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Protein

Gamma-secretase-activating protein

Gene

GSAP

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

Functioni

Regulator of gamma-secretase activity, which specifically activates the production of amyloid-beta protein (amyloid-beta protein 40 and amyloid-beta protein 42), without affecting the cleavage of other gamma-secretase targets such has Notch. The gamma-secretase complex is an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein). Specifically promotes the gamma-cleavage of APP CTF-alpha (also named APP-CTF) by the gamma-secretase complex to generate amyloid-beta, while it reduces the epsilon-cleavage of APP CTF-alpha, leading to a low production of AICD.1 Publication

Miscellaneous

The gamma-secretase regulator activity is specifically inhibited by imatinib (also known as STI571 or Gleevec), an anticancer drug that selectively decreases amyloid-beta protein production. Imatinib binds PION/GSAP and acts by preventing PION/GSAP interaction with the gamma-secretase substrate, CTF-alpha (PubMed:20811458).1 Publication
Its role as an activator of amyloid-beta protein production makes it a promising therapeutic target for the treatment of Alzheimer disease.1 Publication

GO - Molecular functioni

  • amyloid-beta binding Source: UniProtKB

GO - Biological processi

Names & Taxonomyi

Protein namesi
Recommended name:
Gamma-secretase-activating protein
Short name:
GSAP
Alternative name(s):
Protein pigeon homolog
Cleaved into the following chain:
Gene namesi
Name:GSAP
Synonyms:PION
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000186088.15
HGNCiHGNC:28042 GSAP
MIMi613552 gene
neXtProtiNX_A4D1B5

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

Golgi apparatus

Pathology & Biotechi

Organism-specific databases

DisGeNETi54103
OpenTargetsiENSG00000186088
PharmGKBiPA164724500

Chemistry databases

ChEMBLiCHEMBL3638343

Polymorphism and mutation databases

BioMutaiGSAP

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003358091 – 854Gamma-secretase-activating proteinAdd BLAST854
ChainiPRO_0000403728734 – 854Gamma-secretase-activating protein 16 kDa C-terminal formSequence analysisAdd BLAST121

Post-translational modificationi

The protein is first synthesized as a holoprotein form of 98 kDa and rapidly processed into the gamma-secretase-activating protein 16 kDa C-terminal form, which constitutes the predominant form.1 Publication

Proteomic databases

EPDiA4D1B5
MaxQBiA4D1B5
PaxDbiA4D1B5
PRIDEiA4D1B5
ProteomicsDBi609
610 [A4D1B5-2]
611 [A4D1B5-3]
612 [A4D1B5-4]
TopDownProteomicsiA4D1B5-1 [A4D1B5-1]

PTM databases

iPTMnetiA4D1B5
PhosphoSitePlusiA4D1B5

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSG00000186088 Expressed in 210 organ(s), highest expression level in small intestine Peyer's patch
CleanExiHS_PION
ExpressionAtlasiA4D1B5 baseline and differential
GenevisibleiA4D1B5 HS

Organism-specific databases

HPAiHPA023994

Interactioni

Subunit structurei

Interacts with APP; specifically interacts with the CTF-alpha product of APP. Interacts with the gamma-secretase complex.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
APPP050673EBI-15875313,EBI-77613

Protein-protein interaction databases

BioGridi119901, 4 interactors
DIPiDIP-59240N
IntActiA4D1B5, 1 interactor
STRINGi9606.ENSP00000257626

Chemistry databases

BindingDBiA4D1B5

Structurei

3D structure databases

ProteinModelPortaliA4D1B5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the GSAP family.Curated

Phylogenomic databases

eggNOGiENOG410IG5Q Eukaryota
ENOG41129DZ LUCA
GeneTreeiENSGT00390000012875
HOVERGENiHBG095500
InParanoidiA4D1B5
OMAiENISACH
OrthoDBiEOG091G0GEP
PhylomeDBiA4D1B5
TreeFamiTF323853

