HERC6_HUMAN
ID HERC6_HUMAN Reviewed; 1022 AA.
AC Q8IVU3; B4DIY5; Q5GC90; Q5GRH3; Q5HYM6; Q5JPB6; Q6PIF4; Q8NAN3; Q9NWS4;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Probable E3 ubiquitin-protein ligase HERC6;
DE EC=2.3.2.26;
DE AltName: Full=HECT domain and RCC1-like domain-containing protein 6;
DE AltName: Full=HECT-type E3 ubiquitin transferase HERC6;
GN Name=HERC6;
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 AND 2), TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND SUBCELLULAR LOCATION.
RC TISSUE=Endothelial cell, and T-cell;
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 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 24-1022 (ISOFORM 3).
RC TISSUE=Gastric carcinoma, Hippocampus, and Placenta;
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 MRNA] (ISOFORM 1).
RC TISSUE=Ovary, and Uterus;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 48-1022.
RC TISSUE=Endometrium, and Lymph node;
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).
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, cytosol {ECO:0000269|PubMed:15676274}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8IVU3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IVU3-2; Sequence=VSP_023185;
CC Name=3;
CC IsoId=Q8IVU3-3; Sequence=VSP_023183, VSP_023184;
CC -!- TISSUE SPECIFICITY: Detected in brain, heart, placenta and testis.
CC {ECO:0000269|PubMed:15676274}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal brain.
CC {ECO:0000269|PubMed:15676274}.
CC -!- MISCELLANEOUS: [Isoform 1]: Major transcript.
CC -!- MISCELLANEOUS: [Isoform 2]: Minor transcript. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: Minor transcript. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91303.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC03879.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAI46056.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAI46151.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF336798; AAQ14893.1; -; mRNA.
DR EMBL; AY653201; AAV66895.1; -; mRNA.
DR EMBL; AK000644; BAA91303.1; ALT_INIT; mRNA.
DR EMBL; AK092403; BAC03879.1; ALT_INIT; mRNA.
DR EMBL; AK295832; BAG58647.1; -; mRNA.
DR EMBL; BC035775; AAH35775.2; -; mRNA.
DR EMBL; BC042047; AAH42047.2; -; mRNA.
DR EMBL; AL833664; CAI46151.1; ALT_INIT; mRNA.
DR EMBL; BX647121; CAI46056.1; ALT_INIT; mRNA.
DR CCDS; CCDS47098.1; -. [Q8IVU3-1]
DR CCDS; CCDS54777.1; -. [Q8IVU3-2]
DR RefSeq; NP_001158608.1; NM_001165136.1. [Q8IVU3-2]
DR RefSeq; NP_060382.3; NM_017912.3. [Q8IVU3-1]
DR PDB; 5W87; X-ray; 2.20 A; A/B=902-1022.
DR PDBsum; 5W87; -.
DR AlphaFoldDB; Q8IVU3; -.
DR SMR; Q8IVU3; -.
DR BioGRID; 120340; 13.
DR IntAct; Q8IVU3; 3.
DR STRING; 9606.ENSP00000264346; -.
DR iPTMnet; Q8IVU3; -.
DR PhosphoSitePlus; Q8IVU3; -.
DR BioMuta; HERC6; -.
DR DMDM; 74750679; -.
DR EPD; Q8IVU3; -.
DR jPOST; Q8IVU3; -.
DR MassIVE; Q8IVU3; -.
DR MaxQB; Q8IVU3; -.
DR PaxDb; Q8IVU3; -.
DR PeptideAtlas; Q8IVU3; -.
DR PRIDE; Q8IVU3; -.
DR ProteomicsDB; 70770; -. [Q8IVU3-1]
DR ProteomicsDB; 70771; -. [Q8IVU3-2]
DR ProteomicsDB; 70772; -. [Q8IVU3-3]
DR Antibodypedia; 25568; 68 antibodies from 14 providers.
DR DNASU; 55008; -.
DR Ensembl; ENST00000264346.12; ENSP00000264346.8; ENSG00000138642.16. [Q8IVU3-1]
DR Ensembl; ENST00000380265.9; ENSP00000369617.5; ENSG00000138642.16. [Q8IVU3-2]
DR GeneID; 55008; -.
DR KEGG; hsa:55008; -.
DR MANE-Select; ENST00000264346.12; ENSP00000264346.8; NM_017912.4; NP_060382.3.
DR UCSC; uc011cdi.3; human. [Q8IVU3-1]
DR CTD; 55008; -.
DR DisGeNET; 55008; -.
DR GeneCards; HERC6; -.
DR HGNC; HGNC:26072; HERC6.
DR HPA; ENSG00000138642; Low tissue specificity.
DR MIM; 609249; gene.
DR neXtProt; NX_Q8IVU3; -.
DR OpenTargets; ENSG00000138642; -.
DR PharmGKB; PA134894313; -.
DR VEuPathDB; HostDB:ENSG00000138642; -.
DR eggNOG; KOG0941; Eukaryota.
DR GeneTree; ENSGT00940000162279; -.
DR HOGENOM; CLU_002173_5_3_1; -.
DR InParanoid; Q8IVU3; -.
DR OMA; NFVTTYQ; -.
DR OrthoDB; 1062377at2759; -.
DR PhylomeDB; Q8IVU3; -.
