UniProt functional annotation for Q99835



	UniProt functional annotation for Q99835

UniProt code: Q99835.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: G protein-coupled receptor that probably associates with the patched protein (PTCH) to transduce the hedgehog's proteins signal. Binding of sonic hedgehog (SHH) to its receptor patched is thought to prevent normal inhibition by patched of smoothened (SMO). Required for the accumulation of KIF7, GLI2 and GLI3 in the cilia (PubMed:19592253). Interacts with DLG5 at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation (By similarity). {ECO:0000250|UniProtKB:P56726, ECO:0000269|PubMed:19592253}.

Subunit: Homodimer (PubMed:23636324). Interacts with ARRB2 (By similarity). Interacts with KIF7 (PubMed:19592253). Interacts with BBS5 and BBS7; the interactions are indicative for the association of SMO with the BBsome complex to facilitate ciliary localization of SMO (PubMed:22072986). Interacts with DLG5 and SDCBP (By similarity). Interacts with GAS8/DRC4 (PubMed:21659505). {ECO:0000250|UniProtKB:P56726, ECO:0000269|PubMed:19592253, ECO:0000269|PubMed:21659505, ECO:0000269|PubMed:22072986, ECO:0000269|PubMed:23636324}.

Subcellular location: Membrane {ECO:0000269|PubMed:22072986}; Multi- pass membrane protein {ECO:0000269|PubMed:22072986}. Cell projection, cilium {ECO:0000269|PubMed:22072986}.

Disease: Curry-Jones syndrome (CRJS) [MIM:601707]: A multisystem disorder characterized by patchy skin lesions, polysyndactyly, diverse cerebral malformations, unicoronal craniosynostosis, iris colobomas, microphthalmia, and intestinal malrotation with myofibromas or hamartomas. {ECO:0000269|PubMed:24859340, ECO:0000269|PubMed:27236920}. Note=The disease is caused by variants affecting the gene represented in this entry. 8 individuals have been identified with the disease- causing mutation Phe-412 and all were mosaic. The mutation could not be reliably detected in blood, greatest success rates were obtained with affected tissues obtained by invasive procedures. It is thought that the mutation has arisen postzygotically early during embryonic development (PubMed:27236920). This mutation has also been identified in ameloblastoma, medulloblastoma, meningioma, and basal cell carcinoma, and has been reported as the oncogenic driver in some of these tumors (PubMed:24859340). {ECO:0000269|PubMed:24859340, ECO:0000269|PubMed:27236920}.

Similarity: Belongs to the G-protein coupled receptor Fz/Smo family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		G protein-coupled receptor that probably associates with the patched protein (PTCH) to transduce the hedgehog's proteins signal. Binding of sonic hedgehog (SHH) to its receptor patched is thought to prevent normal inhibition by patched of smoothened (SMO). Required for the accumulation of KIF7, GLI2 and GLI3 in the cilia (PubMed:19592253). Interacts with DLG5 at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation (By similarity). {ECO:0000250\|UniProtKB:P56726, ECO:0000269\|PubMed:19592253}.


Subunit:		Homodimer (PubMed:23636324). Interacts with ARRB2 (By similarity). Interacts with KIF7 (PubMed:19592253). Interacts with BBS5 and BBS7; the interactions are indicative for the association of SMO with the BBsome complex to facilitate ciliary localization of SMO (PubMed:22072986). Interacts with DLG5 and SDCBP (By similarity). Interacts with GAS8/DRC4 (PubMed:21659505). {ECO:0000250\|UniProtKB:P56726, ECO:0000269\|PubMed:19592253, ECO:0000269\|PubMed:21659505, ECO:0000269\|PubMed:22072986, ECO:0000269\|PubMed:23636324}.
Subcellular location:		Membrane {ECO:0000269\|PubMed:22072986}; Multi- pass membrane protein {ECO:0000269\|PubMed:22072986}. Cell projection, cilium {ECO:0000269\|PubMed:22072986}.
Disease:		Curry-Jones syndrome (CRJS) [MIM:601707]: A multisystem disorder characterized by patchy skin lesions, polysyndactyly, diverse cerebral malformations, unicoronal craniosynostosis, iris colobomas, microphthalmia, and intestinal malrotation with myofibromas or hamartomas. {ECO:0000269\|PubMed:24859340, ECO:0000269\|PubMed:27236920}. Note=The disease is caused by variants affecting the gene represented in this entry. 8 individuals have been identified with the disease- causing mutation Phe-412 and all were mosaic. The mutation could not be reliably detected in blood, greatest success rates were obtained with affected tissues obtained by invasive procedures. It is thought that the mutation has arisen postzygotically early during embryonic development (PubMed:27236920). This mutation has also been identified in ameloblastoma, medulloblastoma, meningioma, and basal cell carcinoma, and has been reported as the oncogenic driver in some of these tumors (PubMed:24859340). {ECO:0000269\|PubMed:24859340, ECO:0000269\|PubMed:27236920}.
Similarity:		Belongs to the G-protein coupled receptor Fz/Smo family. {ECO:0000305}.