ID HACE1_MOUSE Reviewed; 909 AA. AC Q3U0D9; F6VQI5; F7ALT5; Q5DTY7; Q8BXY2; Q8R160; Q8R3G4; DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot. DT 11-OCT-2005, sequence version 1. DT 07-NOV-2018, entry version 108. 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; Synonyms=Kiaa1320; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC STRAIN=NOD; TISSUE=Cerebellum, and Spleen; 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., RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E., RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., RA 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., RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., RA Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). 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., RA She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., RA Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., RA Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J., RA Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., RA Lindblad-Toh K., Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of RT the mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 567-838 (ISOFORM 3). RC TISSUE=Mammary tumor; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 689-838 (ISOFORM 2), AND RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 519-909 (ISOFORM 4). RC TISSUE=Embryonic intestine; RA Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O., RA Koga H.; RT "Prediction of the coding sequences of mouse homologues of KIAA gene. RT The complete nucleotide sequences of mouse KIAA-homologous cDNAs RT identified by screening of terminal sequences of cDNA clones randomly RT sampled from size-fractionated libraries."; RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP DISRUPTION PHENOTYPE. RX PubMed=17694067; DOI=10.1038/nm1621; RA Zhang L., Anglesio M.S., O'Sullivan M., Zhang F., Yang G., Sarao R., RA Mai P.N., Cronin S., Hara H., Melnyk N., Li L., Wada T., Liu P.P., RA Farrar J., Arceci R.J., Sorensen P.H., Penninger J.M.; RT "The E3 ligase HACE1 is a critical chromosome 6q21 tumor suppressor RT involved in multiple cancers."; RL Nat. Med. 13:1060-1069(2007). RN [6] RP INTERACTION WITH RARB, AND FUNCTION. RX PubMed=19350571; DOI=10.1002/jcb.22146; RA Zhao J., Zhang Z., Vucetic Z., Soprano K.J., Soprano D.R.; RT "HACE1: A novel repressor of RAR transcriptional activity."; RL J. Cell. Biochem. 107:482-493(2009). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Lung, 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 RT expression."; RL Cell 143:1174-1189(2010). CC -!- FUNCTION: E3 ubiquitin-protein ligase involved in Golgi membrane CC fusion and regulation of small GTPases. Acts as a regulator of CC Golgi membrane dynamics during the cell cycle: recruited to Golgi CC membrane by Rab proteins and regulates postmitotic Golgi membrane CC fusion. Acts by mediating ubiquitination during mitotic Golgi CC disassembly, ubiquitination serving as a signal for Golgi CC reassembly later, after cell division. Specifically interacts with CC GTP-bound RAC1, mediating ubiquitination and subsequent CC degradation of active RAC1, thereby playing a role in host defense CC against pathogens (By similarity). May also act as a transcription CC regulator via its interaction with RARB. CC {ECO:0000250|UniProtKB:Q8IYU2, ECO:0000269|PubMed:19350571}. CC -!- CATALYTIC ACTIVITY: S-ubiquitinyl-[E2 ubiquitin-conjugating CC enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin- CC conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor CC protein]-L-lysine. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Interacts with RAB1 (RAB1A, RAB1B or RAB1C), RAB4 (RAB4A CC or RAB4B) and RAB11 (RAB11A or RAB11B); in a GTP-dependent manner. CC Interacts with RAC1; in a GTP-dependent manner. Interacts with the CC 26S proteasomal complex through the 20S core proteasomal subunit CC (By similarity). Interacts with RARB. CC {ECO:0000250|UniProtKB:Q8IYU2, ECO:0000269|PubMed:19350571}. 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 CC endoplasmic reticulum. Targeted to Golgi membrane via its CC interaction with Rab proteins (By similarity). {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q3U0D9-1; Sequence=Displayed; CC Name=2; CC IsoId=Q3U0D9-2; Sequence=VSP_023833, VSP_023834; CC Note=No experimental confirmation available.; CC Name=3; CC IsoId=Q3U0D9-3; Sequence=VSP_023832; CC Note=No experimental confirmation available.; CC Name=4; CC IsoId=Q3U0D9-4; Sequence=VSP_023832, VSP_042379; CC Note=No experimental confirmation available.; CC -!