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Q13075 (BIRC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Baculoviral IAP repeat-containing protein 1
Alternative name(s):
Neuronal apoptosis inhibitory protein
Gene names
Name:NAIP
Synonyms:BIRC1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1403 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Anti-apoptotic protein which acts by inhibiting the activities of CASP3, CASP7 and CASP9. Can inhibit the autocleavage of pro-CASP9 and cleavage of pro-CASP3 by CASP9. Capable of inhibiting CASP9 autoproteolysis at 'Asp-315' and decreasing the rate of auto proteolysis at 'Asp-330'. Acts as a mediator of neuronal survival in pathological conditions. Prevents motor-neuron apoptosis induced by a variety of signals. Possible role in the prevention of spinal muscular atrophy that seems to be caused by inappropriate persistence of motor-neuron apoptosis: mutated or deleted forms of NAIP have been found in individuals with severe spinal muscular atrophy. Ref.1 Ref.8 Ref.9 Ref.11 Ref.12 Ref.13

Acts as a sensor component of the NLRC4 inflammasome that specifically recognizes and binds needle protein CprI from pathogenic bacteria C.violaceum. Association of pathogenic bacteria proteins drives in turn drive assembly and activation of the NLRC4 inflammasome, promoting caspase-1 activation, cytokine production and macrophage pyroptosis. The NLRC4 inflammasome is activated as part of the innate immune response to a range of intracellular bacteria such as C.violaceum and L.pneumophila. Ref.1 Ref.8 Ref.9 Ref.11 Ref.12 Ref.13

Subunit structure

Interacts (via NACHT domain) with APAF1 (via CARD and NACHT domains). Interacts with C.violaceum needle protein CprI. Ref.11 Ref.12

Tissue specificity

Expressed in motor neurons, but not in sensory neurons. Found in liver and placenta, and to a lesser extent in spinal cord.

Domain

Both the BIR and NACHT domains are essential for effective inhibition of pro-CASP9 cleavage. BIR3 domain binds to procaspase-9 and the NACHT domain interacts with the NACHT domain of APAF1 forming a bridge between pro-CASP9 and APAF1. Ref.11

Sequence similarities

Contains 3 BIR repeats.

Contains 1 NACHT domain.

Sequence caution

The sequence AAC62261.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
   Biological processApoptosis
Immunity
Inflammatory response
Innate immunity
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
   LigandATP-binding
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionProtease inhibitor
Thiol protease inhibitor
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processinflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay Ref.9. Source: UniProtKB

negative regulation of neuron apoptotic process

Traceable author statement Ref.10. Source: UniProtKB

nervous system development

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentbasolateral plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from mutant phenotype Ref.11. Source: UniProtKB

cysteine-type endopeptidase inhibitor activity involved in apoptotic process

Inferred from electronic annotation. Source: InterPro

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

nucleoside-triphosphatase activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q13075-1)

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.
Isoform 2 (identifier: Q13075-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-61: MATQQKASDE...GYNSQMRSEA → MPLHIGDFVW...IRLELWINLR
     62-223: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 14031403Baculoviral IAP repeat-containing protein 1
PRO_0000122341

Regions

Repeat60 – 12768BIR 1
Repeat159 – 22769BIR 2
Repeat278 – 34568BIR 3
Domain464 – 758295NACHT

Sites

Metal binding3151Zinc
Metal binding3181Zinc
Metal binding3351Zinc
Metal binding3421Zinc
Binding site4761ATP

Natural variations

Alternative sequence1 – 6161MATQQ…MRSEA → MPLHIGDFVWDSKVHSLQSS LNIFSLLPTKGRTEHLFFSH ILSFHWPAFSSIRLELWINL R in isoform 2.
VSP_047196
Alternative sequence62 – 223162Missing in isoform 2.
VSP_047197
Natural variant5351V → M. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5
VAR_026477

Experimental info

Mutagenesis4761K → T: Prevents the proper cleavage of pro-CASP9, but does not inhibit the cleavage of pro-CASP3 by CASP9. Ref.11
Sequence conflict386 – 3872VP → ST in AAA64504. Ref.6
Sequence conflict5531Y → H in AAA64504. Ref.6
Sequence conflict567 – 5682IQ → FK in BAD92360. Ref.7
Sequence conflict9191P → S in BAD92360. Ref.7
Sequence conflict10661S → T in BAD92360. Ref.7

