AGRA2_HUMAN
ID AGRA2_HUMAN Reviewed; 1338 AA.
AC Q96PE1; A6H8W3; D3DSW4; Q8N3R1; Q8TEM3; Q96KB2; Q9P1Z7; Q9UFY4;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 20-JAN-2009, sequence version 2.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Adhesion G protein-coupled receptor A2 {ECO:0000305};
DE AltName: Full=G-protein coupled receptor 124 {ECO:0000303|PubMed:21421844};
DE AltName: Full=Tumor endothelial marker 5 {ECO:0000303|PubMed:11559528};
DE Flags: Precursor;
GN Name=ADGRA2 {ECO:0000312|HGNC:HGNC:17849};
GN Synonyms=GPR124 {ECO:0000303|PubMed:21421844},
GN KIAA1531 {ECO:0000303|PubMed:10819331}, TEM5 {ECO:0000303|PubMed:11559528};
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] (ISOFORM 1).
RX PubMed=11559528;
RA Carson-Walter E.B., Watkins D.N., Nanda A., Vogelstein B., Kinzler K.W.,
RA St Croix B.;
RT "Cell surface tumor endothelial markers are conserved in mice and humans.";
RL Cancer Res. 61:6649-6655(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=10819331; DOI=10.1093/dnares/7.2.143;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:143-150(2000).
RN [3]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Embryo;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-1338 (ISOFORM 1).
RX PubMed=12565841; DOI=10.1016/s0006-291x(03)00026-3;
RA Fredriksson R., Gloriam D.E.I., Hoeglund P.J., Lagerstroem M.C.,
RA Schioeth H.B.;
RT "There exist at least 30 human G-protein-coupled receptors with long
RT Ser/Thr-rich N-termini.";
RL Biochem. Biophys. Res. Commun. 301:725-734(2003).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 29-1338 (ISOFORM 1).
RC TISSUE=Spleen;
RA Jikuya H., Takano J., Nomura N., Kikuno R., Nagase T., Ohara O.;
RT "The nucleotide sequence of a long cDNA clone isolated from human spleen.";
RL Submitted (MAY-2013) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP PROTEIN SEQUENCE OF 370-374 AND 399-403, SUBCELLULAR LOCATION, PROTEOLYTIC
RP CLEAVAGE, PRESENCE OF DISULFIDE BONDS, TOPOLOGY, AND MUTAGENESIS OF ARG-369
RP AND ARG-398.
RX PubMed=22013897; DOI=10.1042/bj20111682;
RA Vallon M., Aubele P., Janssen K.P., Essler M.;
RT "Thrombin-induced shedding of tumour endothelial marker 5 and exposure of
RT its RGD motif are regulated by cell-surface protein disulfide-isomerase.";
RL Biochem. J. 441:937-944(2012).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 850-1338.
RC TISSUE=Amygdala, and Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [12]
RP TISSUE SPECIFICITY, INTERACTION WITH DLG1, MOTIF PDZ-BINDING, AND
RP MUTAGENESIS OF 1335-GLU--VAL-1338.
RX PubMed=15021905; DOI=10.1038/sj.onc.1207495;
RA Yamamoto Y., Irie K., Asada M., Mino A., Mandai K., Takai Y.;
RT "Direct binding of the human homologue of the Drosophila disc large tumor
RT suppressor gene to seven-pass transmembrane proteins, tumor endothelial
RT marker 5 (TEM5), and a novel TEM5-like protein.";
RL Oncogene 23:3889-3897(2004).
RN [13]
RP FUNCTION, INTERACTION WITH ITGAV AND ITGB3, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, PROTEOLYTIC CLEAVAGE, TOPOLOGY, AND MOTIF RGD.
RX PubMed=16982628; DOI=10.1074/jbc.m605291200;
RA Vallon M., Essler M.;
RT "Proteolytically processed soluble tumor endothelial marker (TEM) 5
RT mediates endothelial cell survival during angiogenesis by linking integrin
RT alpha(v)beta3 to glycosaminoglycans.";
RL J. Biol. Chem. 281:34179-34188(2006).
