ID UBP8_MOUSE Reviewed; 1080 AA. AC Q80U87; A2AI53; Q80YP2; Q8R0D3; Q9EQU1; Q9WVP5; DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2004, sequence version 2. DT 27-MAR-2024, entry version 173. DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 8 {ECO:0000305}; DE EC=3.4.19.12 {ECO:0000269|PubMed:16120644}; DE AltName: Full=Deubiquitinating enzyme 8; DE AltName: Full=Ubiquitin isopeptidase Y; DE Short=mUBPy; DE AltName: Full=Ubiquitin thioesterase 8; DE AltName: Full=Ubiquitin-specific-processing protease 8; GN Name=Usp8 {ECO:0000312|MGI:MGI:1934029}; Synonyms=Kiaa0055, Ubpy; 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], SH3-BINDING, INTERACTION WITH STAM2, AND RP MUTAGENESIS OF PRO-405; GLN-406; VAL-407; ASP-408; ARG-409; THR-410; RP LYS-411; LYS-412 AND PRO-413. RX PubMed=10982817; DOI=10.1074/jbc.m007251200; RA Kato M., Miyazawa K., Kitamura N.; RT "A deubiquitinating enzyme UBPY interacts with the Src homology 3 domain of RT Hrs-binding protein via a novel binding motif PX(V/I)(D/N)RXXKP."; RL J. Biol. Chem. 275:37481-37487(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND INTERACTION RP WITH RASGRF1. RC TISSUE=Embryo; RX PubMed=11500497; DOI=10.1074/jbc.m103454200; RA Gnesutta N., Ceriani M., Innocenti M., Mauri I., Zippel R., Sturani E., RA Borgonovo B., Berruti G., Martegani E.; RT "Cloning and characterization of mouse UBPy, a deubiquitinating enzyme that RT interacts with the ras guanine nucleotide exchange factor CDC25(Mm)/Ras- RT GRF1."; RL J. Biol. Chem. 276:39448-39454(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=12693553; DOI=10.1093/dnares/10.1.35; RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S., RA Nakajima D., Nagase T., Ohara O., Koga H.; RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II. RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs RT identified by screening of terminal sequences of cDNA clones randomly RT sampled from size-fractionated libraries."; RL DNA Res. 10:35-48(2003). 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]. RC STRAIN=C57BL/6J; TISSUE=Brain, and Kidney; 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 [6] RP IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH RNF41, FUNCTION, AND RP MUTAGENESIS OF CYS-748. RX PubMed=15314180; DOI=10.1128/mcb.24.17.7748-7757.2004; RA Wu X., Yen L., Irwin L., Sweeney C., Carraway K.L. III; RT "Stabilization of the E3 ubiquitin ligase Nrdp1 by the deubiquitinating RT enzyme USP8."; RL Mol. Cell. Biol. 24:7748-7757(2004). RN [7] 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 [8] RP INTERACTION WITH OTUB1 AND RNF128, AND MUTAGENESIS OF CYS-748. RX PubMed=14661020; DOI=10.1038/ni1017; RA Soares L., Seroogy C., Skrenta H., Anandasabapathy N., Lovelace P., RA Chung C.D., Engleman E., Fathman C.G.; RT "Two isoforms of otubain 1 regulate T cell anergy via GRAIL."; RL Nat. Immunol. 5:45-54(2004). RN [9] RP TISSUE SPECIFICITY, AND INTERACTION WITH DNAJB3. RX PubMed=15342353; DOI=10.1095/biolreprod.104.030866; RA Berruti G., Martegani E.; RT "The deubiquitinating enzyme mUBPy interacts with the sperm-specific RT molecular chaperone MSJ-1: the relation with the proteasome, acrosome, and RT centrosome in mouse male germ cells."; RL Biol. Reprod. 72:14-21(2005). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, UBIQUITINATION, AND RP MUTAGENESIS OF CYS-748. RX PubMed=16120644; DOI=10.1091/mbc.e05-06-0560; RA Mizuno E., Iura T., Mukai A., Yoshimori T., Kitamura N., Komada M.; RT "Regulation of epidermal growth factor receptor down-regulation by UBPY- RT mediated deubiquitination at endosomes."; RL Mol. Biol. Cell 16:5163-5174(2005). RN [11] RP FUNCTION, MUTAGENESIS OF CYS-748, AND INTERACTION WITH ESP15. RX PubMed=16771824; DOI=10.1111/j.1600-0854.2006.00452.x; RA Mizuno E., Kobayashi K., Yamamoto A., Kitamura N., Komada M.; RT "A deubiquitinating enzyme UBPY regulates the level of protein RT ubiquitination on endosomes."; RL Traffic 7:1017-1031(2006). RN [12] RP PHOSPHORYLATION, INTERACTION WITH EGFR, AND FUNCTION. RX PubMed=17121848; DOI=10.1074/jbc.m604711200; RA Alwan H.A., van Leeuwen J.E.; RT "UBPY-mediated epidermal growth factor receptor (EGFR) de-ubiquitination RT promotes EGFR degradation."; RL J. Biol. Chem. 282:1658-1669(2007). RN [13] RP PHOSPHORYLATION AT SER-680, INTERACTION WITH YWHAE, MUTAGENESIS OF SER-680, RP AND SUBCELLULAR LOCATION. RX PubMed=16944949; DOI=10.1021/pr060206k; RA Ballif B.A., Cao Z., Schwartz D., Carraway K.L. III, Gygi S.P.; RT "Identification of 14-3-3epsilon substrates from embryonic murine brain."; RL J. Proteome Res. 5:2372-2379(2006). RN [14] RP FUNCTION, PHOSPHORYLATION AT SER-680, INTERACTION WITH YWHAE; YWHAG AND RP YWHAZ, MUTAGENESIS OF SER-680, AND SUBCELLULAR LOCATION. RX PubMed=17720156; DOI=10.1016/j.yexcr.2007.07.028; RA Mizuno E., Kitamura N., Komada M.; RT "14-3-3-dependent inhibition of the deubiquitinating activity of UBPY and RT its cancellation in the M phase."; RL Exp. Cell Res. 313:3624-3634(2007). RN [15] RP FUNCTION, PHOSPHORYLATION AT THR-907, AND MUTAGENESIS OF THR-907. RX PubMed=17210635; DOI=10.1128/mcb.01245-06; RA Cao Z., Wu X., Yen L., Sweeney C., Carraway K.L. III; RT "Neuregulin-induced ErbB3 downregulation is mediated by a protein stability RT cascade involving the E3 ubiquitin ligase Nrdp1."; RL Mol. Cell. Biol. 27:2180-2188(2007). RN [16] RP FUNCTION. RX PubMed=17452457; DOI=10.1128/mcb.01566-06; RA Niendorf S., Oksche A., Kisser A., Lohler J., Prinz M., Schorle H., RA Feller S., Lewitzky M., Horak I., Knobeloch K.P.; RT "Essential role of ubiquitin-specific protease 8 for receptor tyrosine RT kinase stability and endocytic trafficking in vivo."; RL Mol. Cell. Biol. 27:5029-5039(2007). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006; RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M., RA Thibault P.; RT "The phagosomal proteome in interferon-gamma-activated macrophages."; RL Immunity 30:143-154(2009). RN [18] RP FUNCTION, ASSOCIATION WITH THE ESCRT-0 COMPLEX, AND MICROTUBULE-BINDING. RX PubMed=20130268; DOI=10.1095/biolreprod.109.081679; RA Berruti G., Ripolone M., Ceriani M.; RT "USP8, a regulator of endosomal sorting, is involved in mouse acrosome RT biogenesis through interaction with the spermatid ESCRT-0 complex and RT microtubules."; RL Biol. Reprod. 82:930-939(2010). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, 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). CC -!- FUNCTION: Hydrolase that can remove conjugated ubiquitin from proteins CC and therefore plays an important regulatory role at the level of CC protein turnover by preventing degradation. Converts both 'Lys-48' an CC 'Lys-63'-linked ubiquitin chains. Catalytic activity is enhanced in the CC M phase. Involved in cell proliferation. Required to enter into S phase CC in response to serum stimulation. May regulate T-cell anergy mediated CC by RNF128 via the formation of a complex containing RNF128 and OTUB1. CC Probably regulates the stability of STAM2 and RASGRF1. Regulates