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Q9H257 (CARD9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Caspase recruitment domain-containing protein 9

Short name=hCARD9
Gene names
Name:CARD9
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length536 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Adapter protein that plays a key role in innate immune response to a number of intracellular pathogens, such as C.albicans and L.monocytogenes. Is at the crossroads of ITAM-tyrosine kinase and the Toll-like receptors (TLR) and NOD2 signaling pathways. Probably controls various innate immune response pathways depending on the intracellular pathogen. In response to L.monocytogenes infection, acts by connecting NOD2 recognition of peptidoglycan to downstream activation of MAP kinases (MAPK) without activating NF-kappa-B. Also involved in activation of myeloid cells via classical ITAM-associated receptors and TLR: required for TLR-mediated activation of MAPK, while it is not required for TLR-induced activation of NF-kappa-B By similarity. Controls CLEC7A (dectin-1)-mediated myeloid cell activation induced by the yeast cell wall component zymosan, leading to cytokine production and innate anti-fungal immunity: acts by regulating BCL10-MALT1-mediated NF-kappa-B activation pathway. Activates NF-kappa-B via BCL10. In response to the hyphal form of C.albicans, mediates CLEC6A (dectin-2)-induced I-kappa-B kinase ubiquitination, leading to NF-kappa-B activation via interaction with BCL10. In response to fungal infection, may be required for the development and subsequent differentiation of interleukin 17-producing T helper (TH-17) cells. Ref.1

Subunit structure

Interacts with NOD2 and RIPK2. Interacts with VHL; without leading to protein degradation By similarity. Self-associates. Interacts (via CARD domain) with BCL10 (via CARD domain). Ref.1

Subcellular location

Cytoplasm Ref.1.

Tissue specificity

Highly expressed in spleen. Also detected in liver, placenta, lung, peripheral blood leukocytes and in brain.

Post-translational modification

Phosphorylated at Thr-531 and Thr-533 by CK2 following interaction with VHL, leading to inhibit the ability to activate NF-kappa-B By similarity.

Involvement in disease

Candidiasis, familial, 2 (CANDF2) [MIM:212050]: A primary immunodeficiency disorder with altered immune responses and impaired clearance of fungal infections, selective against Candida. It is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida, mainly Candida albicans.
Note: The disease is caused by mutations affecting the gene represented in this entry. Defects induce reduced numbers of CD4+ Th17 lymphocytes as well as a lack of monocyte-derived cytokines in response to Candida strains. Neutrophils show a selective Candida albicans killing defect with abnormal ultrastructural phagolysosomes and outgrowth of hyphae (Ref.8). Ref.7 Ref.8 Ref.9

Sequence similarities

Contains 1 CARD domain.

Ontologies

Keywords
   Biological processImmunity
Innate immunity
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainCoiled coil
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdefense response to Gram-positive bacterium

Inferred from electronic annotation. Source: Ensembl

defense response to virus

Inferred from electronic annotation. Source: Ensembl

innate immune response

Traceable author statement. Source: Reactome

nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway

Traceable author statement. Source: Reactome

nucleotide-binding oligomerization domain containing signaling pathway

Traceable author statement. Source: Reactome

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from expression pattern Ref.1. Source: UniProtKB

positive regulation of JNK cascade

Inferred from direct assay PubMed 17187069. Source: MGI

positive regulation of interleukin-6 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of stress-activated MAPK cascade

Inferred from direct assay PubMed 17187069. Source: MGI

positive regulation of tumor necrosis factor production

Inferred from electronic annotation. Source: Ensembl

regulation of apoptotic process

Inferred from electronic annotation. Source: InterPro

regulation of interleukin-2 biosynthetic process

Inferred from electronic annotation. Source: Ensembl

regulation of interleukin-6 biosynthetic process

Inferred from electronic annotation. Source: Ensembl

regulation of tumor necrosis factor biosynthetic process

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to exogenous dsRNA

Inferred from electronic annotation. Source: Ensembl

response to fungus

Inferred from electronic annotation. Source: Ensembl

response to muramyl dipeptide

Inferred from electronic annotation. Source: Ensembl

response to peptidoglycan

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from direct assay Ref.1. Source: UniProtKB

   Molecular_functionCARD domain binding

Inferred from physical interaction Ref.1. Source: UniProtKB

protein homodimerization activity

Inferred from physical interaction Ref.1. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9H257-1)

