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Protein

G-protein coupled receptor 161

Gene

Gpr161

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionDevelopmental 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:2685054 Gpr161

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 46ExtracellularSequence analysisAdd BLAST46
Transmembranei47 – 67Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini68 – 80CytoplasmicSequence analysisAdd BLAST13
Transmembranei81 – 101Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini102 – 117ExtracellularSequence analysisAdd BLAST16
Transmembranei118 – 139Helical; Name=3Sequence analysisAdd BLAST22
Topological domaini140 – 159CytoplasmicSequence analysisAdd BLAST20
Transmembranei160 – 180Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini181 – 205ExtracellularSequence analysisAdd BLAST25
Transmembranei206 – 226Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini227 – 285CytoplasmicSequence analysisAdd BLAST59
Transmembranei286 – 306Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini307 – 322ExtracellularSequence analysisAdd BLAST16
Transmembranei323 – 343Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini344 – 545CytoplasmicSequence analysisAdd BLAST202

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).2 Publications

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)DescriptionActionsGraphical viewLength
Mutagenesisi145V → E: Inactive mutant unable to increase cAMP upon induction. 1 Publication1
Mutagenesisi233 – 237VKARK → AAAAA in mut1; abolishes localization to primary cilia. 1 Publication5
Mutagenesisi238 – 241VHCG → AAAA in mut2; weakly affects localization to primary cilia. 1 Publication4
Mutagenesisi243 – 244VV → AA in mut3; does not affect localization to primary cilia; when associated with A-251. 1 Publication2
Mutagenesisi251Q → A in mut3; does not affect localization to primary cilia; when associated with 243-A-A-244. 1 Publication1
Mutagenesisi254 – 257GRKN → AAAA in mut4; does not affect localization to primary cilia. 1 Publication4
Mutagenesisi258 – 262SSTST → ASAAA in mut5; does not affect localization to primary cilia. 1 Publication5

Keywords - Diseasei

Cataract

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003790731 – 545G-protein coupled receptor 161Add BLAST545

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi21N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi32N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi116 ↔ 194PROSITE-ProRule annotation
Glycosylationi117N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiB2RPY5
PRIDEiB2RPY5

PTM databases

iPTMnetiB2RPY5
PhosphoSitePlusiB2RPY5
SwissPalmiB2RPY5

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

BgeeiENSMUSG00000040836
ExpressionAtlasiB2RPY5 baseline and differential
GenevisibleiB2RPY5 MM

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000136621

Structurei

3D structure databases

ProteinModelPortaliB2RPY5
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
GeneTreeiENSGT00900000140954
HOGENOMiHOG000112777
InParanoidiB2RPY5
KOiK08439
OMAiIWCALLP
OrthoDBiEOG091G0G56
PhylomeDBiB2RPY5
TreeFamiTF331895

Family and domain databases

InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00237 GPCRRHODOPSN
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

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)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0463001 – 3MDF → MDSHHTTHTLLAVFPV in isoform 3. Curated3
Alternative sequenceiVSP_0376351M → MDFVQHALLTASRGALT in isoform 2. 1 Publication1

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
CCDSiCCDS83621.1 [B2RPY5-1]
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_006496850.3
XP_006496914.1, XM_006496851.3
XP_006496915.1, XM_006496852.3
XP_011237123.1, XM_011238821.2
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

Similar proteinsi

Entry informationi

Entry nameiGP161_MOUSE
AccessioniPrimary (citable) accession number: B2RPY5
Secondary accession number(s): B0L0L8, J3QN69, Q80T48
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 7, 2009
Last sequence update: July 1, 2008
Last modified: May 23, 2018
This is version 74 of the entry and version 1 of the sequence. See 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

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