CC endosomal ubiquitin dynamics, cargo sorting, membrane traffic at early CC endosomes, and maintenance of ESCRT-0 stability. The level of protein CC ubiquitination on endosomes is essential for maintaining the morphology CC of the organelle. Deubiquitinates EPS15 and controls tyrosine kinase CC stability. Removes conjugated ubiquitin from EGFR thus regulating EGFR CC degradation and downstream MAPK signaling. Involved in acrosome CC biogenesis through interaction with the spermatid ESCRT-0 complex and CC microtubules. Deubiquitinates BIRC6/bruce and KIF23/MKLP1 (By CC similarity). Deubiquitinates BACE1 which inhibits BACE1 lysosomal CC degradation and modulates BACE-mediated APP cleavage and amyloid-beta CC formation (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P40818, CC ECO:0000269|PubMed:11500497, ECO:0000269|PubMed:15314180, CC ECO:0000269|PubMed:16120644, ECO:0000269|PubMed:16771824, CC ECO:0000269|PubMed:17121848, ECO:0000269|PubMed:17210635, CC ECO:0000269|PubMed:17452457, ECO:0000269|PubMed:17720156, CC ECO:0000269|PubMed:20130268}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76- CC residue protein attached to proteins as an intracellular targeting CC signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:16120644}; CC -!- SUBUNIT: Forms a ternary complex with RNF128 and OTUB1. Interacts (via CC C-terminal UCH catalytic domain) with OTUB1 isoform 1. Interacts with CC STAM2 (via SH3 domain). Interacts with DNAJB3, EGFR, EPS15, RASGRF1, CC RNF41, YWHAE, YWHAG and YWHAZ. Interacts with NBR1, RASGRF1, RNF41 and CC IST1 (By similarity). Associates with the ESCRT-0 complex and with CC microtubules. Interacts with BIRC6/bruce and KIF23/MKLP1. {ECO:0000250, CC ECO:0000269|PubMed:10982817, ECO:0000269|PubMed:11500497, CC ECO:0000269|PubMed:14661020, ECO:0000269|PubMed:15314180, CC ECO:0000269|PubMed:15342353, ECO:0000269|PubMed:16771824, CC ECO:0000269|PubMed:16944949, ECO:0000269|PubMed:17121848, CC ECO:0000269|PubMed:17720156}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17720156}. Nucleus CC {ECO:0000269|PubMed:16944949}. Endosome membrane CC {ECO:0000269|PubMed:16120644}; Peripheral membrane protein CC {ECO:0000305}. Cell membrane {ECO:0000250|UniProtKB:P40818}; Peripheral CC membrane protein {ECO:0000305}. CC -!- TISSUE SPECIFICITY: Highly expressed in testis. Expressed at CC intermediate level in brain. {ECO:0000269|PubMed:11500497, CC ECO:0000269|PubMed:15342353}. CC -!- DOMAIN: The MIT domain is required for endosomal localization, CHMP1B- CC binding, maintenance of ESCRT-0 stability and EGFR degradation. CC {ECO:0000250}. CC -!- DOMAIN: The rhodanese domain is sufficient for RNF41-binding. CC -!- PTM: Phosphorylation of Ser-680 is essential for interaction with YWHAE CC and for cytosol localization. Undergoes dephosphorylation at Ser-680 in CC the M phase. Tyrosine-phosphorylated in its N-terminal half in an EGFR- CC dependent manner. {ECO:0000269|PubMed:16944949, CC ECO:0000269|PubMed:17121848, ECO:0000269|PubMed:17210635, CC ECO:0000269|PubMed:17720156}. CC -!- PTM: Ubiquitinated. Inactive form is mostly monoubiquitinated, but CC polyubiquitination happens too. Ubiquitination is increased in EGF- CC stimulated cells. Ubiquitination of active form is undetectable, CC suggesting a possibility that USP8 deubiquitinates itself, thereby CC regulating its own function. {ECO:0000269|PubMed:16120644}. CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAC65477.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB045709; BAB18534.1; -; mRNA. DR EMBL; AF057146; AAD38869.1; -; mRNA. DR EMBL; AK122195; BAC65477.1; ALT_INIT; mRNA. DR EMBL; AL732330; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC027052; AAH27052.1; -; mRNA. DR EMBL; BC050947; AAH50947.1; -; mRNA. DR EMBL; BC061465; AAH61465.1; -; mRNA. DR EMBL; BC066126; AAH66126.1; -; mRNA. DR CCDS; CCDS16687.1; -. DR RefSeq; NP_062703.2; NM_019729.3. DR PDB; 1UJ0; X-ray; 1.70 A; B=699-709. DR PDBsum; 1UJ0; -. DR AlphaFoldDB; Q80U87; -. DR SMR; Q80U87; -. DR BioGRID; 220000; 23. DR IntAct; Q80U87; 7. DR MINT; Q80U87; -. DR STRING; 10090.ENSMUSP00000106046; -. DR MEROPS; C19.011; -. DR GlyGen; Q80U87; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q80U87; -. DR PhosphoSitePlus; Q80U87; -. DR EPD; Q80U87; -. DR jPOST; Q80U87; -. DR MaxQB; Q80U87; -. DR PaxDb; 10090-ENSMUSP00000106046; -. DR ProteomicsDB; 297795; -. DR Pumba; Q80U87; -. DR Antibodypedia; 1385; 298 antibodies from 28 providers. DR DNASU; 84092; -. DR Ensembl; ENSMUST00000028841.14; ENSMUSP00000028841.8; ENSMUSG00000027363.16. DR GeneID; 84092; -. DR KEGG; mmu:84092; -. DR UCSC; uc008meb.2; mouse. DR AGR; MGI:1934029; -. DR CTD; 9101; -. DR MGI; MGI:1934029; Usp8. DR VEuPathDB; HostDB:ENSMUSG00000027363; -. DR eggNOG; KOG1868; Eukaryota. DR GeneTree; ENSGT00940000157542; -. DR InParanoid; Q80U87; -. DR OMA; TCNKESA; -. DR Reactome; R-MMU-1358803; Downregulation of ERBB2:ERBB3 signaling. DR Reactome; R-MMU-4641263; Regulation of FZD by ubiquitination. DR Reactome; R-MMU-5689880; Ub-specific processing proteases. DR Reactome; R-MMU-6807004; Negative regulation of MET activity. DR BioGRID-ORCS; 84092; 25 hits in 77 CRISPR screens. DR ChiTaRS; Usp8; mouse. DR PRO; PR:Q80U87; -. DR Proteomes; UP000000589; Chromosome 2. DR RNAct; Q80U87; Protein. DR Bgee; ENSMUSG00000027363; Expressed in spermatid and 256 other cell types or tissues. DR ExpressionAtlas; Q80U87; baseline and differential. DR GO; GO:0002080; C:acrosomal membrane; IDA:MGI. DR GO; GO:0005737; C:cytoplasm; ISO:MGI. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0043197; C:dendritic spine; ISO:MGI. DR GO; GO:0005769; C:early endosome; ISO:MGI. DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB. DR GO; GO:0019897; C:extrinsic component of plasma membrane; IBA:GO_Central. DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI. DR GO; GO:0030496; C:midbody; IDA:MGI. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0014069; C:postsynaptic density; ISO:MGI. DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB. DR GO; GO:1990380; F:K48-linked deubiquitinase activity; ISO:MGI. DR GO; GO:0061578; F:K63-linked deubiquitinase activity; ISO:MGI. DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW. DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; ISO:MGI. DR GO; GO:0007032; P:endosome organization; IMP:UniProtKB. DR GO; GO:0000281; P:mitotic cytokinesis; ISO:MGI. DR GO; GO:1905166; P:negative regulation of lysosomal protein catabolic process; ISO:MGI. DR GO; GO:1905908; P:positive regulation of amyloid fibril formation; ISO:MGI. DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISO:MGI. DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR GO; GO:0007265; P:Ras protein signal transduction; IPI:MGI. DR GO; GO:0099576; P:regulation of protein catabolic process at postsynapse, modulating synaptic transmission; ISO:MGI. DR GO; GO:0032880; P:regulation of protein localization; ISS:UniProtKB. DR GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB. DR