Full text data of HACE1
HACE1
(KIAA1320)
[Confidence: low (only semi-automatic identification from reviews)]
E3 ubiquitin-protein ligase HACE1; 6.3.2.- (HECT domain and ankyrin repeat-containing E3 ubiquitin-protein ligase 1)
E3 ubiquitin-protein ligase HACE1; 6.3.2.- (HECT domain and ankyrin repeat-containing E3 ubiquitin-protein ligase 1)
UniProt
Q8IYU2
ID HACE1_HUMAN Reviewed; 909 AA.
AC Q8IYU2; A8K6U5; B3KY89; B4DFM6; B4DTQ4; B7Z9X6; E9PGP0; Q5VU99;
read moreAC Q5VUA0; Q8ND12; Q9P2M6;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-2007, sequence version 2.
DT 22-JAN-2014, entry version 101.
DE RecName: Full=E3 ubiquitin-protein ligase HACE1;
DE EC=6.3.2.-;
DE AltName: Full=HECT domain and ankyrin repeat-containing E3 ubiquitin-protein ligase 1;
GN Name=HACE1; Synonyms=KIAA1320;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.
RT The complete sequences of 150 new cDNA clones from brain which code
RT for large 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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA 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.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., 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
RP HIS-17 AND 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, MUTAGENESIS OF
RP CYS-876, INTERACTION WITH THE 20S CORE PROTEASOMAL SUBUNIT,
RP SUBCELLULAR LOCATION, 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-
RT protein ligase, Hace1, in sporadic Wilms' tumor versus normal
RT 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.,
RA Abbaszadeh F., Pritchard-Jones K., Cole R., Pizer B., Stiller C.,
RA Vujanic G., Scott R.H., Stratton M.R., Rahman N.;
RT "Constitutional translocation breakpoint mapping by genome-wide
RT paired-end sequencing identifies HACE1 as a putative Wilms tumour
RT susceptibility 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
RP INTERACTION 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.,
RA Wang Y.;
RT "The ubiquitin ligase HACE1 regulates Golgi membrane dynamics during
RT the 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.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
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. May also act as a transcription regulator via
CC its interaction with RARB.
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
CC or RAB11B); in a GTP-dependent manner. Interacts with RAC1; in a
CC GTP-dependent manner. Interacts with the 26S proteasomal complex
CC through the 20S core proteasomal subunit.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane.
CC Cytoplasm. Endoplasmic reticulum. Note=A significant portion
CC localizes to the endoplasmic reticulum. Targeted to Golgi membrane
CC via its interaction 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 Note=No experimental confirmation available;
CC Name=4;
CC IsoId=Q8IYU2-4; Sequence=VSP_042378;
CC -!- TISSUE SPECIFICITY: Expressed in multiple tissues including heart,
CC brain and kidney.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal and pediatric kidney
CC cells.
CC -!- INDUCTION: Down-regulated in sporadic Wilms tumor.
CC -!- DISEASE: Note=Defects in HACE1 are a cause of Wilms tumor (WT). WT
CC is a pediatric malignancy of kidney and one of the most common
CC solid cancers in childhood. HACE1 is epigenetically down-regulated
CC in sporadic Wilms tumor. Moreover, a t(5;6)(q21;q21) translocation
CC that truncates HACE1 has been found in a child with bilateral,
CC young-onset Wilms tumor.
CC -!- SIMILARITY: Contains 6 ANK repeats.
CC -!- SIMILARITY: Contains 1 HECT (E6AP-type E3 ubiquitin-protein
CC ligase) domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA92558.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=BAG57487.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BAG62066.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BAH14462.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=CAH71890.1; Type=Erroneous gene model prediction;
CC Sequence=CAH74024.1; Type=Erroneous gene model prediction;
CC Sequence=CAI16815.1; Type=Erroneous gene model prediction;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/HACE1ID44285ch6q16.html";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs 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; AL513472; CAH71889.1; -; Genomic_DNA.
