GSAP_MOUSE
ID GSAP_MOUSE Reviewed; 858 AA.
AC Q3TCV3; Q3UV93; Q8BJR8; Q8BZR8; Q8R1Y4;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Gamma-secretase-activating protein;
DE Short=GSAP;
DE AltName: Full=Protein pigeon homolog;
DE Contains:
DE RecName: Full=Gamma-secretase-activating protein 16 kDa C-terminal form;
DE Short=GSAP-16K;
GN Name=Gsap; Synonyms=Pion;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Aorta, Bone, Cecum, and Vein;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION.
RX PubMed=20811458; DOI=10.1038/nature09325;
RA He G., Luo W., Li P., Remmers C., Netzer W.J., Hendrick J., Bettayeb K.,
RA Flajolet M., Gorelick F., Wennogle L.P., Greengard P.;
RT "Gamma-secretase activating protein is a therapeutic target for Alzheimer's
RT disease.";
RL Nature 467:95-98(2010).
CC -!- FUNCTION: Regulator of gamma-secretase activity, which specifically
CC activates the production of amyloid-beta protein (amyloid-beta protein
CC 40 and amyloid-beta protein 42), without affecting the cleavage of
CC other gamma-secretase targets such has Notch. The gamma-secretase
CC complex is an endoprotease complex that catalyzes the intramembrane
CC cleavage of integral membrane proteins such as Notch receptors and APP
CC (amyloid-beta precursor protein). Specifically promotes the gamma-
CC cleavage of APP CTF-alpha (also named APP-CTF) by the gamma-secretase
CC complex to generate amyloid-beta, while it reduces the epsilon-cleavage
CC of APP CTF-alpha, leading to a low production of AICD.
CC {ECO:0000269|PubMed:20811458}.
CC -!- SUBUNIT: Interacts with APP; specifically interacts with the CTF-alpha
CC product of APP. Interacts with the gamma-secretase complex (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q3TCV3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3TCV3-2; Sequence=VSP_033777, VSP_033778;
CC Name=3;
CC IsoId=Q3TCV3-3; Sequence=VSP_033775, VSP_033776;
CC -!- PTM: The protein is first synthesized as a holoprotein form of 98 kDa
CC and rapidly processed into the gamma-secretase-activating protein 16
CC kDa C-terminal form, which constitutes the predominant form.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the GSAP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH22737.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC28433.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK033694; BAC28433.1; ALT_FRAME; mRNA.
DR EMBL; AK080244; BAC37858.1; -; mRNA.
DR EMBL; AK137494; BAE23378.1; -; mRNA.
DR EMBL; AK170515; BAE41852.1; -; mRNA.
DR EMBL; BC022737; AAH22737.1; ALT_INIT; mRNA.
DR CCDS; CCDS39021.1; -. [Q3TCV3-1]
DR RefSeq; NP_780646.2; NM_175437.3. [Q3TCV3-1]
DR AlphaFoldDB; Q3TCV3; -.
DR BioGRID; 229299; 1.
DR DIP; DIP-59239N; -.
DR IntAct; Q3TCV3; 3.
DR STRING; 10090.ENSMUSP00000043679; -.
DR iPTMnet; Q3TCV3; -.
DR PhosphoSitePlus; Q3TCV3; -.
DR MaxQB; Q3TCV3; -.
DR PaxDb; Q3TCV3; -.
DR PRIDE; Q3TCV3; -.
DR ProteomicsDB; 271339; -. [Q3TCV3-1]
DR ProteomicsDB; 271340; -. [Q3TCV3-2]
DR ProteomicsDB; 271341; -. [Q3TCV3-3]
DR Antibodypedia; 15032; 193 antibodies from 21 providers.
DR DNASU; 212167; -.
DR Ensembl; ENSMUST00000036031; ENSMUSP00000043679; ENSMUSG00000039934. [Q3TCV3-1]
DR Ensembl; ENSMUST00000198071; ENSMUSP00000142407; ENSMUSG00000039934. [Q3TCV3-3]
DR GeneID; 212167; -.
DR KEGG; mmu:212167; -.
DR UCSC; uc008woi.1; mouse. [Q3TCV3-2]
DR UCSC; uc008woj.1; mouse. [Q3TCV3-1]
DR CTD; 54103; -.
DR MGI; MGI:2442259; Gsap.
