ALK_DANRE
ID ALK_DANRE Reviewed; 1705 AA.
AC F8W3R9;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 25-MAY-2022, sequence version 2.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=ALK tyrosine kinase receptor {ECO:0000305};
DE EC=2.7.10.1 {ECO:0000250|UniProtKB:Q9UM73};
DE AltName: Full=Anaplastic lymphoma kinase 2 {ECO:0000303|PubMed:29078341};
DE Short=alk-2 {ECO:0000303|PubMed:29078341};
DE AltName: Full=Anaplastic lymphoma kinase homolog {ECO:0000303|PubMed:23667670};
DE Flags: Precursor;
GN Name=alk {ECO:0000303|PubMed:23667670, ECO:0000312|ZFIN:ZDB-GENE-031027-1};
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
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]
RP ACTIVITY REGULATION.
RX PubMed=22985331; DOI=10.1021/cb300361a;
RA Rodrigues F.S., Yang X., Nikaido M., Liu Q., Kelsh R.N.;
RT "A simple, highly visual in vivo screen for anaplastic lymphoma kinase
RT inhibitors.";
RL ACS Chem. Biol. 7:1968-1974(2012).
RN [3]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=23667670; DOI=10.1371/journal.pone.0063757;
RA Yao S., Cheng M., Zhang Q., Wasik M., Kelsh R., Winkler C.;
RT "Anaplastic lymphoma kinase is required for neurogenesis in the developing
RT central nervous system of zebrafish.";
RL PLoS ONE 8:e63757-e63757(2013).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=29078341; DOI=10.1073/pnas.1710254114;
RA Mo E.S., Cheng Q., Reshetnyak A.V., Schlessinger J., Nicoli S.;
RT "Alk and Ltk ligands are essential for iridophore development in zebrafish
RT mediated by the receptor tyrosine kinase Ltk.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:12027-12032(2017).
CC -!- FUNCTION: Receptor tyrosine kinase required for neurogenesis in the
CC developing central nervous system (PubMed:23667670). Following
CC activation by alkal ligands (alkal1, alkal2a or alkal2b) at the cell
CC surface, transduces an extracellular signal into an intracellular
CC response (PubMed:29078341). Ligand-binding to the extracellular domain
CC induces tyrosine kinase activation, resulting in the activation of the
CC mitogen-activated protein kinase (MAPK) pathway (PubMed:23667670).
CC Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-
CC Y-Y motif (By similarity). {ECO:0000250|UniProtKB:Q9UM73,
CC ECO:0000269|PubMed:23667670, ECO:0000269|PubMed:29078341}.
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=2.7.10.1;
CC Evidence={ECO:0000250|UniProtKB:Q9UM73};
CC -!- ACTIVITY REGULATION: Inhibited by ALK inhibitor TAE684.
CC {ECO:0000269|PubMed:22985331}.
CC -!- SUBUNIT: Homodimer; homodimerizes upon binding to alkal ligands
CC (alkal1, alkal2a or alkal2b). {ECO:0000250|UniProtKB:P29376}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9UM73};
CC Single-pass type I membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the developing central nervous
CC system: highly expressed in brain, with much lower expression in heart,
CC caudal fin and testis. {ECO:0000269|PubMed:23667670}.
CC -!- DEVELOPMENTAL STAGE: First detected at 12 hours post-fertilization
CC (hpf), during the initiation of segmentation and neurulation
CC (PubMed:23667670). Expression increases with the most profound increase
CC at 48 hpf (PubMed:23667670). {ECO:0000269|PubMed:23667670}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the protein causes
CC impaired neuronal differentiation and reduced neuron numbers in the
CC hindbrain (PubMed:23667670). Fishes display normal iridophore
CC development (PubMed:29078341). {ECO:0000269|PubMed:23667670,
CC ECO:0000269|PubMed:29078341}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Insulin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; BX663528; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR STRING; 7955.ENSDARP00000124055; -.
DR PaxDb; F8W3R9; -.
DR ZFIN; ZDB-GENE-031027-1; alk.
DR eggNOG; KOG1095; Eukaryota.
DR InParanoid; F8W3R9; -.
DR PhylomeDB; F8W3R9; -.
DR TreeFam; TF351636; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 17.
DR Bgee; ENSDARG00000095833; Expressed in brain and 9 other tissues.
DR GO; GO:0016021; C:integral component of membrane; ISS:ZFIN.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; ISS:ZFIN.
DR GO; GO:0007399; P:nervous system development; ISS:ZFIN.
DR GO; GO:0048666; P:neuron development; IEA:InterPro.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:UniProtKB.
DR GO; GO:0050769; P:positive regulation of neurogenesis; IMP:UniProtKB.
DR GO; GO:0006487; P:protein N-linked glycosylation; ISS:ZFIN.
DR GO; GO:0042127; P:regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0045664; P:regulation of neuron differentiation; IMP:ZFIN.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd00112; LDLa; 1.
DR CDD; cd06263; MAM; 1.
DR InterPro; IPR026830; ALK.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR002172; LDrepeatLR_classA_rpt.
DR InterPro; IPR000998; MAM_dom.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR002011; Tyr_kinase_rcpt_2_CS.
DR PANTHER; PTHR24416:SF276; PTHR24416:SF276; 1.
