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Conserved domains on  [gi|148671266|gb|EDL03213|]
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RIKEN cDNA A530088I07, isoform CRA_d [Mus musculus]

Protein Classification

GSAP superfamily-containing protein( domain architecture ID 1912264)

GSAP superfamily-containing protein

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
GSAP super family cl45535
gamma-secretase-activating protein and similar proteins; Gamma-secretase activating protein, ...
 1-200 8.03e-80

gamma-secretase-activating protein and similar proteins; Gamma-secretase activating protein, also called GSAP or PION, selectively increases amyloid-beta production through a mechanism involving its interaction with both gamma-secretase and its substrate, the amyloid-beta precursor protein C-terminal fragment (APP-CTF). GSAP cleavage via caspase-3 is regulated and depends upon the availability of 5-lipoxygenase. Alzheimer's disease (AD), the most prevalent cause of dementia, is associated with accumulation of amyloid-beta peptide which is a major characteristic of the AD brain and responsible for some of its clinical manifestations. The anticancer drug imatinib had been shown to inhibit amyloid-beta formation without affecting Notch cleavage, by preventing GSAP interaction with the gamma-secretase substrate, APP-CTF. Thus, GSAP can serve as an amyloid-beta-lowering therapeutic target without affecting other key functions of gamma-secretase.


The actual alignment was detected with superfamily member cd23105:

Pssm-ID: 438516  Cd Length: 514  Bit Score: 247.63  E-value: 8.03e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148671266   1 MPLDITLTGLRFKLVNFGYDYRQDREKLCNQPSLCIFTNHTGSLCMCYSPKSDSREEITYSVFYLHKGYRKIFTAAPGSA 80
Cdd:cd23105  249 LPLDIPLPNTRFTLVNFYYDIPLSNTIPDKSLNLCVLTSHGGSLCICYQHPLGSQESSTYSVFYNHKGETKTFTVSLSHS 328

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148671266  81 DSQVTN----GADSQVTDGIAFLNLGYFVAVYSPGHFLHLLNIQHPDLVCHSLFLTGNN-------KIAAVLPPSPLQSL 149
Cdd:cd23105  329 GYLGHVirhlPKHSATRKRIFFTNLNYYVLVYLPGHFLHLLNVSHEDEPCHHILLHGKDvpwlstrPLLNACLTCPLQSL 408

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 148671266 150 PGSLVLDCYSGKVYRVTLDQSYLLRFLWNAHLDCERMAALHCILSCSQDPG 200
Cdd:cd23105  409 SGSLLFDCCSGKLYKVSLNKDSLLELLWNCSLDSTRLALLHCVLVHLKDYQ 459
 
Name Accession Description Interval E-value
GSAP cd23105
gamma-secretase-activating protein and similar proteins; Gamma-secretase activating protein, ...
 1-200 8.03e-80

gamma-secretase-activating protein and similar proteins; Gamma-secretase activating protein, also called GSAP or PION, selectively increases amyloid-beta production through a mechanism involving its interaction with both gamma-secretase and its substrate, the amyloid-beta precursor protein C-terminal fragment (APP-CTF). GSAP cleavage via caspase-3 is regulated and depends upon the availability of 5-lipoxygenase. Alzheimer's disease (AD), the most prevalent cause of dementia, is associated with accumulation of amyloid-beta peptide which is a major characteristic of the AD brain and responsible for some of its clinical manifestations. The anticancer drug imatinib had been shown to inhibit amyloid-beta formation without affecting Notch cleavage, by preventing GSAP interaction with the gamma-secretase substrate, APP-CTF. Thus, GSAP can serve as an amyloid-beta-lowering therapeutic target without affecting other key functions of gamma-secretase.


Pssm-ID: 438516  Cd Length: 514  Bit Score: 247.63  E-value: 8.03e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148671266   1 MPLDITLTGLRFKLVNFGYDYRQDREKLCNQPSLCIFTNHTGSLCMCYSPKSDSREEITYSVFYLHKGYRKIFTAAPGSA 80
Cdd:cd23105  249 LPLDIPLPNTRFTLVNFYYDIPLSNTIPDKSLNLCVLTSHGGSLCICYQHPLGSQESSTYSVFYNHKGETKTFTVSLSHS 328

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148671266  81 DSQVTN----GADSQVTDGIAFLNLGYFVAVYSPGHFLHLLNIQHPDLVCHSLFLTGNN-------KIAAVLPPSPLQSL 149
Cdd:cd23105  329 GYLGHVirhlPKHSATRKRIFFTNLNYYVLVYLPGHFLHLLNVSHEDEPCHHILLHGKDvpwlstrPLLNACLTCPLQSL 408

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 148671266 150 PGSLVLDCYSGKVYRVTLDQSYLLRFLWNAHLDCERMAALHCILSCSQDPG 200
Cdd:cd23105  409 SGSLLFDCCSGKLYKVSLNKDSLLELLWNCSLDSTRLALLHCVLVHLKDYQ 459
 
Name Accession Description Interval E-value
GSAP cd23105
gamma-secretase-activating protein and similar proteins; Gamma-secretase activating protein, ...
 1-200 8.03e-80

gamma-secretase-activating protein and similar proteins; Gamma-secretase activating protein, also called GSAP or PION, selectively increases amyloid-beta production through a mechanism involving its interaction with both gamma-secretase and its substrate, the amyloid-beta precursor protein C-terminal fragment (APP-CTF). GSAP cleavage via caspase-3 is regulated and depends upon the availability of 5-lipoxygenase. Alzheimer's disease (AD), the most prevalent cause of dementia, is associated with accumulation of amyloid-beta peptide which is a major characteristic of the AD brain and responsible for some of its clinical manifestations. The anticancer drug imatinib had been shown to inhibit amyloid-beta formation without affecting Notch cleavage, by preventing GSAP interaction with the gamma-secretase substrate, APP-CTF. Thus, GSAP can serve as an amyloid-beta-lowering therapeutic target without affecting other key functions of gamma-secretase.


Pssm-ID: 438516  Cd Length: 514  Bit Score: 247.63  E-value: 8.03e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148671266   1 MPLDITLTGLRFKLVNFGYDYRQDREKLCNQPSLCIFTNHTGSLCMCYSPKSDSREEITYSVFYLHKGYRKIFTAAPGSA 80
Cdd:cd23105  249 LPLDIPLPNTRFTLVNFYYDIPLSNTIPDKSLNLCVLTSHGGSLCICYQHPLGSQESSTYSVFYNHKGETKTFTVSLSHS 328

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148671266  81 DSQVTN----GADSQVTDGIAFLNLGYFVAVYSPGHFLHLLNIQHPDLVCHSLFLTGNN-------KIAAVLPPSPLQSL 149
Cdd:cd23105  329 GYLGHVirhlPKHSATRKRIFFTNLNYYVLVYLPGHFLHLLNVSHEDEPCHHILLHGKDvpwlstrPLLNACLTCPLQSL 408

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 148671266 150 PGSLVLDCYSGKVYRVTLDQSYLLRFLWNAHLDCERMAALHCILSCSQDPG 200
Cdd:cd23105  409 SGSLLFDCCSGKLYKVSLNKDSLLELLWNCSLDSTRLALLHCVLVHLKDYQ 459
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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