HERC2_MOUSE
ID HERC2_MOUSE Reviewed; 4836 AA.
AC Q4U2R1; E9PZT6; O88473; Q3TRJ8; Q3TS47; Q3TST2; Q3UFQ6; Q3URH7; Q5DU32;
AC Q7TPR5; Q80VV7; Q9QYT1; Q9Z168; Q9Z171;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=E3 ubiquitin-protein ligase HERC2;
DE EC=2.3.2.26 {ECO:0000250|UniProtKB:O95714};
DE AltName: Full=HECT domain and RCC1-like domain-containing protein 2;
DE AltName: Full=HECT-type E3 ubiquitin transferase HERC2;
GN Name=Herc2 {ECO:0000312|EMBL:AAD08658.1, ECO:0000312|MGI:MGI:103234};
GN Synonyms=Jdf2, Kiaa0393 {ECO:0000312|EMBL:BAD90404.1}, Rjs;
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 [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND DISEASE.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAC31431.1};
RX PubMed=9689098; DOI=10.1073/pnas.95.16.9436;
RA Lehman A.L., Nakatsu Y., Ching A., Bronson R.T., Oakey R.J.,
RA Keiper-Hyrnko N., Finger J.N., Durham-Pierre D., Horton D.B., Newton J.M.,
RA Lyon M.F., Brilliant M.H.;
RT "A very large novel protein with diverse functional motifs is deficient in
RT rjs (runty, jerky, sterile) mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:9436-9441(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND DISEASE.
RX PubMed=9949213; DOI=10.1093/hmg/8.3.533;
RA Ji Y., Walkowicz M.J., Buiting K., Johnson D.K., Tarvin R.E., Rinchik E.M.,
RA Horsthemke B., Stubbs L., Nicholls R.D.;
RT "The ancestral gene for transcribed, low-copy repeats in the Prader-
RT Willi/Angelman region encodes a large protein implicated in protein
RT trafficking, which is deficient in mice with neuromuscular and spermiogenic
RT abnormalities.";
RL Hum. Mol. Genet. 8:533-542(1999).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 953-1553; 1845-2470 AND
RP 4123-4836.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE37031.1};
RC TISSUE=Spinal cord {ECO:0000312|EMBL:BAE24711.1},
RC Testis {ECO:0000312|EMBL:BAE36593.1}, and
RC Vagina {ECO:0000312|EMBL:BAE37031.1};
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2966-4836 (ISOFORM 1).
RC TISSUE=Brain {ECO:0000312|EMBL:BAD90404.1};
RA Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O.,
RA Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene. The
RT complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by
RT screening of terminal sequences of cDNA clones randomly sampled from size-
RT fractionated libraries.";
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3618-4836 (ISOFORM 2).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAH54829.1}, and
RC Czech II {ECO:0000312|EMBL:AAH44667.1};
RC TISSUE=Mammary gland {ECO:0000312|EMBL:AAH44667.1}, and
RC Olfactory epithelium {ECO:0000312|EMBL:AAH54829.1};
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 [7]
RP DISEASE.
RX PubMed=10441737; DOI=10.1007/s003359901106;
RA Walkowicz M., Ji Y., Ren X., Horsthemke B., Russell L.B., Johnson D.,
RA Rinchik E.M., Nicholls R.D., Stubbs L.;
RT "Molecular characterization of radiation- and chemically induced mutations
RT associated with neuromuscular tremors, runting, juvenile lethality, and
RT sperm defects in jdf2 mice.";
RL Mamm. Genome 10:870-878(1999).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1578, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1578; SER-1943; THR-1945 AND
RP SER-2929, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that regulates ubiquitin-
CC dependent retention of repair proteins on damaged chromosomes.
