APEL_HUMAN
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 03-AUG-2022, entry version 151.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX 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 for
RT the human APJ receptor.";
RL Biochem. Biophys. Res. Commun. 251:471-476(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Brain;
RX 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., Tatemoto K.,
RA 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], AND TISSUE SPECIFICITY.
RC TISSUE=Hypothalamus;
RX PubMed=10617103; 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., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., 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., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., 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., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., 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., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., 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., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=11090199; 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 APJ,
RT inhibits human immunodeficiency virus type 1 entry.";
RL J. Virol. 74:11972-11976(2000).
CC -!- FUNCTION: Endogenous ligand for the apelin receptor (APLNR)
CC (PubMed:10525157). Drives internalization of the apelin receptor (By
CC similarity). Apelin-36 dissociates more hardly than (pyroglu)apelin-13
CC from APLNR (By similarity). Hormone involved in the regulation of
CC cardiac precursor cell movements during gastrulation and heart
CC morphogenesis (By similarity). Has an inhibitory effect on cytokine
CC production in response to T-cell receptor/CD3 cross-linking; the oral
CC intake of apelin in the colostrum and the milk might therefore modulate
CC immune responses in neonates (By similarity). Plays a role in early
CC coronary blood vessels formation (By similarity). Mediates myocardial
CC contractility in an ERK1/2-dependent manner (By similarity). May also
CC have a role in the central control of body fluid homeostasis by
CC influencing vasopressin release and drinking behavior (By similarity).
CC {ECO:0000250|UniProtKB:Q4TTN8, ECO:0000250|UniProtKB:Q9R0R3,
CC ECO:0000250|UniProtKB:Q9R0R4, ECO:0000269|PubMed:10525157}.
CC -!- FUNCTION: (Microbial infection) Endogenous ligand for the apelin
CC receptor (APLNR), an alternative coreceptor with CD4 for HIV-1
CC infection (PubMed:11090199). Inhibits HIV-1 entry in cells coexpressing
CC CD4 and APLNR (PubMed:11090199). Apelin-36 has a greater inhibitory
CC activity on HIV infection than other synthetic apelin derivatives
CC (PubMed:11090199). {ECO:0000269|PubMed:11090199}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q9TUI9}.
CC Secreted, extracellular space {ECO:0000250|UniProtKB:Q9TUI9}.
CC Note=Abundantly secreted in the colostrum. Lower level in milk.
CC Decreases rapidly within several days after parturition in milk, but is
CC still detectable even in commercial milk.
CC {ECO:0000250|UniProtKB:Q9TUI9}.
CC -!- TISSUE SPECIFICITY: Expressed in the brain with highest levels in the
CC frontal cortex, thalamus, hypothalamus and midbrain (PubMed:10617103).
CC Secreted by the mammary gland into the colostrum and the milk.
CC {ECO:0000269|PubMed:10617103}.
CC -!- PTM: Several active peptides may be produced by proteolytic processing
CC of the peptide precursor. {ECO:0000250|UniProtKB:Q9TUI9}.
CC -!- SIMILARITY: Belongs to the apelin family. {ECO:0000305}.
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DR EMBL; AB023493; BAA84975.1; -; mRNA.
DR EMBL; AF179680; AAF25815.1; -; Genomic_DNA.
DR EMBL; AL022162; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC021104; AAH21104.2; -; mRNA.
DR CCDS; CCDS48165.1; -.
DR RefSeq; NP_059109.3; NM_017413.4.
DR AlphaFoldDB; Q9ULZ1; -.
DR BMRB; Q9ULZ1; -.
DR BioGRID; 114385; 7.
DR IntAct; Q9ULZ1; 2.
DR STRING; 9606.ENSP00000391800; -.
DR BindingDB; Q9ULZ1; -.
DR BioMuta; APLN; -.
DR MassIVE; Q9ULZ1; -.
DR PaxDb; Q9ULZ1; -.
DR PeptideAtlas; Q9ULZ1; -.
DR PRIDE; Q9ULZ1; -.
DR Antibodypedia; 30097; 307 antibodies from 28 providers.
DR DNASU; 8862; -.
DR Ensembl; ENST00000429967.3; ENSP00000391800.2; ENSG00000171388.12.
