HUWE1_MOUSE
ID HUWE1_MOUSE Reviewed; 4377 AA.
AC Q7TMY8; A2AFQ1; Q4G2Z1; Q5BMM7; Q6NS61; Q8BNJ7; Q8CFH2; Q8VD14; Q921M5;
AC Q9R0P2;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 5.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=E3 ubiquitin-protein ligase HUWE1;
DE EC=2.3.2.26;
DE AltName: Full=E3Histone {ECO:0000303|PubMed:15989956};
DE AltName: Full=HECT, UBA and WWE domain-containing protein 1;
DE AltName: Full=HECT-type E3 ubiquitin transferase HUWE1;
DE AltName: Full=Upstream regulatory element-binding protein 1;
DE Short=URE-B1;
DE Short=URE-binding protein 1;
GN Name=Huwe1; Synonyms=Kiaa0312, Ureb1;
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).
RC STRAIN=C57BL/6J;
RX PubMed=15989956; DOI=10.1016/j.cell.2005.03.037;
RA Chen D., Kon N., Li M., Zhang W., Qin J., Gu W.;
RT "ARF-BP1/Mule is a critical mediator of the ARF tumor suppressor.";
RL Cell 121:1071-1083(2005).
RN [2]
RP SEQUENCE REVISION TO 253; 1728; 2009-2010; 2032 AND 3034-3035.
RA Chen D., Kon N., Li M., Zhang W., Qin J., Gu W.;
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RC STRAIN=C57BL/6J;
RX PubMed=15767685; DOI=10.1128/mcb.25.7.2819-2831.2005;
RA Liu Z., Oughtred R., Wing S.S.;
RT "Characterization of E3Histone, a novel testis ubiquitin protein ligase
RT which ubiquitinates histones.";
RL Mol. Cell. Biol. 25:2819-2831(2005).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1445-4377 (ISOFORM 1).
RC TISSUE=Embryonic intestine;
RX PubMed=12465718; DOI=10.1093/dnares/9.5.179;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Hara Y., Nagase T., Ohara O.,
RA Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: I.
RT The complete nucleotide sequences of 100 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 9:179-188(2002).
RN [6]
RP SEQUENCE REVISION.
RC TISSUE=Brain;
RA Okazaki N., Kikuno R., Nagase T., Ohara O., Koga H.;
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP PROTEIN SEQUENCE OF 1627-1655; 3127-3133 AND 3245-3253, AND IDENTIFICATION
RP BY MASS SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1630-4377 (ISOFORM 2), AND
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3283-4377 (ISOFORM 3).
RC STRAIN=C57BL/6J, and FVB/N-3; TISSUE=Brain, Eye, and Mammary gland;
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3421-4377 (ISOFORM 4).
RC STRAIN=C57BL/6J;
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 [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4005-4377 (ISOFORMS 1/3).
RA Seki N., Hattori A., Hayashi A., Kozuma S., Muramatsu M., Saito T.;
RT "Mouse homolog to KIAA0312.";
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [12]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17823942; DOI=10.1002/dvdy.21302;
RA Liu Z., Miao D., Xia Q., Hermo L., Wing S.S.;
RT "Regulated expression of the ubiquitin protein ligase,
RT E3(Histone)/LASU1/Mule/ARF-BP1/HUWE1, during spermatogenesis.";
RL Dev. Dyn. 236:2889-2898(2007).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1395; SER-1907 AND SER-3810,
RP AND IDENTIFICATION BY 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 [14]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=18488021; DOI=10.1038/ncb1727;
RA Zhao X., Heng J.I.-T., Guardavaccaro D., Jiang R., Pagano M., Guillemot F.,
RA Iavarone A., Lasorella A.;
RT "The HECT-domain ubiquitin ligase Huwe1 controls neural differentiation and
RT proliferation by destabilizing the N-Myc oncoprotein.";
RL Nat. Cell Biol. 10:643-653(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1907, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-648; SER-649; SER-1368;
RP SER-1395; SER-1907; SER-2362; SER-3758; SER-3761; SER-3810; SER-3818;
RP SER-3922; THR-3927 AND THR-3930, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and 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).
RN [17]
RP FUNCTION.