CC Recruited to sites of DNA damage in response to ionizing radiation (IR)
CC and facilitates the assembly of UBE2N and RNF8 promoting DNA damage-
CC induced formation of 'Lys-63'-linked ubiquitin chains. Acts as a
CC mediator of binding specificity between UBE2N and RNF8. Involved in the
CC maintenance of RNF168 levels. E3 ubiquitin-protein ligase that promotes
CC the ubiquitination and proteasomal degradation of XPA which influences
CC the circadian oscillation of DNA excision repair activity. By
CC controlling the steady-state expression of the IGF1R receptor,
CC indirectly regulates the insulin-like growth factor receptor signaling
CC pathway. {ECO:0000250|UniProtKB:O95714}.
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; Evidence={ECO:0000250|UniProtKB:O95714};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts (when phosphorylated at Thr-4829 and sumoylated)
CC with RNF8 (via FHA domain); this interaction increases after ionising
CC radiation (IR) treatment. Interacts with XPA. Interacts with NEURL4.
CC Via its interaction with NEURL4, may indirectly interact with CCP110
CC and CEP97. {ECO:0000250|UniProtKB:O95714}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O95714}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome,
CC centriole {ECO:0000250|UniProtKB:O95714}. Nucleus
CC {ECO:0000250|UniProtKB:O95714}. Note=Recruited to sites of DNA damage
CC in response to ionising radiation (IR) via its interaction with RNF8.
CC May loose association with centrosomes during mitosis.
CC {ECO:0000250|UniProtKB:O95714}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:9689098, ECO:0000269|PubMed:9949213};
CC IsoId=Q4U2R1-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:15489334};
CC IsoId=Q4U2R1-2; Sequence=VSP_051975;
CC -!- TISSUE SPECIFICITY: Highest levels are found in brain and testis with
CC lower levels in heart, lung, liver, skeletal muscle and kidney. Little
CC expression detected in spleen. {ECO:0000269|PubMed:9689098}.
CC -!- DOMAIN: The ZZ-type zinc finger mediates binding to SUMO1, and at low
CC level SUMO2. {ECO:0000250|UniProtKB:O95714}.
CC -!- DOMAIN: The RCC1 repeats are grouped into three seven-bladed beta-
CC propeller regions. {ECO:0000250|UniProtKB:O95714}.
CC -!- PTM: Phosphorylation at Thr-4829 is required for interaction with RNF8.
CC -!- PTM: Sumoylated with SUMO1 by PIAS4 in response to double-strand breaks
CC (DSBs), promoting the interaction with RNF8.
CC {ECO:0000250|UniProtKB:O95714}.
CC -!- DISEASE: Note=Defects in Herc2 are the cause of the runty, jerky,
CC sterile phenotype (rjs), also known as the juvenile development and
CC fertility phenotype (jfd2), which is characterized by reduced size,
CC jerky gait, fertility problems including spermatocyte and oocyte
CC abnormalities, defective maternal behavior and reduced lifespan with
CC juvenile lethality. {ECO:0000269|PubMed:10441737,
CC ECO:0000269|PubMed:9689098, ECO:0000269|PubMed:9949213}.
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DR EMBL; AF061529; AAC31431.1; -; mRNA.
DR EMBL; AF071173; AAD08658.1; -; mRNA.
DR EMBL; AC102121; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC102150; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK141515; BAE24711.1; -; mRNA.
DR EMBL; AK148361; BAE28504.1; -; mRNA.
DR EMBL; AK161826; BAE36593.1; -; mRNA.
DR EMBL; AK162270; BAE36828.1; -; mRNA.
DR EMBL; AK162708; BAE37031.1; -; mRNA.
DR EMBL; AK220338; BAD90404.1; -; mRNA.
DR EMBL; BC044667; AAH44667.1; -; mRNA.
DR EMBL; BC054829; AAH54829.1; -; mRNA.
DR CCDS; CCDS21318.1; -. [Q4U2R1-1]
DR RefSeq; NP_034548.2; NM_010418.2. [Q4U2R1-1]
DR RefSeq; XP_006540700.1; XM_006540637.3. [Q4U2R1-1]
DR RefSeq; XP_006540701.1; XM_006540638.2.
DR RefSeq; XP_006540702.1; XM_006540639.1. [Q4U2R1-2]
DR SMR; Q4U2R1; -.
