DNJB2_HUMAN
ID DNJB2_HUMAN Reviewed; 324 AA.
AC P25686; A8K9P6; Q53QD7; Q8IUK1; Q8IUK2; Q96F52;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 11-SEP-2007, sequence version 3.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=DnaJ homolog subfamily B member 2 {ECO:0000305};
DE AltName: Full=Heat shock 40 kDa protein 3 {ECO:0000312|MIM:604139};
DE AltName: Full=Heat shock protein J1 {ECO:0000303|PubMed:1599432};
DE Short=HSJ-1 {ECO:0000303|PubMed:1599432};
DE Flags: Precursor;
GN Name=DNAJB2 {ECO:0000312|HGNC:HGNC:5228};
GN Synonyms=HSJ1 {ECO:0000303|PubMed:1599432}, HSPF3 {ECO:0000312|MIM:604139};
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 [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=1599432; DOI=10.1042/bj2840469;
RA Cheetham M.E., Brion J.-P., Anderton B.H.;
RT "Human homologues of the bacterial heat-shock protein DnaJ are
RT preferentially expressed in neurons.";
RL Biochem. J. 284:469-476(1992).
RN [2]
RP SEQUENCE REVISION TO 214.
RA Cheetham M.E.;
RL Submitted (JUL-1998) to UniProtKB.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain, and Lung;
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 [5]
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 [6]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Colon, 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 [8]
RP FUNCTION.
RX PubMed=7957263; DOI=10.1111/j.1432-1033.1994.tb20030.x;
RA Cheetham M.E., Jackson A.P., Anderton B.H.;
RT "Regulation of 70-kDa heat-shock-protein ATPase activity and substrate
RT binding by human DnaJ-like proteins, HSJ1a and HSJ1b.";
RL Eur. J. Biochem. 226:99-107(1994).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION (ISOFORMS 1 AND 2), TOPOLOGY (ISOFORM 1),
RP TISSUE SPECIFICITY (ISOFORMS 1 AND 2), MUTAGENESIS OF HIS-31; CYS-321 AND
RP LEU-324, ISOPRENYLATION AT CYS-321, METHYLATION AT CYS-321, AND MOTIF.
RX PubMed=12754272; DOI=10.1074/jbc.m212349200;
RA Chapple J.P., Cheetham M.E.;
RT "The chaperone environment at the cytoplasmic face of the endoplasmic
RT reticulum can modulate rhodopsin processing and inclusion formation.";
RL J. Biol. Chem. 278:19087-19094(2003).
RN [10]
RP FUNCTION, INTERACTION WITH HSPA8 AND PSMA3, UBIQUITINATION BY STUB1,
RP DOMAIN, AND MUTAGENESIS OF 31-HIS--ASP-33; SER-219; GLU-222; SER-262 AND
RP GLU-265.
RX PubMed=15936278; DOI=10.1016/j.cub.2005.04.058;
RA Westhoff B., Chapple J.P., van der Spuy J., Hoehfeld J., Cheetham M.E.;
RT "HSJ1 is a neuronal shuttling factor for the sorting of chaperone clients
RT to the proteasome.";
RL Curr. Biol. 15:1058-1064(2005).
RN [11]
RP FUNCTION, DOMAIN, AND MUTAGENESIS OF HIS-31.
RX PubMed=20889486; DOI=10.1093/hmg/ddq428;
RA Rose J.M., Novoselov S.S., Robinson P.A., Cheetham M.E.;
RT "Molecular chaperone-mediated rescue of mitophagy by a Parkin RING1 domain
RT mutant.";
RL Hum. Mol. Genet. 20:16-27(2011).
RN [12]
RP FUNCTION.
RX PubMed=21719532; DOI=10.1210/me.2011-1020;
RA Meimaridou E., Gooljar S.B., Ramnarace N., Anthonypillai L., Clark A.J.,
RA Chapple J.P.;
RT "The cytosolic chaperone Hsc70 promotes traffic to the cell surface of
RT intracellular retained melanocortin-4 receptor mutants.";
RL Mol. Endocrinol. 25:1650-1660(2011).
RN [13]
RP FUNCTION, INTERACTION WITH HSP70, SUBCELLULAR LOCATION, DOMAIN, AND
RP MUTAGENESIS OF 31-HIS--ASP-33; SER-219; GLU-222; SER-262 AND GLU-265.
