AGRE2_HUMAN
ID AGRE2_HUMAN Reviewed; 823 AA.
AC Q9UHX3; B4DQ96; E7ESD7; E9PBR1; E9PEL6; E9PFQ5; E9PG91; Q8NG96; Q9Y4B1;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2006, sequence version 2.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Adhesion G protein-coupled receptor E2 {ECO:0000303|PubMed:25713288};
DE AltName: Full=EGF-like module receptor 2;
DE AltName: Full=EGF-like module-containing mucin-like hormone receptor-like 2;
DE AltName: CD_antigen=CD312;
DE Flags: Precursor;
GN Name=ADGRE2 {ECO:0000312|HGNC:HGNC:3337}; Synonyms=EMR2;
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), TISSUE SPECIFICITY, ALTERNATIVE
RP SPLICING (ISOFORMS 2; 3; 4 AND 5), AND VARIANT PHE-614.
RX PubMed=10903844; DOI=10.1006/geno.2000.6238;
RA Lin H.-H., Stacey M., Hamann J., Gordon S., McKnight A.J.;
RT "Human EMR2, a novel EGF-TM7 molecule on chromosome 19p13.1, is closely
RT related to CD97.";
RL Genomics 67:188-200(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S.,
RA Tsutsumi S., Aburatani H., Asai K., Akiyama Y.;
RT "Genome-wide discovery and analysis of human seven transmembrane helix
RT receptor genes.";
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6), AND VARIANT PHE-614.
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT PHE-614.
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [5]
RP PROTEIN SEQUENCE OF 518-527, PROTEOLYTIC PROCESSING, AND MUTAGENESIS OF
RP SER-518.
RX PubMed=12860403; DOI=10.1016/s0014-5793(03)00695-1;
RA Chang G.-W., Stacey M., Kwakkenbos M.J., Hamann J., Gordon S., Lin H.-H.;
RT "Proteolytic cleavage of the EMR2 receptor requires both the extracellular
RT stalk and the GPS motif.";
RL FEBS Lett. 547:145-150(2003).
RN [6]
RP CHARACTERIZATION, AND TISSUE SPECIFICITY.
RX PubMed=11994511;
RA Kwakkenbos M.J., Chang G.-W., Lin H.-H., Pouwels W., de Jong E.C.,
RA van Lier R.A.W., Gordon S., Hamann J.;
RT "The human EGF-TM7 family member EMR2 is a heterodimeric receptor expressed
RT on myeloid cells.";
RL J. Leukoc. Biol. 71:854-862(2002).
RN [7]
RP FUNCTION, AND INTERACTION WITH CHONDROITIN SULFATE.
RX PubMed=12829604; DOI=10.1182/blood-2002-11-3540;
RA Stacey M., Chang G.-W., Davies J.Q., Kwakkenbos M.J., Sanderson R.D.,
RA Hamann J., Gordon S., Lin H.-H.;
RT "The epidermal growth factor-like domains of the human EMR2 receptor
RT mediate cell attachment through chondroitin sulfate glycosaminoglycans.";
RL Blood 102:2916-2924(2003).
RN [8]
RP AUTOPROTEOLYTIC CLEAVAGE, AND SUBUNIT.
RX PubMed=15150276; DOI=10.1074/jbc.m402974200;
RA Lin H.H., Chang G.W., Davies J.Q., Stacey M., Harris J., Gordon S.;
RT "Autocatalytic cleavage of the EMR2 receptor occurs at a conserved G
RT protein-coupled receptor proteolytic site motif.";
RL J. Biol. Chem. 279:31823-31832(2004).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17928360; DOI=10.1096/fj.07-9435com;
RA Yona S., Lin H.H., Dri P., Davies J.Q., Hayhoe R.P., Lewis S.M.,
RA Heinsbroek S.E., Brown K.A., Perretti M., Hamann J., Treacher D.F.,
RA Gordon S., Stacey M.;
RT "Ligation of the adhesion-GPCR EMR2 regulates human neutrophil function.";
RL FASEB J. 22:741-751(2008).