RN [14]
RP SUBCELLULAR LOCATION, GLYCOSYLATION, AND TOPOLOGY.
RX PubMed=21421844; DOI=10.1073/pnas.1017192108;
RA Cullen M., Elzarrad M.K., Seaman S., Zudaire E., Stevens J., Yang M.Y.,
RA Li X., Chaudhary A., Xu L., Hilton M.B., Logsdon D., Hsiao E., Stein E.V.,
RA Cuttitta F., Haines D.C., Nagashima K., Tessarollo L., St Croix B.;
RT "GPR124, an orphan G protein-coupled receptor, is required for CNS-specific
RT vascularization and establishment of the blood-brain barrier.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:5759-5764(2011).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1107, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [16]
RP FUNCTION.
RX PubMed=28289266; DOI=10.1242/jcs.198093;
RA Alok A., Lei Z., Jagannathan N.S., Kaur S., Harmston N., Rozen S.G.,
RA Tucker-Kellogg L., Virshup D.M.;
RT "Wnt proteins synergize to activate beta-catenin signaling.";
RL J. Cell Sci. 130:1532-1544(2017).
RN [17]
RP FUNCTION.
RX PubMed=30026314; DOI=10.1126/science.aat1178;
RA Eubelen M., Bostaille N., Cabochette P., Gauquier A., Tebabi P.,
RA Dumitru A.C., Koehler M., Gut P., Alsteens D., Stainier D.Y.R.,
RA Garcia-Pino A., Vanhollebeke B.;
RT "A molecular mechanism for Wnt ligand-specific signaling.";
RL Science 361:0-0(2018).
RN [18]
RP VARIANT LEU-29.
RX PubMed=24501278; DOI=10.1093/hmg/ddu056;
RA Lee H., Lin M.C., Kornblum H.I., Papazian D.M., Nelson S.F.;
RT "Exome sequencing identifies de novo gain of function missense mutation in
RT KCND2 in identical twins with autism and seizures that slows potassium
RT channel inactivation.";
RL Hum. Mol. Genet. 23:3481-3489(2014).
RN [19]
RP VARIANT LYS-375.
RX PubMed=24925318; DOI=10.1093/hmg/ddu296;
RA Di Costanzo S., Balasubramanian A., Pond H.L., Rozkalne A., Pantaleoni C.,
RA Saredi S., Gupta V.A., Sunu C.M., Yu T.W., Kang P.B., Salih M.A., Mora M.,
RA Gussoni E., Walsh C.A., Manzini M.C.;
RT "POMK mutations disrupt muscle development leading to a spectrum of
RT neuromuscular presentations.";
RL Hum. Mol. Genet. 23:5781-5792(2014).
CC -!- FUNCTION: Endothelial receptor which functions together with RECK to
CC enable brain endothelial cells to selectively respond to Wnt7 signals
CC (WNT7A or WNT7B) (PubMed:28289266, PubMed:30026314). Plays a key role
CC in Wnt7-specific responses, such as endothelial cell sprouting and
CC migration in the forebrain and neural tube, and establishment of the
CC blood-brain barrier (By similarity). Acts as a Wnt7-specific
CC coactivator of canonical Wnt signaling: required to deliver RECK-bound
CC Wnt7 to frizzled by assembling a higher-order RECK-ADGRA2-Fzd-LRP5-LRP6
CC complex (PubMed:30026314). ADGRA2-tethering function does not rely on
CC its G-protein coupled receptor (GPCR) structure but instead on its
CC combined capacity to interact with RECK extracellularly and recruit the
CC Dishevelled scaffolding protein intracellularly (PubMed:30026314).
CC Binds to the glycosaminoglycans heparin, heparin sulfate, chondroitin
CC sulfate and dermatan sulfate (PubMed:16982628).
CC {ECO:0000250|UniProtKB:Q91ZV8, ECO:0000269|PubMed:16982628,
CC ECO:0000269|PubMed:28289266, ECO:0000269|PubMed:30026314}.
