ID HACE1_HUMAN Reviewed; 909 AA. AC Q8IYU2; A8K6U5; B3KY89; B4DFM6; B4DTQ4; B7Z9X6; E9PGP0; Q5VU99; Q5VUA0; AC Q8ND12; Q9P2M6; DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot. DT 20-MAR-2007, sequence version 2. DT 24-JAN-2024, entry version 174. 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 Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain; RX PubMed=10718198; DOI=10.1093/dnares/7.1.65; RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XVI. The RT complete sequences of 150 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 7:65-73(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4). RC TISSUE=Amygdala, Placenta, and Thalamus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS HIS-17 AND RP THR-374. RC TISSUE=Testis; 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 [6] RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, MUTAGENESIS OF CYS-876, RP INTERACTION WITH THE 20S CORE PROTEASOMAL SUBUNIT, SUBCELLULAR LOCATION, RP AND INDUCTION. RX PubMed=15254018; DOI=10.1093/hmg/ddh215; RA Anglesio M.S., Evdokimova V., Melnyk N., Zhang L., Fernandez C.V., RA Grundy P.E., Leach S., Marra M.A., Brooks-Wilson A.R., Penninger J., RA Sorensen P.H.B.; RT "Differential expression of a novel ankyrin containing E3 ubiquitin-protein RT ligase, Hace1, in sporadic Wilms' tumor versus normal kidney."; RL Hum. Mol. Genet. 13:2061-2074(2004). RN [7] RP INVOLVEMENT IN WILMS TUMOR, AND INDUCTION. 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 [8] RP INVOLVEMENT IN WILMS TUMOR, AND CHROMOSOMAL TRANSLOCATION. RX PubMed=19948536; DOI=10.1136/jmg.2009.072983; RA Slade I., Stephens P., Douglas J., Barker K., Stebbings L., Abbaszadeh F., RA Pritchard-Jones K., Cole R., Pizer B., Stiller C., Vujanic G., Scott R.H., RA Stratton M.R., Rahman N.; RT "Constitutional translocation breakpoint mapping by genome-wide paired-end RT sequencing identifies HACE1 as a putative Wilms tumour susceptibility RT gene."; RL J. Med. Genet. 47:342-347(2010). RN [9] RP FUNCTION, AND MUTAGENESIS OF CYS-876. RX PubMed=22036506; DOI=10.1016/j.devcel.2011.08.015; RA Torrino S., Visvikis O., Doye A., Boyer L., Stefani C., Munro P., RA Bertoglio J., Gacon G., Mettouchi A., Lemichez E.; RT "The E3 ubiquitin-ligase HACE1 catalyzes the ubiquitylation of active RT Rac1."; RL Dev. Cell 21:959-965(2011). RN [10] RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-876, AND INTERACTION RP WITH RAB1; RAB4 AND RAB11. RX PubMed=21988917; DOI=10.1038/ncomms1509; RA Tang D., Xiang Y., De Renzis S., Rink J., Zheng G., Zerial M., Wang Y.; RT "The ubiquitin ligase HACE1 regulates Golgi membrane dynamics during the RT cell cycle."; RL Nat. Commun. 2:501-501(2011). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [12] RP INVOLVEMENT IN SPPRS. RX PubMed=26424145; DOI=10.1136/jmedgenet-2015-103344; RA Hollstein R., Parry D.A., Nalbach L., Logan C.V., Strom T.M., Hartill V.L., RA Carr I.M., Korenke G.C., Uppal S., Ahmed M., Wieland T., Markham A.F., RA Bennett C.P., Gillessen-Kaesbach G., Sheridan E.G., Kaiser F.J., RA Bonthron D.T.; RT "HACE1 deficiency causes an autosomal recessive neurodevelopmental RT syndrome."; RL J. Med. Genet. 