targeted substrates (By
CC similarity).
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=UBE3B_v1;
CC IsoId=Q7Z3V4-1; Sequence=Displayed;
CC Note=Major isoform;
CC Name=2; Synonyms=UBE3B_v2;
CC IsoId=Q7Z3V4-2; Sequence=VSP_024087, VSP_024088;
CC Name=3;
CC IsoId=Q7Z3V4-3; Sequence=VSP_024085, VSP_024086;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- DISEASE: Blepharophimosis-ptosis-intellectual disability syndrome
CC (BPIDS) [MIM:615057]: A disorder characterized by
CC blepharophimosis, ptosis, mild upslanting of the palpebral
CC fissures, epicanthus, ectodermal anomalies, developmental delay,
CC and severe intellectual disability with absent speech.
CC Proportionate growth retardation with a small head
CC circumference/microcephaly, congenital malformations, muscular
CC hypotonia, anomalies on brain imaging with hypoplasia of the
CC corpus callosum, and low cholesterol levels are variably present.
CC Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Contains 1 HECT (E6AP-type E3 ubiquitin-protein
CC ligase) domain.
CC -!- SIMILARITY: Contains 1 IQ domain.
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DR EMBL; AF251046; AAK28419.2; -; mRNA.
DR EMBL; AL096740; CAH56410.1; -; mRNA.
DR EMBL; BX537403; CAD97645.1; -; mRNA.
DR EMBL; AC007570; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC032301; AAH32301.1; -; mRNA.
DR EMBL; BC051266; AAH51266.1; -; mRNA.
DR EMBL; BC068221; AAH68221.1; -; mRNA.
DR EMBL; BC108705; AAI08706.1; -; mRNA.
DR EMBL; BC141880; AAI41881.1; -; mRNA.
DR RefSeq; NP_001257378.1; NM_001270449.1.
DR RefSeq; NP_001257379.1; NM_001270450.1.
DR RefSeq; NP_001257380.1; NM_001270451.1.
DR RefSeq; NP_569733.2; NM_130466.3.
DR RefSeq; NP_904324.1; NM_183415.2.
DR RefSeq; XP_005254044.1; XM_005253987.1.
DR UniGene; Hs.374067; -.
DR ProteinModelPortal; Q7Z3V4; -.
DR SMR; Q7Z3V4; 683-1059.
DR IntAct; Q7Z3V4; 1.
DR STRING; 9606.ENSP00000340596; -.
DR PhosphoSite; Q7Z3V4; -.
DR DMDM; 296453010; -.
DR PaxDb; Q7Z3V4; -.
DR PRIDE; Q7Z3V4; -.
DR DNASU; 89910; -.
DR Ensembl; ENST00000280774; ENSP00000280774; ENSG00000151148.
DR Ensembl; ENST00000340074; ENSP00000342614; ENSG00000151148.
DR Ensembl; ENST00000342494; ENSP00000340596; ENSG00000151148.
DR Ensembl; ENST00000434735; ENSP00000391529; ENSG00000151148.
DR Ensembl; ENST00000449510; ENSP00000395802; ENSG00000151148.
DR Ensembl; ENST00000536398; ENSP00000440585; ENSG00000151148.
DR Ensembl; ENST00000540230; ENSP00000443565; ENSG00000151148.
DR GeneID; 89910; -.
DR KEGG; hsa:89910; -.
DR UCSC; uc001top.4; human.
DR CTD; 89910; -.
DR GeneCards; GC12P109915; -.
DR H-InvDB; HIX0020836; -.
DR H-InvDB; HIX0036751; -.
DR H-InvDB; HIX0129665; -.
DR HGNC; HGNC:13478; UBE3B.
DR HPA; HPA041012; -.
DR MIM; 608047; gene.
DR MIM; 615057; phenotype.
DR neXtProt; NX_Q7Z3V4; -.
DR Orphanet; 329255; Blepharophimosis-intellectual deficit syndrome due to UBE3B deficiency.
DR Orphanet; 2707; Oculocerebrofacial syndrome, Kaufman type.
DR PharmGKB; PA134872189; -.
DR eggNOG; COG5021; -.
DR HOGENOM; HOG000232154; -.
DR HOVERGEN; HBG108644; -.
DR InParanoid; Q7Z3V4; -.
DR KO; K10588; -.
DR OMA; FQSVHGW; -.
DR OrthoDB; EOG7R56RN; -.
DR PhylomeDB; Q7Z3V4; -.
DR Reactome; REACT_6900; Immune System.
DR UniPathway; UPA00143; -.
DR GenomeRNAi; 89910; -.
DR NextBio; 76429; -.
DR PRO; PR:Q7Z3V4; -.
DR ArrayExpress; Q7Z3V4; -.
DR Bgee; Q7Z3V4; -.
DR CleanEx; HS_UBE3B; -.
DR Genevestigator; Q7Z3V4; -.
DR GO; GO:0005737; C:cytoplasm; IBA:RefGenome.
DR GO; GO:0005634; C:nucleus; IBA:RefGenome.
DR GO; GO:0004842; F:ubiquitin-protein ligase activity; IBA:RefGenome.
DR GO; GO:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IBA:RefGenome.
DR InterPro; IPR000569; HECT.
DR InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR Pfam; PF00632; HECT; 1.
DR Pfam; PF00612; IQ; 1.
DR SMART; SM00119; HECTc; 1.
DR SMART; SM00015; IQ; 1.
DR SUPFAM; SSF56204; SSF56204; 1.
DR PROSITE; PS50237; HECT; 1.
DR PROSITE; PS50096; IQ; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Complete proteome;
KW Disease mutation; Ligase; Mental retardation; Phosphoprotein;
KW Polymorphism; Reference proteome; Ubl conjugation pathway.
FT CHAIN 1 1068 Ubiquitin-protein ligase E3B.
FT /FTId=PRO_0000281882.
FT DOMAIN 29 58 IQ.
FT DOMAIN 702 1068 HECT.
FT ACT_SITE 1036 1036 Glycyl thioester intermediate (By
FT similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 419 419 Phosphoserine.
FT VAR_SEQ 211 244 ILLTRGLARPRPCLSKGTLTAAFSLALRPVIAAQ -> CCD
FT GLFPDLVSYAPHNNPVRWSVGRSWYDWQLSR (in
FT isoform 3).
FT /FTId=VSP_024085.
FT VAR_SEQ 245 1068 Missing (in isoform 3).
FT /FTId=VSP_024086.
FT VAR_SEQ 693 708 DGYEQLRQLSQHAMKG -> SLFECPWPLVINAESC (in
FT isoform 2).
