Q5JWF2 (GNAS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas

Alternative name(s):
Adenylate cyclase-stimulating G alpha protein
Extra large alphas protein
Short name=XLalphas

Gene names

Name:	GNAS
Synonyms:	GNAS1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1037 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(s) protein is involved in hormonal regulation of adenylate cyclase: it activates the cyclase in response to beta-adrenergic stimuli. XLas isoforms interact with the same set of receptors as Gnas isoforms By similarity. UniProtKB Q63803 UniProtKB Q6R0H7
Subunit structure	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. UniProtKB Q63803 UniProtKB Q6R0H7
Subcellular location	Cell membrane; Peripheral membrane protein By similarity UniProtKB Q63803.
Involvement in 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13 Ref.15 ACTH-independent macronodular adrenal hyperplasia (AIMAH) [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 trunkal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.16 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. Note: The disease is caused by mutations 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. Ref.8 Ref.9 Ref.10 Ref.14 Ref.17 Ref.18 Ref.19 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6
Miscellaneous	This protein is produced by a bicistronic gene which also produces the ALEX protein from an overlapping reading frame By similarity. UniProtKB Q63803 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.
Sequence similarities	Belongs to the G-alpha family. G(s) subfamily.
Sequence caution	The sequence CAB83215.1 differs from that shown. Reason: Frameshift at position 40. The sequence CAM28315.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Cushing syndrome Disease mutation
Domain	Coiled coil
Ligand	GTP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Transducer
PTM	ADP-ribosylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA methylation Inferred from electronic annotation. Source: Compara adenylate cyclase-activating dopamine receptor signaling pathway Inferred from Biological aspect of Ancestor. Source: RefGenome behavior Inferred from electronic annotation. Source: Compara cartilage development Inferred from electronic annotation. Source: Compara embryonic cranial skeleton morphogenesis Inferred from electronic annotation. Source: Compara embryonic hindlimb morphogenesis Inferred from electronic annotation. Source: Compara endochondral ossification Inferred from electronic annotation. Source: Compara energy reserve metabolic process Inferred from electronic annotation. Source: Compara genetic imprinting Inferred from electronic annotation. Source: Compara multicellular organism growth Inferred from electronic annotation. Source: Compara positive regulation of osteoblast differentiation Inferred from electronic annotation. Source: Compara positive regulation of osteoclast differentiation Inferred from electronic annotation. Source: Compara post-embryonic body morphogenesis Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara sensory perception of chemical stimulus Inferred from Biological aspect of Ancestor. Source: RefGenome skin development Inferred from electronic annotation. Source: Compara tissue homeostasis Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from sequence or structural similarity. Source: BHF-UCL dendrite Inferred from electronic annotation. Source: Compara heterotrimeric G-protein complex Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	G-protein beta/gamma-subunit complex binding Inferred from Biological aspect of Ancestor. Source: RefGenome GTP binding Inferred from electronic annotation. Source: UniProtKB-KW GTPase activity Inferred from Biological aspect of Ancestor. Source: RefGenome ionotropic glutamate receptor binding Inferred from Biological aspect of Ancestor. Source: RefGenome metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW mu-type opioid receptor binding Inferred from Biological aspect of Ancestor. Source: RefGenome signal transducer activity Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Alternative products

This entry describes 7 isoforms produced by alternative splicing. [Align] [Select]

Isoform XLas-1 Ref.1 (identifier: Q5JWF2-1)

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.

Note: Gene prediction confirmed by EST data.

Isoform XLas-2 Ref.1 (identifier: Q5JWF2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     714-729: EGGEEDPQAARSNSDG → DS

Note: Gene prediction confirmed by EST data.

Isoform XLas-3 Ref.4 (identifier: Q5JWF2-3)

The sequence of this isoform differs from the canonical sequence as follows:
     691-752: AGESGKSTIV...KEAIETIVAA → RKVVPSDTEG...VLENLVKAPL
     753-1037: Missing.

Isoform Gnas-1 (identifier: P63092-1)

Also known as: Alpha-S2; GNASl; Alpha-S-long;

The sequence of this isoform can be found in the external entry P63092.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Isoform 3 (identifier: P63092-3)

The sequence of this isoform can be found in the external entry P63092.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Note: No experimental confirmation available.

