UBR3_MOUSE
ID UBR3_MOUSE Reviewed; 1889 AA.
AC Q5U430; A2AV04; A6MFP4; Q69Z32;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 3.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=E3 ubiquitin-protein ligase UBR3;
DE EC=2.3.2.27;
DE AltName: Full=N-recognin-3;
DE AltName: Full=RING-type E3 ubiquitin transferase UBR3;
DE AltName: Full=Ubiquitin-protein ligase E3-alpha-3;
DE AltName: Full=Ubiquitin-protein ligase E3-alpha-III;
DE AltName: Full=Zinc finger protein 650;
GN Name=Ubr3; Synonyms=Kiaa2024, Zfp650, Znf650;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH UBE2A AND UBE2B,
RP TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=17462990; DOI=10.1074/jbc.m701894200;
RA Tasaki T., Sohr R., Xia Z., Hellweg R., Hortnagl H., Varshavsky A.,
RA Kwon Y.T.;
RT "Biochemical and genetic studies of UBR3, a ubiquitin ligase with a
RT function in olfactory and other sensory systems.";
RL J. Biol. Chem. 282:18510-18520(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C3H/He; TISSUE=Mesenchymal stem cell;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1503-1889 (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-343; SER-344 AND SER-1199,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION.
RX PubMed=27331610; DOI=10.7554/elife.15258;
RA Li T., Giagtzoglou N., Eberl D.F., Jaiswal S.N., Cai T., Godt D.,
RA Groves A.K., Bellen H.J.;
RT "The E3 ligase Ubr3 regulates Usher syndrome and MYH9 disorder proteins in
RT the auditory organs of Drosophila and mammals.";
RL Elife 5:E15258-E15258(2016).
RN [7]
RP FUNCTION.
RX PubMed=27195754; DOI=10.1371/journal.pgen.1006054;
RA Li T., Fan J., Blanco-Sanchez B., Giagtzoglou N., Lin G., Yamamoto S.,
RA Jaiswal M., Chen K., Zhang J., Wei W., Lewis M.T., Groves A.K.,
RA Westerfield M., Jia J., Bellen H.J.;
RT "Ubr3, a Novel Modulator of Hh Signaling Affects the Degradation of Costal-
RT 2 and Kif7 through Poly-ubiquitination.";
RL PLoS Genet. 12:E1006054-E1006054(2016).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which is a component of the N-end
CC rule pathway (PubMed:17462990). Does not bind to proteins bearing
CC specific N-terminal residues that are destabilizing according to the N-
CC end rule, leading to their ubiquitination and subsequent degradation
CC (PubMed:17462990). May play a role in Shh signaling by mediating the
CC ubiquitination of Kif7 (PubMed:27195754). May be important for MYH9
CC function in certain tissues, possibly by regulating the ubiquitination
CC of MYH9 and consequently affecting its interaction with MYO7A
CC (PubMed:27331610). {ECO:0000250|UniProtKB:Q6ZT12,
CC ECO:0000269|PubMed:17462990, ECO:0000269|PubMed:27195754,
CC ECO:0000269|PubMed:27331610}.
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;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with UBE2A and UBE2B. {ECO:0000269|PubMed:17462990}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q5U430-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5U430-2; Sequence=VSP_023143;
CC Name=3;
CC IsoId=Q5U430-3; Sequence=VSP_023144, VSP_023145;
CC -!- TISSUE SPECIFICITY: Expressed in numerous cells of the smell, touch,
CC vision, hearing and taste senses. Expressed in cells of the olfactory
CC pathway, including the olfactory cell layer of the main olfactory
CC epithelium (MOE), a mitral neuron cell layer of the olfactory bulb
CC (OB), and a pyramidal cell layer of the piriform cortex of the
CC olfactory cortex (OC). Expressed in the vomeronasal sensory epithelium
CC of the vomeronasal organ (VNO) and the mitral cells of the accessory
CC olfactory bulb. Expressed in tactile tissues, including the dorsal root
CC ganglion, trigeminal ganglion and follicle-sinus complexes. Expressed
CC in cells between hair follicle and sinus and also in the region of the
CC rete ridge collar. Expressed in taste buds of the fungiform,
CC circumvallate, and foliate papillae. Expressed in the spiral ganglion,
CC the organ of Corti of the cochlea in the inner ear, in the sensory
CC epithelium of macula and vestibular ganglion of the balancing system
CC (at protein level). Expressed in the liver and skeletal muscle.
CC {ECO:0000269|PubMed:17462990}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice for Ubr3 in a B6-enriched
CC background exhibited neonatal lethality associated with suckling
CC impairment, but can be partially rescued if the litter size is reduced.
