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Protein

Protein ALEX

Gene

GNAS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May inhibit the adenylyl cyclase-stimulating activity of guanine nucleotide-binding protein G(s) subunit alpha which is produced from the same locus in a different open reading frame.1 Publication

GO - Biological processi

  • adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: UniProtKB
  • bone development Source: UniProtKB
  • cognition Source: UniProtKB
  • developmental growth Source: UniProtKB
  • hair follicle placode formation Source: UniProtKB
  • platelet aggregation Source: UniProtKB
  • regulation of signal transduction Source: CACAO
Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
Protein ALEX
Alternative name(s):
Alternative gene product encoded by XL-exon
Gene namesi
Name:GNASImported
Synonyms:GNAS1Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:4392. GNAS.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • membrane Source: UniProtKB
  • plasma membrane Source: UniProtKB-SubCell
  • ruffle Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Involvement in diseasei

GNAS hyperfunction (GNASHYP)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionThis 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.
See also OMIM:139320
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti374 – 3741P → T in GNASHYP. 1 Publication
VAR_028774
Natural varianti375 – 3751P → PQPIPTPGRPLTP in GNASHYP.
VAR_028775
Natural varianti397 – 3971L → V in GNASHYP. 1 Publication
VAR_028776
ACTH-independent macronodular adrenal hyperplasia 1 (AIMAH1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:219080
Pseudohypoparathyroidism 1B (PHP1B)7 Publications
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.
Disease descriptionA 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.
See also OMIM:603233
Colorectal cancer (CRC)
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionA complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
See also OMIM:114500

Keywords - Diseasei

Cushing syndrome, Disease mutation

Organism-specific databases

MalaCardsiGNAS.
MIMi114500. phenotype.
139320. gene+phenotype.
219080. phenotype.
603233. phenotype.
PharmGKBiPA175.

Polymorphism and mutation databases

DMDMi116242967.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 626626Protein ALEXPRO_0000253964Add
BLAST

Proteomic databases

PRIDEiP84996.

PTM databases

SwissPalmiP84996.

Expressioni

Gene expression databases

BgeeiP84996.
CleanExiHS_GNAS.
ExpressionAtlasiP84996. baseline and differential.

Organism-specific databases

HPAiCAB010337.

Interactioni

Subunit structurei

Interacts with the N-terminal region of the XLas isoforms of guanine nucleotide-binding protein G(s) subunit alpha.By similarity

Protein-protein interaction databases

BioGridi109040. 81 interactions.
IntActiP84996. 5 interactions.

Structurei

3D structure databases

ProteinModelPortaliP84996.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi238 – 476239Pro-richSequence analysisAdd
BLAST

Sequence similaritiesi

Belongs to the ALEX family.Curated

Phylogenomic databases

HOGENOMiHOG000293422.
OrthoDBiEOG7M3J09.

Sequencei

Sequence statusi: Complete.

