AGRF4_HUMAN
ID AGRF4_HUMAN Reviewed; 695 AA.
AC Q8IZF3; B3KTD0; Q2PNZ0; Q5T5B5; Q5T5B6; Q86SN9; Q8IXE6;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Adhesion G protein-coupled receptor F4;
DE AltName: Full=G-protein coupled receptor 115;
DE AltName: Full=G-protein coupled receptor PGR18;
DE Flags: Precursor;
GN Name=ADGRF4; Synonyms=GPR115, PGR18;
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], AND VARIANT ASN-541.
RC TISSUE=Testis;
RA Bonner T.I., Kauffman D., Nagle J.W., Sloger M.;
RT "Complete coding sequence of GPR115.";
RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
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], AND VARIANT ASN-541.
RC TISSUE=Tongue;
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].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASN-541.
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 125-589.
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 [7]
RP IDENTIFICATION.
RX PubMed=12435584; DOI=10.1016/s0014-5793(02)03574-3;
RA Fredriksson R., Lagerstroem M.C., Hoeglund P.J., Schioeth H.B.;
RT "Novel human G protein-coupled receptors with long N-terminals containing
RT GPS domains and Ser/Thr-rich regions.";
RL FEBS Lett. 531:407-414(2002).
RN [8]
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 [9]
RP VARIANT [LARGE SCALE ANALYSIS] LEU-674.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Orphan receptor.
CC -!- INTERACTION:
CC Q8IZF3; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12137513, EBI-16439278;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- MISCELLANEOUS: Most adhesion GPCRs undergo autoproteolysis at the GPS
CC domain. ADGRF2 is not autoproteolyzed at the GPS motif because of the
CC lack of a consensus catalytic triad sequence within GPS domain.
CC {ECO:0000250|UniProtKB:Q9D2L6}.
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=AAN46671.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=BAC45257.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; DQ315370; ABC41929.1; -; mRNA.
DR EMBL; AB065474; BAC45257.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AK095395; BAG53042.1; -; mRNA.
DR EMBL; AL356421; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX04321.1; -; Genomic_DNA.
DR EMBL; AY255556; AAO85068.1; -; mRNA.
DR EMBL; AY140957; AAN46671.1; ALT_SEQ; mRNA.
DR CCDS; CCDS4922.2; -.
DR RefSeq; NP_001334784.1; NM_001347855.1.
DR RefSeq; NP_722580.3; NM_153838.4.
DR AlphaFoldDB; Q8IZF3; -.
DR BioGRID; 128718; 1.
DR IntAct; Q8IZF3; 1.
DR STRING; 9606.ENSP00000283303; -.
DR ChEMBL; CHEMBL4523889; -.
DR MEROPS; P02.042; -.
DR GlyGen; Q8IZF3; 14 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q8IZF3; -.
DR PhosphoSitePlus; Q8IZF3; -.
DR BioMuta; ADGRF4; -.
DR DMDM; 296439339; -.
DR MassIVE; Q8IZF3; -.
DR PaxDb; Q8IZF3; -.
DR PeptideAtlas; Q8IZF3; -.
DR PRIDE; Q8IZF3; -.
DR ProteomicsDB; 71341; -.
DR Antibodypedia; 1934; 228 antibodies from 29 providers.
DR DNASU; 221393; -.
DR Ensembl; ENST00000283303.3; ENSP00000283303.2; ENSG00000153294.12.
DR Ensembl; ENST00000327753.7; ENSP00000328319.3; ENSG00000153294.12.
DR GeneID; 221393; -.
DR KEGG; hsa:221393; -.
DR MANE-Select; ENST00000283303.3; ENSP00000283303.2; NM_153838.5; NP_722580.3.
DR UCSC; uc003oyz.2; human.
DR CTD; 221393; -.
DR DisGeNET; 221393; -.
DR GeneCards; ADGRF4; -.
DR HGNC; HGNC:19011; ADGRF4.
DR HPA; ENSG00000153294; Tissue enhanced (esophagus, skin).
DR neXtProt; NX_Q8IZF3; -.
DR OpenTargets; ENSG00000153294; -.
DR PharmGKB; PA134954617; -.
DR VEuPathDB; HostDB:ENSG00000153294; -.
DR eggNOG; KOG4193; Eukaryota.
DR GeneTree; ENSGT00940000161797; -.
DR HOGENOM; CLU_002753_3_6_1; -.
DR InParanoid; Q8IZF3; -.
DR OMA; MICCLMF; -.
DR OrthoDB; 611778at2759; -.
DR PhylomeDB; Q8IZF3; -.
