Q9NPP4 (NLRC4_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 29, 2013.
Version 117.
History...
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: NLR family CARD domain-containing protein 4 Alternative name(s): CARD, LRR, and NACHT-containing protein Short name=Clan protein Caspase recruitment domain-containing protein 12 Ice protease-activating factor Short name=Ipaf | ||||||
| Gene names |
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| Organism | Homo sapiens (Human) [Reference proteome] | ||||||
| Taxonomic identifier | 9606 [NCBI] | ||||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 1024 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Key component of inflammasomes that indirectly senses specific proteins from pathogenic bacteria and fungi and responds by assembling an inflammasome complex that promotes caspase-1 activation, cytokine production and macrophage pyroptosis. Ref.11 |
| Subunit structure | Component of the NLRC4 inflammasome By similarity. Homooligomer. Interacts with ASC, pro-caspase-1, NOD2, BCL10 and NALP1 (NAC) by CARD-CARD interaction. Interacts with EIF2AK2/PKR. |
| Subcellular location | Cytoplasm. Cytoplasm › cytosol By similarity. Note: Cytoplasmic filaments. Ref.3 |
| Tissue specificity | Isoform 2 is expressed ubiquitously, although highly expressed in lung and spleen. Isoform 1 is highly expressed in lung, followed by leukocytes especially monocytes, lymph node, colon, brain, prostate, placenta, spleen, bone marrow and fetal liver. Isoform 4 is only detected in brain. |
| Post-translational modification | Phosphorylated at Ser-533 following infection of macrophages with S.typhimurium (Salmonella). Phosphorylation is essential for NLRC4 inflammasome function to promote caspase-1 activation and pyroptosis. PRKCD phosphorylates Ser-533 in vitro By similarity. |
| Sequence similarities | Contains 1 CARD domain. Contains 14 LRR (leucine-rich) repeats. Contains 1 NACHT domain. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| itself | 3 | EBI-1222527,EBI-1222527 | ||
| CASP1 | P29466 | 4 | EBI-1222527,EBI-516667 |
Alternative products
| This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q9NPP4-1) Also known as: CLANA; 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: Q9NPP4-2) Also known as: CLANB; The sequence of this isoform differs from the canonical sequence as follows: 89-753: Missing. | ||||||
| Isoform 3 (identifier: Q9NPP4-3) Also known as: CLANC; The sequence of this isoform differs from the canonical sequence as follows: 155-156: NG → VL 157-1024: Missing. | ||||||
| Isoform 4 (identifier: Q9NPP4-4) Also known as: CLAND; The sequence of this isoform differs from the canonical sequence as follows: 90-92: FHQ → LTA 93-1024: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1024 | 1024 | NLR family CARD domain-containing protein 4 | PRO_0000144087 | |||||
Regions | |||||||||
| Domain | 1 – 88 | 88 | CARD | ||||||
| Repeat | 7 – 30 | 24 | LRR 1 | ||||||
| Domain | 163 – 476 | 314 | NACHT | ||||||
| Repeat | 258 – 281 | 24 | LRR 2 | ||||||
| Repeat | 578 – 598 | 21 | LRR 3 | ||||||
| Repeat | 656 – 679 | 24 | LRR 4 | ||||||
| Repeat | 735 – 758 | 24 | LRR 5 | ||||||
| Repeat | 762 – 785 | 24 | LRR 6 | ||||||
| Repeat | 787 – 812 | 26 | LRR 7 | ||||||
| Repeat | 824 – 847 | 24 | LRR 8 | ||||||
| Repeat | 848 – 870 | 23 | LRR 9 | ||||||
| Repeat | 878 – 902 | 25 | LRR 10 | ||||||
| Repeat | 911 – 933 | 23 | LRR 11 | ||||||
| Repeat | 936 – 963 | 28 | LRR 12 | ||||||
| Repeat | 965 – 985 | 21 | LRR 13 | ||||||
| Repeat | 999 – 1021 | 23 | LRR 14 | ||||||
| Nucleotide binding | 169 – 176 | 8 | ATP Potential | ||||||
Amino acid modifications | |||||||||
| Modified residue | 533 | 1 | Phosphoserine By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 89 – 753 | 665 | Missing in isoform 2. | VSP_000784 | |||||
| Alternative sequence | 90 – 92 | 3 | FHQ → LTA in isoform 4. | VSP_000787 | |||||
| Alternative sequence | 93 – 1024 | 932 | Missing in isoform 4. | VSP_000788 | |||||
| Alternative sequence | 155 – 156 | 2 | NG → VL in isoform 3. | VSP_000785 | |||||
| Alternative sequence | 157 – 1024 | 868 | Missing in isoform 3. | VSP_000786 | |||||
Experimental info | |||||||||
| Sequence conflict | 39 | 1 | N → D in BAF85362. Ref.6 | ||||||
| Sequence conflict | 138 | 1 | V → I in AAK14776. Ref.2 | ||||||
| Sequence conflict | 393 | 1 | C → R in AAK14776. Ref.2 | ||||||
| Sequence conflict | 420 | 1 | V → A in AAK53443. Ref.4 | ||||||
| Sequence conflict | 678 | 1 | R → T in AAK38730. Ref.1 | ||||||
| Sequence conflict | 791 | 1 | K → E in BAG53062. Ref.6 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Human CARD12 is a novel CED4/Apaf-1 family member that induces apoptosis." Geddes B.J., Wang L., Huang W.-J., Lavellee M., Manji G.A., Brown M., Jurman M., Cao J., Morgenstern J., Merriam S., Glucksmann M.A., DiStefano P.S., Bertin J. Biochem. Biophys. Res. Commun. 284:77-82(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [2] | "CLAN, a novel human CED-4-like gene." Damiano J.S., Stehlik C., Pio F., Godzik A., Reed J.C. Genomics 75:77-83(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4). Tissue: Lung. |
| [3] | "Identification of Ipaf, a human caspase-1-activating protein related to Apaf-1." Poyet J.-L., Srinivasula S.M., Tnani M., Razmara M., Fernandes-Alnemri T., Alnemri E.S. J. Biol. Chem. 276:28309-28313(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION. Tissue: Leukocyte. |
| [4] | "Differential expression of the caspase recruitment domain protein 12 (CARD12) during monocytic differentiation." Gingras M., Qiu J., Margolin J.F. Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [5] | "The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. Gray A.M.Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). |
| [6] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Thymus and Uterus. |
| [7] | "Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. Wilson R.K.Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [8] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [9] | "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). Tissue: Brain, Lung and Testis. |
| [10] | The European IMAGE consortium Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 586-1024 (ISOFORM 1). |
| [11] | "Heterotypic interactions among NACHT domains: implications for regulation of innate immune responses." Damiano J.S., Oliveira V., Welsh K., Reed J.C. Biochem. J. 381:213-219(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION. |
| [12] | "Novel role of PKR in inflammasome activation and HMGB1 release." Lu B., Nakamura T., Inouye K., Li J., Tang Y., Lundbaeck P., Valdes-Ferrer S.I., Olofsson P.S., Kalb T., Roth J., Zou Y., Erlandsson-Harris H., Yang H., Ting J.P., Wang H., Andersson U., Antoine D.J., Chavan S.S., Hotamisligil G.S., Tracey K.J. Nature 488:670-674(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EIF2AK2. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AY032589 mRNA. Translation: AAK38730.1. AY027787 mRNA. Translation: AAK14776.1. AY027788 mRNA. Translation: AAK14777.1. AY027789 mRNA. Translation: AAK14778.1. AY027790 mRNA. Translation: AAK14779.1. AY035391 mRNA. Translation: AAK59843.1. AF376061 mRNA. Translation: AAK53443.1. AY358152 mRNA. Translation: AAQ88519.1. AK095467 mRNA. Translation: BAG53062.1. AK292673 mRNA. Translation: BAF85362.1. AK314762 mRNA. Translation: BAG37300.1. AL121653 Genomic DNA. No translation available. CH471053 Genomic DNA. Translation: EAX00452.1. CH471053 Genomic DNA. Translation: EAX00453.1. CH471053 Genomic DNA. Translation: EAX00454.1. CH471053 Genomic DNA. Translation: EAX00455.1. BC031555 mRNA. Translation: AAH31555.1. AL389934 mRNA. Translation: CAB97523.1. |
| IPI | IPI00217430. IPI00217431. IPI00217432. IPI00293227. |
| RefSeq | NP_001186067.1. NM_001199138.1. NP_001186068.1. NM_001199139.1. NP_067032.3. NM_021209.4. |
| UniGene | Hs.574741. |
3D structure databases | |
| ProteinModelPortal | Q9NPP4. |
| ModBase | Search... |
Protein-protein interaction databases | |
| DIP | DIP-38428N. |
| IntAct | Q9NPP4. 4 interactions. |
| MINT | MINT-201147. |
| STRING | 9606.ENSP00000354159. |
PTM databases | |
| PhosphoSite | Q9NPP4. |
Polymorphism databases | |
| DMDM | 20138032. |
Proteomic databases | |
| PaxDb | Q9NPP4. |
| PRIDE | Q9NPP4. |
Protocols and materials databases | |
| DNASU | 58484. |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000342905; ENSP00000339666; ENSG00000091106. ENST00000360906; ENSP00000354159; ENSG00000091106. ENST00000402280; ENSP00000385428; ENSG00000091106. ENST00000404025; ENSP00000385090; ENSG00000091106. |
| GeneID | 58484. |
| KEGG | hsa:58484. |
| UCSC | uc002roi.3. human. uc010ezt.2. human. |
Organism-specific databases | |
| CTD | 58484. |
| GeneCards | GC02M032449. |
| HGNC | HGNC:16412. NLRC4. |
| HPA | HPA006592. |
| MIM | 606831. gene. |
| neXtProt | NX_Q9NPP4. |
| PharmGKB | PA162397671. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | NOG69057. |
| HOGENOM | HOG000059630. |
| HOVERGEN | HBG050790. |
| InParanoid | Q9NPP4. |
| KO | K12805. |
| OMA | DHCGDLA. |
| OrthoDB | EOG4Q84WQ. |
| PhylomeDB | Q9NPP4. |
Enzyme and pathway databases | |
| Reactome | REACT_6900. Immune System. |
Gene expression databases | |
| Bgee | Q9NPP4. |
| CleanEx | HS_NLRC4. |
| Genevestigator | Q9NPP4. |
| GermOnline | ENSG00000091106. Homo sapiens. |
Family and domain databases | |
| Gene3D | 1.10.533.10. 1 hit. |
| InterPro | IPR001315. CARD. IPR011029. DEATH-like_dom. IPR007111. NACHT_NTPase. IPR027417. P-loop_NTPase. [Graphical view] |
| Pfam | PF00619. CARD. 1 hit. [Graphical view] |
| SUPFAM | SSF47986. DEATH_like. 1 hit. SSF52540. SSF52540. 1 hit. |
| PROSITE | PS50209. CARD. 1 hit. PS51450. LRR. False negative. PS50837. NACHT. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| GenomeRNAi | 58484. |
| NextBio | 35464642. |
| SOURCE | Search... |
Entry information
| Entry name | NLRC4_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q9NPP4 Secondary accession number(s): A8K9F8 Q96J83 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any 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
| Human chromosome 2 Human chromosome 2: entries, gene names and cross-references to MIM |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with
