ID JOS2_HUMAN Reviewed; 188 AA. AC Q8TAC2; M0QX25; DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2002, sequence version 1. DT 27-MAR-2024, entry version 147. DE RecName: Full=Josephin-2; DE EC=3.4.19.12; DE AltName: Full=Josephin domain-containing protein 2; GN Name=JOSD2; ORFNames=SBBI54; 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). RA Li N., Wan T., Zhang W., Cao X.; RT "Hypothetical transmembrane protein SBBI54."; RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Macrophage; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Uterus; 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 CATALYTIC ACTIVITY, AND FUNCTION. RX PubMed=17696782; DOI=10.1515/bc.2007.107; RA Tzvetkov N., Breuer P.; RT "Josephin domain-containing proteins from a variety of species are active RT de-ubiquitination enzymes."; RL Biol. Chem. 388:973-978(2007). RN [7] RP CATALYTIC ACTIVITY, AND FUNCTION. RX PubMed=21118805; DOI=10.1074/jbc.m110.177360; RA Weeks S.D., Grasty K.C., Hernandez-Cuebas L., Loll P.J.; RT "Crystal structure of a Josephin-ubiquitin complex: evolutionary restraints RT on ataxin-3 deubiquitinating activity."; RL J. Biol. Chem. 286:4555-4565(2011). RN [8] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-24. RX PubMed=23625928; DOI=10.1074/jbc.m113.463406; RA Seki T., Gong L., Williams A.J., Sakai N., Todi S.V., Paulson H.L.; RT "JosD1, a membrane-targeted deubiquitinating enzyme, is activated by RT ubiquitination and regulates membrane dynamics, cell motility, and RT endocytosis."; RL J. Biol. Chem. 288:17145-17155(2013). RN [9] RP 3D-STRUCTURE MODELING. RX PubMed=12486728; DOI=10.1002/prot.10280; RA Albrecht M., Hoffmann D., Evert B.O., Schmitt I., Wuellner U., Lengauer T.; RT "Structural modeling of ataxin-3 reveals distant homology to adaptins."; RL Proteins 50:355-370(2003). CC -!- FUNCTION: Cleaves 'Lys-63'-linked poly-ubiquitin chains, and with CC lesser efficiency 'Lys-48'-linked poly-ubiquitin chains (in vitro). May CC act as a deubiquitinating enzyme. {ECO:0000269|PubMed:17696782, CC ECO:0000269|PubMed:21118805, ECO:0000269|PubMed:23625928}. 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:17696782, CC ECO:0000269|PubMed:21118805}; CC -!- INTERACTION: CC Q8TAC2; O43865: AHCYL1; NbExp=4; IntAct=EBI-12205593, EBI-2371423; CC Q8TAC2; Q96DZ9-2: CMTM5; NbExp=3; IntAct=EBI-12205593, EBI-11522780; CC Q8TAC2; Q8NI60: COQ8A; NbExp=3; IntAct=EBI-12205593, EBI-745535; CC Q8TAC2; Q9Y680: FKBP7; NbExp=3; IntAct=EBI-12205593, EBI-3918971; CC Q8TAC2; P21741: MDK; NbExp=3; IntAct=EBI-12205593, EBI-722444; CC Q8TAC2; P08247: SYP; NbExp=3; IntAct=EBI-12205593, EBI-9071725; CC Q8TAC2; P0DI81-3: TRAPPC2; NbExp=3; IntAct=EBI-12205593, EBI-11961968; CC Q8TAC2; P49638: TTPA; NbExp=3; IntAct=EBI-12205593, EBI-10210710; CC Q8TAC2; O95070: YIF1A; NbExp=3; IntAct=EBI-12205593, EBI-2799703; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:23625928}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q8TAC2-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8TAC2-2; Sequence=VSP_047537; 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; AF247787; AAL95692.1; -; mRNA. DR EMBL; AK131052; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AC008743; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471135; EAW71877.1; -; Genomic_DNA. DR EMBL; BC062416; AAH62416.1; -; mRNA. DR CCDS; CCDS12797.1; -. [Q8TAC2-1] DR CCDS; CCDS59413.1; -. [Q8TAC2-2] DR RefSeq; NP_001257568.1; NM_001270639.1. [Q8TAC2-1] DR RefSeq; NP_001257569.1; NM_001270640.1. [Q8TAC2-1] DR RefSeq; NP_001257570.1; NM_001270641.1. [Q8TAC2-2] DR RefSeq; NP_001257615.1; NM_001270686.1. [Q8TAC2-1] DR RefSeq; NP_612207.1; NM_138334.3. [Q8TAC2-1] DR RefSeq; XP_011524736.1; XM_011526434.2. DR PDB; 6PGV; X-ray; 2.30 A; A=1-188. DR PDBsum; 6PGV; -. DR AlphaFoldDB; Q8TAC2; -. DR SMR; Q8TAC2; -. DR BioGRID; 125956; 39. DR IntAct; Q8TAC2; 18. DR STRING; 9606.ENSP00000468956; -. DR BindingDB; Q8TAC2; -. DR ChEMBL; CHEMBL4630845; -. DR MEROPS; C86.005; -. DR GlyGen; Q8TAC2; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q8TAC2; -. DR