DUSTY_DANRE
ID DUSTY_DANRE Reviewed; 885 AA.
AC Q4VSN1; Q0VFW4; Q5VJL5; Q6NWI9; Q6XUW8;
DT 02-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 104.
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 Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
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].
RC TISSUE=Eye, and Kidney;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
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: May act as a positive regulator of ERK phosphorylation
CC downstream of fibroblast growth factor-receptor activation. May induce
CC both caspase-dependent apoptosis and caspase-independent cell death (By
CC similarity). Plays a role in the embryonic development.
CC {ECO:0000250|UniProtKB:Q6XUX3, ECO:0000269|PubMed:23862974}.
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: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}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q4VSN1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q4VSN1-2; Sequence=VSP_018040;
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the protein causes growth
CC retardation, as evidenced by small fins, abnormal morphogenesis of the
CC tail, and loss of heartbeat. Pericardial effusion was evident in 5-day-
CC old morphant larvae. {ECO:0000269|PubMed:23862974}.
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; AY208855; AAP42423.1; -; mRNA.
DR EMBL; AY429681; AAS55397.1; -; mRNA.
DR EMBL; AY641096; AAV40862.1; -; mRNA.
DR EMBL; BC067573; AAH67573.1; -; mRNA.
DR EMBL; BC118677; AAI18678.1; -; mRNA.
DR RefSeq; NP_991190.2; NM_205627.2. [Q4VSN1-2]
DR RefSeq; XP_005168327.1; XM_005168270.3. [Q4VSN1-1]
DR AlphaFoldDB; Q4VSN1; -.
DR SMR; Q4VSN1; -.
DR STRING; 7955.ENSDARP00000097423; -.
DR PaxDb; Q4VSN1; -.
DR Ensembl; ENSDART00000067637; ENSDARP00000067636; ENSDARG00000000853. [Q4VSN1-2]
DR Ensembl; ENSDART00000106645; ENSDARP00000097423; ENSDARG00000000853. [Q4VSN1-1]
DR GeneID; 402922; -.
DR KEGG; dre:402922; -.
DR CTD; 25778; -.
DR ZFIN; ZDB-GENE-040826-2; dstyk.
DR eggNOG; KOG0192; Eukaryota.
DR GeneTree; ENSGT00840000129948; -.
DR HOGENOM; CLU_014116_0_0_1; -.
DR InParanoid; Q4VSN1; -.
DR OMA; KSCIHLI; -.
DR OrthoDB; 254886at2759; -.
DR PhylomeDB; Q4VSN1; -.
DR TreeFam; TF331821; -.
DR PRO; PR:Q4VSN1; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 22.
DR Bgee; ENSDARG00000000853; Expressed in mature ovarian follicle and 31 other tissues.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0048568; P:embryonic organ development; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0060036; P:notochord cell vacuolation; IMP:ZFIN.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IBA:GO_Central.
DR GO; GO:0045743; P:positive regulation of fibroblast growth factor receptor signaling pathway; IBA:GO_Central.
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; 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 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Cell junction; Cell membrane; Cytoplasm;
KW Developmental protein; Kinase; Membrane; Nucleotide-binding;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Tyrosine-protein kinase.
FT CHAIN 1..885
FT /note="Dual serine/threonine and tyrosine protein kinase"
FT /id="PRO_0000233123"
FT DOMAIN 614..868
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 739
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 620..628
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 643
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 483..510
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17123648"
FT /id="VSP_018040"
FT CONFLICT 467
FT /note="P -> L (in Ref. 1; AAP42423)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 885 AA; 99548 MW; 86F5AF552ABEA160 CRC64;
MENPQKPREL TRAFNHYNKH SGFLKKNLKE TILFFREIRQ NHSNTCAAAE PGQLSCISFP
RQDEEYLQNV VSSAPYILIL GQDCSARYQL LNCLLGERLL PLGPEAGGAC GAEGGACRRR
KLCFTHGRQT RLSLALPGQY ELVHQLAAHC GRWDTVPRQD LEIQECEDPA QRLAELEITL
HHTLLQEVKI MVLPCRNVQP LEEALEDCKR GILPIVLYAV SRESLSAQQL EDLQTLRESL
PFPVCFIRVS DGGGGGALFT QLASLQLISA SAGNCACGAP AAQSAGRMQG VLCDSLERLQ
RVLVPFTRQV LQNQQVEAAT LLNTIHCRCL DLFIIQAFDM QRDLQITPRR LEYTREKEGE
LFCSLMAIAN RKQEEMKEMI VETLSSMKEQ LLEDAQNLDF TDIIMSSNGE PVSSKDIKVC
ISQIQDLIVN RLNQAVANKL TNSVDYLRES FVGTLERCLG SLEKSTPESC AHNVTSNHLK
QILNAAYHVE VTFHSGSSVT RLFWEQIKQI IHRITWVNPP AITAEWKRKV AQDAIESLSA
AKLAKSICSQ FRTRLNSSHE AFAASLRQLE EGHTGRLERT EDLWLRVRKD HAPRLARLSL
ESRSLRDILL HGKPKLGREL GRGQYGVVYL CDSWAGRHPC ALKSVVPPDD KHWNDLALEF
HYTRSLPKHE RLVNLHGSVI DHSYSGGSSI AVLLIMERLH RDLYTGLKAG LSLKERLLIA
LDVVEGIRFL HSQGLLHRDI KLKNVLLDKQ NRAKITDLGF CKPEAMMSGS IVGTPIHMAP
ELFTGKYDNS VDVYAFGILF WYLCSGSVKL PEAFEKCASK DQLWTNVKKG CRPERLPVFD
EECWQLMEAC WNGDPSQRPL LGIVQPGLQS IMERLCGEKS LEDSN
