ITCH_HUMAN
ID ITCH_HUMAN Reviewed; 903 AA.
AC Q96J02; A6NEW4; B4E234; E1P5P3; F5H217; O43584; Q5QP37; Q5TEL0; Q96F66;
AC Q9BY75; Q9H451; Q9H4U5;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=E3 ubiquitin-protein ligase Itchy homolog;
DE Short=Itch;
DE EC=2.3.2.26 {ECO:0000269|PubMed:14602072, ECO:0000269|PubMed:16387660, ECO:0000269|PubMed:17028573, ECO:0000269|PubMed:18628966, ECO:0000269|PubMed:18718448, ECO:0000269|PubMed:18718449, ECO:0000269|PubMed:19592251};
DE AltName: Full=Atrophin-1-interacting protein 4;
DE Short=AIP4;
DE AltName: Full=HECT-type E3 ubiquitin transferase Itchy homolog;
DE AltName: Full=NFE2-associated polypeptide 1;
DE Short=NAPP1;
GN Name=ITCH;
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] (ISOFORM 2), AND INTERACTION WITH NFE2.
RC TISSUE=Leukemia;
RX PubMed=11318614; DOI=10.1006/geno.2001.6512;
RA Chen X., Wen S.-C., Fukuda M.N., Gavva N.R., Hsu D.-W., Akama T.O.,
RA Yang-Peng T.L., Shen C.K.J.;
RT "Human ITCH is a co-regulator of the hematopoietic transcription factor NF-
RT E2.";
RL Genomics 73:238-241(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Miyazaki K., Okamoto Y., Sakamoto M., Nakagawara A.;
RT "Homo sapiens mRNA for ubiquitin protein ligase Itch, complete cds.";
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Trachea;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [5]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Kidney, and Placenta;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 83-903 (ISOFORM 2), AND INTERACTION WITH
RP ATN1.
RC TISSUE=Fetal brain;
RX PubMed=9647693; DOI=10.1006/mcne.1998.0677;
RA Wood J.D., Yuan J., Margolis R.L., Colomer V., Duan K., Kushi J.,
RA Kaminsky Z., Kleiderlein J.J. Jr., Sharp A.H., Ross C.A.;
RT "Atrophin-1, the DRPLA gene product, interacts with two families of WW
RT domain-containing proteins.";
RL Mol. Cell. Neurosci. 11:149-160(1998).
RN [8]
RP PROTEIN SEQUENCE OF 463-470; 503-510; 514-526; 644-665 AND 875-881,
RP INTERACTION WITH LMP2A, AND MUTAGENESIS OF CYS-871.
RC TISSUE=B-cell;
RX PubMed=11046148; DOI=10.1128/mcb.20.22.8526-8535.2000;
RA Winberg G., Matskova L., Chen F., Plant P., Rotin D., Gish G., Ingham R.,
RA Ernberg I., Pawson T.;
RT "Latent membrane protein 2A of Epstein-Barr virus binds WW domain E3
RT protein-ubiquitin ligases that ubiquitinate B-cell tyrosine kinases.";
RL Mol. Cell. Biol. 20:8526-8535(2000).
RN [9]
RP INTERACTION WITH CBLC, AND PHOSPHORYLATION.
RX PubMed=12226085; DOI=10.1074/jbc.m206460200;
RA Courbard J.-R., Fiore F., Adelaide J., Borg J.P., Birnbaum D.,
RA Ollendorff V.;
RT "Interaction between two ubiquitin-protein isopeptide ligases of different
RT classes, CBLC and AIP4/ITCH.";
RL J. Biol. Chem. 277:45267-45275(2002).
RN [10]
RP INTERACTION WITH RNF11.
RX PubMed=14559117; DOI=10.1016/j.bbadis.2003.07.001;
RA Kitching R., Wong M.J., Koehler D., Burger A.M., Landberg G., Gish G.,
RA Seth A.K.;
RT "The RING-H2 protein RNF11 is differentially expressed in breast tumours
RT and interacts with HECT-type E3 ligases.";
RL Biochim. Biophys. Acta 1639:104-112(2003).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, INTERACTION
RP WITH HGS, AND MUTAGENESIS OF CYS-871.
RX PubMed=14602072; DOI=10.1016/s1534-5807(03)00321-6;
RA Marchese A., Raiborg C., Santini F., Keen J.H., Stenmark H., Benovic J.L.;
RT "The E3 ubiquitin ligase AIP4 mediates ubiquitination and sorting of the G
RT protein-coupled receptor CXCR4.";
RL Dev. Cell 5:709-722(2003).
RN [12]
RP PHOSPHORYLATION AT THR-385 AND SER-450, AND INTERACTION WITH SGK3.
RX PubMed=16888620; DOI=10.1038/sj.emboj.7601267;
RA Slagsvold T., Marchese A., Brech A., Stenmark H.;
RT "CISK attenuates degradation of the chemokine receptor CXCR4 via the
RT ubiquitin ligase AIP4.";
RL EMBO J. 25:3738-3749(2006).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH DTX1, AND
RP UBIQUITINATION OF DTX1.
RX PubMed=17028573; DOI=10.1038/sj.embor.7400822;
RA Chastagner P., Israel A., Brou C.;
RT "Itch/AIP4 mediates Deltex degradation through the formation of K29-linked
RT polyubiquitin chains.";
RL EMBO Rep. 7:1147-1153(2006).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH JUNB AND FYN,
RP PHOSPHORYLATION AT TYR-420, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP MUTAGENESIS OF TYR-343; TYR-420 AND TYR-455.
RX PubMed=16387660; DOI=10.1016/j.molcel.2005.11.014;
RA Yang C., Zhou W., Jeon M.S., Demydenko D., Harada Y., Zhou H., Liu Y.C.;
RT "Negative regulation of the E3 ubiquitin ligase itch via Fyn-mediated
RT tyrosine phosphorylation.";
RL Mol. Cell 21:135-141(2006).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND INTERACTION WITH NFE2.
RX PubMed=18718448; DOI=10.1016/j.bbrc.2008.07.164;
RA Lee T.-L., Shyu Y.-C., Hsu T.-Y., Shen C.-K.J.;
RT "Itch regulates p45/NF-E2 in vivo by Lys63-linked ubiquitination.";
RL Biochem. Biophys. Res. Commun. 375:326-330(2008).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AUTOUBIQUITINATION, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=18718449; DOI=10.1016/j.bcp.2008.07.028;
RA Scialpi F., Malatesta M., Peschiaroli A., Rossi M., Melino G.,
RA Bernassola F.;
RT "Itch self-polyubiquitylation occurs through lysine-63 linkages.";
RL Biochem. Pharmacol. 76:1515-1521(2008).
RN [17]
RP SUBCELLULAR LOCATION.
RX PubMed=18819914; DOI=10.1074/jbc.m804120200;
RA Putz U., Howitt J., Lackovic J., Foot N., Kumar S., Silke J., Tan S.S.;
RT "Nedd4 family-interacting protein 1 (Ndfip1) is required for the exosomal
RT secretion of Nedd4 family proteins.";
RL J. Biol. Chem. 283:32621-32627(2008).
RN [18]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND UBIQUITINATION OF NOTCH1.
RX PubMed=18628966; DOI=10.1371/journal.pone.0002735;
RA Chastagner P., Israel A., Brou C.;
RT "AIP4/Itch regulates Notch receptor degradation in the absence of ligand.";
RL PLoS ONE 3:E2735-E2735(2008).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [20]
RP INTERACTION WITH SPART.
