NAIP3 geenin vaihtoehtoisia nimiä ovat BIRC1, NLDB1, psiNAIP.
(Suomennosta) Suositellut nimet: Bakuloviraali IAP toiston sisältävä proteiini1
Nimet: Neuronaalinen apoptoosia estävä proteiini (NAIP)
Nukleotidiä sitovan oligomerisaatiodomeenin (NOD), leusiinipitoinen toiston (LRR) ja BIR-domeenin sisältävä 1 psi neuronaalinen apoptoosia estävä proteiini (NAIP)
- Preferred Names
- baculoviral IAP repeat-containing protein 1
- Names
- neuronal apoptosis inhibitory protein
- nucleotide-binding oligomerization domain, leucine rich repeat and BIR domain containing 1
- psi neuronal apoptosis inhibitory protein
Sen geeni NAIP3 on 500 kb:n osa invertoituneesta duplikaatiosta kromosomissa 5q13.2. Tämä kaksinkertaistunut alue sisältää ainakin neljä geeniä ja toistoelementtejä, mikä altistaa sitä uudelleenjärjestymisille ja deleetioille. Sekvenssin toistotaipumus ja monimutkaisuus on tuottanut vaikeuksia määrittää sen genomisen alueen organisoituminen. Tämä geenikopio on kokopitkä (NAIPFull). On myös olemassa tästä geenialueesta 5q13 lisäkopioita lyhentyneine muotoineen (truncated) ja sisäisine deleetioineen. In ajateltu, että tämä geeni olisi spinaalisen lihasatrofian modifioija- tätä lihastautia aiheuttaa naapurigeenin SMN1:n mutaatiot.
Tämän geenin koodaama proteiini sisältää homologisia alueita bakuloviruksen kahdelle apoptoosiproteiini -inhibiittorille ja se kykenee vaimentamaan erilaisten signaalien indusoimaa apoptoosia. Vaihtoehtoispleissauksesta ja vaihtoehtoisista promoottoreista seuraa monia transkriptivariantteja. Tätä geeniä ilmenee umpilisäkkeessä, pernassa ja 23 muussa kudoksessa.
- BIRC1; NLRB1; psiNAIP Summary This gene is part of a 500 kb inverted duplication on chromosome 5q13. This duplicated region contains at least four genes and repetitive elements which make it prone to rearrangements and deletions. The repetitiveness and complexity of the sequence have also caused difficulty in determining the organization of this genomic region. This copy of the gene is full length; additional copies with truncations and internal deletions are also present in this region of chromosome 5q13. It is thought that this gene is a modifier of spinal muscular atrophy caused by mutations in a neighboring gene, SMN1. The protein encoded by this gene contains regions of homology to two baculovirus inhibitor of apoptosis proteins, and it is able to suppress apoptosis induced by various signals. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Nov 2016]Expression
- Broad expression in appendix (RPKM 20.5), spleen (RPKM 11.7) and 23 other tissues See moreOrthologs
- Cutting Edge: Inflammasome Activation in Primary Human Macrophages Is Dependent on Flagellin. Kortmann J, et al. J Immunol, 2015 Aug 1. PMID 26109648, Free PMC Article
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Population variation in NAIP functional copy number confers increased cell death upon Legionella pneumophila infection.
Boniotto M, et al. Hum Immunol, 2012 Feb. PMID 22067212 AbstractThe NAIP gene encodes an intracellular innate immunity receptor that senses flagellin. The genomic region containing NAIP presents a complex genomic organization and includes various NAIP paralogs. Here, we assessed the degree of copy number variation of the complete NAIP gene (NAIPFull) in various human populations and studied the functional impact of such variation on host cell fate using Legionella pneumophila as an infection model. We determined that African populations have a NAIPFull duplication at a higher frequency than Europeans and Asians, with an increased transcription of the gene. In addition, we demonstrated that a higher amount of the NAIPFull protein dramatically increases cell death upon infection by L. pneumophila, a mechanism that may account for increased host resistance to infection. We postulate that the NAIPFull gene duplication might have been evolutionary maintained, or even selected for, because it may confer an advantage to the host against flagellated bacteria.
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Neuronal apoptosis inhibitory protein, NAIP, is an inhibitor of procaspase-9.
