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Q9BXL6 (CAR14_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Caspase recruitment domain-containing protein 14
Alternative name(s):
CARD-containing MAGUK protein 2
Short name=Carma 2
Gene names
Name:CARD14
Synonyms:CARMA2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1004 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Plays a role in signaling mediated by TRAF2, TRAF3 and TRAF6 and protects cells against apoptosis. Activates NF-kappa-B via BCL10 and IKK. Stimulates the phosphorylation of BCL10. Ref.4

Subunit structure

Interacts with BCL10 by CARD-CARD interaction. Interacts with TRAF2, TRAF3 and TRAF6. Ref.4

Subcellular location

Isoform 1: Cytoplasm Ref.4.

Isoform 2: Cytoplasm Ref.4.

Isoform 3: Cytoplasm Ref.4.

Tissue specificity

Isoform 1 is detected in placenta and epidermal keratinocytes. Isoform 2 is detected in leukocytes and fetal brain. Ref.8

Involvement in disease

Psoriasis 2 (PSORS2) [MIM:602723]: A common, chronic inflammatory disease of the skin with multifactorial etiology. It is characterized by red, scaly plaques usually found on the scalp, elbows and knees. These lesions are caused by abnormal keratinocyte proliferation and infiltration of inflammatory cells into the dermis and epidermis.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.8 Ref.10

Pityriasis rubra pilaris (PRP) [MIM:173200]: A rare, papulosquamous skin disease characterized by the appearance of keratotic follicular papules, well-demarcated salmon-colored erythematous plaques covered with fine powdery scales interspersed with distinct islands of uninvolved skin, and palmoplantar keratoderma. Most cases are sporadic. The rare familial cases show autosomal dominant inheritance with incomplete penetrance and variable expression. Familial PRP usually presents at birth or appears during the first years of life and runs a chronic course. It is characterized by prominent follicular hyperkeratosis, diffuse palmoplantar keratoderma, and erythema.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9

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.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9BXL6-1)

Also known as: CARMA2fl;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9BXL6-2)

Also known as: Short; CARMA2sh;

The sequence of this isoform differs from the canonical sequence as follows:
     741-1004: Missing.
Isoform 3 (identifier: Q9BXL6-3)

Also known as: Cardless; CARMA2cl;

The sequence of this isoform differs from the canonical sequence as follows:
     1-237: Missing.
     619-671: DYEASEPLFK...KRLLQDLEAK → SRARPLLSPG...WADVKRSAHL
     672-1004: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10041004Caspase recruitment domain-containing protein 14
PRO_0000144088

Regions

Domain15 – 10793CARD
Domain568 – 65891PDZ
Domain807 – 990184Guanylate kinase-like
Coiled coil128 – 409282 Potential