RN [10]
RP FUNCTION.
RX PubMed=22575658; DOI=10.1016/j.febslet.2012.03.014;
RA Gupte J., Swaminath G., Danao J., Tian H., Li Y., Wu X.;
RT "Signaling property study of adhesion G-protein-coupled receptors.";
RL FEBS Lett. 586:1214-1219(2012).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22310662; DOI=10.1128/mcb.06557-11;
RA Huang Y.S., Chiang N.Y., Hu C.H., Hsiao C.C., Cheng K.F., Tsai W.P.,
RA Yona S., Stacey M., Gordon S., Chang G.W., Lin H.H.;
RT "Activation of myeloid cell-specific adhesion class G protein-coupled
RT receptor EMR2 via ligation-induced translocation and interaction of
RT receptor subunits in lipid raft microdomains.";
RL Mol. Cell. Biol. 32:1408-1420(2012).
RN [12]
RP NOMENCLATURE.
RX PubMed=25713288; DOI=10.1124/pr.114.009647;
RA Hamann J., Aust G., Arac D., Engel F.B., Formstone C., Fredriksson R.,
RA Hall R.A., Harty B.L., Kirchhoff C., Knapp B., Krishnan A., Liebscher I.,
RA Lin H.H., Martinelli D.C., Monk K.R., Peeters M.C., Piao X., Promel S.,
RA Schoneberg T., Schwartz T.W., Singer K., Stacey M., Ushkaryov Y.A.,
RA Vallon M., Wolfrum U., Wright M.W., Xu L., Langenhan T., Schioth H.B.;
RT "International union of basic and clinical pharmacology. XCIV. Adhesion G
RT protein-coupled receptors.";
RL Pharmacol. Rev. 67:338-367(2015).
RN [13]
RP INVOLVEMENT IN VBU, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP VARIANT VBU TYR-492, AND CHARACTERIZATION OF VARIANT VBU TYR-492.
RX PubMed=26841242; DOI=10.1056/nejmoa1500611;
RA Boyden S.E., Desai A., Cruse G., Young M.L., Bolan H.C., Scott L.M.,
RA Eisch A.R., Long R.D., Lee C.C., Satorius C.L., Pakstis A.J., Olivera A.,
RA Mullikin J.C., Chouery E., Megarbane A., Medlej-Hashim M., Kidd K.K.,
RA Kastner D.L., Metcalfe D.D., Komarow H.D.;
RT "Vibratory urticaria associated with a missense variant in ADGRE2.";
RL N. Engl. J. Med. 374:656-663(2016).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 25-260, INTERACTION WITH CD55,
RP CALCIUM-BINDING, AND DISULFIDE BONDS.
RX PubMed=17449467; DOI=10.1074/jbc.m702588200;
RA Abbott R.J., Spendlove I., Roversi P., Fitzgibbon H., Knott V., Teriete P.,
RA McDonnell J.M., Handford P.A., Lea S.M.;
RT "Structural and functional characterization of a novel T cell receptor co-
RT regulatory protein complex, CD97-CD55.";
RL J. Biol. Chem. 282:22023-22032(2007).
CC -!- FUNCTION: Cell surface receptor that binds to the chondroitin sulfate
CC moiety of glycosaminoglycan chains and promotes cell attachment.
CC Promotes granulocyte chemotaxis, degranulation and adhesion. In
CC macrophages, promotes the release of inflammatory cytokines, including
CC IL8 and TNF. Signals probably through G-proteins. Is a regulator of
CC mast cell degranulation (PubMed:26841242).
CC {ECO:0000269|PubMed:12829604, ECO:0000269|PubMed:17928360,
CC ECO:0000269|PubMed:22310662, ECO:0000269|PubMed:22575658,
CC ECO:0000269|PubMed:26841242}.
