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Protein

Gamma-secretase-activating protein

Gene

GSAP

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

Functioni

Regulator of gamma-secretase activity, which specifically activates the production of beta-amyloid protein (beta-amyloid protein 40 and beta-amyloid 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 (beta-amyloid precursor protein). Specifically promotes the gamma-cleavage of APP CTF-alpha (also named APP-CTF) by the gamma-secretase complex to generate beta-amyloid, while it reduces the epsilon-cleavage of APP CTF-alpha, leading to a low production of AICD.1 Publication

GO - Molecular functioni

  • beta-amyloid binding Source: UniProtKB

GO - Biological processi

  • positive regulation of beta-amyloid formation Source: UniProtKB
  • regulation of proteolysis Source: UniProtKB
Complete GO annotation...

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

HGNCiHGNC:28042. GSAP.

Subcellular locationi

GO - Cellular componenti

  • trans-Golgi network Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Golgi apparatus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA164724500.

Polymorphism and mutation databases

BioMutaiGSAP.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 854854Gamma-secretase-activating proteinPRO_0000335809Add
BLAST
Chaini734 – 854121Gamma-secretase-activating protein 16 kDa C-terminal formSequence analysisPRO_0000403728Add
BLAST

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.
PeptideAtlasiA4D1B5.
PRIDEiA4D1B5.
TopDownProteomicsiA4D1B5-1. [A4D1B5-1]

PTM databases

iPTMnetiA4D1B5.
PhosphoSiteiA4D1B5.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiA4D1B5.
CleanExiHS_PION.
ExpressionAtlasiA4D1B5. baseline and differential.
GenevisibleiA4D1B5. HS.

Organism-specific databases

HPAiHPA020058.
HPA023994.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi119901. 4 interactions.
DIPiDIP-59240N.
STRINGi9606.ENSP00000257626.

Chemistry

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.
OMAiSATRTCW.
OrthoDBiEOG767391.
PhylomeDBiA4D1B5.
TreeFamiTF323853.

Family and domain databases

InterProiIPR028010. GSAP_C_dom.
IPR026172. GSAP_fam.
[Graphical view]
PANTHERiPTHR13630. PTHR13630. 1 hit.
PfamiPF14959. GSAP-16. 1 hit.
[Graphical view]

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

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

Sequence cautioni

The sequence CAD39023.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti47 – 471H → R.1 Publication
Corresponds to variant rs6949654 [ dbSNP | Ensembl ].
VAR_043467
Natural varianti305 – 3051G → E.
Corresponds to variant rs1527263 [ dbSNP | Ensembl ].
VAR_043468
Natural varianti649 – 6491V → I.
Corresponds to variant rs17151692 [ dbSNP | Ensembl ].
VAR_043469
Natural varianti653 – 6531W → L.
Corresponds to variant rs17151689 [ dbSNP | Ensembl ].
VAR_043470

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 606606Missing in isoform 4. 1 PublicationVSP_033771Add
BLAST
Alternative sequencei446 – 4461Q → QWRQRADLNTNRVLSDFLK in isoform 2. CuratedVSP_033772
Alternative sequencei559 – 5591K → V in isoform 2 and isoform 3. 1 PublicationVSP_033773
Alternative sequencei560 – 854295Missing in isoform 2 and isoform 3. 1 PublicationVSP_033774Add
BLAST

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

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 interactions.
DIPiDIP-59240N.
STRINGi9606.ENSP00000257626.

Chemistry

BindingDBiA4D1B5.

PTM databases

iPTMnetiA4D1B5.
PhosphoSiteiA4D1B5.

Polymorphism and mutation databases

BioMutaiGSAP.

Proteomic databases

EPDiA4D1B5.
MaxQBiA4D1B5.
PaxDbiA4D1B5.
PeptideAtlasiA4D1B5.
PRIDEiA4D1B5.
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.
GeneCardsiGSAP.
H-InvDBHIX0006796.
HGNCiHGNC:28042. GSAP.
HPAiHPA020058.
HPA023994.
MIMi613552. gene.
neXtProtiNX_A4D1B5.
PharmGKBiPA164724500.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IG5Q. Eukaryota.
ENOG41129DZ. LUCA.
GeneTreeiENSGT00390000012875.
HOVERGENiHBG095500.
InParanoidiA4D1B5.
OMAiSATRTCW.
OrthoDBiEOG767391.
PhylomeDBiA4D1B5.
TreeFamiTF323853.

Miscellaneous databases

GeneWikiiProtein_pigeon_homolog.
GenomeRNAii54103.
PROiA4D1B5.
SOURCEiSearch...

Gene expression databases

BgeeiA4D1B5.
CleanExiHS_PION.
ExpressionAtlasiA4D1B5. baseline and differential.
GenevisibleiA4D1B5. HS.

Family and domain databases

InterProiIPR028010. GSAP_C_dom.
IPR026172. GSAP_fam.
[Graphical view]
PANTHERiPTHR13630. PTHR13630. 1 hit.
PfamiPF14959. GSAP-16. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The DNA sequence of human chromosome 7."
    Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L.
    , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
    Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  2. "Human chromosome 7: DNA sequence and biology."
    Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S.
    , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
    Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ARG-47.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
    Tissue: Brain.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 36-854 (ISOFORM 3).
    Tissue: Lymph node.
  6. The European IMAGE consortium
    Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 587-854.
  7. "Gamma-secretase activating protein is a therapeutic target for Alzheimer's disease."
    He G., Luo W., Li P., Remmers C., Netzer W.J., Hendrick J., Bettayeb K., Flajolet M., Gorelick F., Wennogle L.P., Greengard P.
    Nature 467:95-98(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY, PROTEOLYTIC PROCESSING, IMATINIB-BINDING, TISSUE SPECIFICITY, INTERACTION WITH APP AND THE GAMMA-SECRETASE COMPLEX.

Entry informationi

Entry nameiGSAP_HUMAN
AccessioniPrimary (citable) accession number: A4D1B5
Secondary accession number(s): A4D1B6
, Q3MJC0, Q8ND73, Q9UMH3, Q9Y4L9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: May 20, 2008
Last modified: July 6, 2016
This is version 71 of the entry and version 2 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

The gamma-secretase regulator activity is specifically inhibited by imatinib (also known as STI571 or Gleevec), an anticancer drug that selectively decreases beta-amyloid 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 beta-amyloid protein production makes it a promising therapeutic target for the treatment of Alzheimer disease.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: 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.