CDD; cd02674; Peptidase_C19R; 1. DR Gene3D; 3.90.70.10; Cysteine proteinases; 1. DR Gene3D; 1.20.58.80; Phosphotransferase system, lactose/cellobiose-type IIA subunit; 1. DR Gene3D; 3.40.250.10; Rhodanese-like domain; 1. DR InterPro; IPR038765; Papain-like_cys_pep_sf. DR InterPro; IPR001394; Peptidase_C19_UCH. DR InterPro; IPR001763; Rhodanese-like_dom. DR InterPro; IPR036873; Rhodanese-like_dom_sf. DR InterPro; IPR015063; USP8_dimer. DR InterPro; IPR018200; USP_CS. DR InterPro; IPR028889; USP_dom. DR InterPro; IPR048498; WW_USP8. DR PANTHER; PTHR21646; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1. DR PANTHER; PTHR21646:SF27; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 8; 1. DR Pfam; PF00581; Rhodanese; 1. DR Pfam; PF00443; UCH; 1. DR Pfam; PF08969; USP8_dimer; 1. DR Pfam; PF20625; WW_USP8; 1. DR SMART; SM00450; RHOD; 1. DR SUPFAM; SSF54001; Cysteine proteinases; 1. DR SUPFAM; SSF52821; Rhodanese/Cell cycle control phosphatase; 1. DR SUPFAM; SSF140856; USP8 N-terminal domain-like; 1. DR PROSITE; PS50206; RHODANESE_3; 1. DR PROSITE; PS00972; USP_1; 1. DR PROSITE; PS00973; USP_2; 1. DR PROSITE; PS50235; USP_3; 1. DR Genevisible; Q80U87; MM. PE 1: Evidence at protein level; KW 3D-structure; Cell cycle; Cell membrane; Cytoplasm; Endosome; Hydrolase; KW Membrane; Nucleus; Phosphoprotein; Protease; Reference proteome; KW SH3-binding; Thiol protease; Ubl conjugation; Ubl conjugation pathway. FT CHAIN 1..1080 FT /note="Ubiquitin carboxyl-terminal hydrolase 8" FT /id="PRO_0000080628" FT DOMAIN 33..116 FT /note="MIT" FT DOMAIN 195..313 FT /note="Rhodanese" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00173" FT DOMAIN 739..1071 FT /note="USP" FT REGION 119..176 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 379..455 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 468..605 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 642..710 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 405..413 FT /note="SH3-binding" FT COMPBIAS 119..168 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 412..428 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 429..447 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 468..537 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 547..561 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 645..659 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 662..677 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 748 FT /note="Nucleophile" FT ACT_SITE 1029 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, FT ECO:0000255|PROSITE-ProRule:PRU10093" FT MOD_RES 160 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P40818" FT MOD_RES 392 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P40818" FT MOD_RES 446 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P40818" FT MOD_RES 569 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P40818" FT MOD_RES 680 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:16944949, FT ECO:0000269|PubMed:17720156" FT MOD_RES 681 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P40818" FT MOD_RES 907 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:17210635" FT MUTAGEN 405 FT /note="P->A: Abolishes interaction with the SH3 domain of FT STAM2." FT /evidence="ECO:0000269|PubMed:10982817" FT MUTAGEN 406 FT /note="Q->A: Does not affect interaction with the SH3 FT domain of STAM2." FT /evidence="ECO:0000269|PubMed:10982817" FT MUTAGEN 407 FT /note="V->A: Reduces interaction with the SH3 domain of FT STAM2." FT /evidence="ECO:0000269|PubMed:10982817" FT MUTAGEN 408 FT /note="D->A: Reduces interaction with the SH3 domain of FT STAM2." FT /evidence="ECO:0000269|PubMed:10982817" FT MUTAGEN 409 FT /note="R->A: Abolishes interaction with the SH3 domain of FT STAM2." FT /evidence="ECO:0000269|PubMed:10982817" FT MUTAGEN 410 FT /note="T->A: Does not affect interaction with the SH3 FT domain of STAM2." FT /evidence="ECO:0000269|PubMed:10982817" FT MUTAGEN 411 FT /note="K->A: Does not affect interaction with the SH3 FT domain of STAM2." FT /evidence="ECO:0000269|PubMed:10982817" FT MUTAGEN 412 FT /note="K->A: Abolishes interaction with the SH3 domain of FT STAM2." FT /evidence="ECO:0000269|PubMed:10982817" FT MUTAGEN 413 FT /note="P->A: Abolishes interaction with the SH3 domain of FT STAM2." FT /evidence="ECO:0000269|PubMed:10982817" FT MUTAGEN 680 FT /note="S->A: Abolishes the interaction with YWHAE and leads FT to accumulation in the nucleus." FT /evidence="ECO:0000269|PubMed:16944949, FT ECO:0000269|PubMed:17720156" FT MUTAGEN 748 FT /note="C->A: Impairs deubiquitination of EPS15, RNF128 and FT RNF41." FT /evidence="ECO:0000269|PubMed:14661020, FT ECO:0000269|PubMed:15314180, ECO:0000269|PubMed:16120644, FT ECO:0000269|PubMed:16771824" FT MUTAGEN 907 FT /note="T->A: Reduces stabilization activity on RNF41." FT /evidence="ECO:0000269|PubMed:17210635" FT CONFLICT 139 FT /note="Q -> P (in Ref. 2; AAD38869)" FT /evidence="ECO:0000305" FT CONFLICT 151 FT /note="K -> R (in Ref. 1; BAB18534)" FT /evidence="ECO:0000305" FT CONFLICT 349 FT /note="T -> A (in Ref. 1; BAB18534)" FT /evidence="ECO:0000305" FT CONFLICT 370 FT /note="E -> G (in Ref. 1; BAB18534)" FT /evidence="ECO:0000305" FT CONFLICT 557 FT /note="D -> N (in Ref. 1; BAB18534)" FT /evidence="ECO:0000305" FT CONFLICT 576 FT /note="P -> L (in Ref. 1; BAB18534)" FT /evidence="ECO:0000305" FT CONFLICT 837 FT /note="F -> S (in Ref. 1; BAB18534)" FT /evidence="ECO:0000305" FT CONFLICT 865..873 FT /note="DLQAAEHAW -> EPAGGRARL (in Ref. 1; BAB18534)" FT /evidence="ECO:0000305" FT CONFLICT 885..886 FT /note="VA -> RL (in Ref. 1; BAB18534)" FT /evidence="ECO:0000305" FT CONFLICT 894 FT /note="S -> A (in Ref. 1; BAB18534)" FT /evidence="ECO:0000305" FT HELIX 704..706 FT /evidence="ECO:0007829|PDB:1UJ0" SQ SEQUENCE 1080 AA; 122611 MW; 7F458E3B1AF0B7FA CRC64; MPAVASVPKE LYLSSSLKDL NKKTEVKPEK TSTKNYIHSA QKIFKTAEEC RLDRDEERAY VLYMKYVAVY NLIKKRPDFK QQQDYYLSIL GPANIKKAIE EAERLSESLK LRYEEAEVRK QLEEKDRREE EQLQQQKRQE MGREDSGAAA KRSVENLLDS KTKTQRINGE KSEGAAAAER GAITAKELYT MMMDKNTSLI IMDARKIQDY QHSCILDSLS VPEEAISPGV TASWIEANLS DDSKDTWKKR GSVDYVVLLD WFSSAKDLLL GTTLRSLKDA LFKWESKTVL RHEPLVLEGG YENWLLCYPQ FTTNAKVTPP PRSRAEEVSV SLDFTYPSLE EPVPSKLPTQ MPPPPIETNE KALLVTDQDE KLRLSTQPAL AGPGAAPRAE ASPIIQPAPA TKSVPQVDRT KKPSVKLPED HRIKSENTDQ SGRVLSDRST KPVFPSPTTM LTDEEKARIH QETALLMEKN KQEKELWDKQ QKEQKEKLRR EEQERKAGKT QDADERDSTE NQHKAKDGQE KKDSKQTKTE DRELSADGAQ EATGTQRQSK SEHEASDAKV PVEGKRCPTS EAQKRPADVS PASVSGELNA GKAQREPLTR ARSEEMGRIV PGLPLGWAKF LDPITGTFRY YHSPTNTVHM YPPEMAPSSA PPSTPPTHKV KPQVPAERDR EPSKLKRSYS SPDITQALQE EEKRRPAVTP MVNRENKPPC YPKAEISRLS ASQIRNLNPV FGGSGPALTG LRNLGNTCYM NSILQCLCNA PHLADYFNRN CYQDDINRSN LLGHKGEVAE EFGIIMKALW TGQYRYISPK DFKVTIGKIN DQFAGSSQQD SQELLLFLMD GLHEDLNKAD NRKRHKEENN EHLDDLQAAE HAWQKHKQLN ESIIVALFQG QFKSTVQCLT CRRRSRTFEA FMYLSLPLAS TSKCTLQDCL RLFSKEEKLT DNNRFYCSHC RARRDSLKKI EIWKLPPVLL VHLKRFSYDG RWKQKLQTSV DFPLENLDLS QYVIGPKNSL KKYNLFSVSN HYGGLDGGHY TAYCKNAARQ RWFKFDDHEV SDISVSSVRS SAAYILFYTS LGPRITDVAT //