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 24-JAN-2024, entry version 134.
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; 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] (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., 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 [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 1), AND NUCLEOTIDE SEQUENCE
RP [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 project:
RT 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. The
RT complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by
RT screening of terminal sequences of cDNA clones randomly sampled from size-
RT 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 expression.";
RL Cell 143:1174-1189(2010).
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 (By similarity). May
CC also act as a transcription regulator via its interaction with RARB.
CC {ECO:0000250|UniProtKB:Q8IYU2, ECO:0000269|PubMed:19350571}.
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 RAB1 (RAB1A, RAB1B or RAB1C), RAB4 (RAB4A or
CC RAB4B) and RAB11 (RAB11A or RAB11B); in a GTP-dependent manner.
CC Interacts with RAC1; in a GTP-dependent manner. Interacts with the 26S
CC proteasomal complex through the 20S core proteasomal subunit (By
CC similarity). Interacts with RARB. {ECO:0000250|UniProtKB:Q8IYU2,
CC 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 endoplasmic
CC reticulum. Targeted to Golgi membrane via its interaction with Rab
CC 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 Name=3;
CC IsoId=Q3U0D9-3; Sequence=VSP_023832;
CC Name=4;
CC IsoId=Q3U0D9-4; Sequence=VSP_023832, VSP_042379;
CC -!- DISRUPTION PHENOTYPE: Mice develop spontaneous, late-onset cancer.
CC Moreover, tumor incidence in mice heterozygous for a p53/Tp53 mutation
CC in higher in a Hace1-deficient background.
CC {ECO:0000269|PubMed:17694067}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH25474.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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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 AlphaFoldDB; Q3U0D9; -.
DR SMR; Q3U0D9; -.
DR BioGRID; 229081; 4.
DR IntAct; Q3U0D9; 1.
DR STRING; 10090.ENSMUSP00000039206; -.
DR iPTMnet; Q3U0D9; -.
DR PhosphoSitePlus; Q3U0D9; -.
DR SwissPalm; Q3U0D9; -.
DR EPD; Q3U0D9; -.
DR MaxQB; Q3U0D9; -.
DR PaxDb; 10090-ENSMUSP00000039206; -.
DR PeptideAtlas; Q3U0D9; -.
DR ProteomicsDB; 270881; -. [Q3U0D9-1]
DR ProteomicsDB; 270882; -. [Q3U0D9-2]
DR ProteomicsDB; 270883; -. [Q3U0D9-3]
DR ProteomicsDB; 270884; -. [Q3U0D9-4]
DR Pumba; Q3U0D9; -.
DR Antibodypedia; 32098; 308 antibodies from 27 providers.
DR DNASU; 209462; -.
DR Ensembl; ENSMUST00000037044.13; ENSMUSP00000039206.7; ENSMUSG00000038822.16. [Q3U0D9-1]
DR GeneID; 209462; -.
DR KEGG; mmu:209462; -.
DR UCSC; uc007fad.2; mouse. [Q3U0D9-1]
DR AGR; MGI:2446110; -.
DR CTD; 57531; -.
DR MGI; MGI:2446110; Hace1.
DR VEuPathDB; HostDB:ENSMUSG00000038822; -.
DR eggNOG; KOG0939; Eukaryota.
DR eggNOG; KOG4177; Eukaryota.
DR GeneTree; ENSGT00940000155839; -.
DR HOGENOM; CLU_015878_0_0_1; -.
DR InParanoid; Q3U0D9; -.
DR OMA; MPEIDVM; -.
DR OrthoDB; 5480520at2759; -.
DR PhylomeDB; Q3U0D9; -.
DR TreeFam; TF323417; -.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 209462; 5 hits in 77 CRISPR screens.
DR ChiTaRS; Hace1; mouse.
DR PRO; PR:Q3U0D9; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q3U0D9; Protein.
DR Bgee; ENSMUSG00000038822; Expressed in piriform cortex and 251 other cell types or tissues.
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: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: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; Ankyrin repeat-containing domain; 2.
DR Gene3D; 3.30.2160.10; Hect, E3 ligase catalytic domain; 1.
DR Gene3D; 3.30.2410.10; Hect, E3 ligase catalytic domain; 1.
DR Gene3D; 3.90.1750.10; Hect, E3 ligase catalytic domains; 1.
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 PANTHER; PTHR11254:SF363; E3 UBIQUITIN-PROTEIN LIGASE HACE1; 1.
DR PANTHER; PTHR11254; HECT DOMAIN UBIQUITIN-PROTEIN LIGASE; 1.
DR Pfam; PF12796; Ank_2; 2.
DR Pfam; PF13857; Ank_5; 1.
DR Pfam; PF00632; HECT; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 6.
DR SMART; SM00119; HECTc; 1.
DR SUPFAM; SSF48403; Ankyrin repeat; 1.
DR SUPFAM; SSF56204; Hect, E3 ligase catalytic domain; 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; Cytoplasm;
KW Endoplasmic reticulum; Golgi apparatus; Membrane; Reference proteome;
KW Repeat; Transcription; Transcription regulation; Transferase;
KW Ubl conjugation pathway.
FT CHAIN 1..909
FT /note="E3 ubiquitin-protein ligase HACE1"
FT /id="PRO_0000280623"
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 398..433
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"
FT VAR_SEQ 738..781
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.4"
FT /id="VSP_023832"
FT VAR_SEQ 814..832
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_042379"
FT VAR_SEQ 838
FT /note="S -> R (in isoform 2)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_023833"
FT VAR_SEQ 839..909
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_023834"
FT CONFLICT 92
FT /note="N -> S (in Ref. 1; BAC31390)"
FT /evidence="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
//
