AGRE4_HUMAN
ID AGRE4_HUMAN Reviewed; 457 AA.
AC Q86SQ3; Q86SP1;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Putative adhesion G protein-coupled receptor E4P;
DE AltName: Full=EGF-like module receptor 4;
DE AltName: Full=EGF-like module-containing mucin-like hormone receptor-like 4;
DE AltName: Full=G-protein coupled receptor 127;
DE AltName: Full=G-protein coupled receptor PGR16;
DE Flags: Precursor;
GN Name=ADGRE4P {ECO:0000312|HGNC:HGNC:19240};
GN Synonyms=EMR4, EMR4P, GPR127, PGR16;
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=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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=12731063; DOI=10.1002/eji.200323881;
RA Hamann J., Kwakkenbos M.J., de Jong E.C., Heus H., Olsen A.S.,
RA van Lier R.A.W.;
RT "Inactivation of the EGF-TM7 receptor EMR4 after the Pan-Homo divergence.";
RL Eur. J. Immunol. 33:1365-1371(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 262-310.
RX PubMed=12679517; DOI=10.1073/pnas.0230374100;
RA Vassilatis D.K., Hohmann J.G., Zeng H., Li F., Ranchalis J.E.,
RA Mortrud M.T., Brown A., Rodriguez S.S., Weller J.R., Wright A.C.,
RA Bergmann J.E., Gaitanaris G.A.;
RT "The G protein-coupled receptor repertoires of human and mouse.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:4903-4908(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=16753812; DOI=10.1080/10425170500355737;
RA Caminschi I., Vandenabeele S., Sofi M., McKnight A.J., Ward N.,
RA Brodnicki T.C., Toy T., Lahoud M., Maraskovsky E., Shortman K.,
RA Wright M.D.;
RT "Gene structure and transcript analysis of the human and mouse EGF-TM7
RT molecule, FIRE.";
RL DNA Seq. 17:8-14(2006).
RN [5]
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: May mediate the cellular interaction between myeloid cells
CC and B-cells. {ECO:0000250|UniProtKB:Q91ZE5}.
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:Q91ZE5}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC {ECO:0000250|UniProtKB:Q91ZE5}; Multi-pass membrane protein
CC {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q86SQ3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86SQ3-2; Sequence=VSP_057755, VSP_057756, VSP_057757;
CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:Q91ZE5}.
CC -!- PTM: Proteolytically cleaved into 2 subunits, an extracellular alpha
CC subunit and a seven-transmembrane subunit.
CC {ECO:0000250|UniProtKB:Q91ZE5}.
CC -!- MISCELLANEOUS: [Isoform 2]: Due to a frameshift mutation in exon 8
CC would result in a truncated soluble form. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 2 family.
CC Adhesion G-protein coupled receptor (ADGR) subfamily. {ECO:0000305}.
CC -!- CAUTION: Could be the product of a pseudogene. A point deletion in exon
CC 8, which introduces a frame shift leading to a premature stop codon.
CC Thus, a protein expressed by this gene would be soluble rather than
CC expressed on the cell surface. This single-nucleotide deletion has been
CC acquired after human-chimpanzee speciation, about five million years
CC ago. {ECO:0000305|PubMed:12679517, ECO:0000305|PubMed:16753812}.
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DR EMBL; AY181245; AAO27357.1; -; mRNA.
DR EMBL; AF489700; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AY255550; AAO85062.1; -; mRNA.
DR AlphaFoldDB; Q86SQ3; -.
DR SMR; Q86SQ3; -.
DR MEROPS; P02.005; -.
DR GlyGen; Q86SQ3; 4 sites.
DR iPTMnet; Q86SQ3; -.
DR PhosphoSitePlus; Q86SQ3; -.
DR BioMuta; HGNC:19240; -.
DR DMDM; 44887876; -.
DR PRIDE; Q86SQ3; -.
DR GeneCards; ADGRE4P; -.
DR HGNC; HGNC:19240; ADGRE4P.
DR neXtProt; NX_Q86SQ3; -.
DR InParanoid; Q86SQ3; -.
DR PhylomeDB; Q86SQ3; -.
DR PathwayCommons; Q86SQ3; -.
DR Pharos; Q86SQ3; Tdark.
DR Proteomes; UP000005640; Unplaced.
DR RNAct; Q86SQ3; protein.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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: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; 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 Pfam; PF00002; 7tm_2; 1.
DR Pfam; PF07645; EGF_CA; 1.
DR Pfam; PF01825; GPS; 1.
DR PRINTS; PR01128; EMR1HORMONER.
DR PRINTS; PR00249; GPCRSECRETIN.
DR SMART; SM00179; EGF_CA; 1.
DR SMART; SM00303; GPS; 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 5: Uncertain;
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..14
FT /evidence="ECO:0000255"
FT CHAIN 15..457
FT /note="Putative adhesion G protein-coupled receptor E4P"
FT /id="PRO_0000012877"
FT TOPO_DOM 16..191
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 192..212
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 213..223
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 224..244
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 245..250
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 251..271
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 272..299
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 300..320
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 321..336
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 337..357
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 358..384
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 385..405
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 406..413
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 414..434
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 435..457
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 15..53
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 54..104
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 138..185
FT /note="GPS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00098"
FT SITE 173..174
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q91ZE5"
FT CARBOHYD 26
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 106
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 245
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 15..24
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 18..30
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 32..52
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 58..71
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 65..80
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 82..103
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT VAR_SEQ 12
FT /note="G -> GLTVLLALPGSEAKNSG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12731063,
FT ECO:0000303|PubMed:16753812"
FT /id="VSP_057755"
FT VAR_SEQ 120..216
FT /note="VSGVKPGFGKQLPGDKRTKHICVYWEGSEGGWSTEGCSHVHSNGSYTKCKCF
FT HLSSFAVLVALAPKEDPVLTVITQVGLTISLLCLFLAILTFLLCR -> ENLRRNGSRE
FT DFARRATQLIQSVELSIWNASFASPGKGQISEFDIVYETKRCNETRENAFLEAGNNTMD
FT INCADALKGNLRESTAVALSLINLLGIF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12731063,
FT ECO:0000303|PubMed:16753812"
FT /id="VSP_057756"
FT VAR_SEQ 217..457
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12731063,
FT ECO:0000303|PubMed:16753812"
FT /id="VSP_057757"
SQ SEQUENCE 457 AA; 50903 MW; 04A1AF0B89852D34 CRC64;
MGSRFLLVLL SGASCPPCPK YASCHNSTHC TCEDGFRARS GRTYFHDSSE KCEDINECET
GLAKCKYKAY CRNKVGGYIC SCLVKYTLFN FLAGIIDYDH PDCYENNSQG TTQSNVDIWV
SGVKPGFGKQ LPGDKRTKHI CVYWEGSEGG WSTEGCSHVH SNGSYTKCKC FHLSSFAVLV
ALAPKEDPVL TVITQVGLTI SLLCLFLAIL TFLLCRPIQN TSTSLHLELS LCLFLAHLLF
LTGINRTEPE VLCSIIAGLL HFLYLACFTW MLLEGLHLFL TVRNLKVANY TSTGRFKKRF
MYPVGYGIPA VIIAVSAIVG PQNYGTFTCW LKLDKGFIWS FMGPVAVIIL INLVFYFQVL
WILRSKLSSL NKEVSTIQDT RVMTFKAISQ LFILGCSWGL GFFMVEEVGK TIGSIIAYSF
TIINTLQGVL LFVVHCLLNR QVRLIILSVI SLVPKSN
