APEL_MOUSE
ID APEL_MOUSE Reviewed; 77 AA.
AC Q9R0R4;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 131.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mammary gland;
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 [3]
RP FUNCTION.
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 [4]
RP TISSUE SPECIFICITY, AND ABSENCE OF INDUCTION.
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).
RN [5]
RP TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=28854362; DOI=10.1016/j.celrep.2017.08.014;
RA Freyer L., Hsu C.W., Nowotschin S., Pauli A., Ishida J., Kuba K.,
RA Fukamizu A., Schier A.F., Hoodless P.A., Dickinson M.E.,
RA Hadjantonakis A.K.;
RT "Loss of Apela peptide in mice causes low penetrance embryonic lethality
RT and defects in early mesodermal derivatives.";
RL Cell Rep. 20:2116-2130(2017).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28890073; DOI=10.1016/j.devcel.2017.08.008;
RA Sharma B., Ho L., Ford G.H., Chen H.I., Goldstone A.B., Woo Y.J.,
RA Quertermous T., Reversade B., Red-Horse K.;
RT "Alternative progenitor cells compensate to rebuild the coronary
RT vasculature in Elabela- and Apj-deficient hearts.";
RL Dev. Cell 42:655-666(2017).
CC -!- FUNCTION: Endogenous ligand for the apelin receptor (APLNR). Drives
CC internalization of APLNR (By similarity). Apelin-36 dissociates more
CC hardly than (pyroglu)apelin-13 from APLNR (By similarity). Hormone
CC involved in the regulation of cardiac precursor cell movements during
CC gastrulation and heart morphogenesis (By similarity). Has an inhibitory
CC effect on cytokine production in response to T-cell receptor/CD3 cross-
CC linking; the oral intake of apelin in the colostrum and the milk might
CC therefore modulate immune responses in neonates (PubMed:10525157).
CC Plays a role in early coronary blood vessels formation
CC (PubMed:28890073). Mediates myocardial contractility in an ERK1/2-
CC dependent manner (By similarity). May also have a role in the central
CC control of body fluid homeostasis by influencing vasopressin release
CC and drinking behavior (PubMed:11359874). {ECO:0000250|UniProtKB:Q4TTN8,
CC ECO:0000250|UniProtKB:Q9R0R3, ECO:0000269|PubMed:10525157,
CC ECO:0000269|PubMed:11359874, ECO:0000269|PubMed:28890073}.
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 extraembryonic visceral endoderm and
CC in the primitive streak at 6.5 and 7.5 dpc (PubMed:28854362). Expressed
CC in the anterior visceral yolk sac at 8.25 dpc (PubMed:28854362).
CC Expressed weakly in the embryonic heart at 11.5 dpc (PubMed:26611206).
CC Expressed in the adult heart (PubMed:26611206). Expressed in
CC endothelial cells and cardiomyocytes and weakly expressed in
CC fibroblasts (PubMed:26611206). {ECO:0000269|PubMed:26611206,
CC ECO:0000269|PubMed:28854362}.
CC -!- INDUCTION: Not up-regulated following myocardial infarction (MI) (at
CC protein level) (PubMed:26611206). {ECO:0000269|PubMed:26611206}.
CC -!- PTM: Several active peptides may be produced by proteolytic processing
CC of the peptide precursor. {ECO:0000250|UniProtKB:Q9TUI9}.
CC -!- DISRUPTION PHENOTYPE: Mice heart of embryos show increased coronary
CC vessel growth at 13.5 dpc and 15.5 dpc (PubMed:28890073). Double
CC knockout mice of APELA and APLN genes exhibit the same penetrance,
CC embryonic lethality and cardiovascular malformations as single APELA
CC knockout mice (PubMed:28854362). {ECO:0000269|PubMed:28890073}.
CC -!- SIMILARITY: Belongs to the apelin family. {ECO:0000305}.
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DR EMBL; AB023494; BAA84976.1; -; mRNA.
DR EMBL; BC020015; AAH20015.1; -; mRNA.
