A2AIV8
Gene name |
Card9 |
Protein name |
Caspase recruitment domain-containing protein 9 |
Names |
|
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:332579 |
EC number |
|
Protein Class |
CASPASE RECRUITMENT DOMAIN FAMILY (PTHR14559) |

Descriptions
Caspase recruitment domain-containing protein 9 (CARD9) is an adaptor protein that signals downstream of ITAM-containing receptors in myeloid cells. It is implicated in antifungal defense, with at least 24 known loss-of-function mutations that lead to increased susceptibility to fungal infections. CARD9 autoinhibition is mediated by the interactions between the coiled-coil 1 (CC1) domain, the linker region, and the CARD domain. This interaction is disrupted by phosphorylation at S104, which is critical for activation and subsequent inflammatory response signaling through filamentation and assembly of the CARD9-BCL10-MALT1 complex.
Autoinhibitory domains (AIDs)
Target domain |
1-97 (CARD domain) |
Relief mechanism |
PTM |
Assay |
Mutagenesis experiment, Structural analysis |
Accessory elements
No accessory elements
References
- Holliday MJ et al. (2019) "Structures of autoinhibited and polymerized forms of CARD9 reveal mechanisms of CARD9 and CARD11 activation", Nature communications, 10, 3070
- Brandt M et al. (2024) "Translational genetics identifies a phosphorylation switch in CARD9 required for innate inflammatory responses", Cell reports, 43, 113944
Autoinhibited structure

Activated structure

1 structures for A2AIV8
Entry ID | Method | Resolution | Chain | Position | Source |
---|---|---|---|---|---|
AF-A2AIV8-F1 | Predicted | AlphaFoldDB |
22 variants for A2AIV8
Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
---|---|---|---|---|---|
rs3391251467 | 9 | E>G | No | EVA | |
rs3391240492 | 11 | W>C | No | EVA | |
rs3391124084 | 11 | W>S | No | EVA | |
rs3388537529 | 28 | S>P | No | EVA | |
rs3391369404 | 58 | K>* | No | EVA | |
rs3391302286 | 58 | K>M | No | EVA | |
rs3388537731 | 122 | E>D | No | EVA | |
rs27215914 | 319 | T>A | No | EVA | |
rs3388536559 | 326 | E>K | No | EVA | |
rs3388532317 | 327 | L>M | No | EVA | |
rs3388530636 | 349 | Q>P | No | EVA | |
rs3388534083 | 398 | Q>R | No | EVA | |
rs240587227 | 404 | S>G | No | EVA | |
rs3388535044 | 404 | S>N | No | EVA | |
rs3388534979 | 419 | D>G | No | EVA | |
rs3388536649 | 436 | Q>R | No | EVA | |
rs3391395233 | 441 | P>S | No | EVA | |
rs3388539144 | 450 | L>F | No | EVA | |
rs3388536710 | 511 | M>K | No | EVA | |
rs241365358 | 512 | Q>H | No | EVA | |
rs218288087 | 523 | G>W | No | EVA | |
rs3388537534 | 531 | T>I | No | EVA |
No associated diseases with A2AIV8
Functions
Description | ||
---|---|---|
EC Number | ||
Subcellular Localization |
|
|
PANTHER Family | PTHR14559 | CASPASE RECRUITMENT DOMAIN FAMILY |
PANTHER Subfamily | PTHR14559:SF3 | CASPASE RECRUITMENT DOMAIN-CONTAINING PROTEIN 9 |
PANTHER Protein Class | scaffold/adaptor protein | |
PANTHER Pathway Category | No pathway information available |
4 GO annotations of cellular component
Name | Definition |
---|---|
CBM complex | A protein complex comprising Bcl10, MALT1 and a CARD domain-containing protein (CARD9, CARD10 or CARD11); plays a role in signal transduction during NF-kappaB activation. |
cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
protein-containing complex | A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together. |
5 GO annotations of molecular function
Name | Definition |
---|---|
CARD domain binding | Binding to a CARD (N-terminal caspase recruitment) domain, a protein-protein interaction domain that belongs to the death domain-fold superfamily. These protein molecule families are similar in structure with each consisting of six or seven anti-parallel alpha-helices that form highly specific homophilic interactions between signaling partners. CARD exists in the N-terminal prodomains of several caspases and in apoptosis-regulatory proteins and mediates the assembly of CARD-containing proteins that participate in activation or suppression of CARD carrying members of the caspase family. |
identical protein binding | Binding to an identical protein or proteins. |
metal ion binding | Binding to a metal ion. |
protein homodimerization activity | Binding to an identical protein to form a homodimer. |
protein self-association | Binding to a domain within the same polypeptide. |
34 GO annotations of biological process
Name | Definition |
---|---|
antifungal innate immune response | An defense response against a fungus mediated through an innate immune response. An innate immune response is mediated by germline encoded components that directly recognize components of potential pathogens. |
defense response to Gram-positive bacterium | Reactions triggered in response to the presence of a Gram-positive bacterium that act to protect the cell or organism. |
defense response to virus | Reactions triggered in response to the presence of a virus that act to protect the cell or organism. |
host-mediated regulation of intestinal microbiota composition | The biological process involved in maintaining the steady-state number of cells within a population of free-living cells such as the bacteria in the gut. |
immunoglobulin mediated immune response | An immune response mediated by immunoglobulins, whether cell-bound or in solution. |
JNK cascade | An intracellular protein kinase cascade containing at least a JNK (a MAPK), a JNKK (a MAPKK) and a JUN3K (a MAP3K). The cascade can also contain an additional tier |
neutrophil mediated immunity | Any process involved in the carrying out of an immune response by a neutrophil. |
positive regulation of canonical NF-kappaB signal transduction | Any process that activates or increases the frequency, rate or extent of I-kappaB kinase/NF-kappaB signaling. |
positive regulation of chemokine production | Any process that activates or increases the frequency, rate, or extent of chemokine production. |
positive regulation of cytokine production | Any process that activates or increases the frequency, rate or extent of production of a cytokine. |
positive regulation of cytokine production involved in inflammatory response | Any process that activates or increases the frequency, rate or extent of cytokine production involved in inflammatory response. |
positive regulation of ERK1 and ERK2 cascade | Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade. |
positive regulation of granulocyte macrophage colony-stimulating factor production | Any process that activates or increases the frequency, rate, or extent of granulocyte macrophage colony-stimulating factor production. |
positive regulation of innate immune response | Any process that activates or increases the frequency, rate or extent of the innate immune response, the organism's first line of defense against infection. |
positive regulation of interleukin-17 production | Any process that activates or increases the frequency, rate, or extent of production of any member of the interleukin-17 family of cytokines. |
positive regulation of interleukin-6 production | Any process that activates or increases the frequency, rate, or extent of interleukin-6 production. |
positive regulation of JNK cascade | Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the JNK cascade. |
positive regulation of macrophage cytokine production | Any process that increases the rate, frequency or extent of macrophage cytokine production. Macrophage cytokine production is the appearance of a chemokine due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels. |
positive regulation of NF-kappaB transcription factor activity | Any process that activates or increases the frequency, rate or extent of activity of the transcription factor NF-kappaB. |
positive regulation of stress-activated MAPK cascade | Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the stress-activated MAPK cascade. |
positive regulation of T-helper 17 type immune response | Any process that activates or increases the frequency, rate or extent of T-helper 17 type immune response. |
positive regulation of tumor necrosis factor production | Any process that activates or increases the frequency, rate or extent of tumor necrosis factor production. |
protein homooligomerization | The process of creating protein oligomers, compounds composed of a small number, usually between three and ten, of identical component monomers. Oligomers may be formed by the polymerization of a number of monomers or the depolymerization of a large protein polymer. |
regulation of apoptotic process | Any process that modulates the occurrence or rate of cell death by apoptotic process. |
regulation of interleukin-2 production | Any process that modulates the frequency, rate, or extent of interleukin-2 production. |
regulation of interleukin-6 production | Any process that modulates the frequency, rate, or extent of interleukin-6 production. |
regulation of tumor necrosis factor production | Any process that modulates the frequency, rate or extent of tumor necrosis factor production. |
response to aldosterone | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an aldosterone stimulus. |
response to exogenous dsRNA | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an exogenous double-stranded RNA stimulus. |
response to fungus | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a fungus. |
response to muramyl dipeptide | Any process that results in a change in state or activity of an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a muramyl dipeptide stimulus. Muramyl dipeptide is derived from peptidoglycan. |
response to peptidoglycan | Any process that results in a change in state or activity of an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a peptidoglycan stimulus. Peptidoglycan is a bacterial cell wall macromolecule. |
response to xenobiotic stimulus | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a xenobiotic, a compound foreign to the organim exposed to it. It may be synthesized by another organism (like ampicilin) or it can be a synthetic chemical. |
stress-activated MAPK cascade | The series of molecular signals in which a stress-activated MAP kinase cascade relays a signal; MAP kinase cascades involve at least three protein kinase activities and culminate in the phosphorylation and activation of a MAP kinase. |
5 homologous proteins in AiPD
UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
---|---|---|---|---|
Q9H257 | CARD9 | Caspase recruitment domain-containing protein 9 | Homo sapiens (Human) | EV |
Q9BXL7 | CARD11 | Caspase recruitment domain-containing protein 11 | Homo sapiens (Human) | EV |
Q8CIS0 | Card11 | Caspase recruitment domain-containing protein 11 | Mus musculus (Mouse) | SS |
Q99KF0 | Card14 | Caspase recruitment domain-containing protein 14 | Mus musculus (Mouse) | PR |
Q9EPY0 | Card9 | Caspase recruitment domain-containing protein 9 | Rattus norvegicus (Rat) | SS |
10 | 20 | 30 | 40 | 50 | 60 |
MSDYENDDEC | WSTLESFRVK | LISVIDPSRI | TPYLRQCKVL | NPDDEEQVLS | DPNLVIRKRK |
70 | 80 | 90 | 100 | 110 | 120 |
VGVLLDILQR | TGHKGYVAFL | ESLELYYPQL | YRKVTGKEPA | RVFSMIIDAS | GESGLTQLLM |
130 | 140 | 150 | 160 | 170 | 180 |
TEVMKLQKKV | QDLTALLSSK | DDFIKELRVK | DSLLRKHQER | VQRLKEECEL | SSAELKRCKD |
190 | 200 | 210 | 220 | 230 | 240 |
ENYELAMCLA | HLSEEKGAAL | MRNRDLQLEV | DRLRHSLMKA | EDDCKVERKH | TLKLRHAMEQ |
250 | 260 | 270 | 280 | 290 | 300 |
RPSQELLWEL | QQEKDLLQAR | VQELQVSVQE | GKLDRNSPYI | QVLEEDWRQA | LQEHQKQVST |
310 | 320 | 330 | 340 | 350 | 360 |
IFSLRKDLRQ | AETLRARCTE | EKEMFELQCL | ALRKDAKMYK | DRIEAILLQM | EEVSIERDQA |
370 | 380 | 390 | 400 | 410 | 420 |
MASREELHAQ | CTQSFQDKDK | LRKLVRELGE | KADELQLQLF | QTESRLLAAE | GRLKQQQLDM |
430 | 440 | 450 | 460 | 470 | 480 |
LILSSDLEDS | SPRNSQELSL | PQDLEEDAQL | SDKGVLADRE | SPEQPFMALN | KEHLSLTHGM |
490 | 500 | 510 | 520 | 530 | |
GPSSSEPPEK | ERRRLKESFE | NYRRKRALRK | MQNSWRQGEG | DRGNTTGSDN | TDTEGS |