ALPK2_DANRE
ID ALPK2_DANRE Reviewed; 1966 AA.
AC F1QU13;
DT 16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT 16-OCT-2019, sequence version 2.
DT 03-AUG-2022, entry version 56.
DE RecName: Full=Alpha-protein kinase 2 {ECO:0000305|PubMed:29888752};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q86TB3};
DE AltName: Full=Heart alpha-protein kinase {ECO:0000250|UniProtKB:Q86TB3};
GN Name=alpk2 {ECO:0000312|ZFIN:ZDB-GENE-030131-1868};
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] {ECO:0000312|Proteomes:UP000000437}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen {ECO:0000312|Proteomes:UP000000437};
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=29888752; DOI=10.1016/j.isci.2018.03.010;
RA Hofsteen P., Robitaille A.M., Strash N., Palpant N., Moon R.T., Pabon L.,
RA Murry C.E.;
RT "ALPK2 Promotes Cardiogenesis in Zebrafish and Human Pluripotent Stem
RT Cells.";
RL IScience 2:88-100(2018).
CC -!- FUNCTION: Protein kinase that recognizes phosphorylation sites in which
CC the surrounding peptides have an alpha-helical conformation (By
CC similarity). Regulates cardiac development and cardiomyocyte
CC differentiation by negatively regulating Wnt/beta-catenin signaling
CC (PubMed:29888752). {ECO:0000250|UniProtKB:Q86TB3,
CC ECO:0000269|PubMed:29888752}.
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 Evidence={ECO:0000250|UniProtKB:Q86TB3};
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; Evidence={ECO:0000305};
CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane
CC {ECO:0000250|UniProtKB:Q86TB3}.
CC -!- TISSUE SPECIFICITY: Expressed in developing cardiac tissue.
CC {ECO:0000269|PubMed:29888752}.
CC -!- DEVELOPMENTAL STAGE: Detected at 13 hours post-fertilization (hpf) in
CC the precursor cells of adaxial cells (slow twitch muscle fibers) of the
CC paraxial mesoderm (PubMed:29888752). At 22 hpf, detected in the
CC developing heart (PubMed:29888752). {ECO:0000269|PubMed:29888752}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown in the embryo causes reduced
CC heart beating rates and cardiomyocyte numbers at 48 hours post-
CC fertilization (hpf) (PubMed:29888752). At 72 hpf, embryos display
CC pericardial and yolk sac effusion and pronounced cardiac malformation
CC coupled with defects in posterior development (PubMed:29888752).
CC Embryos also lack ventricular epicardium at 96 hpf (PubMed:29888752).
CC {ECO:0000269|PubMed:29888752}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Alpha-type
CC protein kinase family. ALPK subfamily. {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; BX248399; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR925730; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_017208526.1; XM_017353037.1.
DR AlphaFoldDB; F1QU13; -.
DR SMR; F1QU13; -.
DR STRING; 7955.ENSDARP00000122327; -.
DR PaxDb; F1QU13; -.
DR GeneID; 559835; -.
DR KEGG; dre:559835; -.
DR CTD; 115701; -.
DR ZFIN; ZDB-GENE-030131-1868; alpk2.
DR eggNOG; ENOG502QPP5; Eukaryota.
DR HOGENOM; CLU_293483_0_0_1; -.
DR PRO; PR:F1QU13; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
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:0055013; P:cardiac muscle cell development; IMP:ZFIN.
DR GO; GO:1905223; P:epicardium morphogenesis; IMP:ZFIN.
DR GO; GO:0060047; P:heart contraction; IMP:ZFIN.
DR GO; GO:0003007; P:heart morphogenesis; IMP:ZFIN.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR004166; MHCK_EF2_kinase.
DR Pfam; PF02816; Alpha_kinase; 1.
