AGRF5_MOUSE
ID AGRF5_MOUSE Reviewed; 1348 AA.
AC G5E8Q8;
DT 22-JUL-2015, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 69.
DE RecName: Full=Adhesion G protein-coupled receptor F5;
DE AltName: Full=G-protein coupled receptor 116;
DE Flags: Precursor;
GN Name=Adgrf5; Synonyms=Gpr116;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1302 AND SER-1309, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=22837050; DOI=10.1002/dvdy.23841;
RA Promel S., Waller-Evans H., Dixon J., Zahn D., Colledge W.H., Doran J.,
RA Carlton M.B., Grosse J., Schoneberg T., Russ A.P., Langenhan T.;
RT "Characterization and functional study of a cluster of four highly
RT conserved orphan adhesion-GPCR in mouse.";
RL Dev. Dyn. 241:1591-1602(2012).
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=22971422; DOI=10.1016/j.febslet.2012.08.006;
RA Nie T., Hui X., Gao X., Li K., Lin W., Xiang X., Ding M., Kuang Y., Xu A.,
RA Fei J., Wang Z., Wu D.;
RT "Adipose tissue deletion of Gpr116 impairs insulin sensitivity through
RT modulation of adipose function.";
RL FEBS Lett. 586:3618-3625(2012).
RN [6]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=23684610; DOI=10.1016/j.celrep.2013.04.019;
RA Yang M.Y., Hilton M.B., Seaman S., Haines D.C., Nagashima K., Burks C.M.,
RA Tessarollo L., Ivanova P.T., Brown H.A., Umstead T.M., Floros J.,
RA Chroneos Z.C., St Croix B.;
RT "Essential regulation of lung surfactant homeostasis by the orphan G
RT protein-coupled receptor GPR116.";
RL Cell Rep. 3:1457-1464(2013).
RN [7]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=23590306; DOI=10.1165/rcmb.2012-0439oc;
RA Bridges J.P., Ludwig M.G., Mueller M., Kinzel B., Sato A., Xu Y.,
RA Whitsett J.A., Ikegami M.;
RT "Orphan G protein-coupled receptor GPR116 regulates pulmonary surfactant
RT pool size.";
RL Am. J. Respir. Cell Mol. Biol. 49:348-357(2013).
RN [8]
RP INTERACTION WITH SFTPD, AND FUNCTION.
RX PubMed=23922714; DOI=10.1371/journal.pone.0069451;
RA Fukuzawa T., Ishida J., Kato A., Ichinose T., Ariestanti D.M.,
RA Takahashi T., Ito K., Abe J., Suzuki T., Wakana S., Fukamizu A.,
RA Nakamura N., Hirose S.;
RT "Lung surfactant levels are regulated by Ig-Hepta/GPR116 by monitoring
RT surfactant protein D.";
RL PLoS ONE 8:E69451-E69451(2013).
CC -!- FUNCTION: Receptor that plays a critical role in lung surfactant
CC homeostasis (PubMed:23590306, PubMed:23922714, PubMed:23684610). May
CC play a role in controlling adipocyte function (PubMed:22971422).
CC {ECO:0000269|PubMed:22971422, ECO:0000269|PubMed:23590306,
CC ECO:0000269|PubMed:23684610, ECO:0000269|PubMed:23922714}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Heterodimer of 2 chains generated
CC by proteolytic processing; the large extracellular N-terminal fragment
CC and the membrane-bound C-terminal fragment predominantly remain
CC associated and non-covalently linked. Fragment generates by the
CC processing enzyme furin remains attached to the extracellular N-
CC terminal fragment. Interacts (via N-terminal extracellular domain) with
CC SFTPD (PubMed:23922714). {ECO:0000250|UniProtKB:Q9WVT0,
CC ECO:0000269|PubMed:23922714}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9WVT0};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Widely expressed and highly expressed in the lung.
CC In the lung predominantly expressed in the alveolar type II epithelial
CC cells. {ECO:0000269|PubMed:22837050, ECO:0000269|PubMed:22971422,
CC ECO:0000269|PubMed:23590306, ECO:0000269|PubMed:23684610}.
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:0000250|UniProtKB:Q9WVT0}.
CC -!- PTM: Highly glycosylated. {ECO:0000250|UniProtKB:Q9WVT0}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice exhibit premature death, decreased
CC body weight and respiratory distress associated with pulmonary alveolar
CC proteinosis. {ECO:0000269|PubMed:23684610}.
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; AC169504; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CT010585; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CT025700; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466559; EDL23401.1; -; Genomic_DNA.
DR CCDS; CCDS37622.1; -.
DR RefSeq; NP_001074647.1; NM_001081178.1.
DR AlphaFoldDB; G5E8Q8; -.
DR IntAct; G5E8Q8; 1.
DR MINT; G5E8Q8; -.
DR STRING; 10090.ENSMUSP00000109229; -.
DR MEROPS; P02.032; -.
DR GlyConnect; 2110; 2 N-Linked glycans (1 site).
DR GlyGen; G5E8Q8; 8 sites, 2 N-linked glycans (1 site).
DR iPTMnet; G5E8Q8; -.
DR PhosphoSitePlus; G5E8Q8; -.
DR jPOST; G5E8Q8; -.
DR MaxQB; G5E8Q8; -.
DR PaxDb; G5E8Q8; -.
DR PeptideAtlas; G5E8Q8; -.
DR PRIDE; G5E8Q8; -.
DR ProteomicsDB; 282034; -.
DR Antibodypedia; 16896; 244 antibodies from 28 providers.
DR Ensembl; ENSMUST00000113599; ENSMUSP00000109229; ENSMUSG00000056492.
DR Ensembl; ENSMUST00000226087; ENSMUSP00000153049; ENSMUSG00000056492.
DR GeneID; 224792; -.
DR KEGG; mmu:224792; -.
DR UCSC; uc008cpa.1; mouse.
DR CTD; 221395; -.
DR MGI; MGI:2182928; Adgrf5.
DR VEuPathDB; HostDB:ENSMUSG00000056492; -.
DR eggNOG; KOG4193; Eukaryota.
DR GeneTree; ENSGT00940000154603; -.
DR HOGENOM; CLU_002753_3_5_1; -.
DR InParanoid; G5E8Q8; -.
DR OMA; VADTWFI; -.
DR OrthoDB; 611778at2759; -.
DR PhylomeDB; G5E8Q8; -.
DR TreeFam; TF316380; -.
DR Reactome; R-MMU-5683826; Surfactant metabolism.
DR BioGRID-ORCS; 224792; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Adgrf5; mouse.
DR PRO; PR:G5E8Q8; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; G5E8Q8; protein.
DR Bgee; ENSMUSG00000056492; Expressed in right lung and 217 other tissues.
DR ExpressionAtlas; G5E8Q8; baseline and differential.
DR Genevisible; G5E8Q8; MM.
DR GO; GO:0045177; C:apical part of cell; IDA:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; IMP:MGI.
DR GO; GO:0048821; P:erythrocyte development; IGI:MGI.
DR GO; GO:0045444; P:fat cell differentiation; IMP:MGI.
DR GO; GO:0003094; P:glomerular filtration; IGI:MGI.
DR GO; GO:0042593; P:glucose homeostasis; IMP:MGI.
DR GO; GO:0042116; P:macrophage activation; IMP:MGI.
DR GO; GO:0043031; P:negative regulation of macrophage activation; IMP:MGI.
DR GO; GO:0061626; P:pharyngeal arch artery morphogenesis; IGI:MGI.
DR GO; GO:0008654; P:phospholipid biosynthetic process; IMP:MGI.
DR GO; GO:0071073; P:positive regulation of phospholipid biosynthetic process; IMP:MGI.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IMP:MGI.
DR GO; GO:0043129; P:surfactant homeostasis; IMP:UniProtKB.
DR Gene3D; 2.60.220.50; -; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR032471; GAIN_dom_N.
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; 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; IPR013098; Ig_I-set.
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 Pfam; PF00002; 7tm_2; 1.
DR Pfam; PF16489; GAIN; 1.
DR Pfam; PF01825; GPS; 1.
DR Pfam; PF07679; I-set; 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; SSF48726; SSF48726; 2.
