APEL_RAT
ID APEL_RAT Reviewed; 77 AA.
AC Q9R0R3;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 118.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP INDUCTION.
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [4]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11336787; DOI=10.1016/s0167-4889(00)00143-9;
RA Kawamata Y., Habata Y., Fukusumi S., Hosoya M., Fujii R., Hinuma S.,
RA Nishizawa N., Kitada C., Onda H., Nishimura O., Fujino M.;
RT "Molecular properties of apelin: tissue distribution and receptor
RT binding.";
RL Biochim. Biophys. Acta 1538:162-171(2001).
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11359874; DOI=10.1046/j.1471-4159.2001.00320.x;
RA Reaux A., De Mota N., Skultetyova I., Lenkei Z., El Messari S., Gallatz K.,
RA Corvol P., Palkovits M., Llorens-Cortes C.;
RT "Physiological role of a novel neuropeptide, apelin, and its receptor in
RT the rat brain.";
RL J. Neurochem. 77:1085-1096(2001).
RN [6]
RP FUNCTION.
RX PubMed=26611206; DOI=10.1007/s00395-015-0521-6;
RA Perjes A., Kilpioe T., Ulvila J., Magga J., Alakoski T., Szabo Z.,
RA Vainio L., Halmetoja E., Vuolteenaho O., Petaejae-Repo U., Szokodi I.,
RA Kerkelae R.;
RT "Characterization of apela, a novel endogenous ligand of apelin receptor,
RT in the adult heart.";
RL Basic Res. Cardiol. 111:2-2(2016).
CC -!- FUNCTION: Endogenous ligand for the apelin receptor (APLNR)
CC (PubMed:11336787, PubMed:11359874, PubMed:26611206). Drives
CC internalization of the apelin receptor (PubMed:11359874). Apelin-36
CC dissociates more hardly than (pyroglu)apelin-13 from APLNR
CC (PubMed:11336787). Hormone involved in the regulation of cardiac
CC precursor cell movements during gastrulation and heart morphogenesis
CC (By similarity). Has an inhibitory effect on cytokine production in
CC response to T-cell receptor/CD3 cross-linking; the oral intake of
CC apelin in the colostrum and the milk might therefore modulate immune
CC responses in neonates (By similarity). Plays a role in early coronary
CC blood vessels formation (By similarity). Mediates myocardial
CC contractility in an ERK1/2-dependent manner (PubMed:26611206). May also
CC have a role in the central control of body fluid homeostasis by
CC influencing vasopressin release and drinking behavior (PubMed:10617103,
CC PubMed:11359874). {ECO:0000250|UniProtKB:Q4TTN8,
CC ECO:0000250|UniProtKB:Q9R0R4, ECO:0000269|PubMed:10617103,
CC ECO:0000269|PubMed:11336787, ECO:0000269|PubMed:11359874,
CC ECO:0000269|PubMed:26611206}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10525157}. Secreted,
CC extracellular space {ECO:0000269|PubMed:10525157}. Note=Abundantly
CC secreted in the colostrum (By similarity). Lower level in milk
CC (PubMed:10525157). Decreases rapidly within several days after
CC parturition in milk, but is still detectable even in commercial milk
CC (By similarity). {ECO:0000250|UniProtKB:Q9TUI9}.
CC -!- TISSUE SPECIFICITY: Expressed in the lung, testis, ovary, uterus and
CC mammary gland (PubMed:11336787). Expressed in neurons in the thalamic
CC paraventricular and hypothalamic supraoptic nuclei (PubMed:11359874).
CC The lung, testis and uterus mainly contain a large form that looks like
CC apelin-36, whereas the mammary gland seems to contain 2 forms of
CC apelin, a large form close to apelin-36 and a small form close to
CC apelin-13 (at protein level) (PubMed:11336787). Widely expressed in the
CC adult, with highest levels in the mammary gland of lactating animals,
CC very high levels in the lung, intermediate levels in the spinal cord,
CC ovary, adipose tissue, brain (neuronal cell bodies and fibers in the
CC supraoptic and the paraventricular nuclei), heart and testis, and
CC lowest levels in the pituitary gland, kidney, stomach, uterus and
CC pancreas (PubMed:10525157, PubMed:10617103, PubMed:11336787).
CC {ECO:0000269|PubMed:10525157, ECO:0000269|PubMed:10617103,
CC ECO:0000269|PubMed:11336787, ECO:0000269|PubMed:11359874}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in neonatal tissues. In the
CC adult, reaches a maximal level around parturition.
