Q9NPP4 (NLRC4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names 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

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

Protein attributes

Sequence length	1024 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

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.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Domain	Leucine-rich repeat Repeat
Ligand	ATP-binding Nucleotide-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	activation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from direct assay. Source: HGNC activation of innate immune response Traceable author statement. Source: Reactome defense response to bacterium Inferred from direct assay. Source: HGNC detection of bacterium Inferred from direct assay. Source: HGNC innate immune response Traceable author statement. Source: Reactome interleukin-1 beta secretion Inferred from direct assay. Source: HGNC positive regulation of apoptotic process Inferred from mutant phenotype Ref.1. Source: HGNC
Cellular component	cytosol Traceable author statement. Source: Reactome
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...

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
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

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (CLANA) [UniParc]. Last modified January 31, 2002. Version 2. Checksum: 49378DBB54938E0F	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
	Isoform 2 (CLANB) [UniParc]. Checksum: 764417DD658B1DFD	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
	Isoform 3 (CLANC) [UniParc]. Checksum: 933CB2315528D67A	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
	Isoform 4 (CLAND) [UniParc]. Checksum: BD090CD064330D1D	FASTA	92	10,646
	10 20 30 40 50 60 MNFIKDNSRA LIQRMGMTVI KQITDDLFVW NVLNREEVNI ICCEKVEQDA ARGIIHMILK 70 80 90 KGSESCNLFL KSLKEWNYPL FQDLNGQSLL TA

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. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [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. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Uterus.
[7]	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. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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.
[9]	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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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. AK314762 mRNA. Translation: BAG37300.1. 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.
SMR	Q9NPP4. Positions 1-102, 160-186, 686-1021.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NPP4. 2 interactions.
MINT	MINT-201147.
STRING	Q9NPP4.
Polymorphism databases
DMDM	20138032.
Proteomic databases
PRIDE	Q9NPP4.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000360906; ENSP00000354159; ENSG00000091106. ENST00000402280; ENSP00000385428; ENSG00000091106. ENST00000404025; ENSP00000385090; ENSG00000091106.
GeneID	58484.
KEGG	hsa:58484.
UCSC	uc002roi.2. human. uc010ezt.1. human.
Organism-specific databases
CTD	58484.
GeneCards	GC02M032449.
H-InvDB	HIX0001955.
HGNC	HGNC:16412. NLRC4.
MIM	606831. gene.
neXtProt	NX_Q9NPP4.
PharmGKB	PA162397671.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG05722.
GeneTree	ENSGT00530000064142.
HOGENOM	HBG283816.
HOVERGEN	HBG050790.
InParanoid	Q9NPP4.
OMA	CIIEGES.
OrthoDB	EOG4Q84WQ.
PhylomeDB	Q9NPP4.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q9NPP4.
Bgee	Q9NPP4.
CleanEx	HS_NLRC4.
Genevestigator	Q9NPP4.
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.
KO	K12805.
Pfam	PF00619. CARD. 1 hit. [Graphical view]
SUPFAM	SSF47986. DEATH_like. 1 hit.
PROSITE	PS50209. CARD. 1 hit. PS50837. NACHT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	64934.
SOURCE	Search...

Entry information

Entry name

NLRC4_HUMAN

Accession

Primary (citable) accession number: Q9NPP4
Secondary accession number(s): B2RBQ3 , D6W580, Q96J81, Q96J82, Q96J83

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 31, 2002
Last sequence update:	January 31, 2002
Last modified:	January 25, 2012
This is version 102 of the entry and version 2 of the sequence. [Complete 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.