ID   HACE1_RAT               Reviewed;         909 AA.
AC   D3ZBM7; D3ZBM8;
DT   22-FEB-2012, integrated into UniProtKB/Swiss-Prot.
DT   20-APR-2010, sequence version 1.
DT   03-AUG-2022, entry version 78.
DE   RecName: Full=E3 ubiquitin-protein ligase HACE1;
DE            EC=2.3.2.26;
DE   AltName: Full=HECT domain and ankyrin repeat-containing E3 ubiquitin-protein ligase 1;
DE   AltName: Full=HECT-type E3 ubiquitin transferase HACE1;
GN   Name=Hace1;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
CC   -!- FUNCTION: E3 ubiquitin-protein ligase involved in Golgi membrane fusion
CC       and regulation of small GTPases. Acts as a regulator of Golgi membrane
CC       dynamics during the cell cycle: recruited to Golgi membrane by Rab
CC       proteins and regulates postmitotic Golgi membrane fusion. Acts by
CC       mediating ubiquitination during mitotic Golgi disassembly,
CC       ubiquitination serving as a signal for Golgi reassembly later, after
CC       cell division. Specifically interacts with GTP-bound RAC1, mediating
CC       ubiquitination and subsequent degradation of active RAC1, thereby
CC       playing a role in host defense against pathogens. May also act as a
CC       transcription regulator via its interaction with RARB.
CC       {ECO:0000250|UniProtKB:Q8IYU2}.
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;
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC   -!- SUBUNIT: Interacts with RARB. Interacts with RAB1 (RAB1A, RAB1B or
CC       RAB1C), RAB4 (RAB4A or RAB4B) and RAB11 (RAB11A or RAB11B); in a GTP-
CC       dependent manner. Interacts with RAC1; in a GTP-dependent manner.
CC       Interacts with the 26S proteasomal complex through the 20S core
CC       proteasomal subunit. {ECO:0000250|UniProtKB:Q3U0D9,
CC       ECO:0000250|UniProtKB:Q8IYU2}.
CC   -!- SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane
CC       {ECO:0000250}. Cytoplasm {ECO:0000250}. Endoplasmic reticulum
CC       {ECO:0000250}. Note=A significant portion localizes to the endoplasmic
CC       reticulum. Targeted to Golgi membrane via its interaction with Rab
CC       proteins. {ECO:0000250}.
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DR   RefSeq; NP_001102009.2; NM_001108539.3.
DR   AlphaFoldDB; D3ZBM7; -.
DR   SMR; D3ZBM7; -.
DR   STRING; 10116.ENSRNOP00000000365; -.
DR   PaxDb; D3ZBM7; -.
DR   PeptideAtlas; D3ZBM7; -.
DR   PRIDE; D3ZBM7; -.
DR   Ensembl; ENSRNOT00000000365; ENSRNOP00000000365; ENSRNOG00000000327.
DR   GeneID; 361866; -.
DR   KEGG; rno:361866; -.
DR   UCSC; RGD:1306114; rat.
DR   CTD; 57531; -.
DR   RGD; 1306114; Hace1.
DR   eggNOG; KOG0939; Eukaryota.
DR   eggNOG; KOG4177; Eukaryota.
DR   GeneTree; ENSGT00940000155839; -.
DR   HOGENOM; CLU_015878_0_0_1; -.
DR   InParanoid; D3ZBM7; -.
DR   OMA; XELLLSG; -.
DR   OrthoDB; 799706at2759; -.
DR   TreeFam; TF323417; -.
DR   Reactome; R-RNO-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR   UniPathway; UPA00143; -.
DR   PRO; PR:D3ZBM7; -.
DR   Proteomes; UP000002494; Chromosome 20.
DR   Bgee; ENSRNOG00000000327; Expressed in frontal cortex and 19 other tissues.
DR   Genevisible; D3ZBM7; RN.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR   GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0031267; F:small GTPase binding; ISS:UniProtKB.
DR   GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR   GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR   GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0007030; P:Golgi organization; ISS:UniProtKB.
DR   GO; GO:0061025; P:membrane fusion; ISS:UniProtKB.
DR   GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR   GO; GO:0070936; P:protein K48-linked ubiquitination; ISS:UniProtKB.
DR   GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR   GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR   GO; GO:0030334; P:regulation of cell migration; ISS:UniProtKB.
