ID   DUSTY_RAT               Reviewed;         927 AA.
AC   Q6XUX2;
DT   02-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   04-NOV-2026, entry version 128.
DE   RecName: Full=Dual serine/threonine and tyrosine protein kinase;
DE            EC=2.7.12.1;
DE   AltName: Full=Dusty protein kinase;
DE            Short=Dusty PK;
DE   AltName: Full=Receptor-interacting serine/threonine-protein kinase 5;
GN   Name=Dstyk; Synonyms=Ripk5;
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 [MRNA], AND TISSUE SPECIFICITY.
RC   STRAIN=Sprague-Dawley; TISSUE=Brain;
RX   PubMed=17123648; DOI=10.1016/j.bbaexp.2006.10.004;
RA   Peng J., Dong W., Chen Y., Mo R., Cheng J.-F., Hui C.-C., Mohandas N.,
RA   Huang C.-H.;
RT   "Dusty protein kinases: primary structure, gene evolution, tissue specific
RT   expression and unique features of the catalytic domain.";
RL   Biochim. Biophys. Acta 1759:562-572(2006).
CC   -!- FUNCTION: Acts as a positive regulator of ERK phosphorylation
CC       downstream of fibroblast growth factor-receptor activation. Involved in
CC       the regulation of both caspase-dependent apoptosis and caspase-
CC       independent cell death. In the skin, it plays a predominant role in
CC       suppressing caspase-dependent apoptosis in response to UV stress in a
CC       range of dermal cell types. Involved in normal skeletal segmentation
CC       and spine formation, via positively regulating late-stage endosomal
CC       trafficking in notochord cells (By similarity). Required for normal
CC       spatial learning and memory, independent of normal brain development
CC       (By similarity). May be required for normal urinary tract and kidney
CC       formation (By similarity). {ECO:0000250|UniProtKB:Q4VSN1,
CC       ECO:0000250|UniProtKB:Q6XUX1, ECO:0000250|UniProtKB:Q6XUX3}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP +
CC         H(+); 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=2.7.12.1;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] +
CC         ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC         COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.12.1;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] +
CC         ADP + H(+); Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC         COMP:20101, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC         ChEBI:CHEBI:61978, ChEBI:CHEBI:456216; EC=2.7.12.1;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q6XUX1}. Cell
CC       membrane {ECO:0000250|UniProtKB:Q6XUX1}. Apical cell membrane
CC       {ECO:0000250|UniProtKB:Q6XUX1}. Basolateral cell membrane
CC       {ECO:0000250|UniProtKB:Q6XUX1}. Cell junction
CC       {ECO:0000250|UniProtKB:Q6XUX1}. Note=Detected in basolateral and apical
CC       membranes of all tubular epithelia. Detected at apical cell-cell
CC       junctions. Colocalized with FGF receptors to the cell membrane.
CC       {ECO:0000250|UniProtKB:Q6XUX1}.
CC   -!- TISSUE SPECIFICITY: Expressed in many regions of the adult brain.
CC       {ECO:0000269|PubMed:17123648}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC       kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR   EMBL; AY208851; AAP42419.1; -; mRNA.
DR   EMBL; AY429675; AAS55391.1; -; mRNA.
DR   RefSeq; NP_955750.1; NM_199463.2.
DR   AlphaFoldDB; Q6XUX2; -.
DR   SMR; Q6XUX2; -.
DR   BioGRID; 257980; 1.
DR   FunCoup; Q6XUX2; 2725.
DR   STRING; 10116.ENSRNOP00000004810; -.
DR   PhosphoSitePlus; Q6XUX2; -.
DR   jPOST; Q6XUX2; -.
DR   PaxDb; 10116-ENSRNOP00000004810; -.
DR   GeneID; 304791; -.
DR   KEGG; rno:304791; -.
DR   UCSC; RGD:735051; rat.
DR   AGR; RGD:735051; -.
DR   CTD; 25778; -.
DR   RGD; 735051; Dstyk.
DR   VEuPathDB; HostDB:ENSRNOG00000021298; -.
DR   eggNOG; KOG0192; Eukaryota.
DR   HOGENOM; CLU_014116_0_0_1; -.
