Hmdb loader
Identification
HMDB Protein ID HMDBP10759
Secondary Accession Numbers
  • 17026
Name Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas
Synonyms
  1. Adenylate cyclase-stimulating G alpha protein
  2. Extra large alphas protein
  3. XLalphas
Gene Name GNAS
Protein Type Unknown
Biological Properties
General Function Involved in signal transducer activity
Specific 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
Pathways
  • Lysophosphatidic Acid LPA3 Signalling
  • Lysophosphatidic Acid LPA4 Signalling
  • Lysophosphatidic Acid LPA5 Signalling
  • Lysophosphatidic Acid LPA6 Signalling
Reactions Not Available
GO Classification
Function
purine nucleotide binding
binding
nucleotide binding
guanyl nucleotide binding
guanyl ribonucleotide binding
gtp binding
molecular transducer activity
signal transducer activity
Process
biological regulation
regulation of biological process
regulation of cellular process
signal transduction
signaling
signaling pathway
cell surface receptor linked signaling pathway
g-protein coupled receptor protein signaling pathway
Cellular Location
  1. Cell membrane
  2. Peripheral membrane protein
Gene Properties
Chromosome Location Chromosome:2
Locus 20q13.3
SNPs GNAS
Gene Sequence
>3114 bp
ATGGGCGTGCGCAACTGCCTCTACGGCAATAATATGTCAGGACAACGCGATATCCCCCCT
GAAATCGGGGAACAGCCCGAGCAACCACCTTTGGAGGCCCCAGGGGCAGCTGCCCCCGGT
GCTGGGCCTAGCCCAGCCGAAGAGATGGAGACCGAACCGCCTCACAACGAGCCCATCCCC
GTCGAGAATGATGGCGAGGCCTGTGGACCCCCAGAGGTCTCCAGACCCAACTTTCAGGTC
CTCAACCCGGCATTCAGGGAAGCTGGAGCCCATGGAAGCTACAGCCCACCTCCTGAGGAA
GCAATGCCCTTCGAGGCTGAACAGCCCAGCTTGGGAGGCTTCTGGCCTACACTGGAGCAG
CCTGGATTCCCCAGTGGGGTCCATGCAGGCCTTGAGGCCTTCGGCCCAGCACTCATGGAG
CCCGGAGCCTTCAGTGGTGCCAGACCAGGCCTGGGAGGATACAGCCCTCCACCAGAAGAA
GCTATGCCCTTTGAGTTTGACCAGCCTGCCCAGAGAGGCTGCAGTCAACTTCTCTTACAG
GTCCCAGACCTTGCTCCAGGAGGCCCAGGTGCTGCAGGGGTCCCCGGAGCTCCTCCCGAG
GAGCCCCAAGCCCTCAGGCCTGCAAAGGCTGGCTCCAGAGGAGGCTACAGCCCTCCCCCT
GAGGAGACTATGCCATTTGAGCTTGATGGAGAAGGATTTGGGGACGACAGCCCACCCCCG
GGGCTTTCCCGAGTTATCGCACAAGTCGACGGCAGCAGCCAGTTCGCGGCAGTCGCGGCC
TCGAGTGCGGTCCGCCTCACTCCCGCCGCGAACGCGCCTCCCCTCTGGGTCCCAGGCGCC
ATCGGCAGCCCATCCCAAGAGGCTGTCAGACCTCCTTCTAACTTCACGGGCAGCAGCCCC
TGGATGGAGATCTCCGGACCCCCGTTCGAGATTGGCAGCGCCCCCGCTGGGGTCGACGAC
ACTCCCGTCAACATGGACAGCCCCCCAATCGCGCTTGACGGCCCGCCCATCAAGGTCTCC
GGAGCCCCAGATAAGAGAGAGCGAGCAGAGAGACCCCCAGTTGAGGAGGAAGCAGCAGAG
ATGGAAGGAGCCGCTGATGCCGCGGAGGGAGGAAAAGTACCCTCTCCGGGGTACGGATCC