DR BioGRID; 200274; 72.
DR IntAct; Q4U2R1; 61.
DR MINT; Q4U2R1; -.
DR STRING; 10090.ENSMUSP00000075579; -.
DR iPTMnet; Q4U2R1; -.
DR PhosphoSitePlus; Q4U2R1; -.
DR EPD; Q4U2R1; -.
DR jPOST; Q4U2R1; -.
DR MaxQB; Q4U2R1; -.
DR PaxDb; Q4U2R1; -.
DR PeptideAtlas; Q4U2R1; -.
DR PRIDE; Q4U2R1; -.
DR ProteomicsDB; 269656; -. [Q4U2R1-1]
DR ProteomicsDB; 269657; -. [Q4U2R1-2]
DR Antibodypedia; 22335; 53 antibodies from 11 providers.
DR DNASU; 15204; -.
DR Ensembl; ENSMUST00000076226; ENSMUSP00000075579; ENSMUSG00000030451. [Q4U2R1-1]
DR Ensembl; ENSMUST00000164095; ENSMUSP00000131573; ENSMUSG00000030451. [Q4U2R1-1]
DR Ensembl; ENSMUST00000205303; ENSMUSP00000145997; ENSMUSG00000030451. [Q4U2R1-2]
DR GeneID; 15204; -.
DR KEGG; mmu:15204; -.
DR UCSC; uc009hdv.1; mouse. [Q4U2R1-1]
DR CTD; 8924; -.
DR MGI; MGI:103234; Herc2.
DR VEuPathDB; HostDB:ENSMUSG00000030451; -.
DR eggNOG; KOG1426; Eukaryota.
DR GeneTree; ENSGT00940000154975; -.
DR HOGENOM; CLU_000101_0_0_1; -.
DR InParanoid; Q4U2R1; -.
DR OMA; GPRFKCK; -.
DR OrthoDB; 1062377at2759; -.
DR PhylomeDB; Q4U2R1; -.
DR TreeFam; TF320636; -.
DR Reactome; R-MMU-3108214; SUMOylation of DNA damage response and repair proteins.
DR Reactome; R-MMU-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-MMU-5693571; Nonhomologous End-Joining (NHEJ).
DR Reactome; R-MMU-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-MMU-69473; G2/M DNA damage checkpoint.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 15204; 0 hits in 108 CRISPR screens.
DR ChiTaRS; Herc2; mouse.
DR PRO; PR:Q4U2R1; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q4U2R1; protein.
DR Bgee; ENSMUSG00000030451; Expressed in secondary oocyte and 262 other tissues.
DR ExpressionAtlas; Q4U2R1; baseline and differential.
DR Genevisible; Q4U2R1; MM.
DR GO; GO:0005814; C:centriole; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005743; C:mitochondrial inner membrane; HDA:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0032183; F:SUMO binding; ISS:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IMP:MGI.
DR CDD; cd08664; APC10-HERC2; 1.
DR CDD; cd00078; HECTc; 1.
DR CDD; cd02344; ZZ_HERC2; 1.
DR Gene3D; 2.130.10.30; -; 3.
DR Gene3D; 2.30.30.30; -; 1.
DR Gene3D; 3.10.120.10; -; 1.
DR Gene3D; 3.30.60.90; -; 1.
DR InterPro; IPR004939; APC_su10/DOC_dom.
DR InterPro; IPR006624; Beta-propeller_rpt_TECPR.
DR InterPro; IPR021097; CPH_domain.
DR InterPro; IPR001199; Cyt_B5-like_heme/steroid-bd.
DR InterPro; IPR036400; Cyt_B5-like_heme/steroid_sf.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR000569; HECT_dom.
DR InterPro; IPR035983; Hect_E3_ubiquitin_ligase.
DR InterPro; IPR037976; HERC2_APC10.
DR InterPro; IPR010606; Mib_Herc2.
DR InterPro; IPR037252; Mib_Herc2_sf.
DR InterPro; IPR009091; RCC1/BLIP-II.