DR   InParanoid; Q6XUX2; -.
DR   OMA; AAEYQYR; -.
DR   OrthoDB; 31640at9989; -.
DR   PhylomeDB; Q6XUX2; -.
DR   PRO; PR:Q6XUX2; -.
DR   Proteomes; UP000002494; Chromosome 13.
DR   Bgee; ENSRNOG00000021298; Expressed in cerebellum and 18 other cell types or tissues.
DR   GO; GO:0070161; C:anchoring junction; ISS:UniProtKB.
DR   GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR   GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004713; F:protein tyrosine kinase activity; IEA:RHEA.
DR   GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; ISS:UniProtKB.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR   GO; GO:0045743; P:positive regulation of fibroblast growth factor receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:0033674; P:positive regulation of kinase activity; ISS:UniProtKB.
DR   CDD; cd13975; PKc_Dusty; 1.
DR   FunFam; 1.10.510.10:FF:000244; Dual serine/threonine and tyrosine protein kinase; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR051302; Dual_SerThr-Tyr_Kinase.
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   PANTHER; PTHR46392; DUAL SERINE/THREONINE AND TYROSINE PROTEIN KINASE; 1.
DR   PANTHER; PTHR46392:SF1; DUAL SERINE_THREONINE AND TYROSINE PROTEIN KINASE; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE   2: Evidence at transcript level;
KW   ATP-binding; Cell junction; Cell membrane; Coiled coil; Cytoplasm; Kinase;
KW   Membrane; Nucleotide-binding; Reference proteome;
KW   Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase.
FT   CHAIN           1..927
FT                   /note="Dual serine/threonine and tyrosine protein kinase"
FT                   /id="PRO_0000233121"
FT   DOMAIN          650..904
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          1..21
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          393..429
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        1..12
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        775
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         656..664
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         679
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
SQ   SEQUENCE   927 AA;  104898 MW;  88C938259D04472C CRC64;
     MEADGQSWSG ESVSGPGPGG GGMIRELCRG FGRYRRYLGR LRQNLRETQK FFRDIKCSHS
     HSCPSSPAGG GAAELGPAGD VAAAPLPAGQ LSCISFPPME EKYLQQIVDH LPCILILGQD
     CNAKCQLLNL LLAVRVLPTL KLDSDESCKL RRLRFTYGTR TQVSLALPGQ YELVHTLASH
     QDNWETIPEE DLEVQEDSED TARVLADLEV TMHHALLQEV DIVVAPCHSH RPAVDVLSDL
     ANDFLPVITY ALHKDELSER DEQELQEIRK YFSFPVFFFK VPTLEIIRSS SGRADSERSP
     LSGQLMDLGY LSSSHRNCMA SDQDCRAQSM LVEQSEKLRQ LSTFSHQLLQ TRLVDAAKAL
     NAVHSHCLDI FINQAFDMQR DLQITPKRLE YTRKKENELY ESLMNIANRK QEEMKDMIVE
     TLNTMKEELL DDAANMEFKD VIVPENGETV GTREIKSCIR QIQELIISRL NQAVANKLIS
     SVDYLRESFV GTLERCLQSL EKSQDVSVHI TSNYLKQILN AAYHVEVTFH SGSSVTRMLW
     EQIKQIIQRI TWVNPPTITL EWKRKVAQEA IDSLSASKLA KSICSQFRTR LNSSHEAFAA
     SLRQLEAGHS GRLEKTEDLW LKVRKDHAPR LARLSLESRS LQDVLLHRKP KLGQELGRGQ
     YGVVYLCDNW GGHFPCALKS VVPPDEKHWN DLALEFHYMR SLPKHERLVD LHGSVIDYNY
     GGGSSVAVLL IMERLHRDLY TGLKAGLSLE TRLQIALDVV EGIRFLHSQG LVHRDIKLKN
     VLLDKQNRAK ITDLGFCKPE AMMSGSIVGT PIHMAPELFT GKYDNSVDVY AFGILFWYIC
     SGSIKLPEAF ERCASKDHLW NNVRRGTRPE RLPVFDEECW QLMEACWDGD PSKRPLLGIV
     QPILRSIMDR LCKCDSERPS RGLDDST
//