STALP_HUMAN
ID STALP_HUMAN Reviewed; 436 AA.
AC Q96FJ0; B3KPA7; Q5T9N4; Q5T9N9; Q7Z420; Q9P2H4;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 2.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=AMSH-like protease {ECO:0000303|PubMed:12810066};
DE Short=AMSH-LP {ECO:0000303|PubMed:12810066};
DE EC=3.4.19.- {ECO:0000269|PubMed:35114100};
DE AltName: Full=STAM-binding protein-like 1;
GN Name=STAMBPL1 {ECO:0000303|PubMed:35114100, ECO:0000312|HGNC:HGNC:24105};
GN Synonyms=AMSHLP, KIAA1373;
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), TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Peripheral blood lymphocyte;
RX PubMed=12810066; DOI=10.1016/s0006-291x(03)01009-x;
RA Kikuchi K., Ishii N., Asano H., Sugamura K.;
RT "Identification of AMSH-LP containing a Jab1/MPN domain metalloenzyme
RT motif.";
RL Biochem. Biophys. Res. Commun. 306:637-643(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI. The
RT complete sequences of 150 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
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] (ISOFORM 1).
RC TISSUE=Pancreas;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25 AND SER-242, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-242, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
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 [10]
RP FUNCTION, AND MUTAGENESIS OF GLU-292 AND ASP-360.
RX PubMed=35114100; DOI=10.1016/j.molcel.2022.01.002;
RA Wang D., Xu C., Yang W., Chen J., Ou Y., Guan Y., Guan J., Liu Y.;
RT "E3 ligase RNF167 and deubiquitinase STAMBPL1 modulate mTOR and cancer
RT progression.";
RL Mol. Cell 82:770-784(2022).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 263-436 IN COMPLEXES WITH ZINC
RP IONS AND WITH LYS-63-LINKED DI-UBIQUITIN, FUNCTION, COFACTOR, AND
RP MUTAGENESIS OF GLU-292; GLU-329; PHE-332; THR-353; PHE-355; SER-357;
RP SER-358; ASP-360; MET-370; CYS-402 AND PHE-407.
RX PubMed=18758443; DOI=10.1038/nature07254;
RA Sato Y., Yoshikawa A., Yamagata A., Mimura H., Yamashita M., Ookata K.,
RA Nureki O., Iwai K., Komada M., Fukai S.;
RT "Structural basis for specific cleavage of Lys 63-linked polyubiquitin
RT chains.";
RL Nature 455:358-362(2008).
RN [12]
RP ERRATUM OF PUBMED:18758443.
RX DOI=10.1038/nature07515;
RA Sato Y., Yoshikawa A., Yamagata A., Mimura H., Yamashita M., Ookata K.,
RA Nureki O., Iwai K., Komada M., Fukai S.;
RL Nature 456:274-274(2008).
RN [13] {ECO:0007744|PDB:7L97}
RP X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) OF 263-436 IN COMPLEX WITH ZINC AND
RP UBIQUITIN VARIANT INHIBITOR UBVSP.1, 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:18758443, PubMed:35114100). Acts as
CC a positive regulator of the TORC1 signaling pathway by mediating 'Lys-
CC 63'-linked deubiquitination of SESN2, thereby inhibiting SESN2-
CC interaction with the GATOR2 complex (PubMed:35114100). Does not cleave
CC 'Lys-48'-linked polyubiquitin chains (PubMed:18758443).
CC {ECO:0000269|PubMed:18758443, ECO:0000269|PubMed:35114100}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:18758443};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:18758443};
CC -!- ACTIVITY REGULATION: Inhibited by UbV(SP.1), an ubiquitin variant that
CC also inhibits STAMBP. {ECO:0000269|PubMed:34425109}.