CC -!- SUBUNIT: Interacts with RECK; the interaction is direct (By
CC similarity). Interacts (via PDZ-binding motif) with DLG1 (via PDZ
CC domains) (PubMed:15021905). The cleaved extracellular subunit interacts
CC with the integrin heterodimer ITGAV:ITGB3 (PubMed:16982628).
CC {ECO:0000250|UniProtKB:Q91ZV8, ECO:0000269|PubMed:15021905,
CC ECO:0000269|PubMed:16982628}.
CC -!- INTERACTION:
CC Q96PE1; Q12959: DLG1; NbExp=2; IntAct=EBI-10893263, EBI-357481;
CC Q96PE1; Q12959-2: DLG1; NbExp=2; IntAct=EBI-10893263, EBI-357500;
CC Q96PE1-2; O95273: CCNDBP1; NbExp=3; IntAct=EBI-12227349, EBI-748961;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16982628,
CC ECO:0000269|PubMed:21421844, ECO:0000269|PubMed:22013897}; Multi-pass
CC membrane protein {ECO:0000255}. Cell projection, filopodium
CC {ECO:0000269|PubMed:21421844}. Note=Enriched at lateral cell borders
CC and also at sites of cell-ECM (extracellular matrix) contact.
CC {ECO:0000269|PubMed:21421844}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q96PE1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96PE1-2; Sequence=VSP_010076;
CC Name=3;
CC IsoId=Q96PE1-3; Sequence=VSP_036215;
CC -!- TISSUE SPECIFICITY: Expressed in endothelial cells (at protein level)
CC (PubMed:15021905, PubMed:16982628). Abundantly expressed in heart,
CC placenta, ovary, small intestine, and colon (PubMed:15021905).
CC {ECO:0000269|PubMed:15021905, ECO:0000269|PubMed:16982628}.
CC -!- DOMAIN: The leucine-rich repeats (LRRs) are important for potentiation
CC of Wnt7 signaling. {ECO:0000250|UniProtKB:Q91ZV8}.
CC -!- DOMAIN: The RGD motif is involved in integrin ITGAV:ITGB3 binding.
CC {ECO:0000269|PubMed:16982628}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:21421844}.
CC -!- PTM: Proteolytically cleaved into two subunits, an extracellular
CC subunit and a seven-transmembrane subunit (PubMed:22013897,
CC PubMed:16982628). Cleaved by thrombin (F2) and MMP1 (PubMed:22013897).
CC Also cleaved by MMP9, with lower efficiency (PubMed:22013897,
CC PubMed:16982628). Presence of the protein disulfide-isomerase P4HB at
CC the cell surface is additionally required for shedding of the
CC extracellular subunit, suggesting that the subunits are linked by
CC disulfide bonds (PubMed:22013897). Shedding is enhanced by the growth
CC factor FGF2 and may promote cell survival during angiogenesis
CC (PubMed:16982628). {ECO:0000269|PubMed:16982628,
CC ECO:0000269|PubMed:22013897}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 2 family.
CC Adhesion G-protein coupled receptor (ADGR) subfamily. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-8 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI46775.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAL11992.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAO27354.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA96055.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF378755; AAL11992.1; ALT_INIT; mRNA.
DR EMBL; AB040964; BAA96055.2; ALT_INIT; mRNA.
DR EMBL; AK027296; BAB55022.1; -; mRNA.
DR EMBL; AC138356; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471080; EAW63355.1; -; Genomic_DNA.
DR EMBL; CH471080; EAW63356.1; -; Genomic_DNA.
DR EMBL; BC146774; AAI46775.1; ALT_INIT; mRNA.
DR EMBL; AY181242; AAO27354.1; ALT_INIT; mRNA.
DR EMBL; AK074099; BAB84925.2; -; mRNA.
DR EMBL; AL110244; CAB53694.1; -; mRNA.
DR EMBL; AL832524; CAD38629.1; -; mRNA.
DR CCDS; CCDS6097.2; -. [Q96PE1-1]
DR PIR; T14774; T14774.
DR RefSeq; NP_116166.9; NM_032777.9. [Q96PE1-1]
DR AlphaFoldDB; Q96PE1; -.
