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Adhesion G protein-coupled receptor A2 (G-protein coupled receptor 124) (Tumor endothelial marker 5)

 AGRA2_MOUSE             Reviewed;        1336 AA.
Q91ZV8; B2RRK0;
13-APR-2004, integrated into UniProtKB/Swiss-Prot.
20-JAN-2009, sequence version 2.
22-NOV-2017, entry version 132.
RecName: Full=Adhesion G protein-coupled receptor A2 {ECO:0000312|MGI:MGI:1925810};
AltName: Full=G-protein coupled receptor 124 {ECO:0000312|MGI:MGI:1925810};
AltName: Full=Tumor endothelial marker 5 {ECO:0000303|PubMed:11559528};
Flags: Precursor;
Name=Adgra2 {ECO:0000312|MGI:MGI:1925810};
Synonyms=Gpr124 {ECO:0000312|MGI:MGI:1925810},
Tem5 {ECO:0000303|PubMed:11559528};
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
PubMed=11559528;
Carson-Walter E.B., Watkins D.N., Nanda A., Vogelstein B.,
Kinzler K.W., St Croix B.;
"Cell surface tumor endothelial markers are conserved in mice and
humans.";
Cancer Res. 61:6649-6655(2001).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Brain;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[3]
DEVELOPMENTAL STAGE.
PubMed=18848646; DOI=10.1016/j.gep.2008.09.004;
Homma S., Shimada T., Hikake T., Yaginuma H.;
"Expression pattern of LRR and Ig domain-containing protein (LRRIG
protein) in the early mouse embryo.";
Gene Expr. Patterns 9:1-26(2009).
[4]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Lung;
PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
"A tissue-specific atlas of mouse protein phosphorylation and
expression.";
Cell 143:1174-1189(2010).
[5]
FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
PubMed=21071672; DOI=10.1126/science.1196554;
Kuhnert F., Mancuso M.R., Shamloo A., Wang H.T., Choksi V., Florek M.,
Su H., Fruttiger M., Young W.L., Heilshorn S.C., Kuo C.J.;
"Essential regulation of CNS angiogenesis by the orphan G protein-
coupled receptor GPR124.";
Science 330:985-989(2010).
[6]
FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION, AND
DISRUPTION PHENOTYPE.
PubMed=21282641; DOI=10.1073/pnas.1019761108;
Anderson K.D., Pan L., Yang X.M., Hughes V.C., Walls J.R.,
Dominguez M.G., Simmons M.V., Burfeind P., Xue Y., Wei Y.,
Macdonald L.E., Thurston G., Daly C., Lin H.C., Economides A.N.,
Valenzuela D.M., Murphy A.J., Yancopoulos G.D., Gale N.W.;
"Angiogenic sprouting into neural tissue requires Gpr124, an orphan G
protein-coupled receptor.";
Proc. Natl. Acad. Sci. U.S.A. 108:2807-2812(2011).
[7]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=21421844; DOI=10.1073/pnas.1017192108;
Cullen M., Elzarrad M.K., Seaman S., Zudaire E., Stevens J.,
Yang M.Y., Li X., Chaudhary A., Xu L., Hilton M.B., Logsdon D.,
Hsiao E., Stein E.V., Cuttitta F., Haines D.C., Nagashima K.,
Tessarollo L., St Croix B.;
"GPR124, an orphan G protein-coupled receptor, is required for CNS-
specific vascularization and establishment of the blood-brain
barrier.";
Proc. Natl. Acad. Sci. U.S.A. 108:5759-5764(2011).
[8]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=25373781; DOI=10.1016/j.devcel.2014.08.018;
Zhou Y., Nathans J.;
"Gpr124 controls CNS angiogenesis and blood-brain barrier integrity by
promoting ligand-specific canonical wnt signaling.";
Dev. Cell 31:248-256(2014).
[9]
FUNCTION, INTERACTION WITH DLG1, SUBCELLULAR LOCATION, DOMAIN LRR,
MOTIF PDZ-BINDING, AND MUTAGENESIS OF ASP-364 AND 1333-GLU--VAL-1336.
PubMed=25558062; DOI=10.1016/j.celrep.2014.12.020;
Posokhova E., Shukla A., Seaman S., Volate S., Hilton M.B., Wu B.,
Morris H., Swing D.A., Zhou M., Zudaire E., Rubin J.S., St Croix B.;
"GPR124 functions as a WNT7-specific coactivator of canonical beta-
catenin signaling.";
Cell Rep. 10:123-130(2015).
