DNJB6_HUMAN
ID DNJB6_HUMAN Reviewed; 326 AA.
AC O75190; A4D232; A8K7D8; A8KAG0; B4DN73; E9PCZ2; O95806; Q53EN8; Q59EF2;
AC Q6FIC8; Q75MA2; Q9UIK6;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 18-OCT-2001, sequence version 2.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=DnaJ homolog subfamily B member 6;
DE AltName: Full=HHDJ1;
DE AltName: Full=Heat shock protein J2;
DE Short=HSJ-2;
DE AltName: Full=MRJ;
DE AltName: Full=MSJ-1;
GN Name=DNAJB6; Synonyms=HSJ2, MRJ, MSJ1;
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 B), INTERACTION WITH PTTG, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=9915854; DOI=10.1074/jbc.274.5.3151;
RA Pei L.;
RT "Pituitary tumor-transforming gene protein associates with ribosomal
RT protein S10 and a novel human homologue of DnaJ in testicular cells.";
RL J. Biol. Chem. 274:3151-3158(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11896048; DOI=10.1074/jbc.m109613200;
RA Chuang J.-Z., Zhou H., Zhu M., Li S.-H., Li X.-J., Sung C.-H.;
RT "Characterization of a brain-enriched chaperone, MRJ, that inhibits
RT Huntingtin aggregation and toxicity independently.";
RL J. Biol. Chem. 277:19831-19838(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B).
RX PubMed=12974469; DOI=10.1023/a:1024916223616;
RA Hanai R., Mashima K.;
RT "Characterization of two isoforms of a human DnaJ homologue, HSJ2.";
RL Mol. Biol. Rep. 30:149-153(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
RC TISSUE=Pancreas;
RA Zhang J.S., Nelson M., Wang L., Smith D.I.;
RL Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=10319584; DOI=10.1007/s100380050139;
RA Seki N., Hattori A., Hayashi A., Kozuma S., Miyajima N., Saito T.;
RT "Cloning, tissue expression, and chromosomal assignment of human MRJ gene
RT for a member of the DNAJ protein family.";
RL J. Hum. Genet. 44:185-189(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
RA Zhang W., Wan T., Yuan Z., Cao X.;
RT "HSJ2, a novel human homologue of the bacterial heat-shock protein DnaJ.";
RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A; B AND C).
RC TISSUE=Uterus;
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND C).
RC TISSUE=Aortic endothelium, and Kidney;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC TISSUE=Fetal kidney;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [13]
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 [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND B).
RC TISSUE=Placenta, and Skin;
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 [15]
RP PROTEIN SEQUENCE OF 2-12; 48-60; 71-101; 208-242 AND 271-287, CLEAVAGE OF
RP INITIATOR METHIONINE, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
RN [16]
RP FUNCTION, INTERACTION WITH HSP70 AND KRT18, AND SUBCELLULAR LOCATION.
RX PubMed=10954706; DOI=10.1074/jbc.m003492200;
RA Izawa I., Nishizawa M., Ohtakara K., Ohtsuka K., Inada H., Inagaki M.;
RT "Identification of Mrj, a DnaJ/Hsp40 family protein, as a keratin 8/18
RT filament regulatory protein.";
RL J. Biol. Chem. 275:34521-34527(2000).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-277, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [18]
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 [19]
RP FUNCTION AS SUPPRESSOR OF PROTEIN AGGREGATION.
RX PubMed=20159555; DOI=10.1016/j.molcel.2010.01.001;
RA Hageman J., Rujano M.A., van Waarde M.A., Kakkar V., Dirks R.P.,
RA Govorukhina N., Oosterveld-Hut H.M., Lubsen N.H., Kampinga H.H.;
RT "A DNAJB chaperone subfamily with HDAC-dependent activities suppresses
RT toxic protein aggregation.";
RL Mol. Cell 37:355-369(2010).
RN [20]
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 [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-277, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [22]
RP FUNCTION IN INHIBITION OF HUNTINGTIN AGGREGATION, SUBUNIT, INTERACTION WITH
RP BAG3; HSPB8 AND STUB1, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, VARIANTS
RP LGMDD1 ILE-89 AND LEU-93, AND CHARACTERIZATION OF VARIANTS LGMDD1 ILE-89
RP AND LEU-93.