FT /FTId=VSP_024087.
FT VAR_SEQ 709 1068 Missing (in isoform 2).
FT /FTId=VSP_024088.
FT VARIANT 346 346 R -> Q (in dbSNP:rs7298565).
FT /FTId=VAR_031302.
FT VARIANT 727 727 Q -> P (in BPIDS).
FT /FTId=VAR_069712.
FT CONFLICT 151 151 E -> V (in Ref. 2; CAD97645).
FT CONFLICT 907 907 I -> V (in Ref. 2; CAD97645).
FT CONFLICT 942 942 Y -> H (in Ref. 2; CAD97645).
FT CONFLICT 1018 1018 F -> S (in Ref. 2; CAD97645).
SQ SEQUENCE 1068 AA; 123098 MW; A1740A3DDC5E1A4D CRC64;
MFTLSQTSRA WFIDRARQAR EERLVQKERE RAAVVIQAHV RSFLCRSRLQ RDIRREIDDF
FKADDPESTK RSALCIFKIA RKLLFLFRIK EDNERFEKLC RSILSSMDAE NEPKVWYVSL
ACSKDLTLLW IQQIKNILWY CCDFLKQLKP EILQDSRLIT LYLTMLVTFT DTSTWKILRG
KGESLRPAMN HICANIMGHL NQHGFYSVLQ ILLTRGLARP RPCLSKGTLT AAFSLALRPV
IAAQFSDNLI RPFLIHIMSV PALVTHLSTV TPERLTVLES HDMLRKFIIF LRDQDRCRDV
CESLEGCHTL CLMGNLLHLG SLSPRVLEEE TDGFVSLLTQ TLCYCRKYVS QKKSNLTHWH
PVLGWFSQSV DYGLNESMHL ITKQLQFLWG VPLIRIFFCD ILSKKLLESQ EPAHAQPASP
QNVLPVKSLL KRAFQKSASV RNILRPVGGK RVDSAEVQKV CNICVLYQTS LTTLTQIRLQ
ILTGLTYLDD LLPKLWAFIC ELGPHGGLKL FLECLNNDTE ESKQLLAMLM LFCDCSRHLI
TILDDIEVYE EQISFKLEEL VTISSFLNSF VFKMIWDGIV ENAKGETLEL FQSVHGWLMV
LYERDCRRRF TPEDHWLRKD LKPSVLFQEL DRDRKRAQLI LQYIPHVIPH KNRVLLFRTM
VTKEKEKLGL VETSSASPHV THITIRRSRM LEDGYEQLRQ LSQHAMKGVI RVKFVNDLGV
DEAGIDQDGV FKEFLEEIIK RVFDPALNLF KTTSGDERLY PSPTSYIHEN YLQLFEFVGK
MLGKAVYEGI VVDVPFASFF LSQLLGHHHS VFYSSVDELP SLDSEFYKNL TSIKRYDGDI
TDLGLTLSYD EDVMGQLVCH ELIPGGKTIP VTNENKISYI HLMAHFRMHT QIKNQTAALI
SGFRSIIKPE WIRMFSTPEL QRLISGDNAE IDLEDLKKHT VYYGGFHGSH RVIIWLWDIL
ASDFTPDERA MFLKFVTSCS RPPLLGFAYL KPPFSIRCVE VSDDQDTGDT LGSVLRGFFT
IRKREPGGRL PTSSTCFNLL KLPNYSKKSV LREKLRYAIS MNTGFELS
//
ID UBE3B_HUMAN Reviewed; 1068 AA.
AC Q7Z3V4; A5D8Z3; Q05BX9; Q659F7; Q7Z7Q1; Q9BXZ4;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
read moreDT 18-MAY-2010, sequence version 3.
DT 22-JAN-2014, entry version 87.
DE RecName: Full=Ubiquitin-protein ligase E3B;
DE EC=6.3.2.-;
GN Name=UBE3B;
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] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RX PubMed=12837265; DOI=10.1016/S0888-7543(03)00111-3;
RA Gong T.-W.L., Huang L., Warner S.J., Lomax M.I.;
RT "Characterization of the human UBE3B gene: structure, expression,
RT evolution, and alternative splicing.";
RL Genomics 82:143-152(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP GLN-346.
RC TISSUE=Endometrial adenocarcinoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT
RP GLN-346.
RC TISSUE=Brain, Lung, Prostate, and Skin;
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-419, 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 [6]
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).
RN [7]
RP VARIANT BPIDS PRO-727.
RX PubMed=23200864; DOI=10.1016/j.ajhg.2012.10.011;
RA Basel-Vanagaite L., Dallapiccola B., Ramirez-Solis R., Segref A.,
RA Thiele H., Edwards A., Arends M.J., Miro X., White J.K., Desir J.,
RA Abramowicz M., Dentici M.L., Lepri F., Hofmann K., Har-Zahav A.,
RA Ryder E., Karp N.A., Estabel J., Gerdin A.K., Podrini C., Ingham N.J.,
RA Altmueller J., Nuernberg G., Frommolt P., Abdelhak S.,
RA Pasmanik-Chor M., Konen O., Kelley R.I., Shohat M., Nuernberg P.,
RA Flint J., Steel K.P., Hoppe T., Kubisch C., Adams D.J., Borck G.;
RT "Deficiency for the ubiquitin ligase UBE3B in a blepharophimosis-
RT ptosis-intellectual-disability syndrome.";
RL Am. J. Hum. Genet. 91:998-1010(2012).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from
CC an E2 ubiquitin-conjugating enzyme in the form of a thioester and
CC then directly transfers the ubiquitin to targeted substrates (By
CC similarity).
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=UBE3B_v1;
CC IsoId=Q7Z3V4-1; Sequence=Displayed;
CC Note=Major isoform;
CC Name=2; Synonyms=UBE3B_v2;
CC IsoId=Q7Z3V4-2; Sequence=VSP_024087, VSP_024088;
CC Name=3;
CC IsoId=Q7Z3V4-3; Sequence=VSP_024085, VSP_024086;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- DISEASE: Blepharophimosis-ptosis-intellectual disability syndrome
CC (BPIDS) [MIM:615057]: A disorder characterized by
CC blepharophimosis, ptosis, mild upslanting of the palpebral
CC fissures, epicanthus, ectodermal anomalies, developmental delay,
CC and severe intellectual disability with absent speech.
CC Proportionate growth retardation with a small head
CC circumference/microcephaly, congenital malformations, muscular
CC hypotonia, anomalies on brain imaging with hypoplasia of the
CC corpus callosum, and low cholesterol levels are variably present.