52:797-803(2015). RN [13] RP INVOLVEMENT IN SPPRS, AND VARIANT SPPRS LEU-832 DEL. RX PubMed=26437029; DOI=10.1038/ng.3410; RG DDD study; RA Akawi N., McRae J., Ansari M., Balasubramanian M., Blyth M., Brady A.F., RA Clayton S., Cole T., Deshpande C., Fitzgerald T.W., Foulds N., Francis R., RA Gabriel G., Gerety S.S., Goodship J., Hobson E., Jones W.D., Joss S., RA King D., Klena N., Kumar A., Lees M., Lelliott C., Lord J., McMullan D., RA O'Regan M., Osio D., Piombo V., Prigmore E., Rajan D., Rosser E., RA Sifrim A., Smith A., Swaminathan G.J., Turnpenny P., Whitworth J., RA Wright C.F., Firth H.V., Barrett J.C., Lo C.W., FitzPatrick D.R., RA Hurles M.E.; RT "Discovery of four recessive developmental disorders using probabilistic RT genotype and phenotype matching among 4,125 families."; RL Nat. Genet. 47:1363-1369(2015). 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:0000269|PubMed:15254018, ECO:0000269|PubMed:21988917, CC ECO:0000269|PubMed:22036506}. 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 (By similarity). Interacts with RAB1 CC (RAB1A, RAB1B or RAB1C), RAB4 (RAB4A or RAB4B) and RAB11 (RAB11A or CC RAB11B); in a GTP-dependent manner. Interacts with RAC1; in a GTP- CC dependent manner. Interacts with the 26S proteasomal complex through CC the 20S core proteasomal subunit. {ECO:0000250|UniProtKB:Q3U0D9, CC ECO:0000269|PubMed:15254018, ECO:0000269|PubMed:21988917}. CC -!- INTERACTION: CC Q8IYU2; Q96CV9: OPTN; NbExp=15; IntAct=EBI-308277, EBI-748974; CC Q8IYU2; P20338: RAB4A; NbExp=3; IntAct=EBI-308277, EBI-722284; CC Q8IYU2; P63000: RAC1; NbExp=5; IntAct=EBI-308277, EBI-413628; CC -!- SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane. Cytoplasm. CC Endoplasmic reticulum. Note=A significant portion localizes to the CC endoplasmic reticulum. Targeted to Golgi membrane via its interaction CC with Rab proteins. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q8IYU2-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8IYU2-2; Sequence=VSP_023829; CC Name=3; CC IsoId=Q8IYU2-3; Sequence=VSP_023830, VSP_023831; CC Name=4; CC IsoId=Q8IYU2-4; Sequence=VSP_042378; CC -!- TISSUE SPECIFICITY: Expressed in multiple tissues including heart, CC brain and kidney. {ECO:0000269|PubMed:15254018}. CC -!- DEVELOPMENTAL STAGE: Expressed in fetal and pediatric kidney cells. CC {ECO:0000269|PubMed:15254018}. CC -!- INDUCTION: Down-regulated in sporadic Wilms tumor. CC {ECO:0000269|PubMed:15254018, ECO:0000269|PubMed:17694067}. CC -!- DISEASE: Note=Defects in HACE1 are a cause of Wilms tumor (WT). WT is a CC pediatric malignancy of kidney and one of the most common solid cancers CC in childhood. HACE1 is epigenetically down-regulated in sporadic Wilms CC tumor. Moreover, a t(5;6)(q21;q21) translocation that truncates HACE1 CC has been found in a child with bilateral, young-onset Wilms tumor CC (PubMed:19948536). {ECO:0000269|PubMed:17694067, CC ECO:0000269|PubMed:19948536}. CC -!- DISEASE: Spastic paraplegia and psychomotor retardation with or without CC seizures (SPPRS) [MIM:616756]: A form of spastic paraplegia, a CC neurodegenerative disorder characterized by a slow, gradual, CC progressive weakness and spasticity of the lower limbs. Rate of CC progression and the severity of symptoms are quite variable. Initial CC symptoms may include difficulty with balance, weakness and stiffness in CC the legs, muscle spasms, and dragging the toes when walking. In some CC forms of the disorder, bladder symptoms (such as incontinence) may CC appear, or the weakness and stiffness may spread to other parts of the CC body. SPPRS is an autosomal recessive neurodevelopmental disorder CC manifesting in infancy. Affected individuals show hypotonia and CC psychomotor retardation. Most develop seizures. CC {ECO:0000269|PubMed:26424145, ECO:0000269|PubMed:26437029}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SEQUENCE CAUTION: CC Sequence=BAA92558.