PhosphoSitePlus; Q8TAC2; -. DR BioMuta; JOSD2; -. DR DMDM; 29840785; -. DR EPD; Q8TAC2; -. DR jPOST; Q8TAC2; -. DR MassIVE; Q8TAC2; -. DR MaxQB; Q8TAC2; -. DR PaxDb; 9606-ENSP00000468956; -. DR PeptideAtlas; Q8TAC2; -. DR ProteomicsDB; 73855; -. [Q8TAC2-1] DR Pumba; Q8TAC2; -. DR TopDownProteomics; Q8TAC2-1; -. [Q8TAC2-1] DR Antibodypedia; 53685; 98 antibodies from 19 providers. DR DNASU; 126119; -. DR Ensembl; ENST00000595669.5; ENSP00000468860.1; ENSG00000161677.12. [Q8TAC2-2] DR Ensembl; ENST00000598418.6; ENSP00000468956.2; ENSG00000161677.12. [Q8TAC2-1] DR Ensembl; ENST00000601423.5; ENSP00000472116.1; ENSG00000161677.12. [Q8TAC2-1] DR GeneID; 126119; -. DR KEGG; hsa:126119; -. DR MANE-Select; ENST00000598418.6; ENSP00000468956.2; NM_001270639.2; NP_001257568.1. DR UCSC; uc002pso.3; human. [Q8TAC2-1] DR AGR; HGNC:28853; -. DR CTD; 126119; -. DR GeneCards; JOSD2; -. DR HGNC; HGNC:28853; JOSD2. DR HPA; ENSG00000161677; Low tissue specificity. DR MIM; 615324; gene. DR neXtProt; NX_Q8TAC2; -. DR OpenTargets; ENSG00000161677; -. DR PharmGKB; PA142671645; -. DR VEuPathDB; HostDB:ENSG00000161677; -. DR eggNOG; KOG2934; Eukaryota. DR GeneTree; ENSGT00390000009228; -. DR HOGENOM; CLU_103892_2_0_1; -. DR InParanoid; Q8TAC2; -. DR OMA; QRNCEAV; -. DR OrthoDB; 239839at2759; -. DR PhylomeDB; Q8TAC2; -. DR TreeFam; TF313660; -. DR PathwayCommons; Q8TAC2; -. DR Reactome; R-HSA-5689877; Josephin domain DUBs. DR SignaLink; Q8TAC2; -. DR BioGRID-ORCS; 126119; 17 hits in 1190 CRISPR screens. DR ChiTaRS; JOSD2; human. DR GenomeRNAi; 126119; -. DR Pharos; Q8TAC2; Tbio. DR PRO; PR:Q8TAC2; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q8TAC2; Protein. DR Bgee; ENSG00000161677; Expressed in C1 segment of cervical spinal cord and 159 other cell types or tissues. DR ExpressionAtlas; Q8TAC2; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB. DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR Gene3D; 3.90.70.40; -; 1. DR InterPro; IPR040053; JOSD1/2. DR InterPro; IPR006155; Josephin. DR PANTHER; PTHR13291; JOSEPHIN 1, 2; 1. DR PANTHER; PTHR13291:SF2; JOSEPHIN-2; 1. DR Pfam; PF02099; Josephin; 1. DR PRINTS; PR01233; JOSEPHIN. DR SMART; SM01246; Josephin; 1. DR PROSITE; PS50957; JOSEPHIN; 1. DR Genevisible; Q8TAC2; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Hydrolase; Protease; KW Reference proteome; Ubl conjugation pathway. FT CHAIN 1..188 FT /note="Josephin-2" FT /id="PRO_0000053843" FT DOMAIN 11..188 FT /note="Josephin" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00331" FT ACT_SITE 24 FT /note="Nucleophile" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00331" FT ACT_SITE 125 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00331" FT VAR_SEQ 49..90 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_047537" FT MUTAGEN 24 FT /note="C->A: Loss of deubiquitination activity, no change FT in subcellular location." FT /evidence="ECO:0000269|PubMed:23625928" FT HELIX 24..33 FT /evidence="ECO:0007829|PDB:6PGV" FT HELIX 40..49 FT /evidence="ECO:0007829|PDB:6PGV" FT HELIX 70..78 FT /evidence="ECO:0007829|PDB:6PGV" FT TURN 79..81 FT /evidence="ECO:0007829|PDB:6PGV" FT STRAND 82..86 FT /evidence="ECO:0007829|PDB:6PGV" FT HELIX 93..95 FT /evidence="ECO:0007829|PDB:6PGV" FT HELIX 98..100 FT /evidence="ECO:0007829|PDB:6PGV" FT STRAND 102..109 FT /evidence="ECO:0007829|PDB:6PGV" FT STRAND 124..132 FT /evidence="ECO:0007829|PDB:6PGV" FT STRAND 135..138 FT /evidence="ECO:0007829|PDB:6PGV" FT STRAND 143..145 FT /evidence="ECO:0007829|PDB:6PGV" FT STRAND 147..151 FT /evidence="ECO:0007829|PDB:6PGV" FT HELIX 152..165 FT /evidence="ECO:0007829|PDB:6PGV" FT STRAND 169..175 FT /evidence="ECO:0007829|PDB:6PGV" FT HELIX 176..181 FT /evidence="ECO:0007829|PDB:6PGV" FT TURN 182..184 FT /evidence="ECO:0007829|PDB:6PGV" SQ SEQUENCE 188 AA; 20756 MW; A2832B4D9BD675E9 CRC64; MSQAPGAQPS PPTVYHERQR LELCAVHALN NVLQQQLFSQ EAADEICKRL APDSRLNPHR SLLGTGNYDV NVIMAALQGL GLAAVWWDRR RPLSQLALPQ VLGLILNLPS PVSLGLLSLP LRRRHWVALR QVDGVYYNLD SKLRAPEALG DEDGVRAFLA AALAQGLCEV LLVVTKEVEE KGSWLRTD //