RX PubMed=20534529; DOI=10.1073/pnas.1000438107;
RA Yin L., Joshi S., Wu N., Tong X., Lazar M.A.;
RT "E3 ligases Arf-bp1 and Pam mediate lithium-stimulated degradation of the
RT circadian heme receptor Rev-erb alpha.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:11614-11619(2010).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-2267, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [19]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-3149, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which mediates ubiquitination and
CC subsequent proteasomal degradation of target proteins (PubMed:15767685,
CC PubMed:18488021). Regulates apoptosis by catalyzing the
CC polyubiquitination and degradation of MCL1 (By similarity). Mediates
CC monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61'
CC and 'Lys-81', thereby playing a role in base-excision repair (By
CC similarity). Also ubiquitinates the p53/TP53 tumor suppressor and core
CC histones including H1, H2A, H2B, H3 and H4 (PubMed:15767685).
CC Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in
CC response to decreased stearoylation of TFRC (By similarity).
CC Ubiquitination of MFN2 also takes place following induction of
CC mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination
CC (By similarity). Regulates neural differentiation and proliferation by
CC catalyzing the polyubiquitination and degradation of MYCN
CC (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by
CC polyubiquitinating and targeting CDC6 to degradation (By similarity).
CC Mediates polyubiquitination of PA2G4 (By similarity). Acts in concert
CC with MYCBP2 to regulate the circadian clock gene expression by
CC promoting the lithium-induced ubiquination and degradation of NR1D1 (By
CC similarity). Binds to an upstream initiator-like sequence in the
CC preprodynorphin gene (By similarity). {ECO:0000250|UniProtKB:P51593,
CC ECO:0000250|UniProtKB:Q7Z6Z7, ECO:0000269|PubMed:15767685,
CC ECO:0000269|PubMed:18488021}.
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 -!- SUBUNIT: Interacts with isoform p19ARF of CDKN2A which strongly
CC inhibits HUWE1 ubiquitin ligase activity (By similarity). Interacts
CC with MYCN, POLB and CDC6 (By similarity). Interacts with PA2G4 (By
CC similarity). Interacts with NR1D1 (By similarity). Interacts with
CC AMBRA1 (By similarity). {ECO:0000250|UniProtKB:Q7Z6Z7}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17823942}. Nucleus
CC {ECO:0000269|PubMed:17823942}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q7Z6Z7}. Note=Mainly expressed in the cytoplasm
CC of most tissues, except in the nucleus of spermatogonia, primary
CC spermatocytes and neuronal cells (PubMed:17823942). Recruited to
CC mitochondria following interaction with AMBRA1 (By similarity).
CC {ECO:0000250|UniProtKB:Q7Z6Z7, ECO:0000269|PubMed:17823942}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q7TMY8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7TMY8-2; Sequence=VSP_011147, VSP_011148;
CC Name=3;
CC IsoId=Q7TMY8-3; Sequence=VSP_011149;
CC Name=4;
CC IsoId=Q7TMY8-4; Sequence=VSP_011150, VSP_011151;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:17823942}.
CC -!- DEVELOPMENTAL STAGE: Expression increases during neuronal
CC differentiation such that the cortical plate contains the highest
CC level. {ECO:0000269|PubMed:18488021}.
CC -!- DOMAIN: The HECT domain mediates inhibition of the transcriptional
CC activity of p53. {ECO:0000250|UniProtKB:Q7Z6Z7}.
CC -!- PTM: Phosphorylated on tyrosine; phosphorylation is probably required
CC for its ability to inhibit TP53 transactivation.
CC {ECO:0000250|UniProtKB:Q7Z6Z7}.
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DR EMBL; AY772010; AAV90839.3; -; mRNA.
DR EMBL; AY929611; AAX24124.1; -; mRNA.
DR EMBL; AL672180; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL954855; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX571795; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB093227; BAC41411.2; -; mRNA.
DR EMBL; BC011391; AAH11391.1; -; mRNA.
DR EMBL; BC017642; AAH17642.2; -; mRNA.
DR EMBL; BC054372; AAH54372.1; -; mRNA.
DR EMBL; BC070444; AAH70444.1; -; mRNA.
DR EMBL; AK083499; BAC38936.1; -; mRNA.
DR EMBL; AB025966; BAA84697.1; -; mRNA.
DR RefSeq; NP_067498.4; NM_021523.4.
DR SMR; Q7TMY8; -.
DR BioGRID; 208493; 92.
DR IntAct; Q7TMY8; 51.
DR MINT; Q7TMY8; -.
DR STRING; 10090.ENSMUSP00000026292; -.
DR iPTMnet; Q7TMY8; -.
DR PhosphoSitePlus; Q7TMY8; -.
DR SwissPalm; Q7TMY8; -.
DR EPD; Q7TMY8; -.