DR InterPro; IPR000408; Reg_chr_condens.
DR InterPro; IPR014722; Rib_L2_dom2.
DR InterPro; IPR000433; Znf_ZZ.
DR InterPro; IPR043145; Znf_ZZ_sf.
DR InterPro; IPR041987; ZZ_HERC2.
DR Pfam; PF03256; ANAPC10; 1.
DR Pfam; PF11515; Cul7; 1.
DR Pfam; PF00173; Cyt-b5; 1.
DR Pfam; PF00632; HECT; 1.
DR Pfam; PF06701; MIB_HERC2; 1.
DR Pfam; PF00415; RCC1; 16.
DR Pfam; PF00569; ZZ; 1.
DR PRINTS; PR00633; RCCNDNSATION.
DR SMART; SM01337; APC10; 1.
DR SMART; SM01117; Cyt-b5; 1.
DR SMART; SM00119; HECTc; 1.
DR SMART; SM00706; TECPR; 4.
DR SMART; SM00291; ZnF_ZZ; 1.
DR SUPFAM; SSF159034; SSF159034; 1.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF50985; SSF50985; 3.
DR SUPFAM; SSF55856; SSF55856; 1.
DR SUPFAM; SSF56204; SSF56204; 1.
DR PROSITE; PS50255; CYTOCHROME_B5_2; 1.
DR PROSITE; PS51284; DOC; 1.
DR PROSITE; PS50237; HECT; 1.
DR PROSITE; PS51416; MIB_HERC2; 1.
DR PROSITE; PS00626; RCC1_2; 1.
DR PROSITE; PS50012; RCC1_3; 19.
DR PROSITE; PS01357; ZF_ZZ_1; 1.
DR PROSITE; PS50135; ZF_ZZ_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Cytoplasm; Cytoskeleton; DNA damage;
KW DNA repair; Metal-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Transferase; Ubl conjugation; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..4836
FT /note="E3 ubiquitin-protein ligase HERC2"
FT /id="PRO_0000229740"
FT REPEAT 416..462
FT /note="RCC1 1-1"
FT REPEAT 463..513
FT /note="RCC1 1-2"
FT REPEAT 514..569
FT /note="RCC1 1-3"
FT REPEAT 570..621
FT /note="RCC1 1-4"
FT REPEAT 624..675
FT /note="RCC1 1-5"
FT REPEAT 676..727
FT /note="RCC1 1-6"
FT REPEAT 729..779
FT /note="RCC1 1-7"
FT DOMAIN 1208..1284
FT /note="Cytochrome b5 heme-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00279"
FT DOMAIN 1860..1933
FT /note="MIB/HERC2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00749"
FT DOMAIN 2760..2937
FT /note="DOC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00614"
FT REPEAT 2959..3010
FT /note="RCC1 2-1"
FT REPEAT 3011..3065
FT /note="RCC1 2-2"
FT REPEAT 3066..3117
FT /note="RCC1 2-3"
FT REPEAT 3119..3169
FT /note="RCC1 2-4"
FT REPEAT 3172..3223
FT /note="RCC1 2-5"
FT REPEAT 3225..3275
FT /note="RCC1 2-6"
FT REPEAT 3276..3327
FT /note="RCC1 2-7"
FT REPEAT 3953..4004
FT /note="RCC1 3-1"
FT REPEAT 4006..4058
FT /note="RCC1 3-2"
FT REPEAT 4060..4110
FT /note="RCC1 3-3"
FT REPEAT 4112..4164
FT /note="RCC1 3-4"
FT REPEAT 4166..4216
FT /note="RCC1 3-5"
FT REPEAT 4218..4268
FT /note="RCC1 3-6"
FT REPEAT 4270..4320
