ID AGRF5_RAT Reviewed; 1349 AA.
AC Q9WVT0;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 27-MAR-2024, entry version 156.
DE RecName: Full=Adhesion G protein-coupled receptor F5;
DE AltName: Full=G-protein coupled hepta-helical receptor Ig-hepta;
DE AltName: Full=G-protein coupled receptor 116;
DE Flags: Precursor;
GN Name=Adgrf5; Synonyms=Gpr116, Gprhep;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBUNIT, SUBCELLULAR
RP LOCATION, GLYCOSYLATION, AND DEVELOPMENTAL STAGE.
RC TISSUE=Lung;
RX PubMed=10391944; DOI=10.1074/jbc.274.28.19957;
RA Abe J., Suzuki H., Notoya M., Yamamoto T., Hirose S.;
RT "Ig-hepta, a novel member of the G protein-coupled hepta-helical receptor
RT (GPCR) family that has immunoglobulin-like repeats in a long N-terminal
RT extracellular domain and defines a new subfamily of GPCRs.";
RL J. Biol. Chem. 274:19957-19964(1999).
RN [2]
RP PROTEIN SEQUENCE OF 224-233 AND 994-1003, MUTAGENESIS OF THR-994, AND
RP PROTEOLYTIC PROCESSING.
RX PubMed=11973329; DOI=10.1074/jbc.m110877200;
RA Abe J., Fukuzawa T., Hirose S.;
RT "Cleavage of Ig-Hepta at a 'SEA' module and at a conserved G protein-
RT coupled receptor proteolytic site.";
RL J. Biol. Chem. 277:23391-23398(2002).
RN [3]
RP PROTEIN SEQUENCE OF 52-60, PROTEOLYTIC PROCESSING, CLEAVAGE BY FURIN,
RP GLYCOSYLATION, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=16882675; DOI=10.1093/jb/mvj170;
RA Fukuzawa T., Hirose S.;
RT "Multiple processing of Ig-Hepta/GPR116, a G protein-coupled receptor with
RT immunoglobulin (Ig)-like repeats, and generation of EGF2-like fragment.";
RL J. Biochem. 140:445-452(2006).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-819, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Receptor that plays a critical role in lung surfactant
CC homeostasis. May play a role in controlling adipocyte function.
CC {ECO:0000250|UniProtKB:G5E8Q8}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:10391944). Heterodimer of
CC 2 chains generated by proteolytic processing; the large extracellular
CC N-terminal fragment and the membrane-bound C-terminal fragment
CC predominantly remain associated and non-covalently linked
CC (PubMed:11973329). Fragment generates by the processing enzyme furin
CC remains attached to the extracellular N-terminal fragment
CC (PubMed:16882675). Interacts (via N-terminal extracellular domain) with
CC SFTPD (By similarity). {ECO:0000250|UniProtKB:G5E8Q8,
CC ECO:0000269|PubMed:10391944, ECO:0000269|PubMed:11973329,
CC ECO:0000269|PubMed:16882675}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10391944,
CC ECO:0000269|PubMed:16882675}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the lung and to a much lesser
CC extent in the kidney and heart. Dense localization in alveolar walls of
CC the lung and in the intercalated cells of the collecting duct of the
CC kidney. {ECO:0000269|PubMed:10391944}.
CC -!- DEVELOPMENTAL STAGE: Strongly induced postnatally.
CC {ECO:0000269|PubMed:10391944}.
CC -!- PTM: Proteolytically cleaved at multiple sites: one in the GPS domain
CC (S1 site) and the other in the SEA domain (S2 site). The proteolytic
CC cleavage at S1 site generates an extracellular subunit and a seven-
CC transmembrane subunit. The proteolytic cleavage at S2 site generates a
CC fragment that undergoes proteolytic cleavage by the processing enzyme
CC furin. {ECO:0000269|PubMed:11973329, ECO:0000269|PubMed:16882675}.
CC -!- PTM: Highly glycosylated. {ECO:0000269|PubMed:10391944,
CC ECO:0000269|PubMed:16882675}.
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; AB019120; BAA82518.1; -; mRNA.
DR RefSeq; NP_620810.1; NM_139110.1.
DR RefSeq; XP_006244659.1; XM_006244597.3.
DR AlphaFoldDB; Q9WVT0; -.
DR SMR; Q9WVT0; -.
DR STRING; 10116.ENSRNOP00000071238; -.
DR MEROPS; P02.032; -.
DR GlyCosmos; Q9WVT0; 20 sites, No reported glycans.
DR GlyGen; Q9WVT0; 20 sites.
DR iPTMnet; Q9WVT0; -.
DR PhosphoSitePlus; Q9WVT0; -.
