DUSTY_MOUSE
ID DUSTY_MOUSE Reviewed; 927 AA.
AC Q6XUX1; Q3ULK4; Q5EBN5; Q8C7D4; Q8C923; Q9CTP7;
DT 02-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 138.
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 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] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC STRAIN=BALB/cJ; 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).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4), NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 1-392 (ISOFORM 3), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 535-927 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, Pancreas, and Retina;
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] OF 478-927 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Eye;
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 SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23862974; DOI=10.1056/nejmoa1214479;
RA Sanna-Cherchi S., Sampogna R.V., Papeta N., Burgess K.E., Nees S.N.,
RA Perry B.J., Choi M., Bodria M., Liu Y., Weng P.L., Lozanovski V.J.,
RA Verbitsky M., Lugani F., Sterken R., Paragas N., Caridi G., Carrea A.,
RA Dagnino M., Materna-Kiryluk A., Santamaria G., Murtas C.,
RA Ristoska-Bojkovska N., Izzi C., Kacak N., Bianco B., Giberti S.,
RA Gigante M., Piaggio G., Gesualdo L., Kosuljandic Vukic D., Vukojevic K.,
RA Saraga-Babic M., Saraga M., Gucev Z., Allegri L., Latos-Bielenska A.,
RA Casu D., State M., Scolari F., Ravazzolo R., Kiryluk K., Al-Awqati Q.,
RA D'Agati V.D., Drummond I.A., Tasic V., Lifton R.P., Ghiggeri G.M.,
RA Gharavi A.G.;
RT "Mutations in DSTYK and dominant urinary tract malformations.";
RL N. Engl. J. Med. 369:621-629(2013).
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. {ECO:0000250|UniProtKB:Q6XUX3}.
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=2.7.12.1;
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=2.7.12.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.12.1;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23862974}. Cell
CC membrane {ECO:0000269|PubMed:23862974}. Apical cell membrane
CC {ECO:0000269|PubMed:23862974}. Basolateral cell membrane
CC {ECO:0000269|PubMed:23862974}. Cell junction
CC {ECO:0000269|PubMed:23862974}. 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:0000269|PubMed:23862974}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q6XUX1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6XUX1-2; Sequence=VSP_018035;
CC Name=3;
CC IsoId=Q6XUX1-3; Sequence=VSP_018036;
CC Name=4;
CC IsoId=Q6XUX1-4; Sequence=VSP_018037, VSP_018038, VSP_018039;
CC -!- TISSUE SPECIFICITY: Expressed in brain, heart, skeletal muscle, kidney
CC and lung. Expressed in maturing tubular epithelia, with the most
CC prominent expression in the medulla and the papilla. Expressed in thin
CC ascending limb of the loop of Henle and the distal convoluted tubule.
CC Expressed in all layers of transitional ureteric epithelium and in the
CC ureteric smooth-muscle cells (at protein level). Widely expressed.
CC Highly expressed in many brain regions, including in cerebellum,
CC olfactory, hippocampus and cerebral cortex.
CC {ECO:0000269|PubMed:17123648, ECO:0000269|PubMed:23862974}.
CC -!- DEVELOPMENTAL STAGE: At 14.5 dpc detected in lung and skeletal muscle,
CC and by 18.5 dpc detected in skin, whisker, gut and testis.
CC {ECO:0000269|PubMed:17123648}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC34316.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAE26444.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY208852; AAP42420.1; -; mRNA.
DR EMBL; AY429676; AAS55392.1; -; mRNA.
DR EMBL; AK020880; BAB32238.1; -; mRNA.
DR EMBL; AK043199; BAC31487.1; -; mRNA.
DR EMBL; AK050542; BAC34316.1; ALT_INIT; mRNA.
DR EMBL; AK145449; BAE26444.1; ALT_INIT; mRNA.
DR EMBL; BC089380; AAH89380.1; -; mRNA.
DR CCDS; CCDS15285.1; -. [Q6XUX1-1]
DR RefSeq; NP_766104.2; NM_172516.4. [Q6XUX1-1]
DR AlphaFoldDB; Q6XUX1; -.
DR SMR; Q6XUX1; -.
DR BioGRID; 229434; 2.
DR IntAct; Q6XUX1; 2.
DR STRING; 10090.ENSMUSP00000035358; -.
DR iPTMnet; Q6XUX1; -.