FT /note="RCC1 3-7"
FT DOMAIN 4459..4796
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT ZN_FING 2704..2756
FT /note="ZZ-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT REGION 58..90
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2351..2376
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2928..2947
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3479..3499
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3517..3537
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3604..3632
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4806..4836
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 948..981
FT /evidence="ECO:0000255"
FT COMPBIAS 3480..3496
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 4810..4824
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 4764
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT BINDING 2709
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 2712
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 2724
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 2727
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 2733
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 2736
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 2742
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 2746
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT MOD_RES 273
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O95714"
FT MOD_RES 648
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O95714"
FT MOD_RES 1578
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 1943
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1945
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 2455
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95714"
FT MOD_RES 2929
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 4812
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95714"
FT MOD_RES 4813
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95714"
FT MOD_RES 4816
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95714"
FT MOD_RES 4829
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O95714"
FT VAR_SEQ 3637..3672
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_051975"
FT CONFLICT 692
FT /note="H -> L (in Ref. 1; AAC31431)"
FT /evidence="ECO:0000305"
FT CONFLICT 724
FT /note="A -> V (in Ref. 2; AAD08658)"
FT /evidence="ECO:0000305"
FT CONFLICT 747
FT /note="R -> G (in Ref. 2; AAD08658)"
FT /evidence="ECO:0000305"