CC -!- SUBUNIT: Forms a heterodimer, consisting of a large extracellular
CC region non-covalently linked to a seven-transmembrane moiety. Interacts
CC with chondroitin sulfate; the interaction with chondroitin sulfate is
CC calcium-dependent. Interacts with CD55. {ECO:0000269|PubMed:12829604,
CC ECO:0000269|PubMed:15150276, ECO:0000269|PubMed:17449467}.
CC -!- INTERACTION:
CC Q9UHX3; Q13520: AQP6; NbExp=3; IntAct=EBI-11277970, EBI-13059134;
CC Q9UHX3; Q13323: BIK; NbExp=3; IntAct=EBI-11277970, EBI-700794;
CC Q9UHX3; Q8WV48: CCDC107; NbExp=3; IntAct=EBI-11277970, EBI-947033;
CC Q9UHX3; Q03591: CFHR1; NbExp=5; IntAct=EBI-11277970, EBI-3935840;
CC Q9UHX3; Q96BA8: CREB3L1; NbExp=3; IntAct=EBI-11277970, EBI-6942903;
CC Q9UHX3; Q9GZR5: ELOVL4; NbExp=3; IntAct=EBI-11277970, EBI-18535450;
CC Q9UHX3; A1L3X0: ELOVL7; NbExp=3; IntAct=EBI-11277970, EBI-10285373;
CC Q9UHX3; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-11277970, EBI-18304435;
CC Q9UHX3; Q7Z5P4: HSD17B13; NbExp=3; IntAct=EBI-11277970, EBI-18053395;
CC Q9UHX3; P43628: KIR2DL3; NbExp=3; IntAct=EBI-11277970, EBI-8632435;
CC Q9UHX3; O60337: MARCHF6; NbExp=3; IntAct=EBI-11277970, EBI-2684600;
CC Q9UHX3; Q6N075: MFSD5; NbExp=3; IntAct=EBI-11277970, EBI-3920969;
CC Q9UHX3; Q8N4V1: MMGT1; NbExp=3; IntAct=EBI-11277970, EBI-6163737;
CC Q9UHX3; Q96E29: MTERF3; NbExp=3; IntAct=EBI-11277970, EBI-7825321;
CC Q9UHX3; Q9NR31: SAR1A; NbExp=3; IntAct=EBI-11277970, EBI-3920694;
CC Q9UHX3; Q8TBB6: SLC7A14; NbExp=3; IntAct=EBI-11277970, EBI-5235586;
CC Q9UHX3; Q96MV1: TLCD4; NbExp=3; IntAct=EBI-11277970, EBI-12947623;
CC Q9UHX3; Q96HE8: TMEM80; NbExp=3; IntAct=EBI-11277970, EBI-11742770;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22310662,
CC ECO:0000269|PubMed:26841242}; Multi-pass membrane protein. Cell
CC projection, ruffle membrane {ECO:0000269|PubMed:17928360}; Multi-pass
CC membrane protein. Note=Localized at the leading edge of migrating
CC cells. {ECO:0000269|PubMed:17928360}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Comment=A number of isoforms are probably produced. A soluble form
CC due to a frameshift which introduced a stop codon immediately before
CC the first TM domain is also detected.;
CC Name=1;
CC IsoId=Q9UHX3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UHX3-2; Sequence=VSP_041367;
CC Name=3;
CC IsoId=Q9UHX3-3; Sequence=VSP_041366;
CC Name=4;
CC IsoId=Q9UHX3-4; Sequence=VSP_041365;
CC Name=5;
CC IsoId=Q9UHX3-5; Sequence=VSP_041364;
CC Name=6;
CC IsoId=Q9UHX3-6; Sequence=VSP_047535;
CC -!- TISSUE SPECIFICITY: Expression is restricted to myeloid cells. Highest
CC expression was found in peripheral blood leukocytes, followed by spleen
CC and lymph nodes, with intermediate to low levels in thymus, bone
CC marrow, fetal liver, placenta, and lung, and no expression in heart,
CC brain, skeletal muscle, kidney, or pancreas. Expression is also
CC detected in monocyte/macrophage and Jurkat cell lines but not in other
CC cell lines tested. High expression in mast cells (PubMed:26841242).
