DNJC5_HUMAN
ID DNJC5_HUMAN Reviewed; 198 AA.
AC Q9H3Z4; A8K0M0; B3KY68; E1P5G8; Q9H3Z5; Q9H7H2;
DT 14-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=DnaJ homolog subfamily C member 5 {ECO:0000305};
DE AltName: Full=Ceroid-lipofuscinosis neuronal protein 4 {ECO:0000305};
DE AltName: Full=Cysteine string protein {ECO:0000303|PubMed:8764987};
DE Short=CSP {ECO:0000303|PubMed:8764987};
GN Name=DNAJC5 {ECO:0000312|HGNC:HGNC:16235};
GN Synonyms=CLN4 {ECO:0000312|HGNC:HGNC:16235};
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] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RX PubMed=8764987; DOI=10.1016/0014-5793(96)00750-8;
RA Coppola T., Gundersen C.;
RT "Widespread expression of human cysteine string proteins.";
RL FEBS Lett. 391:269-272(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Cerebellum, and Hippocampus;
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=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Blood;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 76-198.
RC TISSUE=Spleen;
RX PubMed=11214971; DOI=10.1093/dnares/7.6.357;
RA Hattori A., Okumura K., Nagase T., Kikuno R., Hirosawa M., Ohara O.;
RT "Characterization of long cDNA clones from human adult spleen.";
RL DNA Res. 7:357-366(2000).
RN [7]
RP MUTAGENESIS OF SER-10.
RX PubMed=11604405; DOI=10.1074/jbc.m108186200;
RA Evans G.J., Wilkinson M.C., Graham M.E., Turner K.M., Chamberlain L.H.,
RA Burgoyne R.D., Morgan A.;
RT "Phosphorylation of cysteine string protein by protein kinase A.
RT Implications for the modulation of exocytosis.";
RL J. Biol. Chem. 276:47877-47885(2001).
RN [8]
RP PHOSPHORYLATION AT SER-10.
RC TISSUE=Pituitary;
RX PubMed=14997482; DOI=10.1002/pmic.200300584;
RA Giorgianni F., Beranova-Giorgianni S., Desiderio D.M.;
RT "Identification and characterization of phosphorylated proteins in the
RT human pituitary.";
RL Proteomics 4:587-598(2004).
RN [9]
RP IDENTIFICATION BY 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 [10]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J.,
RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S.,
RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells
RT and high confident phosphopeptide identification by cross-validation of
RT MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10 AND SER-15, 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 [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-56, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-8 AND SER-10, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
RP SUBCELLULAR LOCATION, VARIANTS CLN4B ARG-115 AND LEU-116 DEL, AND
RP CHARACTERIZATION OF VARIANTS CLN4B ARG-115 AND LEU-116 DEL.
RX PubMed=21820099; DOI=10.1016/j.ajhg.2011.07.003;
RA Noskova L., Stranecky V., Hartmannova H., Pristoupilova A., Baresova V.,
RA Ivanek R., Hulkova H., Jahnova H., van der Zee J., Staropoli J.F.,
RA Sims K.B., Tyynela J., Van Broeckhoven C., Nijssen P.C., Mole S.E.,
RA Elleder M., Kmoch S.;
RT "Mutations in DNAJC5, encoding cysteine-string protein alpha, cause
RT autosomal-dominant adult-onset neuronal ceroid lipofuscinosis.";
RL Am. J. Hum. Genet. 89:241-252(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-8 AND SER-10, AND
RP IDENTIFICATION BY 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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10; SER-12; SER-15 AND
RP TYR-17, AND IDENTIFICATION BY 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 [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [23]
RP REVIEW.
RX PubMed=25800794; DOI=10.1016/j.semcdb.2015.03.008;
RA Burgoyne R.D., Morgan A.;
RT "Cysteine string protein (CSP) and its role in preventing
RT neurodegeneration.";
RL Semin. Cell Dev. Biol. 40:153-159(2015).
RN [24]
RP INTERACTION WITH ZDHHC17.