RX PubMed=22366786; DOI=10.1038/ng.1103;
RA Sarparanta J., Jonson P.H., Golzio C., Sandell S., Luque H., Screen M.,
RA McDonald K., Stajich J.M., Mahjneh I., Vihola A., Raheem O., Penttila S.,
RA Lehtinen S., Huovinen S., Palmio J., Tasca G., Ricci E., Hackman P.,
RA Hauser M., Katsanis N., Udd B.;
RT "Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6
RT cause limb-girdle muscular dystrophy.";
RL Nat. Genet. 44:450-455(2012).
RN [23]
RP IDENTIFICATION BY MASS 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 [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-277, AND IDENTIFICATION BY
RP 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 [25]
RP VARIANTS LGMDD1 LEU-93 AND ARG-96.
RX PubMed=22334415; DOI=10.1002/ana.22683;
RA Harms M.B., Sommerville R.B., Allred P., Bell S., Ma D., Cooper P.,
RA Lopate G., Pestronk A., Weihl C.C., Baloh R.H.;
RT "Exome sequencing reveals DNAJB6 mutations in dominantly-inherited
RT myopathy.";
RL Ann. Neurol. 71:407-416(2012).
RN [26]
RP VARIANT LEU-96, CHARACTERIZATION OF VARIANT LEU-96, AND FUNCTION.
RX PubMed=28233300; DOI=10.1111/cge.13001;
RA Tsai P.C., Tsai Y.S., Soong B.W., Huang Y.H., Wu H.T., Chen Y.H., Lin K.P.,
RA Liao Y.C., Lee Y.C.;
RT "A novel DNAJB6 mutation causes dominantly inherited distal-onset myopathy
RT and compromises DNAJB6 function.";
RL Clin. Genet. 92:150-157(2017).
CC -!- FUNCTION: Plays an indispensable role in the organization of KRT8/KRT18
CC filaments. Acts as an endogenous molecular chaperone for neuronal
CC proteins including huntingtin. Suppresses aggregation and toxicity of
CC polyglutamine-containing, aggregation-prone proteins. Isoform B but not
CC isoform A inhibits huntingtin aggregation. Has a stimulatory effect on
CC the ATPase activity of HSP70 in a dose-dependent and time-dependent
CC manner and hence acts as a co-chaperone of HSP70. Also reduces cellular
CC toxicity and caspase-3 activity. {ECO:0000269|PubMed:10954706,
CC ECO:0000269|PubMed:11896048, ECO:0000269|PubMed:20159555,
CC ECO:0000269|PubMed:22366786, ECO:0000269|PubMed:28233300}.
CC -!- SUBUNIT: Homooligomer. Interacts with BAG3, HSPB8 and STUB1. Interacts
CC with ALKBH1 (By similarity). Interacts with HSP70, KRT18 and PTTG.
CC Isoform B interacts with histone deacetylases HDAC4, HDAC6, and SIRT2,
CC HDAC activity is required for antiaggregation. {ECO:0000250,
CC ECO:0000269|PubMed:10954706, ECO:0000269|PubMed:22366786,
CC ECO:0000269|PubMed:9915854}.
CC -!- INTERACTION:
CC O75190; Q6XD76: ASCL4; NbExp=3; IntAct=EBI-1053164, EBI-10254793;
CC O75190; Q9HCU9: BRMS1; NbExp=2; IntAct=EBI-1053164, EBI-714781;
CC O75190; Q13191: CBLB; NbExp=3; IntAct=EBI-1053164, EBI-744027;
CC O75190; Q494V2-2: CFAP100; NbExp=3; IntAct=EBI-1053164, EBI-11953200;
CC O75190; Q6P1L5: FAM117B; NbExp=3; IntAct=EBI-1053164, EBI-3893327;
CC O75190; Q13123: IK; NbExp=3; IntAct=EBI-1053164, EBI-713456;
CC O75190; P05783: KRT18; NbExp=6; IntAct=EBI-1053164, EBI-297888;
