PRKX_MOUSE
ID PRKX_MOUSE Reviewed; 355 AA.
AC Q922R0; B1AVU0; Q3UCD1; Q8BHD6; Q9QZ12;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=cAMP-dependent protein kinase catalytic subunit PRKX;
DE Short=PrKX;
DE Short=Protein kinase X;
DE Short=Protein kinase X-linked;
DE Short=Serine/threonine-protein kinase PRKX;
DE EC=2.7.11.1;
DE AltName: Full=PKA-related protein kinase;
GN Name=Prkx; Synonyms=Pkare;
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], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Brain;
RX PubMed=10729225; DOI=10.1006/geno.2000.6116;
RA Blaschke R.J., Monaghan P.A., Bock D., Rappold G.A.;
RT "A novel murine PKA-related protein kinase involved in neuronal
RT differentiation.";
RL Genomics 64:187-194(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD;
RC TISSUE=Bone, Bone marrow, Egg, Embryo, Head, Hypothalamus, and Vagina;
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 GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [6]
RP FUNCTION IN NEPHROGENESIS.
RX PubMed=16236808; DOI=10.1681/asn.2005030240;
RA Li X., Hyink D.P., Polgar K., Gusella G.L., Wilson P.D., Burrow C.R.;
RT "Protein kinase X activates ureteric bud branching morphogenesis in
RT developing mouse metanephric kidney.";
RL J. Am. Soc. Nephrol. 16:3543-3552(2005).
RN [7]
RP DEVELOPMENTAL STAGE.
RX PubMed=15879576; DOI=10.1369/jhc.4a6568.2005;
RA Li W., Yu Z.X., Kotin R.M.;
RT "Profiles of PrKX expression in developmental mouse embryo and human
RT tissues.";
RL J. Histochem. Cytochem. 53:1003-1009(2005).
RN [8]
RP FUNCTION IN NEPHROGENESIS, AND INTERACTION WITH PIN1.
RX PubMed=19367327; DOI=10.1038/ki.2009.95;
RA Li X., Hyink D.P., Radbill B., Sudol M., Zhang H., Zheleznova N.N.,
RA Wilson P.D.;
RT "Protein kinase-X interacts with Pin-1 and Polycystin-1 during mouse kidney
RT development.";
RL Kidney Int. 76:54-62(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-200, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, 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 [10]
RP INTERACTION WITH PRKAR1A AND PRKAR1B.
RX PubMed=20819953; DOI=10.1074/jbc.m110.155150;
RA Diskar M., Zenn H.M., Kaupisch A., Kaufholz M., Brockmeyer S., Sohmen D.,
RA Berrera M., Zaccolo M., Boshart M., Herberg F.W., Prinz A.;
RT "Regulation of cAMP-dependent protein kinases: the human protein kinase X
RT (PrKX) reveals the role of the catalytic subunit alphaH-alphaI loop.";
RL J. Biol. Chem. 285:35910-35918(2010).
RN [11]
RP FUNCTION IN ANGIOGENESIS.
RX PubMed=21684272; DOI=10.1016/j.ydbio.2011.05.673;
RA Li X., Iomini C., Hyink D., Wilson P.D.;
RT "PRKX critically regulates endothelial cell proliferation, migration, and
RT vascular-like structure formation.";
RL Dev. Biol. 356:475-485(2011).
CC -!- FUNCTION: Serine/threonine protein kinase regulated by and mediating
CC cAMP signaling in cells. Acts through phosphorylation of downstream
CC targets that may include CREB, SMAD6 and PKD1 and has multiple
CC functions in cellular differentiation and epithelial morphogenesis.
CC Regulates myeloid cell differentiation through SMAD6 phosphorylation.
CC Involved in nephrogenesis by stimulating renal epithelial cell
CC migration and tubulogenesis. Also involved in angiogenesis through
CC stimulation of endothelial cell proliferation, migration and vascular-
CC like structure formation. {ECO:0000269|PubMed:16236808,
CC ECO:0000269|PubMed:19367327, ECO:0000269|PubMed:21684272}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- ACTIVITY REGULATION: Binding of cAMP to the PRKAR1A or PRKAR1B
CC regulatory subunits induces dissociation of the holoenzyme
CC heterotetramer. The released monomeric PRKX is then active and able to
CC phosphorylate its substrates (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Like other cAMP-dependent protein kinases, the inactive
CC holoenzyme is probably composed of 2 PRKX catalytic subunits and a
CC dimer of regulatory subunits. Interacts (cAMP-dependent) specifically
CC with the regulatory subunits PRKAR1A and PRKAR1B. Compared to other
CC cAMP-dependent serine/threonine protein kinases, does not interact with
CC the 2 other PKA regulatory subunits PRKAR2A and PRKAR2B. Interacts with
CC PIN1 (via WW domain). Interacts with cAMP-dependent protein kinase
CC inhibitor/PKI proteins; inhibits PRKX (By similarity). Interacts with
CC GPKOW (By similarity). Interacts with SMAD6 (By similarity). Interacts
CC with PKD1; involved in differentiation and controlled morphogenesis of
CC the kidney (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=cAMP induces nuclear translocation. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:10729225}.
CC -!- DEVELOPMENTAL STAGE: Expressed in central nervous system and heart
CC tissues in early development stages and in most organs at later stages
CC (at protein level). Detected in embryos from 9 dpc onward with higher
CC expression in differentiating neuronal tissues at 11.5 dpc.
CC {ECO:0000269|PubMed:10729225, ECO:0000269|PubMed:15879576}.