RX PubMed=21625540; DOI=10.1371/journal.pone.0019763;
RA Gao X.C., Zhou C.J., Zhou Z.R., Zhang Y.H., Zheng X.M., Song A.X., Hu H.Y.;
RT "Co-chaperone HSJ1a dually regulates the proteasomal degradation of ataxin-
RT 3.";
RL PLoS ONE 6:E19763-E19763(2011).
RN [14]
RP INVOLVEMENT IN DSMA5.
RX PubMed=22522442; DOI=10.1002/ana.22684;
RA Blumen S.C., Astord S., Robin V., Vignaud L., Toumi N., Cieslik A.,
RA Achiron A., Carasso R.L., Gurevich M., Braverman I., Blumen N., Munich A.,
RA Barkats M., Viollet L.;
RT "A rare recessive distal hereditary motor neuropathy with HSJ1 chaperone
RT mutation.";
RL Ann. Neurol. 71:509-519(2012).
RN [15]
RP FUNCTION.
RX PubMed=22396390; DOI=10.1093/brain/aws022;
RA Labbadia J., Novoselov S.S., Bett J.S., Weiss A., Paganetti P., Bates G.P.,
RA Cheetham M.E.;
RT "Suppression of protein aggregation by chaperone modification of high
RT molecular weight complexes.";
RL Brain 135:1180-1196(2012).
RN [16]
RP FUNCTION.
RX PubMed=24023695; DOI=10.1371/journal.pone.0073944;
RA Novoselov S.S., Mustill W.J., Gray A.L., Dick J.R., Kanuga N., Kalmar B.,
RA Greensmith L., Cheetham M.E.;
RT "Molecular chaperone mediated late-stage neuroprotection in the SOD1(G93A)
RT mouse model of amyotrophic lateral sclerosis.";
RL PLoS ONE 8:E73944-E73944(2013).
RN [17]
RP INVOLVEMENT IN DSMA5, AND VARIANT DSMA5 CYS-5.
RX PubMed=24627108; DOI=10.1007/s00415-014-7289-8;
RA Schabhuettl M., Wieland T., Senderek J., Baets J., Timmerman V.,
RA De Jonghe P., Reilly M.M., Stieglbauer K., Laich E., Windhager R., Erwa W.,
RA Trajanoski S., Strom T.M., Auer-Grumbach M.;
RT "Whole-exome sequencing in patients with inherited neuropathies: outcome
RT and challenges.";
RL J. Neurol. 261:970-982(2014).
RN [18]
RP INVOLVEMENT IN DSMA5, AND VARIANT DSMA5 CYS-5.
RX PubMed=25274842; DOI=10.1212/wnl.0000000000000966;
RA Gess B., Auer-Grumbach M., Schirmacher A., Strom T., Zitzelsberger M.,
RA Rudnik-Schoneborn S., Rohr D., Halfter H., Young P., Senderek J.;
RT "HSJ1-related hereditary neuropathies: novel mutations and extended
RT clinical spectrum.";
RL Neurology 83:1726-1732(2014).
RN [19]
RP STRUCTURE BY NMR OF 1-71, FUNCTION, INTERACTION WITH HSP70, AND DOMAIN.
RX PubMed=22219199; DOI=10.1074/jbc.m111.294728;
RA Gao X.C., Zhou C.J., Zhou Z.R., Wu M., Cao C.Y., Hu H.Y.;
RT "The C-terminal helices of heat shock protein 70 are essential for J-domain
RT binding and ATPase activation.";
RL J. Biol. Chem. 287:6044-6052(2012).
CC -!- FUNCTION: Functions as a co-chaperone, regulating the substrate binding
CC and activating the ATPase activity of chaperones of the HSP70/heat
CC shock protein 70 family (PubMed:7957263, PubMed:22219199). In parallel,
CC also contributes to the ubiquitin-dependent proteasomal degradation of
CC misfolded proteins (PubMed:15936278, PubMed:21625540). Thereby, may
CC regulate the aggregation and promote the functional recovery of
CC misfolded proteins like HTT, MC4R, PRKN, RHO and SOD1 and be crucial
CC for many biological processes (PubMed:12754272, PubMed:20889486,
CC PubMed:21719532, PubMed:22396390, PubMed:24023695). Isoform 1 which is
CC localized to the endoplasmic reticulum membranes may specifically
CC function in ER-associated protein degradation of misfolded proteins
CC (PubMed:15936278). {ECO:0000269|PubMed:12754272,
CC ECO:0000269|PubMed:15936278, ECO:0000269|PubMed:20889486,
CC ECO:0000269|PubMed:21625540, ECO:0000269|PubMed:21719532,
CC ECO:0000269|PubMed:22219199, ECO:0000269|PubMed:22396390,
CC ECO:0000269|PubMed:24023695, ECO:0000269|PubMed:7957263}.