CC O75190; Q8TD91-2: MAGEC3; NbExp=3; IntAct=EBI-1053164, EBI-10694180;
CC O75190; P58340: MLF1; NbExp=2; IntAct=EBI-1053164, EBI-721328;
CC O75190; Q15773: MLF2; NbExp=4; IntAct=EBI-1053164, EBI-1051875;
CC O75190; Q9BUL9: RPP25; NbExp=3; IntAct=EBI-1053164, EBI-366570;
CC O75190; Q8NHS9: SPATA22; NbExp=3; IntAct=EBI-1053164, EBI-7067260;
CC O75190; Q3KNS6-3: ZNF829; NbExp=3; IntAct=EBI-1053164, EBI-18036029;
CC O75190; Q8NBB4-2: ZSCAN1; NbExp=3; IntAct=EBI-1053164, EBI-12021938;
CC O75190-2; Q9NP70: AMBN; NbExp=3; IntAct=EBI-12593112, EBI-11893530;
CC O75190-2; Q6ZTN6-2: ANKRD13D; NbExp=3; IntAct=EBI-12593112, EBI-25840993;
CC O75190-2; Q6LES2: ANXA4; NbExp=3; IntAct=EBI-12593112, EBI-10250835;
CC O75190-2; O94778: AQP8; NbExp=3; IntAct=EBI-12593112, EBI-19124986;
CC O75190-2; Q9UII2: ATP5IF1; NbExp=3; IntAct=EBI-12593112, EBI-718459;
CC O75190-2; P15313: ATP6V1B1; NbExp=3; IntAct=EBI-12593112, EBI-2891281;
CC O75190-2; P54687-4: BCAT1; NbExp=3; IntAct=EBI-12593112, EBI-25834445;
CC O75190-2; P06276: BCHE; NbExp=3; IntAct=EBI-12593112, EBI-7936069;
CC O75190-2; Q14457: BECN1; NbExp=3; IntAct=EBI-12593112, EBI-949378;
CC O75190-2; Q9H0W9-3: C11orf54; NbExp=3; IntAct=EBI-12593112, EBI-12108466;
CC O75190-2; Q9NNX6-10: CD209; NbExp=3; IntAct=EBI-12593112, EBI-12300031;
CC O75190-2; Q9UJX2: CDC23; NbExp=3; IntAct=EBI-12593112, EBI-396137;
CC O75190-2; Q6PJW8-3: CNST; NbExp=3; IntAct=EBI-12593112, EBI-25836090;
CC O75190-2; P24310: COX7A1; NbExp=3; IntAct=EBI-12593112, EBI-25876196;
CC O75190-2; P53672: CRYBA2; NbExp=3; IntAct=EBI-12593112, EBI-750444;
CC O75190-2; Q9UBP4: DKK3; NbExp=3; IntAct=EBI-12593112, EBI-954409;
CC O75190-2; O75190-2: DNAJB6; NbExp=2; IntAct=EBI-12593112, EBI-12593112;
CC O75190-2; A0A024RCP2: DOM3Z; NbExp=3; IntAct=EBI-12593112, EBI-25847826;
CC O75190-2; Q86TI2-2: DPP9; NbExp=3; IntAct=EBI-12593112, EBI-21529239;
CC O75190-2; H3BUJ7: E4F1; NbExp=3; IntAct=EBI-12593112, EBI-10178160;
CC O75190-2; Q9BQS8-2: FYCO1; NbExp=3; IntAct=EBI-12593112, EBI-25905795;
CC O75190-2; Q9BRX5: GINS3; NbExp=3; IntAct=EBI-12593112, EBI-2857315;
CC O75190-2; Q6NXT2: H3-5; NbExp=3; IntAct=EBI-12593112, EBI-2868501;
CC O75190-2; Q96CS2: HAUS1; NbExp=3; IntAct=EBI-12593112, EBI-2514791;
CC O75190-2; Q99871: HAUS7; NbExp=3; IntAct=EBI-12593112, EBI-395719;
CC O75190-2; P42858: HTT; NbExp=3; IntAct=EBI-12593112, EBI-466029;
CC O75190-2; P80217-2: IFI35; NbExp=3; IntAct=EBI-12593112, EBI-12823003;
CC O75190-2; Q8NA54: IQUB; NbExp=3; IntAct=EBI-12593112, EBI-10220600;
CC O75190-2; Q8IV33: KIAA0825; NbExp=3; IntAct=EBI-12593112, EBI-17702098;
CC O75190-2; Q6P597: KLC3; NbExp=3; IntAct=EBI-12593112, EBI-1643885;
CC O75190-2; Q13887: KLF5; NbExp=3; IntAct=EBI-12593112, EBI-2696013;
CC O75190-2; Q9UH77: KLHL3; NbExp=3; IntAct=EBI-12593112, EBI-8524663;
CC O75190-2; Q96JB6: LOXL4; NbExp=3; IntAct=EBI-12593112, EBI-749562;
CC O75190-2; Q96LR2: LURAP1; NbExp=3; IntAct=EBI-12593112, EBI-741355;
