DNJC3_BOVIN
ID DNJC3_BOVIN Reviewed; 504 AA.
AC Q27968; A0JN99;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 136.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=7511204; DOI=10.1128/mcb.14.4.2331-2342.1994;
RA Lee T.G., Tang N., Thompson S., Miller J., Katze M.G.;
RT "The 58,000-dalton cellular inhibitor of the interferon-induced double-
RT stranded RNA-activated protein kinase (PKR) is a member of the
RT tetratricopeptide repeat family of proteins.";
RL Mol. Cell. Biol. 14:2331-2342(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Placenta;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP SUBCELLULAR LOCATION.
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).
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 Co-chaperone of HSPA8/HSC70, it stimulates its ATPase activity. May
CC inhibit both the autophosphorylation of EIF2AK2/PKR and the ability of
CC EIF2AK2 to catalyze phosphorylation of the EIF2A (PubMed:7511204). May
CC inhibit EIF2AK3/PERK activity (By similarity).
CC {ECO:0000250|UniProtKB:Q91YW3, ECO:0000269|PubMed:7511204}.
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. Interacts
CC with EIF2AK3. Interacts with EIF2AK2. Forms a trimeric complex with
CC DNAJB1 and HSPA8. Interacts with THAP12. {ECO:0000250|UniProtKB:Q13217,
CC ECO:0000250|UniProtKB:Q91YW3}.
CC -!- INTERACTION:
CC Q27968; P19525: EIF2AK2; Xeno; NbExp=5; IntAct=EBI-640793, EBI-640775;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum {ECO:0000250}.
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.
CC {ECO:0000250}.
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DR EMBL; U04631; AAA17795.1; -; mRNA.
DR EMBL; BC126580; AAI26581.1; -; mRNA.
DR PIR; A56534; A56534.
DR RefSeq; NP_777181.1; NM_174756.3.
DR AlphaFoldDB; Q27968; -.
DR SMR; Q27968; -.
DR BioGRID; 159906; 2.
DR IntAct; Q27968; 1.
DR STRING; 9913.ENSBTAP00000016001; -.
DR PaxDb; Q27968; -.
DR PRIDE; Q27968; -.
DR GeneID; 286770; -.
DR KEGG; bta:286770; -.
DR CTD; 5611; -.
DR eggNOG; KOG0624; Eukaryota.
DR InParanoid; Q27968; -.
DR OrthoDB; 1106865at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISS:UniProtKB.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IDA:WormBase.
DR GO; GO:0070417; P:cellular response to cold; ISS:UniProtKB.
DR GO; GO:1903912; P:negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation; ISS:UniProtKB.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IDA:WormBase.
DR GO; GO:0036494; P:positive regulation of translation initiation in response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0006986; P:response to unfolded protein; IEA:UniProtKB-KW.
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; 8.
DR SUPFAM; SSF46565; SSF46565; 1.
DR SUPFAM; SSF48452; SSF48452; 1.
DR PROSITE; PS50076; DNAJ_2; 1.
DR PROSITE; PS50005; TPR; 8.
DR PROSITE; PS50293; TPR_REGION; 1.
PE 1: Evidence at protein level;
KW Chaperone; Disulfide bond; Endoplasmic reticulum; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; Signal; Stress response; TPR repeat;
KW Translation regulation; 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_0000071044"
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 189..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 CONFLICT 36
FT /note="D -> Y (in Ref. 2; AAI26581)"
FT /evidence="ECO:0000305"
FT CONFLICT 489
FT /note="S -> N (in Ref. 2; AAI26581)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 504 AA; 57704 MW; 2383C36862BD9E4C CRC64;
MVAPGSVTSR LGSVFPFLLV LVDLQYEGAE CGVNADVEKH LELGKKLLAA GQLADALSQF
HAAVDGDPDN YIAYYRRATV FLAMGKSKAA LPDLTKVIEL KMDFTAARLQ RGHLLLKQGK
LDEAEDDFKK VLKSNPSENE EKEAQSQLVK SDEMQRLRSQ ALDAFESSDF TAAITFLDKI
LEVCVWDAEL RELRAECFIK EGEPRKAISD LKASSKLKND NTEAFYKIST LYYELGDHEL
SLSEVRECLK LDQDHKRCFA HYKQVKKLNK LIESAEELIK EGRYTDAISK YESVMKTEPG
VHEYTIRSKE RICHCFSKDE KPVEAIRVCS EVLQVEPDNV NALKDRAEAY LIEEMYDEAI
QDYETAQEHN ENDQQIREGL EKAQRLLKQS QRRDYYKILG VKRNAKKQEI IKAYRKLALQ
WHPDNFQNEE EKKKAEKKFI DIAAAKEVLS DPEMRKKFDD GEDPLDAESQ QGGGGNPFHR
SWNSWQGFSP FSSGGPFRFK FHFN
