DNJC3_MOUSE
ID DNJC3_MOUSE Reviewed; 504 AA.
AC Q91YW3; Q60873;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=DnaJ homolog subfamily C member 3;
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;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
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-kDa
RT inhibitor of the RNA-activated human and mouse protein kinase.";
RL Gene 170:181-188(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; TISSUE=Mammary tumor;
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 [3]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH EIF2AK3, AND INDUCTION.
RX PubMed=12446838; DOI=10.1073/pnas.252341799;
RA Yan W., Frank C.L., Korth M.J., Sopher B.L., Novoa I., Ron D., Katze M.G.;
RT "Control of PERK eIF2alpha kinase activity by the endoplasmic reticulum
RT stress-induced molecular chaperone P58IPK.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:15920-15925(2002).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION, AND INTERACTION WITH EIF2AK4.
RX PubMed=25329545; DOI=10.1042/bj20140852;
RA Roobol A., Roobol J., Bastide A., Knight J.R., Willis A.E., Smales C.M.;
RT "p58IPK is an inhibitor of the eIF2alpha kinase GCN2 and its localization
RT and expression underpin protein synthesis and ER processing capacity.";
RL Biochem. J. 465:213-225(2015).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.51 ANGSTROMS) OF 35-393, FUNCTION, AND MUTAGENESIS
RP OF LEU-48; TYR-71; TYR-75; PHE-104 AND TRP-186.
RX PubMed=20184891; DOI=10.1016/j.jmb.2010.02.028;
RA Tao J., Petrova K., Ron D., Sha B.;
RT "Crystal structure of P58(IPK) TPR fragment reveals the mechanism for its
RT molecular chaperone activity in UPR.";
RL J. Mol. Biol. 397:1307-1315(2010).
CC -!- FUNCTION: Involved in the unfolded protein response (UPR) during
CC endoplasmic reticulum (ER) stress. Acts as a negative regulator of the
CC EIF2AK4/GCN2 kinase activity by preventing the phosphorylation of eIF-
CC 2-alpha at 'Ser-52' and hence attenuating general protein synthesis
CC under ER stress, hypothermic and amino acid starving stress conditions
CC (PubMed:25329545). Co-chaperone of HSPA8/HSC70, it stimulates its
CC ATPase activity. May inhibit both the autophosphorylation of
CC EIF2AK2/PKR and the ability of EIF2AK2 to catalyze phosphorylation of
CC the EIF2A. May inhibit EIF2AK3/PERK activity (By similarity).
CC {ECO:0000250|UniProtKB:Q13217, ECO:0000250|UniProtKB:Q27968,
CC ECO:0000269|PubMed:12446838, ECO:0000269|PubMed:20184891,
CC ECO:0000269|PubMed:25329545}.
CC -!- SUBUNIT: Interacts with EIF2AK4/GCN2; this interaction occurs under
CC endoplasmic reticulum (ER) stress, hypothermic and amino acid starving
CC stress conditions and inhibits EIF2AK4/GCN2 kinase activity
CC (PubMed:25329545). Interacts with EIF2AK3 (PubMed:12446838). Interacts
CC with EIF2AK2. Forms a trimeric complex with DNAJB1 and HSPA8. Interacts
CC with THAP12 (By similarity). {ECO:0000250|UniProtKB:Q13217,
CC ECO:0000269|PubMed:12446838, ECO:0000269|PubMed:25329545}.
CC -!- INTERACTION:
CC Q91YW3; P11021: HSPA5; Xeno; NbExp=2; IntAct=EBI-8381770, EBI-354921;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:12446838}.
CC -!- TISSUE SPECIFICITY: Widely expressed, with high level in the liver.
CC {ECO:0000269|PubMed:8666242}.
CC -!- INDUCTION: Up-regulated during an endoplasmic reticulum stress.
CC {ECO:0000269|PubMed:12446838}.
CC -!- DOMAIN: The J domain mediates interaction with HSPA8. {ECO:0000250}.
CC -!- DOMAIN: Binding to misfolded proteins is mediated by a hydrophobic
CC patch forming a large groove within the first two TPR repeats.
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DR EMBL; U28423; AAC52592.1; -; mRNA.
DR EMBL; BC013766; AAH13766.1; -; mRNA.
DR CCDS; CCDS37012.1; -.
DR RefSeq; NP_032955.2; NM_008929.3.
DR PDB; 3IEG; X-ray; 2.51 A; A/B=35-393.
DR PDBsum; 3IEG; -.
DR AlphaFoldDB; Q91YW3; -.
DR SMR; Q91YW3; -.
DR BioGRID; 781938; 13.