CC O75190-2; Q8N6F8: METTL27; NbExp=3; IntAct=EBI-12593112, EBI-8487781;
CC O75190-2; Q9Y605: MRFAP1; NbExp=3; IntAct=EBI-12593112, EBI-995714;
CC O75190-2; I6L9F6: NEFL; NbExp=3; IntAct=EBI-12593112, EBI-10178578;
CC O75190-2; Q96FW1: OTUB1; NbExp=3; IntAct=EBI-12593112, EBI-1058491;
CC O75190-2; P30154-2: PPP2R1B; NbExp=3; IntAct=EBI-12593112, EBI-11058011;
CC O75190-2; Q96QF0-7: RAB3IP; NbExp=3; IntAct=EBI-12593112, EBI-11984839;
CC O75190-2; Q15293: RCN1; NbExp=3; IntAct=EBI-12593112, EBI-948278;
CC O75190-2; Q96EN9: REX1BD; NbExp=3; IntAct=EBI-12593112, EBI-745810;
CC O75190-2; Q9BY12-3: SCAPER; NbExp=3; IntAct=EBI-12593112, EBI-25837959;
CC O75190-2; Q96H20: SNF8; NbExp=3; IntAct=EBI-12593112, EBI-747719;
CC O75190-2; Q7Z6I5: SPATA12; NbExp=3; IntAct=EBI-12593112, EBI-10696971;
CC O75190-2; Q8IXS7: SRGAP3; NbExp=3; IntAct=EBI-12593112, EBI-18616594;
CC O75190-2; O75558: STX11; NbExp=3; IntAct=EBI-12593112, EBI-714135;
CC O75190-2; O15273: TCAP; NbExp=3; IntAct=EBI-12593112, EBI-954089;
CC O75190-2; Q8WTV1: THAP3; NbExp=3; IntAct=EBI-12593112, EBI-17438286;
CC O75190-2; Q12888: TP53BP1; NbExp=3; IntAct=EBI-12593112, EBI-396540;
CC O75190-2; Q99598: TSNAX; NbExp=3; IntAct=EBI-12593112, EBI-742638;
CC O75190-2; Q6PID6: TTC33; NbExp=3; IntAct=EBI-12593112, EBI-2555404;
CC O75190-2; Q9H270: VPS11; NbExp=3; IntAct=EBI-12593112, EBI-373380;
CC O75190-2; Q9BRX9: WDR83; NbExp=3; IntAct=EBI-12593112, EBI-7705033;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:10954706}. Nucleus {ECO:0000269|PubMed:10954706}.
CC Cytoplasm, myofibril, sarcomere, Z line {ECO:0000269|PubMed:22366786}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=A;
CC IsoId=O75190-1; Sequence=Displayed;
CC Name=B;
CC IsoId=O75190-2; Sequence=VSP_001289, VSP_001290;
CC Name=C; Synonyms=a;
CC IsoId=O75190-3; Sequence=VSP_026180;
CC Name=D;
CC IsoId=O75190-4; Sequence=VSP_053894;
CC -!- TISSUE SPECIFICITY: Widely expressed. Highest levels in testis and
CC brain, and lower levels in heart, spleen, intestine, ovary, placenta,
CC lung, kidney, pancreas, thymus, prostate, skeletal muscle, liver and
CC leukocytes. In testis, expressed in germ cells in the earlier stages of
CC differentiation pathway as well as in spermatids. In brain, expressed
CC at a higher level in hippocampus and thalamus and a lower level in
CC amygdala, substantia nigra, corpus callosum and caudate nucleus.
CC {ECO:0000269|PubMed:10319584, ECO:0000269|PubMed:11896048,
CC ECO:0000269|PubMed:22366786, ECO:0000269|PubMed:9915854}.
CC -!- DOMAIN: The antiaggregation activity of isoform B resides in the
CC serine-rich region and the C-terminus.
CC -!- DISEASE: Muscular dystrophy, limb-girdle, autosomal dominant 1 (LGMDD1)
CC [MIM:603511]: An autosomal dominant myopathy characterized by adult
CC onset of proximal muscle weakness, beginning in the hip girdle region
CC and later progressing to the shoulder girdle region.
