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 07-APR-2021, entry version 147. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 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; P57730; -. DR PeptideAtlas; P57730; -. DR PRIDE; P57730; -. DR ProteomicsDB; 57022; -. DR Antibodypedia; 50206; 57 antibodies. DR Ensembl; ENST00000530950; ENSP00000436691; ENSG00000255501. DR GeneID; 59082; -. DR KEGG; hsa:59082; -. DR UCSC; uc021qpy.2; human. DR CTD; 59082; -. DR DisGeNET; 59082; -. DR GeneCards; CARD18; -. DR HGNC; HGNC:28861; CARD18. DR HPA; ENSG00000255501; Tissue enhanced (breast, skin, tongue). DR MIM; 605354; gene. DR neXtProt; NX_P57730; -. DR OpenTargets; ENSG00000255501; -. DR PharmGKB; PA164717642; -. DR VEuPathDB; HostDB:ENSG00000255501.1; -. DR eggNOG; KOG3573; Eukaryota. DR GeneTree; ENSGT00940000164349; -. DR HOGENOM; CLU_119795_1_0_1; -. DR InParanoid; P57730; -. DR OMA; KSCCKFI; -. DR OrthoDB; 1534275at2759; -. DR PhylomeDB; P57730; -. DR PathwayCommons; P57730; -. DR BioGRID-ORCS; 59082; 6 hits in 982 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 zone of skin and 80 other tissues. DR ExpressionAtlas; P57730; baseline and differential. DR Genevisible; P57730; HS. 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 InterPro; IPR001315; CARD. DR InterPro; IPR011029; DEATH-like_dom_sf. DR Pfam; PF00619; CARD; 1. DR SUPFAM; SSF47986; SSF47986; 1. DR PROSITE; PS50209; CARD; 1. 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:0007744|PDB:1DGN" FT HELIX 10..14 FT /evidence="ECO:0007744|PDB:1DGN" FT HELIX 19..32 FT /evidence="ECO:0007744|PDB:1DGN" FT HELIX 37..44 FT /evidence="ECO:0007744|PDB:1DGN" FT HELIX 50..63 FT /evidence="ECO:0007744|PDB:1DGN" FT HELIX 66..79 FT /evidence="ECO:0007744|PDB:1DGN" FT HELIX 83..87 FT /evidence="ECO:0007744|PDB:1DGN" SQ SEQUENCE 90 AA; 10138 MW; 7E74C74263367101 CRC64; MADQLLRKKR RIFIHSVGAG TINALLDCLL EDEVISQEDM NKVRDENDTV MDKARVLIDL VTGKGPKSCC KFIKHLCEED PQLASKMGLH //