ID BIRC1_HUMAN Reviewed; 1403 AA. AC Q13075; B9EG72; E9PHD1; O75857; Q13730; Q59GI6; Q8TDZ4; Q99796; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 30-MAY-2006, sequence version 3. DT 05-DEC-2018, entry version 171. DE RecName: Full=Baculoviral IAP repeat-containing protein 1; DE AltName: Full=Neuronal apoptosis inhibitory protein; GN Name=NAIP; Synonyms=BIRC1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT MET-535, AND POSSIBLE RP ROLE IN THE PROTECTION FROM SPINAL MUSCULAR ATROPHY. RC TISSUE=Fetal brain; RX PubMed=7813013; DOI=10.1016/0092-8674(95)90461-1; RA Roy N., Mahadevan M.S., McLean M., Shutler G., Yaraghi Z., RA Farahini R., Baird S., Besner-Johnston A., Lefebvre C., Kang X., RA Salih M., Aubry H., Tamai K., Guan X., Ioannou P., Crawford T.O., RA de Jong P.J., Surh L., Ikeda J., Korneluk R.G., Mackenzie A.; RT "The gene for neuronal apoptosis inhibitory protein is partially RT deleted in individuals with spinal muscular atrophy."; RL Cell 80:167-178(1995). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], SEQUENCE REVISION, AND VARIANT RP MET-535. RC TISSUE=Brain; RX PubMed=9503025; DOI=10.1006/geno.1997.5141; RA Chen Q., Baird S.D., Mahadevan M., Besner-Johnston A., Farahani R., RA Xuan J.-Y., Kang X., Lefebvre C., Ikeda J.-E., Korneluk R.G., RA MacKenzie A.E.; RT "Sequence of a 131-kb region of 5q13.1 containing the spinal muscular RT atrophy candidate genes SMN and NAIP."; RL Genomics 48:121-127(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT MET-535. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT RP MET-535. RC TISSUE=Testis; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-1160 (ISOFORM 2), AND VARIANT MET-535. RX PubMed=11955612; DOI=10.1016/S0167-4781(01)00343-8; RA Xu M., Okada T., Sakai H., Miyamoto N., Yanagisawa Y., MacKenzie A.E., RA Hadano S., Ikeda J.-E.; RT "Functional human NAIP promoter transcription regulatory elements for RT the NAIP and PsiNAIP genes."; RL Biochim. Biophys. Acta 1574:35-50(2002). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 386-623 (ISOFORM 1/2). RC TISSUE=Pre-B cell; RX PubMed=7552146; RA van der Steege G., Draaijers T.G., Grootscholten P.M., Osinga J., RA Anzevino R., Velona I., Den Dunnen J.T., Scheffer H., Brahe C., RA van Ommen G.J.B., Buys C.H.C.M.; RT "A provisional transcript map of the spinal muscular atrophy (SMA) RT critical region."; RL Eur. J. Hum. Genet. 3:87-95(1995). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 567-1403 (ISOFORM 1/2). RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP FUNCTION. RC TISSUE=Liver; RX PubMed=8552191; DOI=10.1038/379349a0; RA Liston P., Roy N., Tamai K., Lefebvre C., Baird S., Cherton-Horvat G., RA Farahani R., McLean M., Ikeda J., Mackenzie A., Korneluk R.G.; RT "Suppression of apoptosis in mammalian cells by NAIP and a related RT family of IAP genes."; RL Nature 379:349-353(1996). RN [9] RP FUNCTION. RX PubMed=11896143; RA Maier J.K., Lahoua Z., Gendron N.H., Fetni R., Johnston A., RA Davoodi J., Rasper D., Roy S., Slack R.S., Nicholson D.W., RA MacKenzie A.E.; RT "The neuronal apoptosis inhibitory protein is a direct inhibitor of RT caspases 3 and 7."; RL J. Neurosci. 