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Protein

Neuroendocrine secretory protein 55

Gene

GNAS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

Miscellaneous

This protein is produced by a bicistronic gene which also produces the ALEX protein from an overlapping reading frame.Curated
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.

GO - Biological processi

  • female pregnancy Source: UniProtKB
  • negative regulation of multicellular organism growth Source: UniProtKB
  • positive regulation of cold-induced thermogenesis Source: YuBioLab
  • protein secretion Source: UniProtKB
  • response to parathyroid hormone Source: UniProtKB

Names & Taxonomyi

Protein namesi
Recommended name:
Neuroendocrine secretory protein 55
Short name:
NESP55
Cleaved into the following 2 chains:
Gene namesi
Name:GNASImported
Synonyms:GNAS1Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

EuPathDBiHostDB:ENSG00000087460.23
HGNCiHGNC:4392 GNAS
MIMi139320 gene+phenotype
neXtProtiNX_O95467

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasmic vesicle, Secreted

Pathology & Biotechi

Involvement in diseasei

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
GNAS hyperfunction (GNASHYP)
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

Keywords - Diseasei

Cushing syndrome

Organism-specific databases

DisGeNETi2778
MalaCardsiGNAS
MIMi139320 gene+phenotype
219080 phenotype
603233 phenotype
OpenTargetsiENSG00000087460
PharmGKBiPA175

Polymorphism and mutation databases

BioMutaiNPEPL1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 46By similarityAdd BLAST46
ChainiPRO_000025396747 – 245Neuroendocrine secretory protein 55Add BLAST199
PeptideiPRO_0000253968163 – 166LHAL tetrapeptide1 PublicationSequence analysis4
PeptideiPRO_0000253969238 – 245GPIPIRRH peptide1 PublicationSequence analysis8

Post-translational modificationi

Binds keratan sulfate chains.By similarity
May be proteolytically processed to give rise to a number of active peptides.1 Publication

Keywords - PTMi

Cleavage on pair of basic residues, Glycoprotein, Proteoglycan

Proteomic databases

EPDiO95467
PeptideAtlasiO95467
PRIDEiO95467
ProteomicsDBi50901

PTM databases

iPTMnetiO95467

Expressioni

Gene expression databases

BgeeiENSG00000087460 Expressed in 252 organ(s), highest expression level in telencephalon
CleanExiHS_GNAS
ExpressionAtlasiO95467 baseline and differential
GenevisibleiO95467 HS

Organism-specific databases

HPAiCAB010337
HPA018122

Interactioni

Protein-protein interaction databases

BioGridi109040, 95 interactors

Structurei

3D structure databases

ProteinModelPortaliO95467
SMRiO95467
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi78 – 142Glu-richSequence analysisAdd BLAST65

Sequence similaritiesi

Belongs to the NESP55 family.Sequence analysis

Keywords - Domaini

Signal

Phylogenomic databases

GeneTreeiENSGT00910000144108
HOGENOMiHOG000276539
HOVERGENiHBG081561
KOiK04632

Family and domain databases

InterProiView protein in InterPro
IPR009434 NESP55
PfamiView protein in Pfam
PF06390 NESP55, 1 hit

Sequences (8)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 8 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform Nesp554 Publications (identifier: O95467-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MDRRSRAQQW RRARHNYNDL CPPIGRRAAT ALLWLSCSIA LLRALATSNA
60 70 80 90 100
RAQQRAAAQQ RRSFLNAHHR SGAQVFPESP ESESDHEHEE ADLELSLPEC
110 120 130 140 150
LEYEEEFDYE TESETESEIE SETDFETEPE TAPTTEPETE PEDDRGPVVP
160 170 180 190 200
KHSTFGQSLT QRLHALKLRS PDASPSRAPP STQEPQSPRE GEELKPEDKD
210 220 230 240
PRDPEESKEP KEEKQRRRCK PKKPTRRDAS PESPSKKGPI PIRRH
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.
Length:245
Mass (Da):28,029
Last modified:May 1, 1999 - v1
Checksum:i4F02B8B1115089E2
GO
Isoform XLas-1 (identifier: Q5JWF2-1) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry Q5JWF2.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Gene prediction confirmed by EST data.
Length:1,037
Mass (Da):111,025
GO
Isoform XLas-2 (identifier: Q5JWF2-2) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry Q5JWF2.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Gene prediction confirmed by EST data.
Length:1,023
Mass (Da):109,626
GO
Isoform XLas-3 (identifier: Q5JWF2-3) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry Q5JWF2.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:752
Mass (Da):77,643
GO
Isoform Gnas-1Curated (identifier: P63092-1) [UniParc] [UniParc]FASTAAdd to basket
Also known as: Alpha-S2Curated, GNASlCurated, Alpha-S-longCurated
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.
Length:394
Mass (Da):45,665
GO
Isoform Gnas-2Curated (identifier: P63092-2) [UniParc] [UniParc]FASTAAdd to basket
Also known as: Alpha-S1Curated, GNASsCurated, Alpha-S-shortCurated
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.
Length:380
Mass (Da):44,266
GO
Isoform 3 (identifier: P63092-3) [UniParc]FASTAAdd to basket
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.
Length:379
Mass (Da):44,179
GO
Isoform 4 (identifier: P63092-4) [UniParc]FASTAAdd to basket
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: Gene prediction based on EST data.
Length:395
Mass (Da):45,752
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti26R → C in AAD11804 (Ref. 4) Curated1
Sequence conflicti41L → D in AAD11804 (Ref. 4) Curated1
Sequence conflicti72G → GR in AAD11804 (Ref. 4) Curated1
Sequence conflicti133P → PETAP (Ref. 4) Curated1
Sequence conflicti171P → A in AAD11804 (Ref. 4) Curated1
Sequence conflicti211 – 219KEEKQRRRC → REENSSDSS in AAD11804 (Ref. 4) Curated9
Sequence conflicti230S → F in AAD11804 (Ref. 4) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ009849 Genomic DNA Translation: CAA08889.1
AJ251760 Genomic DNA Translation: CAB83214.1
AF105253 mRNA Translation: AAF63226.1
AF107846 Genomic DNA Translation: AAD11804.1
AK314549 mRNA Translation: BAG37135.1
CH471077 Genomic DNA Translation: EAW75466.1
CH471077 Genomic DNA Translation: EAW75457.1
CCDSiCCDS13471.1 [O95467-1]
RefSeqiNP_000507.1, NM_000516.5
NP_001070956.1, NM_001077488.3
NP_001070957.1, NM_001077489.3
NP_001296790.1, NM_001309861.1
NP_057676.1, NM_016592.3 [O95467-1]
NP_536351.1, NM_080426.3
XP_016883310.1, XM_017027821.1 [O95467-1]
XP_016883311.1, XM_017027822.1 [O95467-1]
UniGeneiHs.125898

