ID   AGRE3_HUMAN             Reviewed;         652 AA.
AC   Q9BY15;
DT   16-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT   18-MAY-2010, sequence version 2.
DT   24-JAN-2024, entry version 190.
DE   RecName: Full=Adhesion G protein-coupled receptor E3 {ECO:0000303|PubMed:25713288};
DE   AltName: Full=EGF-like module receptor 3;
DE   AltName: Full=EGF-like module-containing mucin-like hormone receptor-like 3;
DE   Flags: Precursor;
GN   Name=ADGRE3 {ECO:0000312|HGNC:HGNC:23647}; Synonyms=EMR3;
GN   ORFNames=UNQ683/PRO1562;
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] (ISOFORMS 1 AND 3), VARIANT GLN-385, TISSUE
RP   SPECIFICITY, AND FUNCTION.
RX   PubMed=11279179; DOI=10.1074/jbc.m101147200;
RA   Stacey M., Lin H.-H., Hilyard K.L., Gordon S., McKnight A.J.;
RT   "Human epidermal growth factor (EGF) module-containing mucin-like hormone
RT   receptor 3 is a new member of the EGF-TM7 family that recognizes a ligand
RT   on human macrophages and activated neutrophils.";
RL   J. Biol. Chem. 276:18863-18870(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS GLN-127
RP   AND GLN-385.
RX   PubMed=12975309; DOI=10.1101/gr.1293003;
RA   Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA   Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA   Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA   Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA   Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA   Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA   Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA   Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT   "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT   identify novel human secreted and transmembrane proteins: a bioinformatics
RT   assessment.";
RL   Genome Res. 13:2265-2270(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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   [4]
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).
CC   -!- FUNCTION: Orphan receptor that may play a role myeloid-myeloid
CC       interactions during immune and inflammatory responses. A ligand for the
CC       soluble form of this receptor is present at the surface of monocytes-
CC       derived macrophages and activated neutrophils.
CC       {ECO:0000269|PubMed:11279179}.
CC   -!- SUBUNIT: Forms a heterodimer, consisting of a large extracellular
CC       region (alpha subunit) non-covalently linked to a seven-transmembrane
CC       moiety (beta subunit). {ECO:0000250|UniProtKB:Q9UHX3}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q9BY15-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9BY15-2; Sequence=VSP_009417;
CC       Name=3;
CC         IsoId=Q9BY15-3; Sequence=VSP_009418;
CC   -!- TISSUE SPECIFICITY: Displays a predominantly leukocyte-restricted
CC       expression, with highest levels in neutrophils, monocytes and
CC       macrophages. {ECO:0000269|PubMed:11279179}.
CC   -!- PTM: Proteolytically cleaved into 2 subunits, an extracellular alpha
CC       subunit and a seven-transmembrane subunit.
CC       {ECO:0000250|UniProtKB:Q9UHX3}.
CC   -!- MISCELLANEOUS: Has no murine ortholog. {ECO:0000305}.
CC   -!- MISCELLANEOUS: [Isoform 3]: Due to a 40-nucleotide deletion
CC       (nucleotides 439-479) resulting in a frameshift leading to a premature
CC       stop codon and the production of a truncated soluble form.
CC       {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 2 family.
CC       Adhesion G-protein coupled receptor (ADGR) subfamily. {ECO:0000305}.
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DR   EMBL; AF239764; AAK15076.1; -; mRNA.
DR   EMBL; AY358817; AAQ89176.1; -; mRNA.
DR   EMBL; AC022149; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC090427; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC135052; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS12315.1; -. [Q9BY15-1]
DR   CCDS; CCDS74297.1; -. [Q9BY15-2]
DR   RefSeq; NP_001276087.1; NM_001289158.1. [Q9BY15-2]
DR   RefSeq; NP_001276088.1; NM_001289159.1.
DR   RefSeq; NP_115960.2; NM_032571.4. [Q9BY15-1]
DR   AlphaFoldDB; Q9BY15; -.
DR   SMR; Q9BY15; -.
DR   STRING; 9606.ENSP00000253673; -.
DR   MEROPS; P02.003; -.
DR   GlyCosmos; Q9BY15; 9 sites, No reported glycans.
DR   GlyGen; Q9BY15; 9 sites.
DR   iPTMnet; Q9BY15; -.
