NLR family CARD domain-containing protein 4

Names and origin

Protein names

Recommended name:
    NLR family CARD domain-containing protein 4
Alternative name(s):
    Caspase recruitment domain-containing protein 12
    Ice protease-activating factor
      Short name=Ipaf
    CARD, LRR, and NACHT-containing protein
      Short name=Clan protein

Gene names

Name:	NLRC4
Synonyms:	CARD12, CLAN, CLAN1, IPAF
ORF Names:	UNQ6189/PRO20215

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	1024 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Plays a role in the promotion of apoptosis.
Subunit structure	Self-associates and binds to ASC, pro-caspase-1, NOD2, BCL10 and NALP1 (NAC) by CARD-CARD interaction.
Subcellular location	Cytoplasm. Note: Cytoplasmic filaments.
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.
Sequence similarities	Contains 1 CARD domain. Contains 14 LRR (leucine-rich) repeats. Contains 1 NACHT domain.

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Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Domain	Leucine-rich repeat Repeat
Ligand	ATP-binding Nucleotide-binding
Gene Ontology (GO)
Biological process	activation of caspase activity Inferred from direct assay. Source: HGNC defense response to bacterium Inferred from direct assay. Source: HGNC detection of bacterium Inferred from direct assay. Source: HGNC interleukin-1 beta secretion Inferred from direct assay. Source: HGNC positive regulation of apoptosis Ref.1 Inferred from mutant phenotype. Source: HGNC
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from direct assay. Source: HGNC magnesium ion binding Traceable author statement. Source: HGNC protein homodimerization activity Inferred from direct assay. Source: HGNC
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
CASP1	P29466	1	EBI-1222527,EBI-516667

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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.

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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

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

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

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Sequences

Sequence		Length	Mass (Da)
Isoform 1 (CLANA) [UniParc]. Last modified January 31, 2002. Version 2. Checksum: 49378DBB54938E0F Show »	FASTA	1,024	116,159
10 20 30 40 50 60 MNFIKDNSRA LIQRMGMTVI KQITDDLFVW NVLNREEVNI ICCEKVEQDA ARGIIHMILK 70 80 90 100 110 120 KGSESCNLFL KSLKEWNYPL FQDLNGQSLF HQTSEGDLDD LAQDLKDLYH TPSFLNFYPL 130 140 150 160 170 180 GEDIDIIFNL KSTFTEPVLW RKDQHHHRVE QLTLNGLLQA LQSPCIIEGE SGKGKSTLLQ 190 200 210 220 230 240 RIAMLWGSGK CKALTKFKFV FFLRLSRAQG GLFETLCDQL LDIPGTIRKQ TFMAMLLKLR 250 260 270 280 290 300 QRVLFLLDGY NEFKPQNCPE IEALIKENHR FKNMVIVTTT TECLRHIRQF GALTAEVGDM 310 320 330 340 350 360 TEDSAQALIR EVLIKELAEG LLLQIQKSRC LRNLMKTPLF VVITCAIQMG ESEFHSHTQT 370 380 390 400 410 420 TLFHTFYDLL IQKNKHKHKG VAASDFIRSL DHCGDLALEG VFSHKFDFEL QDVSSVNEDV 430 440 450 460 470 480 LLTTGLLCKY TAQRFKPKYK FFHKSFQEYT AGRRLSSLLT SHEPEEVTKG NGYLQKMVSI 490 500 510 520 530 540 SDITSTYSSL LRYTCGSSVE ATRAVMKHLA AVYQHGCLLG LSIAKRPLWR QESLQSVKNT 550 560 570 580 590 600 TEQEILKAIN INSFVECGIH LYQESTSKSA LSQEFEAFFQ GKSLYINSGN IPDYLFDFFE 610 620 630 640 650 660 HLPNCASALD FIKLDFYGGA MASWEKAAED TGGIHMEEAP ETYIPSRAVS LFFNWKQEFR 670 680 690 700 710 720 TLEVTLRDFS KLNKQDIRYL GKIFSSATSL RLQIKRCAGV AGSLSLVLST CKNIYSLMVE 730 740 750 760 770 780 ASPLTIEDER HITSVTNLKT LSIHDLQNQR LPGGLTDSLG NLKNLTKLIM DNIKMNEEDA 790 800 810 820 830 840 IKLAEGLKNL KKMCLFHLTH LSDIGEGMDY IVKSLSSEPC DLEEIQLVSC CLSANAVKIL 850 860 870 880 890 900 AQNLHNLVKL SILDLSENYL EKDGNEALHE LIDRMNVLEQ LTALMLPWGC DVQGSLSSLL 910 920 930 940 950 960 KHLEEVPQLV KLGLKNWRLT DTEIRILGAF FGKNPLKNFQ QLNLAGNRVS SDGWLAFMGV 970 980 990 1000 1010 1020 FENLKQLVFF DFSTKEFLPD PALVRKLSQV LSKLTFLQEA RLVGWQFDDD DLSVITGAFK LVTA « Hide
Isoform 2 (CLANB). Checksum: 764417DD658B1DFD Show »	FASTA	359	40,623
10 20 30 40 50 60 MNFIKDNSRA LIQRMGMTVI KQITDDLFVW NVLNREEVNI ICCEKVEQDA ARGIIHMILK 70 80 90 100 110 120 KGSESCNLFL KSLKEWNYPL FQDLNGQSGL TDSLGNLKNL TKLIMDNIKM NEEDAIKLAE 130 140 150 160 170 180 GLKNLKKMCL FHLTHLSDIG EGMDYIVKSL SSEPCDLEEI QLVSCCLSAN AVKILAQNLH 190 200 210 220 230 240 NLVKLSILDL SENYLEKDGN EALHELIDRM NVLEQLTALM LPWGCDVQGS LSSLLKHLEE 250 260 270 280 290 300 VPQLVKLGLK NWRLTDTEIR ILGAFFGKNP LKNFQQLNLA GNRVSSDGWL AFMGVFENLK 310 320 330 340 350 QLVFFDFSTK EFLPDPALVR KLSQVLSKLT FLQEARLVGW QFDDDDLSVI TGAFKLVTA « Hide
Isoform 3 (CLANC). Checksum: 933CB2315528D67A Show »	FASTA	156	18,295
10 20 30 40 50 60 MNFIKDNSRA LIQRMGMTVI KQITDDLFVW NVLNREEVNI ICCEKVEQDA ARGIIHMILK 70 80 90 100 110 120 KGSESCNLFL KSLKEWNYPL FQDLNGQSLF HQTSEGDLDD LAQDLKDLYH TPSFLNFYPL 130 140 150 GEDIDIIFNL KSTFTEPVLW RKDQHHHRVE QLTLVL « Hide
Isoform 4 (CLAND). Checksum: BD090CD064330D1D Show »	FASTA	92	10,646
10 20 30 40 50 60 MNFIKDNSRA LIQRMGMTVI KQITDDLFVW NVLNREEVNI ICCEKVEQDA ARGIIHMILK 70 80 90 KGSESCNLFL KSLKEWNYPL FQDLNGQSLL TA « Hide

