AGRE3_HUMAN
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 03-AUG-2022, entry version 182.
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 GlyGen; Q9BY15; 9 sites.
DR iPTMnet; Q9BY15; -.
DR PhosphoSitePlus; Q9BY15; -.
DR BioMuta; ADGRE3; -.
DR DMDM; 296434492; -.
DR jPOST; Q9BY15; -.
DR MassIVE; Q9BY15; -.
DR PaxDb; Q9BY15; -.
DR PeptideAtlas; Q9BY15; -.
DR PRIDE; Q9BY15; -.
DR ProteomicsDB; 79565; -. [Q9BY15-1]
DR ProteomicsDB; 79566; -. [Q9BY15-2]
DR Antibodypedia; 2861; 365 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 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; STHCTCN; -.
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 1068 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 tissues.
DR ExpressionAtlas; Q9BY15; baseline and differential.
DR Genevisible; Q9BY15; HS.
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:0016021; C:integral component of membrane; TAS:GDB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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 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; IPR032471; GAIN_dom_N.
DR InterPro; IPR046338; GAIN_dom_sf.
DR InterPro; IPR017981; GPCR_2-like.
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 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; SSF57184; SSF57184; 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.
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
