ID   CAR18_HUMAN             Reviewed;          90 AA.
AC   P57730; A2RRF8;
DT   11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT   11-JAN-2001, sequence version 1.
DT   27-MAR-2024, entry version 160.
DE   RecName: Full=Caspase recruitment domain-containing protein 18;
DE   AltName: Full=Caspase-1 inhibitor Iceberg;
GN   Name=CARD18; Synonyms=ICEBERG; ORFNames=UNQ5804/PRO19611;
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 [MRNA], STRUCTURE BY NMR, FUNCTION, INTERACTION WITH
RP   CASP1, INDUCTION, AND TISSUE SPECIFICITY.
RX   PubMed=11051551; DOI=10.1016/s0092-8674(00)00108-2;
RA   Humke E.W., Shriver S.K., Starovasnik M.A., Fairbrother W.J., Dixit V.M.;
RT   "ICEBERG: a novel inhibitor of interleukin-1beta generation.";
RL   Cell 103:99-111(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=12975309; DOI=10.1101/gr.1293003;
RA   Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA   Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA   Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA   Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA   Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA   Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA   Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA   Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT   "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT   identify novel human secreted and transmembrane proteins: a bioinformatics
RT   assessment.";
RL   Genome Res. 13:2265-2270(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   INTERACTION WITH CARD8.
RX   PubMed=11821383; DOI=10.1074/jbc.m107811200;
RA   Razmara M., Srinivasula S.M., Wang L., Poyet J.-L., Geddes B.J.,
RA   DiStefano P.S., Bertin J., Alnemri E.S.;
RT   "CARD-8 protein, a new CARD family member that regulates caspase-1
RT   activation and apoptosis.";
RL   J. Biol. Chem. 277:13952-13958(2002).
CC   -!- FUNCTION: Inhibits generation of IL-1-beta by interacting with caspase-
CC       1 and preventing its association with RIP2. Down-regulates the release
CC       of IL1B. {ECO:0000269|PubMed:11051551}.
CC   -!- SUBUNIT: Interacts with pro-CASP1. Interacts with CARD8.
CC       {ECO:0000269|PubMed:11051551, ECO:0000269|PubMed:11821383}.
CC   -!- INTERACTION:
CC       P57730; P29466: CASP1; NbExp=3; IntAct=EBI-16203975, EBI-516667;
CC   -!- TISSUE SPECIFICITY: Primarily expressed in the heart and placenta.
CC       {ECO:0000269|PubMed:11051551}.
CC   -!- INDUCTION: Up-regulated in response to TNF and bacterial
CC       lipopolysaccharides (LPS). {ECO:0000269|PubMed:11051551}.
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DR   EMBL; AF208005; AAG23528.1; -; mRNA.
DR   EMBL; AY358231; AAQ88598.1; -; mRNA.
DR   EMBL; BC131610; AAI31611.1; -; mRNA.
DR   CCDS; CCDS53705.1; -.
DR   RefSeq; NP_067546.1; NM_021571.3.
DR   PDB; 1DGN; NMR; -; A=2-90.
DR   PDBsum; 1DGN; -.
DR   AlphaFoldDB; P57730; -.
DR   SMR; P57730; -.
DR   DIP; DIP-41317N; -.
DR   IntAct; P57730; 1.
DR   STRING; 9606.ENSP00000436691; -.
DR   iPTMnet; P57730; -.
DR   PhosphoSitePlus; P57730; -.
DR   BioMuta; CARD18; -.
DR   DMDM; 12230142; -.
DR   MassIVE; P57730; -.
DR   PaxDb; 9606-ENSP00000436691; -.
DR   PeptideAtlas; P57730; -.
DR   ProteomicsDB; 57022; -.
DR   Antibodypedia; 50206; 76 antibodies from 17 providers.
DR   DNASU; 59082; -.
DR   Ensembl; ENST00000530950.2; ENSP00000436691.1; ENSG00000255501.3.
DR   GeneID; 59082; -.
DR   KEGG; hsa:59082; -.
DR   MANE-Select; ENST00000530950.2; ENSP00000436691.1; NM_021571.4; NP_067546.1.