CC -!- INTERACTION:
CC Q96FJ0; Q13137: CALCOCO2; NbExp=3; IntAct=EBI-745021, EBI-739580;
CC Q96FJ0; Q9P209: CEP72; NbExp=8; IntAct=EBI-745021, EBI-739498;
CC Q96FJ0; Q5JQS6: GCSAML; NbExp=3; IntAct=EBI-745021, EBI-17857617;
CC Q96FJ0; Q3T906: GNPTAB; NbExp=3; IntAct=EBI-745021, EBI-1104907;
CC Q96FJ0; Q08379: GOLGA2; NbExp=3; IntAct=EBI-745021, EBI-618309;
CC Q96FJ0; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-745021, EBI-5916454;
CC Q96FJ0; Q9UKT9: IKZF3; NbExp=3; IntAct=EBI-745021, EBI-747204;
CC Q96FJ0; Q0VD86: INCA1; NbExp=3; IntAct=EBI-745021, EBI-6509505;
CC Q96FJ0; Q8IWV1: LAX1; NbExp=3; IntAct=EBI-745021, EBI-10232942;
CC Q96FJ0; P43357: MAGEA3; NbExp=4; IntAct=EBI-745021, EBI-5651459;
CC Q96FJ0; P43360: MAGEA6; NbExp=6; IntAct=EBI-745021, EBI-1045155;
CC Q96FJ0; Q5VZ52: MORN5; NbExp=3; IntAct=EBI-745021, EBI-12835568;
CC Q96FJ0; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-745021, EBI-742388;
CC Q96FJ0; Q8ND90: PNMA1; NbExp=3; IntAct=EBI-745021, EBI-302345;
CC Q96FJ0; P61019: RAB2A; NbExp=10; IntAct=EBI-745021, EBI-752037;
CC Q96FJ0; Q8WUD1: RAB2B; NbExp=3; IntAct=EBI-745021, EBI-5542466;
CC Q96FJ0; Q04864-2: REL; NbExp=3; IntAct=EBI-745021, EBI-10829018;
CC Q96FJ0; Q9H0A6: RNF32; NbExp=2; IntAct=EBI-745021, EBI-724829;
CC Q96FJ0; Q9BWJ5: SF3B5; NbExp=3; IntAct=EBI-745021, EBI-2555428;
CC Q96FJ0; P15884: TCF4; NbExp=3; IntAct=EBI-745021, EBI-533224;
CC Q96FJ0; P14373: TRIM27; NbExp=6; IntAct=EBI-745021, EBI-719493;
CC Q96FJ0; Q9Y2P0: ZNF835; NbExp=3; IntAct=EBI-745021, EBI-5667516;
CC Q96FJ0; Q9UGI0: ZRANB1; NbExp=3; IntAct=EBI-745021, EBI-527853;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96FJ0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96FJ0-2; Sequence=VSP_014648;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:12810066}.
CC -!- DOMAIN: The JAMM motif is essential for the protease activity.
CC {ECO:0000250|UniProtKB:O35864}.
CC -!- SIMILARITY: Belongs to the peptidase M67C family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA92611.1; Type=Erroneous initiation; 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; AB010120; BAC77766.1; -; mRNA.
DR EMBL; AB037794; BAA92611.1; ALT_INIT; mRNA.
DR EMBL; AK056086; BAG51619.1; -; mRNA.
DR EMBL; AL157394; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW50156.1; -; Genomic_DNA.
DR EMBL; BC010846; AAH10846.2; -; mRNA.
DR CCDS; CCDS7391.1; -. [Q96FJ0-1]
DR RefSeq; NP_065850.1; NM_020799.3. [Q96FJ0-1]
DR RefSeq; XP_006717991.1; XM_006717928.2. [Q96FJ0-1]
DR RefSeq; XP_006717993.1; XM_006717930.3. [Q96FJ0-1]
DR RefSeq; XP_011538285.1; XM_011539983.1. [Q96FJ0-1]
DR RefSeq; XP_011538287.1; XM_011539985.1. [Q96FJ0-1]
DR RefSeq; XP_016871942.1; XM_017016453.1. [Q96FJ0-1]
DR RefSeq; XP_016871943.1; XM_017016454.1.