DR IntAct; Q91YW3; 3.
DR MINT; Q91YW3; -.
DR STRING; 10090.ENSMUSP00000022734; -.
DR iPTMnet; Q91YW3; -.
DR PhosphoSitePlus; Q91YW3; -.
DR REPRODUCTION-2DPAGE; Q91YW3; -.
DR EPD; Q91YW3; -.
DR jPOST; Q91YW3; -.
DR MaxQB; Q91YW3; -.
DR PaxDb; Q91YW3; -.
DR PeptideAtlas; Q91YW3; -.
DR PRIDE; Q91YW3; -.
DR ProteomicsDB; 279561; -.
DR Antibodypedia; 24863; 170 antibodies from 29 providers.
DR DNASU; 100037258; -.
DR Ensembl; ENSMUST00000022734; ENSMUSP00000022734; ENSMUSG00000022136.
DR GeneID; 100037258; -.
DR KEGG; mmu:100037258; -.
DR UCSC; uc007uzd.2; mouse.
DR CTD; 5611; -.
DR MGI; MGI:107373; Dnajc3.
DR VEuPathDB; HostDB:ENSMUSG00000022136; -.
DR eggNOG; KOG0624; Eukaryota.
DR GeneTree; ENSGT00940000159806; -.
DR HOGENOM; CLU_015935_0_0_1; -.
DR InParanoid; Q91YW3; -.
DR OMA; PFAHFQH; -.
DR OrthoDB; 1106865at2759; -.
DR PhylomeDB; Q91YW3; -.
DR TreeFam; TF105162; -.
DR Reactome; R-MMU-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR Reactome; R-MMU-8957275; Post-translational protein phosphorylation.
DR BioGRID-ORCS; 100037258; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Dnajc3; mouse.
DR EvolutionaryTrace; Q91YW3; -.
DR PRO; PR:Q91YW3; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q91YW3; protein.
DR Bgee; ENSMUSG00000022136; Expressed in lacrimal gland and 254 other tissues.
DR ExpressionAtlas; Q91YW3; baseline and differential.
DR Genevisible; Q91YW3; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IDA:BHF-UCL.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; ISO:MGI.
DR GO; GO:0051087; F:chaperone binding; IDA:UniProtKB.
DR GO; GO:0051787; F:misfolded protein binding; IDA:BHF-UCL.
DR GO; GO:0019901; F:protein kinase binding; IDA:UniProtKB.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0070417; P:cellular response to cold; IDA:UniProtKB.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IC:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:1903912; P:negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation; IDA:UniProtKB.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; ISS:MGI.
DR GO; GO:0036494; P:positive regulation of translation initiation in response to endoplasmic reticulum stress; IDA:UniProtKB.
DR GO; GO:0034975; P:protein folding in endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IDA:BHF-UCL.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:UniProtKB.
DR CDD; cd06257; DnaJ; 1.
DR Gene3D; 1.10.287.110; -; 1.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR001623; DnaJ_domain.
DR InterPro; IPR036869; J_dom_sf.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR018704; TPR_21.
DR InterPro; IPR019734; TPR_repeat.
DR Pfam; PF00226; DnaJ; 1.
DR Pfam; PF09976; TPR_21; 1.
DR Pfam; PF13181; TPR_8; 1.
DR PRINTS; PR00625; JDOMAIN.
DR SMART; SM00271; DnaJ; 1.
DR SMART; SM00028; TPR; 7.
DR SUPFAM; SSF46565; SSF46565; 1.
DR SUPFAM; SSF48452; SSF48452; 3.
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; Chaperone; Disulfide bond; Endoplasmic reticulum;
KW Phosphoprotein; Reference proteome; Repeat; Repressor; Signal;
KW Stress response; TPR repeat; Translation regulation;
KW Unfolded protein response.
FT SIGNAL 1..31
FT /evidence="ECO:0000255"
FT CHAIN 32..504
FT /note="DnaJ homolog subfamily C member 3"
FT /id="PRO_0000071046"
FT REPEAT 37..70
FT /note="TPR 1"
FT REPEAT 72..104
FT /note="TPR 2"
FT REPEAT 105..138
FT /note="TPR 3"
FT REPEAT 154..187
FT /note="TPR 4"
FT REPEAT 188..221
FT /note="TPR 5"
FT REPEAT 222..255
FT /note="TPR 6"
FT REPEAT 268..301
FT /note="TPR 7"
FT REPEAT 306..339
FT /note="TPR 8"
FT REPEAT 340..373
FT /note="TPR 9"
FT DOMAIN 394..462
FT /note="J"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00286"
FT REGION 375..393
FT /note="Flexible linker"
FT /evidence="ECO:0000250"
FT REGION 451..481
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 274
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13217"
FT DISULFID 248..258
FT /evidence="ECO:0000250"
FT DISULFID 313..329
FT /evidence="ECO:0000250"
FT MUTAGEN 48
FT /note="L->D: Reduces binding affinity for misfolded
FT proteins by 40%."