Secondary structure

................... 1403
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 30, 2006. Version 3.
Checksum: C1CE163D55900C6D

FASTA1,403159,582
        10         20         30         40         50         60 
MATQQKASDE RISQFDHNLL PELSALLGLD AVQLAKELEE EEQKERAKMQ KGYNSQMRSE 

        70         80         90        100        110        120 
AKRLKTFVTY EPYSSWIPQE MAAAGFYFTG VKSGIQCFCC SLILFGAGLT RLPIEDHKRF 

       130        140        150        160        170        180 
HPDCGFLLNK DVGNIAKYDI RVKNLKSRLR GGKMRYQEEE ARLASFRNWP FYVQGISPCV 

       190        200        210        220        230        240 
LSEAGFVFTG KQDTVQCFSC GGCLGNWEEG DDPWKEHAKW FPKCEFLRSK KSSEEITQYI 

       250        260        270        280        290        300 
QSYKGFVDIT GEHFVNSWVQ RELPMASAYC NDSIFAYEEL RLDSFKDWPR ESAVGVAALA 

       310        320        330        340        350        360 
KAGLFYTGIK DIVQCFSCGG CLEKWQEGDD PLDDHTRCFP NCPFLQNMKS SAEVTPDLQS 

       370        380        390        400        410        420 
RGELCELLET TSESNLEDSI AVGPIVPEMA QGEAQWFQEA KNLNEQLRAA YTSASFRHMS 

       430        440        450        460        470        480 
LLDISSDLAT DHLLGCDLSI ASKHISKPVQ EPLVLPEVFG NLNSVMCVEG EAGSGKTVLL 

       490        500        510        520        530        540 
KKIAFLWASG CCPLLNRFQL VFYLSLSSTR PDEGLASIIC DQLLEKEGSV TEMCVRNIIQ 

       550        560        570        580        590        600 
QLKNQVLFLL DDYKEICSIP QVIGKLIQKN HLSRTCLLIA VRTNRARDIR RYLETILEIK 

       610        620        630        640        650        660 
AFPFYNTVCI LRKLFSHNMT RLRKFMVYFG KNQSLQKIQK TPLFVAAICA HWFQYPFDPS 

       670        680        690        700        710        720 
FDDVAVFKSY MERLSLRNKA TAEILKATVS SCGELALKGF FSCCFEFNDD DLAEAGVDED 

       730        740        750        760        770        780 
EDLTMCLMSK FTAQRLRPFY RFLSPAFQEF LAGMRLIELL DSDRQEHQDL GLYHLKQINS 

       790        800        810        820        830        840 
PMMTVSAYNN FLNYVSSLPS TKAGPKIVSH LLHLVDNKES LENISENDDY LKHQPEISLQ 

       850        860        870        880        890        900 
MQLLRGLWQI CPQAYFSMVS EHLLVLALKT AYQSNTVAAC SPFVLQFLQG RTLTLGALNL 

       910        920        930        940        950        960 
QYFFDHPESL SLLRSIHFPI RGNKTSPRAH FSVLETCFDK SQVPTIDQDY ASAFEPMNEW 

       970        980        990       1000       1010       1020 
ERNLAEKEDN VKSYMDMQRR ASPDLSTGYW KLSPKQYKIP CLEVDVNDID VVGQDMLEIL 

      1030       1040       1050       1060       1070       1080 
MTVFSASQRI ELHLNHSRGF IESIRPALEL SKASVTKCSI SKLELSAAEQ ELLLTLPSLE 

      1090       1100       1110       1120       1130       1140 
SLEVSGTIQS QDQIFPNLDK FLCLKELSVD LEGNINVFSV IPEEFPNFHH MEKLLIQISA 

      1150       1160       1170       1180       1190       1200 
EYDPSKLVKL IQNSPNLHVF HLKCNFFSDF GSLMTMLVSC KKLTEIKFSD SFFQAVPFVA 

      1210       1220       1230       1240       1250       1260 
SLPNFISLKI LNLEGQQFPD EETSEKFAYI LGSLSNLEEL ILPTGDGIYR VAKLIIQQCQ 

      1270       1280       1290       1300       1310       1320 
QLHCLRVLSF FKTLNDDSVV EIAKVAISGG FQKLENLKLS INHKITEEGY RNFFQALDNM 

      1330       1340       1350       1360       1370       1380 
PNLQELDISR HFTECIKAQA TTVKSLSQCV LRLPRLIRLN MLSWLLDADD IALLNVMKER 

      1390       1400 
HPQSKYLTIL QKWILPFSPI IQK 

« Hide

Isoform 2 [UniParc].