DR EMBL; AL590402; CAH71889.1; JOINED; Genomic_DNA.
DR EMBL; AL513472; CAH71890.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL357315; CAH71890.1; JOINED; Genomic_DNA.
DR EMBL; AL590402; CAH71890.1; JOINED; Genomic_DNA.
DR EMBL; AL590402; CAH74023.1; -; Genomic_DNA.
DR EMBL; AL513472; CAH74023.1; JOINED; Genomic_DNA.
DR EMBL; AL590402; CAH74024.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL357315; CAH74024.1; JOINED; Genomic_DNA.
DR EMBL; AL513472; CAH74024.1; JOINED; Genomic_DNA.
DR EMBL; AL357315; CAI16815.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL590402; CAI16815.1; JOINED; Genomic_DNA.
DR EMBL; AL513472; CAI16815.1; JOINED; Genomic_DNA.
DR EMBL; BC034982; AAH34982.1; -; mRNA.
DR RefSeq; NP_065822.2; NM_020771.3.
DR RefSeq; XP_005267129.1; XM_005267072.1.
DR UniGene; Hs.434340; -.
DR ProteinModelPortal; Q8IYU2; -.
DR SMR; Q8IYU2; 25-321, 578-899.
DR IntAct; Q8IYU2; 2.
DR STRING; 9606.ENSP00000262903; -.
DR PhosphoSite; Q8IYU2; -.
DR DMDM; 134034136; -.
DR PaxDb; Q8IYU2; -.
DR PRIDE; Q8IYU2; -.
DR DNASU; 57531; -.
DR Ensembl; ENST00000262903; ENSP00000262903; ENSG00000085382.
DR Ensembl; ENST00000369125; ENSP00000358121; ENSG00000085382.
DR GeneID; 57531; -.
DR KEGG; hsa:57531; -.
DR UCSC; uc003pqu.1; human.
DR CTD; 57531; -.
DR GeneCards; GC06M105221; -.
DR H-InvDB; HIX0006095; -.
DR HGNC; HGNC:21033; HACE1.
DR MIM; 610876; gene.
DR neXtProt; NX_Q8IYU2; -.
DR Orphanet; 635; Neuroblastoma.
DR PharmGKB; PA134983914; -.
DR eggNOG; COG0666; -.
DR HOGENOM; HOG000208454; -.
DR HOVERGEN; HBG004134; -.
DR InParanoid; Q8IYU2; -.
DR KO; K12166; -.
DR OMA; TCEILIQ; -.
DR OrthoDB; EOG73JKTP; -.
DR PhylomeDB; Q8IYU2; -.
DR UniPathway; UPA00143; -.
DR GenomeRNAi; 57531; -.
DR NextBio; 63936; -.
DR PRO; PR:Q8IYU2; -.
DR ArrayExpress; Q8IYU2; -.
DR Bgee; Q8IYU2; -.
DR CleanEx; HS_HACE1; -.
DR Genevestigator; Q8IYU2; -.
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; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:RefGenome.
DR GO; GO:0017137; F:Rab GTPase binding; IDA:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein ligase 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:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; 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:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR020683; Ankyrin_rpt-contain_dom.
DR InterPro; IPR000569; HECT.
DR Pfam; PF12796; Ank_2; 2.
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;
KW Chromosomal rearrangement; Complete proteome; Cytoplasm;
KW Endoplasmic reticulum; Golgi apparatus; Ligase; Membrane;
KW Polymorphism; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Ubl conjugation pathway.
FT CHAIN 1 909 E3 ubiquitin-protein ligase HACE1.
FT /FTId=PRO_0000280622.
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.
FT ACT_SITE 876 876 Glycyl thioester intermediate.
FT VAR_SEQ 1 591 Missing (in isoform 2).
FT /FTId=VSP_023829.
FT VAR_SEQ 1 357 Missing (in isoform 3).
FT /FTId=VSP_023830.
FT VAR_SEQ 358 358 K -> MMFKKHFCFSQ (in isoform 3).