FT CONFLICT 756
FT /note="L -> F (in Ref. 2; AAD08658)"
FT /evidence="ECO:0000305"
FT CONFLICT 929
FT /note="R -> P (in Ref. 2; AAD08658)"
FT /evidence="ECO:0000305"
FT CONFLICT 1114
FT /note="S -> N (in Ref. 2; AAD08658)"
FT /evidence="ECO:0000305"
FT CONFLICT 1235
FT /note="G -> D (in Ref. 2; AAD08658)"
FT /evidence="ECO:0000305"
FT CONFLICT 2348
FT /note="A -> P (in Ref. 1; AAC31431)"
FT /evidence="ECO:0000305"
FT CONFLICT 2470
FT /note="G -> S (in Ref. 4; BAE36828)"
FT /evidence="ECO:0000305"
FT CONFLICT 2523
FT /note="E -> D (in Ref. 1; AAC31431)"
FT /evidence="ECO:0000305"
FT CONFLICT 2567
FT /note="Y -> F (in Ref. 1; AAC31431)"
FT /evidence="ECO:0000305"
FT CONFLICT 2572
FT /note="V -> L (in Ref. 1; AAC31431)"
FT /evidence="ECO:0000305"
FT CONFLICT 3095
FT /note="E -> Q (in Ref. 2; AAD08658)"
FT /evidence="ECO:0000305"
FT CONFLICT 3107
FT /note="C -> Y (in Ref. 2; AAD08658)"
FT /evidence="ECO:0000305"
FT CONFLICT 3114
FT /note="A -> P (in Ref. 2; AAD08658)"
FT /evidence="ECO:0000305"
FT CONFLICT 3161
FT /note="S -> T (in Ref. 1; AAC31431)"
FT /evidence="ECO:0000305"
FT CONFLICT 3385..3386
FT /note="LL -> VV (in Ref. 2; AAD08658)"
FT /evidence="ECO:0000305"
FT CONFLICT 3508
FT /note="A -> V (in Ref. 2; AAD08658)"
FT /evidence="ECO:0000305"
FT CONFLICT 4069
FT /note="E -> K (in Ref. 5; BAD90404)"
FT /evidence="ECO:0000305"
FT CONFLICT 4187
FT /note="C -> S (in Ref. 1; AAC31431)"
FT /evidence="ECO:0000305"
FT CONFLICT 4604
FT /note="P -> S (in Ref. 4; BAE36593)"
FT /evidence="ECO:0000305"
FT CONFLICT 4716
FT /note="T -> A (in Ref. 1; AAC31431)"
FT /evidence="ECO:0000305"
FT CONFLICT 4723
FT /note="R -> C (in Ref. 2; AAD08658)"
FT /evidence="ECO:0000305"
FT CONFLICT 4730
FT /note="R -> S (in Ref. 1; AAC31431)"
FT /evidence="ECO:0000305"
FT CONFLICT 4752
FT /note="N -> Y (in Ref. 1; AAC31431)"
FT /evidence="ECO:0000305"
FT CONFLICT 4790
FT /note="C -> S (in Ref. 1; AAC31431)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 4836 AA; 527456 MW; 481BC90E231C93D8 CRC64;
MPSESFCLAA QSRLDSKWLK TDIQLAFTRD GLCGLWNEMV KDGEIVYTGT ELAQNRELPL
RKDDGVDAQS GTKKEDLNDK EKKEEEETPA PVYRAKSILE SWVWGRQPDV NELKECLSVL
VKEQQALAVQ SATTTLSALR LKQRLVILER YFIALNRTVF QENVKVKWKS SSISVPPTEK
KSARPTGRGV EGLARVGSRA ALSFAFAFLR RAWRSGEDAD LCSELLQESL DALRALPEAS
LFDESTVSSV WLEVVERATR FLRSVVTGDV HGTPGTKGPG GVPLQDQHLA LAILLELAVQ
RGTLSQMLSA ILLLLQLWDS GAQETDNERS AQGTSAPLLP LLQRFQSIIC SKDVPHTESD
MHLLSGPLSP NESFLRYLTL PQDNELAIDL RQTAVVVMAH LDRLATPCMP PLCSSPTSHK