Amino acid modifications

Modified residue5441Phosphoserine Ref.7

Natural variations

Alternative sequence1 – 237237Missing in isoform 3.
VSP_047400
Alternative sequence619 – 67153DYEAS…DLEAK → SRARPLLSPGLLMGTVAAGG VTQADFTSPRRCRSTLGWAS ALSWADVKRSAHL in isoform 3.
VSP_047401
Alternative sequence672 – 1004333Missing in isoform 3.
VSP_047402
Alternative sequence741 – 1004264Missing in isoform 2.
VSP_047403
Natural variant381R → C. Ref.10
Corresponds to variant rs281875217 [ dbSNP | Ensembl ].
VAR_068222
Natural variant621R → Q. Ref.10
Corresponds to variant rs115582620 [ dbSNP | Ensembl ].
VAR_068223
Natural variant1171G → S in PSORS2; may result in altered splicing of exon 3; results in increased NF-kappa-B activation. Ref.8 Ref.10
Corresponds to variant rs281875215 [ dbSNP | Ensembl ].
VAR_068224
Natural variant1381E → A in PSORS2; results in increased NF-kappa-B activation. Ref.8 Ref.10
Corresponds to variant rs281875214 [ dbSNP | Ensembl ].
VAR_068225
Natural variant1381Missing in PRP. Ref.9
VAR_068819
Natural variant1421E → G in PSORS2; results in increased NF-kappa-B activation. Ref.10
Corresponds to variant rs281875213 [ dbSNP | Ensembl ].
VAR_068226
Natural variant1421E → K in PSORS2; results in increased NF-kappa-B activation. Ref.10
Corresponds to variant rs281875212 [ dbSNP | Ensembl ].
VAR_068227
Natural variant1501L → R. Ref.10
Corresponds to variant rs146214639 [ dbSNP | Ensembl ].
VAR_068228
Natural variant1561L → P in PRP. Ref.9
VAR_068820
Natural variant1711H → N May be associated with susceptibility to psoriasis. Ref.10
Corresponds to variant rs281875216 [ dbSNP | Ensembl ].
VAR_068229
Natural variant1761D → H. Ref.10
Corresponds to variant rs144475004 [ dbSNP | Ensembl ].
VAR_068230
Natural variant1791R → H. Ref.10
Corresponds to variant rs199517469 [ dbSNP | Ensembl ].
VAR_068231
Natural variant1911V → L. Ref.10
Corresponds to variant rs281875218 [ dbSNP | Ensembl ].
VAR_068232
Natural variant2001S → N. Ref.10
Corresponds to variant rs114688446 [ dbSNP | Ensembl ].
VAR_068233
Natural variant2851D → G May be associated with susceptibility to psoriasis. Ref.10
Corresponds to variant rs281875219 [ dbSNP | Ensembl ].
VAR_068234
Natural variant5471R → S.
Corresponds to variant rs2066964 [ dbSNP | Ensembl ].
VAR_024401
Natural variant5851V → I.
Corresponds to variant rs34367357 [ dbSNP | Ensembl ].
VAR_048608
Natural variant5931I → N. Ref.10
Corresponds to variant rs281875220 [ dbSNP | Ensembl ].
VAR_068235
Natural variant6821R → W. Ref.10
Corresponds to variant rs117918077 [ dbSNP | Ensembl ].
VAR_068236
Natural variant7141G → S. Ref.10
Corresponds to variant rs151150961 [ dbSNP | Ensembl ].
VAR_068237
Natural variant8201R → W. Ref.1 Ref.2
Corresponds to variant rs11652075 [ dbSNP | Ensembl ].
VAR_059196
Natural variant8831R → H.
Corresponds to variant rs2289541 [ dbSNP | Ensembl ].
VAR_022043
Natural variant9621R → Q.
Corresponds to variant rs34850974 [ dbSNP | Ensembl ].
VAR_061080
Natural variant9731D → E. Ref.10
Corresponds to variant rs144285237 [ dbSNP | Ensembl ].
VAR_068238

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (CARMA2fl) [UniParc].

Last modified May 18, 2010. Version 2.
Checksum: 761CBAC219956076

FASTA1,004113,270
        10         20         30         40         50         60 
MGELCRRDSA LTALDEETLW EMMESHRHRI VRCICPSRLT PYLRQAKVLC QLDEEEVLHS 

        70         80         90        100        110        120 
PRLTNSAMRA GHLLDLLKTR GKNGAIAFLE SLKFHNPDVY TLVTGLQPDV DFSNFSGLME 

       130        140        150        160        170        180 
TSKLTECLAG AIGSLQEELN QEKGQKEVLL RRCQQLQEHL GLAETRAEGL HQLEADHSRM 

       190        200        210        220        230        240 
KREVSAHFHE VLRLKDEMLS LSLHYSNALQ EKELAASRCR SLQEELYLLK QELQRANMVS 

       250        260        270        280        290        300 
SCELELQEQS LRTASDQESG DEELNRLKEE NEKLRSLTFS LAEKDILEQS LDEARGSRQE 

       310        320        330        340        350        360 
LVERIHSLRE RAVAAERQRE QYWEEKEQTL LQFQKSKMAC QLYREKVNAL QAQVCELQKE 

       370        380        390        400        410        420 
RDQAYSARDS AQREISQSLV EKDSLRRQVF ELTDQVCELR TQLRQLQAEP PGVLKQEART 

       430        440        450        460        470        480 
REPCPREKQR LVRMHAICPR DDSDCSLVSS TESQLLSDLS ATSSRELVDS FRSSSPAPPS 

       490        500        510        520        530        540 
QQSLYKRVAE DFGEEPWSFS SCLEIPEGDP GALPGAKAGD PHLDYELLDT ADLPQLESSL 

