ID DNJC3_HUMAN Reviewed; 504 AA.
AC Q13217; Q86WT9; Q8N4N2;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 01-MAY-2013, entry version 116.
DE RecName: Full=DnaJ homolog subfamily C member 3;
DE AltName: Full=Endoplasmic reticulum DnaJ protein 6;
DE Short=ERdj6;
DE AltName: Full=Interferon-induced, double-stranded RNA-activated protein kinase inhibitor;
DE AltName: Full=Protein kinase inhibitor of 58 kDa;
DE Short=Protein kinase inhibitor p58;
DE Flags: Precursor;
GN Name=DNAJC3; Synonyms=P58IPK, PRKRI;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=8666242; DOI=10.1016/0378-1119(95)00883-7;
RA Korth M.J., Lyons C.N., Wambach M., Katze M.G.;
RT "Cloning, expression, and cellular localization of the oncogenic 58-
RT kDa inhibitor of the RNA-activated human and mouse protein kinase.";
RL Gene 170:181-188(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E.,
RA Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T.,
RA Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R.,
RA Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S.,
RA Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M.,
RA Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J.,
RA Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E.,
RA Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L.,
RA Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J.,
RA Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S.,
RA Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J.,
RA Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M.,
RA King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A.,
RA Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S.,
RA Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S.,
RA Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A.,
RA Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L.,
RA Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M.,
RA Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Leukocyte;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, AND INTERACTION WITH EIF2AK2.
RX PubMed=8576172; DOI=10.1074/jbc.271.3.1702;
RA Polyak S.J., Tang N., Wambach M., Barber G.N., Katze M.G.;
RT "The P58 cellular inhibitor complexes with the interferon-induced,
RT double-stranded RNA-dependent protein kinase, PKR, to regulate its
RT autophosphorylation and activity.";
RL J. Biol. Chem. 271:1702-1707(1996).
RN [6]
RP FUNCTION, INTERACTION WITH PRKRIR, AND INDUCTION.
RX PubMed=9447982;
RA Gale M.J. Jr., Blakely C.M., Hopkins D.A., Melville M.W., Wambach M.,
RA Romano P.R., Katze M.G.;
RT "Regulation of interferon-induced protein kinase PKR: modulation of
RT P58IPK inhibitory function by a novel protein, P52rIPK.";
RL Mol. Cell. Biol. 18:859-871(1998).
RN [7]
RP FUNCTION, INTERACTION WITH DNAJB1 AND HSPA8, AND INDUCTION.
RX PubMed=9920933; DOI=10.1074/jbc.274.6.3797;
RA Melville M.W., Tan S.-L., Wambach M., Song J., Morimoto R.I.,
RA Katze M.G.;
RT "The cellular inhibitor of the PKR protein kinase, P58(IPK), is an
RT influenza virus-activated co-chaperone that modulates heat shock
RT protein 70 activity.";
RL J. Biol. Chem. 274:3797-3803(1999).
RN [8]
RP FUNCTION, AND INDUCTION.
RX PubMed=12601012; DOI=10.1074/jbc.M212074200;
RA van Huizen R., Martindale J.L., Gorospe M., Holbrook N.J.;
RT "P58IPK, a novel endoplasmic reticulum stress-inducible protein and
RT potential negative regulator of eIF2alpha signaling.";
RL J. Biol. Chem. 278:15558-15564(2003).
RN [9]
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.,
RA Buerckstuemmer T., 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 [10]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 35-461, AND DISULFIDE BONDS.
RX PubMed=21799829; DOI=10.1371/journal.pone.0022337;
RA Svard M., Biterova E.I., Bourhis J.M., Guy J.E.;
RT "The crystal structure of the human co-chaperone P58(IPK).";
RL PLoS ONE 6:E22337-E22337(2011).
CC -!- FUNCTION: Involved in the unfolded protein response (UPR) during
CC ER stress. Co-chaperone of HSPA8/HSC70, it stimulates its ATPase
CC activity. May inhibit both the autophosphorylation of EIF2AK2/PKR
CC and the ability of EIF2AK2 to catalyze phosphorylation of the
CC EIF2A. May inhibit EIF2AK3/PERK activity.