- DISRUPTION PHENOTYPE: Mice develop spontaneous, late-onset cancer. CC Moreover, tumor incidence in mice heterozygous for a p53/Tp53 CC mutation in higher in a Hace1-deficient background. CC {ECO:0000269|PubMed:17694067}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH25474.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK042879; BAC31390.1; -; mRNA. DR EMBL; AK156958; BAE33915.1; -; mRNA. DR EMBL; AC135669; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC153847; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC025227; AAH25227.1; -; mRNA. DR EMBL; BC025474; AAH25474.1; ALT_INIT; mRNA. DR EMBL; BC120695; AAI20696.1; -; mRNA. DR EMBL; BC120697; AAI20698.1; -; mRNA. DR EMBL; AK220383; BAD90440.1; -; mRNA. DR CCDS; CCDS23829.1; -. [Q3U0D9-1] DR RefSeq; NP_766061.2; NM_172473.3. [Q3U0D9-1] DR UniGene; Mm.458633; -. DR ProteinModelPortal; Q3U0D9; -. DR SMR; Q3U0D9; -. DR BioGrid; 229081; 1. DR IntAct; Q3U0D9; 1. DR STRING; 10090.ENSMUSP00000039206; -. DR iPTMnet; Q3U0D9; -. DR PhosphoSitePlus; Q3U0D9; -. DR MaxQB; Q3U0D9; -. DR PaxDb; Q3U0D9; -. DR PeptideAtlas; Q3U0D9; -. DR PRIDE; Q3U0D9; -. DR Ensembl; ENSMUST00000037044; ENSMUSP00000039206; ENSMUSG00000038822. [Q3U0D9-1] DR GeneID; 209462; -. DR KEGG; mmu:209462; -. DR UCSC; uc007fad.2; mouse. [Q3U0D9-1] DR CTD; 57531; -. DR MGI; MGI:2446110; Hace1. DR eggNOG; KOG0939; Eukaryota. DR eggNOG; KOG4177; Eukaryota. DR eggNOG; COG0666; LUCA. DR eggNOG; COG5021; LUCA. DR GeneTree; ENSGT00760000118966; -. DR HOGENOM; HOG000208454; -. DR HOVERGEN; HBG004134; -. DR InParanoid; Q3U0D9; -. DR KO; K12166; -. DR OrthoDB; EOG091G025R; -. DR PhylomeDB; Q3U0D9; -. DR TreeFam; TF323417; -. DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR UniPathway; UPA00143; -. DR PRO; PR:Q3U0D9; -. DR Proteomes; UP000000589; Chromosome 10. DR Bgee; ENSMUSG00000038822; Expressed in 264 organ(s), highest expression level in liver. DR ExpressionAtlas; Q3U0D9; baseline and differential. DR Genevisible; Q3U0D9; MM. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI. DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell. DR GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB. DR GO; GO:0016604; C:nuclear body; ISO:MGI. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0017137; F:Rab GTPase binding; ISS:UniProtKB. DR GO; GO:0048365; F:Rac GTPase binding; ISO:MGI. 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: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; cd00204; ANK; 1. DR CDD; cd00078; HECTc; 1. DR Gene3D; 1.25.40.20; -; 2. DR InterPro; IPR002110; Ankyrin_rpt. DR InterPro; IPR020683; Ankyrin_rpt-contain_dom. DR InterPro; IPR036770; Ankyrin_rpt-contain_sf. DR InterPro; IPR000569; HECT_dom. DR InterPro; IPR035983; Hect_E3_ubiquitin_ligase. DR Pfam; PF12796; Ank_2; 1. 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 1: Evidence at protein level; KW Alternative splicing; ANK repeat; Cell cycle; Complete proteome; KW Cytoplasm; Endoplasmic reticulum; Golgi apparatus; Membrane; KW Reference proteome; Repeat; Transcription; Transcription regulation; KW Transferase; Ubl conjugation pathway. FT CHAIN 1 909 E3 ubiquitin-protein ligase HACE1. FT /FTId=PRO_0000280623. FT REPEAT 64 93 ANK 1. FT REPEAT 97 126 ANK 2. FT REPEAT 130 159 ANK 3. FT REPEAT 163 192 ANK 4. FT REPEAT 196 226 ANK 5. FT REPEAT 228 257 ANK 6. FT DOMAIN 574 909 HECT. {ECO:0000255|PROSITE- FT ProRule:PRU00104}. FT ACT_SITE 876 876 Glycyl thioester intermediate. FT {ECO:0000255|PROSITE-ProRule:PRU00104}. FT VAR_SEQ 738 781 Missing (in isoform 3 and isoform 4). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|Ref.4}. FT /FTId=VSP_023832. FT VAR_SEQ 814 832 Missing (in isoform 4). FT {ECO:0000303|Ref.4}. FT /FTId=VSP_042379. FT VAR_SEQ 838 838 S -> R (in isoform 2). FT {ECO:0000303|Ref.4}. FT /FTId=VSP_023833. FT VAR_SEQ 839 909 Missing (in isoform 2). FT {ECO:0000303|Ref.4}. FT /FTId=VSP_023834. FT CONFLICT 92 92 N -> S (in Ref. 1; BAC31390). FT {ECO:0000305}. SQ SEQUENCE 909 AA; 102114 MW; 804F62A06E9C78A0 CRC64; MERAMEQLNR LTRSLRRART VELPEDNETA VYTLMPMVMA DQHRSVSELL SNSKFDVNYA FGRVKRSLLH IAANCGSVEC LVLLLKKGAN PNYQDISGCT PLHLAARNGQ KKCMSKLLEY SADVNICNNE GLTAIHWLAV NGRTELLHDL VQHVTDVDVE DAMGQTALHV ACQNGHKTTV QCLLDSGADI NRPNVSGATP LYFACSHGQR DTAQILLLRG AKYLPDKNGV TPLDLCVQGG YGQTCEVLIQ YHPRLFQTIV QMTQNEDLRE NMLRQVLQHL SQQSESQYLK ILTGLAEVAT TNGHKLLSLS SNYDAQMKSL LRIVRIFCHV FRIGPSSPSN GIDMGYNGNK TPRSQVFKPL ELLWHSLDEW LVLIATELMK NKEDSTDITS ILLKQKGQDQ EAPSLSAFEP PGPGSYESLP PGPGDSKPEV LAGEQEASAD 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 EDITQEERVL LLQFVTGSSR VPHGGFANIM GGSGLQNFTI AAVPYTPNLL PTSSTCINML KLPEYPSKEI LKDRLLVALH CGSYGYTMA //