DR RefSeq; XP_016871944.1; XM_017016455.1. [Q96FJ0-1]
DR RefSeq; XP_016871945.1; XM_017016456.1. [Q96FJ0-1]
DR PDB; 2ZNR; X-ray; 1.20 A; A=264-436.
DR PDB; 2ZNV; X-ray; 1.60 A; A/D=264-436.
DR PDB; 7L97; X-ray; 2.01 A; A=263-436.
DR PDBsum; 2ZNR; -.
DR PDBsum; 2ZNV; -.
DR PDBsum; 7L97; -.
DR AlphaFoldDB; Q96FJ0; -.
DR SMR; Q96FJ0; -.
DR BioGRID; 121614; 66.
DR IntAct; Q96FJ0; 58.
DR MINT; Q96FJ0; -.
DR STRING; 9606.ENSP00000360994; -.
DR BindingDB; Q96FJ0; -.
DR ChEMBL; CHEMBL4630848; -.
DR MEROPS; M67.003; -.
DR iPTMnet; Q96FJ0; -.
DR PhosphoSitePlus; Q96FJ0; -.
DR BioMuta; STAMBPL1; -.
DR DMDM; 71153542; -.
DR EPD; Q96FJ0; -.
DR jPOST; Q96FJ0; -.
DR MassIVE; Q96FJ0; -.
DR MaxQB; Q96FJ0; -.
DR PaxDb; Q96FJ0; -.
DR PeptideAtlas; Q96FJ0; -.
DR PRIDE; Q96FJ0; -.
DR ProteomicsDB; 76533; -. [Q96FJ0-1]
DR ProteomicsDB; 76534; -. [Q96FJ0-2]
DR Antibodypedia; 45641; 106 antibodies from 20 providers.
DR DNASU; 57559; -.
DR Ensembl; ENST00000371924.5; ENSP00000360992.1; ENSG00000138134.12. [Q96FJ0-1]
DR Ensembl; ENST00000371926.8; ENSP00000360994.3; ENSG00000138134.12. [Q96FJ0-1]
DR Ensembl; ENST00000371927.7; ENSP00000360995.3; ENSG00000138134.12. [Q96FJ0-2]
DR GeneID; 57559; -.
DR KEGG; hsa:57559; -.
DR MANE-Select; ENST00000371926.8; ENSP00000360994.3; NM_020799.4; NP_065850.1.
DR UCSC; uc001kfk.5; human. [Q96FJ0-1]
DR CTD; 57559; -.
DR DisGeNET; 57559; -.
DR GeneCards; STAMBPL1; -.
DR HGNC; HGNC:24105; STAMBPL1.
DR HPA; ENSG00000138134; Tissue enhanced (adrenal).
DR MIM; 612352; gene.
DR neXtProt; NX_Q96FJ0; -.
DR OpenTargets; ENSG00000138134; -.
DR PharmGKB; PA142670864; -.
DR VEuPathDB; HostDB:ENSG00000138134; -.
DR eggNOG; KOG2880; Eukaryota.
DR GeneTree; ENSGT00940000153710; -.
DR HOGENOM; CLU_023304_0_1_1; -.
DR InParanoid; Q96FJ0; -.
DR OMA; FGVQDQH; -.
DR OrthoDB; 411229at2759; -.
DR PhylomeDB; Q96FJ0; -.
DR TreeFam; TF323215; -.
DR PathwayCommons; Q96FJ0; -.
DR Reactome; R-HSA-5689901; Metalloprotease DUBs.
DR SignaLink; Q96FJ0; -.
DR BioGRID-ORCS; 57559; 11 hits in 1113 CRISPR screens.
DR ChiTaRS; STAMBPL1; human.
DR EvolutionaryTrace; Q96FJ0; -.
DR GeneWiki; STAMBPL1; -.
DR GenomeRNAi; 57559; -.