Isoform Gnas-2 (identifier: P63092-2)

Also known as: Alpha-S1; GNASs; Alpha-S-short;

The sequence of this isoform can be found in the external entry P63092.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Isoform Nesp55 (identifier: O95467-1)

The sequence of this isoform can be found in the external entry O95467.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Note: Shares no sequence similarity with other isoforms due to a novel first exon containing the entire reading frame spliced to shared exon 2 so that exons 2-13 make up the 3'-UTR.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1037	1037	Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas		PRO_0000253984
Regions
	Nucleotide binding	690 – 697	8	GTP By similarity UniProtKB P63096
	Nucleotide binding	841 – 847	7	GTP By similarity
	Nucleotide binding	866 – 870	5	GTP By similarity UniProtKB P63096
	Nucleotide binding	935 – 938	4	GTP By similarity UniProtKB P63096
	Coiled coil	641 – 667	27	Potential
	Coiled coil	730 – 756	27	Potential
	Compositional bias	358 – 522	165	Ala-rich
Sites
	Metal binding	697	1	Magnesium By similarity
	Metal binding	847	1	Magnesium By similarity
	Binding site	1009	1	GTP; via amide nitrogen By similarity
Amino acid modifications
	Modified residue	844	1	ADP-ribosylarginine; by cholera toxin By similarity UniProtKB P63094
	Modified residue	995	1	Phosphoserine Ref.11
Natural variations
	Alternative sequence	691 – 752	62	AGESG…TIVAA → RKVVPSDTEGRFRLDRPAPA TVSWTGRGFSVSSLLIRSPN PPAFTVEKPDTQVLENLVKA PL in isoform XLas-3. Ref.4		VSP_052173
	Alternative sequence	714 – 729	16	EGGEE…SNSDG → DS in isoform XLas-2. Ref.1		VSP_052174
	Alternative sequence	753 – 1037	285	Missing in isoform XLas-3. Ref.4		VSP_052175
	Natural variant	436	1	A → D in GNASHYP. Ref.13 Ref.15		VAR_028777
	Natural variant	437	1	A → APADPDSGAAPDA in GNAS hyperfunction. Ref.13 Ref.15		VAR_028778
	Natural variant	459	1	P → R in GNASHYP. Ref.13 Ref.15		VAR_028779
	Natural variant	1023	1	R → L. Corresponds to variant rs8986 [ dbSNP | Ensembl ].		VAR_059656
Experimental info
	Sequence conflict	15	1	Q → E in CAB83215. Ref.3
	Sequence conflict	46	1	A → S in CAB83215. Ref.3
	Sequence conflict	132	1	E → A in CAB83215. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform XLas-1 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: 02CB52383015E75D	FASTA	1,037	111,025
