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

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

2 regional properties for A2AIV8

Type Name Position InterPro Accession
domain CARD domain 6 - 98 IPR001315
domain CARD9, CARD domain 10 - 95 IPR042142

Functions

Description
EC Number
Subcellular Localization
  • Cytoplasm
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