CCTGCCGCCGGGGCAGCCTCAGCGGATACCGCTGCCAGGGCAGCCCCTGCAGCCCCAGCC
GATCCTGACTCCGGGGCAACCCCAGAAGATCCCGACTCCGGGACAGCACCAGCCGATCCT
GACTCCGGGGCATTCGCAGCCGATCCCGACTCCGGGGCAGCCCCTGCCGCCCCAGCCGAT
CCCGACTCCGGGGCGGCCCCTGACGCCCCAGCCGATCCCGACTCCGGGGCGGCCCCTGAC
GCCCCAGCCGATCCAGATGCCGGGGCGGCCCCTGAGGCTCCCGCCGCCCCTGCGGCTGCT
GAGACCCGGGCAGCCCATGTCGCCCCAGCTGCGCCAGACGCAGGGGCTCCCACTGCCCCA
GCCGCTTCTGCCACCCGGGCAGCCCAAGTCCGCCGGGCGGCCTCTGCAGCCCCTGCCTCC
GGGGCCAGACGCAAGATCCATCTCAGACCCCCCAGCCCCGAGATCCAGGCTGCCGATCCG
CCTACTCCGCGGCCTACTCGCGCGTCTGCCTGGCGGGGCAAGTCCGAGAGCAGCCGCGGC
CGCCGCGTGTACTACGATGAAGGGGTGGCCAGCAGCGACGATGACTCCAGCGGAGACGAG
TCCGACGATGGGACCTCCGGATGCCTCCGCTGGTTTCAGCATCGGCGAAATCGCCGCCGC
CGAAAGCCCCAGCGCAACTTACTCCGCAACTTTCTCGTGCAAGCCTTCGGGGGCTGCTTC
GGTCGATCTGAGAGTCCCCAGCCCAAAGCCTCGCGCTCTCTCAAGGTCAAGAAGGTACCC
CTGGCGGAGAAGCGCAGACAGATGCGCAAAGAAGCCCTGGAGAAGCGGGCCCAGAAGCGC
GCAGAGAAGAAACGCAGTAAGCTCATCGACAAACAACTCCAGGACGAAAAGATGGGCTAC
ATGTGTACGCACCGCCTGCTGCTTCTAGGTGCTGGAGAATCTGGTAAAAGCACCATTGTG
AAGCAGATGAGGATCCTGCATGTTAATGGGTTTAATGGAGAGGGCGGCGAAGAGGACCCG
CAGGCTGCAAGGAGCAACAGCGATGGTGAGAAGGCAACCAAAGTGCAGGACATCAAAAAC
AACCTGAAAGAGGCGATTGAAACCATTGTGGCCGCCATGAGCAACCTGGTGCCCCCCGTG
GAGCTGGCCAACCCCGAGAACCAGTTCAGAGTGGACTACATCCTGAGTGTGATGAACGTG
CCTGACTTTGACTTCCCTCCCGAATTCTATGAGCATGCCAAGGCTCTGTGGGAGGATGAA
GGAGTGCGTGCCTGCTACGAACGCTCCAACGAGTACCAGCTGATTGACTGTGCCCAGTAC
TTCCTGGACAAGATCGACGTGATCAAGCAGGCTGACTATGTGCCGAGCGATCAGGACCTG
CTTCGCTGCCGTGTCCTGACTTCTGGAATCTTTGAGACCAAGTTCCAGGTGGACAAAGTC
AACTTCCACATGTTTGACGTGGGTGGCCAGCGCGATGAACGCCGCAAGTGGATCCAGTGC
TTCAACGATGTGACTGCCATCATCTTCGTGGTGGCCAGCAGCAGCTACAACATGGTCATC
CGGGAGGACAACCAGACCAACCGCCTGCAGGAGGCTCTGAACCTCTTCAAGAGCATCTGG
AACAACAGATGGCTGCGCACCATCTCTGTGATCCTGTTCCTCAACAAGCAAGATCTGCTC
GCTGAGAAAGTCCTTGCTGGGAAATCGAAGATTGAGGACTACTTTCCAGAATTTGCTCGC
TACACTACTCCTGAGGATGCTACTCCCGAGCCCGGAGAGGACCCACGCGTGACCCGGGCC
AAGTACTTCATTCGAGATGAGTTTCTGAGGATCAGCACTGCCAGTGGAGATGGGCGTCAC
TACTGCTACCCTCATTTCACCTGCGCTGTGGACACTGAGAACATCCGCCGTGTGTTCAAC
GACTGCCGTGACATCATTCAGCGCATGCACCTTCGTCAGTACGAGCTGCTCTAA
Protein Properties
Number of Residues 1037
Molecular Weight 111023.3
Theoretical pI 4.65
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas
MGVRNCLYGNNMSGQRDIPPEIGEQPEQPPLEAPGAAAPGAGPSPAEEMETEPPHNEPIP
VENDGEACGPPEVSRPNFQVLNPAFREAGAHGSYSPPPEEAMPFEAEQPSLGGFWPTLEQ
PGFPSGVHAGLEAFGPALMEPGAFSGARPGLGGYSPPPEEAMPFEFDQPAQRGCSQLLLQ
VPDLAPGGPGAAGVPGAPPEEPQALRPAKAGSRGGYSPPPEETMPFELDGEGFGDDSPPP
GLSRVIAQVDGSSQFAAVAASSAVRLTPAANAPPLWVPGAIGSPSQEAVRPPSNFTGSSP
