PRKRA_RAT
ID PRKRA_RAT Reviewed; 313 AA.
AC Q4V8C7;
DT 21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Interferon-inducible double-stranded RNA-dependent protein kinase activator A;
DE AltName: Full=Protein activator of the interferon-induced protein kinase;
DE AltName: Full=Protein kinase, interferon-inducible double-stranded RNA-dependent activator;
GN Name=Prkra;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16396499; DOI=10.1021/pr0503073;
RA Moser K., White F.M.;
RT "Phosphoproteomic analysis of rat liver by high capacity IMAC and LC-
RT MS/MS.";
RL J. Proteome Res. 5:98-104(2006).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18 AND SER-167, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Activates EIF2AK2/PKR in the absence of double-stranded RNA
CC (dsRNA), leading to phosphorylation of EIF2S1/EFI2-alpha and inhibition
CC of translation and induction of apoptosis. Required for siRNA
CC production by DICER1 and for subsequent siRNA-mediated post-
CC transcriptional gene silencing. Does not seem to be required for
CC processing of pre-miRNA to miRNA by DICER1. Promotes UBC9-p53/TP53
CC association, sumoylation and phosphorylation of p53/TP53 at 'Lys-386'
CC at 'Ser-392' respectively and enhances its activity in a EIF2AK2/PKR-
CC dependent manner (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Interacts with EIF2AK2/PKR through its DRBM
CC domains. Interacts with DICER1, AGO2 and TARBP2. Also able to interact
CC with dsRNA (By similarity). Interacts with UBC9 (By similarity). Forms
CC a complex with UBC9 and p53/TP53 (By similarity). Interacts with DUS2L
CC (via DRBM domain) (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region {ECO:0000250}.
CC Cytoplasm {ECO:0000250}.
CC -!- DOMAIN: Self-association may occur via interactions between DRBM
CC domains as follows: DRBM 1/DRBM 1, DRBM 1/DRBM 2, DRBM 2/DRBM 2 or DRBM
CC 3/DRBM3. {ECO:0000250}.
CC -!- PTM: Phosphorylated at Ser-246 in unstressed cells and at Ser-287 in
CC stressed cells. Phosphorylation at Ser-246 appears to be a prerequisite
CC for subsequent phosphorylation at Ser-287. Phosphorylation at Ser-246
CC and Ser-287 are necessary for activation of EIF2AK2/PKR under
CC conditions of stress (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the PRKRA family. {ECO:0000305}.
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DR EMBL; BC097446; AAH97446.1; -; mRNA.
DR RefSeq; NP_001019951.1; NM_001024780.1.
DR AlphaFoldDB; Q4V8C7; -.
DR SMR; Q4V8C7; -.
DR STRING; 10116.ENSRNOP00000015624; -.
DR iPTMnet; Q4V8C7; -.
DR PhosphoSitePlus; Q4V8C7; -.
DR jPOST; Q4V8C7; -.
DR PaxDb; Q4V8C7; -.
DR PRIDE; Q4V8C7; -.
DR GeneID; 311130; -.
DR KEGG; rno:311130; -.
DR UCSC; RGD:1306707; rat.
DR CTD; 8575; -.
DR RGD; 1306707; Prkra.
DR eggNOG; KOG3732; Eukaryota.
DR InParanoid; Q4V8C7; -.
DR OrthoDB; 1093169at2759; -.
DR PhylomeDB; Q4V8C7; -.
DR Reactome; R-RNO-203927; MicroRNA (miRNA) biogenesis.
DR Reactome; R-RNO-426486; Small interfering RNA (siRNA) biogenesis.
DR PRO; PR:Q4V8C7; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016442; C:RISC complex; IBA:GO_Central.
DR GO; GO:0070578; C:RISC-loading complex; ISO:RGD.
DR GO; GO:0003725; F:double-stranded RNA binding; ISO:RGD.
DR GO; GO:0008047; F:enzyme activator activity; IEA:InterPro.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0070883; F:pre-miRNA binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; IPI:RGD.
DR GO; GO:0035197; F:siRNA binding; IBA:GO_Central.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISO:RGD.
DR GO; GO:0043583; P:ear development; ISO:RGD.
DR GO; GO:0042474; P:middle ear morphogenesis; ISO:RGD.
DR GO; GO:0035196; P:miRNA processing; ISO:RGD.
DR GO; GO:0042473; P:outer ear morphogenesis; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:RGD.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0031054; P:pre-miRNA processing; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
DR GO; GO:0050821; P:protein stabilization; ISO:RGD.
DR GO; GO:0070920; P:regulation of production of small RNA involved in gene silencing by RNA; IBA:GO_Central.
DR GO; GO:0070922; P:RISC complex assembly; ISO:RGD.
DR GO; GO:0030422; P:siRNA processing; ISS:UniProtKB.
DR GO; GO:0048705; P:skeletal system morphogenesis; ISO:RGD.
DR CDD; cd19889; DSRM_PRKRA_rpt1; 1.
DR CDD; cd19891; DSRM_PRKRA_rpt2; 1.
DR CDD; cd19892; DSRM_PRKRA_rpt3; 1.
DR InterPro; IPR014720; dsRBD_dom.
DR InterPro; IPR033363; PRKRA.
DR InterPro; IPR044465; PRKRA_DSRM_1.
DR InterPro; IPR044466; PRKRA_DSRM_2.
DR InterPro; IPR044467; PRKRA_DSRM_3.
DR InterPro; IPR032478; Staufen_C.
DR PANTHER; PTHR46205:SF2; PTHR46205:SF2; 1.
DR Pfam; PF00035; dsrm; 2.
DR Pfam; PF16482; Staufen_C; 1.
DR SMART; SM00358; DSRM; 3.
DR PROSITE; PS50137; DS_RBD; 3.
PE 1: Evidence at protein level;
KW Cytoplasm; Phosphoprotein; Reference proteome; Repeat; RNA-binding;
KW RNA-mediated gene silencing.
FT CHAIN 1..313
FT /note="Interferon-inducible double-stranded RNA-dependent
FT protein kinase activator A"
FT /id="PRO_0000223611"
FT DOMAIN 34..101
FT /note="DRBM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00266"
FT DOMAIN 126..194
FT /note="DRBM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00266"
FT DOMAIN 240..308
FT /note="DRBM 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00266"
FT REGION 1..103
FT /note="Sufficient for self-association and interaction with
FT TARBP2"
FT /evidence="ECO:0000250"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 102..195
FT /note="Sufficient for self-association and interaction with
FT TARBP2"
FT /evidence="ECO:0000250"
FT REGION 195..313
FT /note="Sufficient for self-association and interaction with
FT TARBP2"
FT /evidence="ECO:0000250"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 167
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 246
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75569"
FT MOD_RES 287
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75569"
SQ SEQUENCE 313 AA; 34355 MW; 78550978D5B92043 CRC64;
MSHSRHRAEA PPLQREDSGT FSLGKMITAK PGKTPIQVLH EYGTKTKNIP VYECERSDVQ
VHVPTFTFRV TVGDITCTGE GTSKKLAKHR AAEAAINILK ANASICFAVP DPLMPDPSKQ
PKNQLNPIGS LQELAIHHGW RLPEYTLSQE GGPAHKREYT TICRLESFME TGKGASKKQA
KRNAAEKFLA KFSNISPENH ISLTNVVGHS LGCTWHSLRN SPGEKINLLK RSLLSLPNTD
YIQLLSEIAK EQGFSITYLD IEELSANGQY QCLAELSTSP ITVCHGSGIS CGNAQSDAAH
NALQYLKIIA ERK