P84996-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MMARPVDPQR SPDPTFRSST RHSGKLEPME ATAHLLRKQC PSRLNSPAWE
60 70 80 90 100
ASGLHWSSLD SPVGSMQALR PSAQHSWSPE PSVVPDQAWE DTALHQKKLC
110 120 130 140 150
PLSLTSLPRE AAVNFSYRSQ TLLQEAQVLQ GSPELLPRSP KPSGLQRLAP
160 170 180 190 200
EEATALPLRR LCHLSLMEKD LGTTAHPRGF PELSHKSTAA ASSRQSRPRV
210 220 230 240 250
RSASLPPRTR LPSGSQAPSA AHPKRLSDLL LTSRAAAPGW RSPDPRSRLA
260 270 280 290 300
APPLGSTTLP STWTAPQSRL TARPSRSPEP QIRESEQRDP QLRRKQQRWK
310 320 330 340 350
EPLMPRREEK YPLRGTDPLP PGQPQRIPLP GQPLQPQPIL TPGQPQKIPT
360 370 380 390 400
PGQHQPILTP GHSQPIPTPG QPLPPQPIPT PGRPLTPQPI PTPGRPLTPQ
410 420 430 440 450
PIQMPGRPLR LPPPLRLLRP GQPMSPQLRQ TQGLPLPQPL LPPGQPKSAG
460 470 480 490 500
RPLQPLPPGP DARSISDPPA PRSRLPIRLL RGLLARLPGG ASPRAAAAAA
510 520 530 540 550
CTTMKGWPAA TMTPAETSPT MGPPDASAGF SIGEIAAAES PSATYSATFS
560 570 580 590 600
CKPSGAASVD LRVPSPKPRA LSRSRRYPWR RSADRCAKKP WRSGPRSAQR
610 620
RNAVSSSTNN SRTKRWATCV RTACCF
Length:626
Mass (Da):67,948
Last modified:October 17, 2006 - v1
Checksum:iF4CEFA7FA5917EEC
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti201 – 2011R → C in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_035788
Natural varianti201 – 2011R → H in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_035789
Natural varianti374 – 3741P → T in GNASHYP. 1 Publication
VAR_028774
Natural varianti375 – 3751P → PQPIPTPGRPLTP in GNASHYP.
VAR_028775
Natural varianti397 – 3971L → V in GNASHYP. 1 Publication
VAR_028776

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL132655 Genomic DNA. No translation available.
RefSeqiNP_001070958.1. NM_001077490.2.
NP_001296812.1. NM_001309883.1.
UniGeneiHs.125898.

Genome annotation databases

EnsembliENST00000306120; ENSP00000302237; ENSG00000087460.
GeneIDi2778.
UCSCiuc061ybz.1. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL132655 Genomic DNA. No translation available.
RefSeqiNP_001070958.1. NM_001077490.2.
NP_001296812.1. NM_001309883.1.
UniGeneiHs.125898.

3D structure databases

ProteinModelPortaliP84996.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109040. 81 interactions.
IntActiP84996. 5 interactions.

PTM databases

SwissPalmiP84996.

Polymorphism and mutation databases

DMDMi116242967.

Proteomic databases

PRIDEiP84996.

Protocols and materials databases

DNASUi2778.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000306120; ENSP00000302237; ENSG00000087460.
GeneIDi2778.
UCSCiuc061ybz.1. human.

Organism-specific databases

CTDi2778.
GeneCardsiGNAS.
HGNCiHGNC:4392. GNAS.
HPAiCAB010337.
MalaCardsiGNAS.
MIMi114500. phenotype.
139320. gene+phenotype.
219080. phenotype.
603233. phenotype.
neXtProtiNX_P84996.
PharmGKBiPA175.
GenAtlasiSearch...

Phylogenomic databases

HOGENOMiHOG000293422.
OrthoDBiEOG7M3J09.

Miscellaneous databases

ChiTaRSiGNAS. human.
GenomeRNAii2778.
NextBioi10928.
SOURCEiSearch...

Gene expression databases

BgeeiP84996.
CleanExiHS_GNAS.
ExpressionAtlasiP84996. baseline and differential.

Family and domain databases

ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. "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: PUTATIVE FUNCTION, VARIANTS GNASHYP THR-374; GLN-PRO-ILE-PRO-THR-PRO-GLY-ARG-PRO-LEU-THR-PRO-375 INS AND VAL-397.
  3. "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.
  4. "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.
  5. "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.
  6. "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.
  7. "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.
  8. "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 AIMAH1.
  9. "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.
  10. "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.
  11. "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.
  12. Cited for: VARIANTS [LARGE SCALE ANALYSIS] CYS-201 AND HIS-201.

Entry informationi

Entry nameiALEX_HUMAN
AccessioniPrimary (citable) accession number: P84996
Secondary accession number(s): A2A2S4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 17, 2006
Last sequence update: October 17, 2006
Last modified: May 11, 2016
This is version 78 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Miscellaneous

This protein is produced by a bicistronic gene which also produces guanine nucleotide-binding protein G(s) subunit alpha from an overlapping reading frame.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.