GSLQEVIGWG LIGWKYYANV IGPIQCEGLA SLGVMQVACA EKRFLILSRN GRVYTQAYNS
DMLAPQLVQG LASRNIVKIA AHSDGHHYLA LAATGEVYSW GCGDGGRLGH GDTVPLEEPK
VISAFSGKQA GKHVVHIACG STYSAAITAE GELYTWGRGN YGRLGHGSSE DEAIPMLVAG
LKGLKVIDVA CGSGDAQTLA VTENGQVWSW GDGDYGKLGR GGSDGCKTPK LIEKLQDLDV
IKVRCGSQFS IALTKDGQVY SWGKGDNQRL GHGTEEHVRY PKLLEGLQGK KVIDVAAGST
HCLALTEDSE VHSWGSNDQC QHFDTLRVTK PEPTALPGLD SKHIVGIACG PAQSFAWSSC
SEWSIGLRVP FVVDICSMTF EQLDLLLRQV SEGMDGTADW PPPQEKECMA VATLNLLRLQ
LHAAISHQVD PEFLGLGLGS VLLNSLKQTV VTLASSAGVL STVQSAAQAV LQSGWSVLLP
TAEERARALS ALLPCTVSGN EVNISPGRRF MIDLLVGSLM ADGGLESALN AAITAEIQDI
EAKKEAQKEK EIDEQEASAS TFHRSRTPLD KDLINTGIYE SSGKQCLPLV QLIQQLLRNI
ASQTVARLKD VARRISSCLD FEQQSCERSA SLDLLLRFQR LLISKLYPGE KIGPISDTSS
PELMGVGSLL KKYTALVCTH IGDILPVAAS IASSSWQHFA EVACVMEGDF TGVLLPELVV
SIVLLLSKNA SLMQEAGAIP LLGGLLEHLD RFNHLAPGKE RDDHEELAWP GIMESFFTGQ
NCRNNEEVTL IRKADLENHN KDGGFWTVID GKVYGIKDFQ TQSLTGNSIL AQFAGEDPVV
ALEAALQFED TQESMHAFCV GQYLEPDQEV VTIPDLGSLS SPLIDTERNL GLLLGLHASY
LAMSTPLSPV EVECAKWLQS SIFSGGLQTS QIHYSYNEEK DEDHCSSPGG TPISKSRLCS
HRWALGDHSQ AFLQAIADNN IQDYNVKDFL CQIERYCRQC HLTTPITFPP EHPVEEVGRL
LLCCLLKHED LGHVALSLVH VGTLGIEQVK HRTLPKSVVD VCRVVYQAKC SLIKTHQEQG
RSYKEVCAPV IERLRFLFNE LRPAVCSDLS IMSKFKLLGS LPRWRRIAQK IIRERRKKRV
PKKPESIDSE EKIGNEESDL EEACVLPHSP INVDKRPISM KSPKDKWQPL LNTVTGVHKY
KWLKQNVQGL YPQSALLNTI VEFALKEEPV DVEKMRKCLL KQLERAEVRL EGIDTILKLA
AKSFLLPSVQ YAMFCGWQRL IPEGIDIGEP LTDCLRDVDL IPPFNRMLLE VTFGKLYAWA
VQNIRSVLMD ASARFKELGI QPVPLQTITN ENPAGPSLGT IPQARFLLVM LSMLTLQHGA
NNLDLLLNSG TLALTQTALR LIGPTCDSVE DDMNASARGA SATVLEETRK ETAPVQLPVS
GPELAAMMKI GTRVMRGVDW KWGDQDGPPP GLGRVIGELG EDGWIRVQWD TGSTNSYRMG
KEGKYDLKLV ELPVSSQPSA EDSDTEDDSE AEQGERNIHP TAMMLTSVIN LLQTLCLSVG
VHADIMQSEA TKTLCGLLRM LVESGTTDKP APPDRLVARE QHRSWCTLGF VRSIALTPQA
CGALSSPRWI TLLMKVVEGH APFTAASLQR QILAVHLLQA VLPSWDKTER ARDMKCLVEK
LFGFLGSLLT TCSSDVPLLR ESTLRKRRAR PQASLTATHS STLAEEVVGL LRTLHSLTQW
NGLINKYINS QLCSVTQSYA GKTSERAQLE DYFPDSENLE VGGLMAVLAV IGGIDGRLRL
GGQVMHDEFG EGTVTRITPK GRITVQFCDM RMCRVCPLNQ LKPLPAVAFS VNNLPFTEPM
LSVWAELVNL AGSKLEKHKT KKSAKPAFAG QVDLDLLRSQ QLKLYILKAG RALLSHQDKL
RQILSQPAVQ GTGTLQTDDG AAASPDLGDM SPEGPQPPMI LLQQLLSSAT QPSPVKAIFD
KQELEAAALA LCQCLAVEST HPSSPGCEDC SSSEATTPVS VQHIHLARAK KRRQSPAPAL
PIVVQLMEMG FPRKNIEFAL KSLTGTSGNA SGLPGVEALV GWLLDHSDVQ VTEFSDAETL
SDEYSDEEVV EDVDDTPYPV AAGAVVTESQ TYKKRADFLS NDDYAVYVRE NVQVGMMVRC
CRTYEEVCEG DVGKVIKLDR DGLHDLNVQC DWQQKGGTYW VRYIHVELIG YPPPSSSSHI
