AKL2A_DANRE
ID AKL2A_DANRE Reviewed; 169 AA.
AC E7F5F0;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 20-JUN-2018, sequence version 3.
DT 03-AUG-2022, entry version 55.
DE RecName: Full=ALK and LTK ligand 2a {ECO:0000303|PubMed:29317532};
DE AltName: Full=Augmentor alpha-1 {ECO:0000303|PubMed:29078341};
DE Short=AUG-alpha-1 {ECO:0000303|PubMed:29078341};
DE Flags: Precursor;
GN Name=alkal2a {ECO:0000303|PubMed:29317532,
GN ECO:0000312|ZFIN:ZDB-GENE-100922-116};
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 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).
RN [3]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=29317532; DOI=10.1073/pnas.1719137115;
RA Fadeev A., Mendoza-Garcia P., Irion U., Guan J., Pfeifer K., Wiessner S.,
RA Serluca F., Singh A.P., Nuesslein-Volhard C., Palmer R.H.;
RT "ALKALs are in vivo ligands for ALK family receptor tyrosine kinases in the
RT neural crest and derived cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E630-E638(2018).
CC -!- FUNCTION: Cytokine that acts as a physiological ligand for receptor
CC tyrosine kinases LTK and ALK (PubMed:29078341, PubMed:29317532).
CC Required for neural crest cell differentiation and iridophore
CC development during embryonic iridophore development and adult stripe
CC development by acting as a receptor for LTK (PubMed:29078341,
CC PubMed:29317532). {ECO:0000269|PubMed:29078341,
CC ECO:0000269|PubMed:29317532}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q6UX46}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000255}. Cell membrane
CC {ECO:0000250|UniProtKB:Q6UX46}.
CC -!- TISSUE SPECIFICITY: Expressed at high level in the notochord and
CC iridophore stripes of the trunk, as well as in the eye and swim
CC bladder. {ECO:0000269|PubMed:29317532}.
CC -!- DISRUPTION PHENOTYPE: Fishes show reduced dense iridophores in the
CC light stripes of the trunk, particularly in the anterior region,
CC resulting in irregular interruptions of melanophore stripes
CC (PubMed:29078341, PubMed:29317532). Fishes lacking alkal1, alkal2a and
CC alkal2b are embryonic lethal and display total loss of iridophores
CC (PubMed:29317532). {ECO:0000269|PubMed:29078341,
CC ECO:0000269|PubMed:29317532}.
CC -!- SIMILARITY: Belongs to the ALKAL family. {ECO:0000305}.
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DR EMBL; CU694248; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; E7F5F0; -.
DR STRING; 7955.ENSDARP00000111041; -.
DR PaxDb; E7F5F0; -.
DR Ensembl; ENSDART00000122387; ENSDARP00000111041; ENSDARG00000091073.
DR ZFIN; ZDB-GENE-100922-116; alkal2a.
DR eggNOG; ENOG502S2JY; Eukaryota.
DR GeneTree; ENSGT00940000162505; -.
DR HOGENOM; CLU_120534_0_0_1; -.
DR InParanoid; E7F5F0; -.
DR TreeFam; TF333390; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 23.
DR Bgee; ENSDARG00000091073; Expressed in tail and 12 other tissues.
DR ExpressionAtlas; E7F5F0; baseline.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005125; F:cytokine activity; IDA:UniProtKB.
DR GO; GO:0030298; F:receptor signaling protein tyrosine kinase activator activity; IDA:UniProtKB.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IBA:GO_Central.
DR GO; GO:0050935; P:iridophore differentiation; IMP:ZFIN.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IBA:GO_Central.
DR GO; GO:0070378; P:positive regulation of ERK5 cascade; IBA:GO_Central.
DR InterPro; IPR029364; FAM150A/B.
DR PANTHER; PTHR28676; PTHR28676; 1.
DR Pfam; PF15129; FAM150; 2.
PE 2: Evidence at transcript level;
KW Cell membrane; Cytokine; Disulfide bond; Membrane; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..169
FT /note="ALK and LTK ligand 2a"
FT /evidence="ECO:0000255"
FT /id="PRO_5015335589"
FT REGION 45..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 130..166
FT /evidence="ECO:0000250|UniProtKB:Q6UX46"
FT DISULFID 144..153
FT /evidence="ECO:0000250|UniProtKB:Q6UX46"
SQ SEQUENCE 169 AA; 19152 MW; 92FB044F2CFC7767 CRC64;
MRALRAPVLV MGLVLLICTA AQSDASANKV EKTLRRIMEI MRQVENSADD ESAQKTESAP
EPKDTHHLKT ASGETILEIF PRDLSRKEKF ITILTGRRLS NPLRHQSCVF ETSDLVVFHP
SGPLYFGPKC KKDVYRLYHN TRDCTIPAHY KRCARLLTRL AGTRKCQEG