Family and domain databases

InterProiView protein in InterPro
IPR028010 GSAP_C_dom
IPR026172 GSAP_fam
PANTHERiPTHR13630 PTHR13630, 1 hit
PfamiView protein in Pfam
PF14959 GSAP-16, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: A4D1B5-1) [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
MALRLVADFD LGKDVLPWLR AQRAVSEASG AGSGGADVLE NDYESLHVLN
60 70 80 90 100
VERNGNIIYT YKDDKGNVVF GLYDCQTRQN ELLYTFEKDL QVFSCSVNSE
110 120 130 140 150
RTLLAASLVQ STKEGKRNEL QPGSKCLTLL VEIHPVNNVK VLKAVDSYIW
160 170 180 190 200
VQFLYPHIES HPLPENHLLL ISEEKYIEQF RIHVAQEDGN RVVIKNSGHL
210 220 230 240 250
PRDRIAEDFV WAQWDMSEQR LYYIDLKKSR SILKCIQFYA DESYNLMFEV
260 270 280 290 300
PLDISLSNSG FKLVNFGCDY HQYRDKFSKH LTLCVFTNHT GSLCVCYSPK
310 320 330 340 350
CASWGQITYS VFYIHKGHSK TFTTSLENVG SHMTKGITFL NLDYYVAVYL
360 370 380 390 400
PGHFFHLLNV QHPDLICHNL FLTGNNEMID MLPHCPLQSL SGSLVLDCCS
410 420 430 440 450
GKLYRALLSQ SSLLQLLQNT CLDCEKMAAL HCALYCGQGA QFLEAQIIQW
460 470 480 490 500
ISENVSACHS FDLIQEFIIA SSYWSVYSET SNMDKLLPHS SVLTWNTEIP
510 520 530 540 550
GITLVTEDIA LPLMKVLSFK GYWEKLNSNL EYVKYAKPHF HYNNSVVRRE
560 570 580 590 600
WHNLISEEKT GKRRSAAYVR NILDNAVKVI SNLEARNLGP RLTPLLQEED
610 620 630 640 650
SHQRLLMGLM VSELKDHFLR HLQGVEKKKI EQMVLDYISK LLDLICHIVE
660 670 680 690 700
TNWRKHNLHS WVLHFNSRGS AAEFAVFHIM TRILEATNSL FLPLPPGFHT
710 720 730 740 750
LHTILGVQCL PLHNLLHCID SGVLLLTETA VIRLMKDLDN TEKNEKLKFS
760 770 780 790 800
IIVRLPPLIG QKICRLWDHP MSSNIISRNH VTRLLQNYKK QPRNSMINKS
810 820 830 840 850
SFSVEFLPLN YFIEILTDIE SSNQALYPFE GHDNVDAEFV EEAALKHTAM

LLGL
Length:854
Mass (Da):97,802
Last modified:May 20, 2008 - v2
Checksum:iD7B4A3A95E2E8C3B
GO
Isoform 2 (identifier: A4D1B5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     446-446: Q → QWRQRADLNTNRVLSDFLK
     559-559: K → V
     560-854: Missing.

Show »
Length:577
Mass (Da):66,133
Checksum:i20F5F61CB33A4927
GO
Isoform 3 (identifier: A4D1B5-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     559-559: K → V
     560-854: Missing.

Show »
Length:559
Mass (Da):63,918
Checksum:i76E5CF3E65566679
GO
Isoform 4 (identifier: A4D1B5-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-606: Missing.

Show »
Length:248
Mass (Da):28,563
Checksum:i64786DCDA574C8D3
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B7ZL33B7ZL33_HUMAN
Gamma-secretase-activating protein
GSAP PION
175Annotation score:
H7C0Q7H7C0Q7_HUMAN
Gamma-secretase-activating protein
GSAP
188Annotation score:
C9JRG7C9JRG7_HUMAN
Gamma-secretase-activating protein
GSAP
58Annotation score:

Sequence cautioni

The sequence CAD39023 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04346747H → R1 PublicationCorresponds to variant dbSNP:rs6949654Ensembl.1
Natural variantiVAR_043468305G → E. Corresponds to variant dbSNP:rs1527263Ensembl.1
Natural variantiVAR_043469649V → I. Corresponds to variant dbSNP:rs17151692Ensembl.1
Natural variantiVAR_043470653W → L. Corresponds to variant dbSNP:rs17151689Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0337711 – 606Missing in isoform 4. 1 PublicationAdd BLAST606
Alternative sequenceiVSP_033772446Q → QWRQRADLNTNRVLSDFLK in isoform 2. Curated1
Alternative sequenceiVSP_033773559K → V in isoform 2 and isoform 3. 1 Publication1
Alternative sequenceiVSP_033774560 – 854Missing in isoform 2 and isoform 3. 1 PublicationAdd BLAST295