CC {ECO:0000269|PubMed:10903844, ECO:0000269|PubMed:11994511,
CC ECO:0000269|PubMed:26841242}.
CC -!- DOMAIN: The GPS domain is necessary, but not sufficient for receptor
CC cleavage, which require the entire extracellular stalk.
CC {ECO:0000269|PubMed:12860403}.
CC -!- DOMAIN: Binding to chondroitin sulfate is mediated by the fourth EGF
CC domain.
CC -!- PTM: Autoproteolytically cleaved into 2 subunits, an extracellular
CC alpha subunit and a seven-transmembrane beta subunit.
CC {ECO:0000269|PubMed:12860403}.
CC -!- DISEASE: Vibratory urticaria (VBU) [MIM:125630]: An autosomal dominant
CC disorder characterized by localized hives and systemic manifestations
CC in response to dermal vibration, with coincident degranulation of mast
CC cells and increased histamine levels in serum.
CC {ECO:0000269|PubMed:26841242}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Has no murine ortholog. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 2 family.
CC Adhesion G-protein coupled receptor (ADGR) subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC06146.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF114491; AAF21974.1; -; mRNA.
DR EMBL; AB065931; BAC06146.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AK298700; BAG60858.1; -; mRNA.
DR EMBL; AC004262; AAC05172.1; -; Genomic_DNA.
DR EMBL; AC005327; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC090427; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS32935.1; -. [Q9UHX3-1]
DR CCDS; CCDS59361.1; -. [Q9UHX3-6]
DR RefSeq; NP_001257981.1; NM_001271052.1. [Q9UHX3-6]
DR RefSeq; NP_038475.2; NM_013447.3. [Q9UHX3-1]
DR PDB; 2BO2; X-ray; 2.60 A; A/B=25-260.
DR PDB; 2BOU; X-ray; 1.90 A; A=25-118, A=212-260.
DR PDB; 2BOX; X-ray; 2.50 A; A=25-260.
DR PDBsum; 2BO2; -.
DR PDBsum; 2BOU; -.
DR PDBsum; 2BOX; -.
DR AlphaFoldDB; Q9UHX3; -.
DR SMR; Q9UHX3; -.
DR BioGRID; 119041; 41.
DR IntAct; Q9UHX3; 20.
DR STRING; 9606.ENSP00000319883; -.
DR MEROPS; P02.001; -.
DR GlyConnect; 993; 2 N-Linked glycans (2 sites).
DR GlyGen; Q9UHX3; 10 sites, 2 N-linked glycans (2 sites), 1 O-linked glycan (2 sites).
DR iPTMnet; Q9UHX3; -.
DR PhosphoSitePlus; Q9UHX3; -.
DR BioMuta; ADGRE2; -.
DR DMDM; 108935835; -.
DR EPD; Q9UHX3; -.
DR jPOST; Q9UHX3; -.
DR MassIVE; Q9UHX3; -.
DR MaxQB; Q9UHX3; -.
DR PaxDb; Q9UHX3; -.
DR PeptideAtlas; Q9UHX3; -.
DR PRIDE; Q9UHX3; -.
DR ProteomicsDB; 17966; -.
DR ProteomicsDB; 84434; -. [Q9UHX3-1]
DR ProteomicsDB; 84435; -. [Q9UHX3-2]
DR ProteomicsDB; 84436; -. [Q9UHX3-3]
DR ProteomicsDB; 84437; -. [Q9UHX3-4]
DR ProteomicsDB; 84438; -. [Q9UHX3-5]
DR Antibodypedia; 13808; 474 antibodies from 32 providers.
