Apoptosis Database

Description [+]

Synonyms: BIRC1, NLRB1
Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
Short gene description: Baculoviral IAP repeat-containing protein 1 (Neuronal apoptosis inhibitory protein) [Source:UniProtKB/Swiss-Prot;Acc:Q13075]
Family: other
Process: immunity,
Pathways: inflammasome,
Criteria: manually curated
Curator comment:
Mouse ortholog(s): Naip2 Birc1-rs1 Naip6 Naip1 Naip4 Naip5
WIKI: BIRC1-H_sapiens

References [+]

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 JE, MacKenzie A, Korneluk RG
Dysregulation of apoptosis can result in inappropriate suppression of cell death, as occurs in the development of some cancers, or in failure to control the extent of cell death, as is believed to occur in acquired immunodeficiency and certain neurodegenerative disorders, such as spinal muscular atrophy (SMA). Recently, we isolated a candidate gene, encoding neuronal apoptosis inhibitor protein (NAIP), for SMA. This gene is homologous to two baculovirus inhibitor of apoptosis proteins (Cp-IAP and Op-IAP) and is partly deleted in individuals with type I SMA. A second SMA candidate gene encoding survival motor neuron (SMN), which is contiguous with the NAIP locus on 5q13.1, was also reported. Here we demonstrate a NAIP-mediated inhibition of apoptosis induced by a variety of signals, and have identified three additional human complementary DNAs and a Drosophila melanogaster sequence that are also homologous to the baculovirus IAPs. The four open reading frames (ORFs) possess three baculoviral inhibition of apoptosis protein repeat (BIR) domains and a carboxy-terminal RING zinc-finger. The human iap genes have a distinct but overlapping pattern of expression in fetal and adult tissues. These proteins significantly increase the number of known apoptotic suppressors. Nature. 1996 Jan 25;379(6563):349-53.

Inhibitor of apoptosis proteins in eukaryotic evolution and development: a model of thematic conservation.
O'Riordan MX, Bauler LD, Scott FL, Duckett CS
The past decade and a half has witnessed the discovery of a large, evolutionarily conserved family of cellular genes bearing homology to the prototype baculovirus Inhibitor of Apoptosis (IAP). The logical decision in the field to also refer to these cellular proteins as IAPs fails to do justice to this versatile group of factors that play a wide range of roles in eukaryotic development and homeostasis which include, but are not limited to, the regulation of programmed cell death. Here we describe the shared functional characteristics of several well-characterized IAPs whose defining motifs place them more in the category of multifunctional modular protein interaction domains. Dev Cell. 2008 Oct;15(4):497-508.

References from Mouse ortholog(s):

Critical function for Naip5 in inflammasome activation by a conserved carboxy-terminal domain of flagellin.
Lightfield KL, Persson J, Brubaker SW, Witte CE, von Moltke J, Dunipace EA, Henry T, Sun YH, Cado D, Dietrich WF, Monack DM, Tsolis RM, Vance RE
Inflammasomes are cytosolic multiprotein complexes that sense microbial infection and trigger cytokine production and cell death. However, the molecular components of inflammasomes and what they sense remain poorly defined. Here we demonstrate that 35 amino acids of the carboxyl terminus of flagellin triggered inflammasome activation in the absence of bacterial contaminants or secretion systems. To further elucidate the host flagellin-sensing pathway, we generated mice deficient in the intracellular sensor Naip5. These mice failed to activate the inflammasome in response to the 35 amino acids of flagellin or in response to Legionella pneumophila infection. Our data clarify the molecular basis for the cytosolic response to flagellin. Nat Immunol. 2008 Oct;9(10):1171-8. Epub 2008 Aug 24.

Naip5 affects host susceptibility to the intracellular pathogen Legionella pneumophila.
Wright EK, Goodart SA, Growney JD, Hadinoto V, Endrizzi MG, Long EM, Sadigh K, Abney AL, Bernstein-Hanley I, Dietrich WF
BACKGROUND: Legionella pneumophila is a gram-negative bacterial pathogen that is the cause of Legionnaires' Disease. Legionella produces disease because it can replicate inside a specialized compartment of host macrophages. Macrophages isolated from various inbred mice exhibit large differences in permissiveness for intracellular replication of Legionella. A locus affecting this host-resistance phenotype, Lgn1, has been mapped to chromosome 13, but the responsible gene has not been identified. RESULTS: Here, we report that Naip5 (also known as Birc1e) influences susceptibility to Legionella. Naip5 encodes a protein that is homologous to plant innate immunity (so-called resistance) proteins and has been implicated in signaling pathways related to apoptosis regulation. Detailed recombination mapping and analysis of expression implicates Naip5 in the Legionella permissiveness differences among mouse strains. A bacterial artificial chromosome (BAC) transgenic line expressing a nonpermissive allele of Naip5 exhibits a reduction in macrophage Legionella permissiveness. In addition, morpholino-based antisense inhibition of Naip5 causes an increase in the Legionella permissiveness of macrophages. CONCLUSIONS: We conclude that polymorphisms in Naip5 are involved in the permissiveness differences of mouse macrophages for intracellular Legionella replication. We speculate that Naip5 is a functional mammalian homolog of plant resistance proteins that monitor for, and initiate host response to, the presence of secreted bacterial virulence proteins. Curr Biol. 2003 Jan 8;13(1):27-36.

Structure & Sequence [+]

Pfam domains: (Pfam is a large collection of protein families.)

Source	Domain Name	Start	End
PFAM A	BIR	63	128
PFAM A	BIR	162	228
PFAM A	BIR	281	346
PFAM A	NACHT	464	618

Protein sequence [+]

BIRC1 | Homo sapiens | 9606 | length:1403

MATQQKASDERISQFDHNLLPELSALLGLDAVQLAKELEEEEQKERAKMQKGYNSQMRSE
AKRLKTFVTYEPYSSWIPQEMAAAGFYFTGVKSGIQCFCCSLILFGAGLTRLPIEDHKRF
HPDCGFLLNKDVGNIAKYDIRVKNLKSRLRGGKMRYQEEEARLASFRNWPFYVQGISPCV
LSEAGFVFTGKQDTVQCFSCGGCLGNWEEGDDPWKEHAKWFPKCEFLRSKKSSEEITQYI
QSYKGFVDITGEHFVNSWVQRELPMASAYCNDSIFAYEELRLDSFKDWPRESAVGVAALA
KAGLFYTGIKDIVQCFSCGGCLEKWQEGDDPLDDHTRCFPNCPFLQNMKSSAEVTPDLQS
RGELCELLETTSESNLEDSIAVGPIVPEMAQGEAQWFQEAKNLNEQLRAAYTSASFRHMS
LLDISSDLATDHLLGCDLSIASKHISKPVQEPLVLPEVFGNLNSVMCVEGEAGSGKTVLL
KKIAFLWASGCCPLLNRFQLVFYLSLSSTRPDEGLASIICDQLLEKEGSVTEMCVRNIIQ
QLKNQVLFLLDDYKEICSIPQVIGKLIQKNHLSRTCLLIAVRTNRARDIRRYLETILEIK
AFPFYNTVCILRKLFSHNMTRLRKFMVYFGKNQSLQKIQKTPLFVAAICAHWFQYPFDPS
FDDVAVFKSYMERLSLRNKATAEILKATVSSCGELALKGFFSCCFEFNDDDLAEAGVDED
EDLTMCLMSKFTAQRLRPFYRFLSPAFQEFLAGMRLIELLDSDRQEHQDLGLYHLKQINS
PMMTVSAYNNFLNYVSSLPSTKAGPKIVSHLLHLVDNKESLENISENDDYLKHQPEISLQ
MQLLRGLWQICPQAYFSMVSEHLLVLALKTAYQSNTVAACSPFVLQFLQGRTLTLGALNL
QYFFDHPESLSLLRSIHFPIRGNKTSPRAHFSVLETCFDKSQVPTIDQDYASAFEPMNEW
ERNLAEKEDNVKSYMDMQRRASPDLSTGYWKLSPKQYKIPCLEVDVNDIDVVGQDMLEIL
MTVFSASQRIELHLNHSRGFIESIRPALELSKASVTKCSISKLELSAAEQELLLTLPSLE
SLEVSGTIQSQDQIFPNLDKFLCLKELSVDLEGNINVFSVIPEEFPNFHHMEKLLIQISA
EYDPSKLVKLIQNSPNLHVFHLKCNFFSDFGSLMTMLVSCKKLTEIKFSDSFFQAVPFVA
SLPNFISLKILNLEGQQFPDEETSEKFAYILGSLSNLEELILPTGDGIYRVAKLIIQQCQ
QLHCLRVLSFFKTLNDDSVVEIAKVAISGGFQKLENLKLSINHKITEEGYRNFFQALDNM
PNLQELDISRHFTECIKAQATTVKSLSQCVLRLPRLIRLNMLSWLLDADDIALLNVMKER
HPQSKYLTILQKWILPFSPIIQK