DR SMART; SM00811; Alpha_kinase; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51158; ALPHA_KINASE; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Disulfide bond; Immunoglobulin domain; Kinase; Membrane;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..1966
FT /note="Alpha-protein kinase 2"
FT /id="PRO_0000448062"
FT DOMAIN 1577..1659
FT /note="Ig-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 1702..1934
FT /note="Alpha-type protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00501"
FT REGION 23..65
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 211..231
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1211..1259
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1303..1365
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1386..1423
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1437..1463
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1937..1966
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 23..64
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1229..1246
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1312..1346
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1347..1361
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1399..1423
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 1599..1649
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 1966 AA; 217128 MW; 8BC7FADB5B8DB844 CRC64;
MTAKRVDMAA PDNLLFLDSD AVNSSPASVP IEQNEPTHVL DNQTDDSLRS MPDPHTNTAL
ESTGLMPVPC QDETLETHSQ HNEGENESSL VSTQHMDHTR LTEMTINDEK SNNWDFDISG
VKENDNSTNL NPDLIHHAGT DSVMERNLND KQTDLNHKDE TFGSLMSSEV LLLKENRQQE
MSQDTNLHQC SSSESTGIEY SQTANDAISD AMNSEQSPDQ PFSIASNDTD KTTSECSVQT
CWDTVESAAT SKTQPELHDD VKDVMCESFT TSQTLNIDYL STDISVCLAD LPETDSLNIL
TPASTLLGIL GKNNNVLKTA DVPINDSEMV QSINKDLASP NADISKTVFT QMDQNLLHVT
DHNVKVLESN RADTVVDQYV FSENIGQEVS QASSHDEDLN SSVQSHDQQL STANSEIEET
SSEFHTQTCQ DIHEGVIIAE EAMNGHNTLP EMHDIADVTT SQTPIMKDPM IDEPSYLPDL
HKADTPNVIT TASTLSDTLE TDDSIFETAD VSVSDCELIQ TVTLKTVTTY ETLLMMHDVG
EDLTCCDFTT SAIEEPETSH PLSLDDLHES NTPNIPPHAS ALLDSLGMNK NFLETADVPV
SDCEVIQTVT FETVTTYETF PVMHDIAEDL TCCDFTTSET PKIEEPETSH SLSLDDLNEA
NTPNILPHAS ALLESLGMNN NFLEAADMPV SDREIIHPVN KDLDSSSVEI CTVVLTQTDP
KEVQDSDLDE KETESNRIDD SIDGMIDTKF SLDVSKLQPV CSNDLSGTVI HSESLFSQSI
PDTPQIGEKY KNDLLQVISP PTPVTNEDLG NCSEEIDDAC LKFTGTERDV EGDSELWLEP
SQFLAGEEDE GAIFDKWGRS CSSSPPTTHP DNTKASDYTW RENISIDHNA EDWELTFPPV
ERWSSSDSWA SALSDWFQAV NTYPEDSFKS ASTGSKLGMA IQDNILEQRT SSDNANNDEQ
TCLSLNLMQP DEPGQALERG LVKSDNTNGT VFKQGDKERL ASCLDMDKDT TTMESQMSLL
ETSTPESHKA DNNAVMETFN ASLTHEFNAK LHGSLDISGK LLSAKREGNV LVEVTGGKVS
QLGLVFEEER QSIFTSPSSS AYTRDKNLTG CVSNEERCHS SDVHLCICPS QSDSHVSSKA
GHAEGNGSFL HSNIGNCTVK PYVEENIPQF IMPFAPICTG NTFLHRSFLK EDRSQADLDL
PDKKIINKIN LKSNKKSSSS DDSSEDNFHT CPDQSLSSSS GDSDDPSITD SGRKPAYSDT
CDIGKELSKL LLLTGEHFMV SEDKRIAYVT LDLDESQHFG RFSLPNCEKQ SKPDNMPHKT
SKTSSDGKMR SKHKEKPDDK QQHGIQASKK QDPQPQSQVK NEGAGCEDCP VAVIETIVIT
EKIIPKTQGK KKKKHVQHGT PKPENDAPTD VRSESRQKNV NGKAENLELK VASNSLNKPV
AQPSGKTDIT KKDSAQKVMS VRPKVEPSMA KMDPAGVNAT QKSSPIKLKA DTFNTAKMEN
KTCTTDSLST CLPSMLNDDI KRRRIADDLS RAVPIRTRPQ LPAIFRQARK DGEDVTRRAY
SEVVKQKNST PKEVVVPRVV SEIQADPVPA DPQNISLWCQ FSPIPPEATI KWTKEAAVLS
EINKVEKEDG RFTLTIIKAC SKDLGFYKCS LIVANISVST SEYHLTSEVL MELVIPSHDQ
PAEPRVMEGD EENIQCSPLL FKEDFLSDQY FGKNQPASIL TEKVHFGEGM HRKAFRTTLT
EGNLPRFRPG HPCVLKVHNS ISYGTKNNEE LVQKNYSLAV EECHVQNTAR EYIKAYNSVA
KSAESFGDLP EIIPIYLVHR PSNDIPYATL EEELLGDFVK YSVKDGKEIN LMRRDSEAGQ
KCCAFQHWVY TQTEGNLLVT DMQGVGMKLT DVGIATCKKG YKGFRGNCAT SFIDQFKALH
QCNRYCELLG LVSLQPKPKR TVAPPKPKTQ PVPKKKTFGP VLNAKS