DR PaxDb; 10116-ENSRNOP00000015223; -.
DR Ensembl; ENSRNOT00000015223.3; ENSRNOP00000015223.1; ENSRNOG00000011154.7.
DR Ensembl; ENSRNOT00055034326; ENSRNOP00055027807; ENSRNOG00055020095.
DR Ensembl; ENSRNOT00060037919; ENSRNOP00060031267; ENSRNOG00060021816.
DR Ensembl; ENSRNOT00065039830; ENSRNOP00065032401; ENSRNOG00065023255.
DR GeneID; 245977; -.
DR KEGG; rno:245977; -.
DR UCSC; RGD:621679; rat.
DR AGR; RGD:621679; -.
DR CTD; 221395; -.
DR RGD; 621679; Adgrf5.
DR eggNOG; KOG4193; Eukaryota.
DR GeneTree; ENSGT00940000154603; -.
DR HOGENOM; CLU_002753_3_5_1; -.
DR InParanoid; Q9WVT0; -.
DR OrthoDB; 3876300at2759; -.
DR PhylomeDB; Q9WVT0; -.
DR TreeFam; TF316380; -.
DR Reactome; R-RNO-5683826; Surfactant metabolism.
DR PRO; PR:Q9WVT0; -.
DR Proteomes; UP000002494; Chromosome 9.
DR Bgee; ENSRNOG00000011154; Expressed in lung and 19 other cell types or tissues.
DR ExpressionAtlas; Q9WVT0; baseline and differential.
DR Genevisible; Q9WVT0; RN.
DR GO; GO:0045177; C:apical part of cell; ISO:RGD.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
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:0006112; P:energy reserve metabolic process; ISO:RGD.
DR GO; GO:0048821; P:erythrocyte development; ISO:RGD.
DR GO; GO:0045444; P:fat cell differentiation; ISO:RGD.
DR GO; GO:0003094; P:glomerular filtration; ISO:RGD.
DR GO; GO:0042593; P:glucose homeostasis; ISO:RGD.
DR GO; GO:0042116; P:macrophage activation; ISO:RGD.
DR GO; GO:0043031; P:negative regulation of macrophage activation; ISO:RGD.
DR GO; GO:0061626; P:pharyngeal arch artery morphogenesis; ISO:RGD.
DR GO; GO:0008654; P:phospholipid biosynthetic process; ISO:RGD.
DR GO; GO:0071073; P:positive regulation of phospholipid biosynthetic process; ISO:RGD.
DR GO; GO:0019216; P:regulation of lipid metabolic process; ISO:RGD.
DR GO; GO:0043129; P:surfactant homeostasis; ISO:RGD.
DR Gene3D; 2.60.220.50; -; 1.
DR Gene3D; 2.60.40.10; Immunoglobulins; 2.
DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR Gene3D; 3.30.70.960; SEA domain; 1.
DR InterPro; IPR046338; GAIN_dom_sf.
DR InterPro; IPR017981; GPCR_2-like_7TM.
DR InterPro; IPR008078; GPCR_2_Ig-hepta-like_rcpt.
DR InterPro; IPR000832; GPCR_2_secretin-like.
DR InterPro; IPR017983; GPCR_2_secretin-like_CS.
DR InterPro; IPR000203; GPS.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR013151; Immunoglobulin.
DR InterPro; IPR000082; SEA_dom.
DR InterPro; IPR036364; SEA_dom_sf.
DR PANTHER; PTHR45813:SF4; ADHESION G PROTEIN-COUPLED RECEPTOR F5; 1.
DR PANTHER; PTHR45813; EF-HAND DOMAIN-CONTAINING PROTEIN; 1.
DR Pfam; PF00002; 7tm_2; 1.
DR Pfam; PF01825; GPS; 1.
DR Pfam; PF00047; ig; 1.
DR Pfam; PF01390; SEA; 1.
DR PRINTS; PR00249; GPCRSECRETIN.
DR PRINTS; PR01695; IGHEPTARCPTR.
DR SMART; SM00303; GPS; 1.
DR SMART; SM00409; IG; 2.
DR SMART; SM00408; IGc2; 2.
DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR SUPFAM; SSF48726; Immunoglobulin; 2.
DR SUPFAM; SSF82671; SEA domain; 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 PROSITE; PS50835; IG_LIKE; 3.
