HACE1_HUMAN
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 03-AUG-2022, entry version 166.
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="http://atlasgeneticsoncology.org/Genes/HACE1ID44285ch6q16.html";
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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 AlphaFoldDB; Q8IYU2; -.
DR SMR; Q8IYU2; -.
DR BioGRID; 121590; 60.
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; Q8IYU2; -.
DR PeptideAtlas; Q8IYU2; -.
DR PRIDE; Q8IYU2; -.
DR ProteomicsDB; 71238; -. [Q8IYU2-1]
DR ProteomicsDB; 71239; -. [Q8IYU2-2]
DR ProteomicsDB; 71240; -. [Q8IYU2-3]
DR ProteomicsDB; 71241; -. [Q8IYU2-4]
DR ABCD; Q8IYU2; 1 sequenced antibody.
DR Antibodypedia; 32098; 241 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 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; 799706at2759; -.
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; 11 hits in 1120 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 170 other tissues.
DR ExpressionAtlas; Q8IYU2; baseline and differential.
DR Genevisible; Q8IYU2; HS.
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:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
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; -; 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; 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; 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; Chromosomal rearrangement;
KW Cytoplasm; Disease variant; Endoplasmic reticulum; Golgi apparatus;
KW Hereditary spastic paraplegia; Membrane; Neurodegeneration;
KW Reference proteome; Repeat; Transcription; Transcription regulation;
KW 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