DR VEuPathDB; HostDB:ENSMUSG00000039934; -.
DR eggNOG; ENOG502QWQK; Eukaryota.
DR GeneTree; ENSGT00390000012875; -.
DR HOGENOM; CLU_008601_0_0_1; -.
DR InParanoid; Q3TCV3; -.
DR OMA; CANQSRN; -.
DR OrthoDB; 1035231at2759; -.
DR PhylomeDB; Q3TCV3; -.
DR TreeFam; TF323853; -.
DR BioGRID-ORCS; 212167; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Gsap; mouse.
DR PRO; PR:Q3TCV3; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q3TCV3; protein.
DR Bgee; ENSMUSG00000039934; Expressed in lumbar dorsal root ganglion and 126 other tissues.
DR ExpressionAtlas; Q3TCV3; baseline and differential.
DR Genevisible; Q3TCV3; MM.
DR GO; GO:0005802; C:trans-Golgi network; ISS:UniProtKB.
DR GO; GO:0001540; F:amyloid-beta binding; ISS:UniProtKB.
DR GO; GO:1902004; P:positive regulation of amyloid-beta formation; IDA:UniProtKB.
DR GO; GO:0030162; P:regulation of proteolysis; ISS:UniProtKB.
DR InterPro; IPR028010; GSAP_C_dom.
DR InterPro; IPR026172; GSAP_fam.
DR PANTHER; PTHR13630; PTHR13630; 1.
DR Pfam; PF14959; GSAP-16; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Golgi apparatus; Reference proteome.
FT CHAIN 1..858
FT /note="Gamma-secretase-activating protein"
FT /id="PRO_0000335810"
FT CHAIN 738..858
FT /note="Gamma-secretase-activating protein 16 kDa C-terminal
FT form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000403729"
FT VAR_SEQ 172
FT /note="Y -> F (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033775"
FT VAR_SEQ 173..858
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033776"
FT VAR_SEQ 521..526
FT /note="YGLKGY -> SPAPRG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_033777"
FT VAR_SEQ 527..858
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_033778"
FT CONFLICT 392
FT /note="Q -> R (in Ref. 1; BAC37858)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 858 AA; 98694 MW; 326E86B9E35A555B CRC64;
MALRLVTHFD VLEDVLPSLL TQAATTDEGD RAGVLETTYG SLRVLNIERN GNIIYTYKDN
KGNAVFGLYD CQTRQNEHLY TFEKDMQAVS CSVNSERTVL AASFIQYTTE GVKNDLQPGS
KCLTLLVEIH PVNNVKVLKA VDSCVWVQFL YPQAESHLLP QNHLLLISEE KYIERFHIQI
TREDGDRVVI RNSSHLPRDR LAEDFVWAQW DLSEQRLYYI ELKESRSILK CIQFRADESF
NLMFEMPLDI TLTGLRFKLV NFGYDYRQDR EKLCNQPSLC IFTNHTGSLC MCYSPKSDSR
EEITYSVFYL HKGYRKIFTA APGSADSQVT NGADSQVTDG IAFLNLGYFV AVYSPGHFLH
LLNIQHPDLV CHSLFLTGNN KIAAVLPPSP LQSLPGSLVL DCYSGKVYRV TLDQSYLLRF
LWNAHLDCER MAALHCILSC SQDPGFPEEQ IIQWISEHVS ACHSFDLIQE FLIASSYWSV
YAELDDMGML LQYSSVLTWN TEIPGIKFTT EELPLPLMKV YGLKGYWAKL NSNLEYIKYT
KPHLHYHNSV VRREWHNLIS EERTGKRRST MYVRNILENA MKVIASMETR TLEPRLIPFL
QEEDRHQRLL MGLMVSELRD HLLRHLQGVE KKKIEQMVLD YISKLLDLIW CLLETSWRKH
SMHPLVLHLN SHCSAADFEV FHLMTRILDA ASSLCLPLPP GFHSLHTILG VHCLPLYSLL
HYIDNGVLLL TETAVTRLMK DLDNSEKNEQ LKFSIIVRLP PLIGQKVCRL WDHPMSSNII
SRNHVARLLK NYRKEPRNSM IDKSSFPVEF LPLNYFIEIL MGLESSNQAL YGFEGHDNVD
AEFVEEAALK HTTMLLGL