CC Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Contains 1 HECT (E6AP-type E3 ubiquitin-protein
CC ligase) domain.
CC -!- SIMILARITY: Contains 1 IQ domain.
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; AF251046; AAK28419.2; -; mRNA.
DR EMBL; AL096740; CAH56410.1; -; mRNA.
DR EMBL; BX537403; CAD97645.1; -; mRNA.
DR EMBL; AC007570; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC032301; AAH32301.1; -; mRNA.
DR EMBL; BC051266; AAH51266.1; -; mRNA.
DR EMBL; BC068221; AAH68221.1; -; mRNA.
DR EMBL; BC108705; AAI08706.1; -; mRNA.
DR EMBL; BC141880; AAI41881.1; -; mRNA.
DR RefSeq; NP_001257378.1; NM_001270449.1.
DR RefSeq; NP_001257379.1; NM_001270450.1.
DR RefSeq; NP_001257380.1; NM_001270451.1.
DR RefSeq; NP_569733.2; NM_130466.3.
DR RefSeq; NP_904324.1; NM_183415.2.
DR RefSeq; XP_005254044.1; XM_005253987.1.
DR UniGene; Hs.374067; -.
DR ProteinModelPortal; Q7Z3V4; -.
DR SMR; Q7Z3V4; 683-1059.
DR IntAct; Q7Z3V4; 1.
DR STRING; 9606.ENSP00000340596; -.
DR PhosphoSite; Q7Z3V4; -.
DR DMDM; 296453010; -.
DR PaxDb; Q7Z3V4; -.
DR PRIDE; Q7Z3V4; -.
DR DNASU; 89910; -.
DR Ensembl; ENST00000280774; ENSP00000280774; ENSG00000151148.
DR Ensembl; ENST00000340074; ENSP00000342614; ENSG00000151148.
DR Ensembl; ENST00000342494; ENSP00000340596; ENSG00000151148.
DR Ensembl; ENST00000434735; ENSP00000391529; ENSG00000151148.
DR Ensembl; ENST00000449510; ENSP00000395802; ENSG00000151148.
DR Ensembl; ENST00000536398; ENSP00000440585; ENSG00000151148.
DR Ensembl; ENST00000540230; ENSP00000443565; ENSG00000151148.
DR GeneID; 89910; -.
DR KEGG; hsa:89910; -.
DR UCSC; uc001top.4; human.
DR CTD; 89910; -.
DR GeneCards; GC12P109915; -.
DR H-InvDB; HIX0020836; -.
DR H-InvDB; HIX0036751; -.
DR H-InvDB; HIX0129665; -.
DR HGNC; HGNC:13478; UBE3B.
DR HPA; HPA041012; -.
DR MIM; 608047; gene.
DR MIM; 615057; phenotype.
DR neXtProt; NX_Q7Z3V4; -.
DR Orphanet; 329255; Blepharophimosis-intellectual deficit syndrome due to UBE3B deficiency.
DR Orphanet; 2707; Oculocerebrofacial syndrome, Kaufman type.
DR PharmGKB; PA134872189; -.
DR eggNOG; COG5021; -.
DR HOGENOM; HOG000232154; -.
DR HOVERGEN; HBG108644; -.
DR InParanoid; Q7Z3V4; -.
DR KO; K10588; -.
DR OMA; FQSVHGW; -.
DR OrthoDB; EOG7R56RN; -.
DR PhylomeDB; Q7Z3V4; -.
DR Reactome; REACT_6900; Immune System.
DR UniPathway; UPA00143; -.
DR GenomeRNAi; 89910; -.
DR NextBio; 76429; -.
DR PRO; PR:Q7Z3V4; -.
DR ArrayExpress; Q7Z3V4; -.
DR Bgee; Q7Z3V4; -.
DR CleanEx; HS_UBE3B; -.
DR Genevestigator; Q7Z3V4; -.
DR GO; GO:0005737; C:cytoplasm; IBA:RefGenome.
DR GO; GO:0005634; C:nucleus; IBA:RefGenome.
DR GO; GO:0004842; F:ubiquitin-protein ligase activity; IBA:RefGenome.
DR GO; GO:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IBA:RefGenome.
DR InterPro; IPR000569; HECT.
DR InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR Pfam; PF00632; HECT; 1.
DR Pfam; PF00612; IQ; 1.
DR SMART; SM00119; HECTc; 1.
DR SMART; SM00015; IQ; 1.
DR SUPFAM; SSF56204; SSF56204; 1.
DR PROSITE; PS50237; HECT; 1.
DR PROSITE; PS50096; IQ; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Complete proteome;
KW Disease mutation; Ligase; Mental retardation; Phosphoprotein;
KW Polymorphism; Reference proteome; Ubl conjugation pathway.
FT CHAIN 1 1068 Ubiquitin-protein ligase E3B.
FT /FTId=PRO_0000281882.
FT DOMAIN 29 58 IQ.
FT DOMAIN 702 1068 HECT.
FT ACT_SITE 1036 1036 Glycyl thioester intermediate (By
FT similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 419 419 Phosphoserine.
FT VAR_SEQ 211 244 ILLTRGLARPRPCLSKGTLTAAFSLALRPVIAAQ -> CCD
FT GLFPDLVSYAPHNNPVRWSVGRSWYDWQLSR (in
FT isoform 3).
FT /FTId=VSP_024085.
FT VAR_SEQ 245 1068 Missing (in isoform 3).
FT /FTId=VSP_024086.
FT VAR_SEQ 693 708 DGYEQLRQLSQHAMKG -> SLFECPWPLVINAESC (in
FT isoform 2).
FT /FTId=VSP_024087.
FT VAR_SEQ 709 1068 Missing (in isoform 2).
FT /FTId=VSP_024088.
FT VARIANT 346 346 R -> Q (in dbSNP:rs7298565).
FT /FTId=VAR_031302.
FT VARIANT 727 727 Q -> P (in BPIDS).
FT /FTId=VAR_069712.
FT CONFLICT 151 151 E -> V (in Ref. 2; CAD97645).
FT CONFLICT 907 907 I -> V (in Ref. 2; CAD97645).
FT CONFLICT 942 942 Y -> H (in Ref. 2; CAD97645).
FT CONFLICT 1018 1018 F -> S (in Ref. 2; CAD97645).