DR   GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR   CDD; cd00078; HECTc; 1.
DR   Gene3D; 1.25.40.20; -; 2.
DR   InterPro; IPR002110; Ankyrin_rpt.
DR   InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR   InterPro; IPR000569; HECT_dom.
DR   InterPro; IPR035983; Hect_E3_ubiquitin_ligase.
DR   Pfam; PF12796; Ank_2; 3.
DR   Pfam; PF00632; HECT; 1.
DR   PRINTS; PR01415; ANKYRIN.
DR   SMART; SM00248; ANK; 6.
DR   SMART; SM00119; HECTc; 1.
DR   SUPFAM; SSF48403; SSF48403; 1.
DR   SUPFAM; SSF56204; SSF56204; 1.
DR   PROSITE; PS50297; ANK_REP_REGION; 1.
DR   PROSITE; PS50088; ANK_REPEAT; 5.
DR   PROSITE; PS50237; HECT; 1.
PE   3: Inferred from homology;
KW   ANK repeat; Cell cycle; Cytoplasm; Endoplasmic reticulum; Golgi apparatus;
KW   Membrane; Reference proteome; Repeat; Transcription;
KW   Transcription regulation; Transferase; Ubl conjugation pathway.
FT   CHAIN           1..909
FT                   /note="E3 ubiquitin-protein ligase HACE1"
FT                   /id="PRO_0000415843"
FT   REPEAT          64..93
FT                   /note="ANK 1"
FT   REPEAT          97..126
FT                   /note="ANK 2"
FT   REPEAT          130..159
FT                   /note="ANK 3"
FT   REPEAT          163..192
FT                   /note="ANK 4"
FT   REPEAT          196..226
FT                   /note="ANK 5"
FT   REPEAT          228..257
FT                   /note="ANK 6"
FT   DOMAIN          574..909
FT                   /note="HECT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT   REGION          409..428
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        876
FT                   /note="Glycyl thioester intermediate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
SQ   SEQUENCE   909 AA;  102159 MW;  60C1FC2E282C2F99 CRC64;
     MERAMEQLNR LTRSLRRART VELPEDNETA VYTLMPMVMA DQHRSVSELL SNSKFDVNYA
     FGRVKRSLLH IAANCGSVEC LVLLLKKGAN PNYQDISGCT PLHLAARNGQ KKCMSKLLEY
     SADVNICNNE GLTAIHWLAV NGRTELLHDL VQHVTDVDVE DAMGQTALHV ACQNGHKTTV
     QCLLDSGADI NRPNVAGATP LYFACSHGQR DTAQILLLRG AKYLPDKNGV TPLDLCVQGG
     YGQTCEVLIQ YHPRLFQTIV QMTQNEDLRE NMLRQVLQHL SQQSESQYLK ILTGLAEVAT
     TNGHKLLSLS SSYEAQMKSL LRIVRIFCHV FRIGPSSPSN GMDMGYNGNK TPRSQVFKPL
     ELLWHSLDEW LVLIATELMK NKEDSADITS ILLKQKGQDQ EASCISAFEP PGPGSYERLS
     TGPGESKPDV LAGKQEASAD CQDVISVTAN RLSAVIQAFY MCCSCQMPPG MTSPRFIEFV
     CKHDEVLKCF VNRNPKIIFD HFHFLLECPE LMSRFMHIIK AQPFKDRCEW FYEHLHSGQP
     DSDMVHRPVS ENDILLVHRD SIFRSSCEIV SKANCAKLKQ GIAVRFHGEE GMGQGVVREW
     FDILSNEIVN PDYALFTQSA DGTTFQPNSN SYVNPDHLNY FRFAGQILGL ALNHRQLVNI
     YFTRSFYKHI LGIPVNYQDV ASIDPEYAKN LQWILDNDIS DLGLELTFSV ETDVFGAMEE
     VPLKPGGGSI LVTQNNKAEY VQLVTELRMT RAIQPQINAF LQGFHMFIPP SLIQLFDEYE
     LELLLSGMPE IDVNDWIKNT EYTSGYERED PVIQWFWEVV EDMTQEERVL LLQFVTGSSR
     VPHGGFANIM GGSGLQNFTI AAVPYTPNLL PTSSTCINML KLPEYPSKEI LKDRLLVALH
     CGSYGYTMA