BLAST at NCBI | WU-BLAST2 at EBI

Structure links:

Smartdomain prediction information: SM00238
Smartdomain prediction information: SM00382
Prosite motif and domain information: PS01282
Profile motif and domain profile information: PS50837
Profile motif and domain profile information: PS50143
Interpro domain information: Q13075
PFAM domain and domain family information: Q13075
Protein 3D structures from PDB: 2VM5

Evolution [+]

Name	Relationship	Species
P_troglodytes_ENSPTRP00000048273	orthology	Chimpanzee
XM_001156604.1	orthology	Chimpanzee
IPI00689691.3	orthology	Cow
IPI00689691.3	orthology	Cow
E_caballus_ENSECAP00000002314	orthology	Horse
XP_001504091.2	orthology	Horse
A_carolinensis_ENSACAP00000009897	orthology	Lyzard
A_carolinensis_ENSACAP00000009897	orthology	Lyzard
M_mulatta_ENSMMUP00000034549	orthology	Macaca
XM_001093532.1	orthology	Macaca
Birc1-rs1	orthology	Mouse
Naip6	orthology	Mouse
Naip1	orthology	Mouse
Naip4	orthology	Mouse
Naip5	orthology	Mouse
Naip5	orthology	Mouse
Naip2	orthology	Mouse
Naip2	orthology	Mouse
P_pygmaeus_ENSPPYP00000017359	orthology	Orangutan
P_pygmaeus_ENSPPYP00000017359	orthology	Orangutan
RGD1559914_predicted	orthology	Rat
Q8R4U8_RAT	orthology	Rat
NLRC4	paralogy	Chimpanzee
NLRC4	paralogy	Chimpanzee
IPI00708553.3	paralogy	Cow
IPI00708553.3	paralogy	Cow
NLRC4	paralogy	Horse
NLRC4	paralogy	Horse
NLRC4	paralogy	Human
NLRC4	paralogy	Human
AC140134.2	paralogy	Human
AC140134.1	paralogy	Human
NLRC4	paralogy	Lyzard
NLRC4	paralogy	Lyzard
NLRC4	paralogy	Macaca
NLRC4	paralogy	Macaca
Nlrc4	paralogy	Mouse
Nlrc4	paralogy	Mouse
NLRC4	paralogy	Orangutan
NLRC4	paralogy	Orangutan
Nlrc4	paralogy	Rat
NP_001100177.1	paralogy	Rat

Gene Ontology [+]

GO id	Name	Ontology type	Evidence
GO:0006916	anti-apoptosis	biological_proccess	TAS
GO:0007399	nervous system development	biological_proccess	TAS
GO:0006915	apoptosis	biological_proccess	IEA
GO:0006952	defense response	biological_proccess	IEA
GO:0000166	nucleotide binding	mollecular_function	IEA
GO:0017111	nucleoside-triphosphatase activity	mollecular_function	IEA
GO:0008270	zinc ion binding	mollecular_function	IEA
GO:0046872	metal ion binding	mollecular_function	IEA
GO:0005622	intracellular	cell_component	IEA

Information from other databases [+]

Gene related links:

Gene info from HGNC [?] :7634
Gene related info from GeneCards [?] : BIRC1
Ensembl genome browser [?] : ENSG00000081770
Expression info from Arrayexpress [?] : ENSG00000081770
Protein expression from Protein Atlas: [?] ENSG00000081770
Community gene edition from Wikigenes: [?] 4671

Protein related links:

Uniprot protein info: Q13075
PIR protein info: Q13075
Protein interactions from IntAct: Q13075

Gene and disease information from OMIM: (For a full disease description table, click here.)

OMIM gene information: 600355
OMIM disease information: 253300

Other links

entrezgene: 4671
entrezgene: 642009
refseq_dna: NM_022892
refseq_dna: NM_004536
refseq_peptide: NP_004527
refseq_peptide: NP_075043

Click on [?] for more information.

BIRC1 (Homo sapiens)