CC {ECO:0000269|PubMed:22334415, ECO:0000269|PubMed:22366786}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry. There is evidence that LGMDD1 is caused by dysfunction of
CC isoform B (PubMed:22366786). {ECO:0000269|PubMed:22366786}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD16010.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAD93096.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF080569; AAD16010.1; ALT_FRAME; mRNA.
DR EMBL; AB015798; BAA88769.1; -; mRNA.
DR EMBL; AB015799; BAA88770.1; -; mRNA.
DR EMBL; AF060703; AAF21257.1; -; mRNA.
DR EMBL; AB014888; BAA32209.1; -; mRNA.
DR EMBL; AF075601; AAD43194.1; -; mRNA.
DR EMBL; CR533498; CAG38529.1; -; mRNA.
DR EMBL; AB209859; BAD93096.1; ALT_INIT; mRNA.
DR EMBL; AK223601; BAD97321.1; -; mRNA.
DR EMBL; AK291953; BAF84642.1; -; mRNA.
DR EMBL; AK293025; BAF85714.1; -; mRNA.
DR EMBL; AK297796; BAG60135.1; -; mRNA.
DR EMBL; AL136707; CAB66642.1; -; mRNA.
DR EMBL; AC006372; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC079306; AAS07392.1; -; Genomic_DNA.
DR EMBL; AC079306; AAS07393.1; -; Genomic_DNA.
DR EMBL; CH236954; EAL23923.1; -; Genomic_DNA.
DR EMBL; CH236954; EAL23924.1; -; Genomic_DNA.
DR EMBL; CH471149; EAX04570.1; -; Genomic_DNA.
DR EMBL; BC000177; AAH00177.1; -; mRNA.
DR EMBL; BC002446; AAH02446.1; -; mRNA.
DR CCDS; CCDS47755.1; -. [O75190-2]
DR CCDS; CCDS5946.1; -. [O75190-1]
DR RefSeq; NP_005485.1; NM_005494.2. [O75190-2]
DR RefSeq; NP_490647.1; NM_058246.3. [O75190-1]
DR PDB; 6U3R; NMR; -; A=1-127, A=184-231.
DR PDB; 6U3S; NMR; -; A=1-127, A=184-231.
DR PDB; 7JSQ; NMR; -; A=185-231.
DR PDB; 7QBY; NMR; -; A=185-231.
DR PDBsum; 6U3R; -.
DR PDBsum; 6U3S; -.
DR PDBsum; 7JSQ; -.
DR PDBsum; 7QBY; -.
DR AlphaFoldDB; O75190; -.
DR SMR; O75190; -.
DR BioGRID; 115360; 345.
DR IntAct; O75190; 163.
DR MINT; O75190; -.
DR STRING; 9606.ENSP00000262177; -.
DR ChEMBL; CHEMBL4295674; -.
DR iPTMnet; O75190; -.
DR PhosphoSitePlus; O75190; -.
DR SwissPalm; O75190; -.
DR BioMuta; DNAJB6; -.
DR EPD; O75190; -.
DR jPOST; O75190; -.
DR MassIVE; O75190; -.
DR MaxQB; O75190; -.
DR PaxDb; O75190; -.
DR PeptideAtlas; O75190; -.
DR PRIDE; O75190; -.
DR ProteomicsDB; 4676; -.
DR ProteomicsDB; 49860; -. [O75190-1]
DR ProteomicsDB; 49861; -. [O75190-2]
DR ProteomicsDB; 49862; -. [O75190-3]
DR TopDownProteomics; O75190-1; -. [O75190-1]
DR Antibodypedia; 3316; 330 antibodies from 31 providers.
DR DNASU; 10049; -.
DR Ensembl; ENST00000262177.9; ENSP00000262177.4; ENSG00000105993.15. [O75190-1]
DR Ensembl; ENST00000429029.6; ENSP00000397556.2; ENSG00000105993.15. [O75190-2]
DR GeneID; 10049; -.
DR KEGG; hsa:10049; -.
DR MANE-Select; ENST00000262177.9; ENSP00000262177.4; NM_058246.4; NP_490647.1.
DR UCSC; uc003wnj.4; human. [O75190-1]
DR CTD; 10049; -.
DR DisGeNET; 10049; -.
DR GeneCards; DNAJB6; -.
DR HGNC; HGNC:14888; DNAJB6.
DR HPA; ENSG00000105993; Low tissue specificity.