DR DNASU; 30817; -.
DR Ensembl; ENST00000315576.8; ENSP00000319883.3; ENSG00000127507.18. [Q9UHX3-1]
DR Ensembl; ENST00000392965.7; ENSP00000376692.3; ENSG00000127507.18. [Q9UHX3-6]
DR Ensembl; ENST00000594076.5; ENSP00000472735.1; ENSG00000127507.18. [Q9UHX3-4]
DR Ensembl; ENST00000594294.5; ENSP00000470725.1; ENSG00000127507.18. [Q9UHX3-3]
DR Ensembl; ENST00000595839.5; ENSP00000469277.1; ENSG00000127507.18. [Q9UHX3-5]
DR Ensembl; ENST00000596991.6; ENSP00000472280.2; ENSG00000127507.18. [Q9UHX3-2]
DR GeneID; 30817; -.
DR KEGG; hsa:30817; -.
DR MANE-Select; ENST00000315576.8; ENSP00000319883.3; NM_013447.4; NP_038475.2.
DR UCSC; uc002mzp.3; human. [Q9UHX3-1]
DR CTD; 30817; -.
DR DisGeNET; 30817; -.
DR GeneCards; ADGRE2; -.
DR HGNC; HGNC:3337; ADGRE2.
DR HPA; ENSG00000127507; Tissue enhanced (lymphoid).
DR MalaCards; ADGRE2; -.
DR MIM; 125630; phenotype.
DR MIM; 606100; gene.
DR neXtProt; NX_Q9UHX3; -.
DR OpenTargets; ENSG00000127507; -.
DR Orphanet; 493342; Vibratory urticaria.
DR PharmGKB; PA27774; -.
DR VEuPathDB; HostDB:ENSG00000127507; -.
DR eggNOG; KOG4193; Eukaryota.
DR GeneTree; ENSGT00940000162597; -.
DR HOGENOM; CLU_002753_3_7_1; -.
DR InParanoid; Q9UHX3; -.
DR OMA; RYICAYW; -.
DR OrthoDB; 210309at2759; -.
DR PhylomeDB; Q9UHX3; -.
DR TreeFam; TF316380; -.
DR PathwayCommons; Q9UHX3; -.
DR Reactome; R-HSA-373080; Class B/2 (Secretin family receptors).
DR SignaLink; Q9UHX3; -.
DR BioGRID-ORCS; 30817; 9 hits in 1074 CRISPR screens.
DR ChiTaRS; ADGRE2; human.
DR EvolutionaryTrace; Q9UHX3; -.
DR GeneWiki; EMR2; -.
DR GenomeRNAi; 30817; -.
DR Pharos; Q9UHX3; Tbio.
DR PRO; PR:Q9UHX3; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9UHX3; protein.
DR Bgee; ENSG00000127507; Expressed in monocyte and 111 other tissues.
DR ExpressionAtlas; Q9UHX3; baseline and differential.
DR Genevisible; Q9UHX3; HS.
DR GO; GO:0016021; C:integral component of membrane; TAS:GDB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0031256; C:leading edge membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0035374; F:chondroitin sulfate binding; IMP:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; IMP:UniProtKB.
DR GO; GO:0016477; P:cell migration; IMP:UniProtKB.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:InterPro.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:GDB.
DR GO; GO:0071621; P:granulocyte chemotaxis; IMP:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0043304; P:regulation of mast cell degranulation; IMP:UniProtKB.
DR Gene3D; 2.60.220.50; -; 1.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR046338; GAIN_dom_sf.
DR InterPro; IPR017981; GPCR_2-like.
DR InterPro; IPR003056; GPCR_2_ADGRE2_ADGRE5.
DR InterPro; IPR000832; GPCR_2_secretin-like.
