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Q9BXL7 (CAR11_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Caspase recruitment domain-containing protein 11
Alternative name(s):
CARD-containing MAGUK protein 1
Short name=Carma 1
Gene names
Name:CARD11
Synonyms:CARMA1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1154 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Its binding to DPP4 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Activates NF-kappa-B via BCL10 and IKK. Stimulates the phosphorylation of BCL10.

Subunit structure

Found in a membrane raft complex, at least composed of BCL10, CARD11, DPP4 and IKBKB. CARD11 and BCL10 bind to each other by CARD-CARD interaction. Interacts (via PDZ domain) with DPP4 (via cytoplasmic tail). Ref.7

Subcellular location

Cytoplasm. Membrane raft. Note: Colocalized with DPP4 in membrane rafts. Ref.7

Tissue specificity

Detected in adult peripheral blood leukocytes, thymus, spleen and liver. Also found in promyelocytic leukemia HL-60 cells, chronic myelogenous leukemia K-562 cells, Burkitt's lymphoma Raji cells and colorectal adenocarcinoma SW480 cells. Not detected in HeLaS3, MOLT-4, A-549 and G431 cells. Ref.1

Post-translational modification

Phosphorylation at Ser-559, Ser-644 and Ser-652 by PRKCB and PRKCQ leads to a shift from an inactive to an active form that activates the NF-kappa-B signaling By similarity.

Involvement in disease

Persistent polyclonal B-cell lymphocytosis (PPBL) [MIM:606445]: An autosomal dominant condition characterized by onset in infancy of splenomegaly and polyclonal expansion of B cells, resulting in peripheral lymphocytosis. Affected individuals also show mild immune dysfunction, including some defective antibody responses and T-cell anergy. There may be a predisposition to the development of B-cell malignancy.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11

Immunodeficiency 11 (IMD11) [MIM:615206]: An autosomal recessive primary immunodeficiency characterized by normal numbers of T and B lymphocytes, but defective intracellular signaling. There is a block in B-cell differentiation with increased numbers of transitional B cells and hypogammaglobulinemia, as well as decreased numbers of regulatory T cells and defects in T-cell function.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Sequence similarities

Contains 1 CARD domain.

Contains 1 guanylate kinase-like domain.

Contains 1 PDZ (DHR) domain.

Caution

Supposed to contain a SH3 domain which is not detected by PROSITE, Pfam or SMART.

Sequence caution

The sequence AAG53402.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAI11720.2 differs from that shown. Reason: Erroneous initiation.

The sequence AAQ96893.1 differs from that shown. Reason: Erroneous gene model prediction.

The sequence EAL23962.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
   Cellular componentCytoplasm
Membrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainCoiled coil
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

T cell costimulation

Inferred from direct assay Ref.7. Source: UniProtKB

T cell receptor signaling pathway

Traceable author statement. Source: Reactome

innate immune response

Traceable author statement. Source: Reactome

positive regulation of B cell proliferation

Inferred from electronic annotation. Source: Ensembl

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

Inferred from electronic annotation. Source: Ensembl

positive regulation of NF-kappaB transcription factor activity

Inferred from mutant phenotype PubMed 12154360. Source: UniProtKB

positive regulation of T cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of cytokine production

Inferred from mutant phenotype PubMed 12154360. Source: UniProtKB

positive regulation of interleukin-2 biosynthetic process

Inferred from electronic annotation. Source: Ensembl

regulation of B cell differentiation

Inferred from electronic annotation. Source: Ensembl

regulation of T cell differentiation

Inferred from electronic annotation. Source: Ensembl

regulation of apoptotic process

Inferred from electronic annotation. Source: InterPro

thymic T cell selection

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

membrane raft

Inferred from direct assay PubMed 12154360Ref.7. Source: UniProtKB

plasma membrane

Inferred from direct assay PubMed 12154360. Source: UniProtKB

   Molecular_functionguanylate kinase activity

Non-traceable author statement Ref.1. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

BCL10O959994EBI-7006141,EBI-958922

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11541154Caspase recruitment domain-containing protein 11
PRO_0000144086

Regions

Domain18 – 11093CARD
Domain667 – 75589PDZ
Domain973 – 1140168Guanylate kinase-like
Coiled coil130 – 449320 Potential

Amino acid modifications

Modified residue4661Phosphoserine Ref.8
Modified residue5591Phosphoserine; by PKC/PRKCB and PKC/PRKCQ By similarity
Modified residue5931Phosphoserine Ref.8
Modified residue6441Phosphoserine; by PKC/PRKCB and PKC/PRKCQ By similarity
Modified residue6521Phosphoserine; by PKC/PRKCB and PKC/PRKCQ By similarity
Modified residue9251Phosphoserine Ref.8

Natural variations

Natural variant1231G → S in PPBL; results in protein aggregation and constitutive NFKB activation. Ref.11
VAR_069710
Natural variant1341E → G in PPBL; results in protein aggregation and constitutive NFKB activation. Ref.11
VAR_069711
Natural variant6701T → M.
Corresponds to variant rs3735134 [ dbSNP | Ensembl ].
VAR_028117
Natural variant6941S → L.
Corresponds to variant rs3735133 [ dbSNP | Ensembl ].
VAR_028118

Experimental info

Sequence conflict8151L → P in AAG53402. Ref.1

Secondary structure

................ 1154
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9BXL7 [UniParc].