	10 20 30 40 50 60 MGVRNCLYGN NMSGQRDIPP EIGEQPEQPP LEAPGAAAPG AGPSPAEEME TEPPHNEPIP 70 80 90 100 110 120 VENDGEACGP PEVSRPNFQV LNPAFREAGA HGSYSPPPEE AMPFEAEQPS LGGFWPTLEQ 130 140 150 160 170 180 PGFPSGVHAG LEAFGPALME PGAFSGARPG LGGYSPPPEE AMPFEFDQPA QRGCSQLLLQ 190 200 210 220 230 240 VPDLAPGGPG AAGVPGAPPE EPQALRPAKA GSRGGYSPPP EETMPFELDG EGFGDDSPPP 250 260 270 280 290 300 GLSRVIAQVD GSSQFAAVAA SSAVRLTPAA NAPPLWVPGA IGSPSQEAVR PPSNFTGSSP 310 320 330 340 350 360 WMEISGPPFE IGSAPAGVDD TPVNMDSPPI ALDGPPIKVS GAPDKRERAE RPPVEEEAAE 370 380 390 400 410 420 MEGAADAAEG GKVPSPGYGS PAAGAASADT AARAAPAAPA DPDSGATPED PDSGTAPADP 430 440 450 460 470 480 DSGAFAADPD SGAAPAAPAD PDSGAAPDAP ADPDSGAAPD APADPDAGAA PEAPAAPAAA 490 500 510 520 530 540 ETRAAHVAPA APDAGAPTAP AASATRAAQV RRAASAAPAS GARRKIHLRP PSPEIQAADP 550 560 570 580 590 600 PTPRPTRASA WRGKSESSRG RRVYYDEGVA SSDDDSSGDE SDDGTSGCLR WFQHRRNRRR 610 620 630 640 650 660 RKPQRNLLRN FLVQAFGGCF GRSESPQPKA SRSLKVKKVP LAEKRRQMRK EALEKRAQKR 670 680 690 700 710 720 AEKKRSKLID KQLQDEKMGY MCTHRLLLLG AGESGKSTIV KQMRILHVNG FNGEGGEEDP 730 740 750 760 770 780 QAARSNSDGE KATKVQDIKN NLKEAIETIV AAMSNLVPPV ELANPENQFR VDYILSVMNV 790 800 810 820 830 840 PDFDFPPEFY EHAKALWEDE GVRACYERSN EYQLIDCAQY FLDKIDVIKQ ADYVPSDQDL 850 860 870 880 890 900 LRCRVLTSGI FETKFQVDKV NFHMFDVGGQ RDERRKWIQC FNDVTAIIFV VASSSYNMVI 910 920 930 940 950 960 REDNQTNRLQ EALNLFKSIW NNRWLRTISV ILFLNKQDLL AEKVLAGKSK IEDYFPEFAR 970 980 990 1000 1010 1020 YTTPEDATPE PGEDPRVTRA KYFIRDEFLR ISTASGDGRH YCYPHFTCAV DTENIRRVFN 1030 DCRDIIQRMH LRQYELL
	Isoform XLas-2 [UniParc]. Checksum: 22DBCF510AEF25D6	FASTA	1,023	109,626
	10 20 30 40 50 60 MGVRNCLYGN NMSGQRDIPP EIGEQPEQPP LEAPGAAAPG AGPSPAEEME TEPPHNEPIP 70 80 90 100 110 120 VENDGEACGP PEVSRPNFQV LNPAFREAGA HGSYSPPPEE AMPFEAEQPS LGGFWPTLEQ 130 140 150 160 170 180 PGFPSGVHAG LEAFGPALME PGAFSGARPG LGGYSPPPEE AMPFEFDQPA QRGCSQLLLQ 190 200 210 220 230 240 VPDLAPGGPG AAGVPGAPPE EPQALRPAKA GSRGGYSPPP EETMPFELDG EGFGDDSPPP 250 260 270 280 290 300 GLSRVIAQVD GSSQFAAVAA SSAVRLTPAA NAPPLWVPGA IGSPSQEAVR PPSNFTGSSP 310 320 330 340 350 360 WMEISGPPFE IGSAPAGVDD TPVNMDSPPI ALDGPPIKVS GAPDKRERAE RPPVEEEAAE 370 380 390 400 410 420 MEGAADAAEG GKVPSPGYGS PAAGAASADT AARAAPAAPA DPDSGATPED PDSGTAPADP 430 440 450 460 470 480 DSGAFAADPD