Q8IYU2 (HACE1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase HACE1
EC=6.3.2.-

Alternative name(s):
HECT domain and ankyrin repeat-containing E3 ubiquitin-protein ligase 1

Gene names

Name:	HACE1
Synonyms:	KIAA1320

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	909 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	E3 ubiquitin-protein ligase that may function in cellular proteins degradation. Ref.5
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with the 26S proteasomal complex through the 20S core proteasomal subunit. Ref.5
Subcellular location	Cytoplasm. Endoplasmic reticulum. Note: A significant portion localizes to the endoplasmic reticulum. Ref.5
Tissue specificity	Expressed in multiple tissues including heart, brain and kidney. Ref.5
Developmental stage	Expressed in fetal and pediatric kidney cells. Ref.5
Induction	Down-regulated in sporadic Wilms tumor. Ref.5
Sequence similarities	Contains 6 ANK repeats. Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain.
Sequence caution	The sequence BAA92558.1 differs from that shown. Reason: Erroneous initiation. The sequence CAH71890.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAH74024.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI16815.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm Endoplasmic reticulum
Coding sequence diversity	Alternative splicing Polymorphism
Domain	ANK repeat Repeat
Molecular function	Ligase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	protein ubiquitination involved in ubiquitin-dependent protein catabolic process Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ubiquitin-protein ligase activity Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8IYU2-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8IYU2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-591: Missing.

Isoform 3 (identifier: Q8IYU2-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-357: Missing.
     358-358: K → MMFKKHFCFSQ

