JOS2_HUMAN
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 03-AUG-2022, entry version 139.
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;
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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. [Q8TAC2-1]
DR PDB; 6PGV; X-ray; 2.30 A; A=1-188.
DR PDBsum; 6PGV; -.
DR AlphaFoldDB; Q8TAC2; -.
DR SMR; Q8TAC2; -.
DR BioGRID; 125956; 37.
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; Q8TAC2; -.
DR PeptideAtlas; Q8TAC2; -.
DR PRIDE; Q8TAC2; -.
DR ProteomicsDB; 73855; -. [Q8TAC2-1]
DR TopDownProteomics; Q8TAC2-1; -. [Q8TAC2-1]
DR Antibodypedia; 53685; 84 antibodies from 18 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 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; QRWLLPQ; -.
DR PhylomeDB; Q8TAC2; -.
DR TreeFam; TF313660; -.
DR PathwayCommons; Q8TAC2; -.
DR Reactome; R-HSA-5689877; Josephin domain DUBs.
DR SignaLink; Q8TAC2; -.
DR BioGRID-ORCS; 126119; 16 hits in 1118 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 157 other tissues.
DR ExpressionAtlas; Q8TAC2; baseline and differential.
DR Genevisible; Q8TAC2; HS.
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 InterPro; IPR040053; JOSD1/2.
DR InterPro; IPR006155; Josephin.
DR PANTHER; PTHR13291; PTHR13291; 1.
DR Pfam; PF02099; Josephin; 1.
DR SMART; SM01246; Josephin; 1.
DR PROSITE; PS50957; JOSEPHIN; 1.
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