SGAAPAAPAD PDSGAAPDAP ADPDSGAAPD APADPDAGAA PEAPAAPAAA 490 500 510 520 530 540 ETRAAHVAPA APDAGAPTAP AASATRAAQV RRAASAAPAS GARRKIHLRP PSPEIQAADP 550 560 570 580 590 600 PTPRPTRASA WRGKSESSRG RRVYYDEGVA SSDDDSSGDE SDDGTSGCLR WFQHRRNRRR 610 620 630 640 650 660 RKPQRNLLRN FLVQAFGGCF GRSESPQPKA SRSLKVKKVP LAEKRRQMRK EALEKRAQKR 670 680 690 700 710 720 AEKKRSKLID KQLQDEKMGY MCTHRLLLLG AGESGKSTIV KQMRILHVNG FNGDSEKATK 730 740 750 760 770 780 VQDIKNNLKE AIETIVAAMS NLVPPVELAN PENQFRVDYI LSVMNVPDFD FPPEFYEHAK 790 800 810 820 830 840 ALWEDEGVRA CYERSNEYQL IDCAQYFLDK IDVIKQADYV PSDQDLLRCR VLTSGIFETK 850 860 870 880 890 900 FQVDKVNFHM FDVGGQRDER RKWIQCFNDV TAIIFVVASS SYNMVIREDN QTNRLQEALN 910 920 930 940 950 960 LFKSIWNNRW LRTISVILFL NKQDLLAEKV LAGKSKIEDY FPEFARYTTP EDATPEPGED 970 980 990 1000 1010 1020 PRVTRAKYFI RDEFLRISTA SGDGRHYCYP HFTCAVDTEN IRRVFNDCRD IIQRMHLRQY ELL
	Isoform XLas-3 [UniParc]. Checksum: 65A9202D681E861F	FASTA	752	77,643
	10 20 30 40 50 60 MGVRNCLYGN NMSGQRDIPP EIGEQPEQPP LEAPGAAAPG AGPSPAEEME TEPPHNEPIP 70 80 90 100 110 120 VENDGEACGP PEVSRPNFQV LNPAFREAGA HGSYSPPPEE AMPFEAEQPS LGGFWPTLEQ 130 140 150 160 170 180 PGFPSGVHAG LEAFGPALME PGAFSGARPG LGGYSPPPEE AMPFEFDQPA QRGCSQLLLQ 190 200 210 220 230 240 VPDLAPGGPG AAGVPGAPPE EPQALRPAKA GSRGGYSPPP EETMPFELDG EGFGDDSPPP 250 260 270 280 290 300 GLSRVIAQVD GSSQFAAVAA SSAVRLTPAA NAPPLWVPGA IGSPSQEAVR PPSNFTGSSP 310 320 330 340 350 360 WMEISGPPFE IGSAPAGVDD TPVNMDSPPI ALDGPPIKVS GAPDKRERAE RPPVEEEAAE 370 380 390 400 410 420 MEGAADAAEG GKVPSPGYGS PAAGAASADT AARAAPAAPA DPDSGATPED PDSGTAPADP 430 440 450 460 470 480 DSGAFAADPD SGAAPAAPAD PDSGAAPDAP ADPDSGAAPD APADPDAGAA PEAPAAPAAA 490 500 510 520 530 540 ETRAAHVAPA APDAGAPTAP AASATRAAQV RRAASAAPAS GARRKIHLRP PSPEIQAADP 550 560 570 580 590 600 PTPRPTRASA WRGKSESSRG RRVYYDEGVA SSDDDSSGDE SDDGTSGCLR WFQHRRNRRR 610 620 630 640 650 660 RKPQRNLLRN FLVQAFGGCF GRSESPQPKA SRSLKVKKVP LAEKRRQMRK EALEKRAQKR 670 680 690 700 710 720 AEKKRSKLID KQLQDEKMGY MCTHRLLLLG RKVVPSDTEG RFRLDRPAPA TVSWTGRGFS 730 740 750 VSSLLIRSPN PPAFTVEKPD TQVLENLVKA PL
	Isoform Gnas-1 (Alpha-S2) (GNASl) (Alpha-S-long) [UniParc] [UniParc]. See P63092.		–	–
	Isoform 3 [UniParc]. See P63092.		–	–
	Isoform Gnas-2 (Alpha-S1) (GNASs) (Alpha-S-short) [UniParc] [UniParc]. See P63092.		–	–
	Isoform Nesp55 [UniParc]. See O95467.		–	–

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"An imprinted antisense transcript at the human GNAS1 locus." Hayward B.E., Bonthron D.T. Hum. Mol. Genet. 9:835-841(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-689.
[4]	"The human GNAS1 gene is imprinted and encodes distinct paternally and biallelically expressed G proteins." Hayward B.E., Kamiya M., Strain L., Moran V., Campbell R., Hayashizaki Y., Bonthron D.T. Proc. Natl. Acad. Sci. U.S.A. 95:10038-10043(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 197-1037 (ISOFORM XLAS-3).
[5]	"Oscillating evolution of a mammalian locus with overlapping reading frames: an XLalphas/ALEX relay." Nekrutenko A., Wadhawan S., Goetting-Minesky P., Makova K.D. PLoS Genet. 1:197-204(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 302-689.
[6]	"GNAS1 lesions in pseudohypoparathyroidism Ia and Ic: genotype phenotype relationship and evidence of the maternal transmission of the hormonal resistance." Linglart A., Carel J.-C., Garabedian M., Le T., Mallet E., Kottler M.-L. J. Clin. Endocrinol. Metab. 87:189-197(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN PHP1C.
[7]	"XL alpha-s, the extra-long form of the alpha subunit of the Gs G protein, is significantly longer than suspected, and so is its companion Alex." Abramowitz J., Grenet D., Birnbaumer M., Torres H.N., Birnbaumer L. Proc. Natl. Acad. Sci. U.S.A. 101:8366-8371(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION.
[8]	"A GNAS1 imprinting defect in pseudohypoparathyroidism type IB." Liu J., Litman D., Rosenberg M.J., Yu S., Biesecker L.G., Weinstein L.S. J. Clin. Invest. 106:1167-1174(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN PHP1B.
[9]	"Paternal uniparental isodisomy of chromosome 20q -- and the resulting changes in GNAS1 methylation -- as a plausible cause of pseudohypoparathyroidism." Bastepe M., Lane A.H., Jueppner H. Am. J. Hum. Genet. 68:1283-1289(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN PHP1B.
[10]	"Selective resistance to parathyroid hormone caused by a novel uncoupling mutation in the carboxyl terminus of G alpha(s). A cause of pseudohypoparathyroidism type Ib." Wu W.-I., Schwindinger W.F., Aparicio L.F., Levine M.A. J. Biol. Chem. 276:165-171(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN PHP1B.
[11]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-995, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"Genetic variation of the extra-large stimulatory G protein alpha-subunit leads to Gs hyperfunction in platelets and is a risk factor for bleeding." Freson K., Hoylaerts M.F., Jaeken J., Eyssen M., Arnout J., Vermylen J., Van Geet C. Thromb. Haemost. 86:733-738(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GNASHYP ASP-436; PRO-ALA-ASP-PRO-ASP-SER-GLY-ALA-ALA-PRO-ASP-ALA-437 INS AND ARG-459.
[14]	"Discordance between genetic and epigenetic defects in pseudohypoparathyroidism type 1b revealed by inconsistent loss of maternal imprinting at GNAS1." Jan de Beur S., Ding C., Germain-Lee E., Cho J., Maret A., Levine M.A. Am. J. Hum. Genet. 73:314-322(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN PHP1B.
[15]	"Functional polymorphisms in the paternally expressed XLalphas and its cofactor ALEX decrease their mutual interaction and enhance receptor-mediated cAMP formation." Freson K., Jaeken J., Van Helvoirt M., de Zegher F., Wittevrongel C., Thys C., Hoylaerts M.F., Vermylen J., Van Geet C. Hum. Mol. Genet. 12:1121-1130(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GNASHYP ASP-436; PRO-ALA-ASP-PRO-ASP-SER-GLY-ALA-ALA-PRO-ASP-ALA-437 INS AND ARG-459.
[16]	"Cushing's syndrome secondary to adrenocorticotropin-independent macronodular adrenocortical hyperplasia due to activating mutations of GNAS1 gene." Fragoso M.C.B.V., Domenice S., Latronico A.C., Martin R.M., Pereira M.A.A., Zerbini M.C.N., Lucon A.M., Mendonca B.B. J. Clin. Endocrinol. Metab. 88:2147-2151(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN AIMAH.