CC Survived adult knockout mice for Ubr3 had female-specific behavioral
CC anosmia (decreased sense of smell). {ECO:0000269|PubMed:17462990}.
CC -!- SIMILARITY: Belongs to the UBR1 family. {ECO:0000305}.
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DR EMBL; DQ924536; ABK59000.1; -; mRNA.
DR EMBL; AL929249; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC085286; AAH85286.1; -; mRNA.
DR EMBL; AK173334; BAD32612.1; -; mRNA.
DR CCDS; CCDS16104.2; -. [Q5U430-1]
DR RefSeq; NP_808451.2; NM_177783.6. [Q5U430-1]
DR AlphaFoldDB; Q5U430; -.
DR SMR; Q5U430; -.
DR BioGRID; 213054; 1.
DR STRING; 10090.ENSMUSP00000060159; -.
DR iPTMnet; Q5U430; -.
DR PhosphoSitePlus; Q5U430; -.
DR EPD; Q5U430; -.
DR MaxQB; Q5U430; -.
DR PaxDb; Q5U430; -.
DR PeptideAtlas; Q5U430; -.
DR PRIDE; Q5U430; -.
DR ProteomicsDB; 300075; -. [Q5U430-1]
DR ProteomicsDB; 300076; -. [Q5U430-2]
DR ProteomicsDB; 300077; -. [Q5U430-3]
DR Antibodypedia; 33822; 43 antibodies from 14 providers.
DR DNASU; 68795; -.
DR Ensembl; ENSMUST00000055758; ENSMUSP00000060159; ENSMUSG00000044308. [Q5U430-1]
DR GeneID; 68795; -.
DR KEGG; mmu:68795; -.
DR UCSC; uc008jzb.3; mouse. [Q5U430-1]
DR UCSC; uc008jzc.2; mouse. [Q5U430-2]
DR CTD; 130507; -.
DR MGI; MGI:1861100; Ubr3.
DR VEuPathDB; HostDB:ENSMUSG00000044308; -.
DR eggNOG; KOG1139; Eukaryota.
DR GeneTree; ENSGT00950000183075; -.
DR InParanoid; Q5U430; -.
DR PhylomeDB; Q5U430; -.
DR TreeFam; TF323875; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 68795; 4 hits in 72 CRISPR screens.
DR ChiTaRS; Ubr3; mouse.
DR PRO; PR:Q5U430; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q5U430; protein.
DR Bgee; ENSMUSG00000044308; Expressed in vastus lateralis and 252 other tissues.
DR ExpressionAtlas; Q5U430; baseline and differential.
DR Genevisible; Q5U430; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0000151; C:ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:UniProtKB.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0042048; P:olfactory behavior; IMP:MGI.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0007608; P:sensory perception of smell; IMP:UniProtKB.
DR GO; GO:0001967; P:suckling behavior; IMP:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0071596; P:ubiquitin-dependent protein catabolic process via the N-end rule pathway; IBA:GO_Central.
DR InterPro; IPR044046; E3_ligase_UBR-like_C.
DR InterPro; IPR039164; UBR1-like.
DR InterPro; IPR003126; Znf_UBR.
DR PANTHER; PTHR21497; PTHR21497; 1.
DR Pfam; PF18995; PRT6_C; 1.
DR Pfam; PF02207; zf-UBR; 1.
DR SMART; SM00396; ZnF_UBR1; 1.
DR PROSITE; PS51157; ZF_UBR; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Membrane; Metal-binding; Phosphoprotein;
KW Reference proteome; Transferase; Transmembrane; Transmembrane helix;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..1889
FT /note="E3 ubiquitin-protein ligase UBR3"
FT /id="PRO_0000278185"
FT TRANSMEM 761..781
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 919..939
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1807..1827
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ZN_FING 118..189
FT /note="UBR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00508"
FT ZN_FING 1306..1364
FT /note="RING-type; degenerate"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 338..362
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1167..1199
FT /evidence="ECO:0000255"
FT MOD_RES 343
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 344
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1199
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..1494
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023143"
FT VAR_SEQ 1735..1769
FT /note="ALLIQESRWKLPHLLQLPENYNTIFQYYHRKTCSV -> VWREVGGNVLLGR
FT GLMEEVKSRSLVAAGFKLIKLK (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15368895"
FT /id="VSP_023144"
FT VAR_SEQ 1770..1889
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15368895"
FT /id="VSP_023145"
FT CONFLICT 1269
FT /note="N -> S (in Ref. 1; ABK59000)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1889 AA; 212757 MW; F2D5B94FEE7ED562 CRC64;
MAAAAAAAAV GDPQPPQPEA PAQGLALDKA ATAAHLKAAL SRPDNRAGAE ELQALLERVL
NAERPLAGAA GGEEAAGGGG GGPGEAEEDA LEWCKCLLAG GGGYEEFCAA VRAYDPAALC
GLVWTANFVA YRCRTCGISP CMSLCAECFH QGDHTGHDFN MFRSQAGGAC DCGDSNVMRE
SGFCRRHQIK SSSNIPCVPK DLLMMSEFVL PRFIFCLIQY LREGYNEPAA DAPSEKDLNK
VLQLLEPQIS FLEDLTKMGG AMRSVLTQVL TNQQNYKDLT AGLGENACAK KSHEKYLIAL
KSSGLTYPED KLVYGVQEPA AGTSTLAAQG FAGATGTLGQ IDSSDEEDQD GSQGLGKRKR
VKLSSGTKDQ SIMDVLKHKS FLEELLFWTI KYEFPQKMVT FLLNMLPDQE YKVAFTKTFV
QHYAFIMKTL KKSHESDTMS NRIVHISVQL FSNEELARQV TEECQLLDIM VTVLLYMMES
CLIKSELQDE ENSLHVVVNC GEALLKNNTY WPLVSDFINI LSHQSVAQRF LEDHGLLVTW
MNFVSFFQGM NLNKRELNEH VEFESQTYYA AFAAELEACA QPMWGLLSHC KVRETQEYTR
NVVRYCLEAL QDWFDAINFV DEPAPNQVTF HLPLHRYYAM FLSKAVKCQE LDLDSLLPDQ
EMLMKLMIHP LQIQASLAEI HSNMWVRNGL QIKGQAMTYV QSHFCNSMID PDIYLLQVCA
SRLDPDYFIS SVFERFKVVD LLTMASQHHN MVLDVEHERS MLEGALTFLV ILLSLRLHLG
MSDDDILRAE MVAQLCMNDR THSSLLDLIP ENPNPKSGII PGSYSFESVL SAVADFRAPI
FEPGGSMQQG MYTPKAEVWD QEFDPVMVIL RTVYRRDVQS AMDRYTAFLK QSGKFPGNPW
PPYKKRTSLH PSYKGLMRLL HCKTLHIVLF TLLYKILMDH QNLSEHVLCM VLYLIELGLE
NSADDDSEEE VSMGGPERCH DSWFPGSNLV SNMRHFINYV RVRVPETAPE LKRDPLASTS
SDALDSLQNS GTAQVFSLVA ERRKKFQEII NRSNSEANQV VRPKIPSKWS APGSSPQLTT
AILEIKESIL SLLIKLHHKL SGKQNSYYPP WLDDIEVLIQ PEIPKYNHGD GITAVERILL
KAAVQSRMNK RIIEEICRKV TPPVPPKKIT AAEKKTLDKE ERRQKARERQ QKLLAEFASR
QKSFMETAMD VDSPENDIPM EITTAEPQVS EAVYDCVICG QSGPSSEDRP TGLVVLLQAS
SVLGQCRDNA EPKKLPIAEE EQIYPWDTCA AVHDVRLSLL QRYFKDSSCL LAVSIGWEGG
VYVQTCGHTL HIDCHKSYME SLRNDQVLQG FSVDKGEFTC PLCRQFANSV LPCYPGSNVE
NNLWQRPCNK STQDLIKEVE ELQGRPGAFP SETNLSKEME SVMKDIKNTT QKKYRDYSKT
PGSPDNEFLF MYSVARTNLE LELIHRGGSL CSGGPSTAGK RSCLNQLFHV LALHMRLYTI
DSEYNPWKKL TQLVEDMNSQ VGNEDQQPEV PILYHDVTSL LLIQILMMPQ PLRKEHFTCI
VKVLFTLLYT QALAALSVKG TEEDRSAWKH AGALRKDTCD AEKCYEVLLS FVISELSKGK
LYYEEGAQEC AMVSPIAWSP ESMERYIQDF CLPFLRVSSL LQHHLFGEDL PSCQEEEEFS
VLASCLGLLP TFYQTDHPFI SASCLDWPVA AFDIITQWCF EITSFTERHA EQGKALLIQE
SRWKLPHLLQ LPENYNTIFQ YYHRKTCSVC TKVPKDPAVC LVCGTFVCLK GLCCKQQSYC
ECVLHSQNCG AGTGIFLLIN ASVIIIIRGH RFCLWGSVYL DAHGEEDRDL RRGKPLYICE
ERYRVLEQQW VSHTFDHINK RWGPHYNGL