       550        560        570        580        590        600 
QPVSPGRLDV SESGVLMRRR PARRILSQVT MLAFQGDALL EQISVIGGNL TGIFIHRVTP 

       610        620        630        640        650        660 
GSAADQMALR PGTQIVMVDY EASEPLFKAV LEDTTLEEAV GLLRRVDGFC CLSVKVNTDG 

       670        680        690        700        710        720 
YKRLLQDLEA KVATSGDSFY IRVNLAMEGR AKGELQVHCN EVLHVTDTMF QGCGCWHAHR 

       730        740        750        760        770        780 
VNSYTMKDTA AHGTIPNYSR AQQQLIALIQ DMTQQCTVTR KPSSGGPQKL VRIVSMDKAK 

       790        800        810        820        830        840 
ASPLRLSFDR GQLDPSRMEG SSTCFWAESC LTLVPYTLVR PHRPARPRPV LLVPRAVGKI 

       850        860        870        880        890        900 
LSEKLCLLQG FKKCLAEYLS QEEYEAWSQR GDIIQEGEVS GGRCWVTRHA VESLMEKNTH 

       910        920        930        940        950        960 
ALLDVQLDSV CTLHRMDIFP IVIHVSVNEK MAKKLKKGLQ RLGTSEEQLL EAARQEEGDL 

       970        980        990       1000 
DRAPCLYSSL APDGWSDLDG LLSCVRQAIA DEQKKVVWTE QSPR 

« Hide

Isoform 2 (Short) (CARMA2sh) [UniParc].

Checksum: 90FCA1B1C2DB28D1
Show »

FASTA74083,679
Isoform 3 (Cardless) (CARMA2cl) [UniParc].

Checksum: D351699781B6D6EB
Show »

FASTA43448,505

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] (ISOFORM 1), VARIANT TRP-820.
[2]"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] (ISOFORM 1), VARIANT TRP-820.
[3]Erratum
Gaide O., Martinon F., Micheau O., Bonnet D., Thome M., Tschopp J.
FEBS Lett. 505:198-198(2001)
[4]"Alternative splicing of CARMA2/CARD14 transcripts generates protein variants with differential effect on NF-kappaB activation and endoplasmic reticulum stress-induced cell death."
Scudiero I., Zotti T., Ferravante A., Vessichelli M., Vito P., Stilo R.
J. Cell. Physiol. 226:3121-3131(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), FUNCTION, INTERACTION WITH BCL10; TRAF2; TRAF3 AND TRAF6, SUBCELLULAR LOCATION, ALTERNATIVE SPLICING.
[5]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] (ISOFORMS 2 AND 3).
Tissue: Cervix and Colon.
[7]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-544, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"PSORS2 is due to mutations in CARD14."
Jordan C.T., Cao L., Roberson E.D., Pierson K.C., Yang C.F., Joyce C.E., Ryan C., Duan S., Helms C.A., Liu Y., Chen Y., McBride A.A., Hwu W.L., Wu J.Y., Chen Y.T., Menter A., Goldbach-Mansky R., Lowes M.A., Bowcock A.M.
Am. J. Hum. Genet. 90:784-795(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, VARIANTS PSORS2 SER-117 AND ALA-138, CHARACTERIZATION OF VARIANTS PSORS2 SER-117 AND ALA-138.
[9]"Familial pityriasis rubra pilaris is caused by mutations in CARD14."
Fuchs-Telem D., Sarig O., van Steensel M.A., Isakov O., Israeli S., Nousbeck J., Richard K., Winnepenninckx V., Vernooij M., Shomron N., Uitto J., Fleckman P., Richard G., Sprecher E.
Am. J. Hum. Genet. 91:163-170(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PRP GLU-138 DEL AND PRO-156.
[10]"Rare and Common Variants in CARD14, Encoding an Epidermal Regulator of NF-kappaB, in Psoriasis."
Jordan C.T., Cao L., Roberson E.D., Duan S., Helms C.A., Nair R.P., Duffin K.C., Stuart P.E., Goldgar D., Hayashi G., Olfson E.H., Feng B.J., Pullinger C.R., Kane J.P., Wise C.A., Goldbach-Mansky R., Lowes M.A., Peddle L. expand/collapse author list , Chandran V., Liao W., Rahman P., Krueger G.G., Gladman D., Elder J.T., Menter A., Bowcock A.M.
Am. J. Hum. Genet. 90:796-808(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CYS-38; GLN-62; ARG-150; ASN-171; HIS-176; HIS-179; LEU-191; ASN-200; GLY-285; ASN-593; TRP-682; SER-714 AND GLU-973, VARIANTS PSORS2 SER-117; ALA-138; LYS-142 AND GLY-142, CHARACTERIZATION OF VARIANTS PSORS2 LYS-142 AND GLY-142.
+Additional computationally mapped references.

