CAR19_HUMAN
ID CAR19_HUMAN Reviewed; 228 AA.
AC Q96LW7; Q5BJH8; Q9BSY2;
DT 02-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Caspase recruitment domain-containing protein 19;
DE AltName: Full=Bcl10-interacting CARD protein;
DE Short=BinCARD;
GN Name=CARD19; Synonyms=C9orf89;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Leukocyte, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH BCL10,
RP AND MUTAGENESIS OF LEU-17 AND LEU-65.
RX PubMed=15637807; DOI=10.1016/j.febslet.2004.10.094;
RA Woo H.-N., Hong G.-S., Jun J.-I., Cho D.-H., Choi H.-W., Lee H.-J.,
RA Chung C.-W., Kim I.-K., Jo D.-G., Pyo J.-O., Bertin J., Jung Y.-K.;
RT "Inhibition of Bcl10-mediated activation of NF-kappa B by BinCARD, a Bcl10-
RT interacting CARD protein.";
RL FEBS Lett. 578:239-244(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-113 (ISOFORM 2), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 3-101 OF MUTANT MET-16 AND MET-66,
RP ALTERNATIVE SPLICING, DISULFIDE BOND, AND SUBCELLULAR LOCATION (ISOFORMS 1
RP AND 2).
RX PubMed=23633586; DOI=10.1107/s0907444913001558;
RA Chen K.E., Richards A.A., Caradoc-Davies T.T., Vajjhala P.R., Robin G.,
RA Lua L.H., Hill J.M., Schroder K., Sweet M.J., Kellie S., Kobe B.,
RA Martin J.;
RT "The structure of the caspase recruitment domain of BinCARD reveals that
RT all three cysteines can be oxidized.";
RL Acta Crystallogr. D 69:774-784(2013).
CC -!- FUNCTION: Plays a role in inhibiting the effects of BCL10-induced
CC activation of NF-kappa-B. May inhibit the phosphorylation of BCL10 in a
CC CARD-dependent manner. {ECO:0000269|PubMed:15637807}.
CC -!- SUBUNIT: Associates with BCL10 by CARD-CARD interaction
CC (PubMed:15637807). {ECO:0000269|PubMed:15637807}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus
CC {ECO:0000269|PubMed:23633586}. Note=Coexpression with BCL10 induced
CC translocation from nucleus to cytosol.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:23633586}; Single-pass membrane protein
CC {ECO:0000269|PubMed:23633586}. Mitochondrion membrane
CC {ECO:0000269|PubMed:23633586}; Single-pass membrane protein
CC {ECO:0000269|PubMed:23633586}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96LW7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96LW7-2; Sequence=VSP_014723;
CC -!- TISSUE SPECIFICITY: Expressed in ovary, testis, placenta, skeletal
CC muscle, kidney, lung, heart and liver (at protein level). Expressed in
CC thymus and brain. {ECO:0000269|PubMed:15637807}.
CC -!- MISCELLANEOUS: [Isoform 2]: Appears to be the dominant isoform in
CC peripheral blood cell fractions. Contains a transmembrane helix.
CC {ECO:0000305}.
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DR EMBL; AK057716; BAB71550.1; -; mRNA.
DR EMBL; AL451065; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC004500; AAH04500.1; -; mRNA.
DR EMBL; BC038856; AAH38856.1; -; mRNA.
DR CCDS; CCDS6702.2; -. [Q96LW7-2]
DR RefSeq; NP_115686.3; NM_032310.4. [Q96LW7-2]
DR PDB; 4DWN; X-ray; 1.58 A; A/B=3-99.
DR PDB; 4FH0; X-ray; 1.40 A; A/B=3-101.
DR PDBsum; 4DWN; -.
DR PDBsum; 4FH0; -.
DR AlphaFoldDB; Q96LW7; -.
DR SMR; Q96LW7; -.
DR BioGRID; 123997; 27.
DR IntAct; Q96LW7; 9.
DR MINT; Q96LW7; -.
DR STRING; 9606.ENSP00000364613; -.
DR iPTMnet; Q96LW7; -.
DR PhosphoSitePlus; Q96LW7; -.
DR BioMuta; CARD19; -.
DR DMDM; 71658794; -.
DR EPD; Q96LW7; -.
DR jPOST; Q96LW7; -.
DR MassIVE; Q96LW7; -.
DR MaxQB; Q96LW7; -.
DR PeptideAtlas; Q96LW7; -.
DR PRIDE; Q96LW7; -.
DR ProteomicsDB; 77259; -. [Q96LW7-1]
DR ProteomicsDB; 77260; -. [Q96LW7-2]
DR Antibodypedia; 28349; 146 antibodies from 20 providers.
DR DNASU; 84270; -.
DR Ensembl; ENST00000375464.7; ENSP00000364613.2; ENSG00000165233.18. [Q96LW7-2]
DR Ensembl; ENST00000466409.1; ENSP00000437237.1; ENSG00000165233.18. [Q96LW7-1]
DR GeneID; 84270; -.
