PRKRA_MOUSE
ID PRKRA_MOUSE Reviewed; 313 AA.
AC Q9WTX2; Q9CZB7;
DT 21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Interferon-inducible double-stranded RNA-dependent protein kinase activator A;
DE AltName: Full=PKR-associated protein X;
DE AltName: Full=PKR-associating protein X;
DE Short=RAX;
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; Synonyms=Rax;
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], FUNCTION, INTERACTION WITH EIF2AK2, TISSUE
RP SPECIFICITY, AND PHOSPHORYLATION.
RX PubMed=10336432; DOI=10.1074/jbc.274.22.15427;
RA Ito T., Yang M., May W.S.;
RT "RAX, a cellular activator for double-stranded RNA-dependent protein kinase
RT during stress signaling.";
RL J. Biol. Chem. 274:15427-15432(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC 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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Lung, Pancreas, Spleen, and
RC 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 UBC9.
RX PubMed=22214662; DOI=10.4161/cc.11.2.18999;
RA Bennett R.L., Pan Y., Christian J., Hui T., May W.S. Jr.;
RT "The RAX/PACT-PKR stress response pathway promotes p53 sumoylation and
RT activation, leading to G(1) arrest.";
RL Cell Cycle 11:407-417(2012).
CC -!- FUNCTION: Required for siRNA production by DICER1 and for subsequent
CC siRNA-mediated post-transcriptional gene silencing. Does not seem to be
CC required for processing of pre-miRNA to miRNA by DICER1 (By
CC similarity). Activates EIF2AK2/PKR in the absence of double-stranded
CC RNA (dsRNA), leading to phosphorylation of EIF2S1/EFI2-alpha and
CC inhibition of translation and induction of apoptosis. Promotes UBC9-
CC p53/TP53 association and sumoylation and phosphorylation of p53/TP53 at
CC 'Lys-386' at 'Ser-392' respectively and enhances its activity in a
CC EIF2AK2/PKR-dependent manner. {ECO:0000250,
CC ECO:0000269|PubMed:10336432, ECO:0000269|PubMed:22214662}.
CC -!- SUBUNIT: Homodimer. Interacts with DICER1, AGO2 and TARBP2. Also able
CC to interact with dsRNA (By similarity). Interacts with EIF2AK2/PKR
CC through its DRBM domains. Interacts with DUS2L (via DRBM domain) (By
CC similarity). Interacts with UBC9. Forms a complex with UBC9 and
CC p53/TP53. {ECO:0000250, ECO:0000269|PubMed:10336432,
CC ECO:0000269|PubMed:22214662}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region {ECO:0000250}.
CC Cytoplasm {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, heart, kidney, liver, lung,
CC muscle, spleen and testis. {ECO:0000269|PubMed:10336432}.
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; AF083032; AAD33098.1; -; mRNA.
DR EMBL; AK012798; BAB28477.1; -; mRNA.
DR EMBL; AK155112; BAE33056.1; -; mRNA.
DR EMBL; BC011311; AAH11311.1; -; mRNA.
DR CCDS; CCDS16159.1; -.
DR RefSeq; NP_036001.1; NM_011871.2.
DR AlphaFoldDB; Q9WTX2; -.
DR SMR; Q9WTX2; -.
DR BioGRID; 204842; 8.
DR ComplexPortal; CPX-1073; RISC-loading complex, PRKRA variant.
DR IntAct; Q9WTX2; 1.
DR MINT; Q9WTX2; -.
DR STRING; 10090.ENSMUSP00000002808; -.
DR iPTMnet; Q9WTX2; -.
DR PhosphoSitePlus; Q9WTX2; -.
DR EPD; Q9WTX2; -.
DR jPOST; Q9WTX2; -.
DR MaxQB; Q9WTX2; -.
DR PaxDb; Q9WTX2; -.
DR PeptideAtlas; Q9WTX2; -.
DR PRIDE; Q9WTX2; -.
DR ProteomicsDB; 289841; -.
DR Antibodypedia; 3306; 374 antibodies from 35 providers.
DR DNASU; 23992; -.
DR Ensembl; ENSMUST00000002808; ENSMUSP00000002808; ENSMUSG00000002731.
DR GeneID; 23992; -.
DR KEGG; mmu:23992; -.
DR UCSC; uc008kff.1; mouse.
DR CTD; 8575; -.
DR MGI; MGI:1344375; Prkra.
DR VEuPathDB; HostDB:ENSMUSG00000002731; -.
DR eggNOG; KOG3732; Eukaryota.
DR GeneTree; ENSGT00940000157618; -.
DR HOGENOM; CLU_048292_0_0_1; -.
DR InParanoid; Q9WTX2; -.
DR OMA; KKIAKHR; -.
DR OrthoDB; 1093169at2759; -.
DR PhylomeDB; Q9WTX2; -.
DR TreeFam; TF315953; -.
DR Reactome; R-MMU-203927; MicroRNA (miRNA) biogenesis.
DR Reactome; R-MMU-426486; Small interfering RNA (siRNA) biogenesis.
DR BioGRID-ORCS; 23992; 16 hits in 73 CRISPR screens.
DR PRO; PR:Q9WTX2; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9WTX2; protein.
DR Bgee; ENSMUSG00000002731; Expressed in dorsal pancreas and 250 other tissues.
DR Genevisible; Q9WTX2; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
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:MGI.
DR GO; GO:0003725; F:double-stranded RNA binding; ISO:MGI.
DR GO; GO:0008047; F:enzyme activator activity; IEA:InterPro.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0070883; F:pre-miRNA binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0035197; F:siRNA binding; IBA:GO_Central.
DR GO; GO:0034599; P:cellular response to oxidative stress; IDA:MGI.
DR GO; GO:0043583; P:ear development; IMP:MGI.
DR GO; GO:0042474; P:middle ear morphogenesis; IMP:MGI.
DR GO; GO:0035196; P:miRNA processing; ISO:MGI.
DR GO; GO:0042473; P:outer ear morphogenesis; IMP:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; IDA:MGI.
DR GO; GO:0031054; P:pre-miRNA processing; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:0050821; P:protein stabilization; ISO:MGI.
DR GO; GO:0070920; P:regulation of production of small RNA involved in gene silencing by RNA; IBA:GO_Central.
DR GO; GO:0030422; P:siRNA processing; ISS:UniProtKB.
DR GO; GO:0048705; P:skeletal system morphogenesis; IMP:MGI.
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_0000223610"
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:0000250|UniProtKB:O75569"
FT MOD_RES 167
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75569"
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"
FT CONFLICT 177
FT /note="K -> N (in Ref. 2; BAB28477)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 313 AA; 34371 MW; 6EDF248A55A391D2 CRC64;
MSHSRHRAEA PPLQREDSGT FSLGKMITAK PGKTPIQVLH EYGMKTKNIP VYECERSDVQ
VHVPTFTFRV TVGDITCTGE GTSKKLAKHR AAEAAINILK ANASICFAVP DPLMPDPSKQ
PKNQLNPIGS LQELAIHHGW RLPEYTLSQE GGPAHKREYT TICRLESFME TGKGASKKQA
KRNAAEKFLA KFSNISPENH ISLTNVVGHS LGCTWHSLRN SPGEKINLLK RSLLSLPNTD
YIQLLSEIAS EQGFNITYLD IEELSANGQY QCLAELSTSP ITVCHGSGIS CGNAQSDAAH
NALQYLKIIA ERK