CC -!- SUBUNIT: Interacts with HSP70 (HSPA1A or HSPA1B) (PubMed:21625540,
CC PubMed:22219199). Interacts with HSPA8/Hsc70 (PubMed:15936278).
CC Interacts with PSMA3 and most probably with the whole proteasomal
CC complex (PubMed:15936278). {ECO:0000269|PubMed:15936278,
CC ECO:0000269|PubMed:21625540, ECO:0000269|PubMed:22219199}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000269|PubMed:12754272, ECO:0000269|PubMed:21625540}. Nucleus
CC {ECO:0000269|PubMed:12754272}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:12754272}; Lipid-anchor
CC {ECO:0000269|PubMed:12754272}; Cytoplasmic side
CC {ECO:0000269|PubMed:12754272}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=HSJ1b {ECO:0000303|PubMed:1599432};
CC IsoId=P25686-3; Sequence=Displayed;
CC Name=2; Synonyms=HSJ1a {ECO:0000303|PubMed:1599432}, DNAJB2a
CC {ECO:0000303|PubMed:20889486};
CC IsoId=P25686-2; Sequence=VSP_001286, VSP_001287;
CC -!- TISSUE SPECIFICITY: More abundantly expressed in neocortex, cerebellum,
CC spinal cord and retina where it is expressed by neuronal cells (at
CC protein level) (PubMed:1599432, PubMed:12754272). Detected at much
CC lower level in non-neuronal tissues including kidney, lung, heart,
CC skeletal muscle, spleen and testis (at protein level) (PubMed:12754272,
CC PubMed:1599432). Isoform 1 is more abundant in neocortex and cerebellum
CC compared to isoform 2 (at protein level) (PubMed:12754272).
CC {ECO:0000269|PubMed:12754272, ECO:0000269|PubMed:1599432}.
CC -!- DOMAIN: The J domain is sufficient to interact with HSP70 (HSPA1A or
CC HSPA1B) and activate its ATPase activity (PubMed:22219199). The J
CC domain is also required for the HSP70-mediated and ubiquitin-dependent
CC proteasomal degradation of proteins like ATXN3 (PubMed:21625540). The J
CC domain is required to reduce PRKN cytoplasmic aggregation
CC (PubMed:20889486). {ECO:0000269|PubMed:20889486,
CC ECO:0000269|PubMed:21625540, ECO:0000269|PubMed:22219199}.
CC -!- DOMAIN: The UIM domains mediate interaction with ubiquitinated
CC chaperone clients and with the proteasome (PubMed:15936278). The UIM
CC domains may have an opposite activity to the J domain, binding
CC ubiquitinated proteins and protecting them from HSP70-mediated
CC proteasomal degradation (PubMed:21625540). The UIM domains are not
CC required to reduce PRKN cytoplasmic aggregation (PubMed:20889486).
CC {ECO:0000269|PubMed:15936278, ECO:0000269|PubMed:20889486,
CC ECO:0000269|PubMed:21625540}.
CC -!- PTM: Ubiquitinated by STUB1; does not lead to proteasomal degradation.
CC {ECO:0000269|PubMed:15936278}.
CC -!- DISEASE: Distal spinal muscular atrophy, autosomal recessive, 5 (DSMA5)
CC [MIM:614881]: An autosomal recessive neurologic disorder characterized
CC by young adult onset of slowly progressive distal muscle weakness and
CC atrophy resulting in gait impairment and loss of reflexes due to
CC impaired function of motor nerves. Sensation and cognition are not
CC impaired. {ECO:0000269|PubMed:22522442, ECO:0000269|PubMed:24627108,
CC ECO:0000269|PubMed:25274842}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA09035.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; S37375; AAA09034.1; -; mRNA.
DR EMBL; S37374; AAA09035.1; ALT_FRAME; mRNA.