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAG57487.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAG62066.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAH14462.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/44285/HACE1"; 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; AB037741; BAA92558.1; ALT_INIT; mRNA. DR EMBL; AL834202; CAD38890.1; -; mRNA. DR EMBL; AK131207; BAG54751.1; -; mRNA. DR EMBL; AK291760; BAF84449.1; -; mRNA. DR EMBL; AK294164; BAG57487.1; ALT_INIT; mRNA. DR EMBL; AK300314; BAG62066.1; ALT_INIT; mRNA. DR EMBL; AK316091; BAH14462.1; ALT_INIT; mRNA. DR EMBL; AL357315; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL513472; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL590402; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC034982; AAH34982.1; -; mRNA. DR CCDS; CCDS5050.1; -. [Q8IYU2-1] DR RefSeq; NP_001308009.1; NM_001321080.1. DR RefSeq; NP_001308012.1; NM_001321083.1. DR RefSeq; NP_001308013.1; NM_001321084.1. DR RefSeq; NP_065822.2; NM_020771.3. [Q8IYU2-1] DR PDB; 8H8X; EM; 3.92 A; A=1-909. DR PDB; 8HAE; EM; 4.55 A; A/B=1-909. DR PDBsum; 8H8X; -. DR PDBsum; 8HAE; -. DR AlphaFoldDB; Q8IYU2; -. DR EMDB; EMD-34551; -. DR EMDB; EMD-34586; -. DR SMR; Q8IYU2; -. DR BioGRID; 121590; 65. DR IntAct; Q8IYU2; 14. DR MINT; Q8IYU2; -. DR STRING; 9606.ENSP00000262903; -. DR iPTMnet; Q8IYU2; -. DR PhosphoSitePlus; Q8IYU2; -. DR BioMuta; HACE1; -. DR DMDM; 134034136; -. DR EPD; Q8IYU2; -. DR jPOST; Q8IYU2; -. DR MassIVE; Q8IYU2; -. DR MaxQB; Q8IYU2; -. DR PaxDb; 9606-ENSP00000262903; -. DR PeptideAtlas; Q8IYU2; -. DR ProteomicsDB; 71238; -. [Q8IYU2-1] DR ProteomicsDB; 71239; -. [Q8IYU2-2] DR ProteomicsDB; 71240; -. [Q8IYU2-3] DR ProteomicsDB; 71241; -. [Q8IYU2-4] DR Pumba; Q8IYU2; -. DR ABCD; Q8IYU2; 1 sequenced antibody. DR Antibodypedia; 32098; 308 antibodies from 27 providers. DR DNASU; 57531; -. DR Ensembl; ENST00000262903.9; ENSP00000262903.4; ENSG00000085382.12. [Q8IYU2-1] DR Ensembl; ENST00000369125.6; ENSP00000358121.2; ENSG00000085382.12. [Q8IYU2-4] DR GeneID; 57531; -. DR KEGG; hsa:57531; -. DR MANE-Select; ENST00000262903.9; ENSP00000262903.4; NM_020771.4; NP_065822.2. DR UCSC; uc003pqu.1; human. [Q8IYU2-1] DR AGR; HGNC:21033; -. DR CTD; 57531; -. DR DisGeNET; 57531; -. DR GeneCards; HACE1; -. DR HGNC; HGNC:21033; HACE1. DR HPA; ENSG00000085382; Tissue enhanced (placenta). DR MalaCards; HACE1; -. DR MIM; 610876; gene. DR MIM; 616756; phenotype. DR neXtProt; NX_Q8IYU2; -. DR OpenTargets; ENSG00000085382; -. DR Orphanet; 635; Neuroblastoma. DR Orphanet; 464282; Spastic paraplegia-severe developmental delay-epilepsy syndrome. DR PharmGKB; PA134983914; -. DR VEuPathDB; HostDB:ENSG00000085382; -. DR eggNOG; KOG0939; Eukaryota. DR eggNOG; KOG4177; Eukaryota. DR GeneTree; ENSGT00940000155839; -. DR HOGENOM; CLU_015878_0_0_1; -. DR InParanoid; Q8IYU2; -. DR OrthoDB; 5480520at2759; -. DR PhylomeDB; Q8IYU2; -. DR TreeFam; TF323417; -. DR PathwayCommons; Q8IYU2; -. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; Q8IYU2; -. DR SIGNOR; Q8IYU2; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 57531; 20 hits in 1198 CRISPR screens. DR ChiTaRS; HACE1; human. DR GenomeRNAi; 57531; -. DR Pharos; Q8IYU2; Tbio. DR PRO; PR:Q8IYU2; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q8IYU2; Protein. DR Bgee; ENSG00000085382; Expressed in secondary oocyte and 171 other cell types or tissues. DR ExpressionAtlas; Q8IYU2; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA. DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell. DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0031267; F:small GTPase binding; IDA:UniProtKB. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0007030; P:Golgi organization; IDA:UniProtKB. DR GO; GO:0061025; P:membrane fusion; IMP:UniProtKB. DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB. DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central. DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB. DR GO; GO:0016601; P:Rac protein signal transduction; TAS:UniProtKB. DR GO; GO:0030334; P:regulation of cell migration; IMP:UniProtKB. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA: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; 1. DR Pfam; PF13637; Ank_4; 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. DR Genevisible; Q8IYU2; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ANK repeat; Cell cycle; KW Chromosomal rearrangement; Cytoplasm; Disease variant; KW Endoplasmic reticulum; Golgi apparatus; Hereditary spastic paraplegia; KW Membrane; Neurodegeneration; 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_0000280622" 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 VAR_SEQ 1..591 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_023829" FT VAR_SEQ 1..357 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:10718198" FT /id="VSP_023830" FT VAR_SEQ 358 FT /note="K -> MMFKKHFCFSQ (in isoform 3)" FT /evidence="ECO:0000303|PubMed:10718198" FT /id="VSP_023831" FT VAR_SEQ 523..737 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_042378" FT VARIANT 17 FT /note="R -> H (in dbSNP:rs17853353)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_031180" FT VARIANT 374 FT /note="I -> T (in dbSNP:rs17857038)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_031181" FT VARIANT 832 FT /note="Missing (in SPPRS)" FT /evidence="ECO:0000269|PubMed:26437029" FT /id="VAR_076311" FT MUTAGEN 876 FT /note="C->A,S: Loss of E3 ubiquitin ligase activity." FT /evidence="ECO:0000269|PubMed:15254018, FT ECO:0000269|PubMed:21988917, ECO:0000269|PubMed:22036506" FT CONFLICT 132 FT /note="L -> P (in Ref. 3; BAG54751)" FT /evidence="ECO:0000305" FT CONFLICT 299 FT /note="A -> S (in Ref. 3; BAG54751)" FT /evidence="ECO:0000305" FT CONFLICT 581 FT /note="G -> E (in Ref. 3; BAH14462)" FT /evidence="ECO:0000305" FT CONFLICT 875 FT /note="T -> A (in Ref. 3; BAF84449)" FT /evidence="ECO:0000305" SQ SEQUENCE 909 AA; 102342 MW; 8AEC09D9D29DC1D8 CRC64; MERAMEQLNR LTRSLRRART VELPEDNETA VYTLMPMVMA DQHRSVSELL SNSKFDVNYA FGRVKRSLLH IAANCGSVEC LVLLLKKGAN PNYQDISGCT PLHLAARNGQ KKCMSKLLEY SADVNICNNE GLTAIHWLAV NGRTELLHDL VQHVSDVDVE DAMGQTALHV ACQNGHKTTV QCLLDSGADI NRPNVSGATP LYFACSHGQR DTAQILLLRG AKYLPDKNGV TPLDLCVQGG YGETCEVLIQ YHPRLFQTII QMTQNEDLRE NMLRQVLEHL SQQSESQYLK ILTSLAEVAT TNGHKLLSLS SNYDAQMKSL LRIVRMFCHV FRIGPSSPSN GIDMGYNGNK TPRSQVFKPL ELLWHSLDEW LVLIATELMK NKRDSTEITS ILLKQKGQDQ DAASIPPFEP PGPGSYENLS TGTRESKPDA LAGRQEASAD CQDVISMTAN RLSAVIQAFY MCCSCQMPPG MTSPRFIEFV CKHDEVLKCF VNRNPKIIFD HFHFLLECPE LMSRFMHIIK AQPFKDRCEW FYEHLHSGQP DSDMVHRPVN ENDILLVHRD SIFRSSCEVV SKANCAKLKQ GIAVRFHGEE GMGQGVVREW FDILSNEIVN PDYALFTQSA DGTTFQPNSN SYVNPDHLNY FRFAGQILGL ALNHRQLVNI YFTRSFYKHI LGIPVNYQDV ASIDPEYAKN LQWILDNDIS DLGLELTFSV ETDVFGAMEE VPLKPGGGSI LVTQNNKAEY VQLVTELRMT RAIQPQINAF LQGFHMFIPP SLIQLFDEYE LELLLSGMPE IDVSDWIKNT EYTSGYERED PVIQWFWEVV EDITQEERVL LLQFVTGSSR VPHGGFANIM GGSGLQNFTI AAVPYTPNLL PTSSTCINML KLPEYPSKEI LKDRLLVALH CGSYGYTMA //