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 909	909	E3 ubiquitin-protein ligase HACE1		PRO_0000280622
Regions
	Repeat	64 – 93	30	ANK 1
	Repeat	97 – 126	30	ANK 2
	Repeat	130 – 159	30	ANK 3
	Repeat	163 – 192	30	ANK 4
	Repeat	196 – 226	31	ANK 5
	Repeat	228 – 257	30	ANK 6
	Domain	574 – 909	336	HECT
Sites
	Active site	876	1	Glycyl thioester intermediate
Natural variations
	Alternative sequence	1 – 591	591	Missing in isoform 2.		VSP_023829
	Alternative sequence	1 – 357	357	Missing in isoform 3.		VSP_023830
	Alternative sequence	358	1	K → MMFKKHFCFSQ in isoform 3.		VSP_023831
	Natural variant	17	1	R → H. Ref.4 Corresponds to variant rs17853353 [ dbSNP | Ensembl ].		VAR_031180
	Natural variant	374	1	I → T. Ref.4 Corresponds to variant rs17857038 [ dbSNP | Ensembl ].		VAR_031181
Experimental info
	Mutagenesis	876	1	C → S: Loss of E3 ubiquitin ligase activity. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 20, 2007. Version 2. Checksum: 8AEC09D9D29DC1D8	FASTA	909	102,342
	10 20 30 40 50 60 MERAMEQLNR LTRSLRRART VELPEDNETA VYTLMPMVMA DQHRSVSELL SNSKFDVNYA 70 80 90 100 110 120 FGRVKRSLLH IAANCGSVEC LVLLLKKGAN PNYQDISGCT PLHLAARNGQ KKCMSKLLEY 130 140 150 160 170 180 SADVNICNNE GLTAIHWLAV NGRTELLHDL VQHVSDVDVE DAMGQTALHV ACQNGHKTTV 190 200 210 220 230 240 QCLLDSGADI NRPNVSGATP LYFACSHGQR DTAQILLLRG AKYLPDKNGV TPLDLCVQGG 250 260 270 280 290 300 YGETCEVLIQ YHPRLFQTII QMTQNEDLRE NMLRQVLEHL SQQSESQYLK ILTSLAEVAT 310 320 330 340 350 360 TNGHKLLSLS SNYDAQMKSL LRIVRMFCHV FRIGPSSPSN GIDMGYNGNK TPRSQVFKPL 370 380 390 400 410 420 ELLWHSLDEW LVLIATELMK NKRDSTEITS ILLKQKGQDQ DAASIPPFEP PGPGSYENLS 430 440 450 460 470 480 TGTRESKPDA LAGRQEASAD CQDVISMTAN RLSAVIQAFY MCCSCQMPPG MTSPRFIEFV 490 500 510 520 530 540 CKHDEVLKCF VNRNPKIIFD HFHFLLECPE LMSRFMHIIK AQPFKDRCEW FYEHLHSGQP 550 560 570 580 590 600 DSDMVHRPVN ENDILLVHRD SIFRSSCEVV SKANCAKLKQ GIAVRFHGEE GMGQGVVREW 610 620 630 640 650 660 FDILSNEIVN PDYALFTQSA DGTTFQPNSN SYVNPDHLNY FRFAGQILGL ALNHRQLVNI 670 680 690 700 710 720 YFTRSFYKHI LGIPVNYQDV ASIDPEYAKN LQWILDNDIS DLGLELTFSV ETDVFGAMEE 730 740 750 760 770 780 VPLKPGGGSI LVTQNNKAEY VQLVTELRMT RAIQPQINAF LQGFHMFIPP SLIQLFDEYE 790 800 810 820 830 840 LELLLSGMPE IDVSDWIKNT EYTSGYERED PVIQWFWEVV EDITQEERVL LLQFVTGSSR 850 860 870 880 890 900 VPHGGFANIM GGSGLQNFTI AAVPYTPNLL PTSSTCINML KLPEYPSKEI LKDRLLVALH CGSYGYTMA
	Isoform 2 [UniParc]. Checksum: 251ACA3A8869BD9F	FASTA	318	35,968
	10 20 30 40 50 60 MGQGVVREWF DILSNEIVNP DYALFTQSAD GTTFQPNSNS YVNPDHLNYF RFAGQILGLA 70 80 90 100 110 120 LNHRQLVNIY FTRSFYKHIL GIPVNYQDVA SIDPEYAKNL QWILDNDISD LGLELTFSVE 130 140 150 160 170 180 TDVFGAMEEV PLKPGGGSIL VTQNNKAEYV QLVTELRMTR AIQPQINAFL QGFHMFIPPS 190 200 210 220 230 240 LIQLFDEYEL ELLLSGMPEI DVSDWIKNTE YTSGYEREDP VIQWFWEVVE DITQEERVLL 250 260 270 280 290 300 LQFVTGSSRV PHGGFANIMG GSGLQNFTIA AVPYTPNLLP TSSTCINMLK LPEYPSKEIL 310 KDRLLVALHC GSYGYTMA
	Isoform 3 [UniParc]. Checksum: 55710072CAB4023C	FASTA	562	63,889
	10 20 30 40 50 60 MMFKKHFCFS QPLELLWHSL DEWLVLIATE LMKNKRDSTE ITSILLKQKG QDQDAASIPP 70 80 90 100 110 120 FEPPGPGSYE NLSTGTRESK PDALAGRQEA SADCQDVISM TANRLSAVIQ AFYMCCSCQM 130 140 150 160 170 180 PPGMTSPRFI EFVCKHDEVL KCFVNRNPKI IFDHFHFLLE CPELMSRFMH IIKAQPFKDR 190 200 210 220 230 240 CEWFYEHLHS GQPDSDMVHR PVNENDILLV HRDSIFRSSC EVVSKANCAK LKQGIAVRFH 250 260 270 280 290 300 GEEGMGQGVV REWFDILSNE IVNPDYALFT QSADGTTFQP NSNSYVNPDH LNYFRFAGQI 310 320 330 340 350 360 LGLALNHRQL VNIYFTRSFY KHILGIPVNY QDVASIDPEY AKNLQWILDN DISDLGLELT 370 380 390 400 410 420 FSVETDVFGA MEEVPLKPGG GSILVTQNNK AEYVQLVTEL RMTRAIQPQI NAFLQGFHMF 430 440 450 460 470 480 IPPSLIQLFD EYELELLLSG MPEIDVSDWI KNTEYTSGYE REDPVIQWFW EVVEDITQEE 490 500 510 520 530 540 RVLLLQFVTG SSRVPHGGFA NIMGGSGLQN FTIAAVPYTP NLLPTSSTCI NMLKLPEYPS 550 560 KEILKDRLLV ALHCGSYGYT MA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:65-73(2000) [PubMed: 10718198] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Brain.