-!- FUNCTION: Endothelial receptor which functions as a WNT7-specific
coactivator of canonical Wnt signaling (PubMed:25373781,
PubMed:25558062). Required for normal endothelial cell sprouting
and migration in the forebrain and neural tube (PubMed:21071672,
PubMed:21282641, PubMed:21421844, PubMed:25373781). Has a major
role in establishing the blood-brain barrier (PubMed:21421844,
PubMed:25373781). Binds to the glycosaminoglycans heparin, heparin
sulfate, chondroitin sulfate and dermatan sulfate (By similarity).
{ECO:0000250|UniProtKB:Q96PE1, ECO:0000269|PubMed:21071672,
ECO:0000269|PubMed:21282641, ECO:0000269|PubMed:21421844,
ECO:0000269|PubMed:25373781, ECO:0000269|PubMed:25558062}.
-!- SUBUNIT: Interacts (via PDZ-binding motif) with DLG1 (via PDZ
domains) (PubMed:25558062). The cleaved extracellular subunit
interacts with the integrin heterodimer ITGAV:ITGB3 (By
similarity). {ECO:0000250|UniProtKB:Q96PE1,
ECO:0000269|PubMed:25558062}.
-!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:25558062};
Multi-pass membrane protein {ECO:0000255}. Cell projection,
filopodium {ECO:0000250|UniProtKB:Q96PE1}. Note=Enriched at
lateral cell borders and also at sites of cell-ECM (extracellular
matrix) contact. {ECO:0000250|UniProtKB:Q96PE1}.
-!- TISSUE SPECIFICITY: Abundantly expressed in the vasculature of the
developing embryo (PubMed:11559528, PubMed:21071672,
PubMed:21282641). Expression in normal adult tissues is
specifically vascular with endothelial expression in CNS,
including brain and retina and more widespread pericyte expression
in the brain and organs, including the kidney, pancreas and corpus
luteum (PubMed:21071672). {ECO:0000269|PubMed:11559528,
ECO:0000269|PubMed:21071672, ECO:0000269|PubMed:21282641}.
-!- DEVELOPMENTAL STAGE: At embryonic day 10 (E10) expressed in a wide
variety of tissues with relatively more abundant expression in
limb buds (PubMed:18848646). At E10.5-E12.5, detected in vessels
of the developing CNS and perineural vascular plexus (PNVP)
(PubMed:21282641). Expressed in both endothelial cells and
pericytes, most prominently in brain and neural tube, and to a
lesser degrees in non-CNS embryonic organs, including the liver,
heart, and kidney (PubMed:18848646, PubMed:21282641). Expressed
also in embryonic epithelium of lung and esophagus and in
mesenchyme (PubMed:18848646, PubMed:21282641). Detected in
mesenchyme of the palatal shelf at E12.5 (PubMed:21282641).
{ECO:0000269|PubMed:18848646, ECO:0000269|PubMed:21282641}.
-!- INDUCTION: Up-regulated by the growth factors activin AB (INHBA:
INHBB dimer) and TGFB1 in vitro. {ECO:0000269|PubMed:21282641}.
-!- DOMAIN: The leucine-rich repeats (LRRs) are important for
potentiation of WNT7 signaling. {ECO:0000269|PubMed:25558062}.
-!- DOMAIN: The RGD motif is involved in integrin ITGAV:ITGB3 binding.
{ECO:0000250|UniProtKB:Q96PE1}.
-!- PTM: Glycosylated. {ECO:0000250|UniProtKB:Q96PE1}.
-!- PTM: Proteolytically cleaved into two subunits, an extracellular
subunit and a seven-transmembrane subunit. Cleaved by thrombin
(F2) and MMP1. Also cleaved by MMP9, with lower efficiency.
Presence of the protein disulfide-isomerase P4HB at the cell
surface is additionally required for shedding of the extracellular
subunit, suggesting that the subunits are linked by disulfide
bonds. Shedding is enhanced by the growth factor FGF2 and may
promote cell survival during angiogenesis.
{ECO:0000250|UniProtKB:Q96PE1}.
-!- DISRUPTION PHENOTYPE: No viable adults (PubMed:21071672,
PubMed:21282641, PubMed:21421844). Beginning at E11, deficient
embryos exhibit completely penetrant, progressive CNS hemorrhage
originating in forebrain telencephalon and ventral neural tube
leading to embryonic lethality from E15.5 (PubMed:21071672,
PubMed:21282641, PubMed:21421844). Embryos at E11.5 display
selective CNS-specific vascular patterning defects, with markedly
reduced angiogenic sprouting into the forebrain telencephalon and
thickening of the underlying periventricular vascular plexus
rendering the telencephalon virtually avascular (PubMed:21071672,
PubMed:21282641, PubMed:21421844, PubMed:25373781). Remaining CNS
vessels show significantly increased permeability
(PubMed:21421844). Lung size is reduced in E15.5 embryos
(PubMed:21282641). Cleft palate is present at E15.5 or later
(PubMed:21282641). {ECO:0000269|PubMed:21071672,
ECO:0000269|PubMed:21282641, ECO:0000269|PubMed:21421844}.
