ID HERC4_HUMAN Reviewed; 1057 AA.
AC Q5GLZ8; Q5GC98; Q5GC99; Q5GCA0; Q8IXP9; Q9HCH9;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2005, sequence version 1.
DT 27-MAR-2024, entry version 152.
DE RecName: Full=Probable E3 ubiquitin-protein ligase HERC4;
DE EC=2.3.2.26;
DE AltName: Full=HECT domain and RCC1-like domain-containing protein 4;
DE AltName: Full=HECT-type E3 ubiquitin transferase HERC4;
GN Name=HERC4; Synonyms=KIAA1593;
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 [MRNA] (ISOFORMS 1; 3; 4 AND 5), TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND SUBCELLULAR LOCATION.
RC TISSUE=Cervix carcinoma;
RX PubMed=15676274; DOI=10.1016/j.ygeno.2004.10.006;
RA Hochrainer K., Mayer H., Baranyi U., Binder B.R., Lipp J., Kroismayr R.;
RT "The human HERC family of ubiquitin ligases: novel members, genomic
RT organization, expression profiling, and evolutionary aspects.";
RL Genomics 85:153-164(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
RC TISSUE=Brain;
RX PubMed=10997877; DOI=10.1093/dnares/7.4.271;
RA Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:273-281(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Blood;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Probable E3 ubiquitin-protein ligase involved in either
CC protein trafficking or in the distribution of cellular structures.
CC Required for spermatozoon maturation and fertility, and for the removal
CC of the cytoplasmic droplet of the spermatozoon. E3 ubiquitin-protein
CC ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the
CC form of a thioester and then directly transfer it to targeted
CC substrates. {ECO:0000250|UniProtKB:Q6PAV2}.
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 -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:15676274}.
CC Note=shows a punctate cytoplasmic distribution.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1;
CC IsoId=Q5GLZ8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5GLZ8-2; Sequence=VSP_023178;
CC Name=3;
CC IsoId=Q5GLZ8-3; Sequence=VSP_023179;
CC Name=4;
CC IsoId=Q5GLZ8-4; Sequence=VSP_023174, VSP_023175;
CC Name=5; Synonyms=2;
CC IsoId=Q5GLZ8-5; Sequence=VSP_023173, VSP_023176;
CC Name=6;
CC IsoId=Q5GLZ8-6; Sequence=VSP_023172, VSP_039551;
CC -!- TISSUE SPECIFICITY: Expressed in brain and testis and detected in heart
CC and placenta. {ECO:0000269|PubMed:15676274}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal brain.
CC {ECO:0000269|PubMed:15676274}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB13419.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY221963; AAO65480.1; -; mRNA.
DR EMBL; AY650032; AAV66578.1; -; mRNA.
DR EMBL; AY650033; AAV66579.1; -; mRNA.
DR EMBL; AY650034; AAV66580.1; -; mRNA.
DR EMBL; AB046813; BAB13419.1; ALT_INIT; mRNA.
DR EMBL; AC024258; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL133551; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356741; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC039600; AAH39600.1; -; mRNA.
DR CCDS; CCDS41533.1; -. [Q5GLZ8-1]
DR CCDS; CCDS60541.1; -. [Q5GLZ8-3]
DR CCDS; CCDS60542.1; -. [Q5GLZ8-4]
DR CCDS; CCDS7274.1; -. [Q5GLZ8-2]
DR RefSeq; NP_001265114.1; NM_001278185.1. [Q5GLZ8-3]
DR RefSeq; NP_001265115.1; NM_001278186.1.
DR RefSeq; NP_001265116.1; NM_001278187.1. [Q5GLZ8-4]
DR RefSeq; NP_056416.2; NM_015601.3. [Q5GLZ8-2]
DR RefSeq; NP_071362.1; NM_022079.2. [Q5GLZ8-1]
DR AlphaFoldDB; Q5GLZ8; -.
DR SMR; Q5GLZ8; -.
DR BioGRID; 117542; 86.
DR IntAct; Q5GLZ8; 20.
DR STRING; 9606.ENSP00000378624; -.
DR GlyGen; Q5GLZ8; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q5GLZ8; -.
DR MetOSite; Q5GLZ8; -.
DR PhosphoSitePlus; Q5GLZ8; -.
DR SwissPalm; Q5GLZ8; -.
DR BioMuta; HERC4; -.
DR DMDM; 74707832; -.
DR EPD; Q5GLZ8; -.
DR jPOST; Q5GLZ8; -.
DR MassIVE; Q5GLZ8; -.
DR MaxQB; Q5GLZ8; -.
DR PaxDb; 9606-ENSP00000378624; -.
DR PeptideAtlas; Q5GLZ8; -.