SQ SEQUENCE 1068 AA; 123098 MW; A1740A3DDC5E1A4D CRC64;
MFTLSQTSRA WFIDRARQAR EERLVQKERE RAAVVIQAHV RSFLCRSRLQ RDIRREIDDF
FKADDPESTK RSALCIFKIA RKLLFLFRIK EDNERFEKLC RSILSSMDAE NEPKVWYVSL
ACSKDLTLLW IQQIKNILWY CCDFLKQLKP EILQDSRLIT LYLTMLVTFT DTSTWKILRG
KGESLRPAMN HICANIMGHL NQHGFYSVLQ ILLTRGLARP RPCLSKGTLT AAFSLALRPV
IAAQFSDNLI RPFLIHIMSV PALVTHLSTV TPERLTVLES HDMLRKFIIF LRDQDRCRDV
CESLEGCHTL CLMGNLLHLG SLSPRVLEEE TDGFVSLLTQ TLCYCRKYVS QKKSNLTHWH
PVLGWFSQSV DYGLNESMHL ITKQLQFLWG VPLIRIFFCD ILSKKLLESQ EPAHAQPASP
QNVLPVKSLL KRAFQKSASV RNILRPVGGK RVDSAEVQKV CNICVLYQTS LTTLTQIRLQ
ILTGLTYLDD LLPKLWAFIC ELGPHGGLKL FLECLNNDTE ESKQLLAMLM LFCDCSRHLI
TILDDIEVYE EQISFKLEEL VTISSFLNSF VFKMIWDGIV ENAKGETLEL FQSVHGWLMV
LYERDCRRRF TPEDHWLRKD LKPSVLFQEL DRDRKRAQLI LQYIPHVIPH KNRVLLFRTM
VTKEKEKLGL VETSSASPHV THITIRRSRM LEDGYEQLRQ LSQHAMKGVI RVKFVNDLGV
DEAGIDQDGV FKEFLEEIIK RVFDPALNLF KTTSGDERLY PSPTSYIHEN YLQLFEFVGK
MLGKAVYEGI VVDVPFASFF LSQLLGHHHS VFYSSVDELP SLDSEFYKNL TSIKRYDGDI
TDLGLTLSYD EDVMGQLVCH ELIPGGKTIP VTNENKISYI HLMAHFRMHT QIKNQTAALI
SGFRSIIKPE WIRMFSTPEL QRLISGDNAE IDLEDLKKHT VYYGGFHGSH RVIIWLWDIL
ASDFTPDERA MFLKFVTSCS RPPLLGFAYL KPPFSIRCVE VSDDQDTGDT LGSVLRGFFT
IRKREPGGRL PTSSTCFNLL KLPNYSKKSV LREKLRYAIS MNTGFELS
//
MIM
608047
*RECORD*
*FIELD* NO
608047
*FIELD* TI
*608047 UBIQUITIN-PROTEIN LIGASE E3B; UBE3B
*FIELD* TX
DESCRIPTION
Ubiquitination requires the sequential action of 3 enzymes: an
read moreactivating enzyme (E1), a conjugating enzyme (E2), and a ligase (E3).
UBE3B belongs to a class of monomeric ubiquitin ligases that contain a
350-amino acid HECT domain within their active site (Gong et al., 2003).
CLONING
Using mouse Ube3b as probe, Gong et al. (2003) cloned UBE3B from a human
cDNA library. The deduced 1,068-amino acid protein has a calculated
molecular mass of about 123 kD, and the UBE3B transcript contains a
1.9-kb 3-prime untranslated region. Both mouse and human UBE3B contain
an N-terminal IQ domain and a C-terminal HECT domain. Gong et al. (2003)
determined that the transcript encoding the 1,068-amino acid protein
lacks exon 20. A splice variant that includes exon 20 introduces a stop
codon and encodes a deduced 708-amino acid protein with a calculated
molecular mass of about 82 kD. This variant lacks the HECT domain. Gong
et al. (2003) also detected splice variants that introduce changes to
the 5-prime end of UBE3B. Mouse and human UBE3B share 92% amino acid
identity overall and 99% identity in the HECT domain. Homologous
sequences were identified in chick (97% amino acid identity) and in
lower organisms, including plant. Northern blot analysis detected a
transcript of about 5 kb in all mouse tissues examined. Highest levels
were detected in brain, heart, and skeletal muscle, and these tissues
also showed faint bands of 7.5 and 8.8 kb. RT-PCR detected a transcript
lacking exon 20 in all human tissues examined, and a transcript
containing exon 20 was detected in most tissues. RT-PCR of mouse and
chick tissues detected only transcripts corresponding to the human
transcript lacking exon 20.
By in situ hybridization in embryonic and postnatal mouse tissues,
Basel-Vanagaite et al. (2012) found predominant expression of Ube3b in
distinct anatomical structures of the developing central nervous system
and in craniofacial structures.
GENE STRUCTURE
Gong et al. (2003) determined that the mouse and human UBE3B genes
contain 29 exons.
MAPPING
By genomic sequence analysis, Gong et al. (2003) mapped the UBE3B gene
to chromosome 12q21.1-q23. They mapped the mouse Ube3b gene to a region
of chromosome 5 that shows homology of synteny to human chromosome
12q21.1-q23.
GENE FUNCTION
Basel-Vanagaite et al. (2012) demonstrated that the probable C. elegans
ortholog of UBE3B, oxi-1, functions in the ubiquitin/proteasome system
in vivo and may be required under oxidative stress conditions.
MOLECULAR GENETICS
Basel-Vanagaite et al. (2012) performed exome sequencing of 2 unrelated
individuals with blepharophimosis-ptosis intellectual disability
syndrome (BPIDS; 615057) and identified the UBE3B gene as the only gene
with rare or unique biallelic damaging variants in both individuals.
Individual 1 had a homozygous splice site mutation (c.1741+2T-C;
608047.0001), which was present in heterozygous state in her unaffected
first-cousin parents. Individual 2 and her affected brother, who were
previously reported by Dentici et al. (2011), had a maternally inherited
deletion (c.2223_2224delAG; 608047.0002) and a paternally inherited
splice site mutation (c.545-2AG; 608047.0003). By sequencing the coding
exons of the UBE3B gene in a fourth affected individual, Basel-Vanagaite
et al. (2012) detected another homozygous mutation (E727P; 608047.0004),
which was present in heterozygous state in the patient's unaffected
first-cousin parents. None of the mutations were present in 100
ethnically matched control individuals or in the NHLBI Exome Sequencing
Project database.