DR PROSITE; PS50024; SEA; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Direct protein sequencing; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Immunoglobulin domain; Membrane;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transducer;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..1349
FT /note="Adhesion G protein-coupled receptor F5"
FT /id="PRO_0000012897"
FT TOPO_DOM 25..1016
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1017..1036
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1037..1055
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1056..1078
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1079..1097
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1098..1120
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1121..1131
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1132..1154
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1155..1173
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1174..1196
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1197..1216
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1217..1239
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1240..1248
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1249..1271
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1272..1349
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 163..271
FT /note="SEA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00188"
FT DOMAIN 268..366
FT /note="Ig-like 1"
FT DOMAIN 367..464
FT /note="Ig-like 2"
FT DOMAIN 469..559
FT /note="Ig-like 3"
FT DOMAIN 951..1005
FT /note="GPS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00098"
FT REGION 1329..1349
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 51..52
FT /note="Cleavage; by furin"
FT /evidence="ECO:0000269|PubMed:16882675"
FT SITE 223..224
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:11973329"
FT SITE 993..994
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:11973329"
FT MOD_RES 819
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 1303
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:G5E8Q8"
FT MOD_RES 1310
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:G5E8Q8"
FT CARBOHYD 73
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 94
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 185
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 254
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 270
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 299
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 326
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 337
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 349
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 396
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 470
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 503
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 538
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 649
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 666
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 820
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 958
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 963
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1085
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 291..348
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 389..447
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 490..543
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT MUTAGEN 994
FT /note="T->A: Abolishes cleavage."
FT /evidence="ECO:0000269|PubMed:11973329"
SQ SEQUENCE 1349 AA; 149446 MW; 104CF1D9A35B1409 CRC64;
MKSSRTVTLY FVLIVICSSE ATWSRPAEPI VHPLILQEHE LAGEELLRPK RAVAVGGPVA
EEYTVDVEIS FENVSFLESI RAHLNSLRFP VQGNGTDILS MAMTTVCTPT GNDLLCFCEK
GYQWPEERCL SSLTCQEHDS ALPGRYCNCL KGLPPQGPFC QLPETYITLK IKVRLNIGFQ
EDLENTSSAL YRSYKTDLER AFRAGYRTLP GFRSVTVTQF TKGSVVVDYI VEVASAPLPG
SIHKANEQVI QNLNQTYKMD YNSFQGTPSN ETKFTVTPEF IFEGDNVTLE CESEFVSSNT
SWFYGEKRSD IQNSDKFSIH TSIINNISLV TRLTIFNFTQ HDAGLYGCNV TLDIFEYGTV
RKLDVTPIRI LAKEERKVVC DNNPISLNCC SENIANWSRI EWKQEGKINI EGTPETDLES
SCSTYTLKAD GTQCPSGSSG TTVIYTCEFV SVYGAKGSKN IAVTFTSVAN LTITPDPISV
SEGQSFSITC LSDVSSFDEV YWNTSAGIKI HPRFYTMRRY RDGAESVLTV KTSTREWNGT
YHCIFRYKNS YSIATKDVTV HPLPLESDIM MDPLEASGLC TSSHQFKCCI EENDGEEYIV
TFHVDSSSFP AEREVIGKQA CYTYSLPGKL PSRCPKDIDV FCHFTNAANS SVRSPSMKLT
LVPGKNITCQ DPIIGIGEPG KVIQKLCQFA GVSRSPGQTI GGTVTYKCVG SQWKEETRAC
ISAPINGLLQ LAKALIKSPS QDQKLPKYLR DLSVSTGKEE QDIRSSPGSL GAIISILDLL
STVPTQVNSE MMRDILATIN VILDKSTLNS WEKLLQQQSN QSSQFLQSVE RFSKALELGD
STPPFLFHPN VQMKSMVIKR GHAQMYQQKF VFTDSDLWGD VAIDECQLGS LQPDSSIVTV
AFPTLKAILA QDGQRKTPSN SLVMTTTVSH NIVKPFRISM TFKNNHRSGG KPQCVFWNFS
LANNTGGWDS SGCTVEDDGR DNRDRVFCKC NHLTSFSILM SPDSPDPGSL LKILLDIISY
IGLGFSIVSL AACLVVEAMV WKSVTKNRTS YMRHICIVNI ALCLLIADIW FIVAGAIHDG
HYPLNETACV AATFFIHFFY LSVFFWMLTL GLMLFYRLIF ILHDASKSTQ KAIAFSLGYG
CPLIISSITV GVTQPQEVYM RKNACWLNWE DTRALLAFAI PALIIVVVNV SITVVVITKI
LRPSVGDKPG KQEKSSLFQI SKSIGVLTPL LGLTWGFGLA TVIQGSNAVF HIIFTLLNAF
QGLFILLFGC LWDQKVQEAL LHKFSLSRWS SQHSKSTSLG SSTPVFSMSS PISRRFNNLF
GKTGTYNVST PETTSSSVEN SSSAYSLLN
//