DR CCDS; CCDS40958.1; -.
DR RefSeq; NP_038940.1; NM_013912.4.
DR AlphaFoldDB; Q9R0R4; -.
DR BMRB; Q9R0R4; -.
DR STRING; 10090.ENSMUSP00000046012; -.
DR PaxDb; Q9R0R4; -.
DR PRIDE; Q9R0R4; -.
DR Antibodypedia; 30097; 307 antibodies from 28 providers.
DR DNASU; 30878; -.
DR Ensembl; ENSMUST00000039026; ENSMUSP00000046012; ENSMUSG00000037010.
DR GeneID; 30878; -.
DR KEGG; mmu:30878; -.
DR UCSC; uc009tbu.1; mouse.
DR CTD; 8862; -.
DR MGI; MGI:1353624; Apln.
DR VEuPathDB; HostDB:ENSMUSG00000037010; -.
DR eggNOG; ENOG502S9TY; Eukaryota.
DR GeneTree; ENSGT00390000014020; -.
DR HOGENOM; CLU_198461_0_0_1; -.
DR InParanoid; Q9R0R4; -.
DR OMA; CGVPLMQ; -.
DR OrthoDB; 1632257at2759; -.
DR PhylomeDB; Q9R0R4; -.
DR TreeFam; TF339660; -.
DR Reactome; R-MMU-375276; Peptide ligand-binding receptors.
DR Reactome; R-MMU-418594; G alpha (i) signalling events.
DR BioGRID-ORCS; 30878; 3 hits in 74 CRISPR screens.
DR PRO; PR:Q9R0R4; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q9R0R4; protein.
DR Bgee; ENSMUSG00000037010; Expressed in lumbar subsegment of spinal cord and 197 other tissues.
DR ExpressionAtlas; Q9R0R4; baseline and differential.
DR Genevisible; Q9R0R4; MM.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0031704; F:apelin receptor binding; ISS:UniProtKB.
DR GO; GO:0005179; F:hormone activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
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; IMP:UniProtKB.
DR GO; GO:0042756; P:drinking behavior; ISS:UniProtKB.
DR GO; GO:0007631; P:feeding behavior; ISO:MGI.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0007369; P:gastrulation; IEA:UniProtKB-KW.
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; ISO:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0003085; P:negative regulation of systemic arterial blood pressure; ISO:MGI.
DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0045906; P:negative regulation of vasoconstriction; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0051461; P:positive regulation of corticotropin secretion; ISO:MGI.
DR GO; GO:0051466; P:positive regulation of corticotropin-releasing hormone secretion; ISO:MGI.
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:0010460; P:positive regulation of heart rate; ISO:MGI.
DR GO; GO:0031652; P:positive regulation of heat generation; ISO:MGI.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; ISO:MGI.
DR GO; GO:0042327; P:positive regulation of phosphorylation; ISO:MGI.
DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; ISO:MGI.
DR GO; GO:0050878; P:regulation of body fluid levels; ISO:MGI.
DR GO; GO:0002026; P:regulation of the force of heart contraction; ISO:MGI.
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|UniProtKB:Q9TUI9"
FT /id="PRO_0000001764"
FT PEPTIDE 42..77
FT /note="Apelin-36"
FT /evidence="ECO:0000250"
FT /id="PRO_0000001765"
FT PEPTIDE 47..77
FT /note="Apelin-31"
FT /evidence="ECO:0000250"
FT /id="PRO_0000001766"
FT PEPTIDE 50..77
FT /note="Apelin-28"
FT /evidence="ECO:0000250"
FT /id="PRO_0000001767"
FT PEPTIDE 65..77
FT /note="Apelin-13"
FT /evidence="ECO:0000250"
FT /id="PRO_0000001768"
FT REGION 46..77
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 77 AA; 8658 MW; D71E0D58E47D2376 CRC64;
MNLRLCVQAL LLLWLSLTAV CGVPLMLPPD GTGLEEGSMR YLVKPRTSRT GPGAWQGGRR
KFRRQRPRLS HKGPMPF