-!- SIMILARITY: Belongs to the G-protein coupled receptor 2 family.
Adhesion G-protein coupled receptor (ADGR) subfamily.
{ECO:0000305}.
-!- CAUTION: It is uncertain whether Met-1 or Met-8 is the initiator.
{ECO:0000305}.
-!- SEQUENCE CAUTION:
Sequence=AAI38452.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
Sequence=AAI38453.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
Sequence=AAL11996.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
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EMBL; AF378759; AAL11996.1; ALT_INIT; mRNA.
EMBL; BC138451; AAI38452.1; ALT_INIT; mRNA.
EMBL; BC138452; AAI38453.1; ALT_INIT; mRNA.
CCDS; CCDS22210.2; -.
RefSeq; NP_473385.2; NM_054044.2.
UniGene; Mm.87046; -.
ProteinModelPortal; Q91ZV8; -.
SMR; Q91ZV8; -.
STRING; 10090.ENSMUSP00000033876; -.
iPTMnet; Q91ZV8; -.
PhosphoSitePlus; Q91ZV8; -.
MaxQB; Q91ZV8; -.
PaxDb; Q91ZV8; -.
PRIDE; Q91ZV8; -.
Ensembl; ENSMUST00000033876; ENSMUSP00000033876; ENSMUSG00000031486.
GeneID; 78560; -.
KEGG; mmu:78560; -.
UCSC; uc009lhx.2; mouse.
CTD; 25960; -.
MGI; MGI:1925810; Adgra2.
eggNOG; KOG0619; Eukaryota.
eggNOG; COG4886; LUCA.
GeneTree; ENSGT00860000133701; -.
HOGENOM; HOG000112767; -.
HOVERGEN; HBG051777; -.
InParanoid; Q91ZV8; -.
KO; K08461; -.
OMA; RTLCAYP; -.
OrthoDB; EOG091G03GB; -.
PhylomeDB; Q91ZV8; -.
TreeFam; TF331206; -.
PRO; PR:Q91ZV8; -.
Proteomes; UP000000589; Chromosome 8.
Bgee; ENSMUSG00000031486; -.
CleanEx; MM_GPR124; -.
ExpressionAtlas; Q91ZV8; baseline and differential.
Genevisible; Q91ZV8; MM.
GO; GO:0009986; C:cell surface; IDA:MGI.
GO; GO:0030175; C:filopodium; IEA:UniProtKB-SubCell.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0005886; C:plasma membrane; ISO:MGI.
GO; GO:0004930; F:G-protein coupled receptor activity; IEA:UniProtKB-KW.
GO; GO:0001525; P:angiogenesis; IMP:MGI.
GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:InterPro.
GO; GO:0007417; P:central nervous system development; IMP:UniProtKB.
GO; GO:0043542; P:endothelial cell migration; IMP:UniProtKB.
GO; GO:1900747; P:negative regulation of vascular endothelial growth factor signaling pathway; IMP:MGI.
GO; GO:0010595; P:positive regulation of endothelial cell migration; IDA:MGI.
GO; GO:0045765; P:regulation of angiogenesis; IMP:UniProtKB.
GO; GO:0050920; P:regulation of chemotaxis; IMP:UniProtKB.
GO; GO:0090210; P:regulation of establishment of blood-brain barrier; IMP:MGI.
GO; GO:0002040; P:sprouting angiogenesis; IMP:UniProtKB.
Gene3D; 2.60.40.10; -; 1.
Gene3D; 3.80.10.10; -; 1.
Gene3D; 4.10.1240.10; -; 1.
InterPro; IPR000483; Cys-rich_flank_reg_C.
InterPro; IPR017981; GPCR_2-like.
InterPro; IPR036445; GPCR_2_extracell_dom_sf.
InterPro; IPR001879; GPCR_2_extracellular_dom.
InterPro; IPR000832; GPCR_2_secretin-like.
InterPro; IPR017983; GPCR_2_secretin-like_CS.
InterPro; IPR000203; GPS.
InterPro; IPR007110; Ig-like_dom.