DR   PhosphoSitePlus; Q9BY15; -.
DR   BioMuta; ADGRE3; -.
DR   DMDM; 296434492; -.
DR   jPOST; Q9BY15; -.
DR   MassIVE; Q9BY15; -.
DR   PaxDb; 9606-ENSP00000253673; -.
DR   PeptideAtlas; Q9BY15; -.
DR   ProteomicsDB; 79565; -. [Q9BY15-1]
DR   ProteomicsDB; 79566; -. [Q9BY15-2]
DR   Antibodypedia; 2861; 383 antibodies from 31 providers.
DR   DNASU; 84658; -.
DR   Ensembl; ENST00000253673.6; ENSP00000253673.4; ENSG00000131355.15. [Q9BY15-1]
DR   Ensembl; ENST00000344373.8; ENSP00000340758.4; ENSG00000131355.15. [Q9BY15-2]
DR   GeneID; 84658; -.
DR   KEGG; hsa:84658; -.
DR   MANE-Select; ENST00000253673.6; ENSP00000253673.4; NM_032571.5; NP_115960.2.
DR   UCSC; uc002mzi.6; human. [Q9BY15-1]
DR   AGR; HGNC:23647; -.
DR   CTD; 84658; -.
DR   DisGeNET; 84658; -.
DR   GeneCards; ADGRE3; -.
DR   HGNC; HGNC:23647; ADGRE3.
DR   HPA; ENSG00000131355; Tissue enhanced (bone marrow, lymphoid tissue).
DR   MIM; 606101; gene.
DR   neXtProt; NX_Q9BY15; -.
DR   OpenTargets; ENSG00000131355; -.
DR   PharmGKB; PA134956879; -.
DR   VEuPathDB; HostDB:ENSG00000131355; -.
DR   eggNOG; KOG4193; Eukaryota.
DR   GeneTree; ENSGT00940000163037; -.
DR   InParanoid; Q9BY15; -.
DR   OMA; KWFREIM; -.
DR   OrthoDB; 1114672at2759; -.
DR   PhylomeDB; Q9BY15; -.
DR   TreeFam; TF316380; -.
DR   PathwayCommons; Q9BY15; -.
DR   Reactome; R-HSA-373080; Class B/2 (Secretin family receptors).
DR   Reactome; R-HSA-6798695; Neutrophil degranulation.
DR   SignaLink; Q9BY15; -.
DR   BioGRID-ORCS; 84658; 15 hits in 1146 CRISPR screens.
DR   ChiTaRS; ADGRE3; human.
DR   GeneWiki; EMR3; -.
DR   GenomeRNAi; 84658; -.
DR   Pharos; Q9BY15; Tbio.
DR   PRO; PR:Q9BY15; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; Q9BY15; Protein.
DR   Bgee; ENSG00000131355; Expressed in blood and 80 other cell types or tissues.
DR   ExpressionAtlas; Q9BY15; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0101003; C:ficolin-1-rich granule membrane; TAS:Reactome.
DR   GO; GO:0016020; C:membrane; TAS:GDB.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0030667; C:secretory granule membrane; TAS:Reactome.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
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:0007166; P:cell surface receptor signaling pathway; IEA:InterPro.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:GDB.
DR   CDD; cd00054; EGF_CA; 1.
DR   Gene3D; 2.60.220.50; -; 1.
DR   Gene3D; 2.10.25.10; Laminin; 2.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 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; IPR032471; GAIN_dom_N.
DR   InterPro; IPR046338; GAIN_dom_sf.
DR   InterPro; IPR017981; GPCR_2-like_7TM.
DR   InterPro; IPR001740; GPCR_2_EMR1-like_rcpt.
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   PANTHER; PTHR12011:SF455; ADHESION G PROTEIN-COUPLED RECEPTOR E3; 1.
DR   PANTHER; PTHR12011; ADHESION G-PROTEIN COUPLED RECEPTOR; 1.
DR   Pfam; PF00002; 7tm_2; 1.
DR   Pfam; PF07645; EGF_CA; 1.
DR   Pfam; PF16489; GAIN; 1.
DR   Pfam; PF01825; GPS; 1.
DR   PRINTS; PR01128; EMR1HORMONER.