DR Pharos; Q96FJ0; Tbio.
DR PRO; PR:Q96FJ0; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q96FJ0; protein.
DR Bgee; ENSG00000138134; Expressed in ileal mucosa and 182 other tissues.
DR Genevisible; Q96FJ0; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005768; C:endosome; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0070122; F:isopeptidase activity; IEA:InterPro.
DR GO; GO:0061578; F:Lys63-specific 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:0016579; P:protein deubiquitination; TAS:Reactome.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; IBA:GO_Central.
DR CDD; cd08066; MPN_AMSH_like; 1.
DR InterPro; IPR000555; JAMM/MPN+_dom.
DR InterPro; IPR037518; MPN.
DR InterPro; IPR044098; STAMBP/STALP-like_MPN.
DR InterPro; IPR015063; USP8_dimer.
DR Pfam; PF01398; JAB; 1.
DR Pfam; PF08969; USP8_dimer; 1.
DR SMART; SM00232; JAB_MPN; 1.
DR PROSITE; PS50249; MPN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Hydrolase; Metal-binding;
KW Metalloprotease; Phosphoprotein; Protease; Reference proteome;
KW Ubl conjugation pathway; Zinc.
FT CHAIN 1..436
FT /note="AMSH-like protease"
FT /id="PRO_0000194874"
FT DOMAIN 269..397
FT /note="MPN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT MOTIF 347..360
FT /note="JAMM motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01182"
FT BINDING 347
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 ECO:0000269|PubMed:18758443, ECO:0007744|PDB:2ZNR"
FT BINDING 349
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 ECO:0000269|PubMed:18758443, ECO:0007744|PDB:2ZNR"
FT BINDING 360
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 ECO:0000269|PubMed:18758443, ECO:0007744|PDB:2ZNR"
FT BINDING 362
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:18758443,
FT ECO:0000269|PubMed:34425109, ECO:0007744|PDB:2ZNR,
FT ECO:0007744|PDB:7L97"
FT BINDING 402
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:18758443,
FT ECO:0000269|PubMed:34425109, ECO:0007744|PDB:2ZNR,
FT ECO:0007744|PDB:7L97"
FT BINDING 408
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:18758443,
FT ECO:0000269|PubMed:34425109, ECO:0007744|PDB:2ZNR,
FT ECO:0007744|PDB:7L97"
FT BINDING 410
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:18758443,
FT ECO:0000269|PubMed:34425109, ECO:0007744|PDB:2ZNR,
FT ECO:0007744|PDB:7L97"
FT SITE 292
FT /note="Indirect zinc-binding"
FT /evidence="ECO:0000269|PubMed:18758443"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 242
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 420..436
FT /note="CKHVLVKDIKIIVLDLR -> QKFLSGIISGTALEMEPLKIGYGPNGFPLLG
FT ISRSSSPSEQL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10718198"
FT /id="VSP_014648"
FT VARIANT 196
FT /note="S -> N (in dbSNP:rs12254856)"
FT /id="VAR_051817"
FT VARIANT 204
FT /note="E -> K (in dbSNP:rs34270879)"
FT /id="VAR_051818"
FT VARIANT 210
FT /note="A -> T (in dbSNP:rs9988723)"
FT /id="VAR_051819"
FT MUTAGEN 292
FT /note="E->A: Complete loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:18758443,
FT ECO:0000269|PubMed:35114100"
FT MUTAGEN 329
FT /note="E->A: 3-fold decrease in substrate affinity."
FT /evidence="ECO:0000269|PubMed:18758443"
FT MUTAGEN 332
FT /note="F->A: 12-fold decrease in substrate affinity, little
FT effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:18758443"
FT MUTAGEN 353
FT /note="T->A: 19-fold decrease in activity, no change in
FT substrate affinity."
FT /evidence="ECO:0000269|PubMed:18758443"
FT MUTAGEN 355
FT /note="F->A: 161-fold decrease in activity, no change in
FT substrate affinity."