ANIMAL MODEL
Basel-Vanagaite et al. (2012) confirmed by quantitative PCR that Ube3b
knockdown mice do not express detectable levels of Ube3b mRNA. Ube3b -/-
mice had severely reduced body weight, small body size, and reduced
brain section area with reduced size of the hippocampus and dentate
gyrus, reduced grip strength, reduced low-density lipoprotein levels and
a trend toward reduced total and HDL cholesterol levels, mild hearing
impairment, and acute inflammation, calcification, and dilated
lymphovascular channels of the cornea. Basel-Vanagaite et al. (2012)
suggested that Ube3b -/- mice are a model of the UBE3B-deficient BPID
syndrome in anomalies of body and brain size, weight, muscular strength,
and cholesterol levels.
*FIELD* AV
.0001
BLEPHAROPHIMOSIS-PTOSIS-INTELLECTUAL DISABILITY SYNDROME
UBE3B, IVS15DS, T-C, +2
In a girl with BPID syndrome (BPIDS; 615057) who was born to unaffected
first-cousin parents of Israeli-Arab origin, Basel-Vanagaite et al.
(2012) identified a homozygous variant (c.1741+2T-C) affecting the
consensus splice donor site of exon 16. The mutation led to skipping of
exon 16 and, to a lesser extent, skipping of exons 16 and 17 in RNA
derived from blood of the patient. The parents were heterozygous
carriers of the mutation, which was not found in 100 ethnically matched
controls or in the NHLBI Exome Sequencing Project database. The variant
introduces a premature termination codon and is thus expected to result
in nonsense-mediated mRNA decay and/or protein truncation.
.0002
BLEPHAROPHIMOSIS-PTOSIS-INTELLECTUAL DISABILITY SYNDROME
UBE3B, 2-BP DEL, 2223AG
In an Italian sister and brother with BPIDS (615057) reported by Dentici
et al. (2011), Basel-Vanagaite et al. (2012) identified compound
heterozygous mutations in the UBE3B gene: a maternally inherited 2-bp
deletion (c.2223_2224delAG; arg741serfs*3) and a paternally inherited
splice acceptor mutation (c.545-2A-G; 608047.0003). The splice site
mutation caused skipping of exon 8 and skipping of exons 8 and 9 in RNA
derived from the sister's blood. Both variants introduce premature
termination codons and are thus expected to result in nonsense-mediated
mRNA decay and/or protein truncation. The mutations were not found in
100 ethnically matched controls or in the NHLBI Exome Sequencing Project
database.
.0003
BLEPHAROPHIMOSIS-PTOSIS-INTELLECTUAL DISABILITY SYNDROME
UBE3B, IVS7AS, A-G, -2
See 608047.0002 and Basel-Vanagaite et al. (2012).
.0004
BLEPHAROPHIMOSIS-PTOSIS-INTELLECTUAL DISABILITY SYNDROME
UBE3B, GLN727PRO
By sequencing the coding exons of the UBE3B gene in a girl with BPID
syndrome (615057) who was born to unaffected first-cousin parents of
Tunisian origin, Basel-Vanagaite et al. (2012) identified a homozygous
c.2180A-C mutation that was predicted to lead to a glu727-to-pro (Q727P)
substitution at a highly conserved residue in the HECT domain.. Both
parents were heterozygous carriers of the mutation, which was not found
in 100 ethnically matched controls or in the NHLBI Exome Sequencing
Project database. The mutation was located within a 35-Mb region of
homozygosity in the proband as shown by genomewide SNP array genotyping,
consistent with a large region of homozygosity-by-descent.
*FIELD* RF
1. Basel-Vanagaite, L.; Dallapiccola, B.; Ramirez-Solis, R.; Segref,
A.; thiele, H.; Edwards, A.; Arends, M. J.; Miro, X.; White, J. K.;
Desir, J.; Abramowicz, M.; Dentici, M. L.; and 24 others: Deficiency
for the ubiquitin ligase UBE3B in a blepharophimosis-ptosis-intellectual-disability
syndrome. Am. J. Hum. Genet. 91: 998-1010, 2012.
2. Dentici, M. L.; Mingarelli, R.; Dallapiccola, B.: The difficult
nosology of blepharophimosis-mental retardation syndromes: report
on two siblings. Am. J. Med. Genet. 155A: 459-465, 2011.
3. Gong, T.-W. L.; Huang, L.; Warner, S. J.; Lomax, M. I.: Characterization
of the human UBE3B gene: structure, expression, evolution, and alternative
splicing. Genomics 82: 143-152, 2003.
*FIELD* CN
Nara Sobreira - updated: 05/03/2013
*FIELD* CD
Patricia A. Hartz: 8/18/2003
*FIELD* ED
carol: 05/03/2013
alopez: 5/6/2008
mgross: 8/18/2003
*RECORD*
*FIELD* NO
608047
*FIELD* TI
*608047 UBIQUITIN-PROTEIN LIGASE E3B; UBE3B
*FIELD* TX
DESCRIPTION
Ubiquitination requires the sequential action of 3 enzymes: an
read moreactivating enzyme (E1), a conjugating enzyme (E2), and a ligase (E3).
UBE3B belongs to a class of monomeric ubiquitin ligases that contain a
350-amino acid HECT domain within their active site (Gong et al., 2003).
CLONING
Using mouse Ube3b as probe, Gong et al. (2003) cloned UBE3B from a human
cDNA library. The deduced 1,068-amino acid protein has a calculated
molecular mass of about 123 kD, and the UBE3B transcript contains a
1.9-kb 3-prime untranslated region. Both mouse and human UBE3B contain
an N-terminal IQ domain and a C-terminal HECT domain. Gong et al. (2003)
determined that the transcript encoding the 1,068-amino acid protein
lacks exon 20. A splice variant that includes exon 20 introduces a stop
codon and encodes a deduced 708-amino acid protein with a calculated
molecular mass of about 82 kD. This variant lacks the HECT domain. Gong
et al. (2003) also detected splice variants that introduce changes to
the 5-prime end of UBE3B. Mouse and human UBE3B share 92% amino acid
identity overall and 99% identity in the HECT domain. Homologous
sequences were identified in chick (97% amino acid identity) and in
lower organisms, including plant. Northern blot analysis detected a
transcript of about 5 kb in all mouse tissues examined. Highest levels
were detected in brain, heart, and skeletal muscle, and these tissues
also showed faint bands of 7.5 and 8.8 kb. RT-PCR detected a transcript
lacking exon 20 in all human tissues examined, and a transcript
containing exon 20 was detected in most tissues. RT-PCR of mouse and
chick tissues detected only transcripts corresponding to the human
transcript lacking exon 20.
By in situ hybridization in embryonic and postnatal mouse tissues,
Basel-Vanagaite et al. (2012) found predominant expression of Ube3b in
distinct anatomical structures of the developing central nervous system
and in craniofacial structures.