WMEISGPPFEIGSAPAGVDDTPVNMDSPPIALDGPPIKVSGAPDKRERAERPPVEEEAAE
MEGAADAAEGGKVPSPGYGSPAAGAASADTAARAAPAAPADPDSGATPEDPDSGTAPADP
DSGAFAADPDSGAAPAAPADPDSGAAPDAPADPDSGAAPDAPADPDAGAAPEAPAAPAAA
ETRAAHVAPAAPDAGAPTAPAASATRAAQVRRAASAAPASGARRKIHLRPPSPEIQAADP
PTPRPTRASAWRGKSESSRGRRVYYDEGVASSDDDSSGDESDDGTSGCLRWFQHRRNRRR
RKPQRNLLRNFLVQAFGGCFGRSESPQPKASRSLKVKKVPLAEKRRQMRKEALEKRAQKR
AEKKRSKLIDKQLQDEKMGYMCTHRLLLLGAGESGKSTIVKQMRILHVNGFNGEGGEEDP
QAARSNSDGEKATKVQDIKNNLKEAIETIVAAMSNLVPPVELANPENQFRVDYILSVMNV
PDFDFPPEFYEHAKALWEDEGVRACYERSNEYQLIDCAQYFLDKIDVIKQADYVPSDQDL
LRCRVLTSGIFETKFQVDKVNFHMFDVGGQRDERRKWIQCFNDVTAIIFVVASSSYNMVI
REDNQTNRLQEALNLFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFAR
YTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCYPHFTCAVDTENIRRVFN
DCRDIIQRMHLRQYELL
GenBank ID Protein 117938759
UniProtKB/Swiss-Prot ID Q5JWF2
UniProtKB/Swiss-Prot Entry Name GNAS1_HUMAN
PDB IDs
GenBank Gene ID NM_080425.2
GeneCard ID GNAS
GenAtlas ID GNAS
HGNC ID HGNC:4392
References
General References
  1. Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. [PubMed:11780052 ]
  2. Liu J, Litman D, Rosenberg MJ, Yu S, Biesecker LG, Weinstein LS: A GNAS1 imprinting defect in pseudohypoparathyroidism type IB. J Clin Invest. 2000 Nov;106(9):1167-74. [PubMed:11067869 ]
  3. Bastepe M, Lane AH, Juppner H: Paternal uniparental isodisomy of chromosome 20q--and the resulting changes in GNAS1 methylation--as a plausible cause of pseudohypoparathyroidism. Am J Hum Genet. 2001 May;68(5):1283-9. Epub 2001 Apr 9. [PubMed:11294659 ]
  4. Wu WI, Schwindinger WF, Aparicio LF, Levine MA: 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. J Biol Chem. 2001 Jan 5;276(1):165-71. [PubMed:11029463 ]
  5. Jan de Beur S, Ding C, Germain-Lee E, Cho J, Maret A, Levine MA: Discordance between genetic and epigenetic defects in pseudohypoparathyroidism type 1b revealed by inconsistent loss of maternal imprinting at GNAS1. Am J Hum Genet. 2003 Aug;73(2):314-22. Epub 2003 Jul 11. [PubMed:12858292 ]
  6. Fragoso MC, Domenice S, Latronico AC, Martin RM, Pereira MA, Zerbini MC, Lucon AM, Mendonca BB: Cushing's syndrome secondary to adrenocorticotropin-independent macronodular adrenocortical hyperplasia due to activating mutations of GNAS1 gene. J Clin Endocrinol Metab. 2003 May;88(5):2147-51. [PubMed:12727968 ]