RX PubMed=19580544; DOI=10.1042/bj20082398;
RA Edwards T.L., Clowes V.E., Tsang H.T., Connell J.W., Sanderson C.M.,
RA Luzio J.P., Reid E.;
RT "Endogenous spartin (SPG20) is recruited to endosomes and lipid droplets
RT and interacts with the ubiquitin E3 ligases AIP4 and AIP5.";
RL Biochem. J. 423:31-39(2009).
RN [21]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND UBIQUITINATION OF RIPK2.
RX PubMed=19592251; DOI=10.1016/j.cub.2009.06.038;
RA Tao M., Scacheri P.C., Marinis J.M., Harhaj E.W., Matesic L.E.,
RA Abbott D.W.;
RT "ITCH K63-ubiquitinates the NOD2 binding protein, RIP2, to influence
RT inflammatory signaling pathways.";
RL Curr. Biol. 19:1255-1263(2009).
RN [22]
RP FUNCTION, AND INTERACTION WITH RNF11.
RX PubMed=19131965; DOI=10.1038/emboj.2008.285;
RA Shembade N., Parvatiyar K., Harhaj N.S., Harhaj E.W.;
RT "The ubiquitin-editing enzyme A20 requires RNF11 to downregulate NF-kappaB
RT signalling.";
RL EMBO J. 28:513-522(2009).
RN [23]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH CXCR4, AND
RP UBIQUITINATION.
RX PubMed=19116316; DOI=10.1091/mbc.e08-03-0308;
RA Bhandari D., Robia S.L., Marchese A.;
RT "The E3 ubiquitin ligase atrophin interacting protein 4 binds directly to
RT the chemokine receptor CXCR4 via a novel WW domain-mediated interaction.";
RL Mol. Biol. Cell 20:1324-1339(2009).
RN [24]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, UBIQUITINATION OF MAVS, INTERACTION
RP WITH PCBP2, AND MUTAGENESIS OF CYS-871.
RX PubMed=19881509; DOI=10.1038/ni.1815;
RA You F., Sun H., Zhou X., Sun W., Liang S., Zhai Z., Jiang Z.;
RT "PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin
RT ligase AIP4.";
RL Nat. Immunol. 10:1300-1308(2009).
RN [25]
RP INVOLVEMENT IN ADMFD.
RX PubMed=20170897; DOI=10.1016/j.ajhg.2010.01.028;
RA Lohr N.J., Molleston J.P., Strauss K.A., Torres-Martinez W., Sherman E.A.,
RA Squires R.H., Rider N.L., Chikwava K.R., Cummings O.W., Morton D.H.,
RA Puffenberger E.G.;
RT "Human ITCH E3 ubiquitin ligase deficiency causes syndromic multisystem
RT autoimmune disease.";
RL Am. J. Hum. Genet. 86:447-453(2010).
RN [26]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH SNX9 AND SNX18, AND
RP UBIQUITINATION OF SNX9.
RX PubMed=20491914; DOI=10.1111/j.1742-4658.2010.07698.x;
RA Baumann C., Lindholm C.K., Rimoldi D., Levy F.;
RT "The E3 ubiquitin ligase Itch regulates sorting nexin 9 through an
RT unconventional substrate recognition domain.";
RL FEBS J. 277:2803-2814(2010).
RN [27]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH P15 BID, AND
RP UBIQUITINATION OF P15 BID.
RX PubMed=20392206; DOI=10.1111/j.1742-4658.2010.07562.x;
RA Azakir B.A., Desrochers G., Angers A.;
RT "The ubiquitin ligase Itch mediates the antiapoptotic activity of epidermal
RT growth factor by promoting the ubiquitylation and degradation of the
RT truncated C-terminal portion of Bid.";
RL FEBS J. 277:1319-1330(2010).
RN [28]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, INTERACTION WITH TXNIP, AND
RP UBIQUITINATION OF TXNIP.
RX PubMed=20068034; DOI=10.1074/jbc.m109.063321;
RA Zhang P., Wang C., Gao K., Wang D., Mao J., An J., Xu C., Wu D., Yu H.,
RA Liu J.O., Yu L.;
RT "The ubiquitin ligase itch regulates apoptosis by targeting thioredoxin-
RT interacting protein for ubiquitin-dependent degradation.";
RL J. Biol. Chem. 285:8869-8879(2010).
RN [29]
RP IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH ERBB4, AND
RP SUBCELLULAR LOCATION.
RX PubMed=20858735; DOI=10.1158/1541-7786.mcr-10-0042;
RA Gilmore-Hebert M., Ramabhadran R., Stern D.F.;
RT "Interactions of ErbB4 and Kap1 connect the growth factor and DNA damage
RT response pathways.";
RL Mol. Cancer Res. 8:1388-1398(2010).
RN [30]
RP FUNCTION, AND INTERACTION WITH HERPES SIMPLEX VIRUS 2 PROTEIN UL56.
RX PubMed=20682038; DOI=10.1186/1743-422x-7-179;
RA Ushijima Y., Luo C., Kamakura M., Goshima F., Kimura H., Nishiyama Y.;
RT "Herpes simplex virus UL56 interacts with and regulates the Nedd4-family
RT ubiquitin ligase Itch.";
RL Virol. J. 7:179-179(2010).
RN [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [32]
RP INTERACTION WITH ARRDC1; ARRDC2 AND ARRDC3, AND DOMAIN.
RX PubMed=21191027; DOI=10.1128/jvi.02045-10;
RA Rauch S., Martin-Serrano J.;
RT "Multiple interactions between the ESCRT machinery and arrestin-related
RT proteins: implications for PPXY-dependent budding.";
RL J. Virol. 85:3546-3556(2011).
RN [33]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PATHWAY, INTERACTION
RP WITH PI4K2A, SUBCELLULAR LOCATION, UBIQUITINATION, AND MUTAGENESIS OF
RP CYS-871.
RX PubMed=23146885; DOI=10.1038/embor.2012.164;
RA Mossinger J., Wieffer M., Krause E., Freund C., Gerth F., Krauss M.,
RA Haucke V.;
RT "Phosphatidylinositol 4-kinase IIalpha function at endosomes is regulated
RT by the ubiquitin ligase Itch.";
RL EMBO Rep. 13:1087-1094(2012).
RN [34]
RP INTERACTION WITH OTUD7B.
RX PubMed=22179831; DOI=10.1038/onc.2011.587;
RA Pareja F., Ferraro D.A., Rubin C., Cohen-Dvashi H., Zhang F., Aulmann S.,
RA Ben-Chetrit N., Pines G., Navon R., Crosetto N., Kostler W., Carvalho S.,
RA Lavi S., Schmitt F., Dikic I., Yakhini Z., Sinn P., Mills G.B., Yarden Y.;
RT "Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression.";
RL Oncogene 31:4599-4608(2012).
RN [35]
RP INTERACTION WITH ARRDC4.
RX PubMed=23236378; DOI=10.1371/journal.pone.0050557;
RA Shea F.F., Rowell J.L., Li Y., Chang T.H., Alvarez C.E.;
RT "Mammalian alpha arrestins link activated seven transmembrane receptors to
RT Nedd4 family e3 ubiquitin ligases and interact with beta arrestins.";
RL PLoS ONE 7:E50557-E50557(2012).
RN [36]
RP FUNCTION, AND INTERACTION WITH ARRDC1 AND ARRDC3.
RX PubMed=23886940; DOI=10.1242/jcs.130500;
RA Puca L., Chastagner P., Meas-Yedid V., Israel A., Brou C.;
RT "Alpha-arrestin 1 (ARRDC1) and beta-arrestins cooperate to mediate Notch
RT degradation in mammals.";
RL J. Cell Sci. 126:4457-4468(2013).