CC -!- PTM: Phosphorylated; autophosphorylates in vitro. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. cAMP subfamily. {ECO:0000305}.
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DR EMBL; AK034681; BAC28796.1; -; mRNA.
DR EMBL; AK036432; BAC29427.1; -; mRNA.
DR EMBL; AK037141; BAC29717.1; -; mRNA.
DR EMBL; AK039088; BAC30234.1; -; mRNA.
DR EMBL; AK081548; BAC38254.1; -; mRNA.
DR EMBL; AK139510; BAE24043.1; -; mRNA.
DR EMBL; AK150588; BAE29682.1; -; mRNA.
DR EMBL; AK154447; BAE32592.1; -; mRNA.
DR EMBL; AK169322; BAE41076.1; -; mRNA.
DR EMBL; AJ238004; CAB57279.1; -; mRNA.
DR EMBL; AL714017; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006875; AAH06875.1; -; mRNA.
DR CCDS; CCDS30248.1; -.
DR RefSeq; NP_058675.1; NM_016979.1.
DR AlphaFoldDB; Q922R0; -.
DR SMR; Q922R0; -.
DR STRING; 10090.ENSMUSP00000045304; -.
DR iPTMnet; Q922R0; -.
DR PhosphoSitePlus; Q922R0; -.
DR EPD; Q922R0; -.
DR jPOST; Q922R0; -.
DR MaxQB; Q922R0; -.
DR PaxDb; Q922R0; -.
DR PRIDE; Q922R0; -.
DR ProteomicsDB; 291562; -.
DR Antibodypedia; 7924; 237 antibodies from 30 providers.
DR DNASU; 19108; -.
DR Ensembl; ENSMUST00000036333; ENSMUSP00000045304; ENSMUSG00000035725.
DR GeneID; 19108; -.
DR KEGG; mmu:19108; -.
DR UCSC; uc009tqp.2; mouse.
DR CTD; 5613; -.
DR MGI; MGI:1309999; Prkx.
DR VEuPathDB; HostDB:ENSMUSG00000035725; -.
DR eggNOG; KOG0616; Eukaryota.
DR GeneTree; ENSGT00940000159832; -.
DR HOGENOM; CLU_000288_63_5_1; -.
DR InParanoid; Q922R0; -.
DR OMA; QEDPPRY; -.
DR OrthoDB; 963519at2759; -.
DR PhylomeDB; Q922R0; -.
DR TreeFam; TF313399; -.
DR BioGRID-ORCS; 19108; 1 hit in 76 CRISPR screens.
DR PRO; PR:Q922R0; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q922R0; protein.
DR Bgee; ENSMUSG00000035725; Expressed in lumbar dorsal root ganglion and 244 other tissues.
DR ExpressionAtlas; Q922R0; baseline and differential.
DR Genevisible; Q922R0; MM.
DR GO; GO:0005952; C:cAMP-dependent protein kinase complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004691; F:cAMP-dependent protein kinase activity; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:MGI.
DR GO; GO:0001525; P:angiogenesis; IMP:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IMP:UniProtKB.
DR GO; GO:0031589; P:cell-substrate adhesion; ISS:UniProtKB.
DR GO; GO:0043542; P:endothelial cell migration; ISS:UniProtKB.
DR GO; GO:0001935; P:endothelial cell proliferation; IMP:UniProtKB.
DR GO; GO:0060562; P:epithelial tube morphogenesis; ISS:UniProtKB.
DR GO; GO:0060993; P:kidney morphogenesis; ISS:UniProtKB.
DR GO; GO:0030099; P:myeloid cell differentiation; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0030155; P:regulation of cell adhesion; IEA:Ensembl.
DR GO; GO:0030334; P:regulation of cell migration; ISS:UniProtKB.
DR GO; GO:2000696; P:regulation of epithelial cell differentiation involved in kidney development; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Acetylation; Angiogenesis; ATP-binding; cAMP; Cytoplasm;
KW Developmental protein; Differentiation; Kinase; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..355
FT /note="cAMP-dependent protein kinase catalytic subunit
FT PRKX"
FT /id="PRO_0000086583"
FT DOMAIN 46..300
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 301..355
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 1..42
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 316..355
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 340..355
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 169
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 52..60
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 75
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P51817"
FT MOD_RES 200
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 71
FT /note="Y -> C (in Ref. 1; CAB57279)"
FT /evidence="ECO:0000305"
FT CONFLICT 88
FT /note="E -> G (in Ref. 1; CAB57279)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 355 AA; 40467 MW; AD6E682BE9DCBE46 CRC64;
MEPPAGAAAT VKDPDHDPVK TKVSAPAADP KPRTSSQKAG HSLQDWDTIA TVGTGTFGRV
NLVKEKTGRQ YCALKIMSIP DVIRLKQEQH VQNEKAVLKE INHPFLIKLL WTGHDNRFLY
MLMEFVPGGE LFTYLRNRGR FSSVASVFYA TEIVCAIEYL HSKEIVYRDL KPENILLDRE
GHIKLTDFGF AKKLVDRTWT LCGTPEYLAP EVIQSKGHGR AVDWWALGIL IFEMLSGFPP
FFDDNPFGIY QKILACKIDF PRQLDFTSKD LIKKLLVVDR TRRLGNMKNG AEDIKRHRWF
RGVEWESVPQ RKLKPPIVPK LSGDGDISNF ETYPESELDK TPSVSDKDLE TFKNF