Checksum: 51648FB32357B99A
Show »

FASTA1,241141,329

References

« Hide 'large scale' references
[1]"The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy."
Roy N., Mahadevan M.S., McLean M., Shutler G., Yaraghi Z., Farahini R., Baird S., Besner-Johnston A., Lefebvre C., Kang X., Salih M., Aubry H., Tamai K., Guan X., Ioannou P., Crawford T.O., de Jong P.J., Surh L. expand/collapse author list , Ikeda J., Korneluk R.G., Mackenzie A.
Cell 80:167-178(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT MET-535, POSSIBLE ROLE IN THE PROTECTION FROM SPINAL MUSCULAR ATROPHY.
Tissue: Fetal brain.
[2]"Sequence of a 131-kb region of 5q13.1 containing the spinal muscular atrophy candidate genes SMN and NAIP."
Chen Q., Baird S.D., Mahadevan M., Besner-Johnston A., Farahani R., Xuan J.-Y., Kang X., Lefebvre C., Ikeda J.-E., Korneluk R.G., MacKenzie A.E.
Genomics 48:121-127(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], SEQUENCE REVISION, VARIANT MET-535.
Tissue: Brain.
[3]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT MET-535.
[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 1), VARIANT MET-535.
Tissue: Testis.
[5]"Functional human NAIP promoter transcription regulatory elements for the NAIP and PsiNAIP genes."
Xu M., Okada T., Sakai H., Miyamoto N., Yanagisawa Y., MacKenzie A.E., Hadano S., Ikeda J.-E.
Biochim. Biophys. Acta 1574:35-50(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-1160 (ISOFORM 2), VARIANT MET-535.
[6]"A provisional transcript map of the spinal muscular atrophy (SMA) critical region."
van der Steege G., Draaijers T.G., Grootscholten P.M., Osinga J., Anzevino R., Velona I., Den Dunnen J.T., Scheffer H., Brahe C., van Ommen G.J.B., Buys C.H.C.M.
Eur. J. Hum. Genet. 3:87-95(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 386-623 (ISOFORM 1/2).
Tissue: Pre-B cell.
[7]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 567-1403 (ISOFORM 1/2).
Tissue: Brain.
[8]"Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes."
Liston P., Roy N., Tamai K., Lefebvre C., Baird S., Cherton-Horvat G., Farahani R., McLean M., Ikeda J., Mackenzie A., Korneluk R.G.
Nature 379:349-353(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
Tissue: Liver.
[9]"The neuronal apoptosis inhibitory protein is a direct inhibitor of caspases 3 and 7."
Maier J.K., Lahoua Z., Gendron N.H., Fetni R., Johnston A., Davoodi J., Rasper D., Roy S., Slack R.S., Nicholson D.W., MacKenzie A.E.
J. Neurosci. 22:2035-2043(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"IAPs: more than just inhibitors of apoptosis proteins."
Dubrez-Daloz L., Dupoux A., Cartier J.
Cell Cycle 7:1036-1046(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[11]"Integrity of ATP binding site is essential for effective inhibition of the intrinsic apoptosis pathway by NAIP."
Karimpour S., Davoodi J., Ghahremani M.H.
Biochem. Biophys. Res. Commun. 407:158-162(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH APAF1, DOMAIN BIR3 AND NACHT, MUTAGENESIS OF LYS-476.
[12]"The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus."
Zhao Y., Yang J., Shi J., Gong Y.N., Lu Q., Xu H., Liu L., Shao F.
Nature 477:596-600(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN INFLAMMASOME, INTERACTION WITH C.VIOLACEUM CPRI.
[13]"The human apoptosis inhibitor NAIP induces pyroptosis in macrophages infected with Legionella pneumophila."
Katagiri N., Shobuike T., Chang B., Kukita A., Miyamoto H.
Microbes Infect. 14:1123-1132(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN INFLAMMASOME.
[14]"Structures of BIR domains from human NAIP and cIAP2."
Herman M.D., Moche M., Flodin S., Welin M., Tresaugues L., Johansson I., Nilsson M., Nordlund P., Nyman T.
Acta Crystallogr. F 65:1091-1096(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 141-244 IN COMPLEX WITH ZINC IONS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U19251 mRNA. Translation: AAC52045.1.
U80017 Genomic DNA. Translation: AAC52047.1.
AC005031 Genomic DNA. Translation: AAC62261.1. Sequence problems.
AC044797 Genomic DNA. No translation available.
BC136273 mRNA. Translation: AAI36274.1.
AB048534 mRNA. Translation: BAB87181.1.
AH003063 mRNA. Translation: AAA64504.1.
AB209123 mRNA. Translation: BAD92360.1.
RefSeqNP_004527.2. NM_004536.2.
NP_075043.1. NM_022892.1.
UniGeneHs.654500.
Hs.710305.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2VM5X-ray1.80A141-244[»]
ProteinModelPortalQ13075.
SMRQ13075. Positions 55-346, 451-929, 1173-1279.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110752. 9 interactions.
DIPDIP-59150N.
IntActQ13075. 2 interactions.
STRING9606.ENSP00000194097.