DR SMR; Q96PE1; -.
DR BioGRID; 117450; 4.
DR IntAct; Q96PE1; 3.
DR MINT; Q96PE1; -.
DR STRING; 9606.ENSP00000406367; -.
DR ChEMBL; CHEMBL4523909; -.
DR GlyGen; Q96PE1; 11 sites, 3 O-linked glycans (4 sites).
DR iPTMnet; Q96PE1; -.
DR PhosphoSitePlus; Q96PE1; -.
DR BioMuta; ADGRA2; -.
DR DMDM; 221222450; -.
DR jPOST; Q96PE1; -.
DR MassIVE; Q96PE1; -.
DR PaxDb; Q96PE1; -.
DR PeptideAtlas; Q96PE1; -.
DR PRIDE; Q96PE1; -.
DR ProteomicsDB; 77674; -. [Q96PE1-1]
DR ProteomicsDB; 77675; -. [Q96PE1-2]
DR ProteomicsDB; 77676; -. [Q96PE1-3]
DR Antibodypedia; 1931; 330 antibodies from 32 providers.
DR DNASU; 25960; -.
DR Ensembl; ENST00000315215.11; ENSP00000323508.7; ENSG00000020181.18. [Q96PE1-2]
DR Ensembl; ENST00000412232.3; ENSP00000406367.2; ENSG00000020181.18. [Q96PE1-1]
DR GeneID; 25960; -.
DR KEGG; hsa:25960; -.
DR MANE-Select; ENST00000412232.3; ENSP00000406367.2; NM_032777.10; NP_116166.9.
DR UCSC; uc003xkj.4; human. [Q96PE1-1]
DR CTD; 25960; -.
DR DisGeNET; 25960; -.
DR GeneCards; ADGRA2; -.
DR HGNC; HGNC:17849; ADGRA2.
DR HPA; ENSG00000020181; Low tissue specificity.
DR MIM; 606823; gene.
DR neXtProt; NX_Q96PE1; -.
DR OpenTargets; ENSG00000020181; -.
DR PharmGKB; PA134869404; -.
DR VEuPathDB; HostDB:ENSG00000020181; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000158941; -.
DR HOGENOM; CLU_005242_0_0_1; -.
DR InParanoid; Q96PE1; -.
DR OMA; IRWYHNQ; -.
DR OrthoDB; 31536at2759; -.
DR PhylomeDB; Q96PE1; -.
DR TreeFam; TF331206; -.
DR PathwayCommons; Q96PE1; -.
DR SignaLink; Q96PE1; -.
DR BioGRID-ORCS; 25960; 7 hits in 1075 CRISPR screens.
DR ChiTaRS; ADGRA2; human.
DR GeneWiki; GPR124; -.
DR GenomeRNAi; 25960; -.
DR Pharos; Q96PE1; Tbio.
DR PRO; PR:Q96PE1; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q96PE1; protein.
DR Bgee; ENSG00000020181; Expressed in stromal cell of endometrium and 156 other tissues.
DR ExpressionAtlas; Q96PE1; baseline and differential.
DR Genevisible; Q96PE1; HS.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0030175; C:filopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; TAS:GDB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:1990909; C:Wnt signalosome; IDA:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; TAS:GDB.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007417; P:central nervous system development; ISS:UniProtKB.
DR GO; GO:0043542; P:endothelial cell migration; ISS:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:GDB.
DR GO; GO:1900747; P:negative regulation of vascular endothelial growth factor signaling pathway; IEA:Ensembl.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IEA:Ensembl.
DR GO; GO:0045765; P:regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0050920; P:regulation of chemotaxis; ISS:UniProtKB.
DR GO; GO:0090210; P:regulation of establishment of blood-brain barrier; ISS:UniProtKB.
DR GO; GO:0002040; P:sprouting angiogenesis; ISS:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 2.60.220.50; -; 1.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR Gene3D; 4.10.1240.10; -; 1.
DR InterPro; IPR000483; Cys-rich_flank_reg_C.