DR MalaCards; DNAJB6; -.
DR MIM; 603511; phenotype.
DR MIM; 611332; gene.
DR neXtProt; NX_O75190; -.
DR OpenTargets; ENSG00000105993; -.
DR Orphanet; 34516; DNAJB6-related limb-girdle muscular dystrophy D1.
DR PharmGKB; PA27418; -.
DR VEuPathDB; HostDB:ENSG00000105993; -.
DR eggNOG; KOG0714; Eukaryota.
DR GeneTree; ENSGT00940000154205; -.
DR InParanoid; O75190; -.
DR OMA; MFFGDST; -.
DR PhylomeDB; O75190; -.
DR TreeFam; TF105142; -.
DR PathwayCommons; O75190; -.
DR Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response.
DR SignaLink; O75190; -.
DR BioGRID-ORCS; 10049; 190 hits in 1090 CRISPR screens.
DR ChiTaRS; DNAJB6; human.
DR GeneWiki; DNAJB6; -.
DR GenomeRNAi; 10049; -.
DR Pharos; O75190; Tbio.
DR PRO; PR:O75190; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; O75190; protein.
DR Bgee; ENSG00000105993; Expressed in cortical plate and 186 other tissues.
DR ExpressionAtlas; O75190; baseline and differential.
DR Genevisible; O75190; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0030018; C:Z disc; IDA:UniProtKB.
DR GO; GO:0001671; F:ATPase activator activity; IDA:UniProtKB.
DR GO; GO:0051087; F:chaperone binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:Ensembl.
DR GO; GO:0031072; F:heat shock protein binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0044183; F:protein folding chaperone; IBA:GO_Central.
DR GO; GO:0051082; F:unfolded protein binding; IDA:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0061077; P:chaperone-mediated protein folding; IBA:GO_Central.
DR GO; GO:0060710; P:chorio-allantoic fusion; IEA:Ensembl.
DR GO; GO:0060717; P:chorion development; IEA:Ensembl.
DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl.
DR GO; GO:0045109; P:intermediate filament organization; IDA:UniProtKB.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0090084; P:negative regulation of inclusion body assembly; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IEA:Ensembl.
DR GO; GO:0006457; P:protein folding; IDA:UniProtKB.
DR GO; GO:0034504; P:protein localization to nucleus; IEA:Ensembl.
DR GO; GO:1900034; P:regulation of cellular response to heat; TAS:Reactome.
DR GO; GO:0032880; P:regulation of protein localization; IMP:ParkinsonsUK-UCL.
DR GO; GO:0060715; P:syncytiotrophoblast cell differentiation involved in labyrinthine layer development; IEA:Ensembl.
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; IPR036869; J_dom_sf.
DR Pfam; PF00226; DnaJ; 1.
DR PRINTS; PR00625; JDOMAIN.
DR SMART; SM00271; DnaJ; 1.
DR SUPFAM; SSF46565; SSF46565; 1.
DR PROSITE; PS00636; DNAJ_1; 1.
DR PROSITE; PS50076; DNAJ_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chaperone; Cytoplasm;
KW Direct protein sequencing; Disease variant; Limb-girdle muscular dystrophy;
KW Methylation; Nucleus; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.15"
FT CHAIN 2..326
FT /note="DnaJ homolog subfamily B member 6"
FT /id="PRO_0000071025"
FT DOMAIN 2..69
FT /note="J"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00286"
FT REGION 2..146
FT /note="Interaction with HSP70"
FT /evidence="ECO:0000269|PubMed:10954706"
FT REGION 119..242
FT /note="Interaction with KRT18"
FT /evidence="ECO:0000269|PubMed:10954706"
FT REGION 249..326
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 273..287
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 135