RX PubMed=28882895; DOI=10.1074/jbc.m117.799650;
RA Lemonidis K., MacLeod R., Baillie G.S., Chamberlain L.H.;
RT "Peptide array based screening reveals a large number of proteins
RT interacting with the ankyrin repeat domain of the zDHHC17 S-
RT acyltransferase.";
RL J. Biol. Chem. 292:17190-17202(2017).
RN [25]
RP STRUCTURE BY NMR OF 1-100 IN PHOSPHORYLATED AND UNPHOSPHORYLATED STATES,
RP SUBUNIT, MUTAGENESIS OF 113-CYS--CYS-136, AND PHOSPHORYLATION AT SER-10.
RX PubMed=27452402; DOI=10.1016/j.str.2016.06.009;
RA Patel P., Prescott G.R., Burgoyne R.D., Lian L.Y., Morgan A.;
RT "Phosphorylation of Cysteine String Protein triggers a major conformational
RT switch.";
RL Structure 24:1380-1386(2016).
RN [26]
RP VARIANT CLN4B ARG-115.
RX PubMed=22073189; DOI=10.1371/journal.pone.0026741;
RA Benitez B.A., Alvarado D., Cai Y., Mayo K., Chakraverty S., Norton J.,
RA Morris J.C., Sands M.S., Goate A., Cruchaga C.;
RT "Exome-sequencing confirms DNAJC5 mutations as cause of adult neuronal
RT ceroid-lipofuscinosis.";
RL PLoS ONE 6:E26741-E26741(2011).
RN [27]
RP CHARACTERIZATION OF VARIANTS CLN4B ARG-115 AND LEU-116 DEL.
RX PubMed=22902780; DOI=10.1074/jbc.m112.389098;
RA Greaves J., Lemonidis K., Gorleku O.A., Cruchaga C., Grefen C.,
RA Chamberlain L.H.;
RT "Palmitoylation-induced aggregation of cysteine-string protein mutants that
RT cause neuronal ceroid lipofuscinosis.";
RL J. Biol. Chem. 287:37330-37339(2012).
RN [28]
RP VARIANTS CLN4B ARG-115 AND LEU-116 DEL.
RX PubMed=22235333; DOI=10.1371/journal.pone.0029729;
RA Velinov M., Dolzhanskaya N., Gonzalez M., Powell E., Konidari I., Hulme W.,
RA Staropoli J.F., Xin W., Wen G.Y., Barone R., Coppel S.H., Sims K.,
RA Brown W.T., Zuchner S.;
RT "Mutations in the gene DNAJC5 cause autosomal dominant Kufs disease in a
RT proportion of cases: study of the Parry family and 8 other families.";
RL PLoS ONE 7:E29729-E29729(2012).
RN [29]
RP VARIANTS CLN4B ARG-115 AND LEU-116 DEL.
RX PubMed=22978711; DOI=10.1111/cge.12020;
RA Cadieux-Dion M., Andermann E., Lachance-Touchette P., Ansorge O.,
RA Meloche C., Barnabe A., Kuzniecky R.I., Andermann F., Faught E.,
RA Leonberg S., Damiano J.A., Berkovic S.F., Rouleau G.A., Cossette P.;
RT "Recurrent mutations in DNAJC5 cause autosomal dominant Kufs disease.";
RL Clin. Genet. 83:571-575(2013).
CC -!- FUNCTION: Acts as a general chaperone in regulated exocytosis (By
CC similarity). Acts as a co-chaperone for the SNARE protein SNAP-25 (By
CC similarity). Involved in the calcium-mediated control of a late stage
CC of exocytosis (By similarity). May have an important role in
CC presynaptic function. May be involved in calcium-dependent
CC neurotransmitter release at nerve endings (By similarity).
CC {ECO:0000250|UniProtKB:P60904, ECO:0000250|UniProtKB:Q29455}.
CC -!- SUBUNIT: Oligomers (PubMed:27452402). Homodimer (By similarity).
CC Interacts with the chaperone complex consisting of HSC70 and SGTA (By
CC similarity). Interacts with ZDHHC13 (via ANK repeats) (By similarity).