DR TreeFam; TF316380; -.
DR PathwayCommons; Q8IZF3; -.
DR SignaLink; Q8IZF3; -.
DR BioGRID-ORCS; 221393; 9 hits in 1066 CRISPR screens.
DR ChiTaRS; ADGRF4; human.
DR GeneWiki; GPR115; -.
DR GenomeRNAi; 221393; -.
DR Pharos; Q8IZF3; Tdark.
DR PRO; PR:Q8IZF3; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q8IZF3; protein.
DR Bgee; ENSG00000153294; Expressed in skin of abdomen and 92 other tissues.
DR ExpressionAtlas; Q8IZF3; baseline and differential.
DR Genevisible; Q8IZF3; HS.
DR GO; GO:0016021; C:integral component of membrane; TAS:GDB.
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; IPR046338; GAIN_dom_sf.
DR InterPro; IPR017981; GPCR_2-like.
DR InterPro; IPR008078; GPCR_2_Ig-hepta-like_rcpt.
DR InterPro; IPR000832; GPCR_2_secretin-like.
DR InterPro; IPR000203; GPS.
DR Pfam; PF00002; 7tm_2; 1.
DR Pfam; PF01825; GPS; 1.
DR PRINTS; PR00249; GPCRSECRETIN.
DR PRINTS; PR01695; IGHEPTARCPTR.
DR PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1.
DR PROSITE; PS50221; GPS; 1.
PE 1: Evidence at protein level;
KW G-protein coupled receptor; Glycoprotein; Membrane; Receptor;
KW Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..695
FT /note="Adhesion G protein-coupled receptor F4"
FT /id="PRO_0000070336"
FT TOPO_DOM 22..406
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 407..427
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 428..440
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 441..461
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 462..485
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 486..506
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 507..515
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 516..536
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 537..561
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 562..582
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 583..606
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 607..627
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 628..634
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 635..655
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 656..695
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 346..396
FT /note="GPS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00098"
FT REGION 674..695
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 679..695
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 61
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 169
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 177
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 209
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 229
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 257
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 263
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 264
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 286
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 309
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 379
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 507
FT /note="R -> C (in dbSNP:rs12110938)"
FT /id="VAR_055930"
FT VARIANT 541
FT /note="K -> N (in dbSNP:rs9369738)"
FT /evidence="ECO:0000269|PubMed:14702039, ECO:0000269|Ref.1,
FT ECO:0000269|Ref.5"
FT /id="VAR_024476"
FT VARIANT 674
FT /note="S -> L (in a breast cancer sample; somatic mutation;
FT dbSNP:rs572583506)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036224"
FT CONFLICT 491
FT /note="M -> I (in Ref. 6; AAO85068)"
FT /evidence="ECO:0000305"
FT CONFLICT 538..540
FT /note="EPE -> GPV (in Ref. 6; AAO85068)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 695 AA; 77719 MW; B902221DD0804D0E CRC64;
MKMKSQATMI CCLVFFLSTE CSHYRSKIHL KAGDKLQSPE GKPKTGRIQE KCEGPCISSS
NCSQPCAKDF HGEIGFTCNQ KKWQKSAETC TSLSVEKLFK DSTGASRLSV AAPSIPLHIL
DFRAPETIES VAQGIRKNCP FDYACITDMV KSSETTSGNI AFIVELLKNI STDLSDNVTR
EKMKSYSEVA NHILDTAAIS NWAFIPNKNA SSDLLQSVNL FARQLHIHNN SENIVNELFI
QTKGFHINHN TSEKSLNFSM SMNNTTEDIL GMVQIPRQEL RKLWPNASQA ISIAFPTLGA
ILREAHLQNV SLPRQVNGLV LSVVLPERLQ EIILTFEKIN KTRNARAQCV GWHSKKRRWD
EKACQMMLDI RNEVKCRCNY TSVVMSFSIL MSSKSMTDKV LDYITCIGLS VSILSLVLCL
IIEATVWSRV VVTEISYMRH VCIVNIAVSL LTANVWFIIG SHFNIKAQDY NMCVAVTFFS
HFFYLSLFFW MLFKALLIIY GILVIFRRMM KSRMMVIGFA IGYGCPLIIA VTTVAITEPE
KGYMRPEACW LNWDNTKALL AFAIPAFVIV AVNLIVVLVV AVNTQRPSIG SSKSQDVVII
MRISKNVAIL TPLLGLTWGF GIATLIEGTS LTFHIIFALL NAFQGFFILL FGTIMDHKIR
DALRMRMSSL KGKSRAAENA SLGPTNGSKL MNRQG
