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Protein

Neuroendocrine secretory protein 55

Gene

GNAS

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

Functioni

GO - Biological processi

  • female pregnancy Source: UniProtKB
  • negative regulation of multicellular organism growth Source: UniProtKB
  • protein secretion Source: UniProtKB
  • response to parathyroid hormone Source: UniProtKB
Complete GO annotation...

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

HGNCiHGNC:4392. GNAS.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • extracellular region Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • transport vesicle Source: UniProtKB-SubCell
Complete GO annotation...

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

MalaCardsiGNAS.
MIMi139320. gene+phenotype.
219080. phenotype.
603233. phenotype.
PharmGKBiPA175.

Polymorphism and mutation databases

BioMutaiNPEPL1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 4646By similarityAdd
BLAST
Chaini47 – 245199Neuroendocrine secretory protein 55PRO_0000253967Add
BLAST
Peptidei163 – 1664LHAL tetrapeptide1 PublicationSequence analysisPRO_0000253968
Peptidei238 – 2458GPIPIRRH peptide1 PublicationSequence analysisPRO_0000253969

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

PeptideAtlasiO95467.
PRIDEiO95467.

PTM databases

iPTMnetiO95467.

Expressioni

Gene expression databases

BgeeiENSG00000087460.
CleanExiHS_GNAS.
ExpressionAtlasiO95467. baseline and differential.
GenevisibleiO95467. HS.

Organism-specific databases

HPAiCAB010337.
HPA018122.

Interactioni

Protein-protein interaction databases

BioGridi109040. 82 interactions.

Structurei

3D structure databases

ProteinModelPortaliO95467.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi78 – 14265Glu-richSequence analysisAdd
BLAST

Sequence similaritiesi

Belongs to the NESP55 family.Sequence analysis

Keywords - Domaini

Signal

Phylogenomic databases

GeneTreeiENSGT00770000120503.
HOGENOMiHOG000276539.
HOVERGENiHBG081561.
KOiK04632.

Family and domain databases

InterProiIPR009434. NESP55.
[Graphical view]
PfamiPF06390. NESP55. 1 hit.
[Graphical view]

Sequences (7)i

Sequence statusi: Complete.

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

This entry describes 7 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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti26 – 261R → C in AAD11804 (Ref. 4) Curated
Sequence conflicti41 – 411L → D in AAD11804 (Ref. 4) Curated
Sequence conflicti72 – 721G → GR in AAD11804 (Ref. 4) Curated
Sequence conflicti133 – 1331P → PETAP (Ref. 4) Curated
Sequence conflicti171 – 1711P → A in AAD11804 (Ref. 4) Curated
Sequence conflicti211 – 2199KEEKQRRRC → REENSSDSS in AAD11804 (Ref. 4) Curated
Sequence conflicti230 – 2301S → F in AAD11804 (Ref. 4) Curated

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.
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

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.
UniGeneiHs.125898.

3D structure databases

ProteinModelPortaliO95467.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109040. 82 interactions.

PTM databases

iPTMnetiO95467.

Polymorphism and mutation databases

BioMutaiNPEPL1.

Proteomic databases

PeptideAtlasiO95467.
PRIDEiO95467.

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.
GeneCardsiGNAS.
HGNCiHGNC:4392. GNAS.
HPAiCAB010337.
HPA018122.
MalaCardsiGNAS.
MIMi139320. gene+phenotype.
219080. phenotype.
603233. phenotype.
neXtProtiNX_O95467.
PharmGKBiPA175.
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00770000120503.
HOGENOMiHOG000276539.
HOVERGENiHBG081561.
KOiK04632.

Miscellaneous databases

ChiTaRSiGNAS. human.
GeneWikiiGNAS_complex_locus.
GenomeRNAii2778.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000087460.
CleanExiHS_GNAS.
ExpressionAtlasiO95467. baseline and differential.
GenevisibleiO95467. HS.

Family and domain databases

InterProiIPR009434. NESP55.
[Graphical view]
PfamiPF06390. NESP55. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGNAS3_HUMAN
AccessioniPrimary (citable) accession number: O95467
Secondary accession number(s): B2RB88, E1P5G2, O95417
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 17, 2006
Last sequence update: May 1, 1999
Last modified: September 7, 2016
This is version 109 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 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.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. 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.