GP161_MOUSE
ID GP161_MOUSE Reviewed; 545 AA.
AC B2RPY5; B0L0L8; J3QN69; Q80T48;
DT 07-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-2008, sequence version 1.
DT 03-AUG-2022, entry version 95.
DE RecName: Full=G-protein coupled receptor 161;
GN Name=Gpr161; Synonyms=Gm208;
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 [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, AND
RP INVOLVEMENT IN VL PHENOTYPE.
RX PubMed=18250320; DOI=10.1073/pnas.0705657105;
RA Matteson P.G., Desai J., Korstanje R., Lazar G., Borsuk T.E., Rollins J.,
RA Kadambi S., Joseph J., Rahman T., Wink J., Benayed R., Paigen B.,
RA Millonig J.H.;
RT "The orphan G protein-coupled receptor, Gpr161, encodes the vacuolated lens
RT locus and controls neurulation and lens development.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:2088-2093(2008).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 119-266.
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 [5]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF VAL-145; 233-VAL--LYS-237; 238-VAL--GLY-241;
RP 243-VAL-VAL-244; GLN-251; 254-GLY--ASN-257 AND 258-SER--THR-262.
RX PubMed=23332756; DOI=10.1016/j.cell.2012.12.026;
RA Mukhopadhyay S., Wen X., Ratti N., Loktev A., Rangell L., Scales S.J.,
RA Jackson P.K.;
RT "The ciliary G-protein-coupled receptor Gpr161 negatively regulates the
RT Sonic Hedgehog pathway via cAMP signaling.";
RL Cell 152:210-223(2013).
CC -!- FUNCTION: Key negative regulator of Shh signaling, which promotes the
CC processing of GLI3 into GLI3R during neural tube development. Recruited
CC by TULP3 and the IFT-A complex to primary cilia and acts as a regulator
CC of the PKA-dependent basal repression machinery in Shh signaling by
CC increasing cAMP levels, leading to promote the PKA-dependent processing
CC of GLI3 into GLI3R and repress the Shh signaling. In presence of SHH,
CC it is removed from primary cilia and is internalized into recycling
CC endosomes, preventing its activity and allowing activation of the Shh
CC signaling. Its ligand is unknown. {ECO:0000269|PubMed:18250320,
CC ECO:0000269|PubMed:23332756}.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium membrane; Multi-pass
CC membrane protein. Cell membrane; Multi-pass membrane protein.
CC Note=Mainly localizes to primary cilium in a TULP3 and IFT-A complex-
CC dependent manner. In presence of SHH, it is removed from primary cilia
CC and is internalized into recycling endosomes and is apparently not
CC degraded.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=B2RPY5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=B2RPY5-2; Sequence=VSP_037635;
CC Name=3;
CC IsoId=B2RPY5-3; Sequence=VSP_046300;
CC -!- DEVELOPMENTAL STAGE: Expressed ubiquitously from 8.5 dpc and is mostly
CC concentrated in the developing nervous system at later stages. By 10.5
CC dpc, it is mainly expressed in the neural tube. At later embryonic
CC stages (12.5 dpc and 15.5 dpc), it is predominantly expressed in the
CC brain, spinal cord, and dorsal ganglia and weakly expressed in the
CC hindlimb. According to PubMed:18250320, expression is restricted to the
CC lateral neural folds, while PubMed:23332756 detects expression
CC throughout the neural tube. Also expressed at low levels in kidney
CC stroma and retina at 15.5 dpc. {ECO:0000269|PubMed:23332756}.
CC -!- DISEASE: Note=An intragenic deletion in Gpr161 is responsible for the
CC vacuolated lens (vl) phenotype that is characterized by neural tube
CC defects and congenital cataracts. The vl mutation aroses spontaneously.
CC About half of vl/vl embryos display lumbar-sacral spina bifida and die
CC before birth, and the other half have closed neural tubes but show
CC thinning of the midline neuroepithelium and epidermis, dilation of the
CC dorsal ventricle, and presence of ectopic neuroepithelial cells in the
CC ventricle. All surviving adults display congenital cataracts
CC (PubMed:18250320). It is not a null mutant allele (PubMed:23332756).
CC {ECO:0000269|PubMed:18250320, ECO:0000269|PubMed:23332756}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality by 10.5 dpc caused by
CC increased Shh signaling and ventralization throughout the developing
CC neural tube. Defects in Gli3 processing. {ECO:0000269|PubMed:23332756}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; EF197953; ABO93465.1; -; mRNA.
DR EMBL; AC116374; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC137659; AAI37660.1; -; mRNA.
DR EMBL; AY255596; AAO85108.1; -; mRNA.
DR CCDS; CCDS83621.1; -. [B2RPY5-1]
DR RefSeq; NP_001074595.1; NM_001081126.2. [B2RPY5-3]
DR RefSeq; NP_001297358.1; NM_001310429.1. [B2RPY5-1]
DR RefSeq; NP_001297359.1; NM_001310430.1.
DR RefSeq; XP_006496913.1; XM_006496850.3.
DR RefSeq; XP_006496914.1; XM_006496851.3.
DR RefSeq; XP_006496915.1; XM_006496852.3.
DR RefSeq; XP_011237123.1; XM_011238821.2.
DR AlphaFoldDB; B2RPY5; -.
DR SMR; B2RPY5; -.
DR STRING; 10090.ENSMUSP00000136621; -.
DR GlyGen; B2RPY5; 3 sites.
DR iPTMnet; B2RPY5; -.
DR PhosphoSitePlus; B2RPY5; -.