Davoodi J, et al. Int J Biochem Cell Biol. 2010 Jun;42(6):958-64. doi: 10.1016/j.biocel.2010.02.008. Epub 2010 Feb 18.Davoodi J1, Ghahremani MH, Es-Haghi A, Mohammad-Gholi A, Mackenzie A.Ability of the full length NAIP and its BIR3 domain in inhibition of the proteases of the intrinsic apoptosis pathway was investigated. Activity of endogenous executioner caspases was drastically reduced by both recombinant NAIP-BIR3 (NBIR3) and the full length protein. Western blotting experiments showed that the full length NAIP and its BIR3 domain inhibited the cleavage of procaspase-3 by apoptosome activated caspase-9. Moreover, full length NAIP inhibited autocatalytic processing of procaspase-9 in the apoptosome complex indicating that unlike other inhibitor of apoptosis proteins (IAPs) human NAIP is an inhibitor of procaspase-9. Furthermore, inhibition of single-chain caspase-9 (human caspase-9, D315, D330/A point mutations that abrogate the proteolytic processing but not the catalytic activity of caspase-9) by the BIR3 domain indicated that the this domain is the caspase-9 interacting moiety. Consistently, pull-down experiments of single-chain capsase-9 in apoptosome complex by the NBIR3 but not the X-linked inhibitor of apoptosis protein (XIAP)-BIR3 domain confirmed that the protein can associate with procaspase-9 prior to its autoproteolysis upon apoptosome formation. Interaction studies revealed the association of C338W variant of the NBIR3, but not the wild type protein with both SMAC-peptide and the SMAC protein. These data indicate that mutation of C338 to Trp is sufficient to accommodate the interaction of NAIP-BIR3 with SMAC-peptide and protein. Taken together, these results demonstrate that NAIP is evolved to prevent apoptosis right at the initiation stage of apoptosome formation and this inhibition cannot be antagonized by SMAC-type proteins.
- PMID:20171302 DOI: 10.1016/j.biocel.2010.02.008
- Induction of neuronal apoptosis inhibitory protein expression in response to androgen deprivation in prostate cancer. Chiu HH, et al. Cancer Lett, 2010 Jun 28. PMID 20044205, Free PMC ArticleA mechanism for survival of prostate cancer cells in an androgen-deprived environment remains elusive. Here, we find that expression of neuronal apoptosis inhibitory protein (NAIP) was significantly increased in vivo and in vitro in response to androgen deprivation therapy (ADT). Increased expression of NAIP corresponded to increased DNA-binding activity of NF-kappaB that physically associated to previously uncharacterized kappaB-like sites in the NAIP locus. Importantly, expression of NAIP was significantly increased (p=0.04) in clinical samples of prostate cancer from patients receiving ADT. Expression of NAIP may be associated with enhanced survival of prostate cancer in response to castration.
- Apoptotic abnormalities in differential gene expression in peripheral blood mononuclear cells from children with Fabry disease. Moore DF, et al. Acta Paediatr, 2008 Apr. PMID 18339188
- GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?
- NAIP expression is most abundant in M2 macrophages, while cIAP1 and cIAP2 show an
- Modulation of chemotherapeutic drug resistance in neuroblastoma SK-N-AS cells by the neural apoptosis inhibitory protein and miR-520f.
- Copy number variations of SMN2 and NAIP genes in patients are related to spinal muscular atrophy clinical types (P < 0.05).
- /NAIP1 and NAIP2/5 formed a large oligomeric complex with NLRC4 in the presence of corresponding bacterial ligands, and could support reconstitution of the NLRC4 inflammasome in a ligand-specific manner.
- identified an intronic region of the NAIP gene responding to TEAD1/YAP activity, suggesting that regulation of NAIP by TEAD1/YAP is at the transcriptional level
https://www.ncbi.nlm.nih.gov/protein/NP_004527.2
Konservoidut domeenit:
- Conserved Domains (6) summary
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- smart00238
Location:159 → 229 - BIR; Baculoviral inhibition of apoptosis protein repeat
- smart00382
Location:463 → 600 - AAA; ATPases associated with a variety of cellular activities
- cd00116
Location:1171 → 1379 - LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...
- sd00033
Location:1055 → 1078 - LRR_RI; leucine-rich repeat [structural motif]
- sd00034
Location:1157 → 1182 - LRR_AMN1; leucine-rich repeat [structural motif]
- pfam05729
Location:464 → 617 - NACHT; NACHT domain
- smart00238
Selitys 3 BIR- domeenille: Domeeni, joka löytyy apoptoosiproteiinien estäjistä ja muistakin proteiineista: sisältävät Zn-Finger sinkkiä sitovan motiivin
Baculoviral inhibition of apoptosis protein repeat
Domain found in inhibitor of apoptosis proteins (IAPs) and other proteins. Acts as a direct inhibitor of caspase enzymes.
Selitys LRR- domeenille:
Leusiinipitoinen domeeni.
Selityksiä NACHT- domeenille.
NTPaasi-domeeni, jota havaitaan apoptoosiproteiineissa ja myös niissä, jotka osallistuvat MHC-transkription aktivatioon.
NACHT domain
This NTPase domain is found
in apoptosis proteins as well as those involved in MHC transcription
activation. This family is closely related to pfam00931.- The NACHT family - a new group of predicted NTPases implicated in apoptosis and MHC transcription activation.Trends Biochem. Sci. 2000 May; 25(5):223-224
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