DR PhosphoSitePlus; Q6XUX1; -.
DR MaxQB; Q6XUX1; -.
DR PaxDb; Q6XUX1; -.
DR PRIDE; Q6XUX1; -.
DR ProteomicsDB; 279489; -. [Q6XUX1-1]
DR ProteomicsDB; 279490; -. [Q6XUX1-2]
DR ProteomicsDB; 279491; -. [Q6XUX1-3]
DR ProteomicsDB; 279492; -. [Q6XUX1-4]
DR Antibodypedia; 34564; 186 antibodies from 26 providers.
DR DNASU; 213452; -.
DR Ensembl; ENSMUST00000045110; ENSMUSP00000035358; ENSMUSG00000042046. [Q6XUX1-1]
DR GeneID; 213452; -.
DR KEGG; mmu:213452; -.
DR UCSC; uc007cou.1; mouse. [Q6XUX1-1]
DR UCSC; uc007cov.1; mouse. [Q6XUX1-4]
DR CTD; 25778; -.
DR MGI; MGI:1925064; Dstyk.
DR VEuPathDB; HostDB:ENSMUSG00000042046; -.
DR eggNOG; KOG0192; Eukaryota.
DR GeneTree; ENSGT00840000129948; -.
DR HOGENOM; CLU_014116_0_0_1; -.
DR InParanoid; Q6XUX1; -.
DR OMA; KSCIHLI; -.
DR OrthoDB; 254886at2759; -.
DR PhylomeDB; Q6XUX1; -.
DR TreeFam; TF331821; -.
DR BioGRID-ORCS; 213452; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Dstyk; mouse.
DR PRO; PR:Q6XUX1; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q6XUX1; protein.
DR Bgee; ENSMUSG00000042046; Expressed in ciliary body and 245 other tissues.
DR ExpressionAtlas; Q6XUX1; baseline and differential.
DR Genevisible; Q6XUX1; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW.
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 InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 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 Alternative splicing; ATP-binding; Cell junction; Cell membrane;
KW Coiled coil; Cytoplasm; Kinase; Membrane; Nucleotide-binding;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Tyrosine-protein kinase.
FT CHAIN 1..927
FT /note="Dual serine/threonine and tyrosine protein kinase"
FT /id="PRO_0000233119"
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 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"
FT VAR_SEQ 1..536
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_018037"
FT VAR_SEQ 210..218
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_018036"
FT VAR_SEQ 537..544
FT /note="RMLWEQIK -> MISLSSSW (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_018038"
FT VAR_SEQ 701..927
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_018039"
FT VAR_SEQ 923..927
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_018035"
FT CONFLICT 695
FT /note="E -> K (in Ref. 2; BAC31487)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 927 AA; 104901 MW; EF124A73F3509A71 CRC64;
MEADGQSWAG ESVSGPGPGG GGMIRELCRG FSRYRRYLGR LRQNLRETQK FFRDIKCSHS
HSCPSSPAGG GAAELGPAGD VAEAPLPAGQ LSCISFPPME ETYLQQLVDR LPCILILGQD
CNAKCQLLNL LLGVQVLPTL KLDSDESCKL RRLRFTYGTR TRVSLALPGQ YELVHTLASH
QDNWETIPEE DLEVQEDSED AAHVLADLEV TMHHALLQEV DIVVAPCPSH RPSVDVLSDL
ANDFLPVITY ALHKDELSER GEQELREVRQ YFSFPMFFFK VPKLEIISSS SGRAESERSP
LYGQLVDLGY LSSSHRNCVP SDQDCKAQSM LVEQSEKLKQ LSTFSHQLLQ NRLVDAAKAL
NVVHSHCLDI FINQAFDMQR DLQITPKRLE YTRKKENELY ESLMNIANRK QEEMKDMIVE
TLNTMKEELL DDAANMEFKD VIVPENGETI 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 TGLKAGLTLE TRLQIALDVV EGIRFLHSQG LVHRDIKLKN
VLLDKQNRAK ITDLGFCKPE AMMSGSIVGT PIHMAPELFT GKYDNSVDVY AFGILFWYIC
SGSIKLPEAF ERCASKDHLW NNVRRGTRPE RLPVFDEECW QLMEACWDGD PLKRPLLGIV
QPMLRSIMDR LCKCSSEQPN RGLDDST