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:O54946"
FT MOD_RES 277
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..59
FT /note="MVDYYEVLGVQRHASPEDIKKAYRKLALKWHPDKNPENKEEAERKFKQVAEA
FT YEVLSDA -> MPHPRILKRP (in isoform D)"
FT /evidence="ECO:0000305"
FT /id="VSP_053894"
FT VAR_SEQ 232..241
FT /note="VADDDALAEE -> KEQLLRLDNK (in isoform B)"
FT /evidence="ECO:0000303|PubMed:10319584,
FT ECO:0000303|PubMed:11896048, ECO:0000303|PubMed:12974469,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005, ECO:0000303|PubMed:9915854,
FT ECO:0000303|Ref.4, ECO:0000303|Ref.6, ECO:0000303|Ref.7"
FT /id="VSP_001289"
FT VAR_SEQ 242..326
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000303|PubMed:10319584,
FT ECO:0000303|PubMed:11896048, ECO:0000303|PubMed:12974469,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005, ECO:0000303|PubMed:9915854,
FT ECO:0000303|Ref.4, ECO:0000303|Ref.6, ECO:0000303|Ref.7"
FT /id="VSP_001290"
FT VAR_SEQ 301..326
FT /note="LKEGGKRKKQKQREESKKKKSTKGNH -> VQREAAVEQAQSETSLGARGQR
FT GHK (in isoform C)"
FT /evidence="ECO:0000303|PubMed:12974469,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334,
FT ECO:0000303|Ref.9"
FT /id="VSP_026180"
FT VARIANT 89
FT /note="F -> I (in LGMDD1; the mutation results in
FT inefficient inhibition of protein aggregation by isoform B;
FT dbSNP:rs387907150)"
FT /evidence="ECO:0000269|PubMed:22366786"
FT /id="VAR_067833"
FT VARIANT 93
FT /note="F -> L (in LGMDD1; the mutation results in
FT inefficient inhibition of protein aggregation by isoform B;
FT dbSNP:rs387907046)"
FT /evidence="ECO:0000269|PubMed:22334415,
FT ECO:0000269|PubMed:22366786"
FT /id="VAR_067834"
FT VARIANT 96
FT /note="P -> L (found in a family with autosomal-dominantly
FT inherited distal-onset myopathy; significant loss of its
FT ability to suppress aggregation of polyglutamine-containing
FT proteins)"
FT /evidence="ECO:0000269|PubMed:28233300"
FT /id="VAR_079428"
FT VARIANT 96
FT /note="P -> R (in LGMDD1; dbSNP:rs387907047)"
FT /evidence="ECO:0000269|PubMed:22334415"
FT /id="VAR_067835"
FT CONFLICT 128
FT /note="G -> S (in Ref. 9; BAD97321)"
FT /evidence="ECO:0000305"
FT CONFLICT 303
FT /note="E -> G (in Ref. 8; BAF85714)"
FT /evidence="ECO:0000305"
FT HELIX 3..8
FT /evidence="ECO:0007829|PDB:6U3R"
FT HELIX 16..29
FT /evidence="ECO:0007829|PDB:6U3R"
FT TURN 32..34
FT /evidence="ECO:0007829|PDB:6U3R"
FT HELIX 39..56
FT /evidence="ECO:0007829|PDB:6U3R"
FT HELIX 59..68
FT /evidence="ECO:0007829|PDB:6U3R"
FT HELIX 75..79
FT /evidence="ECO:0007829|PDB:6U3R"
FT HELIX 96..103
FT /evidence="ECO:0007829|PDB:6U3R"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:6U3R"
FT TURN 113..115
FT /evidence="ECO:0007829|PDB:6U3R"
FT TURN 185..187
FT /evidence="ECO:0007829|PDB:6U3R"
FT STRAND 188..198
FT /evidence="ECO:0007829|PDB:6U3R"
FT STRAND 201..210
FT /evidence="ECO:0007829|PDB:6U3R"
FT STRAND 213..220
FT /evidence="ECO:0007829|PDB:6U3R"
FT STRAND 223..229
FT /evidence="ECO:0007829|PDB:6U3R"
SQ SEQUENCE 326 AA; 36087 MW; ECF1628BF7A524F3 CRC64;
MVDYYEVLGV QRHASPEDIK KAYRKLALKW HPDKNPENKE EAERKFKQVA EAYEVLSDAK
KRDIYDKYGK EGLNGGGGGG SHFDSPFEFG FTFRNPDDVF REFFGGRDPF SFDFFEDPFE
DFFGNRRGPR GSRSRGTGSF FSAFSGFPSF GSGFSSFDTG FTSFGSLGHG GLTSFSSTSF
GGSGMGNFKS ISTSTKMVNG RKITTKRIVE NGQERVEVEE DGQLKSLTIN GVADDDALAE
ERMRRGQNAL PAQPAGLRPP KPPRPASLLR HAPHCLSEEE GEQDRPRAPG PWDPLASAAG
LKEGGKRKKQ KQREESKKKK STKGNH