DR InterPro; IPR046338; GAIN_dom_sf.
DR InterPro; IPR017981; GPCR_2-like.
DR InterPro; IPR036445; GPCR_2_extracell_dom_sf.
DR InterPro; IPR001879; GPCR_2_extracellular_dom.
DR InterPro; IPR000832; GPCR_2_secretin-like.
DR InterPro; IPR017983; GPCR_2_secretin-like_CS.
DR InterPro; IPR000203; GPS.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR Pfam; PF00002; 7tm_2; 1.
DR Pfam; PF01825; GPS; 1.
DR Pfam; PF13855; LRR_8; 1.
DR SMART; SM00409; IG; 1.
DR SMART; SM00369; LRR_TYP; 4.
DR SMART; SM00082; LRRCT; 1.
DR SUPFAM; SSF111418; SSF111418; 1.
DR PROSITE; PS00650; G_PROTEIN_RECEP_F2_2; 1.
DR PROSITE; PS50227; G_PROTEIN_RECEP_F2_3; 1.
DR PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1.
DR PROSITE; PS50221; GPS; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS51450; LRR; 4.
PE 1: Evidence at protein level;
KW Alternative splicing; Angiogenesis; Cell membrane; Cell projection;
KW Direct protein sequencing; Disulfide bond; G-protein coupled receptor;
KW Glycoprotein; Immunoglobulin domain; Leucine-rich repeat; Membrane;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transducer;
KW Transmembrane; Transmembrane helix; Wnt signaling pathway.
FT SIGNAL 1..33
FT /evidence="ECO:0000255"
FT CHAIN 34..1338
FT /note="Adhesion G protein-coupled receptor A2"
FT /id="PRO_0000012898"
FT TOPO_DOM 34..771
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:16982628,
FT ECO:0000305|PubMed:21421844, ECO:0000305|PubMed:22013897"
FT TRANSMEM 772..792
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 793..807
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 808..828
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 829..832
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 833..853
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 854..886
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 887..907
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 908..924
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 925..945
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 946..1019
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1020..1040
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1041..1047
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1048..1068
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1069..1338
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:21421844"
FT REPEAT 82..106
FT /note="LRR 1"
FT /evidence="ECO:0000255"
FT REPEAT 107..130
FT /note="LRR 2"
FT /evidence="ECO:0000255"
FT REPEAT 131..154
FT /note="LRR 3"
FT /evidence="ECO:0000255"
FT REPEAT 156..178
FT /note="LRR 4"
FT /evidence="ECO:0000255"
FT DOMAIN 190..240
FT /note="LRRCT"
FT /evidence="ECO:0000255"
FT DOMAIN 247..344
FT /note="Ig-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 707..758
FT /note="GPS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00098"
FT REGION 565..591
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 958..991
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1088..1126
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1150..1196
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1218..1309
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 362..364
FT /note="RGD"
FT /evidence="ECO:0000269|PubMed:16982628"
FT MOTIF 1335..1338
FT /note="PDZ-binding"
FT /evidence="ECO:0000269|PubMed:15021905"
FT COMPBIAS 574..588
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1171..1188
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1218..1240
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 369..370
FT /note="Cleavage; by thrombin"
FT /evidence="ECO:0000269|PubMed:22013897"
FT SITE 398..399
FT /note="Cleavage; by thrombin"
FT /evidence="ECO:0000269|PubMed:22013897"
FT MOD_RES 1107
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT CARBOHYD 84
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 162
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 207
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 275
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 602
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 690
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 268..328
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 186..1338
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_036215"
FT VAR_SEQ 537..753
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10819331,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_010076"
FT VARIANT 29
FT /note="P -> L (found in a family with atypical autism and
FT severe epilepsy; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:24501278"
FT /id="VAR_072079"
FT VARIANT 375
FT /note="T -> K"
FT /evidence="ECO:0000269|PubMed:24925318"
FT /id="VAR_072561"
FT MUTAGEN 369
FT /note="R->A: Minimal effect on thrombin cleavage. Abolishes
FT thrombin cleavage; when associated with G-398."