FT /evidence="ECO:0000269|PubMed:20184891"
FT MUTAGEN 71
FT /note="Y->A: Reduces binding affinity for misfolded
FT proteins by 40%."
FT /evidence="ECO:0000269|PubMed:20184891"
FT MUTAGEN 75
FT /note="Y->H: Reduces binding affinity for misfolded
FT proteins by 40%."
FT /evidence="ECO:0000269|PubMed:20184891"
FT MUTAGEN 104
FT /note="F->A: Reduces binding affinity for misfolded
FT proteins by 40%."
FT /evidence="ECO:0000269|PubMed:20184891"
FT MUTAGEN 186
FT /note="W->A: Doesn't affect binding of misfolded proteins."
FT /evidence="ECO:0000269|PubMed:20184891"
FT CONFLICT 89..91
FT /note="AAL -> RRV (in Ref. 1; AAC52592)"
FT /evidence="ECO:0000305"
FT CONFLICT 134
FT /note="S -> C (in Ref. 1; AAC52592)"
FT /evidence="ECO:0000305"
FT CONFLICT 405
FT /note="A -> T (in Ref. 1; AAC52592)"
FT /evidence="ECO:0000305"
FT HELIX 36..49
FT /evidence="ECO:0007829|PDB:3IEG"
FT HELIX 53..66
FT /evidence="ECO:0007829|PDB:3IEG"
FT HELIX 71..84
FT /evidence="ECO:0007829|PDB:3IEG"
FT HELIX 87..100
FT /evidence="ECO:0007829|PDB:3IEG"
FT HELIX 105..118
FT /evidence="ECO:0007829|PDB:3IEG"
FT HELIX 121..132
FT /evidence="ECO:0007829|PDB:3IEG"
FT HELIX 138..166
FT /evidence="ECO:0007829|PDB:3IEG"
FT HELIX 170..183
FT /evidence="ECO:0007829|PDB:3IEG"
FT HELIX 188..200
FT /evidence="ECO:0007829|PDB:3IEG"
FT HELIX 204..215
FT /evidence="ECO:0007829|PDB:3IEG"
FT HELIX 222..235
FT /evidence="ECO:0007829|PDB:3IEG"
FT HELIX 238..251
FT /evidence="ECO:0007829|PDB:3IEG"
FT HELIX 256..280
FT /evidence="ECO:0007829|PDB:3IEG"
FT HELIX 284..297
FT /evidence="ECO:0007829|PDB:3IEG"
FT HELIX 302..318
FT /evidence="ECO:0007829|PDB:3IEG"
FT HELIX 322..335
FT /evidence="ECO:0007829|PDB:3IEG"
FT HELIX 340..352
FT /evidence="ECO:0007829|PDB:3IEG"
FT HELIX 356..367
FT /evidence="ECO:0007829|PDB:3IEG"
FT HELIX 374..391
FT /evidence="ECO:0007829|PDB:3IEG"
SQ SEQUENCE 504 AA; 57464 MW; 510C27782C6EDF66 CRC64;
MVAPGSVGSR LGAVFPFLLV LVDLQYEGAE CGVNADVEKH LELGKKLLAA GQLADALSQF
HAAVDGDPDN YIAYYRRATV FLAMGKSKAA LPDLTKVIAL KMDFTAARLQ RGHLLLKQGK
LDEAEDDFKK VLKSNPSEQE EKEAESQLVK ADEMQRLRSQ ALDAFDGADY TAAITFLDKI
LEVCVWDAEL RELRAECFIK EGEPRKAISD LKAASKLKSD NTEAFYKIST LYYQLGDHEL
SLSEVRECLK LDQDHKRCFA HYKQVKKLNK LIESAEELIR DGRYTDATSK YESVMKTEPS
VAEYTVRSKE RICHCFSKDE KPVEAIRICS EVLQMEPDNV NALKDRAEAY LIEEMYDEAI
QDYEAAQEHN ENDQQIREGL EKAQRLLKQS QKRDYYKILG VKRNAKKQEI IKAYRKLALQ
WHPDNFQNEE EKKKAEKKFI DIAAAKEVLS DPEMRKKFDD GEDPLDAESQ QGGGGNPFHR
SWNSWQGFNP FSSGGPFRFK FHFN