DR SwissPalm; B2RPY5; -.
DR PaxDb; B2RPY5; -.
DR PRIDE; B2RPY5; -.
DR ProteomicsDB; 271136; -. [B2RPY5-1]
DR ProteomicsDB; 271137; -. [B2RPY5-2]
DR ProteomicsDB; 271138; -. [B2RPY5-3]
DR Antibodypedia; 2941; 280 antibodies from 31 providers.
DR Ensembl; ENSMUST00000178700; ENSMUSP00000136621; ENSMUSG00000040836. [B2RPY5-1]
DR GeneID; 240888; -.
DR KEGG; mmu:240888; -.
DR UCSC; uc007dja.1; mouse. [B2RPY5-3]
DR UCSC; uc011wux.1; mouse. [B2RPY5-1]
DR CTD; 23432; -.
DR MGI; MGI:2685054; Gpr161.
DR VEuPathDB; HostDB:ENSMUSG00000040836; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00940000157829; -.
DR InParanoid; B2RPY5; -.
DR OrthoDB; 1262707at2759; -.
DR PhylomeDB; B2RPY5; -.
DR TreeFam; TF331895; -.
DR Reactome; R-MMU-5610787; Hedgehog 'off' state.
DR Reactome; R-MMU-5632684; Hedgehog 'on' state.
DR BioGRID-ORCS; 240888; 0 hits in 52 CRISPR screens.
DR ChiTaRS; Gpr161; mouse.
DR PRO; PR:B2RPY5; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; B2RPY5; protein.
DR Bgee; ENSMUSG00000040836; Expressed in cleaving embryo and 176 other tissues.
DR ExpressionAtlas; B2RPY5; baseline and differential.
DR Genevisible; B2RPY5; MM.
DR GO; GO:0060170; C:ciliary membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR GO; GO:0097386; C:glial cell projection; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043005; C:neuron projection; IDA:MGI.
DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IDA:UniProtKB.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:1901621; P:negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning; IMP:UniProtKB.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cataract; Cell membrane; Cell projection; Cilium;
KW Developmental protein; Disulfide bond; G-protein coupled receptor;
KW Glycoprotein; Membrane; Receptor; Reference proteome; Transducer;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..545
FT /note="G-protein coupled receptor 161"
FT /id="PRO_0000379073"
FT TOPO_DOM 1..46
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 47..67
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 68..80
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 81..101
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 102..117
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 118..139
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 140..159
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 160..180
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 181..205
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 206..226
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 227..285
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 286..306
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 307..322
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 323..343
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 344..545
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 21
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 32
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 117
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 116..194
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VAR_SEQ 1..3
FT /note="MDF -> MDSHHTTHTLLAVFPV (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_046300"
FT VAR_SEQ 1
FT /note="M -> MDFVQHALLTASRGALT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_037635"
FT MUTAGEN 145
FT /note="V->E: Inactive mutant unable to increase cAMP upon
FT induction."
FT /evidence="ECO:0000269|PubMed:23332756"
FT MUTAGEN 233..237
FT /note="VKARK->AAAAA: In mut1; abolishes localization to
FT primary cilia."
FT /evidence="ECO:0000269|PubMed:23332756"
FT MUTAGEN 238..241
FT /note="VHCG->AAAA: In mut2; weakly affects localization to
FT primary cilia."
FT /evidence="ECO:0000269|PubMed:23332756"
FT MUTAGEN 243..244
FT /note="VV->AA: In mut3; does not affect localization to
FT primary cilia; when associated with A-251."
FT /evidence="ECO:0000269|PubMed:23332756"
FT MUTAGEN 251
FT /note="Q->A: In mut3; does not affect localization to
FT primary cilia; when associated with 243-A-A-244."
FT /evidence="ECO:0000269|PubMed:23332756"
FT MUTAGEN 254..257
FT /note="GRKN->AAAA: In mut4; does not affect localization to
FT primary cilia."
FT /evidence="ECO:0000269|PubMed:23332756"
FT MUTAGEN 258..262
FT /note="SSTST->ASAAA: In mut5; does not affect localization
FT to primary cilia."
FT /evidence="ECO:0000269|PubMed:23332756"
SQ SEQUENCE 545 AA; 60303 MW; AF2C9F191D8211DA CRC64;
MDFVQHALLT ASRGALTMSL NSSLSYRKEL SNLTATEGGE GGAVSEFIAI IIITVLVCLG
NLVIVVTLYK KSYLLTLSNK FVFSLTLSNF LLSVLVLPFV VTSSIRREWI FGVVWCNFSA
LLYLLISSAS MLTLGVIAID RYYAVLYPMV YPMKITGNRA VMALVYIWLH SLIGCLPPLF
GWSSVEFDEF KWMCVAAWHQ EPGYTIFWQI WCALFPFLIM LVCYGFIFRV ARVKARKVHC
GTVVTVEEDS QRSGRKNSST STSSSGSRRN ALQGVVYSAN QCKALITILV VIGAFMVTWG
PYMVVITSEA LWGKNCVSPT LETWATWLSF TSAICHPLIY GLWNKTVRKE LLGMCFGDRY
YRESFVQRQR TSRLFSISNR ITDLGLSPHL TALMAGGQSL GHSSSTGDTG FSYSQDSGTD
VMLLEDGTSE DNPPQHCTCP PKRRSSVTFE DEVEQIKEAA KNSLLHVKAE VHKSLDSYAA
SLAKAIEAEA KINLFGEEAL PGVLFTARTV PGAGFGGRRG SRTLVNQRLQ LQSIKEGNVL
AAEQR