DR Pfam; PF00629; MAM; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00192; LDLa; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF49899; SSF49899; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50060; MAM_2; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS00239; RECEPTOR_TYR_KIN_II; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cell membrane; Disulfide bond; Glycoprotein; Kinase; Membrane;
KW Nucleotide-binding; Receptor; Reference proteome; Signal; Transferase;
KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..1705
FT /note="ALK tyrosine kinase receptor"
FT /evidence="ECO:0000255"
FT /id="PRO_0000455467"
FT TOPO_DOM 22..1035
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1036..1056
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1057..1705
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 486..644
FT /note="MAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00128"
FT DOMAIN 1113..1389
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 54..76
FT /note="Heparin-binding region"
FT /evidence="ECO:0000250|UniProtKB:Q9UM73"
FT REGION 842..892
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 980..1016
FT /note="EGF-like"
FT /evidence="ECO:0000250|UniProtKB:Q9UM73"
FT REGION 1395..1499
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1505..1524
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1532..1557
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1588..1613
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1646..1681
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1420..1439
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1479..1497
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1532..1551
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1246
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1119..1127
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1147
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT CARBOHYD 40
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 124
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 259
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 334
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 434
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 442
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 458
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 484
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 578
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 590
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 635
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 717
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 808
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 881
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 979
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1014
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 694..707
FT /evidence="ECO:0000250|UniProtKB:Q9UM73"
FT DISULFID 788..799
FT /evidence="ECO:0000250|UniProtKB:Q9UM73"
FT DISULFID 903..921
FT /evidence="ECO:0000250|UniProtKB:Q9UM73"
FT DISULFID 980..988
FT /evidence="ECO:0000250|UniProtKB:Q9UM73"
FT DISULFID 983..997
FT /evidence="ECO:0000250|UniProtKB:Q9UM73"
SQ SEQUENCE 1705 AA; 186696 MW; A0E0FF1CB682CC0D CRC64;
MIARILYFFL WSAAFLPELQ CASQRTADAL TTFPTSAFIN GTDRKDSNQT STSRIKRKTL
SVDFAVPSLL RYYLALFIKR PLNGDCLSFN GCYTVRANLL MRCVPLQKTI AGLLDAKLAA
MNVNRSSTGQ LPYRQKRPVP KVLNLGLTSA SRKSNQVVVE VGEEMVKTGC GGLHVYEDAP
VVFLEMDLTR ILEWWLGAEG GRLRVRLMPE RKVQVPGKED KYSAAIRASD ARLFIQIASS
ERPSSTISRN PTVAPKYWNF SWIAEDELTF PEDPVSTSDC TSKAKSCDRR PDGYYPEFAW
SLTSAEDSWA IDQTMVKTKA SSQGWEEGRF LTVNSSALTG PWVLSPWFRA AHRPCGLDIT
VFLHPRQSGR YTVWLIERDK PPLALLTTEH PHVIGWAVVH LSLAARSKPF RISSSYSQPG
EIETATYDPR YSTNCTTRSS QNVTLRGRYH CRGGREINVS QLCDFSIDCP QGDDEGEHCR
QFLNGSYCSF GREDCGWQPV QGRGPQWRAH PSIPQSLRSS CPSPGALLAI DSQPKGQRGS
AQVRSPLFFY PLRNAPCMVK FWVCGSSNGA LSLWITENST GPEGQRSLWN STSEANMGKG
WKLITLPLFG LVDLFYLQFS ADISSSSGIA FAVDNFTLSM ECFLETNGEF PPVAPISPTQ
ALFTQSNENI KTTTTLYGGP GASTESVKWI FHTCGATGQD GPTPTQCSNS YRNTNVNVTV
GTKGPFKGIQ MWQVPETRKY RITAYGAAGG RSVLAVHKSH GVYMTGDFLL QKDELLYILV
GQEGEDACPN MVPTMDRICR EQQGPSINKT QLKGGGGGGG GGTYVFKVVN GVHIPLLIAA
GGGGRGYSSQ SETPEEVMDR DPSIPGRNGK SGTAGGGGGW NDSAPVPQGG RPLILGGQGG
EPCQAMGWKT RGGFGGGGGA CTAGGGGGGY RGGSAWHDND PRKDGDDGTS YISPDGEMYL
EPLKGMEGNG EVIINPVQNC SHCESGDCHE TSEGMVCYCD EELTLAPDGV SCINSTELPL
LPAQPSLSHL ALGLSVGTSA LIAALLLAVS GVMIMYRRKH TELQSIQLEL QSPDCKLSKL
RASTIMTDYN PNYCFGGKTA SVNDLKEVPR RNISLTRGLG HGAFGEVYEG LAVGIPGEPS
PMQVAVKTLP EVCSEQDELD FLMEALIISK FSHQNIVRCI GVSLQALPHF ILLELMAGGD
LKSFLRETRP RLEHPSSLTM VDLLNIARDI ARGCQYLEEN QFIHRDIAAR NCLLTCKGPG
RVAKIGDFGM ARDIYRASYY RKGGRAMLPV KWMPPEAFME GIFTSKTDTW SFGVLLWEIF
SLGYMPYPSR SNQEVLEFVT NGGRMDPPKN CPGPVYRIMT QSWQHQPEDR PNFSTILERI
DYCLQDPDVV NVPLPVEYGP IPEEEERVPM RPEDPSAPSL LVSPQGTEDV PSATHSAQSK
KDGEAIHMAN LSTDSKLPPV PPSQPHPHHH LQTPVVTAPV PASKPSSTTS NAQDGGHVNL
GFMQAHSSEK ESRNRKPTNL WNPTYGSWFL QQQQKRQQVQ AQRQTSGPRI PGEGQEQVGR
TVTVAEALGL QQQHKQQQYQ QQLQRQQQQQ QQQQQQQGLC RPLLPPPPPP APTPLLLDSA
TLAPVPLYRL RRFPCGNIGY GYQEQGLPME PMQGPQLPPP HPGQQRPISL TRASGPEDSR
PLLVTMGTVQ DSRLPKMEGH NATVL