DR InterPro; IPR017983; GPCR_2_secretin-like_CS.
DR InterPro; IPR000203; GPS.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR Pfam; PF00002; 7tm_2; 1.
DR Pfam; PF07645; EGF_CA; 4.
DR Pfam; PF01825; GPS; 1.
DR PRINTS; PR01278; CD97PROTEIN.
DR PRINTS; PR00249; GPCRSECRETIN.
DR SMART; SM00181; EGF; 5.
DR SMART; SM00179; EGF_CA; 4.
DR SMART; SM00303; GPS; 1.
DR SUPFAM; SSF57184; SSF57184; 1.
DR PROSITE; PS00010; ASX_HYDROXYL; 4.
DR PROSITE; PS50026; EGF_3; 4.
DR PROSITE; PS01187; EGF_CA; 4.
DR PROSITE; PS00650; G_PROTEIN_RECEP_F2_2; 1.
DR PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1.
DR PROSITE; PS50221; GPS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Autocatalytic cleavage; Calcium;
KW Cell adhesion; Cell membrane; Cell projection; Direct protein sequencing;
KW Disease variant; Disulfide bond; EGF-like domain;
KW G-protein coupled receptor; Glycoprotein; Inflammatory response; Membrane;
KW Receptor; Reference proteome; Repeat; Signal; Transducer; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..823
FT /note="Adhesion G protein-coupled receptor E2"
FT /id="PRO_0000012875"
FT TOPO_DOM 24..540
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 541..561
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 562..569
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 570..590
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 591..605
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 606..626
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 627..644
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 645..665
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 666..683
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 684..704
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 705..735
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 736..756
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 757..760
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 761..781
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 782..823
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 25..66
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 67..118
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 119..162
FT /note="EGF-like 3; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 163..211
FT /note="EGF-like 4; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 212..260
FT /note="EGF-like 5; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 479..529
FT /note="GPS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00098"
FT SITE 517..518
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:15150276"
FT CARBOHYD 41
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 111
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 206
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 298
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 347
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 354
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 456
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 460
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 29..39
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:17449467"
FT DISULFID 33..45
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:17449467"
FT DISULFID 47..65
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:17449467"
FT DISULFID 71..85
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:17449467"
FT DISULFID 79..94
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:17449467"
FT DISULFID 96..117
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:17449467"
FT DISULFID 123..136
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:17449467"
FT DISULFID 130..145
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:17449467"
FT DISULFID 147..161
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 167..180
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 174..189
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 191..210
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 216..229
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 223..238
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 240..259
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT VAR_SEQ 119..260
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_041364"
FT VAR_SEQ 119..211
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_041365"
FT VAR_SEQ 163..211
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_041366"
FT VAR_SEQ 397..407
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_041367"
FT VAR_SEQ 473..530
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_047535"
FT VARIANT 314
FT /note="A -> V (in dbSNP:rs35612307)"
FT /id="VAR_061229"
FT VARIANT 492
FT /note="C -> Y (in VBU; affects the regulation of mast cells
FT degranulation; results in increased vibration-induced mast
FT cells degranulation; no effect on localization to plasma
FT membrane; dbSNP:rs199718602)"
FT /evidence="ECO:0000269|PubMed:26841242"
FT /id="VAR_078578"
FT VARIANT 605
FT /note="T -> I (in dbSNP:rs4410209)"
FT /id="VAR_026719"
FT VARIANT 614
FT /note="L -> F (in dbSNP:rs2524383)"
FT /evidence="ECO:0000269|PubMed:10903844,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15057824"
FT /id="VAR_026720"
FT VARIANT 665
FT /note="S -> F (in dbSNP:rs3752187)"
FT /id="VAR_026721"
FT VARIANT 720
FT /note="E -> D (in dbSNP:rs57865820)"
FT /id="VAR_061230"
FT MUTAGEN 518
FT /note="S->A: Abolishes cleavage."