DR   PRINTS; PR00249; GPCRSECRETIN.
DR   SMART; SM00181; EGF; 2.
DR   SMART; SM00179; EGF_CA; 1.
DR   SMART; SM00303; GPS; 1.
DR   SUPFAM; SSF57196; EGF/Laminin; 1.
DR   SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR   SUPFAM; SSF57184; Growth factor receptor domain; 1.
DR   PROSITE; PS00010; ASX_HYDROXYL; 1.
DR   PROSITE; PS50026; EGF_3; 1.
DR   PROSITE; PS01187; EGF_CA; 1.
DR   PROSITE; PS00650; G_PROTEIN_RECEP_F2_2; 1.
DR   PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1.
DR   PROSITE; PS50221; GPS; 1.
DR   Genevisible; Q9BY15; HS.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Calcium; Cell membrane; Disulfide bond;
KW   EGF-like domain; G-protein coupled receptor; Glycoprotein; Membrane;
KW   Receptor; Reference proteome; Repeat; Secreted; Signal; Transducer;
KW   Transmembrane; Transmembrane helix.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   CHAIN           22..652
FT                   /note="Adhesion G protein-coupled receptor E3"
FT                   /id="PRO_0000012876"
FT   TOPO_DOM        22..357
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        358..378
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        379..389
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        390..410
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        411..416
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        417..437
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        438..464
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        465..485
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        486..508
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        509..529
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        530..557
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        558..578
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        579..580
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        581..601
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        602..652
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          24..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          301..350
FT                   /note="GPS"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00098"
FT   REGION          621..652
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            338..339
FT                   /note="Cleavage"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        34
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        39
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        145
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        189
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        202
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        250
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        279
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        327
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        334
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        28..37
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        31..43
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        45..65
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        71..85
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        79..94
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        96..117
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   VAR_SEQ         67..118
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:12975309"
FT                   /id="VSP_009417"
FT   VAR_SEQ         118..652
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_009418"
FT   VARIANT         127
FT                   /note="E -> Q (in dbSNP:rs4606855)"
FT                   /evidence="ECO:0000269|PubMed:12975309"
FT                   /id="VAR_024472"
FT   VARIANT         236
FT                   /note="A -> V (in dbSNP:rs34226397)"
FT                   /id="VAR_055926"
FT   VARIANT         385
FT                   /note="R -> Q (in dbSNP:rs45508602)"
FT                   /evidence="ECO:0000269|PubMed:11279179,
FT                   ECO:0000269|PubMed:12975309"
FT                   /id="VAR_060442"
SQ   SEQUENCE   652 AA;  72621 MW;  60DCD73BB0DBEB74 CRC64;
     MQGPLLLPGL CFLLSLFGAV TQKTKTSCAK CPPNASCVNN THCTCNHGYT SGSGQKLFTF
     PLETCNDINE CTPPYSVYCG FNAVCYNVEG SFYCQCVPGY RLHSGNEQFS NSNENTCQDT
     TSSKTTEGRK ELQKIVDKFE SLLTNQTLWR TEGRQEISST ATTILRDVES KVLETALKDP
     EQKVLKIQND SVAIETQAIT DNCSEERKTF NLNVQMNSMD IRCSDIIQGD TQGPSAIAFI
     SYSSLGNIIN ATFFEEMDKK DQVYLNSQVV SAAIGPKRNV SLSKSVTLTF QHVKMTPSTK
     KVFCVYWKST GQGSQWSRDG CFLIHVNKSH TMCNCSHLSS FAVLMALTSQ EEDPVLTVIT
     YVGLSVSLLC LLLAALTFLL CKAIRNTSTS LHLQLSLCLF LAHLLFLVGI DRTEPKVLCS
     IIAGALHYLY LAAFTWMLLE GVHLFLTARN LTVVNYSSIN RLMKWIMFPV GYGVPAVTVA
     ISAASWPHLY GTADRCWLHL DQGFMWSFLG PVCAIFSANL VLFILVFWIL KRKLSSLNSE
     VSTIQNTRML AFKATAQLFI LGCTWCLGLL QVGPAAQVMA YLFTIINSLQ GFFIFLVYCL
     LSQQVQKQYQ KWFREIVKSK SESETYTLSS KMGPDSKPSE GDVFPGQVKR KY
//