KIGDKVRVKA SVTTPKYKWG SVTHQSVGLV KAFSANGKDI IVDFPQQSHW TGLLSEMELV
PSIHPGVTCD GCQTFPINGS RFKCRNCDDF DFCETCFKTK KHNTRHTFGR INEPGQSAVF
CGRSGKQLKR CHSSQPGMLL DSWSRMVKSL NVSSSVNQAS RLIDGSEPCW QSSGSQGKHW
IRLEIFPDVL VHRLKMIVDP ADSSYMPSLV VVSGGNSLNN LIELKTININ QTDTTVPLLS
DCAEYHRYIE IAIKQCRSSG IDCKIHGLIL LGRIRAEEED LAAVPFLASD NEEEEDDKGS
TGSLIRKKTP GLESTATIRT KVFVWGLNDK DQLGGLKGSK IKVPSFSETL SALNVVQVAG
GSKSLFAVTV EGKVYSCGEA TNGRLGLGMS SGTVPIPRQI TALSSYVVKK VAVHSGGRHA
TALTVDGKVF SWGEGDDGKL GHFSRMNCDK PRLIEALKTK RIRDIACGSS HSAALTSSGE
LYTWGLGEYG RLGHGDNTTQ LKPKMVKVLL GHRVIQVACG SRDAQTLALT DEGLVFSWGD
GDFGKLGRGG SEGCNIPQNI ERLNGQGVCQ IECGAQFSLA LTKSGVVWTW GKGDYFRLGH
GSDVHVRKPQ VVEGLRGKKI VHVAVGALHC LAVTDSGQVY AWGDNDHGQQ GNGTTTVNRK
PTLVQGLEGQ KITRVACGSS HSVAWTTVDV ATPSVHEPVL FQTARDPLGA SYLGVPSDAD
SSSSSNKISG ANNCKPNRPS LAKILLSLEG NLAKQQALSH ILTALQIMYA RDAVVGALMP
AGMLAPVECP SFSSSAPASD VSAMASPMHM EDSTLAADLE DRLSPNLWQE KREIVSSEDA
VTPSAVTPSA PSASSRPFIP VTDDPGAASI IAETMTKTKE DVESQNKTSG PEPQSLDEFT
SLLIPDDTRV VVELLKLSVC SRAGDKGREV LSAVLSGMGT AYPQVADMLL ELCVTELEDV
ATDSQSGRLS SQPVVVESSH PYTDDTSTSG TVKIPGAEGL RVEFDRQCST ERRHDPLTVM
DGVNRIVSVR SGREWSDWSS ELRIPGDELK WKFISDGSVN GWGWRFTVYP IMPAAGPKDL
LSDRCVLSCP SMDLVTCLLD FRLNLTSNRS IVPRLAASLA ACAQLSALAA SHRMWALQRL
RRLLTTEFGQ SININRLLGE NDGESRALSF TGSALAALVK GLPEALQRQF EYEDPIVRGG
KQLLHSPFFK VLVALACDLE LDTLPCCAET HKWAWFRRYC MASRVAVALD KRTPLPRLFL
DEVAKKIREL MADSESMDVL HESHSIFKRE QDEQLVQWMN RRPDDWTLSA GGSGTIYGWG
HNHRGQLGGI EGAKVKVPTP CEALATLRPV QLIGGEQTLF AVTADGKLYA TGYGAGGRLG
IGGTESVSTP TLLESIQHVF IKKVAVNSGG KHCLALSSEG EVYSWGEAED GKLGHGNRSP
CDRPRVIESL RGIEVVDVAA GGAHSACVTA AGDLYTWGKG RYGRLGHSDS EDQLKPKLVE
ALQGHRVIDI ACGSGDAQTL CLTDDDTVWS WGDGDYGKLG RGGSDGCKVP MKIDSLTGLG
VVKVECGSQF SVALTKSGAV YTWGKGDYHR LGHGSDDHVR RPRQVQGLQG KKVIAIATGS
LHCVCCTEDG EVYTWGDNDE GQLGDGTTNA IQRPRLVAAL QGKKVNRVAC GSAHTLAWST
SKPASAGKLP AQVPMEYNHL QEIPIIALRN RLLLLHHISE LFCPCIPMFD LEGSLDETGL
GPSVGFDTLR GILISQGKEA AFRKVVQATM VRDRQHGPVV ELNRIQVKRS RSKGGLAGPD
GTKSVFGQMC AKMSSFSPDS LLLPHRVWKV KFVGESVDDC GGGYSESIAE ICEELQNGLT
PLLIVTPNGR DESGANRDCY LLNPATRAPV HCSMFRFLGV LLGIAIRTGS PLSLNLAEPV
WKQLAGMSLT IADLSEVDKD FIPGLMYIRD NEATSEEFEA MSLPFTVPSA SGQDIQLSSK
HTHITLDNRA EYVRLAINYR LHEFDEQVAA VREGMARVVP VPLLSLFTGY ELETMVCGSP
DIPLHLLKSV ATYKGIEPSA SLVQWFWEVM ESFSNTERSL FLRFVWGRTR LPRTIADFRG
RDFVIQVLDK YNPPDHFLPE SYTCFFLLKL PRYSCKQVLE EKLKYAIHFC KSIDTDDYAR
IALTGEPAAD DSSEDSDNED ADSFASDSTQ DYLTGH