RN [37]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PATHWAY, INTERACTION
RP WITH DTX3L, IDENTIFICATION IN A COMPLEX WITH DTX3L; STAM AND HGS,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-871.
RX PubMed=24790097; DOI=10.1091/mbc.e13-10-0612;
RA Holleman J., Marchese A.;
RT "The ubiquitin ligase deltex-3l regulates endosomal sorting of the G
RT protein-coupled receptor CXCR4.";
RL Mol. Biol. Cell 25:1892-1904(2014).
RN [38]
RP FUNCTION IN UBIQUITINATION OF BRAT1, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, AND PATHWAY.
RX PubMed=25631046; DOI=10.1074/jbc.m114.613687;
RA Low L.H., Chow Y.L., Li Y., Goh C.P., Putz U., Silke J., Ouchi T.,
RA Howitt J., Tan S.S.;
RT "Nedd4 family interacting protein 1 (Ndfip1) is required for ubiquitination
RT and nuclear trafficking of BRCA1-associated ATM activator 1 (BRAT1) during
RT the DNA damage response.";
RL J. Biol. Chem. 290:7141-7150(2015).
RN [39]
RP INTERACTION WITH UBE2L3.
RX PubMed=25632008; DOI=10.4049/jimmunol.1402742;
RA Kathania M., Zeng M., Yadav V.N., Moghaddam S.J., Yang B., Venuprasad K.;
RT "Ndfip1 regulates itch ligase activity and airway inflammation via UbcH7.";
RL J. Immunol. 194:2160-2167(2015).
RN [40]
RP INTERACTION WITH LDLRAD3.
RX PubMed=26854353; DOI=10.1021/acs.biochem.5b01218;
RA Noyes N.C., Hampton B., Migliorini M., Strickland D.K.;
RT "Regulation of Itch and Nedd4 E3 Ligase Activity and Degradation by
RT LRAD3.";
RL Biochemistry 55:1204-1213(2016).
RN [41]
RP INTERACTION WITH EBOLA VIRUS PROTEIN VP40 (MICROBIAL INFECTION).
RX PubMed=27489272; DOI=10.1128/jvi.01078-16;
RA Han Z., Sagum C.A., Bedford M.T., Sidhu S.S., Sudol M., Harty R.N.;
RT "ITCH E3 Ubiquitin Ligase Interacts with Ebola Virus VP40 To Regulate
RT Budding.";
RL J. Virol. 90:9163-9171(2016).
RN [42]
RP INTERACTION WITH HCMV PROTEIN UL42 (MICROBIAL INFECTION).
RX PubMed=26555021; DOI=10.1099/jgv.0.000336;
RA Koshizuka T., Tanaka K., Suzutani T.;
RT "Degradation of host ubiquitin E3 ligase Itch by human cytomegalovirus
RT UL42.";
RL J. Gen. Virol. 97:196-208(2016).
RN [43]
RP INTERACTION WITH HHV-1 UL56 (MICROBIAL INFECTION), INTERACTION WITH VZV
RP ORF0 (MICROBIAL INFECTION), INTERACTION WITH HCMV UL42 (MICROBIAL
RP INFECTION), AND INTERACTION WITH HHV-6A U24 (MICROBIAL INFECTION).
RX PubMed=29535361; DOI=10.1038/s41598-018-22682-2;
RA Koshizuka T., Kobayashi T., Ishioka K., Suzutani T.;
RT "Herpesviruses possess conserved proteins for interaction with Nedd4 family
RT ubiquitin E3 ligases.";
RL Sci. Rep. 8:4447-4447(2018).
RN [44]
RP FUNCTION, AND INTERACTION WITH INFLUENZA A VIRUS MATRIX PROTEIN 1
RP (MICROBIAL INFECTION).
RX PubMed=30328013; DOI=10.1007/s12250-018-0058-6;
RA Mahesutihan M., Zheng W., Cui L., Li Y., Jiao P., Yang W., Liu W., Li J.,
RA Fan W., Yang L., Liu W., Sun L.;
RT "CypA Regulates AIP4-Mediated M1 Ubiquitination of Influenza A Virus.";
RL Virol. Sin. 33:440-448(2018).
RN [45]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 246-270 IN COMPLEX WITH ARHGEF7.
RX PubMed=17652093; DOI=10.1074/jbc.m702678200;
RA Janz J.M., Sakmar T.P., Min K.C.;
RT "A novel interaction between atrophin-interacting protein 4 and beta-p21-
RT activated kinase-interactive exchange factor is mediated by an SH3
RT domain.";
RL J. Biol. Chem. 282:28893-28903(2007).
RN [46]
RP STRUCTURE BY NMR OF 328-357.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the second WW domain of ITCHY homolog E3 ubiquitin
RT protein ligase (ITCH).";
RL Submitted (OCT-2006) to the PDB data bank.
CC -!- FUNCTION: Acts as an E3 ubiquitin-protein ligase which accepts
CC ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a
CC thioester and then directly transfers the ubiquitin to targeted
CC substrates (PubMed:14602072, PubMed:17028573, PubMed:16387660,
CC PubMed:18718448, PubMed:18718449, PubMed:11046148, PubMed:19592251,
CC PubMed:19116316, PubMed:19881509, PubMed:20491914, PubMed:20392206,
CC PubMed:20068034, PubMed:23146885, PubMed:24790097, PubMed:25631046).
CC Catalyzes 'Lys-29'-, 'Lys-48'- and 'Lys-63'-linked ubiquitin
CC conjugation (PubMed:17028573, PubMed:18718448, PubMed:19131965,
CC PubMed:19881509). Involved in the control of inflammatory signaling
CC pathways (PubMed:19131965). Essential component of a ubiquitin-editing
CC protein complex, comprising also TNFAIP3, TAX1BP1 and RNF11, that
CC ensures the transient nature of inflammatory signaling pathways
CC (PubMed:19131965). Promotes the association of the complex after TNF
CC stimulation (PubMed:19131965). Once the complex is formed, TNFAIP3
CC deubiquitinates 'Lys-63' polyubiquitin chains on RIPK1 and catalyzes
CC the formation of 'Lys-48'-polyubiquitin chains (PubMed:19131965). This
CC leads to RIPK1 proteasomal degradation and consequently termination of
CC the TNF- or LPS-mediated activation of NFKB1 (PubMed:19131965).
CC Ubiquitinates RIPK2 by 'Lys-63'-linked conjugation and influences NOD2-
CC dependent signal transduction pathways (PubMed:19592251). Regulates the
CC transcriptional activity of several transcription factors, and probably
CC plays an important role in the regulation of immune response
CC (PubMed:18718448, PubMed:20491914). Ubiquitinates NFE2 by 'Lys-63'
CC linkages and is implicated in the control of the development of
CC hematopoietic lineages (PubMed:18718448). Mediates JUN ubiquitination
CC and degradation (By similarity). Mediates JUNB ubiquitination and
CC degradation (PubMed:16387660). Critical regulator of type 2 helper T
CC (Th2) cell cytokine production by inducing JUNB ubiquitination and
CC degradation (By similarity). Involved in the negative regulation of
CC MAVS-dependent cellular antiviral responses (PubMed:19881509).