DR ProteomicsDB; 62837; -. [Q5GLZ8-1]
DR ProteomicsDB; 62838; -. [Q5GLZ8-2]
DR ProteomicsDB; 62839; -. [Q5GLZ8-3]
DR ProteomicsDB; 62840; -. [Q5GLZ8-4]
DR ProteomicsDB; 62841; -. [Q5GLZ8-5]
DR ProteomicsDB; 62842; -. [Q5GLZ8-6]
DR Pumba; Q5GLZ8; -.
DR Antibodypedia; 28396; 197 antibodies from 27 providers.
DR DNASU; 26091; -.
DR Ensembl; ENST00000277817.10; ENSP00000277817.6; ENSG00000148634.16. [Q5GLZ8-6]
DR Ensembl; ENST00000373700.9; ENSP00000362804.4; ENSG00000148634.16. [Q5GLZ8-2]
DR Ensembl; ENST00000395198.7; ENSP00000378624.3; ENSG00000148634.16. [Q5GLZ8-1]
DR Ensembl; ENST00000412272.6; ENSP00000416504.2; ENSG00000148634.16. [Q5GLZ8-3]
DR Ensembl; ENST00000473533.6; ENSP00000423671.1; ENSG00000148634.16. [Q5GLZ8-5]
DR Ensembl; ENST00000492996.6; ENSP00000422383.1; ENSG00000148634.16. [Q5GLZ8-4]
DR GeneID; 26091; -.
DR KEGG; hsa:26091; -.
DR MANE-Select; ENST00000373700.9; ENSP00000362804.4; NM_015601.4; NP_056416.2. [Q5GLZ8-2]
DR UCSC; uc001jng.5; human. [Q5GLZ8-1]
DR AGR; HGNC:24521; -.
DR CTD; 26091; -.
DR DisGeNET; 26091; -.
DR GeneCards; HERC4; -.
DR HGNC; HGNC:24521; HERC4.
DR HPA; ENSG00000148634; Low tissue specificity.
DR MIM; 609248; gene.
DR neXtProt; NX_Q5GLZ8; -.
DR OpenTargets; ENSG00000148634; -.
DR PharmGKB; PA134949021; -.
DR VEuPathDB; HostDB:ENSG00000148634; -.
DR eggNOG; KOG0941; Eukaryota.
DR GeneTree; ENSGT00940000158924; -.
DR HOGENOM; CLU_2084036_0_0_1; -.
DR InParanoid; Q5GLZ8; -.
DR OMA; FKSQACW; -.
DR OrthoDB; 5475808at2759; -.
DR PhylomeDB; Q5GLZ8; -.
DR TreeFam; TF315189; -.
DR PathwayCommons; Q5GLZ8; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q5GLZ8; -.
DR SIGNOR; Q5GLZ8; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 26091; 12 hits in 1201 CRISPR screens.
DR ChiTaRS; HERC4; human.
DR GenomeRNAi; 26091; -.
DR Pharos; Q5GLZ8; Tbio.
DR PRO; PR:Q5GLZ8; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q5GLZ8; Protein.
DR Bgee; ENSG00000148634; Expressed in adrenal tissue and 185 other cell types or tissues.
DR ExpressionAtlas; Q5GLZ8; baseline and differential.
DR Genevisible; Q5GLZ8; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IMP:FlyBase.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR CDD; cd00078; HECTc; 1.
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 Gene3D; 2.130.10.30; Regulator of chromosome condensation 1/beta-lactamase-inhibitor protein II; 2.
DR InterPro; IPR000569; HECT_dom.
DR InterPro; IPR035983; Hect_E3_ubiquitin_ligase.
DR InterPro; IPR009091; RCC1/BLIP-II.
DR InterPro; IPR000408; Reg_chr_condens.
DR PANTHER; PTHR45622:SF5; E3 UBIQUITIN-PROTEIN LIGASE HERC4-RELATED; 1.
DR PANTHER; PTHR45622; UBIQUITIN-PROTEIN LIGASE E3A-RELATED; 1.
DR Pfam; PF00632; HECT; 1.
DR Pfam; PF00415; RCC1; 7.
DR PRINTS; PR00633; RCCNDNSATION.
DR SMART; SM00119; HECTc; 1.
DR SUPFAM; SSF56204; Hect, E3 ligase catalytic domain; 1.
DR SUPFAM; SSF50985; RCC1/BLIP-II; 1.
DR PROSITE; PS50237; HECT; 1.
DR PROSITE; PS00626; RCC1_2; 3.
DR PROSITE; PS50012; RCC1_3; 7.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Differentiation; Reference proteome;
KW Repeat; Spermatogenesis; Transferase; Ubl conjugation pathway.
