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Protein

G-protein coupled receptor 161

Gene

Gpr161

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Key negative regulator of Shh signaling, which promotes the processing of GLI3 into GLI3R during neural tube development. Recruited by TULP3 and the IFT-A complex to primary cilia and acts as a regulator of the PKA-dependent basal repression machinery in Shh signaling by increasing cAMP levels, leading to promote the PKA-dependent processing of GLI3 into GLI3R and repress the Shh signaling. In presence of SHH, it is removed from primary cilia and is internalized into recycling endosomes, preventing its activity and allowing activation of the Shh signaling. Its ligand is unknown.2 Publications

GO - Molecular functioni

  • G-protein coupled receptor activity Source: UniProtKB

GO - Biological processi

  • G-protein coupled receptor signaling pathway Source: UniProtKB
  • multicellular organism development Source: UniProtKB-KW
  • negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning Source: UniProtKB
  • positive regulation of cAMP biosynthetic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-MMU-5610787. Hedgehog 'off' state.
R-MMU-5632684. Hedgehog 'on' state.

Names & Taxonomyi

Protein namesi
Recommended name:
G-protein coupled receptor 161
Gene namesi
Name:Gpr161
Synonyms:Gm208
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:2685054. Gpr161.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 4646ExtracellularSequence analysisAdd
BLAST
Transmembranei47 – 6721Helical; Name=1Sequence analysisAdd
BLAST
Topological domaini68 – 8013CytoplasmicSequence analysisAdd
BLAST
Transmembranei81 – 10121Helical; Name=2Sequence analysisAdd
BLAST
Topological domaini102 – 11716ExtracellularSequence analysisAdd
BLAST
Transmembranei118 – 13922Helical; Name=3Sequence analysisAdd
BLAST
Topological domaini140 – 15920CytoplasmicSequence analysisAdd
BLAST
Transmembranei160 – 18021Helical; Name=4Sequence analysisAdd
BLAST
Topological domaini181 – 20525ExtracellularSequence analysisAdd
BLAST
Transmembranei206 – 22621Helical; Name=5Sequence analysisAdd
BLAST
Topological domaini227 – 28559CytoplasmicSequence analysisAdd
BLAST
Transmembranei286 – 30621Helical; Name=6Sequence analysisAdd
BLAST
Topological domaini307 – 32216ExtracellularSequence analysisAdd
BLAST
Transmembranei323 – 34321Helical; Name=7Sequence analysisAdd
BLAST
Topological domaini344 – 545202CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • ciliary membrane Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB-KW
  • primary cilium Source: UniProtKB
  • recycling endosome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cilium, Membrane

Pathology & Biotechi

Involvement in diseasei

An intragenic deletion in Gpr161 is responsible for the vacuolated lens (vl) phenotype that is characterized by neural tube defects and congenital cataracts. The vl mutation aroses spontaneously. About half of vl/vl embryos display lumbar-sacral spina bifida and die before birth, and the other half have closed neural tubes but show thinning of the midline neuroepithelium and epidermis, dilation of the dorsal ventricle, and presence of ectopic neuroepithelial cells in the ventricle. All surviving adults display congenital cataracts (PubMed:18250320). It is not a null mutant allele (PubMed:23332756).

Disruption phenotypei

Embryonic lethality by E10.5 caused by increased Shh signaling and ventralization throughout the developing neural tube. Defects in Gli3 processing.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi145 – 1451V → E: Inactive mutant unable to increase cAMP upon induction. 1 Publication
Mutagenesisi233 – 2375VKARK → AAAAA in mut1; abolishes localization to primary cilia. 1 Publication
Mutagenesisi238 – 2414VHCG → AAAA in mut2; weakly affects localization to primary cilia. 1 Publication
Mutagenesisi243 – 2442VV → AA in mut3; does not affect localization to primary cilia; when associated with A-251. 1 Publication
Mutagenesisi251 – 2511Q → A in mut3; does not affect localization to primary cilia; when associated with 243-A-A-244. 1 Publication
Mutagenesisi254 – 2574GRKN → AAAA in mut4; does not affect localization to primary cilia. 1 Publication
Mutagenesisi258 – 2625SSTST → ASAAA in mut5; does not affect localization to primary cilia. 1 Publication

Keywords - Diseasei

Cataract

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 545545G-protein coupled receptor 161PRO_0000379073Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi21 – 211N-linked (GlcNAc...)Sequence analysis
Glycosylationi32 – 321N-linked (GlcNAc...)Sequence analysis
Disulfide bondi116 ↔ 194PROSITE-ProRule annotation
Glycosylationi117 – 1171N-linked (GlcNAc...)Sequence analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiB2RPY5.
PRIDEiB2RPY5.