Protein family/group databases

MEROPSI32.001.

PTM databases

PhosphoSiteQ13075.

Polymorphism databases

DMDM109940027.

Proteomic databases

PaxDbQ13075.
PRIDEQ13075.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000194097; ENSP00000443944; ENSG00000249437. [Q13075-1]
ENST00000503719; ENSP00000424913; ENSG00000249437. [Q13075-2]
ENST00000517649; ENSP00000428657; ENSG00000249437. [Q13075-1]
ENST00000523981; ENSP00000428363; ENSG00000249437. [Q13075-2]
ENST00000576435; ENSP00000458196; ENSG00000263062.
ENST00000576583; ENSP00000459350; ENSG00000263062.
GeneID4671.
KEGGhsa:4671.
UCSCuc003jyj.1. human. [Q13075-1]

Organism-specific databases

CTD4671.
GeneCardsGC05M070267.
H-InvDBHIX0164257.
HGNCHGNC:7634. NAIP.
HPAHPA042438.
MIM600355. gene.
neXtProtNX_Q13075.
Orphanet83330. Proximal spinal muscular atrophy type 1.
83418. Proximal spinal muscular atrophy type 2.
83419. Proximal spinal muscular atrophy type 3.
PharmGKBPA162396805.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG291696.
HOGENOMHOG000236326.
HOVERGENHBG050689.
InParanoidQ13075.
KOK12807.
OMADISRHIP.
PhylomeDBQ13075.
TreeFamTF105356.

Enzyme and pathway databases

SignaLinkQ13075.

Gene expression databases

ArrayExpressQ13075.
BgeeQ13075.
CleanExHS_NAIP.
GenevestigatorQ13075.

Family and domain databases

Gene3D1.10.1170.10. 3 hits.
3.40.50.300. 1 hit.
InterProIPR003593. AAA+_ATPase.
IPR001370. BIR.
IPR007111. NACHT_NTPase.
IPR028789. Naip.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERPTHR10044:SF5. PTHR10044:SF5. 1 hit.
PfamPF00653. BIR. 3 hits.
[Graphical view]
SMARTSM00382. AAA. 1 hit.
SM00238. BIR. 3 hits.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
PROSITEPS01282. BIR_REPEAT_1. 3 hits.
PS50143. BIR_REPEAT_2. 3 hits.
PS50837. NACHT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNAIP. human.
EvolutionaryTraceQ13075.
GeneWikiNAIP_(gene).
GenomeRNAi4671.
NextBio18000.
PROQ13075.
SOURCESearch...

Entry information

Entry nameBIRC1_HUMAN
AccessionPrimary (citable) accession number: Q13075
Secondary accession number(s): B9EG72 expand/collapse secondary AC list , E9PHD1, O75857, Q13730, Q59GI6, Q8TDZ4, Q99796
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 30, 2006
Last modified: April 16, 2014
This is version 128 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM