UniProt functional annotation for Q5JWF2



	UniProt functional annotation for Q5JWF2

UniProt code: Q5JWF2.

Organism: Homo sapiens (Human).

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

Function: Guanine nucleotide-binding proteins (G proteins) function as transducers in numerous signaling pathways controlled by G protein- coupled receptors (GPCRs). Signaling involves the activation of adenylyl cyclases, resulting in increased levels of the signaling molecule cAMP. GNAS functions downstream of several GPCRs, including beta-adrenergic receptors. XLas isoforms interact with the same set of receptors as GNAS isoforms (By similarity). {ECO:0000250|UniProtKB:Q6R0H7}.

Subunit: G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site. Interacts through its N-terminal region with ALEX which is produced from the same locus in a different open reading frame. This interaction may inhibit its adenylyl cyclase-stimulating activity (By similarity). Interacts with MAGED2 (PubMed:27120771). {ECO:0000250|UniProtKB:Q63803, ECO:0000250|UniProtKB:Q6R0H7, ECO:0000269|PubMed:27120771}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:27120771}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q63803}. Apical cell membrane {ECO:0000269|PubMed:27120771}.

Disease: GNAS hyperfunction (GNASHYP) [MIM:139320]: This condition is characterized by increased trauma-related bleeding tendency, prolonged bleeding time, brachydactyly and mental retardation. Both the XLas isoforms and the ALEX protein are mutated which strongly reduces the interaction between them and this may allow unimpeded activation of the XLas isoforms. {ECO:0000269|PubMed:11583302, ECO:0000269|PubMed:12719376}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: ACTH-independent macronodular adrenal hyperplasia 1 (AIMAH1) [MIM:219080]: A rare adrenal defect characterized by multiple, bilateral, non-pigmented, benign, adrenocortical nodules. It results in excessive production of cortisol leading to ACTH-independent Cushing syndrome. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. {ECO:0000269|PubMed:12727968}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Pseudohypoparathyroidism 1B (PHP1B) [MIM:603233]: A disorder characterized by end-organ resistance to parathyroid hormone, hypocalcemia and hyperphosphatemia. Patients affected with PHP1B lack developmental defects characteristic of Albright hereditary osteodystrophy, and typically show no other endocrine abnormalities besides resistance to PTH. {ECO:0000269|PubMed:11029463, ECO:0000269|PubMed:11067869, ECO:0000269|PubMed:11294659, ECO:0000269|PubMed:12858292, ECO:0000269|PubMed:14561710, ECO:0000269|PubMed:15592469, ECO:0000269|PubMed:15800843}. Note=The disease is caused by variants affecting the gene represented in this entry. Most affected individuals have defects in methylation of the gene. In some cases microdeletions involving the STX16 appear to cause loss of methylation at exon A/B of GNAS, resulting in PHP1B. Paternal uniparental isodisomy have also been observed.

Disease: Pseudohypoparathyroidism 1C (PHP1C) [MIM:612462]: A disorder characterized by end-organ resistance to parathyroid hormone, hypocalcemia and hyperphosphatemia. It is commonly associated with Albright hereditary osteodystrophy whose features are short stature, obesity, round facies, short metacarpals and ectopic calcification. {ECO:0000269|PubMed:11788646}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: This protein is produced by a bicistronic gene which also produces the ALEX protein from an overlapping reading frame. {ECO:0000250|UniProtKB:Q63803}.

Miscellaneous: The GNAS locus is imprinted in a complex manner, giving rise to distinct paternally, maternally and biallelically expressed proteins. The XLas isoforms are paternally derived, the Gnas isoforms are biallelically derived and the Nesp55 isoforms are maternally derived.

Similarity: Belongs to the G-alpha family. G(s) subfamily. {ECO:0000255}.

Sequence caution: Sequence=CAB83215.1; Type=Frameshift; Evidence={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:		Guanine nucleotide-binding proteins (G proteins) function as transducers in numerous signaling pathways controlled by G protein- coupled receptors (GPCRs). Signaling involves the activation of adenylyl cyclases, resulting in increased levels of the signaling molecule cAMP. GNAS functions downstream of several GPCRs, including beta-adrenergic receptors. XLas isoforms interact with the same set of receptors as GNAS isoforms (By similarity). {ECO:0000250\|UniProtKB:Q6R0H7}.


Subunit:		G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site. Interacts through its N-terminal region with ALEX which is produced from the same locus in a different open reading frame. This interaction may inhibit its adenylyl cyclase-stimulating activity (By similarity). Interacts with MAGED2 (PubMed:27120771). {ECO:0000250\|UniProtKB:Q63803, ECO:0000250\|UniProtKB:Q6R0H7, ECO:0000269\|PubMed:27120771}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:27120771}; Peripheral membrane protein {ECO:0000250\|UniProtKB:Q63803}. Apical cell membrane {ECO:0000269\|PubMed:27120771}.
Disease:		GNAS hyperfunction (GNASHYP) [MIM:139320]: This condition is characterized by increased trauma-related bleeding tendency, prolonged bleeding time, brachydactyly and mental retardation. Both the XLas isoforms and the ALEX protein are mutated which strongly reduces the interaction between them and this may allow unimpeded activation of the XLas isoforms. {ECO:0000269\|PubMed:11583302, ECO:0000269\|PubMed:12719376}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		ACTH-independent macronodular adrenal hyperplasia 1 (AIMAH1) [MIM:219080]: A rare adrenal defect characterized by multiple, bilateral, non-pigmented, benign, adrenocortical nodules. It results in excessive production of cortisol leading to ACTH-independent Cushing syndrome. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. {ECO:0000269\|PubMed:12727968}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Pseudohypoparathyroidism 1B (PHP1B) [MIM:603233]: A disorder characterized by end-organ resistance to parathyroid hormone, hypocalcemia and hyperphosphatemia. Patients affected with PHP1B lack developmental defects characteristic of Albright hereditary osteodystrophy, and typically show no other endocrine abnormalities besides resistance to PTH. {ECO:0000269\|PubMed:11029463, ECO:0000269\|PubMed:11067869, ECO:0000269\|PubMed:11294659, ECO:0000269\|PubMed:12858292, ECO:0000269\|PubMed:14561710, ECO:0000269\|PubMed:15592469, ECO:0000269\|PubMed:15800843}. Note=The disease is caused by variants affecting the gene represented in this entry. Most affected individuals have defects in methylation of the gene. In some cases microdeletions involving the STX16 appear to cause loss of methylation at exon A/B of GNAS, resulting in PHP1B. Paternal uniparental isodisomy have also been observed.
Disease:		Pseudohypoparathyroidism 1C (PHP1C) [MIM:612462]: A disorder characterized by end-organ resistance to parathyroid hormone, hypocalcemia and hyperphosphatemia. It is commonly associated with Albright hereditary osteodystrophy whose features are short stature, obesity, round facies, short metacarpals and ectopic calcification. {ECO:0000269\|PubMed:11788646}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		This protein is produced by a bicistronic gene which also produces the ALEX protein from an overlapping reading frame. {ECO:0000250\|UniProtKB:Q63803}.
Miscellaneous:		The GNAS locus is imprinted in a complex manner, giving rise to distinct paternally, maternally and biallelically expressed proteins. The XLas isoforms are paternally derived, the Gnas isoforms are biallelically derived and the Nesp55 isoforms are maternally derived.
Similarity:		Belongs to the G-alpha family. G(s) subfamily. {ECO:0000255}.
Sequence caution:		Sequence=CAB83215.1; Type=Frameshift; Evidence={ECO:0000305};