DR jPOST; Q7TMY8; -.
DR MaxQB; Q7TMY8; -.
DR PaxDb; Q7TMY8; -.
DR PeptideAtlas; Q7TMY8; -.
DR PRIDE; Q7TMY8; -.
DR ProteomicsDB; 273355; -. [Q7TMY8-1]
DR ProteomicsDB; 273356; -. [Q7TMY8-2]
DR ProteomicsDB; 273357; -. [Q7TMY8-3]
DR ProteomicsDB; 273358; -. [Q7TMY8-4]
DR Antibodypedia; 448; 174 antibodies from 35 providers.
DR DNASU; 59026; -.
DR Ensembl; ENSMUST00000112622; ENSMUSP00000108241; ENSMUSG00000025261. [Q7TMY8-1]
DR GeneID; 59026; -.
DR KEGG; mmu:59026; -.
DR UCSC; uc009upq.2; mouse. [Q7TMY8-1]
DR UCSC; uc009upr.1; mouse. [Q7TMY8-2]
DR CTD; 10075; -.
DR MGI; MGI:1926884; Huwe1.
DR VEuPathDB; HostDB:ENSMUSG00000025261; -.
DR eggNOG; KOG0939; Eukaryota.
DR GeneTree; ENSGT00940000156319; -.
DR HOGENOM; CLU_000058_0_0_1; -.
DR InParanoid; Q7TMY8; -.
DR OrthoDB; 25515at2759; -.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 59026; 33 hits in 115 CRISPR screens.
DR ChiTaRS; Huwe1; mouse.
DR PRO; PR:Q7TMY8; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q7TMY8; protein.
DR Bgee; ENSMUSG00000025261; Expressed in embryonic post-anal tail and 261 other tissues.
DR ExpressionAtlas; Q7TMY8; baseline and differential.
DR Genevisible; Q7TMY8; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0000139; C:Golgi membrane; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0006284; P:base-excision repair; ISS:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0032922; P:circadian regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0007030; P:Golgi organization; IBA:GO_Central.
DR GO; GO:0016574; P:histone ubiquitination; ISS:UniProtKB.
DR GO; GO:0061025; P:membrane fusion; IBA:GO_Central.
DR GO; GO:0010637; P:negative regulation of mitochondrial fusion; ISO:MGI.
DR GO; GO:0098779; P:positive regulation of mitophagy in response to mitochondrial depolarization; ISO:MGI.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0006513; P:protein monoubiquitination; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR CDD; cd00078; HECTc; 1.
DR CDD; cd14288; UBA_HUWE1; 1.
DR Gene3D; 3.30.720.50; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR010309; E3_Ub_ligase_DUF908.
DR InterPro; IPR010314; E3_Ub_ligase_DUF913.
DR InterPro; IPR000569; HECT_dom.
DR InterPro; IPR035983; Hect_E3_ubiquitin_ligase.
DR InterPro; IPR025527; HUWE1/Rev1_UBM.
DR InterPro; IPR015940; UBA.
DR InterPro; IPR009060; UBA-like_sf.
DR InterPro; IPR041918; UBA_HUWE1.
DR InterPro; IPR004170; WWE-dom.
DR InterPro; IPR037197; WWE_dom_sf.
DR Pfam; PF06012; DUF908; 1.
DR Pfam; PF06025; DUF913; 1.
DR Pfam; PF00632; HECT; 1.
DR Pfam; PF00627; UBA; 1.
DR Pfam; PF14377; UBM; 3.
DR Pfam; PF02825; WWE; 1.
DR SMART; SM00119; HECTc; 1.
DR SMART; SM00165; UBA; 1.
DR SUPFAM; SSF117839; SSF117839; 1.
DR SUPFAM; SSF46934; SSF46934; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF56204; SSF56204; 1.
DR PROSITE; PS50237; HECT; 1.
DR PROSITE; PS50030; UBA; 1.
DR PROSITE; PS50918; WWE; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Biological rhythms; Cytoplasm;
KW Differentiation; Direct protein sequencing; DNA damage; DNA repair;
KW DNA-binding; Methylation; Mitochondrion; Nucleus; Phosphoprotein;
KW Reference proteome; Transferase; Ubl conjugation pathway.