FT /FTId=VSP_023831.
FT VAR_SEQ 523 737 Missing (in isoform 4).
FT /FTId=VSP_042378.
FT VARIANT 17 17 R -> H (in dbSNP:rs17853353).
FT /FTId=VAR_031180.
FT VARIANT 374 374 I -> T (in dbSNP:rs17857038).
FT /FTId=VAR_031181.
FT MUTAGEN 876 876 C->A,S: Loss of E3 ubiquitin ligase
FT activity.
FT CONFLICT 132 132 L -> P (in Ref. 3; BAG54751).
FT CONFLICT 299 299 A -> S (in Ref. 3; BAG54751).
FT CONFLICT 581 581 G -> E (in Ref. 3; BAH14462).
FT CONFLICT 875 875 T -> A (in Ref. 3; BAF84449).
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
//
ID HACE1_HUMAN Reviewed; 909 AA.
AC Q8IYU2; A8K6U5; B3KY89; B4DFM6; B4DTQ4; B7Z9X6; E9PGP0; Q5VU99;
read moreAC Q5VUA0; Q8ND12; Q9P2M6;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-2007, sequence version 2.
DT 22-JAN-2014, entry version 101.
DE RecName: Full=E3 ubiquitin-protein ligase HACE1;
DE EC=6.3.2.-;
DE AltName: Full=HECT domain and ankyrin repeat-containing E3 ubiquitin-protein ligase 1;
GN Name=HACE1; Synonyms=KIAA1320;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.
RT The complete sequences of 150 new cDNA clones from brain which code
RT for large 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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA 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.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., 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
RP HIS-17 AND 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, MUTAGENESIS OF
RP CYS-876, INTERACTION WITH THE 20S CORE PROTEASOMAL SUBUNIT,
RP SUBCELLULAR LOCATION, 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-
RT protein ligase, Hace1, in sporadic Wilms' tumor versus normal
RT 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.,
RA Abbaszadeh F., Pritchard-Jones K., Cole R., Pizer B., Stiller C.,
RA Vujanic G., Scott R.H., Stratton M.R., Rahman N.;
RT "Constitutional translocation breakpoint mapping by genome-wide
RT paired-end sequencing identifies HACE1 as a putative Wilms tumour
RT susceptibility 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
RP INTERACTION 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.,
RA Wang Y.;
RT "The ubiquitin ligase HACE1 regulates Golgi membrane dynamics during
RT the 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.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
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. May also act as a transcription regulator via
CC its interaction with RARB.
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
CC or RAB11B); in a GTP-dependent manner. Interacts with RAC1; in a
CC GTP-dependent manner. Interacts with the 26S proteasomal complex
CC through the 20S core proteasomal subunit.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane.
CC Cytoplasm. Endoplasmic reticulum. Note=A significant portion
CC localizes to the endoplasmic reticulum. Targeted to Golgi membrane
CC via its interaction 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 Note=No experimental confirmation available;
CC Name=4;
CC IsoId=Q8IYU2-4; Sequence=VSP_042378;
CC -!- TISSUE SPECIFICITY: Expressed in multiple tissues including heart,
CC brain and kidney.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal and pediatric kidney
CC cells.
CC -!- INDUCTION: Down-regulated in sporadic Wilms tumor.
CC -!- DISEASE: Note=Defects in HACE1 are a cause of Wilms tumor (WT). WT
CC is a pediatric malignancy of kidney and one of the most common
CC solid cancers in childhood. HACE1 is epigenetically down-regulated
CC in sporadic Wilms tumor. Moreover, a t(5;6)(q21;q21) translocation
CC that truncates HACE1 has been found in a child with bilateral,
CC young-onset Wilms tumor.
CC -!- SIMILARITY: Contains 6 ANK repeats.