FT /evidence="ECO:0000269|PubMed:18758443"
FT MUTAGEN 357
FT /note="S->A: 34-fold decrease in activity."
FT /evidence="ECO:0000269|PubMed:18758443"
FT MUTAGEN 358
FT /note="S->A: 10-fold decrease in activity, no change in
FT substrate affinity."
FT /evidence="ECO:0000269|PubMed:18758443"
FT MUTAGEN 360
FT /note="D->A: Complete loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:18758443,
FT ECO:0000269|PubMed:35114100"
FT MUTAGEN 370
FT /note="M->A: 18-fold decrease in substrate affinity, little
FT effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:18758443"
FT MUTAGEN 402
FT /note="C->S: 402-fold decrease in activity, slight increase
FT in substrate affinity."
FT /evidence="ECO:0000269|PubMed:18758443"
FT MUTAGEN 407
FT /note="F->A: 35-fold decrease in activity, slight increase
FT in substrate affinity."
FT /evidence="ECO:0000269|PubMed:18758443"
FT STRAND 269..272
FT /evidence="ECO:0007829|PDB:2ZNR"
FT HELIX 275..287
FT /evidence="ECO:0007829|PDB:2ZNR"
FT TURN 288..290
FT /evidence="ECO:0007829|PDB:2ZNR"
FT STRAND 294..302
FT /evidence="ECO:0007829|PDB:2ZNR"
FT STRAND 305..313
FT /evidence="ECO:0007829|PDB:2ZNR"
FT STRAND 316..319
FT /evidence="ECO:0007829|PDB:2ZNR"
FT STRAND 322..325
FT /evidence="ECO:0007829|PDB:2ZNR"
FT HELIX 328..338
FT /evidence="ECO:0007829|PDB:2ZNR"
FT STRAND 341..348
FT /evidence="ECO:0007829|PDB:2ZNR"
FT STRAND 350..352
FT /evidence="ECO:0007829|PDB:2ZNR"
FT HELIX 358..370
FT /evidence="ECO:0007829|PDB:2ZNR"
FT STRAND 375..380
FT /evidence="ECO:0007829|PDB:2ZNR"
FT HELIX 381..383
FT /evidence="ECO:0007829|PDB:2ZNR"
FT STRAND 385..391
FT /evidence="ECO:0007829|PDB:2ZNR"
FT HELIX 393..401
FT /evidence="ECO:0007829|PDB:2ZNR"
FT STRAND 416..419
FT /evidence="ECO:0007829|PDB:2ZNR"
FT STRAND 421..426
FT /evidence="ECO:0007829|PDB:2ZNR"
FT STRAND 431..434
FT /evidence="ECO:0007829|PDB:2ZNR"
SQ SEQUENCE 436 AA; 49783 MW; 722662C76A734102 CRC64;
MDQPFTVNSL KKLAAMPDHT DVSLSPEERV RALSKLGCNI TISEDITPRR YFRSGVEMER
MASVYLEEGN LENAFVLYNK FITLFVEKLP NHRDYQQCAV PEKQDIMKKL KEIAFPRTDE
LKNDLLKKYN VEYQEYLQSK NKYKAEILKK LEHQRLIEAE RKRIAQMRQQ QLESEQFLFF
EDQLKKQELA RGQMRSQQTS GLSEQIDGSA LSCFSTHQNN SLLNVFADQP NKSDATNYAS
HSPPVNRALT PAATLSAVQN LVVEGLRCVV LPEDLCHKFL QLAESNTVRG IETCGILCGK
LTHNEFTITH VIVPKQSAGP DYCDMENVEE LFNVQDQHDL LTLGWIHTHP TQTAFLSSVD
LHTHCSYQLM LPEAIAIVCS PKHKDTGIFR LTNAGMLEVS ACKKKGFHPH TKEPRLFSIC
KHVLVKDIKI IVLDLR