PTM databases

PhosphoSiteiB2RPY5.

Expressioni

Developmental stagei

Expressed ubiquitously from embryonic days 8.5 (E8.5) and is mostly concentrated in the developing nervous system at later stages. By E10.5, it is mainly expressed in the neural tube. At later embryonic stages (E12.5 and E15.5), it is predominantly expressed in the brain, spinal cord, and dorsal ganglia and weakly expressed in the hindlimb. According to PubMed:18250320, expression is restricted to the lateral neural folds, while PubMed:23332756 detects expression throughout the neural tube. Also expressed at low levels in kidney stroma and retina at E15.5.1 Publication

Gene expression databases

BgeeiB2RPY5.
GenevisibleiB2RPY5. MM.

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000136621.

Structurei

3D structure databases

ProteinModelPortaliB2RPY5.
SMRiB2RPY5. Positions 51-349.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00790000123027.
HOGENOMiHOG000112777.
InParanoidiB2RPY5.
KOiK08439.
OMAiIWCALLP.
PhylomeDBiB2RPY5.
TreeFamiTF331895.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: B2RPY5-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDFVQHALLT ASRGALTMSL NSSLSYRKEL SNLTATEGGE GGAVSEFIAI
60 70 80 90 100
IIITVLVCLG NLVIVVTLYK KSYLLTLSNK FVFSLTLSNF LLSVLVLPFV
110 120 130 140 150
VTSSIRREWI FGVVWCNFSA LLYLLISSAS MLTLGVIAID RYYAVLYPMV
160 170 180 190 200
YPMKITGNRA VMALVYIWLH SLIGCLPPLF GWSSVEFDEF KWMCVAAWHQ
210 220 230 240 250
EPGYTIFWQI WCALFPFLIM LVCYGFIFRV ARVKARKVHC GTVVTVEEDS
260 270 280 290 300
QRSGRKNSST STSSSGSRRN ALQGVVYSAN QCKALITILV VIGAFMVTWG
310 320 330 340 350
PYMVVITSEA LWGKNCVSPT LETWATWLSF TSAICHPLIY GLWNKTVRKE
360 370 380 390 400
LLGMCFGDRY YRESFVQRQR TSRLFSISNR ITDLGLSPHL TALMAGGQSL
410 420 430 440 450
GHSSSTGDTG FSYSQDSGTD VMLLEDGTSE DNPPQHCTCP PKRRSSVTFE
460 470 480 490 500
DEVEQIKEAA KNSLLHVKAE VHKSLDSYAA SLAKAIEAEA KINLFGEEAL
510 520 530 540
PGVLFTARTV PGAGFGGRRG SRTLVNQRLQ LQSIKEGNVL AAEQR
Length:545
Mass (Da):60,303
Last modified:July 1, 2008 - v1
Checksum:iAF2C9F191D8211DA
GO
Isoform 2 (identifier: B2RPY5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MDFVQHALLTASRGALT

Show »
Length:561
Mass (Da):61,985
Checksum:i4B730D6192BC7E57
GO
Isoform 3 (identifier: B2RPY5-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-3: MDF → MDSHHTTHTLLAVFPV

Show »
Length:558
Mass (Da):61,698
Checksum:iD8830A61698321CB
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 33MDF → MDSHHTTHTLLAVFPV in isoform 3. CuratedVSP_046300
Alternative sequencei1 – 11M → MDFVQHALLTASRGALT in isoform 2. 1 PublicationVSP_037635

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EF197953 mRNA. Translation: ABO93465.1.
AC116374 Genomic DNA. No translation available.
BC137659 mRNA. Translation: AAI37660.1.
AY255596 mRNA. Translation: AAO85108.1.
RefSeqiNP_001074595.1. NM_001081126.2. [B2RPY5-3]
NP_001297358.1. NM_001310429.1. [B2RPY5-1]
NP_001297359.1. NM_001310430.1.
XP_006496913.1. XM_006496850.2.
XP_006496914.1. XM_006496851.2.
XP_006496915.1. XM_006496852.2.
XP_011237123.1. XM_011238821.1.
UniGeneiMm.329929.
Mm.441364.