CC -!- SUBUNIT: Interacts with EIF2AK3 (By similarity) and EIF2AK2. Forms
CC a trimeric complex with DNAJB1 and HSPA8. Interacts with
CC PRKRIR/P52RIPK.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum (By similarity).
CC -!- TISSUE SPECIFICITY: Widely expressed with high level in the
CC pancreas and testis. Also expressed in cell lines with different
CC levels.
CC -!- INDUCTION: Up-regulated during an endoplasmic reticulum stress via
CC ATF6. Activated in response to infection by influenza virus
CC through the dissociation of DNAJB1. Down-regulated by DNAJB1 and
CC PRKRIR/P52RIPK.
CC -!- DOMAIN: The J domain mediates interaction with HSPA8.
CC -!- DOMAIN: Binding to misfolded proteins is mediated by a hydrophobic
CC patch forming a large groove within the first two TPR repeats (By
CC similarity).
CC -!- SIMILARITY: Contains 1 J domain.
CC -!- SIMILARITY: Contains 9 TPR repeats.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/dnajc3/";
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DR EMBL; U28424; AAC50502.1; -; mRNA.
DR EMBL; AY795482; AAV40838.1; -; Genomic_DNA.
DR EMBL; AL138955; CAH70090.1; -; Genomic_DNA.
DR EMBL; BC047936; AAH47936.2; -; mRNA.
DR IPI; IPI00006713; -.
DR PIR; JC4775; JC4775.
DR RefSeq; NP_006251.1; NM_006260.4.
DR UniGene; Hs.59214; -.
DR PDB; 2Y4T; X-ray; 3.00 A; A/B/C=35-461.
DR PDB; 2Y4U; X-ray; 3.20 A; A=35-461.
DR PDBsum; 2Y4T; -.
DR PDBsum; 2Y4U; -.
DR ProteinModelPortal; Q13217; -.
DR IntAct; Q13217; 1.
DR STRING; 9606.ENSP00000365991; -.
DR PhosphoSite; Q13217; -.
DR DMDM; 73620807; -.
DR PaxDb; Q13217; -.
DR PeptideAtlas; Q13217; -.
DR PRIDE; Q13217; -.
DR Ensembl; ENST00000376795; ENSP00000365991; ENSG00000102580.
DR GeneID; 5611; -.
DR KEGG; hsa:5611; -.
DR UCSC; uc001vmq.3; human.
DR CTD; 5611; -.
DR GeneCards; GC13P096329; -.
DR HGNC; HGNC:9439; DNAJC3.
DR HPA; HPA039336; -.
DR HPA; HPA041326; -.
DR MIM; 601184; gene.
DR neXtProt; NX_Q13217; -.
DR PharmGKB; PA27420; -.
DR eggNOG; COG0484; -.
DR HOGENOM; HOG000193351; -.
DR HOVERGEN; HBG053820; -.
DR InParanoid; Q13217; -.
DR KO; K09523; -.
DR OMA; SIVEYTV; -.
DR OrthoDB; EOG44TP7Q; -.
DR PhylomeDB; Q13217; -.
DR Reactome; REACT_116125; Disease.
DR ChiTaRS; DNAJC3; human.
DR GenomeRNAi; 5611; -.
DR NextBio; 21810; -.
DR ArrayExpress; Q13217; -.
DR Bgee; Q13217; -.
DR CleanEx; HS_DNAJC3; -.
DR Genevestigator; Q13217; -.
DR GermOnline; ENSG00000102580; Homo sapiens.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0031205; C:endoplasmic reticulum Sec complex; IEA:Compara.
DR GO; GO:0004860; F:protein kinase inhibitor activity; TAS:ProtInc.
DR GO; GO:0006987; P:activation of signaling protein activity involved in unfolded protein response; TAS:Reactome.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0051603; P:proteolysis involved in cellular protein catabolic process; IEA:Compara.
DR Gene3D; 1.10.287.110; -; 1.