CC Interacts with ZDHHC17 (via ANK repeats) (PubMed:28882895). Interacts
CC with SYT1, SYT5 and SYT7, and with SYT9, forming a complex with SNAP25
CC (By similarity). {ECO:0000250|UniProtKB:P60904,
CC ECO:0000269|PubMed:27452402, ECO:0000269|PubMed:28882895}.
CC -!- INTERACTION:
CC Q9H3Z4; Q8IUH5: ZDHHC17; NbExp=5; IntAct=EBI-4324577, EBI-524753;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q29455}. Membrane
CC {ECO:0000250|UniProtKB:Q29455}; Lipid-anchor
CC {ECO:0000250|UniProtKB:Q29455}. Cytoplasmic vesicle, secretory vesicle,
CC chromaffin granule membrane {ECO:0000250|UniProtKB:Q29455}. Melanosome
CC {ECO:0000269|PubMed:17081065}. Cell membrane
CC {ECO:0000269|PubMed:21820099}. Note=The association with membranes is
CC regulated by palmitoylation (By similarity). Identified by mass
CC spectrometry in melanosome fractions from stage I to stage IV
CC (PubMed:17081065). {ECO:0000250|UniProtKB:Q29455,
CC ECO:0000269|PubMed:17081065}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H3Z4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H3Z4-2; Sequence=VSP_001292;
CC -!- TISSUE SPECIFICITY: Expressed in pancreas, kidney, skeletal muscle,
CC liver, lung, placenta, brain and heart. {ECO:0000269|PubMed:8764987}.
CC -!- PTM: Ser-10 phosphorylation induces an order-to-disorder transition
CC triggering the interaction with Lys-58 (PubMed:27452402). This
CC conformational switch modulates DNAJC5's cellular functions by reducing
CC binding to syntaxin and synaptogamin without altering HSC70
CC interactions (PubMed:27452402). {ECO:0000269|PubMed:27452402}.
CC -!- PTM: Palmitoylated. Could be palmitoylated by DHHC3, DHHC7, DHHC15 and
CC DHHC17. Palmitoylation occurs probably in the cysteine-rich domain and
CC regulates DNAJC5 membrane attachment. {ECO:0000250|UniProtKB:Q29455}.
CC -!- DISEASE: Ceroid lipofuscinosis, neuronal, 4B (Kufs type), autosomal
CC dominant (CLN4B) [MIM:162350]: An adult-onset neuronal ceroid
CC lipofuscinosis. Neuronal ceroid lipofuscinoses are progressive
CC neurodegenerative, lysosomal storage diseases characterized by
CC intracellular accumulation of autofluorescent liposomal material, and
CC clinically by seizures, dementia, visual loss, and/or cerebral atrophy.
CC CLN4B has no visual involvement and is characterized by seizures and
CC other neurologic symptoms. {ECO:0000269|PubMed:21820099,
CC ECO:0000269|PubMed:22073189, ECO:0000269|PubMed:22235333,
CC ECO:0000269|PubMed:22902780, ECO:0000269|PubMed:22978711}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: Upon phosphorylation, Ser-10 interacts with Lys-58, a
CC highly conserved residue in DnaJ proteins that is also a ubiquitination
CC site in DNAJC5. {ECO:0000305|PubMed:27452402}.
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; AL118506; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW75191.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW75192.1; -; Genomic_DNA.
DR EMBL; BC053642; AAH53642.1; -; mRNA.
DR EMBL; AK024508; BAB15798.1; -; mRNA.
DR EMBL; AK128776; BAG54730.1; -; mRNA.
DR EMBL; AK289585; BAF82274.1; -; mRNA.
DR CCDS; CCDS13546.1; -. [Q9H3Z4-1]
DR PIR; S70515; S70515.
DR RefSeq; NP_079495.1; NM_025219.2. [Q9H3Z4-1]
DR RefSeq; XP_011527350.1; XM_011529048.2. [Q9H3Z4-1]
DR RefSeq; XP_011527351.1; XM_011529049.1. [Q9H3Z4-1]
DR PDB; 2N04; NMR; -; A=1-100.
DR PDB; 2N05; NMR; -; A=1-100.
DR PDBsum; 2N04; -.
DR PDBsum; 2N05; -.
DR AlphaFoldDB; Q9H3Z4; -.