DR EMBL; X63368; CAA44968.2; -; Genomic_DNA.
DR EMBL; X63368; CAA44969.2; -; Genomic_DNA.
DR EMBL; BT007088; AAP35751.1; -; mRNA.
DR EMBL; AK292761; BAF85450.1; -; mRNA.
DR EMBL; AK312723; BAG35597.1; -; mRNA.
DR EMBL; AC114803; AAY24037.1; -; Genomic_DNA.
DR EMBL; CH471063; EAW70722.1; -; Genomic_DNA.
DR EMBL; BC011609; AAH11609.1; -; mRNA.
DR EMBL; BC047056; AAH47056.1; -; mRNA.
DR CCDS; CCDS2439.1; -. [P25686-3]
DR CCDS; CCDS46519.1; -. [P25686-2]
DR PIR; S23508; S23508.
DR RefSeq; NP_001034639.1; NM_001039550.1. [P25686-2]
DR RefSeq; NP_006727.2; NM_006736.5. [P25686-3]
DR PDB; 2LGW; NMR; -; A=1-91.
DR PDBsum; 2LGW; -.
DR AlphaFoldDB; P25686; -.
DR BMRB; P25686; -.
DR SMR; P25686; -.
DR BioGRID; 109533; 111.
DR CORUM; P25686; -.
DR DIP; DIP-29051N; -.
DR IntAct; P25686; 37.
DR MINT; P25686; -.
DR STRING; 9606.ENSP00000338019; -.
DR GlyGen; P25686; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P25686; -.
DR PhosphoSitePlus; P25686; -.
DR BioMuta; DNAJB2; -.
DR DMDM; 158518384; -.
DR EPD; P25686; -.
DR jPOST; P25686; -.
DR MassIVE; P25686; -.
DR MaxQB; P25686; -.
DR PaxDb; P25686; -.
DR PeptideAtlas; P25686; -.
DR PRIDE; P25686; -.
DR ProteomicsDB; 54281; -. [P25686-3]
DR ProteomicsDB; 54282; -. [P25686-2]
DR Antibodypedia; 34321; 372 antibodies from 32 providers.
DR DNASU; 3300; -.
DR Ensembl; ENST00000336576.10; ENSP00000338019.5; ENSG00000135924.17. [P25686-3]
DR Ensembl; ENST00000392086.8; ENSP00000375936.4; ENSG00000135924.17. [P25686-2]
DR GeneID; 3300; -.
DR KEGG; hsa:3300; -.
DR MANE-Select; ENST00000336576.10; ENSP00000338019.5; NM_006736.6; NP_006727.2.
DR UCSC; uc002vkw.2; human. [P25686-3]
DR UCSC; uc002vkx.2; human.
DR CTD; 3300; -.
DR DisGeNET; 3300; -.
DR GeneCards; DNAJB2; -.
DR HGNC; HGNC:5228; DNAJB2.
DR HPA; ENSG00000135924; Tissue enhanced (brain).
DR MalaCards; DNAJB2; -.
DR MIM; 604139; gene.
DR MIM; 614881; phenotype.
DR neXtProt; NX_P25686; -.
DR OpenTargets; ENSG00000135924; -.
DR Orphanet; 443950; DNAJB2-related Charcot-Marie-Tooth disease type 2.
DR Orphanet; 314485; Young adult-onset distal hereditary motor neuropathy.
DR PharmGKB; PA27415; -.
DR VEuPathDB; HostDB:ENSG00000135924; -.
DR eggNOG; KOG0714; Eukaryota.
DR GeneTree; ENSGT00940000160220; -.
DR InParanoid; P25686; -.
DR OMA; FFDDMLP; -.
DR OrthoDB; 1472647at2759; -.
DR PhylomeDB; P25686; -.
DR TreeFam; TF105142; -.
DR PathwayCommons; P25686; -.
DR SignaLink; P25686; -.
DR BioGRID-ORCS; 3300; 24 hits in 1080 CRISPR screens.
DR ChiTaRS; DNAJB2; human.
DR GeneWiki; DNAJB2; -.
DR GenomeRNAi; 3300; -.
DR Pharos; P25686; Tbio.
DR PRO; PR:P25686; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P25686; protein.
DR Bgee; ENSG00000135924; Expressed in C1 segment of cervical spinal cord and 199 other tissues.
DR ExpressionAtlas; P25686; baseline and differential.