CC Ubiquitinates MAVS through 'Lys-48'-linked conjugation resulting in
CC MAVS proteasomal degradation (PubMed:19881509). Following ligand
CC stimulation, regulates sorting of Wnt receptor FZD4 to the degradative
CC endocytic pathway probably by modulating PI42KA activity
CC (PubMed:23146885). Ubiquitinates PI4K2A and negatively regulates its
CC catalytic activity (PubMed:23146885). Ubiquitinates chemokine receptor
CC CXCR4 and regulates sorting of CXCR4 to the degradative endocytic
CC pathway following ligand stimulation by ubiquitinating endosomal
CC sorting complex required for transport ESCRT-0 components HGS and STAM
CC (PubMed:14602072, PubMed:23146885). Targets DTX1 for lysosomal
CC degradation and controls NOTCH1 degradation, in the absence of ligand,
CC through 'Lys-29'-linked polyubiquitination (PubMed:17028573,
CC PubMed:18628966, PubMed:23886940). Ubiquitinates SNX9
CC (PubMed:20491914). Ubiquitinates MAP3K7 through 'Lys-48'-linked
CC conjugation (By similarity). Involved in the regulation of apoptosis
CC and reactive oxygen species levels through the ubiquitination and
CC proteasomal degradation of TXNIP (PubMed:20068034). Mediates the
CC antiapoptotic activity of epidermal growth factor through the
CC ubiquitination and proteasomal degradation of p15 BID
CC (PubMed:20392206). Ubiquitinates BRAT1 and this ubiquitination is
CC enhanced in the presence of NDFIP1 (PubMed:25631046). Inhibits the
CC replication of influenza A virus (IAV) via ubiquitination of IAV matrix
CC protein 1 (M1) through 'Lys-48'-linked conjugation resulting in M1
CC proteasomal degradation (PubMed:30328013).
CC {ECO:0000250|UniProtKB:Q8C863, ECO:0000269|PubMed:14602072,
CC ECO:0000269|PubMed:16387660, ECO:0000269|PubMed:17028573,
CC ECO:0000269|PubMed:18628966, ECO:0000269|PubMed:18718448,
CC ECO:0000269|PubMed:18718449, ECO:0000269|PubMed:19116316,
CC ECO:0000269|PubMed:19131965, ECO:0000269|PubMed:19592251,
CC ECO:0000269|PubMed:19881509, ECO:0000269|PubMed:20068034,
CC ECO:0000269|PubMed:20392206, ECO:0000269|PubMed:20491914,
CC ECO:0000269|PubMed:23146885, ECO:0000269|PubMed:23886940,
CC ECO:0000269|PubMed:24790097, ECO:0000269|PubMed:25631046,
CC ECO:0000269|PubMed:30328013}.
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:0000269|PubMed:14602072,
CC ECO:0000269|PubMed:16387660, ECO:0000269|PubMed:17028573,
CC ECO:0000269|PubMed:18628966, ECO:0000269|PubMed:18718448,
CC ECO:0000269|PubMed:18718449, ECO:0000269|PubMed:19116316,
CC ECO:0000269|PubMed:19592251, ECO:0000269|PubMed:19881509,
CC ECO:0000269|PubMed:20068034, ECO:0000269|PubMed:20392206,
CC ECO:0000269|PubMed:20491914, ECO:0000269|PubMed:23146885,
CC ECO:0000269|PubMed:24790097, ECO:0000269|PubMed:25631046};
CC -!- ACTIVITY REGULATION: Activated by NDFIP1- and NDFIP2-binding
CC (PubMed:25631046). Activated by PI4K2A-binding (PubMed:23146885).
CC Inhibited by DTX3L-binding (PubMed:24790097). Inhibited by N4BP1
CC binding (By similarity). {ECO:0000250|UniProtKB:Q8C863,
CC ECO:0000269|PubMed:23146885, ECO:0000269|PubMed:24790097,
CC ECO:0000269|PubMed:25631046}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:14602072, ECO:0000269|PubMed:16387660,
CC ECO:0000269|PubMed:17028573, ECO:0000269|PubMed:18628966,
CC ECO:0000269|PubMed:18718448, ECO:0000269|PubMed:18718449,
CC ECO:0000269|PubMed:19116316, ECO:0000269|PubMed:19592251,
CC ECO:0000269|PubMed:19881509, ECO:0000269|PubMed:20068034,
CC ECO:0000269|PubMed:20392206, ECO:0000269|PubMed:20491914,
CC ECO:0000269|PubMed:23146885, ECO:0000269|PubMed:24790097,
CC ECO:0000269|PubMed:25631046}.
CC -!- SUBUNIT: Monomer. Interacts (via WW domains) with OCNL (By similarity).
CC Interacts (via WW domains) with NOTCH1 (By similarity). Interacts (via
CC WW domains) with JUN (By similarity). Interacts with JUNB; the
CC interaction promotes ITCH-mediated ubiquitination and degradation of
CC JUNB (PubMed:16387660). Interacts with FYN; the interaction
CC phosphorylates ITCH on Tyr-420 decreasing binding of JUNB
CC (PubMed:16387660). Interacts (via WW domain 2) with N4BP1; the
CC interaction inhibits the E3 ubiquitin-protein ligase activity (By
CC similarity). Interacts with NDFIP1 and NDFIP2; this interaction
CC activates the E3 ubiquitin-protein ligase and may induce its
CC recruitment to exosomes (By similarity). Interacts with ARHGEF7
CC (PubMed:17652093). Interacts with RNF11 (PubMed:14559117,
CC PubMed:19131965). Interacts (via the WW 1 domain) with NFE2 (via the
CC PXY motif 1); the interaction promotes 'Lys-63'-linked ubiquitination
CC of NFE2, retains it in the cytoplasm and prevents its transactivation
CC activity (PubMed:11318614, PubMed:18718448). Interacts (via WW domains)
CC with CXCR4 (via C-terminus); the interaction depends on CXCR4
CC phosphorylation (PubMed:19116316). Found in a complex with E3 ligase
CC DTX3L and ESCRT-0 components HGS and STAM (PubMed:24790097). Interacts
CC with DTX3L (via C-terminus); the interaction is increased upon CXCL12
CC stimulation and inhibits ITCH catalytic activity (the interaction is
CC direct) (PubMed:24790097). Interacts with HGS (PubMed:14602072).
CC Interacts (via WW domains) with PCBP2 within a complex containing ITCH,
CC MAVS and PCBP2 (PubMed:19881509). Interacts (via WW domains) with TXNIP
CC (via C-terminus) (PubMed:20068034). Interacts with p15 BID
CC (PubMed:20392206). Interacts with ERBB4 (PubMed:20858735). Interacts
CC with DTX1 (PubMed:17028573). Interacts with SPART (PubMed:19580544).
CC Interacts with SNX9 and SNX18 (PubMed:20491914). Interacts (via its WW
CC domains) with ATN1 (PubMed:9647693). Interacts (via WW domains) with
CC SGK3 (PubMed:16888620). Interacts with CBLC (PubMed:12226085).