InterPro; IPR036179; Ig-like_dom_sf.
InterPro; IPR013783; Ig-like_fold.
InterPro; IPR003599; Ig_sub.
InterPro; IPR001611; Leu-rich_rpt.
InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
InterPro; IPR032675; LRR_dom_sf.
Pfam; PF00002; 7tm_2; 1.
Pfam; PF01825; GPS; 1.
Pfam; PF13855; LRR_8; 1.
SMART; SM00409; IG; 1.
SMART; SM00369; LRR_TYP; 4.
SMART; SM00082; LRRCT; 1.
SUPFAM; SSF111418; SSF111418; 1.
SUPFAM; SSF48726; SSF48726; 1.
SUPFAM; SSF52058; SSF52058; 1.
PROSITE; PS00650; G_PROTEIN_RECEP_F2_2; 1.
PROSITE; PS50227; G_PROTEIN_RECEP_F2_3; 1.
PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1.
PROSITE; PS50221; GPS; 1.
PROSITE; PS50835; IG_LIKE; 1.
PROSITE; PS51450; LRR; 3.
1: Evidence at protein level;
Angiogenesis; Cell membrane; Cell projection; Complete proteome;
Disulfide bond; G-protein coupled receptor; Glycoprotein;
Immunoglobulin domain; Leucine-rich repeat; Membrane; Phosphoprotein;
Receptor; Reference proteome; Repeat; Signal; Transducer;
Transmembrane; Transmembrane helix.
SIGNAL 1 33 {ECO:0000255}.
CHAIN 34 1336 Adhesion G protein-coupled receptor A2.
/FTId=PRO_0000012899.
TOPO_DOM 34 769 Extracellular.
{ECO:0000250|UniProtKB:Q96PE1}.
TRANSMEM 770 790 Helical; Name=1. {ECO:0000255}.
TOPO_DOM 791 805 Cytoplasmic. {ECO:0000255}.
TRANSMEM 806 826 Helical; Name=2. {ECO:0000255}.
TOPO_DOM 827 830 Extracellular. {ECO:0000255}.
TRANSMEM 831 851 Helical; Name=3. {ECO:0000255}.
TOPO_DOM 852 884 Cytoplasmic. {ECO:0000255}.
TRANSMEM 885 905 Helical; Name=4. {ECO:0000255}.
TOPO_DOM 906 922 Extracellular. {ECO:0000255}.
TRANSMEM 923 943 Helical; Name=5. {ECO:0000255}.
TOPO_DOM 944 1016 Cytoplasmic. {ECO:0000255}.
TRANSMEM 1017 1037 Helical; Name=6. {ECO:0000255}.
TOPO_DOM 1038 1044 Extracellular. {ECO:0000255}.
TRANSMEM 1045 1065 Helical; Name=7. {ECO:0000255}.
TOPO_DOM 1066 1336 Cytoplasmic.
{ECO:0000250|UniProtKB:Q96PE1}.
REPEAT 85 106 LRR 1. {ECO:0000255}.
REPEAT 109 130 LRR 2. {ECO:0000255}.
REPEAT 133 154 LRR 3. {ECO:0000255}.
REPEAT 157 178 LRR 4. {ECO:0000255}.
DOMAIN 190 241 LRRCT. {ECO:0000255}.
DOMAIN 247 344 Ig-like. {ECO:0000255|PROSITE-
ProRule:PRU00114}.
DOMAIN 708 756 GPS. {ECO:0000255|PROSITE-
ProRule:PRU00098}.
MOTIF 362 364 RGD. {ECO:0000250|UniProtKB:Q96PE1}.
MOTIF 1333 1336 PDZ-binding.
{ECO:0000269|PubMed:25558062}.
COMPBIAS 777 782 Poly-Leu. {ECO:0000255}.
COMPBIAS 1126 1129 Poly-Pro. {ECO:0000255}.
SITE 369 370 Cleavage; by thrombin.
{ECO:0000250|UniProtKB:Q96PE1}.
SITE 398 399 Cleavage; by thrombin.
{ECO:0000250|UniProtKB:Q96PE1}.
MOD_RES 1104 1104 Phosphoserine.
{ECO:0000250|UniProtKB:Q96PE1}.
CARBOHYD 84 84 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 101 101 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 162 162 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 275 275 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 602 602 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 691 691 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 735 735 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 268 328 {ECO:0000255|PROSITE-ProRule:PRU00114}.
MUTAGEN 364 364 D->E: No effect on potentiation of WNT7A
signaling. {ECO:0000269|PubMed:25558062}.
MUTAGEN 1333 1336 Missing: Fails to interact with DLG1. No
effect on cell surface localization.
{ECO:0000269|PubMed:25558062}.
SEQUENCE 1336 AA; 143170 MW; C65354E5331F049F CRC64;
MGAGGRRMPV PPARLLLLPL LPCLLLLAPG TRGAPGCPVP IRGCKCSGER PKGLSGGAHN
PARRRVVCGG GDLPEPPDPG LLPNGTITLL LSNNKITGLR NGSFLGLSLL EKLDLRSNVI
STVQPGAFLG LGELKRLDLS NNRIGCLTSE TFQGLPRLLR LNISGNIYSS LQPGVFDELP
ALKIVDFGTE FLTCDCRLRW LLPWARNHSL QLSERTLCAY PSALHAHALS SLQESQLRCE
GALELHTHYL IPSLRQVVFQ GDRLPFQCSA SYLGNDTRIH WYHNGAPMES DEQAGIVLAE
NLIHDCTFIT SELTLSHIGV WASGEWECSV STVQGNTSKK VEIVVLETSA SYCPAERVTN
NRGDFRWPRT LAGITAYQSC LQYPFTSVPL SGGAPGTRAS RRCDRAGRWE PGDYSHCLYT
NDITRVLYTF VLMPINASNA LTLAHQLRVY TAEAASFSDM MDVVYVAQMI QKFLGYVDQI
KELVEVMVDM ASNLMLVDEH LLWLAQREDK ACSGIVGALE RIGGAALSPH AQHISVNSRN
VALEAYLIKP HSYVGLTCTA FQRREVGVSG AQPSSVGQDA PVEPEPLADQ QLRFRCTTGR
PNISLSSFHI KNSVALASIQ LPPSLFSTLP AALAPPVPPD CTLQLLVFRN GRLFRSHGNN
TSRPGAAGPG KRRGVATPVI FAGTSGCGVG NLTEPVAVSL RHWAEGADPM AAWWNQDGPG
GWSSEGCRLR YSQPNVSSLY CQHLGNVAVL MELNAFPREA GGSGAGLHPV VYPCTALLLL
CLFSTIITYI LNHSSIHVSR KGWHMLLNLC FHMAMTSAVF VGGVTLTNYQ MVCQAVGITL
HYSSLSSLLW MGVKARVLHK ELSWRAPPLE EGEAAPPGPR PMLRFYLIAG GIPLIICGIT
AAVNIHNYRD HSPYCWLVWR PSLGAFYIPV ALILPITWIY FLCAGLHLRS HVAQNPKQGN
RISLEPGEEL RGSTRLRSSG VLLNDSGSLL ATVSAGVGTP APPEDGDGVY SPGVQLGALM
TTHFLYLAMW ACGALAVSQR WLPRVVCSCL YGVAASALGL FVFTHHCARR RDVRASWRAC
CPPASPSASH VPARALPTAT EDGSPVLGEG PASLKSSPSG SSGRAPPPPC KLTNLQVAQS
QVCEASVAAR GDGEPEPTGS RGSLAPRHHN NLHHGRRVHK SRAKGHRAGE TGGKSRLKAL
RAGTSPGAPE LLSSESGSLH NSPSDSYPGS SRNSPGDGLP LEGEPMLTPS EGSDTSAAPI
AETGRPGQRR SASRDNLKGS GSALERESKR RSYPLNTTSL NGAPKGGKYE DASVTGAEAI
AGGSMKTGLW KSETTV


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EIAAB27655 GPR74,G-protein coupled receptor 74,G-protein coupled receptor HLWAR77,Homo sapiens,Human,Neuropeptide FF receptor 2,Neuropeptide G-protein coupled receptor,NPFF2,NPFFR2,NPGPR
18-461-10708 G-protein coupled receptor 120 - G-protein coupled receptor PGR4; G-protein coupled receptor GT01; G-protein coupled receptor 129 Polyclonal 0.05 ml
18-461-10414 G-protein coupled receptor 120 - G-protein coupled receptor PGR4; G-protein coupled receptor GT01; G-protein coupled receptor 129 Polyclonal 0.05 ml
18-461-10415 G-protein coupled receptor 120 - G-protein coupled receptor PGR4; G-protein coupled receptor GT01; G-protein coupled receptor 129 Polyclonal 0.05 ml
18-461-10413 G-protein coupled receptor 120 - G-protein coupled receptor PGR4; G-protein coupled receptor GT01; G-protein coupled receptor 129 Polyclonal 0.05 ml


 

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