DR Genevisible; P25686; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0098554; C:cytoplasmic side of endoplasmic reticulum membrane; TAS:ARUK-UCL.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0042406; C:extrinsic component of endoplasmic reticulum membrane; TAS:ARUK-UCL.
DR GO; GO:0016234; C:inclusion body; IDA:BHF-UCL.
DR GO; GO:0031227; C:intrinsic component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:ARUK-UCL.
DR GO; GO:0001671; F:ATPase activator activity; IDA:UniProtKB.
DR GO; GO:0051087; F:chaperone binding; IPI:UniProtKB.
DR GO; GO:0030544; F:Hsp70 protein binding; IDA:UniProtKB.
DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0070628; F:proteasome binding; IDA:BHF-UCL.
DR GO; GO:0043130; F:ubiquitin binding; IDA:ARUK-UCL.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0140036; F:ubiquitin-dependent protein binding; IDA:ARUK-UCL.
DR GO; GO:0051082; F:unfolded protein binding; IDA:UniProtKB.
DR GO; GO:0061077; P:chaperone-mediated protein folding; IMP:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; IGI:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IGI:UniProtKB.
DR GO; GO:0090084; P:negative regulation of inclusion body assembly; IDA:BHF-UCL.
DR GO; GO:0032091; P:negative regulation of protein binding; IDA:UniProtKB.
DR GO; GO:0090086; P:negative regulation of protein deubiquitination; IDA:BHF-UCL.
DR GO; GO:0070050; P:neuron cellular homeostasis; TAS:ARUK-UCL.
DR GO; GO:0032781; P:positive regulation of ATP-dependent activity; IDA:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:BHF-UCL.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:BHF-UCL.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0042026; P:protein refolding; IDA:UniProtKB.
DR GO; GO:1903644; P:regulation of chaperone-mediated protein folding; IDA:UniProtKB.
DR GO; GO:0032880; P:regulation of protein localization; IMP:ParkinsonsUK-UCL.
DR GO; GO:0031396; P:regulation of protein ubiquitination; IMP:UniProtKB.
DR GO; GO:0006986; P:response to unfolded protein; TAS:ProtInc.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IDA:BHF-UCL.
DR CDD; cd06257; DnaJ; 1.
DR Gene3D; 1.10.287.110; -; 1.
DR InterPro; IPR001623; DnaJ_domain.
DR InterPro; IPR018253; DnaJ_domain_CS.
DR InterPro; IPR043183; DNJB2.
DR InterPro; IPR036869; J_dom_sf.
DR InterPro; IPR003903; UIM_dom.
DR PANTHER; PTHR45168; PTHR45168; 1.
DR Pfam; PF00226; DnaJ; 1.
DR PRINTS; PR00625; JDOMAIN.
DR SMART; SM00271; DnaJ; 1.
DR SMART; SM00726; UIM; 2.
DR SUPFAM; SSF46565; SSF46565; 1.
DR PROSITE; PS00636; DNAJ_1; 1.
DR PROSITE; PS50076; DNAJ_2; 1.
DR PROSITE; PS50330; UIM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Chaperone; Cytoplasm;
KW Endoplasmic reticulum; Lipoprotein; Membrane; Methylation;
KW Neurodegeneration; Nucleus; Phosphoprotein; Prenylation;
KW Reference proteome; Repeat; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9QYI5"
FT CHAIN 2..321
FT /note="DnaJ homolog subfamily B member 2"
FT /id="PRO_0000071018"
FT PROPEP 322..324
FT /note="Removed in mature form"
FT /evidence="ECO:0000305|PubMed:12754272"
FT /id="PRO_0000438687"
FT DOMAIN 2..71
FT /note="J"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00286"
FT DOMAIN 210..226
FT /note="UIM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT DOMAIN 250..269
FT /note="UIM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT REGION 70..90
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 218..324
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 321..324
FT /note="CAAX motif"
FT /evidence="ECO:0000269|PubMed:12754272"
FT COMPBIAS 221..245
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 271..289
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q9QYI5"
FT MOD_RES 311
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QYI5"
FT MOD_RES 321
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000305|PubMed:12754272"
FT LIPID 321
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000269|PubMed:12754272"
FT VAR_SEQ 275..277
FT /note="GGR -> DVF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_001286"
FT VAR_SEQ 278..324
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_001287"
FT VARIANT 5
FT /note="Y -> C (in DSMA5; dbSNP:rs730882140)"
FT /evidence="ECO:0000269|PubMed:24627108,
FT ECO:0000269|PubMed:25274842"
FT /id="VAR_073286"
FT VARIANT 270
FT /note="G -> R (in dbSNP:rs34127289)"
FT /id="VAR_048910"
FT MUTAGEN 31..33
FT /note="HPD->QPN: Loss of interaction with HSP70 and loss of
FT the ability to promote ATXN3 proteasomal degradation."