FT CHAIN 1..4377
FT /note="E3 ubiquitin-protein ligase HUWE1"
FT /id="PRO_0000120341"
FT DOMAIN 1316..1355
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT DOMAIN 1370..1389
FT /note="UIM"
FT /evidence="ECO:0000305"
FT DOMAIN 1603..1680
FT /note="WWE"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00248"
FT DOMAIN 4041..4377
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT REGION 706..758
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 978..1001
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1018..1038
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1291..1320
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1396..1415
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1690..1735
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2019..2065
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2262..2343
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2355..2479
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2704..2970
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2991..3012
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3036..3059
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3243..3266
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3352..3383
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3405..3429
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3471..3514
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3539..3566
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3738..3759
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3782..3850
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3897..3951
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 737..756
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 987..1001
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1291..1310
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1699..1721
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2019..2035
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2036..2060
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2262..2293
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2384..2402
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2406..2471
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2704..2718
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2719..2769
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2815..2867
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2877..2891
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2905..2934
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2991..3009
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3041..3059
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3244..3260
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3471..3505
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3539..3557
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3784..3801
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3815..3832
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3897..3914
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3932..3951
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 4344
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT MOD_RES 648
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 649
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 740
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 1084
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 1368
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1370
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 1382
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 1395
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 1907
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:19131326, ECO:0007744|PubMed:21183079"
FT MOD_RES 2035
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 2266
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 2267
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 2362
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 2365