CC -!- SIMILARITY: Contains 1 HECT (E6AP-type E3 ubiquitin-protein
CC ligase) domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA92558.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC Sequence=BAG57487.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BAG62066.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=BAH14462.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=CAH71890.1; Type=Erroneous gene model prediction;
CC Sequence=CAH74024.1; Type=Erroneous gene model prediction;
CC Sequence=CAI16815.1; Type=Erroneous gene model prediction;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/HACE1ID44285ch6q16.html";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs 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; AL513472; CAH71889.1; -; Genomic_DNA.
DR EMBL; AL590402; CAH71889.1; JOINED; Genomic_DNA.
DR EMBL; AL513472; CAH71890.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL357315; CAH71890.1; JOINED; Genomic_DNA.
DR EMBL; AL590402; CAH71890.1; JOINED; Genomic_DNA.
DR EMBL; AL590402; CAH74023.1; -; Genomic_DNA.
DR EMBL; AL513472; CAH74023.1; JOINED; Genomic_DNA.
DR EMBL; AL590402; CAH74024.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL357315; CAH74024.1; JOINED; Genomic_DNA.
DR EMBL; AL513472; CAH74024.1; JOINED; Genomic_DNA.
DR EMBL; AL357315; CAI16815.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL590402; CAI16815.1; JOINED; Genomic_DNA.
DR EMBL; AL513472; CAI16815.1; JOINED; Genomic_DNA.
DR EMBL; BC034982; AAH34982.1; -; mRNA.
DR RefSeq; NP_065822.2; NM_020771.3.
DR RefSeq; XP_005267129.1; XM_005267072.1.
DR UniGene; Hs.434340; -.
DR ProteinModelPortal; Q8IYU2; -.
DR SMR; Q8IYU2; 25-321, 578-899.
DR IntAct; Q8IYU2; 2.
DR STRING; 9606.ENSP00000262903; -.
DR PhosphoSite; Q8IYU2; -.
DR DMDM; 134034136; -.
DR PaxDb; Q8IYU2; -.
DR PRIDE; Q8IYU2; -.
DR DNASU; 57531; -.
DR Ensembl; ENST00000262903; ENSP00000262903; ENSG00000085382.
DR Ensembl; ENST00000369125; ENSP00000358121; ENSG00000085382.
DR GeneID; 57531; -.
DR KEGG; hsa:57531; -.
DR UCSC; uc003pqu.1; human.
DR CTD; 57531; -.
DR GeneCards; GC06M105221; -.
DR H-InvDB; HIX0006095; -.
DR HGNC; HGNC:21033; HACE1.
DR MIM; 610876; gene.
DR neXtProt; NX_Q8IYU2; -.
DR Orphanet; 635; Neuroblastoma.
DR PharmGKB; PA134983914; -.
DR eggNOG; COG0666; -.
DR HOGENOM; HOG000208454; -.
DR HOVERGEN; HBG004134; -.
DR InParanoid; Q8IYU2; -.
DR KO; K12166; -.
DR OMA; TCEILIQ; -.
DR OrthoDB; EOG73JKTP; -.
DR PhylomeDB; Q8IYU2; -.
DR UniPathway; UPA00143; -.
DR GenomeRNAi; 57531; -.
DR NextBio; 63936; -.
DR PRO; PR:Q8IYU2; -.
DR ArrayExpress; Q8IYU2; -.
DR Bgee; Q8IYU2; -.
DR CleanEx; HS_HACE1; -.
DR Genevestigator; Q8IYU2; -.
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; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:RefGenome.
DR GO; GO:0017137; F:Rab GTPase binding; IDA:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein ligase 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:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; 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:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR020683; Ankyrin_rpt-contain_dom.
DR InterPro; IPR000569; HECT.
DR Pfam; PF12796; Ank_2; 2.
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;
KW Chromosomal rearrangement; Complete proteome; Cytoplasm;
KW Endoplasmic reticulum; Golgi apparatus; Ligase; Membrane;
KW Polymorphism; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Ubl conjugation pathway.
FT CHAIN 1 909 E3 ubiquitin-protein ligase HACE1.
FT /FTId=PRO_0000280622.
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.
FT ACT_SITE 876 876 Glycyl thioester intermediate.