Genome annotation databases

EnsembliENST00000313949; ENSP00000323571; ENSG00000087460 [O95467-1]
ENST00000371075; ENSP00000360115; ENSG00000087460 [O95467-1]
ENST00000371098; ENSP00000360139; ENSG00000087460 [O95467-1]
GeneIDi2778
KEGGihsa:2778
UCSCiuc002xzt.5 human [O95467-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ009849 Genomic DNA Translation: CAA08889.1
AJ251760 Genomic DNA Translation: CAB83214.1
AF105253 mRNA Translation: AAF63226.1
AF107846 Genomic DNA Translation: AAD11804.1
AK314549 mRNA Translation: BAG37135.1
CH471077 Genomic DNA Translation: EAW75466.1
CH471077 Genomic DNA Translation: EAW75457.1
CCDSiCCDS13471.1 [O95467-1]
RefSeqiNP_000507.1, NM_000516.5
NP_001070956.1, NM_001077488.3
NP_001070957.1, NM_001077489.3
NP_001296790.1, NM_001309861.1
NP_057676.1, NM_016592.3 [O95467-1]
NP_536351.1, NM_080426.3
XP_016883310.1, XM_017027821.1 [O95467-1]
XP_016883311.1, XM_017027822.1 [O95467-1]
UniGeneiHs.125898

3D structure databases

ProteinModelPortaliO95467
SMRiO95467
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109040, 95 interactors

PTM databases

iPTMnetiO95467

Polymorphism and mutation databases

BioMutaiNPEPL1

Proteomic databases

EPDiO95467
PeptideAtlasiO95467
PRIDEiO95467
ProteomicsDBi50901

Protocols and materials databases

DNASUi2778
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000313949; ENSP00000323571; ENSG00000087460 [O95467-1]
ENST00000371075; ENSP00000360115; ENSG00000087460 [O95467-1]
ENST00000371098; ENSP00000360139; ENSG00000087460 [O95467-1]
GeneIDi2778
KEGGihsa:2778
UCSCiuc002xzt.5 human [O95467-1]

Organism-specific databases

CTDi2778
DisGeNETi2778
EuPathDBiHostDB:ENSG00000087460.23
GeneCardsiGNAS
HGNCiHGNC:4392 GNAS
HPAiCAB010337
HPA018122
MalaCardsiGNAS
MIMi139320 gene+phenotype
219080 phenotype
603233 phenotype
neXtProtiNX_O95467
OpenTargetsiENSG00000087460
PharmGKBiPA175
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00910000144108
HOGENOMiHOG000276539
HOVERGENiHBG081561
KOiK04632

Miscellaneous databases

ChiTaRSiGNAS human
GeneWikiiGNAS_complex_locus
GenomeRNAii2778
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000087460 Expressed in 252 organ(s), highest expression level in telencephalon
CleanExiHS_GNAS
ExpressionAtlasiO95467 baseline and differential
GenevisibleiO95467 HS

Family and domain databases

InterProiView protein in InterPro
IPR009434 NESP55
PfamiView protein in Pfam
PF06390 NESP55, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiGNAS3_HUMAN
AccessioniPrimary (citable) accession number: O95467
Secondary accession number(s): B2RB88, E1P5G2, O95417
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 17, 2006
Last sequence update: May 1, 1999
Last modified: September 12, 2018
This is version 121 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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