DR   UCSC; uc021qpy.2; human.
DR   AGR; HGNC:28861; -.
DR   CTD; 59082; -.
DR   DisGeNET; 59082; -.
DR   GeneCards; CARD18; -.
DR   HGNC; HGNC:28861; CARD18.
DR   HPA; ENSG00000255501; Tissue enriched (skin).
DR   MIM; 605354; gene.
DR   neXtProt; NX_P57730; -.
DR   OpenTargets; ENSG00000255501; -.
DR   PharmGKB; PA164717642; -.
DR   VEuPathDB; HostDB:ENSG00000255501; -.
DR   eggNOG; KOG3573; Eukaryota.
DR   GeneTree; ENSGT00940000164349; -.
DR   HOGENOM; CLU_119795_1_0_1; -.
DR   InParanoid; P57730; -.
DR   OMA; IFIQSVG; -.
DR   OrthoDB; 4739063at2759; -.
DR   PhylomeDB; P57730; -.
DR   PathwayCommons; P57730; -.
DR   SignaLink; P57730; -.
DR   BioGRID-ORCS; 59082; 12 hits in 1141 CRISPR screens.
DR   ChiTaRS; CARD18; human.
DR   EvolutionaryTrace; P57730; -.
DR   GenomeRNAi; 59082; -.
DR   Pharos; P57730; Tbio.
DR   PRO; PR:P57730; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; P57730; Protein.
DR   Bgee; ENSG00000255501; Expressed in upper arm skin and 97 other cell types or tissues.
DR   ExpressionAtlas; P57730; baseline and differential.
DR   GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR   GO; GO:0050700; F:CARD domain binding; IPI:UniProtKB.
DR   GO; GO:0089720; F:caspase binding; IPI:UniProtKB.
DR   GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR   GO; GO:0006954; P:inflammatory response; NAS:UniProtKB.
DR   GO; GO:0097340; P:inhibition of cysteine-type endopeptidase activity; IDA:UniProtKB.
DR   GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IDA:UniProtKB.
DR   GO; GO:0032091; P:negative regulation of protein binding; IDA:UniProtKB.
DR   GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
DR   CDD; cd08325; CARD_CASP1-like; 1.
DR   Gene3D; 1.10.533.10; Death Domain, Fas; 1.
DR   InterPro; IPR001315; CARD.
DR   InterPro; IPR011029; DEATH-like_dom_sf.
DR   PANTHER; PTHR47901; CASPASE RECRUITMENT DOMAIN-CONTAINING PROTEIN 18; 1.
DR   PANTHER; PTHR47901:SF3; CASPASE-1; 1.
DR   Pfam; PF00619; CARD; 1.
DR   SUPFAM; SSF47986; DEATH domain; 1.
DR   PROSITE; PS50209; CARD; 1.
DR   Genevisible; P57730; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Protease inhibitor; Reference proteome;
KW   Thiol protease inhibitor.
FT   CHAIN           1..90
FT                   /note="Caspase recruitment domain-containing protein 18"
FT                   /id="PRO_0000084145"
FT   DOMAIN          1..90
FT                   /note="CARD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT   HELIX           5..8
FT                   /evidence="ECO:0007829|PDB:1DGN"
FT   HELIX           10..14
FT                   /evidence="ECO:0007829|PDB:1DGN"
FT   HELIX           19..32
FT                   /evidence="ECO:0007829|PDB:1DGN"
FT   HELIX           37..44
FT                   /evidence="ECO:0007829|PDB:1DGN"
FT   HELIX           50..63
FT                   /evidence="ECO:0007829|PDB:1DGN"
FT   HELIX           66..79
FT                   /evidence="ECO:0007829|PDB:1DGN"
FT   HELIX           83..87
FT                   /evidence="ECO:0007829|PDB:1DGN"
SQ   SEQUENCE   90 AA;  10138 MW;  7E74C74263367101 CRC64;
     MADQLLRKKR RIFIHSVGAG TINALLDCLL EDEVISQEDM NKVRDENDTV MDKARVLIDL
     VTGKGPKSCC KFIKHLCEED PQLASKMGLH
//