CC Interacts with OTUD7B (PubMed:22179831). Interacts (via WW domain 1,2
CC and 3) with PI4K2A; the interaction inhibits PI4K2A catalytic activity
CC and promotes ITCH catalytic activity (PubMed:23146885). Interacts with
CC ARRDC4 (PubMed:23236378). Part of a complex containing ITCH, NDFIP1 and
CC MAP3K7 (By similarity). Interacts with UBE2L3; the interaction is
CC mediated by NDFIP1 (PubMed:25632008). Interacts with MAPK8/JNK1 (By
CC similarity). Interacts (via WW domains) with ARRDC1 (via PPxY motifs);
CC the interaction is direct and participates in the recruitment of the
CC ubiquitin-protein ligase ITCH to the NOTCH1 receptor (PubMed:21191027,
CC PubMed:23886940). Interacts (via WW domains) with ARRDC2
CC (PubMed:21191027). Interacts (via WW domains) with ARRDC3
CC (PubMed:21191027, PubMed:23886940). Interacts directly with LDLRAD3;
CC this interaction promotes ITCH auto-ubiquitination leading to its
CC degradation (PubMed:26854353). {ECO:0000250|UniProtKB:Q8C863,
CC ECO:0000269|PubMed:11318614, ECO:0000269|PubMed:12226085,
CC ECO:0000269|PubMed:14559117, ECO:0000269|PubMed:14602072,
CC ECO:0000269|PubMed:16387660, ECO:0000269|PubMed:16888620,
CC ECO:0000269|PubMed:17028573, ECO:0000269|PubMed:17652093,
CC ECO:0000269|PubMed:18718448, ECO:0000269|PubMed:19116316,
CC ECO:0000269|PubMed:19131965, ECO:0000269|PubMed:19580544,
CC ECO:0000269|PubMed:19881509, ECO:0000269|PubMed:20068034,
CC ECO:0000269|PubMed:20392206, ECO:0000269|PubMed:20491914,
CC ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:21191027,
CC ECO:0000269|PubMed:22179831, ECO:0000269|PubMed:23146885,
CC ECO:0000269|PubMed:23236378, ECO:0000269|PubMed:23886940,
CC ECO:0000269|PubMed:24790097, ECO:0000269|PubMed:25632008,
CC ECO:0000269|PubMed:26854353, ECO:0000269|PubMed:9647693}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein-Barr virus LMP2A.
CC {ECO:0000269|PubMed:11046148}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Human cytomegalovirus
CC (HCMV) protein UL42; this interaction induces ubiquitination and
CC degradation of ITCH. {ECO:0000269|PubMed:26555021,
CC ECO:0000269|PubMed:29535361}.
CC -!- SUBUNIT: (Microbial infection) Interacts with herpesvirus 1 (HHV-1)
CC UL56 protein; this interaction induces ubiquitination and probably
CC degradation of ITCH. {ECO:0000269|PubMed:29535361}.
CC -!- SUBUNIT: (Microbial infection) Interacts with herpesvirus 2 (HHV-2)
CC UL56 protein. {ECO:0000269|PubMed:20682038}.
CC -!- SUBUNIT: (Microbial infection) Interacts with varicella-zoster virus
CC (VZV) Orf0 protein. {ECO:0000269|PubMed:29535361}.
CC -!- SUBUNIT: (Microbial infection) Interacts with herpesvirus 6A (HHV-6A)
CC U24 protein. {ECO:0000269|PubMed:29535361}.
CC -!- SUBUNIT: (Microbial infection) Interacts with ebola virus protein VP40;
CC this interaction is required for efficient viral egress from the
CC infected cell. {ECO:0000269|PubMed:27489272}.
CC -!- SUBUNIT: (Microbial infection) Interacts with influenza A virus matrix
CC protein 1. {ECO:0000269|PubMed:30328013}.
CC -!- INTERACTION:
CC Q96J02; Q96B67: ARRDC3; NbExp=3; IntAct=EBI-1564678, EBI-2875665;
CC Q96J02; Q9NQC7: CYLD; NbExp=3; IntAct=EBI-1564678, EBI-2117940;
CC Q96J02; P08151: GLI1; NbExp=4; IntAct=EBI-1564678, EBI-308084;
CC Q96J02; O75113: N4BP1; NbExp=3; IntAct=EBI-1564678, EBI-5278391;
CC Q96J02; Q9BTU6: PI4K2A; NbExp=5; IntAct=EBI-1564678, EBI-3239392;
CC Q96J02; Q9Y3C5: RNF11; NbExp=2; IntAct=EBI-1564678, EBI-396669;
CC Q96J02; Q96BR1: SGK3; NbExp=5; IntAct=EBI-1564678, EBI-2801236;
CC Q96J02; Q9Y5X1: SNX9; NbExp=7; IntAct=EBI-1564678, EBI-77848;
CC Q96J02; Q13625: TP53BP2; NbExp=2; IntAct=EBI-1564678, EBI-77642;
CC Q96J02; Q9H3D4: TP63; NbExp=2; IntAct=EBI-1564678, EBI-2337775;
CC Q96J02; O15350: TP73; NbExp=3; IntAct=EBI-1564678, EBI-389606;
CC Q96J02; O15350-1: TP73; NbExp=5; IntAct=EBI-1564678, EBI-389619;
CC Q96J02; O15350-8: TP73; NbExp=2; IntAct=EBI-1564678, EBI-5651259;
CC Q96J02; P13285: LMP2; Xeno; NbExp=3; IntAct=EBI-1564678, EBI-7181113;
CC Q96J02; Q9QZS3-2: Numb; Xeno; NbExp=2; IntAct=EBI-1564678, EBI-3896014;
CC Q96J02-2; P61073: CXCR4; NbExp=3; IntAct=EBI-6672198, EBI-489411;
CC Q96J02-2; Q9NQC7: CYLD; NbExp=2; IntAct=EBI-6672198, EBI-2117940;
CC Q96J02-2; Q15303: ERBB4; NbExp=3; IntAct=EBI-6672198, EBI-80371;
CC Q96J02-2; Q15303-3: ERBB4; NbExp=2; IntAct=EBI-6672198, EBI-15692884;
CC Q96J02-2; Q15884: FAM189A2; NbExp=6; IntAct=EBI-6672198, EBI-8636612;
CC Q96J02-2; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-6672198, EBI-1055254;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14602072};
CC Peripheral membrane protein {ECO:0000305|PubMed:14602072}; Cytoplasmic
CC side {ECO:0000305|PubMed:14602072}. Cytoplasm
CC {ECO:0000269|PubMed:14602072}. Nucleus {ECO:0000269|PubMed:20858735}.
CC Early endosome membrane {ECO:0000269|PubMed:14602072,
CC ECO:0000269|PubMed:23146885, ECO:0000269|PubMed:24790097}; Peripheral
CC membrane protein {ECO:0000305|PubMed:14602072,
CC ECO:0000305|PubMed:23146885, ECO:0000305|PubMed:24790097}; Cytoplasmic
CC side {ECO:0000305|PubMed:14602072, ECO:0000305|PubMed:23146885,
CC ECO:0000305|PubMed:24790097}. Endosome membrane
CC {ECO:0000269|PubMed:23146885}; Peripheral membrane protein
CC {ECO:0000305|PubMed:23146885}; Cytoplasmic side
CC {ECO:0000305|PubMed:23146885}. Note=May be recruited to exosomes by
CC NDFIP1 (PubMed:18819914). Localizes to plasma membrane upon CXCL12
CC stimulation where it co-localizes with CXCL4 (PubMed:14602072).
CC Localization to early endosomes is increased upon CXCL12 stimulation
CC where it co-localizes with DTX3L and CXCL4 (PubMed:24790097).
CC {ECO:0000269|PubMed:14602072, ECO:0000269|PubMed:18819914,
CC ECO:0000269|PubMed:24790097}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q96J02-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96J02-2; Sequence=VSP_008451;
CC Name=3;
CC IsoId=Q96J02-3; Sequence=VSP_044732, VSP_008451;
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- DOMAIN: The WW domains mediate interaction with PPxY motif-containing
CC proteins. {ECO:0000269|PubMed:21191027}.
CC -!- PTM: On T-cell activation, phosphorylation by the JNK cascade on serine
CC and threonine residues surrounding the PRR domain accelerates the
CC ubiquitination and degradation of JUN and JUNB. The increased ITCH
CC catalytic activity due to phosphorylation by JNK1 may occur due to a
CC conformational change disrupting the interaction between the PRR/WW
CC motifs domain and the HECT domain and, thus exposing the HECT domain
CC (By similarity). Phosphorylation by FYN reduces interaction with JUNB
CC and negatively controls JUN ubiquitination and degradation.