FT VAR_SEQ 1 591 Missing (in isoform 2).
FT /FTId=VSP_023829.
FT VAR_SEQ 1 357 Missing (in isoform 3).
FT /FTId=VSP_023830.
FT VAR_SEQ 358 358 K -> MMFKKHFCFSQ (in isoform 3).
FT /FTId=VSP_023831.
FT VAR_SEQ 523 737 Missing (in isoform 4).
FT /FTId=VSP_042378.
FT VARIANT 17 17 R -> H (in dbSNP:rs17853353).
FT /FTId=VAR_031180.
FT VARIANT 374 374 I -> T (in dbSNP:rs17857038).
FT /FTId=VAR_031181.
FT MUTAGEN 876 876 C->A,S: Loss of E3 ubiquitin ligase
FT activity.
FT CONFLICT 132 132 L -> P (in Ref. 3; BAG54751).
FT CONFLICT 299 299 A -> S (in Ref. 3; BAG54751).
FT CONFLICT 581 581 G -> E (in Ref. 3; BAH14462).
FT CONFLICT 875 875 T -> A (in Ref. 3; BAF84449).
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
//
MIM
610876
*RECORD*
*FIELD* NO
610876
*FIELD* TI
*610876 HECT DOMAIN- AND ANKYRIN REPEAT-CONTAINING E3 UBIQUITIN PROTEIN LIGASE
1; HACE1
read more;;KIAA1320
*FIELD* TX
CLONING
By sequencing clones obtained from a fetal brain cDNA library, Nagase et
al. (2000) cloned HACE1, which they designated KIAA1320. RT-PCR ELISA
detected moderate expression in all regions of the brain examined and in
lung, kidney, testis, and ovary, with low expression in heart, liver,
skeletal muscle, pancreas, and spleen.
Fernandez et al. (2001) identified a balanced t6;15(q21;q21)
translocation in a Wilms tumor (194070) from a 6-month old infant. By
database analysis of the chromosome 6q21 breakpoint region, Anglesio et
al. (2004) identified HACE1. The predicted 909-amino acid protein has a
calculated molecular mass of about 103 kD and contains 6 N-terminal
ankyrin repeats and a C-terminal HECT domain. Northern blot analysis of
human tissues detected a 4.6-kb transcript with strong expression in
heart, brain, placenta, pancreas, and adult and fetal kidney. By
subcellular fractionation and immunofluorescence studies in NIH3T3
fibroblasts, the authors found that HACE1 localized primarily to
endoplasmic reticulum and the cytoplasm with small amounts of endogenous
protein present in other fractions.
GENE FUNCTION
By in vitro and in vivo studies, Anglesio et al. (2004) showed that
HACE1 has ubiquitin ligase activity, utilizing UBCH7 (UBE2L3; 603721) as
a candidate partner E2 enzyme. HACE1 associated with ubiquitinated
proteins and components of the 26S proteasomal complex (see 602706),
indicating that at least some proteins targeted for ubiquitination by
HACE1 are degraded by the proteasome.
Zhang et al. (2007) demonstrated that the E3 ubiquitin ligase HACE1 is
frequently downregulated in human tumors and maps to a region of
chromosome 6q21 implicated in multiple human cancers. Genetic
inactivation of HACE1 in mice resulted in the development of
spontaneous, late-onset cancer. A second hit from either environmental
triggers or genetic heterozygosity of another tumor suppressor, p53
(191170), markedly increased tumor incidence in a Hace1-deficient
background. Reexpression of HACE1 in human tumor cells directly
abrogated in vitro and in vivo tumor growth, whereas downregulation of
HACE1 via siRNA allowed nontumorigenic human cells to form tumors in
vivo. Mechanistically, the tumor suppressor function of HACE1 is
dependent on its E3 ligase activity, and HACE1 controls
adhesion-dependent growth and cell cycle progression during cell stress
through degradation of cyclin D1 (168461). Thus, Zhang et al. (2007)
concluded that HACE1 is a candidate chromosome 6q21 tumor suppressor
gene involved in multiple cancers.