[2]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Testis.
[3]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS HIS-17 AND THR-374. Tissue: Testis.
[5]	"Differential expression of a novel ankyrin containing E3 ubiquitin-protein ligase, Hace1, in sporadic Wilms' tumor versus normal kidney." 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. Hum. Mol. Genet. 13:2061-2074(2004) [PubMed: 15254018] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, MUTAGENESIS OF CYS-876, INTERACTION WITH THE 20S CORE PROTEASOMAL SUBUNIT, SUBCELLULAR LOCATION, INDUCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB037741 mRNA. Translation: BAA92558.1. Different initiation. AL834202 mRNA. Translation: CAD38890.1. AL513472, AL590402 Genomic DNA. Translation: CAH71889.1. AL513472, AL357315, AL590402 Genomic DNA. Translation: CAH71890.1. Sequence problems. AL590402, AL513472 Genomic DNA. Translation: CAH74023.1. AL590402, AL357315, AL513472 Genomic DNA. Translation: CAH74024.1. Sequence problems. AL357315, AL590402, AL513472 Genomic DNA. Translation: CAI16815.1. Sequence problems. BC034982 mRNA. Translation: AAH34982.1.
IPI	IPI00337371. IPI00642351. IPI00829725.
RefSeq	NP_065822.2. NM_020771.3.
UniGene	Hs.434340.
3D structure databases
HSSP	HSSP built from PDB template 1ND7 based on UniProtKB Q9H0M0.
ProteinModelPortal	Q8IYU2.
SMR	Q8IYU2. Positions 12-332, 523-901.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8IYU2. 1 interaction.
STRING	Q8IYU2.
PTM databases
PhosphoSite	Q8IYU2.
Polymorphism databases
DMDM	134034136.
Proteomic databases
PRIDE	Q8IYU2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000262903; ENSP00000262903; ENSG00000085382.
GeneID	57531.
KEGG	hsa:57531.
UCSC	uc003pqt.1. human. uc003pqu.1. human.
Organism-specific databases
CTD	57531.
GeneCards	GC06M105221.
H-InvDB	HIX0006095.
HGNC	HGNC:21033. HACE1.
MIM	610876. gene.
neXtProt	NX_Q8IYU2.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG15345.
GeneTree	ENSGT00570000078981.
HOGENOM	HBG358212.
HOVERGEN	HBG004134.
InParanoid	Q8IYU2.
OMA	TSIPPFE.
OrthoDB	EOG4TMR19.
PhylomeDB	Q8IYU2.
Gene expression databases
ArrayExpress	Q8IYU2.
Bgee	Q8IYU2.
CleanEx	HS_HACE1.
Genevestigator	Q8IYU2.
Family and domain databases
InterPro	IPR002110. Ankyrin_rpt. IPR020683. Ankyrin_rpt-contain_dom. IPR000569. HECT. [Graphical view]
Gene3D	G3DSA:1.25.40.20. ANK. 1 hit.
KO	K12166.
Pfam	PF12796. Ank_2. 2 hits. PF00632. HECT. 1 hit. [Graphical view]
PRINTS	PR01415. ANKYRIN.
SMART	SM00248. ANK. 6 hits. SM00119. HECTc. 1 hit. [Graphical view]
SUPFAM	SSF48403. ANK. 1 hit. SSF56204. HECT. 1 hit.
PROSITE	PS50297. ANK_REP_REGION. 1 hit. PS50088. ANK_REPEAT. 5 hits. PS50237. HECT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	63936.
SOURCE	Search...

Entry information

Entry name

HACE1_HUMAN

Accession

Primary (citable) accession number: Q8IYU2
Secondary accession number(s): Q5VU99 , Q5VUA0, Q8ND12, Q9P2M6

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 20, 2007
Last sequence update:	March 20, 2007
Last modified:	January 25, 2012
This is version 83 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.