FT CHAIN 1..1057
FT /note="Probable E3 ubiquitin-protein ligase HERC4"
FT /id="PRO_0000278216"
FT REPEAT 1..51
FT /note="RCC1 1"
FT REPEAT 52..101
FT /note="RCC1 2"
FT REPEAT 102..154
FT /note="RCC1 3"
FT REPEAT 156..207
FT /note="RCC1 4"
FT REPEAT 208..259
FT /note="RCC1 5"
FT REPEAT 261..311
FT /note="RCC1 6"
FT REPEAT 313..368
FT /note="RCC1 7"
FT DOMAIN 730..1057
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT ACT_SITE 1025
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT VAR_SEQ 1..110
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:10997877"
FT /id="VSP_023172"
FT VAR_SEQ 77..117
FT /note="QVVALDAQNIVAVSCGEAHTLALNDKGQVYAWGLDSDGQLG -> ILKVCQI
FT SRLYRLLVVTIIHLHFLKQVKSSVGDRINMANWV (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:15676274"
FT /id="VSP_023173"
FT VAR_SEQ 77..110
FT /note="QVVALDAQNIVAVSCGEAHTLALNDKGQVYAWGL -> FRSCFPGRSAMAPS
FT RLTATSASQVQAILLPQPPE (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15676274"
FT /id="VSP_023174"
FT VAR_SEQ 111..1057
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15676274"
FT /id="VSP_023175"
FT VAR_SEQ 111..128
FT /note="DSDGQLGLVGSEECIRVP -> MCVDSLVRICSGLSYGRI (in isoform
FT 6)"
FT /evidence="ECO:0000303|PubMed:10997877"
FT /id="VSP_039551"
FT VAR_SEQ 118..1057
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:15676274"
FT /id="VSP_023176"
FT VAR_SEQ 643..650
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023178"
FT VAR_SEQ 788..865
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15676274"
FT /id="VSP_023179"
FT CONFLICT 1032
FT /note="P -> S (in Ref. 1; AAV66579)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1057 AA; 118563 MW; 7F06DA755A68243A CRC64;
MLCWGNASFG QLGLGGIDEE IVLEPRKSDF FINKRVRDVG CGLRHTVFVL DDGTVYTCGC
NDLGQLGHEK SRKKPEQVVA LDAQNIVAVS CGEAHTLALN DKGQVYAWGL DSDGQLGLVG
SEECIRVPRN IKSLSDIQIV QVACGYYHSL ALSKASEVFC WGQNKYGQLG LGTDCKKQTS
PQLLKSLLGI PFMQVAAGGA HSFVLTLSGA IFGWGRNKFG QLGLNDENDR YVPNLLKSLR
SQKIVYICCG EDHTAALTKE GGVFTFGAGG YGQLGHNSTS HEINPRKVFE LMGSIVTEIA
CGRQHTSAFV PSSGRIYSFG LGGNGQLGTG STSNRKSPFT VKGNWYPYNG QCLPDIDSEE
YFCVKRIFSG GDQSFSHYSS PQNCGPPDDF RCPNPTKQIW TVNEALIQKW LSYPSGRFPV
EIANEIDGTF SSSGCLNGSF LAVSNDDHYR TGTRFSGVDM NAARLLFHKL IQPDHPQISQ
QVAASLEKNL IPKLTSSLPD VEALRFYLTL PECPLMSDSN NFTTIAIPFG TALVNLEKAP
LKVLENWWSV LEPPLFLKIV ELFKEVVVHL LKLYKIGIPP SERRIFNSFL HTALKVLEIL
HRVNEKMGQI IQYDKFYIHE VQELIDIRND YINWVQQQAY GMDVNHGLTE LADIPVTICT
YPFVFDAQAK TTLLQTDAVL QMQMAIDQAH RQNVSSLFLP VIESVNPCLI LVVRRENIVG
DAMEVLRKTK NIDYKKPLKV IFVGEDAVDA GGVRKEFFLL IMRELLDPKY GMFRYYEDSR
LIWFSDKTFE DSDLFHLIGV ICGLAIYNCT IVDLHFPLAL YKKLLKKKPS LDDLKELMPD
VGRSMQQLLD YPEDDIEETF CLNFTITVEN FGATEVKELV LNGADTAVNK QNRQEFVDAY
VDYIFNKSVA SLFDAFHAGF HKVCGGKVLL LFQPNELQAM VIGNTNYDWK ELEKNTEYKG
EYWAEHPTIK IFWEVFHELP LEKKKQFLLF LTGSDRIPIL GMKSLKLVIQ STGGGEEYLP
VSHTCFNLLD LPKYTEKETL RSKLIQAIDH NEGFSLI
//
