ID   HERC6_MOUSE             Reviewed;        1003 AA.
AC   F2Z461; Q3UEA7; Q9CU70;
DT   05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT   31-MAY-2011, sequence version 1.
DT   03-AUG-2022, entry version 81.
DE   RecName: Full=E3 ISG15--protein ligase Herc6;
DE            EC=2.3.2.-;
GN   Name=Herc6;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-926.
RC   STRAIN=C57BL/6J; TISSUE=Bone marrow, and Thymus;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   FUNCTION, INDUCTION BY INTERFERON, DISRUPTION PHENOTYPE, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=22272257; DOI=10.1371/journal.pone.0029870;
RA   Oudshoorn D., van Boheemen S., Sanchez-Aparicio M.T., Rajsbaum R.,
RA   Garcia-Sastre A., Versteeg G.A.;
RT   "HERC6 is the main E3 ligase for global ISG15 conjugation in mouse cells.";
RL   PLoS ONE 7:E29870-E29870(2012).
CC   -!- FUNCTION: Major E3 ligase for ISG15 conjugation. Acts as a positive
CC       regulator of innate antiviral response in cells induced by interferon.
CC       {ECO:0000269|PubMed:22272257}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:22272257}.
CC       Note=Exclusively cytoplasmic.
CC   -!- INDUCTION: By type I interferons. {ECO:0000269|PubMed:22272257}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes global ISGylation.
CC       {ECO:0000269|PubMed:22272257}.
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DR   EMBL; AC127307; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC142212; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AK017888; BAB30989.3; -; mRNA.
DR   EMBL; AK149648; BAE29004.1; -; mRNA.
DR   CCDS; CCDS51796.1; -.
DR   RefSeq; NP_080268.1; NM_025992.2.
DR   AlphaFoldDB; F2Z461; -.
DR   SMR; F2Z461; -.
DR   IntAct; F2Z461; 1.
DR   STRING; 10090.ENSMUSP00000031817; -.
DR   iPTMnet; F2Z461; -.
DR   PhosphoSitePlus; F2Z461; -.
DR   EPD; F2Z461; -.
DR   jPOST; F2Z461; -.
DR   MaxQB; F2Z461; -.
DR   PaxDb; F2Z461; -.
DR   PRIDE; F2Z461; -.
DR   ProteomicsDB; 269825; -.
DR   Antibodypedia; 25568; 68 antibodies from 14 providers.
DR   Ensembl; ENSMUST00000031817; ENSMUSP00000031817; ENSMUSG00000029798.
DR   GeneID; 67138; -.
DR   KEGG; mmu:67138; -.
DR   UCSC; uc009cci.2; mouse.
DR   CTD; 55008; -.
DR   MGI; MGI:1914388; Herc6.
DR   VEuPathDB; HostDB:ENSMUSG00000029798; -.
DR   eggNOG; KOG0941; Eukaryota.
DR   GeneTree; ENSGT00940000162279; -.
DR   HOGENOM; CLU_002173_5_3_1; -.
DR   InParanoid; F2Z461; -.
DR   OMA; NFVTTYQ; -.
DR   OrthoDB; 1062377at2759; -.
DR   PhylomeDB; F2Z461; -.
DR   TreeFam; TF315189; -.
DR   Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR   BioGRID-ORCS; 67138; 2 hits in 74 CRISPR screens.
DR   ChiTaRS; Herc6; mouse.
DR   PRO; PR:F2Z461; -.
DR   Proteomes; UP000000589; Chromosome 6.
DR   RNAct; F2Z461; protein.
DR   Bgee; ENSMUSG00000029798; Expressed in small intestine Peyer's patch and 175 other tissues.
DR   ExpressionAtlas; F2Z461; baseline and differential.
DR   Genevisible; F2Z461; MM.
DR   GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0030332; F:cyclin binding; ISO:MGI.