FT /evidence="ECO:0000269|PubMed:12860403"
FT CONFLICT 531
FT /note="Missing (in Ref. 4; AAC05172)"
FT /evidence="ECO:0000305"
FT CONFLICT 823
FT /note="N -> R (in Ref. 2; BAC06146)"
FT /evidence="ECO:0000305"
FT STRAND 37..43
FT /evidence="ECO:0007829|PDB:2BOU"
FT STRAND 45..47
FT /evidence="ECO:0007829|PDB:2BOU"
FT STRAND 54..58
FT /evidence="ECO:0007829|PDB:2BOU"
FT HELIX 70..72
FT /evidence="ECO:0007829|PDB:2BOU"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:2BO2"
FT STRAND 83..87
FT /evidence="ECO:0007829|PDB:2BOU"
FT STRAND 92..96
FT /evidence="ECO:0007829|PDB:2BOU"
FT STRAND 100..102
FT /evidence="ECO:0007829|PDB:2BOU"
FT STRAND 109..111
FT /evidence="ECO:0007829|PDB:2BOU"
FT HELIX 112..114
FT /evidence="ECO:0007829|PDB:2BOU"
FT STRAND 117..119
FT /evidence="ECO:0007829|PDB:2BOU"
FT TURN 217..219
FT /evidence="ECO:0007829|PDB:2BOU"
FT STRAND 227..231
FT /evidence="ECO:0007829|PDB:2BOU"
FT STRAND 236..239
FT /evidence="ECO:0007829|PDB:2BOU"
FT STRAND 242..244
FT /evidence="ECO:0007829|PDB:2BOU"
FT STRAND 248..250
FT /evidence="ECO:0007829|PDB:2BO2"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:2BOU"
SQ SEQUENCE 823 AA; 90472 MW; 4D38C30A07B46FF4 CRC64;
MGGRVFLVFL AFCVWLTLPG AETQDSRGCA RWCPQDSSCV NATACRCNPG FSSFSEIITT
PMETCDDINE CATLSKVSCG KFSDCWNTEG SYDCVCSPGY EPVSGAKTFK NESENTCQDV
DECQQNPRLC KSYGTCVNTL GSYTCQCLPG FKLKPEDPKL CTDVNECTSG QNPCHSSTHC
LNNVGSYQCR CRPGWQPIPG SPNGPNNTVC EDVDECSSGQ HQCDSSTVCF NTVGSYSCRC
RPGWKPRHGI PNNQKDTVCE DMTFSTWTPP PGVHSQTLSR FFDKVQDLGR DYKPGLANNT
IQSILQALDE LLEAPGDLET LPRLQQHCVA SHLLDGLEDV LRGLSKNLSN GLLNFSYPAG
TELSLEVQKQ VDRSVTLRQN QAVMQLDWNQ AQKSGDPGPS VVGLVSIPGM GKLLAEAPLV
LEPEKQMLLH ETHQGLLQDG SPILLSDVIS AFLSNNDTQN LSSPVTFTFS HRSVIPRQKV
LCVFWEHGQN GCGHWATTGC STIGTRDTST ICRCTHLSSF AVLMAHYDVQ EEDPVLTVIT
YMGLSVSLLC LLLAALTFLL CKAIQNTSTS LHLQLSLCLF LAHLLFLVAI DQTGHKVLCS
IIAGTLHYLY LATLTWMLLE ALYLFLTARN LTVVNYSSIN RFMKKLMFPV GYGVPAVTVA
ISAASRPHLY GTPSRCWLQP EKGFIWGFLG PVCAIFSVNL VLFLVTLWIL KNRLSSLNSE
VSTLRNTRML AFKATAQLFI LGCTWCLGIL QVGPAARVMA YLFTIINSLQ GVFIFLVYCL
LSQQVREQYG KWSKGIRKLK TESEMHTLSS SAKADTSKPS TVN