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC004921 Genomic DNA No translation available.
AC073635 Genomic DNA No translation available.
CH236949 Genomic DNA Translation: EAL24199.1
CH236949 Genomic DNA Translation: EAL24200.1
CH471091 Genomic DNA Translation: EAW77039.1
BC101499 mRNA Translation: AAI01500.2
AL834358 mRNA Translation: CAD39023.2 Different initiation.
AL079277 mRNA Translation: CAB45152.1
AL079297 mRNA Translation: CAB45193.1
CCDSiCCDS34672.2 [A4D1B5-1]
RefSeqiNP_059135.2, NM_017439.3 [A4D1B5-1]
UniGeneiHs.186649

Genome annotation databases

EnsembliENST00000257626; ENSP00000257626; ENSG00000186088 [A4D1B5-1]
GeneIDi54103
KEGGihsa:54103
UCSCiuc003ugf.3 human [A4D1B5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC004921 Genomic DNA No translation available.
AC073635 Genomic DNA No translation available.
CH236949 Genomic DNA Translation: EAL24199.1
CH236949 Genomic DNA Translation: EAL24200.1
CH471091 Genomic DNA Translation: EAW77039.1
BC101499 mRNA Translation: AAI01500.2
AL834358 mRNA Translation: CAD39023.2 Different initiation.
AL079277 mRNA Translation: CAB45152.1
AL079297 mRNA Translation: CAB45193.1
CCDSiCCDS34672.2 [A4D1B5-1]
RefSeqiNP_059135.2, NM_017439.3 [A4D1B5-1]
UniGeneiHs.186649

3D structure databases

ProteinModelPortaliA4D1B5
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119901, 4 interactors
DIPiDIP-59240N
IntActiA4D1B5, 1 interactor
STRINGi9606.ENSP00000257626

Chemistry databases

BindingDBiA4D1B5
ChEMBLiCHEMBL3638343

PTM databases

iPTMnetiA4D1B5
PhosphoSitePlusiA4D1B5

Polymorphism and mutation databases

BioMutaiGSAP

Proteomic databases

EPDiA4D1B5
MaxQBiA4D1B5
PaxDbiA4D1B5
PRIDEiA4D1B5
ProteomicsDBi609
610 [A4D1B5-2]
611 [A4D1B5-3]
612 [A4D1B5-4]
TopDownProteomicsiA4D1B5-1 [A4D1B5-1]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000257626; ENSP00000257626; ENSG00000186088 [A4D1B5-1]
GeneIDi54103
KEGGihsa:54103
UCSCiuc003ugf.3 human [A4D1B5-1]

Organism-specific databases

CTDi54103
DisGeNETi54103
EuPathDBiHostDB:ENSG00000186088.15
GeneCardsiGSAP
H-InvDBiHIX0006796
HGNCiHGNC:28042 GSAP
HPAiHPA023994
MIMi613552 gene
neXtProtiNX_A4D1B5
OpenTargetsiENSG00000186088
PharmGKBiPA164724500
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IG5Q Eukaryota
ENOG41129DZ LUCA
GeneTreeiENSGT00390000012875
HOVERGENiHBG095500
InParanoidiA4D1B5
OMAiENISACH
OrthoDBiEOG091G0GEP
PhylomeDBiA4D1B5
TreeFamiTF323853

Miscellaneous databases

ChiTaRSiGSAP human
GeneWikiiProtein_pigeon_homolog
GenomeRNAii54103
PROiPR:A4D1B5
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000186088 Expressed in 210 organ(s), highest expression level in small intestine Peyer's patch
CleanExiHS_PION
ExpressionAtlasiA4D1B5 baseline and differential
GenevisibleiA4D1B5 HS

Family and domain databases

InterProiView protein in InterPro
IPR028010 GSAP_C_dom
IPR026172 GSAP_fam
PANTHERiPTHR13630 PTHR13630, 1 hit
PfamiView protein in Pfam
PF14959 GSAP-16, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiGSAP_HUMAN
AccessioniPrimary (citable) accession number: A4D1B5
Secondary accession number(s): A4D1B6
, Q3MJC0, Q8ND73, Q9UMH3, Q9Y4L9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: May 20, 2008
Last modified: November 7, 2018
This is version 86 of the entry and version 2 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. 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. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
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