FT /evidence="ECO:0000269|PubMed:22013897"
FT MUTAGEN 398
FT /note="R->G: Minimal effect on thrombin cleavage. Abolishes
FT thrombin cleavage; when associated with A-369."
FT /evidence="ECO:0000269|PubMed:22013897"
FT MUTAGEN 1335..1338
FT /note="Missing: Fails to interact with DLG1."
FT /evidence="ECO:0000269|PubMed:15021905"
FT CONFLICT 407
FT /note="G -> S (in Ref. 9; BAB84925)"
FT /evidence="ECO:0000305"
FT CONFLICT 1221
FT /note="S -> G (in Ref. 2; BAA96055 and 7; AAI46775)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1338 AA; 142647 MW; 322838CB31E99A97 CRC64;
MGAGGRRMRG APARLLLPLL PWLLLLLAPE ARGAPGCPLS IRSCKCSGER PKGLSGGVPG
PARRRVVCSG GDLPEPPEPG LLPNGTVTLL LSNNKITGLR NGSFLGLSLL EKLDLRNNII
STVQPGAFLG LGELKRLDLS NNRIGCLTSE TFQGLPRLLR LNISGNIFSS LQPGVFDELP
ALKVVDLGTE FLTCDCHLRW LLPWAQNRSL QLSEHTLCAY PSALHAQALG SLQEAQLCCE
GALELHTHHL IPSLRQVVFQ GDRLPFQCSA SYLGNDTRIR WYHNRAPVEG DEQAGILLAE
SLIHDCTFIT SELTLSHIGV WASGEWECTV SMAQGNASKK VEIVVLETSA SYCPAERVAN
NRGDFRWPRT LAGITAYQSC LQYPFTSVPL GGGAPGTRAS RRCDRAGRWE PGDYSHCLYT
NDITRVLYTF VLMPINASNA LTLAHQLRVY TAEAASFSDM MDVVYVAQMI QKFLGYVDQI
KELVEVMVDM ASNLMLVDEH LLWLAQREDK ACSRIVGALE RIGGAALSPH AQHISVNARN
VALEAYLIKP HSYVGLTCTA FQRREGGVPG TRPGSPGQNP PPEPEPPADQ QLRFRCTTGR
PNVSLSSFHI KNSVALASIQ LPPSLFSSLP AALAPPVPPD CTLQLLVFRN GRLFHSHSNT
SRPGAAGPGK RRGVATPVIF AGTSGCGVGN LTEPVAVSLR HWAEGAEPVA AWWSQEGPGE
AGGWTSEGCQ LRSSQPNVSA LHCQHLGNVA VLMELSAFPR EVGGAGAGLH PVVYPCTALL
LLCLFATIIT YILNHSSIRV SRKGWHMLLN LCFHIAMTSA VFAGGITLTN YQMVCQAVGI
TLHYSSLSTL LWMGVKARVL HKELTWRAPP PQEGDPALPT PSPMLRFYLI AGGIPLIICG
ITAAVNIHNY RDHSPYCWLV WRPSLGAFYI PVALILLITW IYFLCAGLRL RGPLAQNPKA
GNSRASLEAG EELRGSTRLR GSGPLLSDSG SLLATGSARV GTPGPPEDGD SLYSPGVQLG
ALVTTHFLYL AMWACGALAV SQRWLPRVVC SCLYGVAASA LGLFVFTHHC ARRRDVRASW
RACCPPASPA APHAPPRALP AAAEDGSPVF GEGPPSLKSS PSGSSGHPLA LGPCKLTNLQ
LAQSQVCEAG AAAGGEGEPE PAGTRGNLAH RHPNNVHHGR RAHKSRAKGH RAGEACGKNR
LKALRGGAAG ALELLSSESG SLHNSPTDSY LGSSRNSPGA GLQLEGEPML TPSEGSDTSA
APLSEAGRAG QRRSASRDSL KGGGALEKES HRRSYPLNAA SLNGAPKGGK YDDVTLMGAE
VASGGCMKTG LWKSETTV