DR   GO; GO:0061630; F:ubiquitin protein ligase activity; ISO:MGI.
DR   GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IGI:MGI.
DR   GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR   GO; GO:0016567; P:protein ubiquitination; ISO:MGI.
DR   GO; GO:0009617; P:response to bacterium; IEP:MGI.
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; 3.
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; 4.
DR   PROSITE; PS50012; RCC1_3; 5.
PE   2: Evidence at transcript level;
KW   Cytoplasm; Immunity; Innate immunity; Reference proteome; Repeat;
KW   Transferase; Ubl conjugation pathway.
FT   CHAIN           1..1003
FT                   /note="E3 ISG15--protein ligase Herc6"
FT                   /id="PRO_0000418833"
FT   REPEAT          40..91
FT                   /note="RCC1 1"
FT   REPEAT          92..144
FT                   /note="RCC1 2"
FT   REPEAT          146..197
FT                   /note="RCC1 3"
FT   REPEAT          199..252
FT                   /note="RCC1 4"
FT   REPEAT          253..303
FT                   /note="RCC1 5"
FT   DOMAIN          679..1002
FT                   /note="HECT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT   REGION          261..281
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        261..275
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        970
FT                   /note="Glycyl thioester intermediate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT   CONFLICT        97
FT                   /note="A -> P (in Ref. 2; BAB30989)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1003 AA;  112928 MW;  1ABE2FE1B71B3CDC CRC64;
     MYFSWAAGSR KPRRLKAGTS GIELLQAASG EHHSLLLFSN HRVYSCGDNS WGQLGQRRDQ
     STERPEPIQA LNDLHVDLVS CGKEHSVAVC HKGKVFAWGA GSEGQLGIGE FKEISFMPTK
     IKALAGIKII QVSCGHYHSL ALSEDGHVFS WGRNSEGQLG LGKNSRSQAI PQKVKSLEGI
     PLAQVAAGGT HSFALSLTGT SFGWGSNRSG QLALSGNKVK EQIYKPHSIG ALKNLSVIYI
     SCGYEHTAVL TEEGQVFTFG GNSSGQLQPS PRSGQRGPQL IEGIGGRVSQ IECASYHTIA
     YVYTTGQVVS LGRGPSHTSN PTHQEAPAEN SDITCLLAAE DLVDIEVKDI FAGAHANFVT
     TRRVSHTRST GVSMKILPEI IRINQSLVKK WRAANKRKDR EGAKREISLI FSSSACLTAS
     FLKKRDAGEN NLIDVDLKLA RDVFKKLTTE KWISSLITTC LEEYLLRDLP YSSPHQEALL
     VFLLLPECSI MQDPKNWKTL AFEFAKAIHK MGPQSLAFLR TCWASLEVSS LNILVQMLKK
     AIISQIQYGV ATEQYITNIK VLLEVIKEVH KANCQLPESA FIINELSGIF NFDAEAGRMF
     IRHNDLDCTE SSDMVVFSDF LFVFDLPSKI KLMKCDSFVK LMSEVMAFPE KMSSPPYLIL
     KVRRSHLVED TLRQLRQVED FDLRKQLSVG FINEIRPEAG GVSSEFFHCI FEEMTDPKYE
     MFIYPEKGSS MWFPVNPKFE KSSYFLFGIL CGLSLHNLKV INLPFPLALY KKLLNQKPSL
     EDLKELSLPL GRNLQEVLNC EAGDIEELHM YFSIYWDQKD VDLIPDGISV PVNETNKRDY
     VSKYVDYIFN ISIKTIYEEF HRGFYKVCNW DIIRQFQPEE LMTAIIGNAT CDWKQFENNS
     KYKDGYDKSH PTILLFWKAF HDLTLDEKKK FLLFLTGCDR LHVKGLQNEG IVFRCSETFS
     EEDNPRSLTC HRMLDLPKYS SMRRMKEALQ VAINNSTGFV SQE