GENE STRUCTURE
Gong et al. (2003) determined that the mouse and human UBE3B genes
contain 29 exons.
MAPPING
By genomic sequence analysis, Gong et al. (2003) mapped the UBE3B gene
to chromosome 12q21.1-q23. They mapped the mouse Ube3b gene to a region
of chromosome 5 that shows homology of synteny to human chromosome
12q21.1-q23.
GENE FUNCTION
Basel-Vanagaite et al. (2012) demonstrated that the probable C. elegans
ortholog of UBE3B, oxi-1, functions in the ubiquitin/proteasome system
in vivo and may be required under oxidative stress conditions.
MOLECULAR GENETICS
Basel-Vanagaite et al. (2012) performed exome sequencing of 2 unrelated
individuals with blepharophimosis-ptosis intellectual disability
syndrome (BPIDS; 615057) and identified the UBE3B gene as the only gene
with rare or unique biallelic damaging variants in both individuals.
Individual 1 had a homozygous splice site mutation (c.1741+2T-C;
608047.0001), which was present in heterozygous state in her unaffected
first-cousin parents. Individual 2 and her affected brother, who were
previously reported by Dentici et al. (2011), had a maternally inherited
deletion (c.2223_2224delAG; 608047.0002) and a paternally inherited
splice site mutation (c.545-2AG; 608047.0003). By sequencing the coding
exons of the UBE3B gene in a fourth affected individual, Basel-Vanagaite
et al. (2012) detected another homozygous mutation (E727P; 608047.0004),
which was present in heterozygous state in the patient's unaffected
first-cousin parents. None of the mutations were present in 100
ethnically matched control individuals or in the NHLBI Exome Sequencing
Project database.
ANIMAL MODEL
Basel-Vanagaite et al. (2012) confirmed by quantitative PCR that Ube3b
knockdown mice do not express detectable levels of Ube3b mRNA. Ube3b -/-
mice had severely reduced body weight, small body size, and reduced
brain section area with reduced size of the hippocampus and dentate
gyrus, reduced grip strength, reduced low-density lipoprotein levels and
a trend toward reduced total and HDL cholesterol levels, mild hearing
impairment, and acute inflammation, calcification, and dilated
lymphovascular channels of the cornea. Basel-Vanagaite et al. (2012)
suggested that Ube3b -/- mice are a model of the UBE3B-deficient BPID
syndrome in anomalies of body and brain size, weight, muscular strength,
and cholesterol levels.
*FIELD* AV
.0001
BLEPHAROPHIMOSIS-PTOSIS-INTELLECTUAL DISABILITY SYNDROME
UBE3B, IVS15DS, T-C, +2
In a girl with BPID syndrome (BPIDS; 615057) who was born to unaffected
first-cousin parents of Israeli-Arab origin, Basel-Vanagaite et al.
(2012) identified a homozygous variant (c.1741+2T-C) affecting the
consensus splice donor site of exon 16. The mutation led to skipping of
exon 16 and, to a lesser extent, skipping of exons 16 and 17 in RNA
derived from blood of the patient. The parents were heterozygous
carriers of the mutation, which was not found in 100 ethnically matched
controls or in the NHLBI Exome Sequencing Project database. The variant
introduces a premature termination codon and is thus expected to result
in nonsense-mediated mRNA decay and/or protein truncation.
.0002
BLEPHAROPHIMOSIS-PTOSIS-INTELLECTUAL DISABILITY SYNDROME
UBE3B, 2-BP DEL, 2223AG
In an Italian sister and brother with BPIDS (615057) reported by Dentici
et al. (2011), Basel-Vanagaite et al. (2012) identified compound
heterozygous mutations in the UBE3B gene: a maternally inherited 2-bp
deletion (c.2223_2224delAG; arg741serfs*3) and a paternally inherited
splice acceptor mutation (c.545-2A-G; 608047.0003). The splice site
mutation caused skipping of exon 8 and skipping of exons 8 and 9 in RNA
derived from the sister's blood. Both variants introduce premature
termination codons and are thus expected to result in nonsense-mediated
mRNA decay and/or protein truncation. The mutations were not found in
100 ethnically matched controls or in the NHLBI Exome Sequencing Project
database.
.0003
BLEPHAROPHIMOSIS-PTOSIS-INTELLECTUAL DISABILITY SYNDROME
UBE3B, IVS7AS, A-G, -2
See 608047.0002 and Basel-Vanagaite et al. (2012).
.0004
BLEPHAROPHIMOSIS-PTOSIS-INTELLECTUAL DISABILITY SYNDROME
UBE3B, GLN727PRO
By sequencing the coding exons of the UBE3B gene in a girl with BPID
syndrome (615057) who was born to unaffected first-cousin parents of
Tunisian origin, Basel-Vanagaite et al. (2012) identified a homozygous
c.2180A-C mutation that was predicted to lead to a glu727-to-pro (Q727P)
substitution at a highly conserved residue in the HECT domain.. Both
parents were heterozygous carriers of the mutation, which was not found
in 100 ethnically matched controls or in the NHLBI Exome Sequencing
Project database. The mutation was located within a 35-Mb region of
homozygosity in the proband as shown by genomewide SNP array genotyping,
consistent with a large region of homozygosity-by-descent.
*FIELD* RF
1. Basel-Vanagaite, L.; Dallapiccola, B.; Ramirez-Solis, R.; Segref,
A.; thiele, H.; Edwards, A.; Arends, M. J.; Miro, X.; White, J. K.;
Desir, J.; Abramowicz, M.; Dentici, M. L.; and 24 others: Deficiency
for the ubiquitin ligase UBE3B in a blepharophimosis-ptosis-intellectual-disability
syndrome. Am. J. Hum. Genet. 91: 998-1010, 2012.
2. Dentici, M. L.; Mingarelli, R.; Dallapiccola, B.: The difficult
nosology of blepharophimosis-mental retardation syndromes: report
on two siblings. Am. J. Med. Genet. 155A: 459-465, 2011.
3. Gong, T.-W. L.; Huang, L.; Warner, S. J.; Lomax, M. I.: Characterization
of the human UBE3B gene: structure, expression, evolution, and alternative
splicing. Genomics 82: 143-152, 2003.