FT /evidence="ECO:0000269|PubMed:21625540"
FT MUTAGEN 31
FT /note="H->Q: Probable loss of interaction with HSP70 and
FT loss of the ability to reduce PRKN aggregation."
FT /evidence="ECO:0000269|PubMed:12754272,
FT ECO:0000269|PubMed:20889486"
FT MUTAGEN 219
FT /note="S->A: Loss of interaction with polyubiquitin chains,
FT loss of interaction with PSMA3, and loss of the ability to
FT protect ATXN3 from proteasomal degradation; when associated
FT with A-222; A-262 and A-265."
FT /evidence="ECO:0000269|PubMed:15936278,
FT ECO:0000269|PubMed:21625540"
FT MUTAGEN 222
FT /note="E->A: Loss of interaction with polyubiquitin chains,
FT loss of interaction with PSMA3, and loss of the ability to
FT protect ATXN3 from proteasomal degradation; when associated
FT with A-219; A-262 and A-265."
FT /evidence="ECO:0000269|PubMed:15936278,
FT ECO:0000269|PubMed:21625540"
FT MUTAGEN 262
FT /note="S->A: Loss of interaction with polyubiquitin chains,
FT loss of interaction with PSMA3, and loss of the ability to
FT protect ATXN3 from proteasomal degradation; when associated
FT with A-219; A-222 and A-265."
FT /evidence="ECO:0000269|PubMed:15936278,
FT ECO:0000269|PubMed:21625540"
FT MUTAGEN 265
FT /note="E->A: Loss of interaction with polyubiquitin chains,
FT loss of interaction with PSMA3, and loss of the ability to
FT protect ATXN3 from proteasomal degradation; when associated
FT with A-219; A-222 and A-262."
FT /evidence="ECO:0000269|PubMed:15936278,
FT ECO:0000269|PubMed:21625540"
FT MUTAGEN 321
FT /note="C->S: Loss of localization to the endoplasmic
FT reticulum and relocalization to cytoplasm and nucleus."
FT /evidence="ECO:0000269|PubMed:12754272"
FT MUTAGEN 324
FT /note="L->M: No effect on localization to the endoplasmic
FT reticulum membrane."
FT /evidence="ECO:0000269|PubMed:12754272"
FT CONFLICT 214
FT /note="L -> R (in Ref. 1; AAA09034/AAA09035)"
FT /evidence="ECO:0000305"
FT HELIX 4..7
FT /evidence="ECO:0007829|PDB:2LGW"
FT STRAND 8..10
FT /evidence="ECO:0007829|PDB:2LGW"
FT HELIX 16..29
FT /evidence="ECO:0007829|PDB:2LGW"
FT TURN 32..34
FT /evidence="ECO:0007829|PDB:2LGW"
FT HELIX 40..57
FT /evidence="ECO:0007829|PDB:2LGW"
FT HELIX 59..70
FT /evidence="ECO:0007829|PDB:2LGW"
SQ SEQUENCE 324 AA; 35580 MW; 0154ED3E29F34B4A CRC64;
MASYYEILDV PRSASADDIK KAYRRKALQW HPDKNPDNKE FAEKKFKEVA EAYEVLSDKH
KREIYDRYGR EGLTGTGTGP SRAEAGSGGP GFTFTFRSPE EVFREFFGSG DPFAELFDDL
GPFSELQNRG SRHSGPFFTF SSSFPGHSDF SSSSFSFSPG AGAFRSVSTS TTFVQGRRIT
TRRIMENGQE RVEVEEDGQL KSVTINGVPD DLALGLELSR REQQPSVTSR SGGTQVQQTP
ASCPLDSDLS EDEDLQLAMA YSLSEMEAAG KKPAGGREAQ HRRQGRPKAQ HQDPGLGGTQ
EGARGEATKR SPSPEEKASR CLIL