DR KEGG; hsa:84270; -.
DR MANE-Select; ENST00000375464.7; ENSP00000364613.2; NM_032310.5; NP_115686.3. [Q96LW7-2]
DR UCSC; uc004atd.4; human. [Q96LW7-1]
DR CTD; 84270; -.
DR DisGeNET; 84270; -.
DR GeneCards; CARD19; -.
DR HGNC; HGNC:28148; CARD19.
DR HPA; ENSG00000165233; Low tissue specificity.
DR MIM; 617726; gene.
DR neXtProt; NX_Q96LW7; -.
DR OpenTargets; ENSG00000165233; -.
DR PharmGKB; PA134909664; -.
DR VEuPathDB; HostDB:ENSG00000165233; -.
DR GeneTree; ENSGT00390000016408; -.
DR HOGENOM; CLU_103797_0_0_1; -.
DR InParanoid; Q96LW7; -.
DR OMA; TLQNSDC; -.
DR PhylomeDB; Q96LW7; -.
DR TreeFam; TF335747; -.
DR PathwayCommons; Q96LW7; -.
DR SignaLink; Q96LW7; -.
DR BioGRID-ORCS; 84270; 11 hits in 1062 CRISPR screens.
DR ChiTaRS; CARD19; human.
DR GenomeRNAi; 84270; -.
DR Pharos; Q96LW7; Tbio.
DR PRO; PR:Q96LW7; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q96LW7; protein.
DR Bgee; ENSG00000165233; Expressed in monocyte and 172 other tissues.
DR ExpressionAtlas; Q96LW7; baseline and differential.
DR Genevisible; Q96LW7; HS.
DR GO; GO:0005829; C:cytosol; NAS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005634; C:nucleus; NAS:UniProtKB.
DR GO; GO:0050700; F:CARD domain binding; NAS:UniProtKB.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; NAS:UniProtKB.
DR CDD; cd13785; CARD_BinCARD_like; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR043574; CARD19.
DR InterPro; IPR042146; CARD_BinCARD.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR PANTHER; PTHR34765; PTHR34765; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Disulfide bond; Endoplasmic reticulum;
KW Membrane; Mitochondrion; Nucleus; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..228
FT /note="Caspase recruitment domain-containing protein 19"
FT /id="PRO_0000064927"
FT DOMAIN 8..99
FT /note="CARD"
FT DISULFID 7..77
FT /note="Redox-active"
FT /evidence="ECO:0000269|PubMed:23633586"
FT VAR_SEQ 102..228
FT /note="RKFHITNHACLVLARGGHPSLPLMAWMSSMTTQVCCSPGLASPLASAPPQRP
FT PSGPEGRVWQAQAVQMLVSVSHFLPLPPSLSHGSFHTAWGILYVHSCPSFSNLIPRGSL
FT HVCVDSNLVPTAAWRS -> QNSDCTELDSGSQSGELSNRGPMSFLAGLGLAVGLALLL
FT YCYPPDPKGLPGTRRVLGFSPVIIDRHVSRYLLAFLADDLGGL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_014723"
FT MUTAGEN 17
FT /note="L->A: Abolishes the NF-kappa-B inhibitory activity."
FT /evidence="ECO:0000269|PubMed:15637807"
FT MUTAGEN 65
FT /note="L->A: Abolishes the NF-kappa-B inhibitory activity."
FT /evidence="ECO:0000269|PubMed:15637807"
FT HELIX 6..17
FT /evidence="ECO:0007829|PDB:4FH0"
FT HELIX 25..36
FT /evidence="ECO:0007829|PDB:4FH0"
FT STRAND 37..40
FT /evidence="ECO:0007829|PDB:4FH0"
FT HELIX 45..51
FT /evidence="ECO:0007829|PDB:4FH0"
FT HELIX 58..72
FT /evidence="ECO:0007829|PDB:4FH0"
FT HELIX 74..87
FT /evidence="ECO:0007829|PDB:4FH0"
FT HELIX 89..94
FT /evidence="ECO:0007829|PDB:4FH0"
FT HELIX 96..98
FT /evidence="ECO:0007829|PDB:4DWN"
FT MOD_RES Q96LW7-2:113
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
SQ SEQUENCE 228 AA; 25589 MW; 7A58F5AB69882CF8 CRC64;
MTDQTYCDRL VQDTPFLTGH GRLSEQQVDR IILQLNRYYP QILTNKEAEK FRNPKASLRV
RLCDLLSHLQ RSGERDCQEF YRALYIHAQP LHSRLPSRHA LRKFHITNHA CLVLARGGHP
SLPLMAWMSS MTTQVCCSPG LASPLASAPP QRPPSGPEGR VWQAQAVQML VSVSHFLPLP
PSLSHGSFHT AWGILYVHSC PSFSNLIPRG SLHVCVDSNL VPTAAWRS