Last modified February 26, 2008. Version 3.
Checksum: 2F3512D903795D18

FASTA1,154133,284
        10         20         30         40         50         60 
MPGGGPEMDD YMETLKDEED ALWENVECNR HMLSRYINPA KLTPYLRQCK VIDEQDEDEV 

        70         80         90        100        110        120 
LNAPMLPSKI NRAGRLLDIL HTKGQRGYVV FLESLEFYYP ELYKLVTGKE PTRRFSTIVV 

       130        140        150        160        170        180 
EEGHEGLTHF LMNEVIKLQQ QMKAKDLQRC ELLARLRQLE DEKKQMTLTR VELLTFQERY 

       190        200        210        220        230        240 
YKMKEERDSY NDELVKVKDD NYNLAMRYAQ LSEEKNMAVM RSRDLQLEID QLKHRLNKME 

       250        260        270        280        290        300 
EECKLERNQS LKLKNDIENR PKKEQVLELE RENEMLKTKN QELQSIIQAG KRSLPDSDKA 

       310        320        330        340        350        360 
ILDILEHDRK EALEDRQELV NRIYNLQEEA RQAEELRDKY LEEKEDLELK CSTLGKDCEM 

       370        380        390        400        410        420 
YKHRMNTVML QLEEVERERD QAFHSRDEAQ TQYSQCLIEK DKYRKQIREL EEKNDEMRIE 

       430        440        450        460        470        480 
MVRREACIVN LESKLRRLSK DSNNLDQSLP RNLPVTIISQ DFGDASPRTN GQEADDSSTS 

       490        500        510        520        530        540 
EESPEDSKYF LPYHPPQRRM NLKGIQLQRA KSPISLKRTS DFQAKGHEEE GTDASPSSCG 

       550        560        570        580        590        600 
SLPITNSFTK MQPPRSRSSI MSITAEPPGN DSIVRRYKED APHRSTVEED NDSGGFDALD 

       610        620        630        640        650        660 
LDDDSHERYS FGPSSIHSSS SSHQSEGLDA YDLEQVNLMF RKFSLERPFR PSVTSVGHVR 

       670        680        690        700        710        720 
GPGPSVQHTT LNGDSLTSQL TLLGGNARGS FVHSVKPGSL AEKAGLREGH QLLLLEGCIR 

       730        740        750        760        770        780 
GERQSVPLDT CTKEEAHWTI QRCSGPVTLH YKVNHEGYRK LVKDMEDGLI TSGDSFYIRL 

       790        800        810        820        830        840 
NLNISSQLDA CTMSLKCDDV VHVRDTMYQD RHEWLCARVD PFTDHDLDMG TIPSYSRAQQ 

       850        860        870        880        890        900 
LLLVKLQRLM HRGSREEVDG THHTLRALRN TLQPEEALST SDPRVSPRLS RASFLFGQLL 

       910        920        930        940        950        960 
QFVSRSENKY KRMNSNERVR IISGSPLGSL ARSSLDATKL LTEKQEELDP ESELGKNLSL 

       970        980        990       1000       1010       1020 
IPYSLVRAFY CERRRPVLFT PTVLAKTLVQ RLLNSGGAME FTICKSDIVT RDEFLRRQKT 

      1030       1040       1050       1060       1070       1080 
ETIIYSREKN PNAFECIAPA NIEAVAAKNK HCLLEAGIGC TRDLIKSNIY PIVLFIRVCE 

      1090       1100       1110       1120       1130       1140 
KNIKRFRKLL PRPETEEEFL RVCRLKEKEL EALPCLYATV EPDMWGSVEE LLRVVKDKIG 

      1150 
EEQRKTIWVD EDQL 

« Hide

References

« Hide 'large scale' references
[1]"CARD11 and CARD14 are novel caspase recruitment domain (CARD)/membrane-associated guanylate kinase (MAGUK) family members that interact with Bcl10 and activate NF-kappaB."
Bertin J., Wang L., Guo Y., Jacobson M.D., Poyet J.-L., Srinivasula S.M., Merriam S., DiStefano P.S., Alnemri E.S.
J. Biol. Chem. 276:11877-11882(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[2]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"Human chromosome 7: DNA sequence and biology."
Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. expand/collapse author list , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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].
[5]"Carma1, a CARD-containing binding partner of Bcl10, induces Bcl10 phosphorylation and NF-kappaB activation."
Gaide O., Martinon F., Micheau O., Bonnet D., Thome M., Tschopp J.
FEBS Lett. 496:121-127(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 8-1154.
[6]Erratum
Gaide O., Martinon F., Micheau O., Bonnet D., Thome M., Tschopp J.
FEBS Lett. 505:198-198(2001)
[7]"Caveolin-1 triggers T-cell activation via CD26 in association with CARMA1."
Ohnuma K., Uchiyama M., Yamochi T., Nishibashi K., Hosono O., Takahashi N., Kina S., Tanaka H., Lin X., Dang N.H., Morimoto C.
J. Biol. Chem. 282:10117-10131(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A MEMBRANE RAFT COMPLEX, INTERACTION WITH DPP4, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY.
[8]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-466; SER-593 AND SER-925, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Deficiency of caspase recruitment domain family, member 11 (CARD11), causes profound combined immunodeficiency in human subjects."
Stepensky P., Keller B., Buchta M., Kienzler A.K., Elpeleg O., Somech R., Cohen S., Shachar I., Miosge L.A., Schlesier M., Fuchs I., Enders A., Eibel H., Grimbacher B., Warnatz K.
J. Allergy Clin. Immunol. 131:477-485(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN IMD11.
[11]"Congenital B cell lymphocytosis explained by novel germline CARD11 mutations."
Snow A.L., Xiao W., Stinson J.R., Lu W., Chaigne-Delalande B., Zheng L., Pittaluga S., Matthews H.F., Schmitz R., Jhavar S., Kuchen S., Kardava L., Wang W., Lamborn I.T., Jing H., Raffeld M., Moir S., Fleisher T.A. expand/collapse author list , Staudt L.M., Su H.C., Lenardo M.J.
J. Exp. Med. 209:2247-2261(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PPBL SER-123 AND GLY-134, CHARACTERIZATION OF VARIANTS PPBL SER-123 AND GLY-134.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF322641 mRNA. Translation: AAG53402.1. Different initiation.
AC004906 Genomic DNA. Translation: AAQ96893.1. Sequence problems.
CH236953 Genomic DNA. Translation: EAL23962.1. Sequence problems.
BC111719 mRNA. Translation: AAI11720.2. Different initiation.
AF352576 mRNA. Translation: AAL34460.1.
RefSeqNP_115791.3. NM_032415.5.
XP_005249947.1. XM_005249890.1.
XP_005249948.1. XM_005249891.1.
UniGeneHs.648101.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4LWDX-ray1.79A18-110[»]
ProteinModelPortalQ9BXL7.
SMRQ9BXL7. Positions 21-110, 403-441, 673-845.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124073. 21 interactions.
DIPDIP-41797N.
IntActQ9BXL7. 7 interactions.
MINTMINT-193901.
STRING9606.ENSP00000380150.

PTM databases

PhosphoSiteQ9BXL7.

Polymorphism databases

DMDM172046231.

Proteomic databases

PaxDbQ9BXL7.
PRIDEQ9BXL7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000396946; ENSP00000380150; ENSG00000198286.
GeneID84433.
KEGGhsa:84433.
UCSCuc003smv.3. human.

Organism-specific databases

CTD84433.
GeneCardsGC07M002912.
H-InvDBHIX0033921.
HGNCHGNC:16393. CARD11.
HPAHPA052984.
MIM606445. phenotype.
607210. gene.
615206. phenotype.
neXtProtNX_Q9BXL7.
Orphanet300324. Persistent polyclonal B-cell lymphocytosis.
357237. Severe combined immunodeficiency due to CARD11 deficiency.
PharmGKBPA26073.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG47732.
HOVERGENHBG099790.
InParanoidQ9BXL7.
KOK07367.
OMAEALPCLY.
OrthoDBEOG747PH5.
TreeFamTF351139.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SignaLinkQ9BXL7.

Gene expression databases

ArrayExpressQ9BXL7.
BgeeQ9BXL7.
CleanExHS_CARD11.
GenevestigatorQ9BXL7.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
InterProIPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR027417. P-loop_NTPase.
IPR001478. PDZ.
[Graphical view]
PfamPF00619. CARD. 1 hit.
[Graphical view]
SMARTSM00228. PDZ. 1 hit.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
SSF50156. SSF50156. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEPS50209. CARD. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCARD11. human.
GeneWikiCARD11.
GenomeRNAi84433.
NextBio74170.
PROQ9BXL7.
SOURCESearch...

Entry information

Entry nameCAR11_HUMAN
AccessionPrimary (citable) accession number: Q9BXL7
Secondary accession number(s): A4D1Z7, Q2NKN7, Q548H3
Entry history
Integrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: February 26, 2008
Last modified: March 19, 2014
This is version 120 of the entry and version 3 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 7

Human chromosome 7: entries, gene names and cross-references to MIM