GENE STRUCTURE
Anglesio et al. (2004) determined that the HACE1 gene contains 24 exons.
MAPPING
By sequence and database analysis of the chromosome 6q21 breakpoint
reported by Fernandez et al. (2001), Anglesio et al. (2004) mapped the
HACE1 gene to 50 kB downstream from the breakpoint. Zhang et al. (2007)
noted that this region is frequently deleted in a wide spectrum of tumor
types.
MOLECULAR GENETICS
Anglesio et al. (2004) analyzed the chromosome 6q21 breakpoint of a
nonconstitutional t(6;15)(q21;q21) rearrangement in a sporadic Wilms
tumor. Although the HACE1 locus was not directly interrupted by the
translocation in the index Wilms case, HACE1 expression was markedly
lower in tumor tissue compared with adjacent normal kidney. HACE1
expression was virtually undetectable in the SK-NEP-1 Wilms tumor cell
line and in 4 of 5 additional primary Wilms tumor cases compared with
patient-matched normal kidney. There was no evidence of HACE1 mutation
or deletion, but hypermethylation of 2 upstream CpG islands correlated
with low HACE1 expression in tumor samples.
Slade et al. (2010) identified a constitutional de novo balanced
translocation t(5;6)(q21;q21) in a boy who developed bilateral Wilms
tumor at age 6 months. Breakpoint analysis showed that the translocation
transected intron 6 of the HACE1 gene. Further analysis of the HACE1
gene in 450 individuals with Wilms tumor identified 1 patient with a
constitutional truncating mutation (W364X) who inherited the mutation
from her unaffected mother, suggesting either reduced penetrance or that
the mutation was an unrelated finding. Slade et al. (2010) concluded
that abrogation of HACE1 activity may predispose to the development of
Wilms tumor, although HACE1 mutation is rare and makes only a small
contribution to disease incidence.
*FIELD* RF
1. Anglesio, M. S.; Evdokimova, V.; Melnyk, N.; Zhang, L.; Fernandez,
C. V.; Grundy, P. E.; Leach, S.; Marra, M. A.; Brooks-Wilson, A. R.;
Penninger, J.; Sorensen, P. H. B.: Differential expression of a novel
ankyrin containing E3 ubiquitin-protein ligase, Hace1, in sporadic
Wilms' tumor versus normal kidney. Hum. Molec. Genet. 13: 2061-2074,
2004.
2. Fernandez, C. V.; Lestou, V. S.; Wildish, J.; Lee, C. L. Y.; Sorensen,
P. H. B.: Detection of a novel t(6;15)(q21;q21) in a pediatric Wilms
tumor. Cancer Genet. Cytogenet. 129: 165-167, 2001.
3. Nagase, T.; Kikuno, R.; Ishikawa, K.; Hirosawa, M.; Ohara, O.:
Prediction of the coding sequences of unidentified human genes. XVI.
The complete sequences of 150 new cDNA clones from brain which code
for large proteins in vitro. DNA Res. 7: 65-73, 2000.
4. Slade, I.; Stephens, P.; Douglas, J.; Barker, K.; Stebbings, L.;
Abbaszadeh, F.; Pritchard-Jones, K.; FACT Collaboration; Cole, R.;
Pizer, B.; Stiller, C.; Vujanic, G.; Scott, R. H.; Stratton, M. R.;
Rahman, N.: Constitutional translocation breakpoint mapping by genome-wide
paired-end sequencing identifies HACE1 as a putative Wilms tumour
susceptibility gene. J. Med. Genet. 47: 342-347, 2010.
5. Zhang, L.; Anglesio, M. S.; O'Sullivan, M.; Zhang, F.; Yang, G.;
Sarao, R.; Nghiem, M. P.; Cronin, S.; Hara, H.; Melnyk, N.; Li, L.;
Wada, T.; Liu, P. P.; Farrar, J.; Arceci, R. J.; Sorensen, P. H.;
Penninger, J. M.: The E3 ligase HACE1 is a critical chromosome 6q21
tumor suppressor involved in multiple cancers. Nature Med. 13: 1060-1069,
2007.
