NLRC4

Protein identityUniProt · HPA

UniProt accession

Q9NPP4

Gene

NLRC4

Ensembl

ENSG00000091106

Chromosome

2

Canonical length

1024 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins

Subcellular location

Vesicles,Plasma membrane,Cytosol

Quaternary structure

Homooligomer

OverviewNCBI Gene

This gene encodes a member of the caspase recruitment domain-containing NLR family. Family members play essential roles in innate immune response to a wide range of pathogenic organisms, tissue damage and other cellular stresses. Mutations in this gene result in autoinflammation with infantile enterocolitis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

Canonical amino-acid sequenceUniProt

1024 residues, UniProt reviewed canonical sequence.

>Q9NPP4|NLRC4
     1  MNFIKDNSRA LIQRMGMTVI KQITDDLFVW NVLNREEVNI ICCEKVEQDA ARGIIHMILK
    61  KGSESCNLFL KSLKEWNYPL FQDLNGQSLF HQTSEGDLDD LAQDLKDLYH TPSFLNFYPL
   121  GEDIDIIFNL KSTFTEPVLW RKDQHHHRVE QLTLNGLLQA LQSPCIIEGE SGKGKSTLLQ
   181  RIAMLWGSGK CKALTKFKFV FFLRLSRAQG GLFETLCDQL LDIPGTIRKQ TFMAMLLKLR
   241  QRVLFLLDGY NEFKPQNCPE IEALIKENHR FKNMVIVTTT TECLRHIRQF GALTAEVGDM
   301  TEDSAQALIR EVLIKELAEG LLLQIQKSRC LRNLMKTPLF VVITCAIQMG ESEFHSHTQT
   361  TLFHTFYDLL IQKNKHKHKG VAASDFIRSL DHCGDLALEG VFSHKFDFEL QDVSSVNEDV
   421  LLTTGLLCKY TAQRFKPKYK FFHKSFQEYT AGRRLSSLLT SHEPEEVTKG NGYLQKMVSI
   481  SDITSTYSSL LRYTCGSSVE ATRAVMKHLA AVYQHGCLLG LSIAKRPLWR QESLQSVKNT
   541  TEQEILKAIN INSFVECGIH LYQESTSKSA LSQEFEAFFQ GKSLYINSGN IPDYLFDFFE
   601  HLPNCASALD FIKLDFYGGA MASWEKAAED TGGIHMEEAP ETYIPSRAVS LFFNWKQEFR
   661  TLEVTLRDFS KLNKQDIRYL GKIFSSATSL RLQIKRCAGV AGSLSLVLST CKNIYSLMVE
   721  ASPLTIEDER HITSVTNLKT LSIHDLQNQR LPGGLTDSLG NLKNLTKLIM DNIKMNEEDA
   781  IKLAEGLKNL KKMCLFHLTH LSDIGEGMDY IVKSLSSEPC DLEEIQLVSC CLSANAVKIL
   841  AQNLHNLVKL SILDLSENYL EKDGNEALHE LIDRMNVLEQ LTALMLPWGC DVQGSLSSLL
   901  KHLEEVPQLV KLGLKNWRLT DTEIRILGAF FGKNPLKNFQ QLNLAGNRVS SDGWLAFMGV
   961  FENLKQLVFF DFSTKEFLPD PALVRKLSQV LSKLTFLQEA RLVGWQFDDD DLSVITGAFK
  1021  LVTA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NLRC4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.23

Highest tissue expression

11 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NLRC4.

Disease | AllUniProt

Conditions NLRC4 is implicated in, by any mechanism.

• Autoinflammation with infantile enterocolitis (AIFEC) MIM:616050
• Familial cold autoinflammatory syndrome 4 (FCAS4) MIM:616115

Disease | GeneticClinVar

14 pathogenic / likely-pathogenic of 927 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Periodic fever-infantile enterocolitis-autoinflammatory syndrome
• Familial cold autoinflammatory syndrome 4
• Autoinflammatory syndrome
• Syndrome of entercolitis and autoinflmmation caused by mutation of NLRC4 (SCAN4)

Disease | ImmuneIEDB

Conditions an epitope on NLRC4 was assayed in.

• berylliosis T cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.92

gnomAD pLI

0

gnomAD missense Z

0.98

DepMap mean gene effect

0.07

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• activation of innate immune response
• apoptotic process
• defense response to bacterium
• detection of bacterium
• icosanoid biosynthetic process
• inflammatory response
• innate immune response
• pattern recognition receptor signaling pathway
• positive regulation of apoptotic process
• positive regulation of inflammatory response
• positive regulation of interleukin-1 beta production
• positive regulation of NF-kappaB transcription factor activity
• positive regulation of protein processing
• protein homooligomerization
• pyroptotic inflammatory response

Molecular functions

• ATP binding
• caspase binding
• endopeptidase activator activity
• identical protein binding
• magnesium ion binding
• protein homodimerization activity

Cellular components

• canonical inflammasome complex
• cytoplasm
• cytosol
• IPAF inflammasome complex
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• CARD domain
• NACHT nucleoside triphosphatase
• Death-like domain superfamily
• P-loop containing nucleoside triphosphate hydrolase
• Leucine-rich repeat domain superfamily
• NLRC4, helical domain
• Nlrc4-like, winged helix domain
• Caspase recruitment domain
• NACHT domain
• NLRC4 helical domain
• Nlrc4-like, winged helix domain
• NLR family CARD domain-containing protein 4

KeywordsUniProt

• Apoptosis
• ATP-binding
• Cytoplasm
• Immunity
• Inflammasome
• Inflammatory response
• Innate immunity
• Leucine-rich repeat
• Nucleotide-binding
• Phosphoprotein
• Repeat

InteractionsUniProt · HPA

Protein binding partners of NLRC4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• EIF2AK2
• PYCARD
• CASP1