NLRP4
NACHT, LRR and PYD domains-containing protein 4
Also known as: CLR19.5, CT58, FLJ32126, NALP4, NALP4_HUMAN, PAN2, PYPAF4, RNH2
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q96MN2
- Gene
- NLRP4
- Ensembl
- ENSG00000160505
- Chromosome
- 19
- Canonical length
- 994 aa
- Protein class
- Predicted intracellular proteins
- Subcellular location
- Mitochondria
OverviewNCBI Gene
The protein encoded by this gene is a member of the nucleotide-binding and leucine-rich repeat receptor (NLR) family, and is predicted to contain an N-terminal pyrin effector domain (PYD), a centrally-located nucleotide-binding and oligomerization domain (NACHT) and C-terminal leucine-rich repeats (LRR). This gene product has a demonstrated role as a negative regulator of autophagy and type I interferon signaling pathways as a result of protein interactions with its NACHT domain. The PYD domain has also been shown to be important in the inhibition of NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells). [provided by RefSeq, Dec 2016]
Canonical amino-acid sequenceUniProt
994 residues, UniProt reviewed canonical sequence.
>Q96MN2|NLRP4
1 MAASFFSDFG LMWYLEELKK EEFRKFKEHL KQMTLQLELK QIPWTEVKKA SREELANLLI
61 KHYEEQQAWN ITLRIFQKMD RKDLCMKVMR ERTGYTKTYQ AHAKQKFSRL WSSKSVTEIH
121 LYFEEEVKQE ECDHLDRLFA PKEAGKQPRT VIIQGPQGIG KTTLLMKLMM AWSDNKIFRD
181 RFLYTFYFCC RELRELPPTS LADLISREWP DPAAPITEIV SQPERLLFVI DSFEELQGGL
241 NEPDSDLCGD LMEKRPVQVL LSSLLRKKML PEASLLIAIK PVCPKELRDQ VTISEIYQPR
301 GFNESDRLVY FCCFFKDPKR AMEAFNLVRE SEQLFSICQI PLLCWILCTS LKQEMQKGKD
361 LALTCQSTTS VYSSFVFNLF TPEGAEGPTP QTQHQLKALC SLAAEGMWTD TFEFCEDDLR
421 RNGVVDADIP ALLGTKILLK YGERESSYVF LHVCIQEFCA ALFYLLKSHL DHPHPAVRCV
481 QELLVANFEK ARRAHWIFLG CFLTGLLNKK EQEKLDAFFG FQLSQEIKQQ IHQCLKSLGE
541 RGNPQGQVDS LAIFYCLFEM QDPAFVKQAV NLLQEANFHI IDNVDLVVSA YCLKYCSSLR
601 KLCFSVQNVF KKEDEHSSTS DYSLICWHHI CSVLTTSGHL RELQVQDSTL SESTFVTWCN
661 QLRHPSCRLQ KLGINNVSFS GQSVLLFEVL FYQPDLKYLS FTLTKLSRDD IRSLCDALNY
721 PAGNVKELAL VNCHLSPIDC EVLAGLLTNN KKLTYLNVSC NQLDTGVPLL CEALCSPDTV
781 LVYLMLAFCH LSEQCCEYIS EMLLRNKSVR YLDLSANVLK DEGLKTLCEA LKHPDCCLDS
841 LCLVKCFITA AGCEDLASAL ISNQNLKILQ IGCNEIGDVG VQLLCRALTH TDCRLEILGL
901 EECGLTSTCC KDLASVLTCS KTLQQLNLTL NTLDHTGVVV LCEALRHPEC ALQVLGLRKT
961 DFDEETQALL TAEEERNPNL TITDDCDTIT RVEILocalizationUniProt · AlphaFold · HPA
Whether an antibody against NLRP4 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
- 6.6 nTPM
Expression across tissuesHPA
Tissue
- testis: 6.6 nTPM
- tonsil: 4.7 nTPM
- lymph node: 1.5 nTPM
- ovary: 1.4 nTPM
- appendix: 0.5 nTPM
- spinal cord: 0.2 nTPM
Single-cell type
- oocytes: 51 nCPM
- late primary spermatocytes: 16 nCPM
- early spermatids: 14 nCPM
- undifferentiated spermatogonia: 9.4 nCPM
- late spermatids: 6.7 nCPM
- microglia: 5.5 nCPM
Immune cell
- naive B-cell: 0.3 nTPM
- basophil: 0 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
- gdT-cell: 0 nTPM
- intermediate monocyte: 0 nTPM
Brain region
- white matter: 1.1 nTPM
- medulla oblongata: 0.7 nTPM
- pons: 0.6 nTPM
- cerebellum: 0.5 nTPM
- hippocampal formation: 0.5 nTPM
- thalamus: 0.5 nTPM
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)
- 0.78
- gnomAD pLI
- 0
- gnomAD missense Z
- -0.74
- DepMap mean gene effect
- 0.02
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- inflammatory response
- negative regulation of innate immune response
- regulation of inflammatory response
Molecular functions
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Leucine-rich repeat
- DAPIN domain
- NACHT nucleoside triphosphatase
- Death-like domain superfamily
- P-loop containing nucleoside triphosphate hydrolase
- Leucine-rich repeat domain superfamily
- NOD1/2, winged helix domain
- NACHT, LRR and PYD domains-containing protein, helical domain HD2
- NLRP family, innate immunity and inflammation regulators
- PAAD/DAPIN/Pyrin domain
- NACHT domain
- Leucine Rich repeat
- NLRC4 helical domain HD2
- NOD2 winged helix domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of NLRP4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads NLRP4 as an antibody target. Whether an autoantibody or antibody against NLRP4 could matter depends on whether native NLRP4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
NLRP4 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label NLRP4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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