ID   STABP_HUMAN             Reviewed;         424 AA.
AC   O95630; B5M0B6; D6W5H7; Q3MJE7;
DT   19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   10-JUN-2026, entry version 203.
DE   RecName: Full=STAM-binding protein;
DE            EC=3.4.19.- {ECO:0000269|PubMed:15314065, ECO:0000269|PubMed:23542699, ECO:0000269|PubMed:34425109};
DE   AltName: Full=Associated molecule with the SH3 domain of STAM {ECO:0000303|PubMed:10383417};
DE   AltName: Full=Endosome-associated ubiquitin isopeptidase {ECO:0000303|PubMed:15314065};
GN   Name=STAMBP; Synonyms=AMSH {ECO:0000303|PubMed:10383417};
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 1), FUNCTION, TISSUE SPECIFICITY, AND
RP   INTERACTION WITH STAM.
RC   TISSUE=Peripheral blood lymphocyte;
RX   PubMed=10383417; DOI=10.1074/jbc.274.27.19129;
RA   Tanaka N., Kaneko K., Asao H., Kasai H., Endo Y., Fujita T., Takeshita T.,
RA   Sugamura K.;
RT   "Possible involvement of a novel STAM-associated molecule 'AMSH' in
RT   intracellular signal transduction mediated by cytokines.";
RL   J. Biol. Chem. 274:19129-19135(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [3]
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Brain, Eye, and Lymph;
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   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 3-346 (ISOFORM 2).
RX   PubMed=19906316; DOI=10.1186/1471-2164-10-518;
RA   Wang P., Yu P., Gao P., Shi T., Ma D.;
RT   "Discovery of novel human transcript variants by analysis of intronic
RT   single-block EST with polyadenylation site.";
RL   BMC Genomics 10:518-518(2009).
RN   [6]
RP   FUNCTION, INTERACTION WITH SMAD6 AND SMAD7, SUBCELLULAR LOCATION, AND
RP   PHOSPHORYLATION AT SER-2; SER-48; SER-243; SER-245 AND SER-247.
RX   PubMed=11483516; DOI=10.1093/emboj/20.15.4132;
RA   Itoh F., Asao H., Sugamura K., Heldin C.-H., ten Dijke P., Itoh S.;
RT   "Promoting bone morphogenetic protein signaling through negative regulation
RT   of inhibitory Smads.";
RL   EMBO J. 20:4132-4142(2001).
RN   [7]
RP   INVOLVEMENT OF GLU-280; HIS-335 AND HIS-337 IN ZINC-BINDING.
RX   PubMed=12370088; DOI=10.1186/1471-2091-3-28;
RA   Maytal-Kivity V., Reis N., Hofmann K., Glickman M.H.;
RT   "MPN+, a putative catalytic motif found in a subset of MPN domain proteins
RT   from eukaryotes and prokaryotes, is critical for Rpn11 function.";
RL   BMC Biochem. 3:28-28(2002).
RN   [8]
RP   MUTAGENESIS OF ASP-348, FUNCTION, ACTIVITY REGULATION, SUBCELLULAR
RP   LOCATION, AND INTERACTION WITH STAM.
RX   PubMed=15314065; DOI=10.1083/jcb.200401141;
RA   McCullough J., Clague M.J., Urbe S.;
RT   "AMSH is an endosome-associated ubiquitin isopeptidase.";
RL   J. Cell Biol. 166:487-492(2004).
RN   [9]
RP   INTERACTION WITH SMURF2 AND RNF11, AND UBIQUITINATION.
RX   PubMed=14755250; DOI=10.1038/sj.onc.1207319;
RA   Li H., Seth A.K.;
RT   "An RNF11: Smurf2 complex mediates ubiquitination of the AMSH protein.";
RL   Oncogene 23:1801-1808(2004).
RN   [10]
RP   INTERACTION WITH CHMP3.
RX   PubMed=17146056; DOI=10.1073/pnas.0603788103;
RA   Zamborlini A., Usami Y., Radoshitzky S.R., Popova E., Palu G.,
RA   Goettlinger H.;
RT   "Release of autoinhibition converts ESCRT-III components into potent
RT   inhibitors of HIV-1 budding.";
RL   Proc. Natl. Acad. Sci. U.S.A. 103:19140-19145(2006).