CC {ECO:0000250, ECO:0000269|PubMed:12226085, ECO:0000269|PubMed:16387660,
CC ECO:0000269|PubMed:16888620, ECO:0000269|PubMed:18718449}.
CC -!- PTM: Monoubiquitinated (PubMed:19116316). Autopolyubiquitinated with
CC 'Lys-63' linkages which does not lead to protein degradation
CC (PubMed:18718449, PubMed:23146885, PubMed:24790097).
CC {ECO:0000269|PubMed:18718449, ECO:0000269|PubMed:19116316,
CC ECO:0000269|PubMed:23146885, ECO:0000269|PubMed:24790097}.
CC -!- DISEASE: Autoimmune disease, multisystem, with facial dysmorphism
CC (ADMFD) [MIM:613385]: A disorder characterized by organomegaly, failure
CC to thrive, developmental delay, dysmorphic features and autoimmune
CC inflammatory cell infiltration of the lungs, liver and gut.
CC {ECO:0000269|PubMed:20170897}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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DR EMBL; AF095745; AAK39399.1; -; mRNA.
DR EMBL; AB056663; BAB39389.1; -; mRNA.
DR EMBL; AK304090; BAG64996.1; -; mRNA.
DR EMBL; AK315212; BAG37647.1; -; mRNA.
DR EMBL; AL109923; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356299; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW76272.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76274.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76276.1; -; Genomic_DNA.
DR EMBL; BC006848; AAH06848.1; -; mRNA.
DR EMBL; BC011571; AAH11571.1; -; mRNA.
DR EMBL; AF038564; AAC04845.1; -; mRNA.
DR CCDS; CCDS13234.1; -. [Q96J02-2]
DR CCDS; CCDS58768.1; -. [Q96J02-1]
DR CCDS; CCDS58769.1; -. [Q96J02-3]
DR RefSeq; NP_001244066.1; NM_001257137.2. [Q96J02-1]
DR RefSeq; NP_001244067.1; NM_001257138.2. [Q96J02-3]
DR RefSeq; NP_001311126.1; NM_001324197.1. [Q96J02-1]
DR RefSeq; NP_001311127.1; NM_001324198.1. [Q96J02-2]
DR RefSeq; NP_113671.3; NM_031483.6. [Q96J02-2]
DR RefSeq; XP_016883578.1; XM_017028089.1. [Q96J02-1]
DR RefSeq; XP_016883580.1; XM_017028091.1. [Q96J02-3]
DR PDB; 2DMV; NMR; -; A=328-357.
DR PDB; 2KYK; NMR; -; A=359-392.
DR PDB; 2NQ3; X-ray; 1.80 A; A=1-155.
DR PDB; 2P4R; X-ray; 2.00 A; T=246-270.
DR PDB; 2YSF; NMR; -; A=480-512.
DR PDB; 3TUG; X-ray; 2.27 A; A=524-903.
DR PDB; 4ROF; X-ray; 2.03 A; A/B=436-474.
DR PDB; 5C7M; X-ray; 3.03 A; A=524-899.
DR PDB; 5CQ2; X-ray; 1.40 A; A=433-521.
DR PDB; 5DWS; X-ray; 1.65 A; A/C/E/G=436-474.
DR PDB; 5DZD; X-ray; 1.57 A; A/B=475-514.
DR PDB; 5SXP; X-ray; 1.65 A; F/G=249-269.
DR PDBsum; 2DMV; -.
DR PDBsum; 2KYK; -.
DR PDBsum; 2NQ3; -.
DR PDBsum; 2P4R; -.
DR PDBsum; 2YSF; -.
DR PDBsum; 3TUG; -.
DR PDBsum; 4ROF; -.
DR PDBsum; 5C7M; -.
DR PDBsum; 5CQ2; -.
DR PDBsum; 5DWS; -.
DR PDBsum; 5DZD; -.
DR PDBsum; 5SXP; -.
DR AlphaFoldDB; Q96J02; -.
DR SMR; Q96J02; -.
DR BioGRID; 123747; 300.
DR CORUM; Q96J02; -.
DR DIP; DIP-29849N; -.
DR ELM; Q96J02; -.
DR IntAct; Q96J02; 65.
DR MINT; Q96J02; -.
DR STRING; 9606.ENSP00000480499; -.
DR ChEMBL; CHEMBL4295925; -.
DR GlyGen; Q96J02; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96J02; -.
DR PhosphoSitePlus; Q96J02; -.
DR BioMuta; ITCH; -.
DR DMDM; 37537897; -.
DR EPD; Q96J02; -.
DR jPOST; Q96J02; -.
DR MassIVE; Q96J02; -.
DR MaxQB; Q96J02; -.
DR PaxDb; Q96J02; -.
DR PeptideAtlas; Q96J02; -.
DR PRIDE; Q96J02; -.
DR ProteomicsDB; 25826; -.
DR ProteomicsDB; 76882; -. [Q96J02-1]
DR ProteomicsDB; 76883; -. [Q96J02-2]
DR Antibodypedia; 10897; 338 antibodies from 42 providers.
DR CPTC; Q96J02; 3 antibodies.
DR DNASU; 83737; -.
DR Ensembl; ENST00000262650.10; ENSP00000262650.5; ENSG00000078747.16. [Q96J02-1]
DR Ensembl; ENST00000374864.10; ENSP00000363998.4; ENSG00000078747.16. [Q96J02-2]
DR Ensembl; ENST00000535650.7; ENSP00000445608.1; ENSG00000078747.16. [Q96J02-3]
DR Ensembl; ENST00000665346.1; ENSP00000499786.1; ENSG00000078747.16. [Q96J02-1]
DR GeneID; 83737; -.
DR KEGG; hsa:83737; -.
DR MANE-Select; ENST00000374864.10; ENSP00000363998.4; NM_031483.7; NP_113671.3. [Q96J02-2]
DR UCSC; uc002xak.3; human. [Q96J02-1]
DR CTD; 83737; -.
DR DisGeNET; 83737; -.
DR GeneCards; ITCH; -.
DR HGNC; HGNC:13890; ITCH.
DR HPA; ENSG00000078747; Low tissue specificity.
DR MalaCards; ITCH; -.
DR MIM; 606409; gene.
DR MIM; 613385; phenotype.
DR neXtProt; NX_Q96J02; -.
DR OpenTargets; ENSG00000078747; -.
DR Orphanet; 228426; Syndromic multisystem autoimmune disease due to Itch deficiency.
DR PharmGKB; PA29934; -.
DR VEuPathDB; HostDB:ENSG00000078747; -.
DR eggNOG; KOG0940; Eukaryota.
DR GeneTree; ENSGT00940000157014; -.
DR HOGENOM; CLU_002173_0_1_1; -.
DR InParanoid; Q96J02; -.
DR OMA; DDWVIVP; -.
DR OrthoDB; 167687at2759; -.
DR PhylomeDB; Q96J02; -.
DR TreeFam; TF323658; -.
DR BRENDA; 2.3.2.26; 2681.
DR BRENDA; 2.3.2.B8; 2681.
DR PathwayCommons; Q96J02; -.
DR Reactome; R-HSA-1253288; Downregulation of ERBB4 signaling.
DR Reactome; R-HSA-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-HSA-2122948; Activated NOTCH1 Transmits Signal to the Nucleus.
DR Reactome; R-HSA-5610780; Degradation of GLI1 by the proteasome.
DR Reactome; R-HSA-5632684; Hedgehog 'on' state.
DR Reactome; R-HSA-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs.