DR TreeFam; TF315189; -.
DR PathwayCommons; Q8IVU3; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q8IVU3; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 55008; 14 hits in 1120 CRISPR screens.
DR ChiTaRS; HERC6; human.
DR GenomeRNAi; 55008; -.
DR Pharos; Q8IVU3; Tbio.
DR PRO; PR:Q8IVU3; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q8IVU3; protein.
DR Bgee; ENSG00000138642; Expressed in secondary oocyte and 173 other tissues.
DR ExpressionAtlas; Q8IVU3; baseline and differential.
DR Genevisible; Q8IVU3; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Ensembl.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
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; 5.
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; 5.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Reference proteome; Repeat;
KW Transferase; Ubl conjugation pathway.
FT CHAIN 1..1022
FT /note="Probable E3 ubiquitin-protein ligase HERC6"
FT /id="PRO_0000278219"
FT REPEAT 41..92
FT /note="RCC1 1"
FT REPEAT 93..145
FT /note="RCC1 2"
FT REPEAT 147..198
FT /note="RCC1 3"
FT REPEAT 200..253
FT /note="RCC1 4"
FT REPEAT 254..304
FT /note="RCC1 5"
FT DOMAIN 693..1017
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT ACT_SITE 985
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT VAR_SEQ 296..306
FT /note="SYHTLAYVHTT -> RNSKHGFMTFF (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_023183"
FT VAR_SEQ 307..1022
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_023184"
FT VAR_SEQ 610..645
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15676274"
FT /id="VSP_023185"
FT VARIANT 123
FT /note="M -> T (in dbSNP:rs7677237)"
FT /id="VAR_051725"
FT VARIANT 199
FT /note="C -> R (in dbSNP:rs12510688)"
FT /id="VAR_051726"
FT VARIANT 343
FT /note="F -> L (in dbSNP:rs17014118)"
FT /id="VAR_051727"
FT VARIANT 614
FT /note="T -> I (in dbSNP:rs6532068)"
FT /id="VAR_051728"
FT CONFLICT 742
FT /note="G -> C (in Ref. 2; BAA91303)"
FT /evidence="ECO:0000305"
FT HELIX 908..913
FT /evidence="ECO:0007829|PDB:5W87"
FT HELIX 926..935
FT /evidence="ECO:0007829|PDB:5W87"
FT HELIX 940..950
FT /evidence="ECO:0007829|PDB:5W87"
FT HELIX 958..963
FT /evidence="ECO:0007829|PDB:5W87"
FT STRAND 967..969
FT /evidence="ECO:0007829|PDB:5W87"
FT STRAND 984..990
FT /evidence="ECO:0007829|PDB:5W87"
FT HELIX 997..1008
FT /evidence="ECO:0007829|PDB:5W87"
SQ SEQUENCE 1022 AA; 115126 MW; 713646243F269AD9 CRC64;
MYFCWGADSR ELQRRRTAGS PGAELLQAAS GERHSLLLLT NHRVLSCGDN SRGQLGRRGA
QRGELPEPIQ ALETLIVDLV SCGKEHSLAV CHKGRVFAWG AGSEGQLGIG EFKEISFTPK
KIMTLNDIKI IQVSCGHYHS LALSKDSQVF SWGKNSHGQL GLGKEFPSQA SPQRVRSLEG
IPLAQVAAGG AHSFALSLCG TSFGWGSNSA GQLALSGRNV PVQSNKPLSV GALKNLGVVY
ISCGDAHTAV LTQDGKVFTF GDNRSGQLGY SPTPEKRGPQ LVERIDGLVS QIDCGSYHTL
AYVHTTGQVV SFGHGPSDTS KPTHPEALTE NFDISCLISA EDFVDVQVKH IFAGTYANFV
TTHQDTSSTR APGKTLPEIS RISQSMAEKW IAVKRRSTEH EMAKSEIRMI FSSPACLTAS
FLKKRGTGET TSIDVDLEMA RDTFKKLTKK EWISSMITTC LEDDLLRALP CHSPHQEALS
VFLLLPECPV MHDSKNWKNL VVPFAKAVCE MSKQSLQVLK KCWAFLQESS LNPLIQMLKA
AIISQLLHQT KTEQDHCNVK ALLGMMKELH KVNKANCRLP ENTFNINELS NLLNFYIDRG
RQLFRDNHLI PAETPSPVIF SDFPFIFNSL SKIKLLQADS HIKMQMSEKK AYMLMHETIL
QKKDEFPPSP RFILRVRRSR LVKDALRQLS QAEATDFCKV LVVEFINEIC PESGGVSSEF
FHCMFEEMTK PEYGMFMYPE MGSCMWFPAK PKPEKKRYFL FGMLCGLSLF NLNVANLPFP
LALYKKLLDQ KPSLEDLKEL SPRLGKSLQE VLDDAADDIG DALCIRFSIH WDQNDVDLIP
NGISIPVDQT NKRDYVSKYI DYIFNVSVKA VYEEFQRGFY RVCEKEILRH FYPEELMTAI
IGNTDYDWKQ FEQNSKYEQG YQKSHPTIQL FWKAFHKLTL DEKKKFLFFL TGRDRLHARG
IQKMEIVFRC PETFSERDHP TSITCHNILS LPKYSTMERM EEALQVAINN NRGFVSPMLT
QS