DR Gene3D; 1.25.40.10; -; 3.
DR InterPro; IPR001623; DnaJ_domain.
DR InterPro; IPR026901; DNAJC3.
DR InterPro; IPR001440; TPR-1.
DR InterPro; IPR013026; TPR-contain_dom.
DR InterPro; IPR011990; TPR-like_helical.
DR InterPro; IPR019734; TPR_repeat.
DR PANTHER; PTHR24078:SF1; PTHR24078:SF1; 1.
DR Pfam; PF00226; DnaJ; 1.
DR Pfam; PF00515; TPR_1; 2.
DR PRINTS; PR00625; JDOMAIN.
DR SMART; SM00271; DnaJ; 1.
DR SMART; SM00028; TPR; 7.
DR PROSITE; PS00636; DNAJ_1; FALSE_NEG.
DR PROSITE; PS50076; DNAJ_2; 1.
DR PROSITE; PS50005; TPR; 8.
DR PROSITE; PS50293; TPR_REGION; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antiviral defense; Chaperone; Complete proteome;
KW Disulfide bond; Endoplasmic reticulum; Reference proteome; Repeat;
KW Signal; TPR repeat; Unfolded protein response.
FT SIGNAL 1 31 Potential.
FT CHAIN 32 504 DnaJ homolog subfamily C member 3.
FT /FTId=PRO_0000071045.
FT REPEAT 37 70 TPR 1.
FT REPEAT 72 104 TPR 2.
FT REPEAT 105 138 TPR 3.
FT REPEAT 154 187 TPR 4.
FT REPEAT 189 221 TPR 5.
FT REPEAT 222 255 TPR 6.
FT REPEAT 268 301 TPR 7.
FT REPEAT 306 339 TPR 8.
FT REPEAT 340 373 TPR 9.
FT DOMAIN 394 462 J.
FT REGION 375 393 Flexible linker.
FT DISULFID 248 258
FT DISULFID 313 329
FT HELIX 35 49
FT HELIX 53 66
FT HELIX 71 83
FT HELIX 87 100
FT TURN 101 103
FT HELIX 105 117
FT HELIX 121 132
FT HELIX 138 167
FT HELIX 170 183
FT HELIX 188 200
FT HELIX 204 207
FT HELIX 208 218
FT HELIX 222 234
FT HELIX 238 251
FT HELIX 256 281
FT HELIX 284 297
FT HELIX 302 317
FT TURN 318 320
FT HELIX 322 335
FT HELIX 340 352
FT HELIX 356 367
FT STRAND 370 372
FT HELIX 374 391
FT HELIX 396 398
FT HELIX 409 420
FT HELIX 423 425
FT HELIX 429 448
FT HELIX 451 454
SQ SEQUENCE 504 AA; 57580 MW; E720A1E7F618B912 CRC64;
MVAPGSVTSR LGSVFPFLLV LVDLQYEGAE CGVNADVEKH LELGKKLLAA GQLADALSQF
HAAVDGDPDN YIAYYRRATV FLAMGKSKAA LPDLTKVIQL KMDFTAARLQ RGHLLLKQGK
LDEAEDDFKK VLKSNPSENE EKEAQSQLIK SDEMQRLRSQ ALNAFGSGDY TAAIAFLDKI
LEVCVWDAEL RELRAECFIK EGEPRKAISD LKAASKLKND NTEAFYKIST LYYQLGDHEL
SLSEVRECLK LDQDHKRCFA HYKQVKKLNK LIESAEELIR DGRYTDATSK YESVMKTEPS
IAEYTVRSKE RICHCFSKDE KPVEAIRVCS EVLQMEPDNV NALKDRAEAY LIEEMYDEAI
QDYETAQEHN ENDQQIREGL EKAQRLLKQS QKRDYYKILG VKRNAKKQEI IKAYRKLALQ
WHPDNFQNEE EKKKAEKKFI DIAAAKEVLS DPEMRKKFDD GEDPLDAESQ QGGGGNPFHR
SWNSWQGFNP FSSGGPFRFK FHFN
//