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References

	« Hide 'large scale' referencesShow '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: 11374873] [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: 11472070] [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: 11390368] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). 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: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain, Lung and Testis.
[7]	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).
+	Additional computationally mapped references.

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Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Cross-references

Sequence databases
	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. BC031555 mRNA. Translation: AAH31555.1. AL389934 mRNA. Translation: CAB97523.1.
IPI	IPI00217430. IPI00217431. IPI00217432. IPI00293227.
RefSeq	NP_067032.3.
UniGene	Hs.574741
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NPP4. 2 interactions.
Proteomic databases
PRIDE	Q9NPP4.
Genome annotation databases
Ensembl	ENSG00000091106. Homo sapiens. [Contig view]
GeneID	58484.
KEGG	hsa:58484.
Organism-specific databases
GeneCards	GC02M032303.
H-InvDB	HIX0001955.
HGNC	HGNC:16412. NLRC4.
MIM	606831. gene.
PharmGKB	PA134944029.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9NPP4.
HOVERGEN	Q9NPP4.
OMA	Q9NPP4. RNLMKTP.
Gene expression databases
ArrayExpress	Q9NPP4.
Bgee	Q9NPP4.
CleanEx	HS_NLRC4.
GermOnline	ENSG00000091106. Homo sapiens.
Family and domain databases
InterPro	IPR001315. CARD. IPR011029. DEATH-like. IPR007111. NACHT_NTPase. [Graphical view]
Gene3D	G3DSA:1.10.533.10. DEATH_like. 1 hit.
Pfam	PF00619. CARD. 1 hit. PF05729. NACHT. 1 hit. [Graphical view]
PROSITE	PS50209. CARD. 1 hit. PS50837. NACHT. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	64934.
SOURCE	Search...

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Entry information

Entry name

NLRC4_HUMAN

Accession

Primary (citable) accession number: Q9NPP4
Secondary accession number(s): Q96J81, Q96J82, Q96J83

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 31, 2002
Last sequence update:	January 31, 2002
Last modified:	June 16, 2009
This is version 78 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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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

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Natural variations

Experimental info

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents