CASPC_HUMAN
ID CASPC_HUMAN Reviewed; 341 AA.
AC Q6UXS9; D6RBN7;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 12-SEP-2018, sequence version 3.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Inactive caspase-12;
DE Short=CASP-12;
GN Name=CASP12; ORFNames=UNQ9415/PRO34398;
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] (ISOFORMS 1; 2 AND 3), FUNCTION, POLYMORPHISM,
RP TISSUE SPECIFICITY, AND VARIANT 125-ARG--ASN-341 DEL.
RC TISSUE=Lung;
RX PubMed=12054529; DOI=10.1016/s0006-291x(02)00289-9;
RA Fischer H., Koenig U., Eckhart L., Tschachler E.;
RT "Human caspase 12 has acquired deleterious mutations.";
RL Biochem. Biophys. Res. Commun. 293:722-726(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
RP POLYMORPHISM, FUNCTION, AND VARIANT 125-ARG--ASN-341 DEL.
RX PubMed=15129283; DOI=10.1038/nature02451;
RA Saleh M., Vaillancourt J.P., Graham R.K., Huyck M., Srinivasula S.M.,
RA Alnemri E.S., Steinberg M.H., Nolan V., Baldwin C.T., Hotchkiss R.S.,
RA Buchman T.G., Zehnbauer B.A., Hayden M.R., Farrer L.A., Roy S.,
RA Nicholson D.W.;
RT "Differential modulation of endotoxin responsiveness by human caspase-12
RT polymorphisms.";
RL Nature 429:75-79(2004).
RN [5]
RP POLYMORPHISM, AND VARIANT 125-ARG--ASN-341 DEL.
RX PubMed=16917906; DOI=10.1002/humu.9448;
RA Kachapati K., O'Brien T.R., Bergeron J., Zhang M., Dean M.;
RT "Population distribution of the functional caspase-12 allele.";
RL Hum. Mutat. 27:975-975(2006).
RN [6]
RP POLYMORPHISM, AND VARIANT 125-ARG--ASN-341 DEL.
RX PubMed=16532395; DOI=10.1086/503116;
RA Xue Y., Daly A., Yngvadottir B., Liu M., Coop G., Kim Y., Sabeti P.,
RA Chen Y., Stalker J., Huckle E., Burton J., Leonard S., Rogers J.,
RA Tyler-Smith C.;
RT "Spread of an inactive form of caspase-12 in humans is due to recent
RT positive selection.";
RL Am. J. Hum. Genet. 78:659-670(2006).
CC -!- FUNCTION: Has no protease activity. May reduce cytokine release in
CC response to bacterial lipopolysaccharide during infections. Reduces
CC activation of NF-kappa-B in response to TNF.
CC {ECO:0000269|PubMed:12054529, ECO:0000269|PubMed:15129283}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6UXS9-1; Sequence=Displayed;
CC Name=2; Synonyms=Alpha, Beta;
CC IsoId=Q6UXS9-2; Sequence=VSP_030954, VSP_030955;
CC Name=3;
CC IsoId=Q6UXS9-3; Sequence=VSP_030953;
CC -!- TISSUE SPECIFICITY: Detected in heart, kidney, liver, lung, pancreas,
CC small intestine, spleen, stomach, thymus and testis.
CC {ECO:0000269|PubMed:12054529}.
CC -!- POLYMORPHISM: The most frequent variant has a stop codon instead of
CC Arg-125, giving rise to truncated forms of isoform 1 (named delta,
CC epsilon, eta, gamma) and isoform 3 (iota, teta). The variant Arg-125
CC (Csp12-L) is rare, except in some populations from sub-Saharan Africa.
CC Csp12-L may increase the susceptibility to severe sepsis, and may also
CC increase the mortality rate in sepsis patients.
CC {ECO:0000269|PubMed:12054529, ECO:0000269|PubMed:15129283,
CC ECO:0000269|PubMed:16532395, ECO:0000269|PubMed:16917906}.
CC -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000305}.
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; AF464191; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AF464192; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AF464193; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AF464194; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AF464195; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AF486844; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AF486845; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AF486846; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AF486847; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AY358222; AAQ88589.1; -; mRNA.
DR RefSeq; NP_001177945.2; NM_001191016.2. [Q6UXS9-1]
DR AlphaFoldDB; Q6UXS9; -.
DR SMR; Q6UXS9; -.
DR BioGRID; 125680; 13.
DR IntAct; Q6UXS9; 5.
DR BindingDB; Q6UXS9; -.
DR ChEMBL; CHEMBL3831289; -.
DR MEROPS; C14.P01; -.
DR iPTMnet; Q6UXS9; -.
DR PhosphoSitePlus; Q6UXS9; -.
DR BioMuta; CASP12; -.
DR DMDM; 395398427; -.
DR jPOST; Q6UXS9; -.
DR MassIVE; Q6UXS9; -.
DR PaxDb; Q6UXS9; -.
DR PeptideAtlas; Q6UXS9; -.
DR PRIDE; Q6UXS9; -.
DR ProteomicsDB; 67653; -. [Q6UXS9-1]
DR ProteomicsDB; 67654; -. [Q6UXS9-2]
DR ProteomicsDB; 67655; -. [Q6UXS9-3]
DR DNASU; 100506742; -.
DR Ensembl; ENST00000417998.5; ENSP00000424963.1; ENSG00000204403.10. [Q6UXS9-2]
DR Ensembl; ENST00000458137.5; ENSP00000421408.1; ENSG00000204403.10. [Q6UXS9-2]
DR GeneID; 100506742; -.
DR KEGG; hsa:100506742; -.
DR UCSC; uc031qdp.3; human. [Q6UXS9-1]
DR CTD; 100506742; -.
DR DisGeNET; 100506742; -.
DR GeneCards; CASP12; -.
DR HGNC; HGNC:19004; CASP12.
DR MIM; 608633; gene.
DR neXtProt; NX_Q6UXS9; -.
DR OpenTargets; ENSG00000204403; -.
DR VEuPathDB; HostDB:ENSG00000204403; -.
DR GeneTree; ENSGT00940000162555; -.
DR HOGENOM; CLU_1585906_0_0_1; -.
DR InParanoid; Q6UXS9; -.
DR PhylomeDB; Q6UXS9; -.
DR TreeFam; TF102023; -.
DR BRENDA; 3.4.22.B66; 2681.
DR PathwayCommons; Q6UXS9; -.
DR SignaLink; Q6UXS9; -.
DR SIGNOR; Q6UXS9; -.
DR BioGRID-ORCS; 100506742; 10 hits in 643 CRISPR screens.
DR ChiTaRS; CASP12; human.
DR GenomeRNAi; 100506742; -.
DR Pharos; Q6UXS9; Tbio.
DR PRO; PR:Q6UXS9; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q6UXS9; protein.
DR Bgee; ENSG00000204403; Expressed in right lung and 93 other tissues.
DR ExpressionAtlas; Q6UXS9; baseline and differential.
DR Genevisible; Q6UXS9; HS.
DR GO; GO:0097169; C:AIM2 inflammasome complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:ParkinsonsUK-UCL.
DR GO; GO:0072557; C:IPAF inflammasome complex; IBA:GO_Central.
DR GO; GO:0072559; C:NLRP3 inflammasome complex; IBA:GO_Central.
DR GO; GO:0097199; F:cysteine-type endopeptidase activity involved in apoptotic signaling pathway; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IEA:InterPro.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
DR GO; GO:0050727; P:regulation of inflammatory response; IBA:GO_Central.
DR CDD; cd00032; CASc; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR029030; Caspase-like_dom_sf.
DR InterPro; IPR035713; Caspase_12.
DR InterPro; IPR033139; Caspase_cys_AS.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR002398; Pept_C14.
DR InterPro; IPR002138; Pept_C14_p10.
DR InterPro; IPR001309; Pept_C14_p20.
DR InterPro; IPR015917; Pept_C14A.
DR PANTHER; PTHR10454; PTHR10454; 2.
DR PANTHER; PTHR10454:SF134; PTHR10454:SF134; 2.
DR Pfam; PF00619; CARD; 1.
DR PRINTS; PR00376; IL1BCENZYME.
DR SMART; SM00115; CASc; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF52129; SSF52129; 1.
DR PROSITE; PS50209; CARD; 1.
DR PROSITE; PS01122; CASPASE_CYS; 1.
DR PROSITE; PS50207; CASPASE_P10; 1.
DR PROSITE; PS50208; CASPASE_P20; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Phosphoprotein; Reference proteome.
FT CHAIN 1..341
FT /note="Inactive caspase-12"
FT /id="PRO_0000317441"
FT DOMAIN 1..92
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT ACT_SITE 172
FT /evidence="ECO:0000255"
FT ACT_SITE 220
FT /evidence="ECO:0000255"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q920D5"
FT MOD_RES 90
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q920D5"
FT VAR_SEQ 3..86
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12054529"
FT /id="VSP_030953"
FT VAR_SEQ 87..168
FT /note="DISSDGEREANMPGLNIRNKEFNYLHNRNGSELDLLGMRDLLENLGYSVVIK
FT ENLTAQEMETALRQFAAHPEHQSSDSTFLV -> AFLEIQGAQPSGKLKLCPHAHFHEL
FT KTKRADEIYPVMEKERRTCLASTSATKNSTIFIIEMVLNLTFWGCEIYLKTLDTQWL
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12054529"
FT /id="VSP_030954"
FT VAR_SEQ 169..341
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12054529"
FT /id="VSP_030955"
FT VARIANT 68
FT /note="I -> T (in dbSNP:rs693001)"
FT /id="VAR_080638"
FT VARIANT 125..341
FT /note="Missing (in dbSNP:rs497116)"
FT /evidence="ECO:0000269|PubMed:12054529,
FT ECO:0000269|PubMed:15129283, ECO:0000269|PubMed:16532395,
FT ECO:0000269|PubMed:16917906"
FT /id="VAR_080639"
FT VARIANT 238
FT /note="S -> G (in dbSNP:rs647039)"
FT /id="VAR_080640"
FT CONFLICT Q6UXS9-2:88
FT /note="F -> L (in Ref. 1; AF486844/AF486845)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 341 AA; 38907 MW; 5D7DFAA40D91B18A CRC64;
MADEKPSNGV LVHMVKLLIK TFLDGIFDDL MENNVLNTDE IHLIGKCLKF VVSNAENLVD
DITETAQIAG KIFREHLWNS KKQLSSDISS DGEREANMPG LNIRNKEFNY LHNRNGSELD
LLGMRDLLEN LGYSVVIKEN LTAQEMETAL RQFAAHPEHQ SSDSTFLVFM SHSILNGICG
TKHWDQEPDV LHDDTIFEIF NNRNCQSLKD KPKVIIMQAC RGNGAGIVWF TTDSGKASAD
THGRLLQGNI CNDAVTKAHV EKDFIAFKSS TPHNVSWRHE TNGSVFISQI IYYFREYSWS
HHLEEIFQKV QHSFETPNIL TQLPTIERLS MTRYFYLFPG N