22:2035-2043(2002). RN [10] RP REVIEW ON FUNCTION. RX PubMed=18414036; DOI=10.4161/cc.7.8.5783; RA Dubrez-Daloz L., Dupoux A., Cartier J.; RT "IAPs: more than just inhibitors of apoptosis proteins."; RL Cell Cycle 7:1036-1046(2008). RN [11] RP FUNCTION, INTERACTION WITH APAF1, DOMAIN BIR3 AND NACHT, AND RP MUTAGENESIS OF LYS-476. RX PubMed=21371431; DOI=10.1016/j.bbrc.2011.02.130; RA Karimpour S., Davoodi J., Ghahremani M.H.; RT "Integrity of ATP binding site is essential for effective inhibition RT of the intrinsic apoptosis pathway by NAIP."; RL Biochem. Biophys. Res. Commun. 407:158-162(2011). RN [12] RP FUNCTION IN INFLAMMASOME, AND INTERACTION WITH C.VIOLACEUM CPRI. RX PubMed=21918512; DOI=10.1038/nature10510; RA Zhao Y., Yang J., Shi J., Gong Y.N., Lu Q., Xu H., Liu L., Shao F.; RT "The NLRC4 inflammasome receptors for bacterial flagellin and type III RT secretion apparatus."; RL Nature 477:596-600(2011). RN [13] RP FUNCTION IN INFLAMMASOME. RX PubMed=22504023; DOI=10.1016/j.micinf.2012.03.006; RA Katagiri N., Shobuike T., Chang B., Kukita A., Miyamoto H.; RT "The human apoptosis inhibitor NAIP induces pyroptosis in macrophages RT infected with Legionella pneumophila."; RL Microbes Infect. 14:1123-1132(2012). RN [14] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 141-244 IN COMPLEX WITH ZINC RP IONS. RX PubMed=19923725; DOI=10.1107/S1744309109038597; RA Herman M.D., Moche M., Flodin S., Welin M., Tresaugues L., RA Johansson I., Nilsson M., Nordlund P., Nyman T.; RT "Structures of BIR domains from human NAIP and cIAP2."; RL Acta Crystallogr. F 65:1091-1096(2009). CC -!- FUNCTION: Anti-apoptotic protein which acts by inhibiting the CC activities of CASP3, CASP7 and CASP9. Can inhibit the autocleavage CC of pro-CASP9 and cleavage of pro-CASP3 by CASP9. Capable of CC inhibiting CASP9 autoproteolysis at 'Asp-315' and decreasing the CC rate of auto proteolysis at 'Asp-330'. Acts as a mediator of CC neuronal survival in pathological conditions. Prevents motor- CC neuron apoptosis induced by a variety of signals. Possible role in CC the prevention of spinal muscular atrophy that seems to be caused CC by inappropriate persistence of motor-neuron apoptosis: mutated or CC deleted forms of NAIP have been found in individuals with severe CC spinal muscular atrophy. CC -!