RN   [11]
RP   FUNCTION, INTERACTION WITH CHMP3, AND SUBCELLULAR LOCATION.
RX   PubMed=17261583; DOI=10.1074/jbc.m611635200;
RA   Ma Y.M., Boucrot E., Villen J., Affar el B., Gygi S.P., Goettlinger H.G.,
RA   Kirchhausen T.;
RT   "Targeting of AMSH to endosomes is required for epidermal growth factor
RT   receptor degradation.";
RL   J. Biol. Chem. 282:9805-9812(2007).
RN   [12]
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   [13]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; SER-243 AND SER-247, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma, and Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [14]
RP   FUNCTION, AND VARIANTS MICCAP PRO-14; CYS-38; GLY-42; CYS-63; TYR-100 AND
RP   ILE-313.
RX   PubMed=23542699; DOI=10.1038/ng.2602;
RG   FORGE Canada Consortium;
RA   McDonell L.M., Mirzaa G.M., Alcantara D., Schwartzentruber J., Carter M.T.,
RA   Lee L.J., Clericuzio C.L., Graham J.M. Jr., Morris-Rosendahl D.J.,
RA   Polster T., Acsadi G., Townshend S., Williams S., Halbert A., Isidor B.,
RA   David A., Smyser C.D., Paciorkowski A.R., Willing M., Woulfe J., Das S.,
RA   Beaulieu C.L., Marcadier J., Geraghty M.T., Frey B.J., Majewski J.,
RA   Bulman D.E., Dobyns W.B., O'Driscoll M., Boycott K.M.;
RT   "Mutations in STAMBP, encoding a deubiquitinating enzyme, cause
RT   microcephaly-capillary malformation syndrome.";
RL   Nat. Genet. 45:556-562(2013).
RN   [15]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [16]
RP   FUNCTION, AND ACTIVITY REGULATION.
RX   PubMed=34425109; DOI=10.1016/j.jbc.2021.101107;
RA   Guo Y., Liu Q., Mallette E., Caba C., Hou F., Fux J., LaPlante G., Dong A.,
RA   Zhang Q., Zheng H., Tong Y., Zhang W.;
RT   "Structural and functional characterization of ubiquitin variant inhibitors
RT   for the JAMM-family deubiquitinases STAMBP and STAMBPL1.";
RL   J. Biol. Chem. 297:101107-101107(2021).
CC   -!- FUNCTION: Zinc metalloprotease that specifically cleaves 'Lys-63'-
CC       linked polyubiquitin chains (PubMed:15314065, PubMed:23542699,
CC       PubMed:34425109). Does not cleave 'Lys-48'-linked polyubiquitin chains
CC       (PubMed:15314065). Plays a role in signal transduction for cell growth
CC       and MYC induction mediated by IL-2 and GM-CSF (PubMed:10383417).
CC       Potentiates BMP (bone morphogenetic protein) signaling by antagonizing
CC       the inhibitory action of SMAD6 and SMAD7 (PubMed:11483516). Has a key
CC       role in regulation of cell surface receptor-mediated endocytosis and
CC       ubiquitin-dependent sorting of receptors to lysosomes (PubMed:15314065,
CC       PubMed:17261583). Endosomal localization of STAMBP is required for
CC       efficient EGFR degradation but not for its internalization
CC       (PubMed:15314065, PubMed:17261583). Involved in the negative regulation
CC       of PI3K-AKT-mTOR and RAS-MAP signaling pathways (PubMed:23542699).
CC       {ECO:0000269|PubMed:10383417, ECO:0000269|PubMed:11483516,
CC       ECO:0000269|PubMed:15314065, ECO:0000269|PubMed:17261583,
CC       ECO:0000269|PubMed:23542699, ECO:0000269|PubMed:34425109}.
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:O35864};
CC       Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:O35864};
CC   -!- ACTIVITY REGULATION: Inhibited by N-ethylmaleimide (PubMed:15314065).