DR SMR; Q9H3Z4; -.
DR BioGRID; 123242; 360.
DR IntAct; Q9H3Z4; 63.
DR STRING; 9606.ENSP00000354111; -.
DR iPTMnet; Q9H3Z4; -.
DR PhosphoSitePlus; Q9H3Z4; -.
DR SwissPalm; Q9H3Z4; -.
DR BioMuta; DNAJC5; -.
DR DMDM; 15213953; -.
DR EPD; Q9H3Z4; -.
DR jPOST; Q9H3Z4; -.
DR MassIVE; Q9H3Z4; -.
DR MaxQB; Q9H3Z4; -.
DR PaxDb; Q9H3Z4; -.
DR PeptideAtlas; Q9H3Z4; -.
DR PRIDE; Q9H3Z4; -.
DR ProteomicsDB; 80772; -. [Q9H3Z4-1]
DR ProteomicsDB; 80773; -. [Q9H3Z4-2]
DR Antibodypedia; 2284; 258 antibodies from 33 providers.
DR DNASU; 80331; -.
DR Ensembl; ENST00000360864.9; ENSP00000354111.4; ENSG00000101152.11. [Q9H3Z4-1]
DR Ensembl; ENST00000470551.1; ENSP00000434744.1; ENSG00000101152.11. [Q9H3Z4-2]
DR GeneID; 80331; -.
DR KEGG; hsa:80331; -.
DR MANE-Select; ENST00000360864.9; ENSP00000354111.4; NM_025219.3; NP_079495.1.
DR UCSC; uc002yhf.4; human. [Q9H3Z4-1]
DR CTD; 80331; -.
DR DisGeNET; 80331; -.
DR GeneCards; DNAJC5; -.
DR HGNC; HGNC:16235; DNAJC5.
DR HPA; ENSG00000101152; Low tissue specificity.
DR MalaCards; DNAJC5; -.
DR MIM; 162350; phenotype.
DR MIM; 611203; gene.
DR neXtProt; NX_Q9H3Z4; -.
DR OpenTargets; ENSG00000101152; -.
DR Orphanet; 228343; CLN4B disease.
DR PharmGKB; PA27422; -.
DR VEuPathDB; HostDB:ENSG00000101152; -.
DR eggNOG; KOG0716; Eukaryota.
DR GeneTree; ENSGT00940000155597; -.
DR HOGENOM; CLU_017633_14_1_1; -.
DR InParanoid; Q9H3Z4; -.
DR OMA; CKPRPRD; -.
DR PhylomeDB; Q9H3Z4; -.
DR TreeFam; TF105164; -.
DR PathwayCommons; Q9H3Z4; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-888590; GABA synthesis, release, reuptake and degradation.
DR Reactome; R-HSA-9662360; Sensory processing of sound by inner hair cells of the cochlea.
DR SignaLink; Q9H3Z4; -.
DR SIGNOR; Q9H3Z4; -.
DR BioGRID-ORCS; 80331; 18 hits in 1075 CRISPR screens.
DR ChiTaRS; DNAJC5; human.
DR GeneWiki; DNAJC5; -.
DR GenomeRNAi; 80331; -.
DR Pharos; Q9H3Z4; Tbio.
DR PRO; PR:Q9H3Z4; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9H3Z4; protein.
DR Bgee; ENSG00000101152; Expressed in cardiac muscle of right atrium and 175 other tissues.
DR Genevisible; Q9H3Z4; HS.
DR GO; GO:0031225; C:anchored component of membrane; ISS:UniProtKB.
DR GO; GO:0098993; C:anchored component of synaptic vesicle membrane; IEA:Ensembl.
DR GO; GO:0035577; C:azurophil granule membrane; TAS:Reactome.
DR GO; GO:0042584; C:chromaffin granule membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0061202; C:clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane; TAS:Reactome.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; HDA:UniProtKB.
DR GO; GO:0031594; C:neuromuscular junction; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0098793; C:presynapse; IBA:GO_Central.
DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome.
DR GO; GO:0043008; F:ATP-dependent protein binding; IEA:Ensembl.
DR GO; GO:0061077; P:chaperone-mediated protein folding; IBA:GO_Central.