*FIELD* CN
Nara Sobreira - updated: 05/03/2013
*FIELD* CD
Patricia A. Hartz: 8/18/2003
*FIELD* ED
carol: 05/03/2013
alopez: 5/6/2008
mgross: 8/18/2003
MIM
615057
*RECORD*
*FIELD* NO
615057
*FIELD* TI
#615057 BLEPHAROPHIMOSIS-PTOSIS-INTELLECTUAL DISABILITY SYNDROME; BPIDS
;;BPID SYNDROME;;
read moreBLEPHAROPHIMOSIS-PTOSIS-MENTAL RETARDATION SYNDROME
*FIELD* TX
A number sign (#) is used with this entry because the
blepharophimosis-ptosis-intellectual disability syndrome (BPIDS) is
caused by homozygous or compound heterozygous mutation in the UBE3B gene
(608047) on chromosome 12q23.
DESCRIPTION
BPIDS is characterized by blepharophimosis, ptosis, mild upslanting of
the palpebral fissures, epicanthus, ectodermal anomalies, developmental
delay, and severe intellectual disability with absent speech.
Proportionate growth retardation with a small head
circumference/microcephaly, congenital malformations, muscular
hypotonia, anomalies on brain imaging with hypoplasia of the corpus
callosum, and low cholesterol levels are variably present
(Basel-Vanagaite et al., 2012).
CLINICAL FEATURES
Dentici et al. (2011) described 2 Italian sibs, a 6-year-old girl and an
18-month-old boy, who presented with overlapping clinical findings.
Major characteristics included facial dysmorphisms with upward slanting
palpebral fissures, blepharophimosis, telecanthus, hypertelorism,
posteriorly rotated and abnormal ears, and micrognathia. Ectodermal
abnormalities consisted of fine hair, sparse eyebrows, and thin skin.
Both sibs had feeding difficulties with gastroesophageal reflux and
growth retardation with microcephaly. Psychomotor skills were severely
delayed with no verbal capacity. The brother displayed low growth
hormone levels, whereas the sister had low cholesterol and mildly
elevated TSH levels. Additional features included renal anomalies, axial
hypotonia, and abnormal neurologic findings.
Basel-Vanagaite et al. (2012) described 4 affected individuals from 3
unrelated families, including the family reported by Dentici et al.
(2011), with blepharophimosis, ptosis, mild upslanting of the palpebral
fissures, epicanthus, ectodermal anomalies, developmental delay, and
severe intellectual disability with absent speech. Proportionate growth
retardation with a small head circumference/microcephaly, congenital
malformations, muscular hypotonia, and anomalies on brain imaging with
hypoplasia of the corpus callosum were variably present. Three of the 4
affected individuals had low cholesterol levels.
MOLECULAR GENETICS
Basel-Vanagaite et al. (2012) performed exome sequencing of 2 unrelated
individuals with BPIDS and identified the UBE3B gene as the only gene
with rare or unique biallelic damaging variants in both individuals.
Individual 1 had a homozygous splice site mutation (c.1741+2T-C;
608047.0001), which was present in heterozygous state in her unaffected
first-cousin parents. Individual 2 and her affected brother had a
maternally inherited deletion (c.2223_2224delAG; 608047.0002) and a
paternally inherited splice site mutation (c.545-2AG; 608047.0003). All
3 of these mutations introduce premature termination codons and are thus
expected to result in nonsense-mediated mRNA decay and/or protein
truncation. By sequencing the coding exons of the UBE3B gene in a fourth
affected individual, Basel-Vanagaite et al. (2012) detected another
homozygous mutation (E727P; 608047.0004), which was present in
heterozygous state in her unaffected first-cousin parents. None of the
mutations were present in 100 ethnically matched control individuals or
in the NHLBI Exome Sequencing Project database.
*FIELD* RF
1. Basel-Vanagaite, L.; Dallapiccola, B.; Ramirez-Solis, R.; Segref,
A.; thiele, H.; Edwards, A.; Arends, M. J.; Miro, X.; White, J. K.;
Desir, J.; Abramowicz, M.; Dentici, M. L.; and 24 others: Deficiency
for the ubiquitin ligase UBE3B in a blepharophimosis-ptosis-intellectual-disability
syndrome. Am. J. Hum. Genet. 91: 998-1010, 2012.
2. Dentici, M. L.; Mingarelli, R.; Dallapiccola, B.: The difficult
nosology of blepharophimosis-mental retardation syndromes: report
on two siblings. Am. J. Med. Genet. 155A: 459-465, 2011.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Height];
Short stature;
[Other];
Failure to thrive
HEAD AND NECK:
[Head];
Microcephaly;
[Ears];
Low-set ears;
Dysplastic ears;
[Eyes];
Blepharophimosis;
Ptosis;
Upward-slanting palpebral fissures;
Telecanthus;
Hypertelorism;
Astigmatism;
Strabismus, mild;
Myopia;
[Nose];
Depressed nasal bridge;
Anteverted nares;
[Mouth];
Palate anomalies;
Micrognathia;
Small mouth
CARDIOVASCULAR:
[Heart];
Atrial septal defect (ASD);
Ventricular septal defect (VSD);
Aortic coarctation
RESPIRATORY:
[Larynx];
Laryngomalacia
ABDOMEN:
[Gastrointestinal];
Feeding problems;
Gastrectasia;
Constipation;
Distension of gall-bladder;
Intestinal malrotation
GENITOURINARY:
[External genitalia, female];
Hypoplastic labia majora;
[Kidneys];
Pyelectasis;
Double right kidney
SKELETAL:
[Pelvis];
Congenital dislocation of the hip;
[Hands];
Clinodactyly of 5th fingers
SKIN, NAILS, HAIR:
[Skin];
Eczema;
Thin skin;
[Hair];
Sparse, thin hair;
Sparse, thin eyebrows
NEUROLOGIC:
[Central nervous system];
Delayed motor milestones;
Absent speech;
Intellectual disability, severe;
Chiari type I malformation;
Ventricular dilatation;
Hypoplastic corpus callosum;
Agenesis of the rostrum of corpus callosum;
Anterior commissure not evident;
Reduced size of the pituitary gland;
Partial empty sella turcica;
Hypotonia
IMMUNOLOGY:
Frequent infections
LABORATORY ABNORMALITIES:
Elevated TSH;
Low growth hormone levels;
Low ACTH level;
Anomalies of cholesterol levels
MOLECULAR BASIS:
Caused by mutation in the ubiquitin-protein ligase E3B gene (UBE3B,
608047.0001)
*FIELD* CD
Nara Sobreira: 5/3/2013
*FIELD* ED
joanna: 01/21/2014
joanna: 5/3/2013
*FIELD* CD
Nara Sobreira: 1/30/2013
*FIELD* ED
joanna: 01/21/2014
carol: 5/3/2013
*RECORD*
*FIELD* NO
615057
*FIELD* TI
#615057 BLEPHAROPHIMOSIS-PTOSIS-INTELLECTUAL DISABILITY SYNDROME; BPIDS
;;BPID SYNDROME;;
read moreBLEPHAROPHIMOSIS-PTOSIS-MENTAL RETARDATION SYNDROME
*FIELD* TX
A number sign (#) is used with this entry because the
blepharophimosis-ptosis-intellectual disability syndrome (BPIDS) is
caused by homozygous or compound heterozygous mutation in the UBE3B gene
(608047) on chromosome 12q23.
