Card9
entrez
64171
canonical
uniprot
Q9EPY0
canonical
ensembl
ENSRNOG00000051470
resolver
ensp
ENSRNOP00000074450
resolver
enst
ENSRNOT00000091484
resolver
genesymbol
Card9
resolver
uniprot
F1LQK8
resolver
uniprot_entry
CARD9_RAT
resolver
uniprot_sec
F1LQK8
resolver
activity_regulation
ACTIVITY REGULATION: Maintained in an autoinhibited state via homodimerization in which the CARD domain forms an extensive interaction with the adjacent linker and coiled-coil regions (By similarity). Activation downstream of C-type lectin receptors, by phosphorylation by PRKCD and/or ubiquitination by TRIM62, triggers disruption of the CARD domain-coiled coil interface, CARD9 homooligomerization and BCL10 recruitment, followed by activation of NF-kappa-B and MAP kinase p38 pathways (By similarity). Zinc-binding inhibits activation by stabilizing the CARD ground-state conformation and restricting its capacity to form BCL10-nucleating filaments (By similarity). {ECO:0000250|UniProtKB:A2AIV8, ECO:0000250|UniProtKB:Q9H257}.
uniprot
proteins
amino_acid_sequence
MSDYENDDECWSALESFRVKLISVIDPSRITPYLRQCKVLNPDDEEQVLSDPNLVIRKRKVGVLLDILQRTGHKGYVAFLESLELYYPQLYRKVTGKEPARVFSMIIDASGESGLTQLLMTEVMKLQKKVQDLTALLSSKDDFIKELRVKDSLLRKHQERVQRLKEECELSSAELKRCKDENYDLAMRLAHLSEEKGAALMRNRDLQLEVDQLRHSLMKAEDDCKVERKHTLKLRHAMEQRPSQELLWDLQQERDLLQARVQELEVSVQEGKLHRNSPYIQVLEEDWRQALQEHQEQASTIFSLRKDLRQAEALRTRCMEEKEMFELQCLALRKDAKMYKDRIEAILQQMEEVSIERDQAMTSREELHAQCAQSFQDKDKLRKQVRELDEKADELQLQLFQTESRLLAAEGRLKQQQLDMLILSSDLEDSSPRNSQELSLPQDLEEDAQLSDKGVLADRESPEQPFVVLNKKHLSQTHDTVPSSSEPPEKERRRLKESFENYRRKRALRKMQNSWRQGEGDHGNTTGSDNTDTEGS
uniprot
proteins
function
FUNCTION: Adapter protein that plays a key role in innate immune response against fungi by forming signaling complexes downstream of C-type lectin receptors (By similarity). CARD9-mediated signals are essential for antifungal immunity against a subset of fungi from the phylum Ascomycota (By similarity). Transduces signals in myeloid cells downstream of C-type lectin receptors CLEC7A (dectin-1), CLEC6A (dectin-2) and CLEC4E (Mincle), which detect pathogen-associated molecular pattern metabolites (PAMPs), such as fungal carbohydrates, and trigger CARD9 activation (PubMed:17936701). Upon activation, CARD9 homooligomerizes to form a nucleating helical template that recruits BCL10 via CARD-CARD interaction, thereby promoting polymerization of BCL10 and subsequent recruitment of MALT1: this leads to activation of NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways which stimulate expression of genes encoding pro-inflammatory cytokines and chemokines (PubMed:17936701). CARD9 signaling in antigen-presenting cells links innate sensing of fungi to the activation of adaptive immunity and provides a cytokine milieu that induces the development and subsequent of interleukin 17-producing T helper (Th17) cells (By similarity). 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). CARD9 can also be engaged independently of BCL10: forms a complex with RASGRF1 downstream of C-type lectin receptors, which recruits and activates HRAS, leading to ERK activation and the production of cytokines (By similarity). Acts as an important regulator of the intestinal commensal fungi (mycobiota) component of the gut microbiota (By similarity). Plays an essential role in antifungal immunity against dissemination of gut fungi: acts by promoting induction of antifungal IgG antibodies response in CX3CR1(+) macrophages to confer protection against disseminated C.albicans or C.auris infection (By similarity). Also mediates immunity against other pathogens, such as certain bacteria, viruses and parasites; CARD9 signaling is however redundant with other innate immune responses (By similarity). In response to L.monocytogenes infection, required for the production of inflammatory cytokines activated by intracellular peptidoglycan: acts by connecting NOD2 recognition of peptidoglycan to downstream activation of MAP kinases (MAPK) without activating NF-kappa-B (By similarity). {ECO:0000250|UniProtKB:A2AIV8, ECO:0000269|PubMed:17936701}.
uniprot
proteins
mass_dalton
62632
uniprot
proteins
mutagenesis
MUTAGEN 526; /note="T->A: Abolished phosphorylation by CK2 and increased activation of NF-kappa-B; when associated with A-528; A-531 and A-533."; /evidence="ECO:0000269|PubMed:17936701"; MUTAGEN 528; /note="S->A: Abolished phosphorylation by CK2 and increased activation of NF-kappa-B; when associated with A-526; A-531 and A-533."; /evidence="ECO:0000269|PubMed:17936701"; MUTAGEN 531; /note="T->A: Abolished phosphorylation by CK2 and increased activation of NF-kappa-B; when associated with A-526; A-528 and A-533."; /evidence="ECO:0000269|PubMed:17936701"; MUTAGEN 533; /note="T->A: Abolished phosphorylation by CK2 and increased activation of NF-kappa-B; when associated with A-526; A-528 and A-531."; /evidence="ECO:0000269|PubMed:17936701
uniprot
proteins
post_translational_modification
PTM: Phosphorylated at Thr-231 by PRKCD downstream of C-type lectin receptors activation: phosphorylation promotes interaction with BCL10, followed by activation of NF-kappa-B and MAP kinase p38 pathways (By similarity). Phosphorylated at Thr-531 and Thr-533 by CK2 following interaction with VHL, leading to inhibit the ability to activate NF-kappa-B (PubMed:17936701). {ECO:0000250|UniProtKB:A2AIV8, ECO:0000269|PubMed:17936701}.; PTM: Ubiquitinated at Lys-125 via 'Lys-27'-linked ubiquitin by TRIM62 downstream of C-type lectin receptors activation; leading to CARD9 activation, followed by activation of NF-kappa-B and MAP kinase p38 pathways. Deubiquitinated at Lys-125 by USP15, inhibiting CARD9. {ECO:0000250|UniProtKB:Q9H257}.
uniprot
proteins
pubmed
11053425
uniprot
proteins
pubmed
15057822
uniprot
proteins
pubmed
17936701
uniprot
proteins
pubmed
22673903
uniprot
proteins
sequence_length
536
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9H257}.
uniprot
proteins