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 2391
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 2527
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 2532
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 2535
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 2554
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 2584
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 2595
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 2619
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 2751
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 2826
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 2833
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 2835
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 2861
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 2887
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 2888
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 2889
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 2918
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 3116
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 3117
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 3122
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 3127
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 3135
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 3149
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 3557
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 3663
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 3753
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 3758
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 3760
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 3761
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 3810
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 3818
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 3830
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 3833
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 3909
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z6Z7"
FT MOD_RES 3922
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 3927
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 3930
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 4274
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P51593"
FT VAR_SEQ 3347..3364
FT /note="FPSHFTQQRTKETNCESD -> RSLKESLTPGFFGHQHLG (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_011147"
FT VAR_SEQ 3365..4377
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_011148"
FT VAR_SEQ 3780..3794
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_011149"
FT VAR_SEQ 3795..3832
FT /note="SESSNQSETSVRREESPMDVDQPSPSAQDTQSIVISDG -> VSMMPVAPHS
FT FLYPPSCTMSSVGVHCPYLVCFCITFAK (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_011150"
FT VAR_SEQ 3833..4377
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_011151"
FT CONFLICT 253
FT /note="K -> R (in Ref. 3; AAX24124 and 1; AAV90839)"
FT /evidence="ECO:0000305"
FT CONFLICT 1728
FT /note="S -> I (in Ref. 1; AAV90839 and 5; BAC41411)"
FT /evidence="ECO:0000305"
FT CONFLICT 2032
FT /note="E -> EG (in Ref. 1; AAV90839, 5; BAC41411 and 8;
FT AAH70444)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 4377 AA; 482635 MW; 22700C859CD9AF83 CRC64;
MKVDRTKLKK TPTEAPADCR ALIDKLKVCN DEQLLLELQQ IKTWNIGKCE LYHWVDLLDR
FDGILADAGQ TVENMSWMLV CDRPEKEQLK MLLLAVLNFT ALLIEYSFSR HLYSSIEHLT
TLLASSDMQV VLAVLNLLYV FSKRSNYITR LGSDKRTPLL TRLQHLAESW GGKENGFGLA
ECCRDLQMLK YPPSATTLHF EFYADPGAEV KIEKRTTSNT LHYIHIEQLD KISESPSEIM
ESLTKMYSIP KDKQMLLFTH IRLAHGFSNH RKRLQAVQAR LHAISILVYS NALQESANSI
LYNGLIEELV DVLQITDKQL MEIKAASLRT LTSIVHLERT PKLSSIIDCT GTASYHGFLP
VLVRNCIQAM IDPSMDPYPH QFATALFSFL YHLASYDAGG EALVSCGMME ALLKVIKFLG
DEQDQITFVT RAVRVVDLIT NLDMAAFQSH SGLSIFIYRL EHEVDLCRKE CPFVIKPKIQ
RPSTTQEGEE METDMDGVQC IPQRAALLKS MLNFLKKAIQ DPAFSDGIRH VMDGSLPTSL
KHIISNAEYY GPSLFLLATE VVTVFVFQEP SLLSSLQDNG LTDVMLHALL IKDVPATREV
LGSLPNVFSA LCLNARGLQS FVQCQPFERL FKVLLSPDYL PAMRRRRSSD PLGDTASNLG
SAVDELMRHQ PTLKTDATTA IIKLLEEICN LGRDPKYICQ KPSIQKADGT ATAPPPRSNH
