ID   APEL_DANRE              Reviewed;          77 AA.
AC   Q4TTN8;
DT   28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT   06-MAR-2007, sequence version 2.
DT   03-AUG-2022, entry version 111.
DE   RecName: Full=Apelin;
DE   AltName: Full=APJ endogenous ligand;
DE   Flags: Precursor;
GN   Name=apln {ECO:0000312|ZFIN:ZDB-GENE-070521-8};
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 {ECO:0000312|EMBL:AAY46798.2};
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP   PHENOTYPE.
RX   PubMed=17336905; DOI=10.1016/j.devcel.2007.01.011;
RA   Zeng X.-X.I., Wilm T.P., Sepich D.S., Solnica-Krezel L.;
RT   "Apelin and its receptor control heart field formation during zebrafish
RT   gastrulation.";
RL   Dev. Cell 12:391-402(2007).
RN   [2]
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   [3]
RP   DEVELOPMENTAL STAGE.
RX   PubMed=24407481; DOI=10.1126/science.1248636;
RA   Pauli A., Norris M.L., Valen E., Chew G.L., Gagnon J.A., Zimmerman S.,
RA   Mitchell A., Ma J., Dubrulle J., Reyon D., Tsai S.Q., Joung J.K.,
RA   Saghatelian A., Schier A.F.;
RT   "Toddler: an embryonic signal that promotes cell movement via apelin
RT   receptors.";
RL   Science 343:1248636-1248636(2014).
RN   [4]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=26017639; DOI=10.7554/elife.06726;
RA   Helker C.S., Schuermann A., Pollmann C., Chng S.C., Kiefer F.,
RA   Reversade B., Herzog W.;
RT   "The hormonal peptide Elabela guides angioblasts to the midline during
RT   vasculogenesis.";
RL   Elife 4:0-0(2015).
CC   -!- FUNCTION: Endogenous ligand for the apelin receptor (aplnra and/or
CC       aplnrb) (PubMed:17336905). Drives internalization of the apelin
CC       receptor (By similarity). Hormone involved in the regulation of cardiac
CC       precursor cell movements during gastrulation and heart morphogenesis
CC       (PubMed:17336905). Plays a role in early coronary blood vessels
CC       formation. Mediates myocardial contractility in an ERK1/2-dependent
CC       manner. May also have a role in the central control of body fluid
CC       homeostasis (By similarity). {ECO:0000250|UniProtKB:Q9R0R3,
CC       ECO:0000250|UniProtKB:Q9R0R4, ECO:0000269|PubMed:17336905}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q9TUI9}.
CC       Secreted, extracellular space {ECO:0000250|UniProtKB:Q9TUI9}.
CC   -!- DEVELOPMENTAL STAGE: Expressed at the end of gastrulation (at protein
CC       level) (PubMed:24407481). Expressed in the embryo from 7 to 48 hours
CC       post-fertilization (hpf) (PubMed:17336905). Expressed in the axial
CC       mesoderm and its later derivative, the notochord at 11.5 hpf
CC       (PubMed:17336905). Expressed in the forming head and heart and in the
CC       posterior notochord at 18 hpf (PubMed:17336905).
CC   -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the protein show impaired
CC       gastrulation and heart formation (PubMed:17336905). Embryos display
CC       reduced migration of anterior lateral plate mesoderm (LPM) cells and
CC       cardiac progenitor cells (angioblasts) toward the midline during late
CC       gastrulation (PubMed:17336905, PubMed:26017639). Embryos show altered
CC       cardiac gene expression (PubMed:17336905). Embryos with CRISPR-induced
CC       apelin and apela null mutations show a strong decrease in the
CC       angioblast migration to the embryonic midline during late gastrulation
CC       (PubMed:26017639). {ECO:0000269|PubMed:17336905,
CC       ECO:0000269|PubMed:26017639}.
CC   -!- SIMILARITY: Belongs to the apelin family. {ECO:0000305}.
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DR   EMBL; DQ062434; AAY46798.2; -; mRNA.
DR   EMBL; AL929104; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   RefSeq; NP_001159596.1; NM_001166124.3.
DR   AlphaFoldDB; Q4TTN8; -.
DR   STRING; 7955.ENSDARP00000069796; -.
DR   PaxDb; Q4TTN8; -.
DR   Ensembl; ENSDART00000075312; ENSDARP00000069796; ENSDARG00000053279.
DR   Ensembl; ENSDART00000132488; ENSDARP00000116403; ENSDARG00000053279.
DR   GeneID; 798375; -.
DR   KEGG; dre:798375; -.
DR   CTD; 8862; -.
DR   ZFIN; ZDB-GENE-070521-8; apln.
DR   eggNOG; ENOG502S5ZZ; Eukaryota.
DR   GeneTree; ENSGT00390000014020; -.
DR   HOGENOM; CLU_198461_0_0_1; -.
DR   InParanoid; Q4TTN8; -.
DR   OMA; CGVPLMQ; -.
DR   OrthoDB; 1632257at2759; -.
DR   TreeFam; TF339660; -.
DR   Reactome; R-DRE-375276; Peptide ligand-binding receptors.
DR   Reactome; R-DRE-418594; G alpha (i) signalling events.
DR   PRO; PR:Q4TTN8; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Chromosome 14.
DR   Bgee; ENSDARG00000053279; Expressed in spleen and 30 other tissues.
DR   GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell.
DR   GO; GO:0031704; F:apelin receptor binding; IDA:ZFIN.
DR   GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR   GO; GO:0048018; F:receptor ligand activity; TAS:ZFIN.
DR   GO; GO:0035479; P:angioblast cell migration from lateral mesoderm to midline; IGI:ZFIN.
DR   GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR   GO; GO:0042074; P:cell migration involved in gastrulation; IDA:ZFIN.
DR   GO; GO:0090134; P:cell migration involved in mesendoderm migration; IGI:ZFIN.
DR   GO; GO:0060976; P:coronary vasculature development; ISS:UniProtKB.
DR   GO; GO:0061371; P:determination of heart left/right asymmetry; IMP:ZFIN.
DR   GO; GO:0071910; P:determination of liver left/right asymmetry; IMP:ZFIN.
DR   GO; GO:0042756; P:drinking behavior; ISS:UniProtKB.
DR   GO; GO:0007507; P:heart development; IMP:ZFIN.
DR   GO; GO:0001945; P:lymph vessel development; IMP:ZFIN.
DR   GO; GO:0008078; P:mesodermal cell migration; IMP:ZFIN.
DR   GO; GO:0045776; P:negative regulation of blood pressure; ISS:UniProtKB.
DR   GO; GO:0045823; P:positive regulation of heart contraction; ISS:UniProtKB.
DR   GO; GO:0001666; P:response to hypoxia; IDA:ZFIN.
DR   InterPro; IPR026155; Apelin.
DR   PANTHER; PTHR15953; PTHR15953; 1.
DR   Pfam; PF15360; Apelin; 1.
PE   1: Evidence at protein level;
KW   Angiogenesis; Developmental protein; Gastrulation; Hormone;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   CHAIN           23..77
FT                   /note="Apelin"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_5011209528"
FT   REGION          21..77
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        56..70
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   77 AA;  8572 MW;  A766EB27EB84237B CRC64;
     MNVKILTLVI VLVVSLLCSA SAGPMASTEH SKEIEEVGSM RTPLRQNPAR AGRSQRPAGW
     RRRRPRPRLS HKGPMPF