[17]	"Autosomal dominant pseudohypoparathyroidism type Ib is associated with a heterozygous microdeletion that likely disrupts a putative imprinting control element of GNAS." Bastepe M., Froehlich L.F., Hendy G.N., Indridason O.S., Josse R.G., Koshiyama H., Koerkkoe J., Nakamoto J.M., Rosenbloom A.L., Slyper A.H., Sugimoto T., Tsatsoulis A., Crawford J.D., Jueppner H. J. Clin. Invest. 112:1255-1263(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN PHP1B.
[18]	"A novel STX16 deletion in autosomal dominant pseudohypoparathyroidism type Ib redefines the boundaries of a cis-acting imprinting control element of GNAS." Linglart A., Gensure R.C., Olney R.C., Jueppner H., Bastepe M. Am. J. Hum. Genet. 76:804-814(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN PHP1B.
[19]	"Deletion of the NESP55 differentially methylated region causes loss of maternal GNAS imprints and pseudohypoparathyroidism type Ib." Bastepe M., Froehlich L.F., Linglart A., Abu-Zahra H.S., Tojo K., Ward L.M., Jueppner H. Nat. Genet. 37:25-27(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN PHP1B.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AL109840, AL121917, AL132655 Genomic DNA. Translation: CAI42932.2. AL109840, AL121917, AL132655 Genomic DNA. Translation: CAI42933.2. AL121917, AL109840, AL132655 Genomic DNA. Translation: CAI42566.2. AL121917, AL109840, AL132655 Genomic DNA. Translation: CAI42567.2. AL132655, AL109840, AL121917 Genomic DNA. Translation: CAI43073.2. AL132655, AL109840, AL121917 Genomic DNA. Translation: CAI43074.2. AL132655 Genomic DNA. Translation: CAM28315.1. Sequence problems. CH471077 Genomic DNA. Translation: EAW75462.1. CH471077 Genomic DNA. Translation: EAW75469.1. AJ251760 Genomic DNA. Translation: CAB83215.1. Frameshift. AJ224867 mRNA. Translation: CAA12164.1. AJ224868 Genomic DNA. Translation: CAA12165.1. AY898804 Genomic DNA. Translation: AAX51890.1.
IPI	IPI00095891. IPI00154366. IPI00646491.
RefSeq	NP_536350.2. NM_080425.2.
UniGene	Hs.125898.
3D structure databases
HSSP	HSSP built from PDB template 1AZS based on UniProtKB P04896.
ProteinModelPortal	Q5JWF2.
ModBase	Search...
Polymorphism databases
DMDM	116248089.
Proteomic databases
PRIDE	Q5JWF2.
Protocols and materials databases
DNASU	2778.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000371099; ENSP00000360140; ENSG00000087460. ENST00000371100; ENSP00000360141; ENSG00000087460. ENST00000371102; ENSP00000360143; ENSG00000087460.
GeneID	2778.
KEGG	hsa:2778.
UCSC	uc002xzw.3. human.
Organism-specific databases
CTD	2778.
GeneCards	GC20P057414.
HGNC	HGNC:4392. GNAS.
HPA	CAB010337. HPA027478. HPA028386.
MIM	139320. gene+phenotype. 219080. phenotype. 603233. phenotype. 612462. phenotype.
neXtProt	NX_Q5JWF2.
Orphanet	249. Fibrous dysplasia of bone. 57782. Mazabraud syndrome. 562. McCune-Albright syndrome. 2762. Progressive osseous heteroplasia. 79443. Pseudohypoparathyroidism type 1A. 94089. Pseudohypoparathyroidism type 1B. 79444. Pseudohypoparathyroidism type 1C. 79445. Pseudopseudohypoparathyroidism.
PharmGKB	PA175.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	HBG079975.
InParanoid	Q5JWF2.
KO	K04632.
OrthoDB	EOG490792.
Gene expression databases
ArrayExpress	Q5JWF2.
Bgee	Q5JWF2.
CleanEx	HS_GNAS.
Genevestigator	Q5JWF2.
GermOnline	ENSG00000087460. Homo sapiens.
Family and domain databases
Gene3D	1.10.400.10. 1 hit.
InterPro	IPR000367. Gprotein_alpha_S. IPR001019. Gprotein_alpha_su. IPR011025. GproteinA_insert. [Graphical view]
PANTHER	PTHR10218. PTHR10218. 1 hit.
Pfam	PF00503. G-alpha. 1 hit. [Graphical view]
PRINTS	PR00318. GPROTEINA. PR00443. GPROTEINAS.
SMART	SM00275. G_alpha. 1 hit. [Graphical view]
SUPFAM	SSF47895. Transducn_insert. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	GNAS. human.
GenomeRNAi	2778.
NextBio	10928.
SOURCE	Search...

Entry information

Entry name

GNAS1_HUMAN

Accession

Primary (citable) accession number: Q5JWF2
Secondary accession number(s): A2A2S3 , E1P5G3, O75684, O75685, Q5JW67, Q5JWF1, Q9NY42

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 17, 2006
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 92 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.