- FUNCTION: Acts as a sensor component of the NLRC4 inflammasome CC that specifically recognizes and binds needle protein CprI from CC pathogenic bacteria C.violaceum. Association of pathogenic CC bacteria proteins drives in turn drive assembly and activation of CC the NLRC4 inflammasome, promoting caspase-1 activation, cytokine CC production and macrophage pyroptosis. The NLRC4 inflammasome is CC activated as part of the innate immune response to a range of CC intracellular bacteria such as C.violaceum and L.pneumophila. CC -!- SUBUNIT: Interacts (via NACHT domain) with APAF1 (via CARD and CC NACHT domains). Interacts with C.violaceum needle protein CprI. CC {ECO:0000269|PubMed:19923725, ECO:0000269|PubMed:21371431, CC ECO:0000269|PubMed:21918512}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q13075-1; Sequence=Displayed; CC Name=2; CC IsoId=Q13075-2; Sequence=VSP_047196, VSP_047197; CC -!- TISSUE SPECIFICITY: Expressed in motor neurons, but not in sensory CC neurons. Found in liver and placenta, and to a lesser extent in CC spinal cord. CC -!- DOMAIN: Both the BIR and NACHT domains are essential for effective CC inhibition of pro-CASP9 cleavage. BIR3 domain binds to procaspase- CC 9 and the NACHT domain interacts with the NACHT domain of APAF1 CC forming a bridge between pro-CASP9 and APAF1. CC {ECO:0000269|PubMed:21371431}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC62261.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U19251; AAC52045.1; -; mRNA. DR EMBL; U80017; AAC52047.1; -; Genomic_DNA. DR EMBL; AC005031; AAC62261.1; ALT_SEQ; Genomic_DNA. DR EMBL; AC044797; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC136273; AAI36274.1; -; mRNA. DR EMBL; AB048534; BAB87181.1; -; mRNA. DR EMBL; AH003063; AAA64504.1; -; mRNA. DR EMBL; AB209123; BAD92360.1; -; mRNA. DR CCDS; CCDS4009.1; -. [Q13075-1] DR CCDS; CCDS43327.1; -. [Q13075-2] DR RefSeq; NP_001333799.1; NM_001346870.1. [Q13075-1] DR RefSeq; NP_004527.2; NM_004536.2. [Q13075-1] DR RefSeq; NP_075043.1; NM_022892.1. [Q13075-2] DR UniGene; Hs.646951; -. DR UniGene; Hs.654500; -. DR UniGene; Hs.710305; -. DR PDB; 2VM5; X-ray; 1.80 A; A=141-244. DR PDBsum; 2VM5; -. DR ProteinModelPortal; Q13075; -. DR SMR; Q13075; -. DR BioGrid; 110752; 10. DR CORUM; Q13075; -. DR DIP; DIP-59150N; -. DR IntAct; Q13075; 3. DR STRING; 9606.ENSP00000428657; -. DR MEROPS; I32.001; -. DR iPTMnet; Q13075; -. DR PhosphoSitePlus; Q13075; -. DR BioMuta; NAIP; -. DR DMDM; 109940027; -. DR PaxDb; Q13075; -. DR PeptideAtlas; Q13075; -. DR PRIDE; Q13075; -. DR ProteomicsDB; 59135; -. DR Ensembl; ENST00000194097; ENSP00000443944; ENSG00000249437. [Q13075-1] DR Ensembl; ENST00000503719; ENSP00000424913; ENSG00000249437. [Q13075-2] DR Ensembl; ENST00000517649; ENSP00000428657; ENSG00000249437. [Q13075-1] DR Ensembl; ENST00000523981; ENSP00000428363; ENSG00000249437. [Q13075-2] DR Ensembl; ENST00000612328; ENSP00000484107; ENSG00000278613. DR Ensembl; ENST00000620988; ENSP00000484731; ENSG00000278613. DR GeneID; 4671; -. DR KEGG; hsa:4671; -. DR UCSC; uc003kar.2; human. [Q13075-1] DR CTD; 4671; -. DR DisGeNET; 4671; -. DR