CC -!- INDUCTION: During pregnancy and lactation (PubMed:10525157).
CC {ECO:0000269|PubMed:10525157}.
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; AB023495; BAA84977.1; -; mRNA.
DR EMBL; AF179679; AAF25814.1; -; mRNA.
DR EMBL; BC080843; AAH80843.1; -; mRNA.
DR RefSeq; NP_113800.1; NM_031612.3.
DR AlphaFoldDB; Q9R0R3; -.
DR BMRB; Q9R0R3; -.
DR STRING; 10116.ENSRNOP00000005331; -.
DR BindingDB; Q9R0R3; -.
DR PaxDb; Q9R0R3; -.
DR GeneID; 58812; -.
DR KEGG; rno:58812; -.
DR UCSC; RGD:620672; rat.
DR CTD; 8862; -.
DR RGD; 620672; Apln.
DR eggNOG; ENOG502S9TY; Eukaryota.
DR HOGENOM; CLU_198461_0_0_1; -.
DR InParanoid; Q9R0R3; -.
DR OMA; CGVPLMQ; -.
DR OrthoDB; 1632257at2759; -.
DR PhylomeDB; Q9R0R3; -.
DR TreeFam; TF339660; -.
DR Reactome; R-RNO-375276; Peptide ligand-binding receptors.
DR Reactome; R-RNO-418594; G alpha (i) signalling events.
DR PRO; PR:Q9R0R3; -.
DR Proteomes; UP000002494; Chromosome X.
DR Bgee; ENSRNOG00000003984; Expressed in lung and 17 other tissues.
DR Genevisible; Q9R0R3; RN.
DR GO; GO:0005576; C:extracellular region; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0031704; F:apelin receptor binding; IDA:UniProtKB.
DR GO; GO:0005179; F:hormone activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
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; IMP:UniProtKB.
DR GO; GO:0007631; P:feeding behavior; IMP:RGD.
DR GO; GO:0007369; P:gastrulation; IEA:UniProtKB-KW.
DR GO; GO:0045776; P:negative regulation of blood pressure; IDA:RGD.
DR GO; GO:0040037; P:negative regulation of fibroblast growth factor receptor signaling pathway; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0003085; P:negative regulation of systemic arterial blood pressure; IDA:RGD.
DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; ISO:RGD.
DR GO; GO:0045906; P:negative regulation of vasoconstriction; IMP:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:RGD.
DR GO; GO:0051461; P:positive regulation of corticotropin secretion; IMP:RGD.
DR GO; GO:0051466; P:positive regulation of corticotropin-releasing hormone secretion; IMP:RGD.
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; IMP:UniProtKB.
DR GO; GO:0010460; P:positive regulation of heart rate; IDA:RGD.
DR GO; GO:0031652; P:positive regulation of heat generation; IMP:RGD.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; ISO:RGD.
DR GO; GO:0042327; P:positive regulation of phosphorylation; IMP:RGD.
DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; ISO:RGD.
DR GO; GO:0050878; P:regulation of body fluid levels; IMP:RGD.
DR GO; GO:0002026; P:regulation of the force of heart contraction; IMP:RGD.
DR InterPro; IPR026155; Apelin.
DR PANTHER; PTHR15953; PTHR15953; 1.
DR Pfam; PF15360; Apelin; 1.
PE 1: Evidence at protein level;
KW Angiogenesis; Cleavage on pair of basic residues; Developmental protein;
KW Gastrulation; Hormone; Reference proteome; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..41
FT /evidence="ECO:0000250"
FT /id="PRO_0000001769"
FT PEPTIDE 42..77
FT /note="Apelin-36"
FT /id="PRO_0000001770"
FT PEPTIDE 47..77
FT /note="Apelin-31"
FT /evidence="ECO:0000250"
FT /id="PRO_0000001771"
FT PEPTIDE 50..77
FT /note="Apelin-28"
FT /evidence="ECO:0000250"
FT /id="PRO_0000001772"
FT PEPTIDE 65..77
FT /note="Apelin-13"
FT /id="PRO_0000001773"
FT REGION 45..77
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 77 AA; 8677 MW; 944D52154F824EC4 CRC64;
MNLSFCVQAL LLLWLSLTAV CGVPLMLPPD GKGLEEGNMR YLVKPRTSRT GPGAWQGGRR
KFRRQRPRLS HKGPMPF