DR Reactome; R-HSA-936440; Negative regulators of DDX58/IFIH1 signaling.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q96J02; -.
DR SIGNOR; Q96J02; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 83737; 18 hits in 1130 CRISPR screens.
DR ChiTaRS; ITCH; human.
DR EvolutionaryTrace; Q96J02; -.
DR GenomeRNAi; 83737; -.
DR Pharos; Q96J02; Tbio.
DR PRO; PR:Q96J02; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q96J02; protein.
DR Bgee; ENSG00000078747; Expressed in sperm and 186 other tissues.
DR ExpressionAtlas; Q96J02; baseline and differential.
DR Genevisible; Q96J02; HS.
DR GO; GO:0005938; C:cell cortex; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:ARUK-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:1990763; F:arrestin family protein binding; IPI:UniProtKB.
DR GO; GO:0045236; F:CXCR chemokine receptor binding; IPI:UniProtKB.
DR GO; GO:0016874; F:ligase activity; IEA:Ensembl.
DR GO; GO:0043021; F:ribonucleoprotein complex binding; IPI:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI.
DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; IPI:UniProtKB.
DR GO; GO:0019787; F:ubiquitin-like protein transferase activity; TAS:Reactome.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0035739; P:CD4-positive, alpha-beta T cell proliferation; IEA:Ensembl.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0006954; P:inflammatory response; NAS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:2000562; P:negative regulation of CD4-positive, alpha-beta T cell proliferation; IEA:Ensembl.
DR GO; GO:0050687; P:negative regulation of defense response to virus; IMP:UniProtKB.
DR GO; GO:0046329; P:negative regulation of JNK cascade; ISS:BHF-UCL.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISS:BHF-UCL.
DR GO; GO:0032480; P:negative regulation of type I interferon production; TAS:Reactome.
DR GO; GO:0070423; P:nucleotide-binding oligomerization domain containing signaling pathway; TAS:Reactome.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IEA:Ensembl.
DR GO; GO:2000646; P:positive regulation of receptor catabolic process; IMP:UniProtKB.
DR GO; GO:0002669; P:positive regulation of T cell anergy; IEA:Ensembl.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:ARUK-UCL.
DR GO; GO:0051865; P:protein autoubiquitination; IMP:UniProtKB.
DR GO; GO:0035519; P:protein K29-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0001558; P:regulation of cell growth; NAS:UniProtKB.
DR GO; GO:1902036; P:regulation of hematopoietic stem cell differentiation; TAS:Reactome.
DR GO; GO:0090085; P:regulation of protein deubiquitination; ISS:BHF-UCL.
DR GO; GO:0002870; P:T cell anergy; IEA:Ensembl.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:MGI.
DR GO; GO:0046718; P:viral entry into host cell; TAS:UniProtKB.
DR CDD; cd00078; HECTc; 1.
DR CDD; cd00201; WW; 4.
DR Gene3D; 2.60.40.150; -; 1.
DR IDEAL; IID00178; -.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR024928; E3_ub_ligase_SMURF1.
DR InterPro; IPR000569; HECT_dom.
DR InterPro; IPR035983; Hect_E3_ubiquitin_ligase.
DR InterPro; IPR001202; WW_dom.
DR InterPro; IPR036020; WW_dom_sf.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF00632; HECT; 1.
DR Pfam; PF00397; WW; 4.
DR PIRSF; PIRSF001569; E3_ub_ligase_SMURF1; 1.
DR SMART; SM00239; C2; 1.
DR SMART; SM00119; HECTc; 1.
DR SMART; SM00456; WW; 4.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF51045; SSF51045; 4.
DR SUPFAM; SSF56204; SSF56204; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS50237; HECT; 1.
DR PROSITE; PS01159; WW_DOMAIN_1; 4.
DR PROSITE; PS50020; WW_DOMAIN_2; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Antiviral defense;
KW Apoptosis; Cell membrane; Cytoplasm; Direct protein sequencing; Endosome;
KW Host-virus interaction; Immunity; Innate immunity; Membrane; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Transferase; Ubl conjugation;
KW Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..903
FT /note="E3 ubiquitin-protein ligase Itchy homolog"
FT /id="PRO_0000120317"
FT DOMAIN 1..115
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 326..359
FT /note="WW 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 358..391
FT /note="WW 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 438..471
FT /note="WW 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 478..511
FT /note="WW 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 569..903
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT REGION 197..301
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 395..471
FT /note="Required for interaction with FYN"
FT /evidence="ECO:0000269|PubMed:16387660"
FT REGION 574..583
FT /note="MAP kinase docking site"
FT /evidence="ECO:0000250"
FT COMPBIAS 206..230
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 233..247
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 252..268
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 269..301
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 871
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 240
FT /note="Phosphoserine; by MAPK8"
FT /evidence="ECO:0000250|UniProtKB:Q8C863"
FT MOD_RES 263
FT /note="Phosphothreonine; by MAPK8"
FT /evidence="ECO:0000250|UniProtKB:Q8C863"
FT MOD_RES 273
FT /note="Phosphoserine; by MAPK8"
FT /evidence="ECO:0000250|UniProtKB:Q8C863"
FT MOD_RES 385
FT /note="Phosphothreonine; by SGK3"
FT /evidence="ECO:0000269|PubMed:16888620"
FT MOD_RES 420
FT /note="Phosphotyrosine; by FYN"
FT /evidence="ECO:0000269|PubMed:16387660"
FT MOD_RES 450
FT /note="Phosphoserine; by SGK3"
FT /evidence="ECO:0000269|PubMed:16888620"
FT VAR_SEQ 1..110
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044732"
FT VAR_SEQ 159..200
FT /note="NGVSLCLPRLECNSAISAHCNLCLPGLSDSPISASRVAGFTG -> S (in
FT isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:11318614,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9647693, ECO:0000303|Ref.2"
FT /id="VSP_008451"
FT MUTAGEN 343
FT /note="Y->F: No effect on phosphorylation on T-cell
FT stimulation nor in the presence of FYN."
FT /evidence="ECO:0000269|PubMed:16387660"
FT MUTAGEN 420
FT /note="Y->F: Greatly reduced phosphorylation on T-cell
FT stimulation and in the presence of FYN. Increased ITCH-
FT mediated Ub conjugation and degradation of JUNB."
FT /evidence="ECO:0000269|PubMed:16387660"
FT MUTAGEN 455
FT /note="Y->F: No effect on phosphorylation on T-cell
FT stimulation nor in the presence of FYN."
FT /evidence="ECO:0000269|PubMed:16387660"
FT MUTAGEN 871
FT /note="C->A: Loss of ubiquitin protein ligase activity.
FT Results in altered endosomal sorting and reduced
FT degradation of CXCR4. Unable to inhibit MAVS-induced
FT activation of INFB."