DR GeneID; 8862; -.
DR KEGG; hsa:8862; -.
DR MANE-Select; ENST00000429967.3; ENSP00000391800.2; NM_017413.5; NP_059109.3.
DR UCSC; uc004eus.4; human.
DR CTD; 8862; -.
DR DisGeNET; 8862; -.
DR GeneCards; APLN; -.
DR HGNC; HGNC:16665; APLN.
DR HPA; ENSG00000171388; Tissue enhanced (brain, placenta).
DR MIM; 300297; gene.
DR neXtProt; NX_Q9ULZ1; -.
DR OpenTargets; ENSG00000171388; -.
DR PharmGKB; PA134984493; -.
DR VEuPathDB; HostDB:ENSG00000171388; -.
DR GeneTree; ENSGT00390000014020; -.
DR HOGENOM; CLU_198461_0_0_1; -.
DR InParanoid; Q9ULZ1; -.
DR OMA; CGVPLMQ; -.
DR OrthoDB; 1632257at2759; -.
DR PhylomeDB; Q9ULZ1; -.
DR TreeFam; TF339660; -.
DR PathwayCommons; Q9ULZ1; -.
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SignaLink; Q9ULZ1; -.
DR SIGNOR; Q9ULZ1; -.
DR BioGRID-ORCS; 8862; 3 hits in 662 CRISPR screens.
DR ChiTaRS; APLN; human.
DR GeneWiki; Apelin; -.
DR GenomeRNAi; 8862; -.
DR Pharos; Q9ULZ1; Tbio.
DR PRO; PR:Q9ULZ1; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q9ULZ1; protein.
DR Bgee; ENSG00000171388; Expressed in C1 segment of cervical spinal cord and 140 other tissues.
DR Genevisible; Q9ULZ1; HS.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0031704; F:apelin receptor binding; IDA:UniProtKB.
DR GO; GO:0005179; F:hormone activity; IMP:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0060183; P:apelin receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0060976; P:coronary vasculature development; ISS:UniProtKB.
DR GO; GO:0042756; P:drinking behavior; ISS:UniProtKB.
DR GO; GO:0007369; P:gastrulation; IEA:UniProtKB-KW.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR GO; GO:0007595; P:lactation; TAS:ProtInc.
DR GO; GO:0045776; P:negative regulation of blood pressure; ISS:UniProtKB.
DR GO; GO:0040037; P:negative regulation of fibroblast growth factor receptor signaling pathway; IGI:BHF-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; IGI:BHF-UCL.
DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; IMP:BHF-UCL.
DR GO; GO:1904022; P:positive regulation of G protein-coupled receptor internalization; IDA:UniProtKB.
DR GO; GO:0045823; P:positive regulation of heart contraction; ISS:UniProtKB.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; IDA:BHF-UCL.
DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; IDA:BHF-UCL.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR InterPro; IPR026155; Apelin.
DR PANTHER; PTHR15953; PTHR15953; 1.
DR Pfam; PF15360; Apelin; 1.
PE 2: Evidence at transcript level;
KW Angiogenesis; Cleavage on pair of basic residues; Developmental protein;
KW Gastrulation; Hormone; Host-virus interaction; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..41
FT /evidence="ECO:0000250"
FT /id="PRO_0000001759"
FT PEPTIDE 42..77
FT /note="Apelin-36"
FT /evidence="ECO:0000250"
FT /id="PRO_0000001760"
FT PEPTIDE 47..77
FT /note="Apelin-31"
FT /evidence="ECO:0000250"
FT /id="PRO_0000001761"
FT PEPTIDE 50..77
FT /note="Apelin-28"
FT /evidence="ECO:0000250"
FT /id="PRO_0000001762"
FT PEPTIDE 65..77
FT /note="Apelin-13"
FT /evidence="ECO:0000250"
FT /id="PRO_0000001763"
FT REGION 43..77
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 77 AA; 8569 MW; 41521E0DBE97BFDA CRC64;
MNLRLCVQAL LLLWLSLTAV CGGSLMPLPD GNGLEDGNVR HLVQPRGSRN GPGPWQGGRR
KFRRQRPRLS HKGPMPF