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: Q9H257-2)

The sequence of this isoform differs from the canonical sequence as follows:
     482-492: LSSGEPPEKER → PAGLPGIGAVC
     493-536: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q9H257-3)

The sequence of this isoform differs from the canonical sequence as follows:
     360-366: AIATREE → STQMEGL
     367-536: Missing.
Note: No experimental confirmation available. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 536536Caspase recruitment domain-containing protein 9
PRO_0000144082

Regions

Domain6 – 9893CARD
Coiled coil117 – 277161 Potential
Coiled coil332 – 41988 Potential

Amino acid modifications

Modified residue4601Phosphoserine Ref.6
Modified residue5311Phosphothreonine; by CK2 By similarity
Modified residue5331Phosphothreonine; by CK2 By similarity

Natural variations

Alternative sequence360 – 3667AIATREE → STQMEGL in isoform 3.
VSP_024390
Alternative sequence367 – 536170Missing in isoform 3.
VSP_024391
Alternative sequence482 – 49211LSSGEPPEKER → PAGLPGIGAVC in isoform 2.
VSP_024392
Alternative sequence493 – 53644Missing in isoform 2.
VSP_024393
Natural variant121S → N. Ref.1 Ref.2
Corresponds to variant rs4077515 [ dbSNP | Ensembl ].
VAR_048607
Natural variant721G → S in CANDF2; loss of protein expression. Ref.8
VAR_070828
Natural variant1011R → C in CANDF2. Ref.9
VAR_070829
Natural variant3731R → P in CANDF2; loss of protein expression. Ref.8
VAR_070830

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified April 3, 2007. Version 2.
Checksum: 6EB18353112F2BAC

FASTA53662,241
        10         20         30         40         50         60 
MSDYENDDEC WSVLEGFRVT LTSVIDPSRI TPYLRQCKVL NPDDEEQVLS DPNLVIRKRK 

        70         80         90        100        110        120 
VGVLLDILQR TGHKGYVAFL ESLELYYPQL YKKVTGKEPA RVFSMIIDAS GESGLTQLLM 

       130        140        150        160        170        180 
TEVMKLQKKV QDLTALLSSK DDFIKELRVK DSLLRKHQER VQRLKEECEA GSRELKRCKE 

       190        200        210        220        230        240 
ENYDLAMRLA HQSEEKGAAL MRNRDLQLEI DQLKHSLMKA EDDCKVERKH TLKLRHAMEQ 

       250        260        270        280        290        300 
RPSQELLWEL QQEKALLQAR VQELEASVQE GKLDRSSPYI QVLEEDWRQA LRDHQEQANT 

       310        320        330        340        350        360 
IFSLRKDLRQ GEARRLRCME EKEMFELQCL ALRKDSKMYK DRIEAILLQM EEVAIERDQA 

       370        380        390        400        410        420 
IATREELHAQ HARGLQEKDA LRKQVRELGE KADELQLQVF QCEAQLLAVE GRLRRQQLET 

       430        440        450        460        470        480 
LVLSSDLEDG SPRRSQELSL PQDLEDTQLS DKGCLAGGGS PKQPFAALHQ EQVLRNPHDA 

       490        500        510        520        530 
GLSSGEPPEK ERRRLKESFE NYRRKRALRK MQKGWRQGEE DRENTTGSDN TDTEGS 

« Hide

Isoform 2 [UniParc].

Checksum: AADBCF6A5E81125F
Show »

FASTA49256,667
Isoform 3 [UniParc].

Checksum: EC1CB0ABCF6C7CF4
Show »

FASTA36642,953

References

« Hide 'large scale' references
[1]"CARD9 is a novel caspase recruitment domain-containing protein that interacts with Bcl10/CLAP and activates NF-kappa B."
Bertin J., Guo Y., Wang L., Srinivasula S.M., Jacobson M.D., Poyet J.-L., Merriam S., Du M.-Q., Dyer M.J.S., Robison K.E., DiStefano P.S., Alnemri E.S.
J. Biol. Chem. 275:41082-41086(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ASN-12, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH BCL10.
[2]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), VARIANT ASN-12.
Tissue: Retinoblastoma and Synovium.
[3]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton 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. expand/collapse author list , 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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 2).
Tissue: Muscle.
[6]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-460, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[7]"A homozygous CARD9 mutation in a family with susceptibility to fungal infections."
Glocker E.-O., Hennigs A., Nabavi M., Schaeffer A.A., Woellner C., Salzer U., Pfeifer D., Veelken H., Warnatz K., Tahami F., Jamal S., Manguiat A., Rezaei N., Amirzargar A.A., Plebani A., Hannesschlaeger N., Gross O., Ruland J., Grimbacher B.
N. Engl. J. Med. 361:1727-1735(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CANDF2.
[8]"Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency."
Drewniak A., Gazendam R.P., Tool A.T., van Houdt M., Jansen M.H., van Hamme J.L., van Leeuwen E.M., Roos D., Scalais E., de Beaufort C., Janssen H., van den Berg T.K., Kuijpers T.W.
Blood 121:2385-2392(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CANDF2 SER-72 AND PRO-373.
[9]"Deep dermatophytosis and inherited CARD9 deficiency."
Lanternier F., Pathan S., Vincent Q.B., Liu L., Cypowyj S., Prando C., Migaud M., Taibi L., Ammar-Khodja A., Boudghene Stambouli O., Guellil B., Jacobs F., Goffard J.C., Schepers K., del Marmol V., Boussofara L., Denguezli M., Larif M. expand/collapse author list , Bachelez H., Michel L., Lefranc G., Hay R., Jouvion G., Chretien F., Fraitag S., Bougnoux M.E., Boudia M., Abel L., Lortholary O., Casanova J.L., Picard C., Grimbacher B., Puel A.
N. Engl. J. Med. 369:1704-1714(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CANDF2 CYS-101.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF311287 mRNA. Translation: AAG28790.1.
AK024001 mRNA. Translation: BAB14766.1.
AK292081 mRNA. Translation: BAF84770.1.
AL592301 Genomic DNA. Translation: CAI13931.1.
AL592301 Genomic DNA. Translation: CAI13932.1.
CH471090 Genomic DNA. Translation: EAW88220.1.
BC008877 mRNA. Translation: AAH08877.1.
RefSeqNP_434700.2. NM_052813.4.
NP_434701.1. NM_052814.3.
UniGeneHs.528581.
Hs.694071.

3D structure databases

ProteinModelPortalQ9H257.
SMRQ9H257. Positions 11-98, 160-185.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122094. 6 interactions.
IntActQ9H257. 6 interactions.
STRING9606.ENSP00000360797.

PTM databases

PhosphoSiteQ9H257.

Polymorphism databases

DMDM143811370.

Proteomic databases

PaxDbQ9H257.
PRIDEQ9H257.

Protocols and materials databases

DNASU64170.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000315908; ENSP00000323719; ENSG00000187796. [Q9H257-3]
ENST00000371732; ENSP00000360797; ENSG00000187796. [Q9H257-1]
ENST00000371734; ENSP00000360799; ENSG00000187796. [Q9H257-2]
ENST00000489932; ENSP00000451368; ENSG00000187796. [Q9H257-3]
GeneID64170.
KEGGhsa:64170.
hsa:728489.
UCSCuc004chg.3. human. [Q9H257-1]
uc010nbj.2. human. [Q9H257-3]
uc022bpo.1. human. [Q9H257-2]

Organism-specific databases

CTD64170.
728489.
GeneCardsGC09M139259.
HGNCHGNC:16391. CARD9.
MIM212050. phenotype.
607212. gene.
neXtProtNX_Q9H257.
Orphanet1334. Chronic mucocutaneous candidiasis.
PharmGKBPA26077.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG243105.
HOGENOMHOG000231538.
HOVERGENHBG058091.
InParanoidQ9H257.
KOK12794.
K17808.
OMAQLLMSEV.
OrthoDBEOG747PH5.
PhylomeDBQ9H257.
TreeFamTF351139.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

BgeeQ9H257.
CleanExHS_CARD9.
GenevestigatorQ9H257.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
InterProIPR001315. CARD.
IPR011029. DEATH-like_dom.
[Graphical view]
PfamPF00619. CARD. 1 hit.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
PROSITEPS50209. CARD. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCARD9.
NextBio66079.
PROQ9H257.
SOURCESearch...

Entry information

Entry nameCARD9_HUMAN
AccessionPrimary (citable) accession number: Q9H257
Secondary accession number(s): Q5SXM5, Q5SXM6, Q9H854
Entry history
Integrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: April 3, 2007
Last modified: April 16, 2014
This is version 113 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM