ID   UBE3C_MOUSE             Reviewed;        1083 AA.
AC   Q80U95; Q0VB95; Q8BQZ6; Q8C7W6; Q8CDJ1; Q8VDL5;
DT   07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT   07-JUN-2005, sequence version 2.
DT   03-AUG-2022, entry version 137.
DE   RecName: Full=Ubiquitin-protein ligase E3C {ECO:0000305};
DE            EC=2.3.2.26 {ECO:0000250|UniProtKB:Q15386};
DE   AltName: Full=HECT-type ubiquitin transferase E3C {ECO:0000305};
DE   AltName: Full=RTA-associated ubiquitin ligase {ECO:0000303|PubMed:21167755};
DE            Short=RAUL {ECO:0000303|PubMed:21167755};
GN   Name=Ube3c {ECO:0000312|MGI:MGI:2140998};
GN   Synonyms=Kiaa0010 {ECO:0000303|PubMed:12693553},
GN   Kiaa10 {ECO:0000250|UniProtKB:Q15386};
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 [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   PubMed=12693553; DOI=10.1093/dnares/10.1.35;
RA   Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S.,
RA   Nakajima D., Nagase T., Ohara O., Koga H.;
RT   "Prediction of the coding sequences of mouse homologues of KIAA gene: II.
RT   The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs
RT   identified by screening of terminal sequences of cDNA clones randomly
RT   sampled from size-fractionated libraries.";
RL   DNA Res. 10:35-48(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Corpora quadrigemina, and Testis;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Brain, and Mammary gland;
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   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC   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   [5]
RP   FUNCTION.
RX   PubMed=21167755; DOI=10.1016/j.immuni.2010.11.027;
RA   Yu Y., Hayward G.S.;
RT   "The ubiquitin E3 ligase RAUL negatively regulates type i interferon
RT   through ubiquitination of the transcription factors IRF7 and IRF3.";
RL   Immunity 33:863-877(2010).
CC   -!- FUNCTION: E3 ubiquitin-protein ligase that specifically catalyzes 'Lys-
CC       29'- and 'Lys-48'-linked polyubiquitin chains (By similarity). Accepts
CC       ubiquitin from the E2 ubiquitin-conjugating enzyme UBE2D1 in the form
CC       of a thioester and then directly transfers the ubiquitin to targeted
CC       substrates (By similarity). Associates with the proteasome and promotes
CC       elongation of ubiquitin chains on substrates bound to the 26S
CC       proteasome (By similarity). Also catalyzes 'Lys-29'- and 'Lys-48'-
CC       linked ubiquitination of 26S proteasome subunit ADRM1/RPN13 in response
CC       to proteotoxic stress, impairing the ability of the proteasome to bind
CC       and degrade ubiquitin-conjugated proteins (By similarity). Acts as a
CC       negative regulator of autophagy by mediating 'Lys-29'- and 'Lys-48'-
CC       linked ubiquitination of PIK3C3/VPS34, promoting its degradation (By
CC       similarity). Can assemble unanchored poly-ubiquitin chains in either
CC       'Lys-29'- or 'Lys-48'-linked polyubiquitin chains; with some preference
CC       for 'Lys-48' linkages (By similarity). Acts as a negative regulator of
CC       type I interferon by mediating 'Lys-48'-linked ubiquitination of IRF3
CC       and IRF7, leading to their degradation by the proteasome
CC       (PubMed:21167755). Catalyzes ubiquitination and degradation of CAND2
CC       (By similarity). {ECO:0000250|UniProtKB:Q15386,
CC       ECO:0000269|PubMed:21167755}.
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=2.3.2.26; Evidence={ECO:0000250|UniProtKB:Q15386};
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC       {ECO:0000250|UniProtKB:Q15386}.
CC   -!- SUBUNIT: Interacts with 26S proteasomes. Interacts (via the HECT
CC       domain) with UBE2D1 and, less efficiently, with UBE2L3.
CC       {ECO:0000250|UniProtKB:Q15386}.
CC   -!- PTM: Autoubiquitinated; promoting its own degradation.
CC       {ECO:0000250|UniProtKB:Q15386}.
CC   -!- SIMILARITY: Belongs to the UBE3C family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH21525.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AK122187; BAC65469.1; -; mRNA.
DR   EMBL; AK029973; BAC26709.1; -; mRNA.
DR   EMBL; AK046056; BAC32585.1; -; mRNA.
DR   EMBL; AK049125; BAC33557.1; -; mRNA.
DR   EMBL; BC021525; AAH21525.1; ALT_INIT; mRNA.
DR   EMBL; BC120731; AAI20732.1; -; mRNA.
DR   EMBL; BC137626; AAI37627.1; -; mRNA.
DR   CCDS; CCDS39042.1; -.
DR   RefSeq; NP_598668.1; NM_133907.3.
DR   AlphaFoldDB; Q80U95; -.
DR   SMR; Q80U95; -.
DR   BioGRID; 221524; 6.
DR   IntAct; Q80U95; 3.
DR   MINT; Q80U95; -.
DR   STRING; 10090.ENSMUSP00000045998; -.
DR   iPTMnet; Q80U95; -.
DR   PhosphoSitePlus; Q80U95; -.
DR   EPD; Q80U95; -.
DR   MaxQB; Q80U95; -.
DR   PaxDb; Q80U95; -.
DR   PeptideAtlas; Q80U95; -.
DR   PRIDE; Q80U95; -.
DR   ProteomicsDB; 298447; -.
DR   Antibodypedia; 33178; 163 antibodies from 26 providers.
DR   DNASU; 100763; -.
DR   Ensembl; ENSMUST00000049453; ENSMUSP00000045998; ENSMUSG00000039000.
DR   GeneID; 100763; -.
DR   KEGG; mmu:100763; -.
DR   UCSC; uc008wum.1; mouse.
DR   CTD; 9690; -.
DR   MGI; MGI:2140998; Ube3c.
DR   VEuPathDB; HostDB:ENSMUSG00000039000; -.
DR   eggNOG; KOG0942; Eukaryota.
DR   GeneTree; ENSGT00940000156321; -.
DR   HOGENOM; CLU_002173_2_1_1; -.
DR   InParanoid; Q80U95; -.
DR   OMA; TDNKLYP; -.
DR   OrthoDB; 1163565at2759; -.
DR   PhylomeDB; Q80U95; -.
DR   TreeFam; TF106144; -.
DR   Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 100763; 2 hits in 73 CRISPR screens.
DR   ChiTaRS; Ube3c; mouse.
DR   PRO; PR:Q80U95; -.
DR   Proteomes; UP000000589; Chromosome 5.
DR   RNAct; Q80U95; protein.
DR   Bgee; ENSMUSG00000039000; Expressed in spermatocyte and 269 other tissues.
DR   ExpressionAtlas; Q80U95; baseline and differential.
DR   Genevisible; Q80U95; MM.
DR   GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB.
DR   GO; GO:0035519; P:protein K29-linked ubiquitination; ISS:UniProtKB.
DR   GO; GO:0070936; P:protein K48-linked ubiquitination; ISS:UniProtKB.
DR   GO; GO:0000209; P:protein polyubiquitination; ISO:MGI.
DR   GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR   CDD; cd00078; HECTc; 1.
DR   InterPro; IPR044611; E3B/C.
DR   InterPro; IPR000569; HECT_dom.
DR   InterPro; IPR035983; Hect_E3_ubiquitin_ligase.
DR   InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR   PANTHER; PTHR45700; PTHR45700; 1.
DR   Pfam; PF00632; HECT; 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   Isopeptide bond; Reference proteome; Transferase; Ubl conjugation;
KW   Ubl conjugation pathway.
FT   CHAIN           1..1083
FT                   /note="Ubiquitin-protein ligase E3C"
FT                   /id="PRO_0000194983"
FT   DOMAIN          45..74
FT                   /note="IQ"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT   DOMAIN          744..1083
FT                   /note="HECT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT   REGION          1..60
FT                   /note="Cis-determinant of acceptor ubiquitin-binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q15386"
FT   REGION          1..40
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          354..386
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        16..40
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        1051
FT                   /note="Glycyl thioester intermediate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT   CROSSLNK        903
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin); by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:Q15386"
FT   CONFLICT        570
FT                   /note="E -> G (in Ref. 2; BAC26709)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1083 AA;  123976 MW;  B7098CB9792946BE CRC64;
     MFSFEGDFKT RPKVSLGGAS RKEEKASLLH RTQEERRKRE EERRRLKNAV IIQSFIRGYR
     DRKQQYFIQR SAFDQCTDSA QPGGTFCLAD GPNLTLLVRQ LLFFYKQSED SKRLIWLYQN
     LIKHSSLFVK QLDGSERLTC LFQIKRLMSL CCRLLQNCSD DSLNVALPMR MLEVFTSENT
     YLPVLQDSSY VVSVIEQILH YMVHSGYYRS LYLLINSKLP SSIEYSDLSR VPIAKILLEN
     VLKPLHFTYS SCPEASRHQV FSAFTEEFLG APFTDQIFHF VIPAFADAQT VFPYEPFLNA
     LLLLESQSSK RCSGVPWLFY FVLTVGENYL GALSEDGLLV YLRVLQTFLS QLPASPTGTG
     CPDSTSDSED DNEETDQPNS PEDGRVSAPY ITEECLRKLD TKQQTNTLLN LVWRDSASEE
     VFTRMASICH TLMVQHRMMV PKVRLLYSLA FNARFLRHLW FLISSMTTQM ITGSMVPLLQ
     LISRGSPMSF EDSSRIIPLF YLFSSLFSHS LISIHDNEFF GDPIEVVGQR QSSMMPFTLE
     ELILLSRCLR DACLGIIKLA YPETKPEVRE EYVTAFQSIG VTTNSEMQQC IQMEQKRWVQ
     LFKVITNLVK MLKSRDTRRN FCPPNHWLSE QEDIKADKVT QLYVPASRHV WRFRRMGRIG
     PLQSTLEVGL ESLPLSVSEE RQLAILTELP FVVPFEERVK IFQRLIYADK QEVQGDGPFL
     DGINVTIRRN YIYEDAYDKL SPENEPDLKK RIRVHLLNAH GLDEAGIDGG GIFREFLNEL
     LKSGFNPNQG FFKTTNEGLL YPNPAAQMLV GDSFARHYYF LGRMLGKALY ENMLVELPFA
     GFFLSKLLGT SADVDIHHLA SLDPEVYRNL LFLKSYEEDV EELGLNFTVV NNDLGEAQVV
     ELKFGGKDIP VTGANRIAYI HLVADYRLNK QIRPHCLAFR QGLANVVSLE WLRMFDQQEI
     QVLISGAQVP VSLEDLKSFT NYSGGYSADH PVIKIFWRVV EGFTDEEKRK LLKFVTSCSR
     PPLLGFKELY PAFCIHNGGS DLERLPTAST CMNLLKLPEF YDEALLRSKL LYAIECAAGF
     ELS