DR GO; GO:0006887; P:exocytosis; NAS:ParkinsonsUK-UCL.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0045055; P:regulated exocytosis; TAS:ParkinsonsUK-UCL.
DR GO; GO:0098693; P:regulation of synaptic vesicle cycle; IBA:GO_Central.
DR GO; GO:0016079; P:synaptic vesicle exocytosis; TAS:ParkinsonsUK-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; 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; Acetylation; Alternative splicing; Cell membrane; Chaperone;
KW Cytoplasm; Cytoplasmic vesicle; Disease variant; Lipoprotein; Membrane;
KW Neurodegeneration; Neuronal ceroid lipofuscinosis; Palmitate;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..198
FT /note="DnaJ homolog subfamily C member 5"
FT /id="PRO_0000071052"
FT DOMAIN 13..82
FT /note="J"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00286"
FT MOD_RES 8
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:14997482,
FT ECO:0000269|PubMed:27452402, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 12
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 17
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 56
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 151
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P60904"
FT VAR_SEQ 165..198
FT /note="EATDTPIVIQPASATETTQLTADSHPSYHTDGFN -> GGH (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_001292"
FT VARIANT 115
FT /note="L -> R (in CLN4B; results in near absence of
FT palmitoylated monomeric forms of the protein and formation
FT of high molecular mass aggregates with diffuse
FT intracellular localization; dbSNP:rs387907043)"
FT /evidence="ECO:0000269|PubMed:21820099,
FT ECO:0000269|PubMed:22073189, ECO:0000269|PubMed:22235333,
FT ECO:0000269|PubMed:22902780, ECO:0000269|PubMed:22978711"
FT /id="VAR_066555"
FT VARIANT 116
FT /note="Missing (in CLN4B; results in near absence of
FT palmitoylated monomeric forms of the protein and formation
FT of high molecular mass aggregates with diffuse
FT intracellular localization; dbSNP:rs587776892)"
FT /evidence="ECO:0000269|PubMed:21820099,
FT ECO:0000269|PubMed:22235333, ECO:0000269|PubMed:22902780,
FT ECO:0000269|PubMed:22978711"
FT /id="VAR_066556"
FT MUTAGEN 10
FT /note="S->A,E: Increased syntaxin binding."
FT /evidence="ECO:0000269|PubMed:11604405"
FT MUTAGEN 113..136
FT /note="CGLLTCCYCCCCLCCCFNCCCGKC->SGLLTSSYSSSSLSSSFNSSSGKS:
FT No effect on oligomerization."
FT /evidence="ECO:0000269|PubMed:27452402"
FT HELIX 7..10
FT /evidence="ECO:0007829|PDB:2N05"
FT HELIX 13..15
FT /evidence="ECO:0007829|PDB:2N04"
FT HELIX 16..20
FT /evidence="ECO:0007829|PDB:2N04"
FT STRAND 23..26
FT /evidence="ECO:0007829|PDB:2N04"
FT HELIX 30..42
FT /evidence="ECO:0007829|PDB:2N04"
FT TURN 44..46
FT /evidence="ECO:0007829|PDB:2N04"
FT HELIX 51..66
FT /evidence="ECO:0007829|PDB:2N04"
FT HELIX 70..76
FT /evidence="ECO:0007829|PDB:2N04"
FT HELIX 81..87
FT /evidence="ECO:0007829|PDB:2N04"
FT TURN 88..90
FT /evidence="ECO:0007829|PDB:2N04"
FT TURN 92..98
FT /evidence="ECO:0007829|PDB:2N04"
SQ SEQUENCE 198 AA; 22149 MW; A3F89270EBAD8A25 CRC64;
MADQRQRSLS TSGESLYHVL GLDKNATSDD IKKSYRKLAL KYHPDKNPDN PEAADKFKEI
NNAHAILTDA TKRNIYDKYG SLGLYVAEQF GEENVNTYFV LSSWWAKALF VFCGLLTCCY
CCCCLCCCFN CCCGKCKPKA PEGEETEFYV SPEDLEAQLQ SDEREATDTP IVIQPASATE
TTQLTADSHP SYHTDGFN