  7. Bastepe M, Frohlich LF, Hendy GN, Indridason OS, Josse RG, Koshiyama H, Korkko J, Nakamoto JM, Rosenbloom AL, Slyper AH, Sugimoto T, Tsatsoulis A, Crawford JD, Juppner H: Autosomal dominant pseudohypoparathyroidism type Ib is associated with a heterozygous microdeletion that likely disrupts a putative imprinting control element of GNAS. J Clin Invest. 2003 Oct;112(8):1255-63. [PubMed:14561710 ]
  8. Linglart A, Gensure RC, Olney RC, Juppner H, Bastepe M: A novel STX16 deletion in autosomal dominant pseudohypoparathyroidism type Ib redefines the boundaries of a cis-acting imprinting control element of GNAS. Am J Hum Genet. 2005 May;76(5):804-14. Epub 2005 Mar 30. [PubMed:15800843 ]
  9. Bastepe M, Frohlich LF, Linglart A, Abu-Zahra HS, Tojo K, Ward LM, Juppner H: Deletion of the NESP55 differentially methylated region causes loss of maternal GNAS imprints and pseudohypoparathyroidism type Ib. Nat Genet. 2005 Jan;37(1):25-7. Epub 2004 Dec 12. [PubMed:15592469 ]
  10. Freson K, Jaeken J, Van Helvoirt M, de Zegher F, Wittevrongel C, Thys C, Hoylaerts MF, Vermylen J, Van Geet C: Functional polymorphisms in the paternally expressed XLalphas and its cofactor ALEX decrease their mutual interaction and enhance receptor-mediated cAMP formation. Hum Mol Genet. 2003 May 15;12(10):1121-30. [PubMed:12719376 ]
  11. Abramowitz J, Grenet D, Birnbaumer M, Torres HN, Birnbaumer L: XLalphas, the extra-long form of the alpha-subunit of the Gs G protein, is significantly longer than suspected, and so is its companion Alex. Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8366-71. Epub 2004 May 17. [PubMed:15148396 ]
  12. Hayward BE, Bonthron DT: An imprinted antisense transcript at the human GNAS1 locus. Hum Mol Genet. 2000 Mar 22;9(5):835-41. [PubMed:10749992 ]
  13. Hayward BE, Kamiya M, Strain L, Moran V, Campbell R, Hayashizaki Y, Bonthron DT: The human GNAS1 gene is imprinted and encodes distinct paternally and biallelically expressed G proteins. Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):10038-43. [PubMed:9707596 ]
  14. Nekrutenko A, Wadhawan S, Goetting-Minesky P, Makova KD: Oscillating evolution of a mammalian locus with overlapping reading frames: an XLalphas/ALEX relay. PLoS Genet. 2005 Aug;1(2):e18. Epub 2005 Aug 12. [PubMed:16110341 ]
  15. Freson K, Hoylaerts MF, Jaeken J, Eyssen M, Arnout J, Vermylen J, Van Geet C: Genetic variation of the extra-large stimulatory G protein alpha-subunit leads to Gs hyperfunction in platelets and is a risk factor for bleeding. Thromb Haemost. 2001 Sep;86(3):733-8. [PubMed:11583302 ]