Web resources

Caspase recruitment domain family, member 14 (CARD14)

Leiden Open Variation Database (LOVD)

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF322642 mRNA. Translation: AAG53403.1.
AY032927 mRNA. Translation: AAK54453.1.
EU652409 mRNA. Translation: ACF49506.1.
AC087741 Genomic DNA. No translation available.
BC018142 mRNA. Translation: AAH18142.1.
BC001326 mRNA. Translation: AAH01326.1.
RefSeqNP_001244899.1. NM_001257970.1.
NP_077015.2. NM_024110.4.
NP_438170.1. NM_052819.2.
UniGeneHs.675480.
Hs.696253.
Hs.735899.

3D structure databases

ProteinModelPortalQ9BXL6.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122540. 3 interactions.
IntActQ9BXL6. 1 interaction.
MINTMINT-193865.
STRING9606.ENSP00000344549.

PTM databases

PhosphoSiteQ9BXL6.

Polymorphism databases

DMDM296434421.

Proteomic databases

PaxDbQ9BXL6.
PRIDEQ9BXL6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000344227; ENSP00000344549; ENSG00000141527. [Q9BXL6-1]
ENST00000570421; ENSP00000461806; ENSG00000141527. [Q9BXL6-2]
ENST00000573882; ENSP00000458715; ENSG00000141527. [Q9BXL6-1]
GeneID79092.
KEGGhsa:79092.
UCSCuc002jxv.3. human. [Q9BXL6-1]
uc002jxx.3. human.

Organism-specific databases

CTD79092.
GeneCardsGC17P078152.
H-InvDBHIX0173685.
HGNCHGNC:16446. CARD14.
HPAHPA022533.
HPA023388.
MIM173200. phenotype.
602723. phenotype.
607211. gene.
neXtProtNX_Q9BXL6.
Orphanet2897. Pityriasis rubra pilaris.
PharmGKBPA134959119.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG314915.
HOGENOMHOG000049174.
HOVERGENHBG106927.
InParanoidQ9BXL6.
OMAMEKNTHA.
OrthoDBEOG747PH5.
PhylomeDBQ9BXL6.
TreeFamTF315606.

Gene expression databases

ArrayExpressQ9BXL6.
BgeeQ9BXL6.
CleanExHS_CARD14.
GenevestigatorQ9BXL6.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
2.30.42.10. 1 hit.
3.40.50.300. 1 hit.
InterProIPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR008145. GK/Ca_channel_bsu.
IPR008144. Guanylate_kin-like.
IPR027417. P-loop_NTPase.
IPR001478. PDZ.
[Graphical view]
PfamPF00619. CARD. 1 hit.
[Graphical view]
SMARTSM00072. GuKc. 1 hit.
SM00228. PDZ. 1 hit.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
SSF50156. SSF50156. 1 hit.
SSF52540. SSF52540. 1 hit.
PROSITEPS50209. CARD. 1 hit.
PS50052. GUANYLATE_KINASE_2. 1 hit.
PS50106. PDZ. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCARD14. human.
GeneWikiCARD14.
GenomeRNAi79092.
NextBio67933.
PROQ9BXL6.
SOURCESearch...

Entry information

Entry nameCAR14_HUMAN
AccessionPrimary (citable) accession number: Q9BXL6
Secondary accession number(s): B8QQJ3, Q9BVB5
Entry history
Integrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: May 18, 2010
Last modified: April 16, 2014
This is version 115 of the entry and version 2 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

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 17

Human chromosome 17: entries, gene names and cross-references to MIM