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Protein

Caspase recruitment domain-containing protein 9

Gene

Card9

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (PubMed:17514206). Probably controls various innate immune response pathways depending on the intracellular pathogen. 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 (PubMed:16862125). 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 (PubMed:20538615). 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 (PubMed:17187069). In response to fungal infection, may be required for the development and subsequent differentiation of interleukin 17-producing T helper (TH-17) cells (PubMed:17450144). 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 (PubMed:17486093).6 Publications

GO - Molecular functioni

GO - Biological processi

  • defense response to Gram-positive bacterium Source: MGI
  • defense response to virus Source: MGI
  • I-kappaB kinase/NF-kappaB signaling Source: Ensembl
  • innate immune response Source: UniProtKB-KW
  • nucleotide-binding oligomerization domain containing signaling pathway Source: Reactome
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
  • positive regulation of innate immune response Source: MGI
  • positive regulation of interleukin-6 production Source: MGI
  • positive regulation of JNK cascade Source: MGI
  • positive regulation of stress-activated MAPK cascade Source: MGI
  • positive regulation of tumor necrosis factor production Source: MGI
  • regulation of apoptotic process Source: InterPro
  • regulation of interleukin-2 biosynthetic process Source: MGI
  • regulation of interleukin-6 biosynthetic process Source: MGI
  • regulation of tumor necrosis factor biosynthetic process Source: MGI
  • response to drug Source: MGI
  • response to exogenous dsRNA Source: MGI
  • response to fungus Source: MGI
  • response to muramyl dipeptide Source: MGI
  • response to peptidoglycan Source: MGI
Complete GO annotation...

Keywords - Biological processi

Immunity, Innate immunity

Enzyme and pathway databases

ReactomeiR-MMU-168638. NOD1/2 Signaling Pathway.
R-MMU-5607764. CLEC7A (Dectin-1) signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Caspase recruitment domain-containing protein 9
Gene namesi
Name:Card9
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:2685628. Card9.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

Mice were born at the normal Mendelian ratio without obvious anatomical defects but display impaired innate immunity (PubMed:16862125, PubMed:17187069). All mice die within 5 days after infection by C.albicans whereas more than half of the control mice survive for more than 12 days. Impaired zymosan-induced cytokine production. No defects in adaptive immunity (PubMed:16862125). Following infection by L.monocytogenes, mice fail to clear infection and show altered cytokine production (PubMed:17187069).4 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 536536Caspase recruitment domain-containing protein 9PRO_0000428725Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21PhosphoserineBy similarity
Modified residuei277 – 2771PhosphoserineBy similarity
Modified residuei424 – 4241PhosphoserineBy similarity
Modified residuei425 – 4251PhosphoserineBy similarity
Modified residuei431 – 4311PhosphoserineCombined sources
Modified residuei451 – 4511PhosphoserineBy similarity
Modified residuei461 – 4611PhosphoserineCombined sources
Modified residuei483 – 4831PhosphoserineBy similarity
Modified residuei498 – 4981PhosphoserineBy similarity
Modified residuei531 – 5311Phosphothreonine; by CK2By similarity
Modified residuei533 – 5331Phosphothreonine; by CK2By similarity

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiA2AIV8.
PaxDbiA2AIV8.
PeptideAtlasiA2AIV8.
PRIDEiA2AIV8.

PTM databases

iPTMnetiA2AIV8.
PhosphoSiteiA2AIV8.

Expressioni

Tissue specificityi

Expressed in myeloid cells. Not expressed in non-lymphoid organs.2 Publications

Gene expression databases

BgeeiENSMUSG00000026928.

Interactioni

Subunit structurei

Interacts with VHL; without leading to protein degradation (By similarity). Self-associates. Interacts (via CARD domain) with BCL10 (via CARD domain) (By similarity). Interacts with NOD2 (via NACHT domain)(PubMed:17187069, PubMed:24960071). Interacts with RIPK2 (PubMed:17187069).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

IntActiA2AIV8. 1 interaction.
STRINGi10090.ENSMUSP00000028294.

Structurei

3D structure databases

ProteinModelPortaliA2AIV8.
SMRiA2AIV8. Positions 11-98.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini6 – 9893CARDPROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili117 – 272156Sequence analysisAdd
BLAST
Coiled coili303 – 415113Sequence analysisAdd
BLAST

Sequence similaritiesi

Contains 1 CARD domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410IE3N. Eukaryota.
ENOG410Y2EE. LUCA.
GeneTreeiENSGT00530000063108.
HOGENOMiHOG000231538.
HOVERGENiHBG058091.
InParanoidiA2AIV8.
KOiK12794.
OMAiKEPARAF.
OrthoDBiEOG091G0T58.
PhylomeDBiA2AIV8.
TreeFamiTF351139.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR001315. CARD.
IPR011029. DEATH-like_dom.
[Graphical view]
PfamiPF00619. CARD. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiPS50209. CARD. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

A2AIV8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSDYENDDEC WSTLESFRVK LISVIDPSRI TPYLRQCKVL NPDDEEQVLS
60 70 80 90 100
DPNLVIRKRK VGVLLDILQR TGHKGYVAFL ESLELYYPQL YRKVTGKEPA
110 120 130 140 150
RVFSMIIDAS GESGLTQLLM TEVMKLQKKV QDLTALLSSK DDFIKELRVK
160 170 180 190 200
DSLLRKHQER VQRLKEECEL SSAELKRCKD ENYELAMCLA HLSEEKGAAL
210 220 230 240 250
MRNRDLQLEV DRLRHSLMKA EDDCKVERKH TLKLRHAMEQ RPSQELLWEL
260 270 280 290 300
QQEKDLLQAR VQELQVSVQE GKLDRNSPYI QVLEEDWRQA LQEHQKQVST
310 320 330 340 350
IFSLRKDLRQ AETLRARCTE EKEMFELQCL ALRKDAKMYK DRIEAILLQM
360 370 380 390 400
EEVSIERDQA MASREELHAQ CTQSFQDKDK LRKLVRELGE KADELQLQLF
410 420 430 440 450
QTESRLLAAE GRLKQQQLDM LILSSDLEDS SPRNSQELSL PQDLEEDAQL
460 470 480 490 500
SDKGVLADRE SPEQPFMALN KEHLSLTHGM GPSSSEPPEK ERRRLKESFE
510 520 530
NYRRKRALRK MQNSWRQGEG DRGNTTGSDN TDTEGS
Length:536
Mass (Da):62,462
Last modified:February 20, 2007 - v1
Checksum:i3A5403C7A04EA2C9
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL732541 Genomic DNA. No translation available.
BC151023 mRNA. Translation: AAI51024.1.
CCDSiCCDS38084.1.
RefSeqiNP_001032836.1. NM_001037747.1.
XP_006498199.1. XM_006498136.2.
UniGeneiMm.330064.

Genome annotation databases

EnsembliENSMUST00000028294; ENSMUSP00000028294; ENSMUSG00000026928.
ENSMUST00000100303; ENSMUSP00000097876; ENSMUSG00000026928.
GeneIDi332579.
KEGGimmu:332579.
UCSCiuc008iut.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL732541 Genomic DNA. No translation available.
BC151023 mRNA. Translation: AAI51024.1.
CCDSiCCDS38084.1.
RefSeqiNP_001032836.1. NM_001037747.1.
XP_006498199.1. XM_006498136.2.
UniGeneiMm.330064.

3D structure databases

ProteinModelPortaliA2AIV8.
SMRiA2AIV8. Positions 11-98.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiA2AIV8. 1 interaction.
STRINGi10090.ENSMUSP00000028294.

PTM databases

iPTMnetiA2AIV8.
PhosphoSiteiA2AIV8.

Proteomic databases

MaxQBiA2AIV8.
PaxDbiA2AIV8.
PeptideAtlasiA2AIV8.
PRIDEiA2AIV8.

Protocols and materials databases

DNASUi332579.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000028294; ENSMUSP00000028294; ENSMUSG00000026928.
ENSMUST00000100303; ENSMUSP00000097876; ENSMUSG00000026928.
GeneIDi332579.
KEGGimmu:332579.
UCSCiuc008iut.1. mouse.

Organism-specific databases

CTDi64170.
MGIiMGI:2685628. Card9.

Phylogenomic databases

eggNOGiENOG410IE3N. Eukaryota.
ENOG410Y2EE. LUCA.
GeneTreeiENSGT00530000063108.
HOGENOMiHOG000231538.
HOVERGENiHBG058091.
InParanoidiA2AIV8.
KOiK12794.
OMAiKEPARAF.
OrthoDBiEOG091G0T58.
PhylomeDBiA2AIV8.
TreeFamiTF351139.

Enzyme and pathway databases

ReactomeiR-MMU-168638. NOD1/2 Signaling Pathway.
R-MMU-5607764. CLEC7A (Dectin-1) signaling.

Miscellaneous databases

PROiA2AIV8.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000026928.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
InterProiIPR001315. CARD.
IPR011029. DEATH-like_dom.
[Graphical view]
PfamiPF00619. CARD. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiPS50209. CARD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCARD9_MOUSE
AccessioniPrimary (citable) accession number: A2AIV8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 16, 2014
Last sequence update: February 20, 2007
Last modified: September 7, 2016
This is version 84 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.