CC       Strongly and specifically inhibited by ubiquitin variants UbV(SP.2) and
CC       UbV(SP.3) (PubMed:34425109). Also inhibited by UbV(SP.1); an ubiquitin
CC       variant that also inhibits STAMBPL1 (PubMed:34425109).
CC       {ECO:0000269|PubMed:15314065, ECO:0000269|PubMed:34425109}.
CC   -!- SUBUNIT: Interacts with STAM (PubMed:10383417, PubMed:15314065).
CC       Interacts with SMAD6 and SMAD7 (PubMed:11483516). Interacts with CHMP3;
CC       the interaction appears to relieve the autoinhibition of CHMP3
CC       (PubMed:17146056, PubMed:17261583). Interacts with SMURF2 and RNF11;
CC       this interaction promotes ubiquitination (PubMed:14755250).
CC       {ECO:0000269|PubMed:10383417, ECO:0000269|PubMed:11483516,
CC       ECO:0000269|PubMed:14755250, ECO:0000269|PubMed:15314065,
CC       ECO:0000269|PubMed:17146056, ECO:0000269|PubMed:17261583}.
CC   -!- INTERACTION:
CC       O95630; P31941: APOBEC3A; NbExp=3; IntAct=EBI-396676, EBI-13050366;
CC       O95630; P54253: ATXN1; NbExp=6; IntAct=EBI-396676, EBI-930964;
CC       O95630; Q9NSY1: BMP2K; NbExp=3; IntAct=EBI-396676, EBI-1383367;
CC       O95630; P48643: CCT5; NbExp=3; IntAct=EBI-396676, EBI-355710;
CC       O95630; Q8IVW4: CDKL3; NbExp=2; IntAct=EBI-396676, EBI-3919850;
CC       O95630; Q9HD42: CHMP1A; NbExp=8; IntAct=EBI-396676, EBI-1057156;
CC       O95630; Q7LBR1: CHMP1B; NbExp=21; IntAct=EBI-396676, EBI-2118090;
CC       O95630; O43633: CHMP2A; NbExp=3; IntAct=EBI-396676, EBI-2692789;
CC       O95630; Q9Y3E7: CHMP3; NbExp=27; IntAct=EBI-396676, EBI-2118119;
CC       O95630; Q9Y3E7-1: CHMP3; NbExp=6; IntAct=EBI-396676, EBI-15613847;
CC       O95630; Q9H444: CHMP4B; NbExp=3; IntAct=EBI-396676, EBI-749627;
CC       O95630; Q9NZZ3: CHMP5; NbExp=2; IntAct=EBI-396676, EBI-751303;
CC       O95630; O75791: GRAP2; NbExp=6; IntAct=EBI-396676, EBI-740418;
CC       O95630; P62993: GRB2; NbExp=11; IntAct=EBI-396676, EBI-401755;
CC       O95630; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-396676, EBI-1055254;
CC       O95630; O60260-5: PRKN; NbExp=3; IntAct=EBI-396676, EBI-21251460;
CC       O95630; Q9Y3C5: RNF11; NbExp=5; IntAct=EBI-396676, EBI-396669;
CC       O95630; O43541-2: SMAD6; NbExp=2; IntAct=EBI-396676, EBI-4324970;
CC       O95630; Q92783: STAM; NbExp=7; IntAct=EBI-396676, EBI-752333;
CC       O95630; O75886: STAM2; NbExp=9; IntAct=EBI-396676, EBI-373258;
CC       O95630; Q13148: TARDBP; NbExp=3; IntAct=EBI-396676, EBI-372899;
CC       O95630; Q15645: TRIP13; NbExp=4; IntAct=EBI-396676, EBI-358993;
CC       O95630; P0CG47: UBB; NbExp=4; IntAct=EBI-396676, EBI-413034;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17261583,
CC       ECO:0000305|PubMed:10383417}. Membrane {ECO:0000269|PubMed:17261583};
CC       Peripheral membrane protein {ECO:0000269|PubMed:17261583}. Cytoplasm
CC       {ECO:0000269|PubMed:17261583}. Early endosome
CC       {ECO:0000269|PubMed:15314065, ECO:0000269|PubMed:17261583}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=O95630-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O95630-2; Sequence=VSP_057197;
CC   -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC       {ECO:0000269|PubMed:10383417}.
CC   -!- DOMAIN: The JAMM motif is essential for the protease activity.
CC       {ECO:0000250|UniProtKB:O35864}.
CC   -!- PTM: Phosphorylated after BMP type I receptor activation.
CC       {ECO:0000269|PubMed:11483516}.
CC   -!- PTM: Ubiquitinated by SMURF2 in the presence of RNF11.
CC       {ECO:0000269|PubMed:14755250}.
CC   -!- DISEASE: Microcephaly-capillary malformation syndrome (MICCAP)
CC       [MIM:614261]: A congenital disorder characterized by severe progressive
CC       microcephaly, early-onset refractory epilepsy, profound developmental
CC       delay, and multiple small capillary malformations spread diffusely on
CC       the body. Additional more variable features include dysmorphic facial
CC       features, distal limb abnormalities, and mild heart defects.
CC       {ECO:0000269|PubMed:23542699}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- MISCELLANEOUS: X-ray crystallography studies of STAMBPL1, another
CC       member of the peptidase M67C family, has shown that Glu-280 binds zinc
CC       indirectly via a water molecule. Nevertheless, this residue is
CC       essential for catalytic activity. {ECO:0000250|UniProtKB:Q96FJ0}.
CC   -!- SIMILARITY: Belongs to the peptidase M67C family. {ECO:0000305}.
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DR   EMBL; U73522; AAD05037.1; -; mRNA.
DR   EMBL; AC073046; AAX88908.1; -; Genomic_DNA.
DR   EMBL; CH471053; EAW99715.1; -; Genomic_DNA.
DR   EMBL; CH471053; EAW99716.1; -; Genomic_DNA.
DR   EMBL; BC007682; AAH07682.1; -; mRNA.
DR   EMBL; BC065574; AAH65574.1; -; mRNA.
DR   EMBL; BC101467; AAI01468.1; -; mRNA.
DR   EMBL; BC101469; AAI01470.1; -; mRNA.
DR   EMBL; EU927390; ACH57452.1; -; mRNA.
DR   CCDS; CCDS1929.1; -. [O95630-1]
DR   RefSeq; NP_001340896.1; NM_001353967.2. [O95630-1]
DR   RefSeq; NP_001340897.1; NM_001353968.2. [O95630-1]
DR   RefSeq; NP_001425829.1; NM_001438900.1. [O95630-1]
DR   RefSeq; NP_006454.1; NM_006463.6. [O95630-1]
DR   RefSeq; NP_964010.1; NM_201647.4. [O95630-1]
DR   RefSeq; NP_998787.1; NM_213622.4. [O95630-1]
DR   RefSeq; XP_047298917.1; XM_047442961.1. [O95630-1]
DR   RefSeq; XP_047298918.1; XM_047442962.1. [O95630-1]
DR   RefSeq; XP_047298919.1; XM_047442963.1. [O95630-1]
DR   RefSeq; XP_047298920.1; XM_047442964.1. [O95630-1]
DR   RefSeq; XP_047298926.1; XM_047442970.1. [O95630-1]
DR   RefSeq; XP_047298927.1; XM_047442971.1. [O95630-1]
DR   RefSeq; XP_054196176.1; XM_054340201.1. [O95630-1]
DR   RefSeq; XP_054196177.1; XM_054340202.1. [O95630-1]
DR   RefSeq; XP_054196178.1; XM_054340203.1. [O95630-1]
DR   RefSeq; XP_054196179.1; XM_054340204.1. [O95630-1]
DR   RefSeq; XP_054196181.1; XM_054340206.1. [O95630-1]
DR   RefSeq; XP_054196182.1; XM_054340207.1. [O95630-1]
DR   PDB; 2XZE; X-ray; 1.75 A; A/B=1-146.
DR   PDB; 3RZU; X-ray; 2.50 A; A/B/C/D/E/F/G=243-424.
DR   PDB; 3RZV; X-ray; 1.67 A; A=219-424.
DR   PDB; 5IXF; NMR; -; B=228-241.
DR   PDB; 9LE4; X-ray; 2.60 A; A/C/E/G=1-146, B/D/F/H=243-424.
DR   PDBsum; 2XZE; -.
DR   PDBsum; 3RZU; -.
DR   PDBsum; 3RZV; -.
DR   PDBsum; 5IXF; -.
DR   PDBsum; 9LE4; -.
DR   AlphaFoldDB; O95630; -.
DR   SMR; O95630; -.
DR   BioGRID; 115863; 112.
DR   CORUM; O95630; -.
DR   DIP; DIP-33062N; -.
DR   FunCoup; O95630; 3853.
DR   IntAct; O95630; 75.
DR   MINT; O95630; -.
DR   NDEx; IQUERY-CP-STAMBP; 2 NDEx IQuery Curated Pathways.
DR   STRING; 9606.ENSP00000377633; -.
DR   BindingDB; O95630; -.
DR   ChEMBL; CHEMBL4105848; -.
DR   MEROPS; M67.006; -.
DR   GlyGen; O95630; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; O95630; -.
DR   MetOSite; O95630; -.
DR   PhosphoSitePlus; O95630; -.
DR   BioMuta; STAMBP; -.
DR   REPRODUCTION-2DPAGE; IPI00007943; -.
DR   jPOST; O95630; -.
DR   MassIVE; O95630; -.
DR   PaxDb; 9606-ENSP00000377633; -.
DR   PeptideAtlas; O95630; -.
DR   ProteomicsDB; 50966; -. [O95630-1]
DR   Pumba; O95630; -.
DR   Antibodypedia; 31376; 313 antibodies from 38 providers.
DR   DNASU; 10617; -.
DR   Ensembl; ENST00000339566.7; ENSP00000344742.3; ENSG00000124356.18. [O95630-1]
DR   Ensembl; ENST00000394070.7; ENSP00000377633.2; ENSG00000124356.18. [O95630-1]
DR   Ensembl; ENST00000394073.6; ENSP00000377636.1; ENSG00000124356.18. [O95630-1]
DR   Ensembl; ENST00000409707.6; ENSP00000386548.1; ENSG00000124356.18. [O95630-1]
DR   Ensembl; ENST00000432295.7; ENSP00000413874.3; ENSG00000124356.18. [O95630-2]
DR   Ensembl; ENST00000682351.1; ENSP00000506833.1; ENSG00000124356.18. [O95630-1]
DR   Ensembl; ENST00000682379.1; ENSP00000507081.1; ENSG00000124356.18. [O95630-1]
DR   Ensembl; ENST00000682558.1; ENSP00000507014.1; ENSG00000124356.18. [O95630-1]
DR   Ensembl; ENST00000682847.1; ENSP00000507864.1; ENSG00000124356.18. [O95630-1]
DR   Ensembl; ENST00000683036.1; ENSP00000507639.1; ENSG00000124356.18. [O95630-1]
DR   Ensembl; ENST00000683317.1; ENSP00000507092.1; ENSG00000124356.18. [O95630-1]
DR   Ensembl; ENST00000683518.1; ENSP00000506865.1; ENSG00000124356.18. [O95630-1]
DR   Ensembl; ENST00000683818.1; ENSP00000507658.1; ENSG00000124356.18. [O95630-1]
DR   Ensembl; ENST00000684095.1; ENSP00000506845.1; ENSG00000124356.18. [O95630-1]
DR   Ensembl; ENST00000684312.1; ENSP00000506958.1; ENSG00000124356.18. [O95630-1]
DR   Ensembl; ENST00000684585.1; ENSP00000507054.1; ENSG00000124356.18. [O95630-1]
DR   Ensembl; ENST00000879042.1; ENSP00000549101.1; ENSG00000124356.18. [O95630-1]
DR   Ensembl; ENST00000879044.1; ENSP00000549103.1; ENSG00000124356.18. [O95630-1]
DR   Ensembl; ENST00000933900.1; ENSP00000603959.1; ENSG00000124356.18. [O95630-1]
DR   Ensembl; ENST00000933901.1; ENSP00000603960.1; ENSG00000124356.18. [O95630-1]
DR   Ensembl; ENST00000933902.1; ENSP00000603961.1; ENSG00000124356.18. [O95630-1]
DR   Ensembl; ENST00000958034.1; ENSP00000628093.1; ENSG00000124356.18. [O95630-1]
DR   GeneID; 10617; -.
DR   KEGG; hsa:10617; -.
DR   MANE-Select; ENST00000394070.7; ENSP00000377633.2; NM_213622.4; NP_998787.1.
DR   UCSC; uc002sjs.3; human. [O95630-1]
DR   AGR; HGNC:16950; -.
DR   ClinPGx; PA134955569; -.
DR   CTD; 10617; -.
DR   DisGeNET; 10617; -.
DR   GeneCards; STAMBP; -.
DR   GeneReviews; STAMBP; -.
DR   HGNC; HGNC:16950; STAMBP.
DR   HPA; ENSG00000124356; Low tissue specificity.
DR   MalaCards; STAMBP; -.
DR   MIM; 606247; gene.
DR   MIM; 614261; phenotype.
DR   OpenTargets; ENSG00000124356; -.
DR   Orphanet; 294016; Microcephaly-capillary malformation syndrome.
DR   VEuPathDB; HostDB:ENSG00000124356; -.
DR   eggNOG; KOG2880; Eukaryota.
DR   GeneTree; ENSGT00940000153710; -.
DR   HOGENOM; CLU_023304_0_1_1; -.
DR   InParanoid; O95630; -.
DR   OMA; NSFTITH; -.
DR   OrthoDB; 3640at2759; -.
DR   PAN-GO; O95630; 4 GO annotations based on evolutionary models.
DR   PhylomeDB; O95630; -.
DR   PathwayCommons; O95630; -.
DR   Reactome; R-HSA-5689901; Metalloprotease DUBs.
DR   SignaLink; O95630; -.
DR   SIGNOR; O95630; -.
DR   Agora; ENSG00000124356; -.
DR   BioGRID-ORCS; 10617; 138 hits in 1206 CRISPR screens.
DR   ChiTaRS; STAMBP; human.
DR   EvolutionaryTrace; O95630; -.
DR   GeneWiki; STAMBP; -.
DR   GenomeRNAi; 10617; -.
DR   Pharos; O95630; Tchem.
DR   PRO; PR:O95630; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; O95630; protein.
DR   Bgee; ENSG00000124356; Expressed in C1 segment of cervical spinal cord and 216 other cell types or tissues.
DR   ExpressionAtlas; O95630; baseline and differential.
DR   GO; GO:0032154; C:cleavage furrow; IDA:MGI.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005768; C:endosome; IBA:GO_Central.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR   GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR   GO; GO:0101005; F:deubiquitinase activity; IDA:MGI.
DR   GO; GO:0061578; F:K63-linked deubiquitinase activity; IDA:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0140492; F:metal-dependent deubiquitinase activity; IEA:InterPro.
DR   GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR   GO; GO:0007259; P:cell surface receptor signaling pathway via JAK-STAT; TAS:ProtInc.
DR   GO; GO:0000281; P:mitotic cytokinesis; IMP:MGI.
DR   GO; GO:0051898; P:negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:UniProtKB.
DR   GO; GO:0046580; P:negative regulation of Ras protein signal transduction; IMP:UniProtKB.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; TAS:ProtInc.
DR   GO; GO:0016579; P:protein deubiquitination; IMP:MGI.
DR   GO; GO:0070536; P:protein K63-linked deubiquitination; IEA:InterPro.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   CDD; cd08066; MPN_AMSH_like; 1.
DR   DisProt; DP01872; -.
DR   FunFam; 3.40.140.10:FF:000010; AMSH-like protease isoform X1; 1.
DR   FunFam; 1.20.58.80:FF:000013; STAM-binding protein-like A; 1.
DR   Gene3D; 3.40.140.10; Cytidine Deaminase, domain 2; 1.
DR   Gene3D; 1.20.58.80; Phosphotransferase system, lactose/cellobiose-type IIA subunit; 1.
DR   IDEAL; IID00261; -.
DR   InterPro; IPR000555; JAMM/MPN+_dom.
DR   InterPro; IPR037518; MPN.
DR   InterPro; IPR044098; STAMBP/STALP-like_MPN.
DR   InterPro; IPR015063; USP8_dimer.
DR   PANTHER; PTHR12947; AMSH-LIKE PROTEASE; 1.
DR   PANTHER; PTHR12947:SF8; STAM-BINDING PROTEIN; 1.
DR   Pfam; PF01398; JAB; 1.
DR   Pfam; PF08969; USP8_dimer; 1.
DR   SMART; SM00232; JAB_MPN; 1.
DR   SUPFAM; SSF102712; JAB1/MPN domain; 1.
DR   SUPFAM; SSF140856; USP8 N-terminal domain-like; 1.
DR   PROSITE; PS50249; MPN; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cytoplasm; Disease variant; Endosome;
KW   Hydrolase; Membrane; Metal-binding; Metalloprotease; Nucleus;
KW   Phosphoprotein; Protease; Proteomics identification; Reference proteome;
KW   Ubl conjugation; Ubl conjugation pathway; Zinc.
FT   CHAIN           1..424
FT                   /note="STAM-binding protein"
FT                   /id="PRO_0000194869"
FT   DOMAIN          257..388
FT                   /note="MPN"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT   REGION          1..127
FT                   /note="Interaction with CHMP3"
FT                   /evidence="ECO:0000269|PubMed:17146056"
FT   REGION          227..231
FT                   /note="Interaction with STAM"
FT                   /evidence="ECO:0000269|PubMed:10383417"
FT   MOTIF           335..348
FT                   /note="JAMM motif"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT   BINDING         335
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT   BINDING         337
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT   BINDING         348
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT   BINDING         350
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q96FJ0"
FT   BINDING         390
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q96FJ0"
FT   BINDING         396
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q96FJ0"
FT   BINDING         398
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:Q96FJ0"
FT   SITE            280
FT                   /note="Indirect zinc-binding"
FT                   /evidence="ECO:0000250|UniProtKB:Q96FJ0"
FT   MOD_RES         2
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:11483516,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         48
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:11483516"
FT   MOD_RES         243
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:11483516,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         245
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:11483516"
FT   MOD_RES         247
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:11483516,
FT                   ECO:0007744|PubMed:23186163"
FT   VAR_SEQ         336..424
FT                   /note="THPTQTAFLSSVDLHTHCSYQMMLPESVAIVCSPKFQETGFFKLTDHGLEEI
FT                   SSCRQKGFHPHSKDPPLFCSCSHVTVVDRAVTITDLR -> VETLWSLKSLHAP (in
FT                   isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:19906316"
FT                   /id="VSP_057197"
FT   VARIANT         14
FT                   /note="R -> P (in MICCAP)"
FT                   /evidence="ECO:0000269|PubMed:23542699"
FT                   /id="VAR_069806"
FT   VARIANT         38
FT                   /note="R -> C (in MICCAP; dbSNP:rs143739249)"
FT                   /evidence="ECO:0000269|PubMed:23542699"
FT                   /id="VAR_069807"
FT   VARIANT         42
FT                   /note="E -> G (in MICCAP; dbSNP:rs397509387)"
FT                   /evidence="ECO:0000269|PubMed:23542699"
FT                   /id="VAR_069808"
FT   VARIANT         63
FT                   /note="Y -> C (in MICCAP; dbSNP:rs781694797)"
FT                   /evidence="ECO:0000269|PubMed:23542699"
FT                   /id="VAR_069809"
FT   VARIANT         100
FT                   /note="F -> Y (in MICCAP; dbSNP:rs397514697)"
FT                   /evidence="ECO:0000269|PubMed:23542699"
FT                   /id="VAR_069810"
FT   VARIANT         313
FT                   /note="T -> I (in MICCAP; dbSNP:rs202100019)"
FT                   /evidence="ECO:0000269|PubMed:23542699"
FT                   /id="VAR_069811"
FT   MUTAGEN         348
FT                   /note="D->A: Promotes accumulation of ubiquitin on
FT                   endosomes, ablates enzymatic activity toward polyubiquitin
FT                   substrate and allows ubiquitinated STAM stabilization."