FT /evidence="ECO:0000269|PubMed:11046148,
FT ECO:0000269|PubMed:14602072, ECO:0000269|PubMed:19881509,
FT ECO:0000269|PubMed:23146885, ECO:0000269|PubMed:24790097"
FT CONFLICT 297
FT /note="T -> I (in Ref. 3; BAG64996)"
FT /evidence="ECO:0000305"
FT STRAND 18..29
FT /evidence="ECO:0007829|PDB:2NQ3"
FT STRAND 41..47
FT /evidence="ECO:0007829|PDB:2NQ3"
FT STRAND 50..53
FT /evidence="ECO:0007829|PDB:2NQ3"
FT STRAND 64..73
FT /evidence="ECO:0007829|PDB:2NQ3"
FT STRAND 78..85
FT /evidence="ECO:0007829|PDB:2NQ3"
FT STRAND 88..90
FT /evidence="ECO:0007829|PDB:2NQ3"
FT STRAND 93..101
FT /evidence="ECO:0007829|PDB:2NQ3"
FT HELIX 102..108
FT /evidence="ECO:0007829|PDB:2NQ3"
FT TURN 109..111
FT /evidence="ECO:0007829|PDB:2NQ3"
FT STRAND 112..126
FT /evidence="ECO:0007829|PDB:2NQ3"
FT STRAND 130..143
FT /evidence="ECO:0007829|PDB:2NQ3"
FT STRAND 332..336
FT /evidence="ECO:0007829|PDB:2DMV"
FT STRAND 342..346
FT /evidence="ECO:0007829|PDB:2DMV"
FT TURN 347..349
FT /evidence="ECO:0007829|PDB:2DMV"
FT STRAND 352..355
FT /evidence="ECO:0007829|PDB:2DMV"
FT STRAND 365..368
FT /evidence="ECO:0007829|PDB:2KYK"
FT STRAND 374..377
FT /evidence="ECO:0007829|PDB:2KYK"
FT STRAND 379..381
FT /evidence="ECO:0007829|PDB:2KYK"
FT STRAND 444..448
FT /evidence="ECO:0007829|PDB:5CQ2"
FT STRAND 454..458
FT /evidence="ECO:0007829|PDB:5CQ2"
FT TURN 459..462
FT /evidence="ECO:0007829|PDB:5CQ2"
FT STRAND 463..467
FT /evidence="ECO:0007829|PDB:5CQ2"
FT HELIX 469..471
FT /evidence="ECO:0007829|PDB:5DWS"
FT STRAND 484..488
FT /evidence="ECO:0007829|PDB:5CQ2"
FT STRAND 494..498
FT /evidence="ECO:0007829|PDB:5CQ2"
FT TURN 499..502
FT /evidence="ECO:0007829|PDB:5CQ2"
FT STRAND 503..507
FT /evidence="ECO:0007829|PDB:5CQ2"
FT TURN 509..511
FT /evidence="ECO:0007829|PDB:5CQ2"
FT HELIX 528..539
FT /evidence="ECO:0007829|PDB:3TUG"
FT TURN 540..542
FT /evidence="ECO:0007829|PDB:3TUG"
FT STRAND 545..551
FT /evidence="ECO:0007829|PDB:3TUG"
FT STRAND 554..556
FT /evidence="ECO:0007829|PDB:3TUG"
FT HELIX 557..567
FT /evidence="ECO:0007829|PDB:3TUG"
FT HELIX 572..574
FT /evidence="ECO:0007829|PDB:3TUG"
FT STRAND 575..580
FT /evidence="ECO:0007829|PDB:3TUG"
FT HELIX 589..603
FT /evidence="ECO:0007829|PDB:3TUG"
FT TURN 607..609
FT /evidence="ECO:0007829|PDB:3TUG"
FT STRAND 611..614
FT /evidence="ECO:0007829|PDB:3TUG"
FT STRAND 621..624
FT /evidence="ECO:0007829|PDB:3TUG"
FT HELIX 626..630
FT /evidence="ECO:0007829|PDB:3TUG"
FT HELIX 634..650
FT /evidence="ECO:0007829|PDB:3TUG"
FT HELIX 661..667
FT /evidence="ECO:0007829|PDB:3TUG"
FT HELIX 675..677
FT /evidence="ECO:0007829|PDB:3TUG"
FT TURN 678..680
FT /evidence="ECO:0007829|PDB:3TUG"
FT HELIX 682..692
FT /evidence="ECO:0007829|PDB:3TUG"
FT HELIX 696..699
FT /evidence="ECO:0007829|PDB:5C7M"
FT STRAND 704..709
FT /evidence="ECO:0007829|PDB:5C7M"
FT STRAND 716..721
FT /evidence="ECO:0007829|PDB:5C7M"
FT HELIX 724..726
FT /evidence="ECO:0007829|PDB:5C7M"
FT TURN 731..733
FT /evidence="ECO:0007829|PDB:5C7M"
FT HELIX 735..747
FT /evidence="ECO:0007829|PDB:3TUG"
FT HELIX 751..764
FT /evidence="ECO:0007829|PDB:3TUG"
FT HELIX 767..770
FT /evidence="ECO:0007829|PDB:3TUG"
FT HELIX 775..783
FT /evidence="ECO:0007829|PDB:3TUG"
FT HELIX 790..795
FT /evidence="ECO:0007829|PDB:3TUG"
FT STRAND 798..801
FT /evidence="ECO:0007829|PDB:3TUG"
FT HELIX 807..818
FT /evidence="ECO:0007829|PDB:3TUG"
FT HELIX 821..832
FT /evidence="ECO:0007829|PDB:3TUG"
FT HELIX 842..844
FT /evidence="ECO:0007829|PDB:3TUG"
FT STRAND 848..851
FT /evidence="ECO:0007829|PDB:3TUG"
FT STRAND 855..858
FT /evidence="ECO:0007829|PDB:3TUG"
FT STRAND 867..869
FT /evidence="ECO:0007829|PDB:3TUG"
FT HELIX 870..872
FT /evidence="ECO:0007829|PDB:3TUG"
FT STRAND 874..877
FT /evidence="ECO:0007829|PDB:3TUG"
FT HELIX 883..895
FT /evidence="ECO:0007829|PDB:3TUG"
SQ SEQUENCE 903 AA; 102803 MW; 6777A2043C7B67BC CRC64;
MSDSGSQLGS MGSLTMKSQL QITVISAKLK ENKKNWFGPS PYVEVTVDGQ SKKTEKCNNT
NSPKWKQPLT VIVTPVSKLH FRVWSHQTLK SDVLLGTAAL DIYETLKSNN MKLEEVVVTL
QLGGDKEPTE TIGDLSICLD GLQLESEVVT NGETTCSENG VSLCLPRLEC NSAISAHCNL
CLPGLSDSPI SASRVAGFTG ASQNDDGSRS KDETRVSTNG SDDPEDAGAG ENRRVSGNNS
PSLSNGGFKP SRPPRPSRPP PPTPRRPASV NGSPSATSES DGSSTGSLPP TNTNTNTSEG
ATSGLIIPLT ISGGSGPRPL NPVTQAPLPP GWEQRVDQHG RVYYVDHVEK RTTWDRPEPL
PPGWERRVDN MGRIYYVDHF TRTTTWQRPT LESVRNYEQW QLQRSQLQGA MQQFNQRFIY
GNQDLFATSQ SKEFDPLGPL PPGWEKRTDS NGRVYFVNHN TRITQWEDPR SQGQLNEKPL
PEGWEMRFTV DGIPYFVDHN RRTTTYIDPR TGKSALDNGP QIAYVRDFKA KVQYFRFWCQ
QLAMPQHIKI TVTRKTLFED SFQQIMSFSP QDLRRRLWVI FPGEEGLDYG GVAREWFFLL
SHEVLNPMYC LFEYAGKDNY CLQINPASYI NPDHLKYFRF IGRFIAMALF HGKFIDTGFS
LPFYKRILNK PVGLKDLESI DPEFYNSLIW VKENNIEECD LEMYFSVDKE ILGEIKSHDL
KPNGGNILVT EENKEEYIRM VAEWRLSRGV EEQTQAFFEG FNEILPQQYL QYFDAKELEV
LLCGMQEIDL NDWQRHAIYR HYARTSKQIM WFWQFVKEID NEKRMRLLQF VTGTCRLPVG
GFADLMGSNG PQKFCIEKVG KENWLPRSHT CFNRLDLPPY KSYEQLKEKL LFAIEETEGF
GQE