AAEEASSEDE EEEEVQAMQS FNSAQQNETE PNQQVVGTEE RIPIPLMDYI LNVMKFVESI
LSNNTTDDHC QEFVNQKGLL PLVTILGLPN LPIDFPTSAA CQAVAGVCKS ILTLSHEPKV
LQEGLLQLDL ILSSLEPLHR PIESPGGSVL LRELACAGNV ADATLSAQAT PLLHALTAAH
AYIMMFVHTC RVGQSEIRSI SVNQWGSQLG LSVLSKLSQL YCSLVWESTV LLSLCTPNSL
PSGCEFGQAD MQKLVPKDEK AGTTQGGKRS DGEQDGTAGS MDASAQGLLE GIELDGDTLA
PMETDEPSSS DSKGKSKITP AMAARIKQIK PLLSASSRLG RALAELFGLL VKLCVGSPVR
QRRSHHAAST TTAPTPAARS TASALTKLLT KGLSWQPPPY TPTPRFRLTF FICSVGFTSP
MLFDERKYPY HLMLQKFLCS GGHNALFETF NWALSMGGKV PVSEGLEHSD LPDGTGEFLD
AWLMLVEKMV NPTTVLESPH SLPAKLPGGV QSFPQFSALR FLVVTQKAAF TCIKNLWNRK
PLKVYGGRMA ESMLAILCHI LRGEPVIRER LSKEKEGSRG EEEAGQEEGG SRREPQVNQQ
QLQQLMDMGF TREHAMEALL NTSTMEQATE YLLTHPPPII GGVVRDLSMS EEDQMMRAIA
MSLGQDIPMD QRAESPEEVA CRKEEEERKA REKQEEEEAK CLEKFQDADP LEQDELHTFT
DTMLPGCFHL LDELPDTVYR VCDLIMTAIK RNGADYRDMI LKQVVNQVWE AADVLIKAAL
PLTTSDTKTV SEWISQMATL PQASNLATRI LLLTLLFEEL KLPCAWVVES SGILNVLIKL
LEVVQPCLQA AKEQKEVQTP KWITPVLLLI DFYEKTAISS KRRAQMTKYL QSNSNNWRWF
DDRSGRWCSY SASNNSTIDS AWKSGETSVR FTAGRRRYTV QFTTMVQVNE ETGNRRPVML
TLLRVPRLSK NSKSSNGQEL EKTLEESKET DIKHKENKGN DIPLALESTN TEKEASLDET
KIGEILIQGL TEDMVTVLIR ACVSMLGVPV DPDTLHATLR LCLRLTRDHK YAMMFAELKS
TRMILNLTQS SGFNGFTPLV TLLLRHIIED PCTLRHTMEK VVRSAATSGA GSTTSGVVSG
SLGSREINYI LRVLGPAACR NPDIFTEVAN CCIRIALPAP RGSGTASDDE FENLRIKGPN
AVQLVKTTPL KPSSLPVIPD TIKEVIYDML NALAAYHAPE EADKSDPKPG GTTQEVGQLL
QDMGDDVYQQ YRSLTRQSSD FDTQSGFSLN SQVFAADGAP AETSTTGTSQ GEASTPEETR
EGKKDKEGDR TSEEGKQKSK GSKPLMPTST ILRLLAELVR SYVGIATLIA NYSYTVGQSE
LIKEDCSVLA FVLDHLLPHT QNAEDKDTPA LARLFLASLA AAGSGTDAQV ALVNEVKAAL
GRALAMAEST EKHARLQAVM CIISTIMESC PSTSSFYSSA TAKTQHNGMN NIIRLFLKKG
LVNDLARVPH SLDLSSPNMA NTVNAALKPL ETLSRIVNQP SSLFGSKSAS SKNKSEQDAQ
GASQDSSSHQ QDPGEPGEAE VQEEDHDVTQ TEVADGDIMD GEAETDSVVI AGQPEVLSSQ
EMQVENELED LIDELLERDG GSGNSTIIVS RSGEDESQED VLMDEAPSNL SQASTLQANR
EDSMNILDPE DEEEHTQEED SSGSNEDEDD SQDEEEEEEE DEEDDQEDDE GEEGDEDDDD
DGSEMELDED YPDMNASPLV RFERFDREDD LIIEFDNMFS SATDIPPSPG NIPTTHPLMV
RHADHSSLTL GSGSSTTRLT QGIGRSQRTL RQLTANTGHT IHVHYPGNRQ PNPPLILQRL
LGPSAAADIL QLSSSLPLQS RGRARLLVGN DDVHIIARSD DELLDDFFHD QSTATSQAGT
LSSIPTALTR WTEECKVLDA ESMHDCVSVV KVPIVNHLEF LRDEELEERR EKRRKQLAEE
ETKIIDKGKE DKENRDQSAQ CTVTKTNDST EQNVSDGTPM PDSYPTTPSS TDAPTSESKE
TLGTLQPSQQ QPALPPPPSL GEIPQELQSP AEEVANSTQL LMPIELEELG PTRPSGEAET
TQMELSPAPT ITSLSPERAE DSDALTAVSS QLEGSPMDTS SLASCTLEEA VGDTPAAGSS
EQPTAGSSTP GDAPSVVAEV QGRPDVSRES NQPPEDSSPP ASSESSSTRD SAVAISGADS
RGILEEPLPS TSSEEEDPLA GISLPEGVDP SFLAALPDDI RREVLQNQLG IRPPTRSAPS
SNSSAPAVVG NPGVTEVSPE FLAALPPAIQ EEVLAQQRAE QQRRELAQNA SSDTPMDPVT
FIQTLPSDLR RSVLEDMEDS VLAVMPPDIA AEAQALRREQ EARQRQLMHE RLFGHSSTSA
LSAILRSPAF TSRLSGNRGV QYTRLAVQRG GTFQMGGSSS HNRPSGSNVD TLLRLRGRLL
LDHEALSCLL VLLFVDEPKL NTSRLHRVLR NLCYHAQTRH WVIRSLLSIL QRSSESELCI
ETPKLSTSEE RGKKSSKSCA SSSHENRPLD LLHKMESKSS NQLSWLSVSM DAALGCRTNI
FQIQRSGGRK HTEKHASSGS TVHIHPQAAP VVCRHVLDTL IQLAKVFPSH FTQQRTKETN
CESDRERGSK QACSPCSSQS SSSGICTDFW DLLVKLDNMN VSRKGKNSVK SVPVSSGGEG
ETSPHSLEAS PLGQLMNMLS HPVIRRSSLL TEKLLRLLSL ISIALPENKV SEVQTNSSNS
GSSTAATSNT STTTTTTTTA TAPTPTPPAA TTPVTSAPAL VAATAISTIT VAASTTVTTP
TTATTTVSTS TTKGSKSPAK VGEGGSGIDF KMVSSGLTEN QLQLSVEVLT SHSCSEEGLE
DAANVLLQLS RGDSGTRDTV LKLLLNGARH LGYTLCKQIG TLLAELREYN LEQQRRAQCE
TLSPDGLPEE QPQTTKLKGK MQSRFDMAEN VVIVASQKRP LGGRELQLPS MSMLTSKTST
QKFFLRVLQV IIQLRDDTRR ANKKAKQTGR LGSSGLGSAS SIQAAVRQLE AEADAIIQMV
REGQRARRQQ QAATSESSNQ SETSVRREES PMDVDQPSPS AQDTQSIVIS DGTPQGEKEK
EEKPPELPLL SEQLSLDELW DMLGECLKEL EESHDQHAVL VLQPAVEAFF LVHATERESK
PPVRDTRESQ LAHIKDEPPP LSPAPLTPAT PSSLDPFFSR EPSSMHISSS LPPDTQKFLR
FAETHRTVLN QILRQSTTHL ADGPFAVLVD YIRVLDFDVK RKYFRQELER LDEGLRKEDM
AVHVRRDHVF EDSYRELHRK SPEEMKNRLY IVFEGEEGQD AGGLLREWYM IISREMFNPM
YALFRTSPGD RVTYTINPSS HCNPNHLSYF KFVGRIVAKA VYDNRLLECY FTRSFYKHIL
GKSVRYTDME SEDYHFYQGL VYLLENDVST LGYDLTFSTE VQEFGVCEVR DLKPNGANIL
VTEENKKEYV HLVCQMRMTG AIRKQLAAFL EGFYEIIPKR LISIFTEQEL ELLISGLPTI
DIDDLKSNTE YHKYQSNSIQ IQWFWRALRS FDQADRAKFL QFVTGTSKVP LQGFAALEGM
NGIQKFQIHR DDRSTDRLPS AHTCFNQLDL PAYESFEKLR HMLLLAIQEC SEGFGLA