*FIELD* CN
Cassandra L. Kniffin - updated: 6/3/2010
Patricia A. Hartz - updated: 3/26/2008
*FIELD* CD
George E. Tiller: 3/23/2007
*FIELD* ED
wwang: 06/07/2010
ckniffin: 6/3/2010
alopez: 3/27/2008
terry: 3/26/2008
wwang: 3/23/2007
*RECORD*
*FIELD* NO
610876
*FIELD* TI
*610876 HECT DOMAIN- AND ANKYRIN REPEAT-CONTAINING E3 UBIQUITIN PROTEIN LIGASE
1; HACE1
read more;;KIAA1320
*FIELD* TX
CLONING
By sequencing clones obtained from a fetal brain cDNA library, Nagase et
al. (2000) cloned HACE1, which they designated KIAA1320. RT-PCR ELISA
detected moderate expression in all regions of the brain examined and in
lung, kidney, testis, and ovary, with low expression in heart, liver,
skeletal muscle, pancreas, and spleen.
Fernandez et al. (2001) identified a balanced t6;15(q21;q21)
translocation in a Wilms tumor (194070) from a 6-month old infant. By
database analysis of the chromosome 6q21 breakpoint region, Anglesio et
al. (2004) identified HACE1. The predicted 909-amino acid protein has a
calculated molecular mass of about 103 kD and contains 6 N-terminal
ankyrin repeats and a C-terminal HECT domain. Northern blot analysis of
human tissues detected a 4.6-kb transcript with strong expression in
heart, brain, placenta, pancreas, and adult and fetal kidney. By
subcellular fractionation and immunofluorescence studies in NIH3T3
fibroblasts, the authors found that HACE1 localized primarily to
endoplasmic reticulum and the cytoplasm with small amounts of endogenous
protein present in other fractions.
GENE FUNCTION
By in vitro and in vivo studies, Anglesio et al. (2004) showed that
HACE1 has ubiquitin ligase activity, utilizing UBCH7 (UBE2L3; 603721) as
a candidate partner E2 enzyme. HACE1 associated with ubiquitinated
proteins and components of the 26S proteasomal complex (see 602706),
indicating that at least some proteins targeted for ubiquitination by
HACE1 are degraded by the proteasome.
Zhang et al. (2007) demonstrated that the E3 ubiquitin ligase HACE1 is
frequently downregulated in human tumors and maps to a region of
chromosome 6q21 implicated in multiple human cancers. Genetic
inactivation of HACE1 in mice resulted in the development of
spontaneous, late-onset cancer. A second hit from either environmental
triggers or genetic heterozygosity of another tumor suppressor, p53
(191170), markedly increased tumor incidence in a Hace1-deficient
background. Reexpression of HACE1 in human tumor cells directly
abrogated in vitro and in vivo tumor growth, whereas downregulation of
HACE1 via siRNA allowed nontumorigenic human cells to form tumors in
vivo. Mechanistically, the tumor suppressor function of HACE1 is
dependent on its E3 ligase activity, and HACE1 controls
adhesion-dependent growth and cell cycle progression during cell stress
through degradation of cyclin D1 (168461). Thus, Zhang et al. (2007)
concluded that HACE1 is a candidate chromosome 6q21 tumor suppressor
gene involved in multiple cancers.
GENE STRUCTURE
Anglesio et al. (2004) determined that the HACE1 gene contains 24 exons.
MAPPING
By sequence and database analysis of the chromosome 6q21 breakpoint
reported by Fernandez et al. (2001), Anglesio et al. (2004) mapped the
HACE1 gene to 50 kB downstream from the breakpoint. Zhang et al. (2007)
noted that this region is frequently deleted in a wide spectrum of tumor
types.