Genome annotation databases

EnsembliENSMUST00000178700; ENSMUSP00000136621; ENSMUSG00000040836. [B2RPY5-1]
GeneIDi240888.
KEGGimmu:240888.
UCSCiuc007dja.1. mouse. [B2RPY5-3]
uc011wux.1. mouse. [B2RPY5-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
EF197953 mRNA. Translation: ABO93465.1.
AC116374 Genomic DNA. No translation available.
BC137659 mRNA. Translation: AAI37660.1.
AY255596 mRNA. Translation: AAO85108.1.
RefSeqiNP_001074595.1. NM_001081126.2. [B2RPY5-3]
NP_001297358.1. NM_001310429.1. [B2RPY5-1]
NP_001297359.1. NM_001310430.1.
XP_006496913.1. XM_006496850.2.
XP_006496914.1. XM_006496851.2.
XP_006496915.1. XM_006496852.2.
XP_011237123.1. XM_011238821.1.
UniGeneiMm.329929.
Mm.441364.

3D structure databases

ProteinModelPortaliB2RPY5.
SMRiB2RPY5. Positions 51-349.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000136621.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiB2RPY5.

Proteomic databases

PaxDbiB2RPY5.
PRIDEiB2RPY5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000178700; ENSMUSP00000136621; ENSMUSG00000040836. [B2RPY5-1]
GeneIDi240888.
KEGGimmu:240888.
UCSCiuc007dja.1. mouse. [B2RPY5-3]
uc011wux.1. mouse. [B2RPY5-1]

Organism-specific databases

CTDi23432.
MGIiMGI:2685054. Gpr161.

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00790000123027.
HOGENOMiHOG000112777.
InParanoidiB2RPY5.
KOiK08439.
OMAiIWCALLP.
PhylomeDBiB2RPY5.
TreeFamiTF331895.

Enzyme and pathway databases

ReactomeiR-MMU-5610787. Hedgehog 'off' state.
R-MMU-5632684. Hedgehog 'on' state.

Miscellaneous databases

NextBioi35563022.
PROiB2RPY5.
SOURCEiSearch...

Gene expression databases

BgeeiB2RPY5.
GenevisibleiB2RPY5. MM.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The orphan G protein-coupled receptor, Gpr161, encodes the vacuolated lens locus and controls neurulation and lens development."
    Matteson P.G., Desai J., Korstanje R., Lazar G., Borsuk T.E., Rollins J., Kadambi S., Joseph J., Rahman T., Wink J., Benayed R., Paigen B., Millonig J.H.
    Proc. Natl. Acad. Sci. U.S.A. 105:2088-2093(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, INVOLVEMENT IN VL PHENOTYPE.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Brain.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 119-266.
  5. "The ciliary G-protein-coupled receptor Gpr161 negatively regulates the Sonic Hedgehog pathway via cAMP signaling."
    Mukhopadhyay S., Wen X., Ratti N., Loktev A., Rangell L., Scales S.J., Jackson P.K.
    Cell 152:210-223(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, MUTAGENESIS OF VAL-145; 233-VAL--LYS-237; 238-VAL--GLY-241; 243-VAL-VAL-244; GLN-251; 254-GLY--ASN-257 AND 258-SER--THR-262.

Entry informationi

Entry nameiGP161_MOUSE
AccessioniPrimary (citable) accession number: B2RPY5
Secondary accession number(s): B0L0L8, J3QN69, Q80T48
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 7, 2009
Last sequence update: July 1, 2008
Last modified: May 11, 2016
This is version 63 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.