EuPathDB; HostDB:ENSG00000249437.7; -. DR GeneCards; NAIP; -. DR H-InvDB; HIX0031942; -. DR H-InvDB; HIX0164257; -. DR HGNC; HGNC:7634; NAIP. DR HPA; HPA042438; -. DR MalaCards; NAIP; -. DR MIM; 600355; gene. DR neXtProt; NX_Q13075; -. DR OpenTargets; ENSG00000249437; -. DR Orphanet; 83330; Proximal spinal muscular atrophy type 1. DR Orphanet; 83418; Proximal spinal muscular atrophy type 2. DR Orphanet; 83419; Proximal spinal muscular atrophy type 3. DR PharmGKB; PA162396805; -. DR eggNOG; KOG1101; Eukaryota. DR eggNOG; ENOG410YPNM; LUCA. DR GeneTree; ENSGT00940000163559; -. DR HOGENOM; HOG000236326; -. DR HOVERGEN; HBG050689; -. DR InParanoid; Q13075; -. DR KO; K12807; -. DR OMA; AQGEAQW; -. DR OrthoDB; EOG091G0115; -. DR PhylomeDB; Q13075; -. DR TreeFam; TF105356; -. DR SignaLink; Q13075; -. DR SIGNOR; Q13075; -. DR ChiTaRS; NAIP; human. DR EvolutionaryTrace; Q13075; -. DR GeneWiki; NAIP_(gene); -. DR GenomeRNAi; 4671; -. DR PRO; PR:Q13075; -. DR Proteomes; UP000005640; Chromosome 5. DR Bgee; ENSG00000249437; Expressed in 183 organ(s), highest expression level in blood. DR CleanEx; HS_NAIP; -. DR ExpressionAtlas; Q13075; baseline and differential. DR Genevisible; Q13075; HS. DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IMP:UniProtKB. DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IEA:InterPro. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; TAS:UniProtKB. DR GO; GO:0007399; P:nervous system development; TAS:ProtInc. DR CDD; cd00022; BIR; 3. DR Gene3D; 3.80.10.10; -; 1. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR001370; BIR_rpt. DR InterPro; IPR032675; LRR_dom_sf. DR InterPro; IPR007111; NACHT_NTPase. DR InterPro; IPR028789; Naip. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR10044:SF134; PTHR10044:SF134; 1. DR Pfam; PF00653; BIR; 3. DR Pfam; PF05729; NACHT; 1. DR SMART; SM00382; AAA; 1. DR SMART; SM00238; BIR; 3. DR SUPFAM; SSF52540; SSF52540; 1. DR PROSITE; PS01282; BIR_REPEAT_1; 3. DR PROSITE; PS50143; BIR_REPEAT_2; 3. DR PROSITE; PS50837; NACHT; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; ATP-binding; KW Complete proteome; Immunity; Inflammatory response; Innate immunity; KW Metal-binding; Nucleotide-binding; Polymorphism; Protease inhibitor; KW Reference proteome; Repeat; Thiol protease inhibitor; Zinc. FT CHAIN 1 1403 Baculoviral IAP repeat-containing protein FT 1. FT /FTId=PRO_0000122341. FT REPEAT 60 127 BIR 1. FT REPEAT 159 227 BIR 2. FT REPEAT 278 345 BIR 3. FT DOMAIN 464 758 NACHT. {ECO:0000255|PROSITE- FT ProRule:PRU00136}. FT NP_BIND 473 478 ATP. {ECO:0000250|UniProtKB:Q3UP24}. FT METAL 315 315 Zinc. FT METAL 318 318 Zinc. FT METAL 335 335 Zinc. FT METAL 342 342 Zinc. FT VAR_SEQ 1 61 MATQQKASDERISQFDHNLLPELSALLGLDAVQLAKELEEE FT EQKERAKMQKGYNSQMRSEA -> MPLHIGDFVWDSKVHSL FT QSSLNIFSLLPTKGRTEHLFFSHILSFHWPAFSSIRLELWI FT NLR (in isoform 2). FT {ECO:0000303|PubMed:11955612}. FT /FTId=VSP_047196. FT VAR_SEQ 62 223 Missing (in isoform 2). FT {ECO:0000303|PubMed:11955612}. FT /FTId=VSP_047197. FT VARIANT 535 535 V -> M. {ECO:0000269|PubMed:11955612, FT ECO:0000269|PubMed:15372022, FT ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:7813013, FT ECO:0000269|PubMed:9503025}. FT /FTId=VAR_026477. FT MUTAGEN 476 476 K->T: Prevents the proper cleavage of FT pro-CASP9, but does not inhibit the FT cleavage of pro-CASP3 by CASP9. FT {ECO:0000269|PubMed:21371431}. FT CONFLICT 386 387 VP -> ST (in Ref. 6; AAA64504). FT {ECO:0000305}. FT CONFLICT 553 553 Y -> H (in Ref. 6; AAA64504). FT {ECO:0000305}. FT CONFLICT 567 568 IQ -> FK (in Ref. 7; BAD92360). FT {ECO:0000305}. FT CONFLICT 919 919 P -> S (in Ref. 7; BAD92360). FT {ECO:0000305}. FT CONFLICT 1066 1066 S -> T (in Ref. 7; BAD92360). FT {ECO:0000305}. FT HELIX 159 164 {ECO:0000244|PDB:2VM5}. FT HELIX 165 168 {ECO:0000244|PDB:2VM5}. FT HELIX 171 173 {ECO:0000244|PDB:2VM5}. FT HELIX 178 183 {ECO:0000244|PDB:2VM5}. FT STRAND 186 188 {ECO:0000244|PDB:2VM5}. FT STRAND 195 197 {ECO:0000244|PDB:2VM5}. FT TURN 198 200 {ECO:0000244|PDB:2VM5}. FT STRAND 203 206 {ECO:0000244|PDB:2VM5}. FT HELIX 213 220 {ECO:0000244|PDB:2VM5}. FT HELIX 225 231 {ECO:0000244|PDB:2VM5}. SQ SEQUENCE 1403 AA; 159582 MW; C1CE163D55900C6D CRC64; MATQQKASDE RISQFDHNLL PELSALLGLD AVQLAKELEE EEQKERAKMQ KGYNSQMRSE AKRLKTFVTY EPYSSWIPQE MAAAGFYFTG VKSGIQCFCC SLILFGAGLT RLPIEDHKRF HPDCGFLLNK DVGNIAKYDI RVKNLKSRLR GGKMRYQEEE ARLASFRNWP FYVQGISPCV LSEAGFVFTG KQDTVQCFSC GGCLGNWEEG DDPWKEHAKW FPKCEFLRSK KSSEEITQYI QSYKGFVDIT GEHFVNSWVQ RELPMASAYC NDSIFAYEEL RLDSFKDWPR ESAVGVAALA KAGLFYTGIK DIVQCFSCGG CLEKWQEGDD PLDDHTRCFP NCPFLQNMKS SAEVTPDLQS RGELCELLET TSESNLEDSI AVGPIVPEMA QGEAQWFQEA KNLNEQLRAA YTSASFRHMS LLDISSDLAT DHLLGCDLSI ASKHISKPVQ EPLVLPEVFG NLNSVMCVEG EAGSGKTVLL KKIAFLWASG CCPLLNRFQL VFYLSLSSTR PDEGLASIIC DQLLEKEGSV TEMCVRNIIQ QLKNQVLFLL DDYKEICSIP QVIGKLIQKN HLSRTCLLIA VRTNRARDIR RYLETILEIK AFPFYNTVCI LRKLFSHNMT RLRKFMVYFG KNQSLQKIQK TPLFVAAICA HWFQYPFDPS FDDVAVFKSY MERLSLRNKA TAEILKATVS SCGELALKGF FSCCFEFNDD DLAEAGVDED EDLTMCLMSK FTAQRLRPFY RFLSPAFQEF LAGMRLIELL DSDRQEHQDL GLYHLKQINS PMMTVSAYNN FLNYVSSLPS TKAGPKIVSH LLHLVDNKES LENISENDDY LKHQPEISLQ MQLLRGLWQI CPQAYFSMVS EHLLVLALKT AYQSNTVAAC SPFVLQFLQG RTLTLGALNL QYFFDHPESL SLLRSIHFPI RGNKTSPRAH FSVLETCFDK SQVPTIDQDY ASAFEPMNEW ERNLAEKEDN VKSYMDMQRR ASPDLSTGYW KLSPKQYKIP CLEVDVNDID VVGQDMLEIL MTVFSASQRI ELHLNHSRGF IESIRPALEL SKASVTKCSI SKLELSAAEQ ELLLTLPSLE SLEVSGTIQS QDQIFPNLDK FLCLKELSVD LEGNINVFSV IPEEFPNFHH MEKLLIQISA EYDPSKLVKL IQNSPNLHVF HLKCNFFSDF GSLMTMLVSC KKLTEIKFSD SFFQAVPFVA SLPNFISLKI LNLEGQQFPD EETSEKFAYI LGSLSNLEEL ILPTGDGIYR VAKLIIQQCQ QLHCLRVLSF FKTLNDDSVV EIAKVAISGG FQKLENLKLS INHKITEEGY RNFFQALDNM PNLQELDISR HFTECIKAQA TTVKSLSQCV LRLPRLIRLN MLSWLLDADD IALLNVMKER HPQSKYLTIL QKWILPFSPI IQK //