HERC3_HUMAN
ID HERC3_HUMAN Reviewed; 1050 AA.
AC Q15034; A8K1S5; Q8IXX3;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Probable E3 ubiquitin-protein ligase HERC3;
DE EC=2.3.2.26;
DE AltName: Full=HECT domain and RCC1-like domain-containing protein 3;
DE AltName: Full=HECT-type E3 ubiquitin transferase HERC3;
GN Name=HERC3; Synonyms=KIAA0032;
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 1).
RC TISSUE=Bone marrow;
RX PubMed=7584026; DOI=10.1093/dnares/1.1.27;
RA Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y., Sato S.,
RA Nagase T., Seki N., Ishikawa K., Tabata S.;
RT "Prediction of the coding sequences of unidentified human genes. I. The
RT coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of
RT randomly sampled cDNA clones from human immature myeloid cell line KG-1.";
RL DNA Res. 1:27-35(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Hippocampus;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Skin;
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 CHARACTERIZATION.
RX PubMed=11163799; DOI=10.1016/s0014-5793(00)02371-1;
RA Cruz C., Ventura F., Bartrons R., Rosa J.L.;
RT "HERC3 binding to and regulation by ubiquitin.";
RL FEBS Lett. 488:74-80(2001).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from an
CC E2 ubiquitin-conjugating enzyme in the form of a thioester and then
CC directly transfers the ubiquitin to targeted substrates. {ECO:0000250}.
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. Cytoplasmic vesicle. Note=Also found
CC in vesicular-like structures.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q15034-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15034-2; Sequence=VSP_056343, VSP_056344;
CC -!- PTM: Ubiquitinated; which promotes degradation by the proteasome.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA04945.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; D25215; BAA04945.2; ALT_INIT; mRNA.
DR EMBL; AK289990; BAF82679.1; -; mRNA.
DR EMBL; AC083829; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC098582; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC108065; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471057; EAX06024.1; -; Genomic_DNA.
DR EMBL; BC038960; AAH38960.1; -; mRNA.
DR CCDS; CCDS34028.1; -. [Q15034-1]
DR CCDS; CCDS82939.1; -. [Q15034-2]
DR RefSeq; NP_001258531.1; NM_001271602.1.
DR RefSeq; NP_001305434.1; NM_001318505.1. [Q15034-2]
DR RefSeq; NP_055421.1; NM_014606.2. [Q15034-1]
DR RefSeq; XP_005263384.1; XM_005263327.3. [Q15034-1]
DR AlphaFoldDB; Q15034; -.
DR SMR; Q15034; -.
DR BioGRID; 114430; 57.
DR IntAct; Q15034; 17.
DR MINT; Q15034; -.
DR STRING; 9606.ENSP00000385684; -.
DR iPTMnet; Q15034; -.
DR PhosphoSitePlus; Q15034; -.
DR BioMuta; HERC3; -.
DR DMDM; 2495699; -.
DR EPD; Q15034; -.
DR jPOST; Q15034; -.
DR MassIVE; Q15034; -.
DR MaxQB; Q15034; -.
DR PaxDb; Q15034; -.
DR PeptideAtlas; Q15034; -.
DR PRIDE; Q15034; -.
DR ProteomicsDB; 60383; -. [Q15034-1]
DR ProteomicsDB; 71073; -.
DR Antibodypedia; 25635; 233 antibodies from 25 providers.
DR DNASU; 8916; -.
DR Ensembl; ENST00000264345.7; ENSP00000264345.3; ENSG00000138641.18. [Q15034-1]
DR Ensembl; ENST00000402738.6; ENSP00000385684.1; ENSG00000138641.18. [Q15034-1]
DR Ensembl; ENST00000407637.5; ENSP00000384005.1; ENSG00000138641.18. [Q15034-2]
DR GeneID; 8916; -.
DR KEGG; hsa:8916; -.
DR MANE-Select; ENST00000402738.6; ENSP00000385684.1; NM_014606.3; NP_055421.1.
DR UCSC; uc003hrv.5; human. [Q15034-1]
DR CTD; 8916; -.
DR DisGeNET; 8916; -.
DR GeneCards; HERC3; -.
DR HGNC; HGNC:4876; HERC3.
DR HPA; ENSG00000138641; Tissue enriched (retina).
DR MIM; 605200; gene.
DR neXtProt; NX_Q15034; -.
DR OpenTargets; ENSG00000138641; -.
DR PharmGKB; PA29251; -.
DR VEuPathDB; HostDB:ENSG00000138641; -.
DR eggNOG; KOG0941; Eukaryota.