FT                   /evidence="ECO:0000269|PubMed:15314065"
FT   HELIX           11..22
FT                   /evidence="ECO:0007829|PDB:2XZE"
FT   HELIX           33..53
FT                   /evidence="ECO:0007829|PDB:2XZE"
FT   HELIX           56..67
FT                   /evidence="ECO:0007829|PDB:2XZE"
FT   HELIX           68..73
FT                   /evidence="ECO:0007829|PDB:2XZE"
FT   HELIX           74..76
FT                   /evidence="ECO:0007829|PDB:2XZE"
FT   TURN            78..82
FT                   /evidence="ECO:0007829|PDB:2XZE"
FT   HELIX           88..94
FT                   /evidence="ECO:0007829|PDB:2XZE"
FT   HELIX           95..99
FT                   /evidence="ECO:0007829|PDB:2XZE"
FT   HELIX           100..137
FT                   /evidence="ECO:0007829|PDB:2XZE"
FT   HELIX           247..250
FT                   /evidence="ECO:0007829|PDB:3RZV"
FT   STRAND          257..260
FT                   /evidence="ECO:0007829|PDB:3RZV"
FT   HELIX           263..276
FT                   /evidence="ECO:0007829|PDB:3RZV"
FT   STRAND          282..290
FT                   /evidence="ECO:0007829|PDB:3RZV"
FT   STRAND          293..301
FT                   /evidence="ECO:0007829|PDB:3RZV"
FT   STRAND          304..306
FT                   /evidence="ECO:0007829|PDB:3RZV"
FT   STRAND          311..313
FT                   /evidence="ECO:0007829|PDB:3RZV"
FT   HELIX           316..326
FT                   /evidence="ECO:0007829|PDB:3RZV"
FT   STRAND          329..336
FT                   /evidence="ECO:0007829|PDB:3RZV"
FT   STRAND          338..340
FT                   /evidence="ECO:0007829|PDB:3RZU"
FT   HELIX           346..358
FT                   /evidence="ECO:0007829|PDB:3RZV"
FT   STRAND          363..368
FT                   /evidence="ECO:0007829|PDB:3RZV"
FT   TURN            369..372
FT                   /evidence="ECO:0007829|PDB:3RZV"
FT   STRAND          373..379
FT                   /evidence="ECO:0007829|PDB:3RZV"
FT   HELIX           381..389
FT                   /evidence="ECO:0007829|PDB:3RZV"
FT   STRAND          404..407
FT                   /evidence="ECO:0007829|PDB:3RZV"
FT   STRAND          409..414
FT                   /evidence="ECO:0007829|PDB:3RZV"
FT   STRAND          419..422
FT                   /evidence="ECO:0007829|PDB:3RZV"
SQ   SEQUENCE   424 AA;  48077 MW;  7B6E08A245BD9D43 CRC64;
     MSDHGDVSLP PEDRVRALSQ LGSAVEVNED IPPRRYFRSG VEIIRMASIY SEEGNIEHAF
     ILYNKYITLF IEKLPKHRDY KSAVIPEKKD TVKKLKEIAF PKAEELKAEL LKRYTKEYTE
     YNEEKKKEAE ELARNMAIQQ ELEKEKQRVA QQKQQQLEQE QFHAFEEMIR NQELEKERLK
     IVQEFGKVDP GLGGPLVPDL EKPSLDVFPT LTVSSIQPSD CHTTVRPAKP PVVDRSLKPG
     ALSNSESIPT IDGLRHVVVP GRLCPQFLQL ASANTARGVE TCGILCGKLM RNEFTITHVL
     IPKQSAGSDY CNTENEEELF LIQDQQGLIT LGWIHTHPTQ TAFLSSVDLH THCSYQMMLP
     ESVAIVCSPK FQETGFFKLT DHGLEEISSC RQKGFHPHSK DPPLFCSCSH VTVVDRAVTI
     TDLR
//