ID   APEL_HUMAN              Reviewed;          77 AA.
AC   Q9ULZ1; Q4VY08; Q8WU89;
DT   23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   24-NOV-2009, entry version 61.
DE   RecName: Full=Apelin;
DE   AltName: Full=APJ endogenous ligand;
DE   Contains:
DE     RecName: Full=Apelin-36;
DE   Contains:
DE     RecName: Full=Apelin-31;
DE   Contains:
DE     RecName: Full=Apelin-28;
DE   Contains:
DE     RecName: Full=Apelin-13;
DE   Flags: Precursor;
GN   Name=APLN; Synonyms=APEL;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Brain;
RX   MEDLINE=99011403; PubMed=9792798; DOI=10.1006/bbrc.1998.9489;
RA   Tatemoto K., Hosoya M., Habata Y., Fujii R., Kakegawa T., Zou M.-X.,
RA   Kawamata Y., Fukusumi S., Hinuma S., Kitada C., Kurokawa T., Onda H.,
RA   Fujino M.;
RT   "Isolation and characterization of a novel endogenous peptide ligand
RT   for the human APJ receptor.";
RL   Biochem. Biophys. Res. Commun. 251:471-476(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Brain;
RX   MEDLINE=99454637; PubMed=10525157; DOI=10.1016/S0167-4889(99)00114-7;
RA   Habata Y., Fujii R., Hosoya M., Fukusumi S., Kawamata Y., Hinuma S.,
RA   Kitada C., Nishizawa N., Murosaki S., Kurokawa T., Onda H.,
RA   Tatemoto K., Fujino M.;
RT   "Apelin, the natural ligand of the orphan receptor APJ, is abundantly
RT   secreted in the colostrum.";
RL   Biochim. Biophys. Acta 1452:25-35(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Hypothalamus;
RX   MEDLINE=20083393; PubMed=10617103;
RX   DOI=10.1046/j.1471-4159.2000.0740034.x;
RA   Lee D.K., Cheng R., Nguyen T., Fan T., Kariyawasam A.P., Liu Y.,
RA   Osmond D.H., George S.R., O'Dowd B.F.;
RT   "Characterization of apelin, the ligand for the APJ receptor.";
RL   J. Neurochem. 74:34-41(2000).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15772651; DOI=10.1038/nature03440;
RA   Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA   Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
RA   Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA   Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA   Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA   Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA   Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA   Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA   Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA   Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA   Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA   Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA   Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA   Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA   Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA   Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA   Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA   Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
RA   Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA   Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA   Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA   Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA   Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA   Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA   Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA   Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA   Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA   de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA   Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA   Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA   Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA   Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA   McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
RA   Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA   Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA   Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA   Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA   Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA   Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA   Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA   Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA   Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
RA   Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA   Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA   Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA   Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA   Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA   Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA   Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA   Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA   Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
RA   Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA   Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence of the human X chromosome.";
RL   Nature 434:325-337(2005).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   FUNCTION.
RX   MEDLINE=20541999; PubMed=11090199;
RX   DOI=10.1128/JVI.74.24.11972-11976.2000;
RA   Cayabyab M., Hinuma S., Farzan M., Choe H., Fukusumi S., Kitada C.,
RA   Nishizawa N., Hosoya M., Nishimura O., Messele T., Pollakis G.,
RA   Goudsmit J., Fujino M., Sodroski J.;
RT   "Apelin, the natural ligand of the orphan seven-transmembrane receptor
RT   APJ, inhibits human immunodeficiency virus type 1 entry.";
RL   J. Virol. 74:11972-11976(2000).
CC   -!- FUNCTION: Endogenous ligand for APJ, an alternative coreceptor
CC       with CD4 for HIV-1 infection. Inhibits HIV-1 entry in cells
CC       coexpressing CD4 and APJ. Apelin-36 has a greater inhibitory
CC       activity on HIV infection than other synthetic apelin derivatives.
CC       The oral intake in the colostrum and the milk could have a role in
CC       the modulation of the immune responses in neonates. May also have
CC       a role in the central control of body fluid homeostasis by
CC       influencing AVP release and drinking behavior.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Expressed in the brain with highest levels in
CC       the frontal cortex, thalamus, hypothalamus and midbrain. Secreted
CC       by the mammary gland into the colostrum and the milk.
CC   -!- PTM: Several active peptides may be produced by proteolytic
CC       processing of the peptide precursor.
CC   -!- SIMILARITY: Belongs to the apelin family.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAI95697.1; Type=Erroneous gene model prediction;
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DR   EMBL; AB023493; BAA84975.1; -; mRNA.
DR   EMBL; AF179680; AAF25815.1; -; Genomic_DNA.
DR   EMBL; AL022162; CAI95697.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; BC021104; AAH21104.2; -; mRNA.
DR   IPI; IPI00010087; -.
DR   RefSeq; NP_059109.3; -.
DR   UniGene; Hs.303084; -.
DR   IntAct; Q9ULZ1; 1.
DR   Ensembl; ENST00000307484; ENSP00000305464; ENSG00000171388; Homo sapiens.
DR   GeneID; 8862; -.
DR   KEGG; hsa:8862; -.
DR   UCSC; uc004eus.1; human.
DR   CTD; 8862; -.
DR   GeneCards; GC0XM128607; -.
DR   H-InvDB; HIX0017039; -.
DR   HGNC; HGNC:16665; APLN.
DR   MIM; 300297; gene.
DR   PharmGKB; PA134984493; -.
DR   HOVERGEN; Q9ULZ1; -.
DR   OrthoDB; EOG9G7FK1; -.
DR   Reactome; REACT_14797; Signaling by GPCR.
DR   NextBio; 33277; -.
DR   ArrayExpress; Q9ULZ1; -.
DR   Bgee; Q9ULZ1; -.
DR   CleanEx; HS_APLN; -.
DR   Genevestigator; Q9ULZ1; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR   GO; GO:0007186; P:G-protein coupled receptor protein signalin...; EXP:Reactome.
DR   GO; GO:0006955; P:immune response; TAS:ProtInc.
DR   GO; GO:0007595; P:lactation; TAS:ProtInc.
PE   2: Evidence at transcript level;
KW   Cleavage on pair of basic residues; Complete proteome; Hormone;
KW   Pyrrolidone carboxylic acid; Secreted; Signal.
FT   SIGNAL        1     22       Potential.
FT   PROPEP       23     41       By similarity.
FT                                /FTId=PRO_0000001759.
FT   PEPTIDE      42     77       Apelin-36 (By similarity).
FT                                /FTId=PRO_0000001760.
FT   PEPTIDE      47     77       Apelin-31 (By similarity).
FT                                /FTId=PRO_0000001761.
FT   PEPTIDE      50     77       Apelin-28 (By similarity).
FT                                /FTId=PRO_0000001762.
FT   PEPTIDE      65     77       Apelin-13 (By similarity).
FT                                /FTId=PRO_0000001763.
FT   MOD_RES      65     65       Pyrrolidone carboxylic acid (By
FT                                similarity).
SQ   SEQUENCE   77 AA;  8569 MW;  41521E0DBE97BFDA CRC64;
     MNLRLCVQAL LLLWLSLTAV CGGSLMPLPD GNGLEDGNVR HLVQPRGSRN GPGPWQGGRR
     KFRRQRPRLS HKGPMPF
//