DESCRIPTION
BPIDS is characterized by blepharophimosis, ptosis, mild upslanting of
the palpebral fissures, epicanthus, ectodermal anomalies, developmental
delay, and severe intellectual disability with absent speech.
Proportionate growth retardation with a small head
circumference/microcephaly, congenital malformations, muscular
hypotonia, anomalies on brain imaging with hypoplasia of the corpus
callosum, and low cholesterol levels are variably present
(Basel-Vanagaite et al., 2012).
CLINICAL FEATURES
Dentici et al. (2011) described 2 Italian sibs, a 6-year-old girl and an
18-month-old boy, who presented with overlapping clinical findings.
Major characteristics included facial dysmorphisms with upward slanting
palpebral fissures, blepharophimosis, telecanthus, hypertelorism,
posteriorly rotated and abnormal ears, and micrognathia. Ectodermal
abnormalities consisted of fine hair, sparse eyebrows, and thin skin.
Both sibs had feeding difficulties with gastroesophageal reflux and
growth retardation with microcephaly. Psychomotor skills were severely
delayed with no verbal capacity. The brother displayed low growth
hormone levels, whereas the sister had low cholesterol and mildly
elevated TSH levels. Additional features included renal anomalies, axial
hypotonia, and abnormal neurologic findings.
Basel-Vanagaite et al. (2012) described 4 affected individuals from 3
unrelated families, including the family reported by Dentici et al.
(2011), with blepharophimosis, ptosis, mild upslanting of the palpebral
fissures, epicanthus, ectodermal anomalies, developmental delay, and
severe intellectual disability with absent speech. Proportionate growth
retardation with a small head circumference/microcephaly, congenital
malformations, muscular hypotonia, and anomalies on brain imaging with
hypoplasia of the corpus callosum were variably present. Three of the 4
affected individuals had low cholesterol levels.
MOLECULAR GENETICS
Basel-Vanagaite et al. (2012) performed exome sequencing of 2 unrelated
individuals with BPIDS and identified the UBE3B gene as the only gene
with rare or unique biallelic damaging variants in both individuals.
Individual 1 had a homozygous splice site mutation (c.1741+2T-C;
608047.0001), which was present in heterozygous state in her unaffected
first-cousin parents. Individual 2 and her affected brother had a
maternally inherited deletion (c.2223_2224delAG; 608047.0002) and a
paternally inherited splice site mutation (c.545-2AG; 608047.0003). All
3 of these mutations introduce premature termination codons and are thus
expected to result in nonsense-mediated mRNA decay and/or protein
truncation. By sequencing the coding exons of the UBE3B gene in a fourth
affected individual, Basel-Vanagaite et al. (2012) detected another
homozygous mutation (E727P; 608047.0004), which was present in
heterozygous state in her unaffected first-cousin parents. None of the
mutations were present in 100 ethnically matched control individuals or
in the NHLBI Exome Sequencing Project database.
*FIELD* RF
1. Basel-Vanagaite, L.; Dallapiccola, B.; Ramirez-Solis, R.; Segref,
A.; thiele, H.; Edwards, A.; Arends, M. J.; Miro, X.; White, J. K.;
Desir, J.; Abramowicz, M.; Dentici, M. L.; and 24 others: Deficiency
for the ubiquitin ligase UBE3B in a blepharophimosis-ptosis-intellectual-disability
syndrome. Am. J. Hum. Genet. 91: 998-1010, 2012.
2. Dentici, M. L.; Mingarelli, R.; Dallapiccola, B.: The difficult
nosology of blepharophimosis-mental retardation syndromes: report
on two siblings. Am. J. Med. Genet. 155A: 459-465, 2011.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Height];
Short stature;
[Other];
Failure to thrive
HEAD AND NECK:
[Head];
Microcephaly;
[Ears];
Low-set ears;
Dysplastic ears;
[Eyes];
Blepharophimosis;
Ptosis;
Upward-slanting palpebral fissures;
Telecanthus;
Hypertelorism;
Astigmatism;
Strabismus, mild;
Myopia;
[Nose];
Depressed nasal bridge;
Anteverted nares;
[Mouth];
Palate anomalies;
Micrognathia;
Small mouth
CARDIOVASCULAR:
[Heart];
Atrial septal defect (ASD);
Ventricular septal defect (VSD);
Aortic coarctation
RESPIRATORY:
[Larynx];
Laryngomalacia
ABDOMEN:
[Gastrointestinal];
Feeding problems;
Gastrectasia;
Constipation;
Distension of gall-bladder;
Intestinal malrotation
GENITOURINARY:
[External genitalia, female];
Hypoplastic labia majora;
[Kidneys];
Pyelectasis;
Double right kidney
SKELETAL:
[Pelvis];
Congenital dislocation of the hip;
[Hands];
Clinodactyly of 5th fingers
SKIN, NAILS, HAIR:
[Skin];
Eczema;
Thin skin;
[Hair];
Sparse, thin hair;
Sparse, thin eyebrows
NEUROLOGIC:
[Central nervous system];
Delayed motor milestones;
Absent speech;
Intellectual disability, severe;
Chiari type I malformation;
Ventricular dilatation;
Hypoplastic corpus callosum;
Agenesis of the rostrum of corpus callosum;
Anterior commissure not evident;
Reduced size of the pituitary gland;
Partial empty sella turcica;
Hypotonia
IMMUNOLOGY:
Frequent infections
LABORATORY ABNORMALITIES:
Elevated TSH;
Low growth hormone levels;
Low ACTH level;
Anomalies of cholesterol levels
MOLECULAR BASIS:
Caused by mutation in the ubiquitin-protein ligase E3B gene (UBE3B,
608047.0001)
*FIELD* CD
Nara Sobreira: 5/3/2013
*FIELD* ED
joanna: 01/21/2014
joanna: 5/3/2013
*FIELD* CD
Nara Sobreira: 1/30/2013
*FIELD* ED
joanna: 01/21/2014
carol: 5/3/2013