DR GeneTree; ENSGT00940000158189; -.
DR HOGENOM; CLU_002173_5_3_1; -.
DR InParanoid; Q15034; -.
DR OMA; NLSIHEW; -.
DR OrthoDB; 1062377at2759; -.
DR PhylomeDB; Q15034; -.
DR TreeFam; TF315189; -.
DR PathwayCommons; Q15034; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q15034; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 8916; 9 hits in 1119 CRISPR screens.
DR ChiTaRS; HERC3; human.
DR GenomeRNAi; 8916; -.
DR Pharos; Q15034; Tbio.
DR PRO; PR:Q15034; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q15034; protein.
DR Bgee; ENSG00000138641; Expressed in sural nerve and 110 other tissues.
DR ExpressionAtlas; Q15034; baseline and differential.
DR Genevisible; Q15034; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR CDD; cd00078; HECTc; 1.
DR Gene3D; 2.130.10.30; -; 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 Pfam; PF00632; HECT; 1.
DR Pfam; PF00415; RCC1; 6.
DR PRINTS; PR00633; RCCNDNSATION.
DR SMART; SM00119; HECTc; 1.
DR SUPFAM; SSF50985; SSF50985; 1.
DR SUPFAM; SSF56204; SSF56204; 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; Cytoplasmic vesicle; Reference proteome;
KW Repeat; Transferase; Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..1050
FT /note="Probable E3 ubiquitin-protein ligase HERC3"
FT /id="PRO_0000206651"
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..366
FT /note="RCC1 7"
FT DOMAIN 951..1050
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT ACT_SITE 1018
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT VAR_SEQ 357..368
FT /note="DRFKYHIVKQIF -> GKNDCLWNLKVF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056343"
FT VAR_SEQ 369..1050
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056344"
FT VARIANT 946
FT /note="E -> Q (in dbSNP:rs1804080)"
FT /id="VAR_051729"
SQ SEQUENCE 1050 AA; 117188 MW; 5F08A1DE1F40B912 CRC64;
MLCWGYWSLG QPGISTNLQG IVAEPQVCGF ISDRSVKEVA CGGNHSVFLL EDGEVYTCGL
NTKGQLGHER EGNKPEQIGA LADQHIIHVA CGESHSLALS DRGQLFSWGA GSDGQLGLMT
TEDSVAVPRL IQKLNQQTIL QVSCGNWHCL ALAADGQFFT WGKNSHGQLG LGKEFPSQAS
PQRVRSLEGI PLAQVAAGGA HSFALSLSGA VFGWGMNNAG QLGLSDEKDR ESPCHVKLLR
TQKVVYISCG EEHTAVLTKS GGVFTFGAGS CGQLGHDSMN DEVNPRRVLE LMGSEVTQIA
CGRQHTLAFV PSSGLIYAFG CGARGQLGTG HTCNVKCPSP VKGYWAAHSG QLSARADRFK
YHIVKQIFSG GDQTFVLCSK YENYSPAVDF RTMNQAHYTS LINDETIAVW RQKLSEHNNA
NTINGVVQIL SSAACWNGSF LEKKIDEHFK TSPKIPGIDL NSTRVLFEKL MNSQHSMILE
QILNSFESCL IPQLSSSPPD VEAMRIYLIL PEFPLLQDSK YYITLTIPLA MAILRLDTNP
SKVLDNWWSQ VCPKYFMKLV NLYKGAVLYL LRGRKTFLIP VLFNNYITAA LKLLEKLYKV
NLKVKHVEYD TFYIPEISNL VDIQEDYLMW FLHQAGMKAR PSIIQDTVTL CSYPFIFDAQ
AKTKMLQTDA ELQMQVAVNG ANLQNVFMLL TLEPLLARSP FLVLHVRRNN LVGDALRELS
IHSDIDLKKP LKVIFDGEEA VDAGGVTKEF FLLLLKELLN PIYGMFTYYQ DSNLLWFSDT
CFVEHNWFHL IGITCGLAIY NSTVVDLHFP LALYKKLLNV KPGLEDLKEL SPTEGRSLQE
LLDYPGEDVE ETFCLNFTIC RESYGVIEQK KLIPGGDNVT VCKDNRQEFV DAYVNYVFQI
SVHEWYTAFS SGFLKVCGGK VLELFQPSEL RAMMVGNSNY NWEELEETAI YKGDYSATHP
TVKLFWETFH EFPLEKKKKF LLFLTGSDRI PIYGMASLQI VIQSTASGEE YLPVAHTCYN
LLDLPKYSSK EILSARLTQA LDNYEGFSLA