DR SUPFAM; SSF82671; SSF82671; 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 Autocatalytic cleavage; Cell membrane; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Membrane; Phosphoprotein; Reference proteome;
KW Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..1348
FT /note="Adhesion G protein-coupled receptor F5"
FT /id="PRO_0000433564"
FT TOPO_DOM 22..1019
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1020..1040
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1041..1055
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1056..1076
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1077..1092
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1093..1113
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1114..1130
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1131..1151
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1152..1175
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1176..1196
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1197..1221
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1222..1242
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1243..1250
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1251..1271
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1272..1348
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 /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 367..464
FT /note="Ig-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 469..559
FT /note="Ig-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 950..1004
FT /note="GPS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00098"
FT REGION 1328..1348
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 51..52
FT /note="Cleavage; by furin"
FT /evidence="ECO:0000250|UniProtKB:Q9WVT0"
FT SITE 223..224
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q9WVT0"
FT SITE 992..993
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q9WVT0"
FT MOD_RES 818
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9WVT0"
FT MOD_RES 1302
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1309
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
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 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 470
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 665
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"
SQ SEQUENCE 1348 AA; 149387 MW; BC2CDA96C63B7018 CRC64;
MRSPRTFTFY FLLLVICSSE AALSTPTEPI VQPSILQEHE LAGEELLRPK RAAAAGDRVA
EEYMVDIEIS FENVSFLESI RAHLNNLSFP IRGTEADILN IAMTTVCTPA GNDLLCFCEK
GYQWSEERCL HSLTCQDYDS ALPGGYCSCL KGLPPQGPFC QLPEAFITLK LKVRLNIGFQ
EDLKNTSSAL YRSYKTDLER AFRAGYRTLP GFRSVTVTQF TKGSVVVNYV VRVTSAPLPG
SIHKANEQVI QNLNHTYKMD YNSFQGTPSN ETKFTVIPEF IFEGDNVTLE CETEFVTSNT
SWYYGEKRSD IQNSDKYSIH TTVINNISLI TRLTIYNFTQ HDAGMYGCNV TLDIFEYGTV
RKLDVTPIRI LAKEERKVVC DNHPISLNCC SENIANWSSI EWKQEGKISI LGNPESDLES
SCSTYTLKAD GTQCPSGSSG TTVIYTCEFV SAYGARGSKN IAVTFTSVAN LTITRDPISV
SEGQSFSITC LSDVSSFDEV YWNTSAGIKI HPRFYTMRRY QDGAESVLMV KTSTREWNGT
YHCIFRYKNS YSIATKDVTV HPLPLVSDIM MDPLEASGLC TSSHQFKCCV EEDAGEEYAV
TFHVDSSSFP AEREVIGKQA CYTYSLPANL PRCPKDIAVF CHFTNAANSS VRSPSMKLKL
IPRENVTCQD PIIGIGDPGK VIQKLCQFSG VYGSPGQAIG GTVTYKCVGT QWKEESRACI
SAPINGLLQV AKALIKSPTQ DQKLPTYLRD LSVSAGKEEQ DIRSSPGSLG AIISILDLLS
TVPTQVNSEM MRDILATINV ILDKSALNSW EKLLQQQSNQ SSQFLHSVER FSQALQLGDS
TPPFLAHPNV QMKSMVIKRG HPQIYQQQFI FKDSDLWGDV AIDECQLGNL QPDSSIVTVA
FPTLKAILAQ DVQRKTSSNS LVMTTTVSHN IVKPFRISMT FKNNHRSGGK PQCVFWNFSL
ANNTGGWDSS GCSVEDDGRD NRDRVFCKCN HLTSFSILMS PDSPDPGSLL KILLDIISYI
GLGFSIVSLA ACLVVEAMVW KSVTKNRTSY MRHICIVNIA FCLLIADIWF IVAGAIHDGR
YPLNETACVA ATFFIHFFYL SVFFWMLTLG LMLFYRLIFI LHDASKSTQK AIAFSLGYGC
PLIISSITVG VTQPQEVYMR KNACWLNWED TRALLAFAIP ALIIVVVNVS ITVVVITKIL
RPSIGDKPGK QEKSSLFQIS KSIGVLTPLL GLTWGFGLAT VIQGSNAVFH IIFTLLNAFQ
GLFILLFGCL WDQKVQEALL HKFSLSRWSS QHSKSTSIGS STPVFSMSSP ISRRFNNLFG
KTGTYNVSTP ETTSSSLENS SSAYSLLN