MOLECULAR GENETICS
Anglesio et al. (2004) analyzed the chromosome 6q21 breakpoint of a
nonconstitutional t(6;15)(q21;q21) rearrangement in a sporadic Wilms
tumor. Although the HACE1 locus was not directly interrupted by the
translocation in the index Wilms case, HACE1 expression was markedly
lower in tumor tissue compared with adjacent normal kidney. HACE1
expression was virtually undetectable in the SK-NEP-1 Wilms tumor cell
line and in 4 of 5 additional primary Wilms tumor cases compared with
patient-matched normal kidney. There was no evidence of HACE1 mutation
or deletion, but hypermethylation of 2 upstream CpG islands correlated
with low HACE1 expression in tumor samples.
Slade et al. (2010) identified a constitutional de novo balanced
translocation t(5;6)(q21;q21) in a boy who developed bilateral Wilms
tumor at age 6 months. Breakpoint analysis showed that the translocation
transected intron 6 of the HACE1 gene. Further analysis of the HACE1
gene in 450 individuals with Wilms tumor identified 1 patient with a
constitutional truncating mutation (W364X) who inherited the mutation
from her unaffected mother, suggesting either reduced penetrance or that
the mutation was an unrelated finding. Slade et al. (2010) concluded
that abrogation of HACE1 activity may predispose to the development of
Wilms tumor, although HACE1 mutation is rare and makes only a small
contribution to disease incidence.
*FIELD* RF
1. Anglesio, M. S.; Evdokimova, V.; Melnyk, N.; Zhang, L.; Fernandez,
C. V.; Grundy, P. E.; Leach, S.; Marra, M. A.; Brooks-Wilson, A. R.;
Penninger, J.; Sorensen, P. H. B.: Differential expression of a novel
ankyrin containing E3 ubiquitin-protein ligase, Hace1, in sporadic
Wilms' tumor versus normal kidney. Hum. Molec. Genet. 13: 2061-2074,
2004.
2. Fernandez, C. V.; Lestou, V. S.; Wildish, J.; Lee, C. L. Y.; Sorensen,
P. H. B.: Detection of a novel t(6;15)(q21;q21) in a pediatric Wilms
tumor. Cancer Genet. Cytogenet. 129: 165-167, 2001.
3. Nagase, T.; Kikuno, R.; Ishikawa, K.; Hirosawa, M.; Ohara, O.:
Prediction of the coding sequences of unidentified human genes. XVI.
The complete sequences of 150 new cDNA clones from brain which code
for large proteins in vitro. DNA Res. 7: 65-73, 2000.
4. Slade, I.; Stephens, P.; Douglas, J.; Barker, K.; Stebbings, L.;
Abbaszadeh, F.; Pritchard-Jones, K.; FACT Collaboration; Cole, R.;
Pizer, B.; Stiller, C.; Vujanic, G.; Scott, R. H.; Stratton, M. R.;
Rahman, N.: Constitutional translocation breakpoint mapping by genome-wide
paired-end sequencing identifies HACE1 as a putative Wilms tumour
susceptibility gene. J. Med. Genet. 47: 342-347, 2010.
5. Zhang, L.; Anglesio, M. S.; O'Sullivan, M.; Zhang, F.; Yang, G.;
Sarao, R.; Nghiem, M. P.; Cronin, S.; Hara, H.; Melnyk, N.; Li, L.;
Wada, T.; Liu, P. P.; Farrar, J.; Arceci, R. J.; Sorensen, P. H.;
Penninger, J. M.: The E3 ligase HACE1 is a critical chromosome 6q21
tumor suppressor involved in multiple cancers. Nature Med. 13: 1060-1069,
2007.
*FIELD* CN
Cassandra L. Kniffin - updated: 6/3/2010
Patricia A. Hartz - updated: 3/26/2008
*FIELD* CD
George E. Tiller: 3/23/2007
*FIELD* ED
wwang: 06/07/2010
ckniffin: 6/3/2010
alopez: 3/27/2008
terry: 3/26/2008
wwang: 3/23/2007