ID CASPA_HUMAN Reviewed; 521 AA. AC Q92851; Q68HC0; Q6KF62; Q6KF63; Q8IUP5; Q8WYQ8; Q99845; Q9Y2U6; AC Q9Y2U7; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2001, sequence version 3. DT 11-NOV-2015, entry version 172. DE RecName: Full=Caspase-10; DE Short=CASP-10; DE EC=3.4.22.63; DE AltName: Full=Apoptotic protease Mch-4; DE AltName: Full=FAS-associated death domain protein interleukin-1B-converting enzyme 2; DE Short=FLICE2; DE AltName: Full=ICE-like apoptotic protease 4; DE Contains: DE RecName: Full=Caspase-10 subunit p23/17; DE Contains: DE RecName: Full=Caspase-10 subunit p12; DE Flags: Precursor; GN Name=CASP10; Synonyms=MCH4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), AND VARIANT ILE-479 (ISOFORM RP B). RC TISSUE=T-cell; RX PubMed=8755496; DOI=10.1073/pnas.93.15.7464; RA Fernandes-Alnemri T., Armstrong R.C., Krebs J.F., Srinivasula S.M., RA Wang L., Bullrich F., Fritz L.C., Trapani J.A., Tomaselli K.J., RA Litwack G., Alnemri E.S.; RT "In vitro activation of CPP32 and Mch3 by Mch4, a novel human RT apoptotic cysteine protease containing two FADD-like domains."; RL Proc. Natl. Acad. Sci. U.S.A. 93:7464-7469(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A). RX PubMed=9045686; DOI=10.1074/jbc.272.10.6578; RA Vincenz C., Dixit V.M.; RT "Fas-associated death domain protein interleukin-1beta-converting RT enzyme 2 (FLICE2), an ICE/Ced-3 homologue, is proximally involved in RT CD95- and p55-mediated death signaling."; RL J. Biol. Chem. 272:6578-6583(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS C AND D), VARIANT ILE-410, AND RP VARIANT ILE-522 (ISOFORM D). RC TISSUE=Spleen, and Thymus; RX PubMed=10187817; DOI=10.1074/jbc.274.15.10301; RA Ng P.W., Porter A.G., Janicke R.U.; RT "Molecular cloning and characterization of two novel pro-apoptotic RT isoforms of caspase-10."; RL J. Biol. Chem. 274:10301-10308(1999). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORMS A RP AND B), AND VARIANT ILE-479 (ISOFORM B). RX PubMed=11161814; DOI=10.1006/geno.2000.6392; RA Hadano S., Yanagisawa Y., Skaug J., Fichter K., Nasir J., RA Martindale D., Koop B.F., Scherer S.W., Nicholson D.W., Rouleau G.A., RA Ikeda J.-E., Hayden M.R.; RT "Cloning and characterization of three novel genes, ALS2CR1, ALS2CR2, RT and ALS2CR3, in the juvenile amyotrophic lateral sclerosis (ALS2) RT critical region at chromosome 2q33-q34: candidate genes for ALS2."; RL Genomics 71:200-213(2001). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5 AND 6), AND VARIANT ILE-455 RP (ISOFORM 6). RC TISSUE=Blood; RA Vonarbourg C., Fischer A., Rieux-Laucat F.; RT "A novel human caspase 10 isoform participating in Fas-induced RT apoptosis."; RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7). RA Wang P.Z.; RT "Three novel isoforms of caspase family that are deficient of RT conservative CASP domain."; RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS CYS-239; ILE-410; RP SER-444; CYS-446 AND ILE-522 (ISOFORM 2). RG NIEHS SNPs program; RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 4."; RL Nature 434:724-731(2005). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM D). RC TISSUE=Brain; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP PARTIAL PROTEIN SEQUENCE, AND PROTEOLYTIC PROCESSING. RX PubMed=8962078; DOI=10.1073/pnas.93.25.14486; RA Srinivasula S.M., Ahmad M., Fernandes-Alnemri T., Litwack G., RA Alnemri E.S.; RT "Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 RT protease Mch5 is a CrmA-inhibitable protease that activates multiple RT Ced-3/ICE-like cysteine proteases."; RL Proc. Natl. Acad. Sci. U.S.A. 93:14486-14491(1996). RN [12] RP FUNCTION, SELF-ASSOCIATION, INTERACTION WITH FADD, INTERACTION WITH RP CASP8, IDENTIFICATION IN A COMPLEX WITH FAS; FADD AND CASP8, AND RP MUTAGENESIS OF CYS-401. RX PubMed=11717445; DOI=10.1073/pnas.241358198; RA Wang J., Chun H.J., Wong W., Spencer D.M., Lenardo M.J.; RT "Caspase-10 is an initiator caspase in death receptor signaling."; RL Proc. Natl. Acad. Sci. U.S.A. 98:13884-13888(2001). RN [13] RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S). RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8; RA Hillman R.T., Green R.E., Brenner S.E.; RT "An unappreciated role for RNA surveillance."; RL Genome Biol. 5:R8.1-R8.16(2004). RN [14] RP INTERACTION WITH RFFL AND RNF34. RX PubMed=15069192; DOI=10.1073/pnas.0307459101; RA McDonald E.R. III, El-Deiry W.S.; RT "Suppression of caspase-8- and -10-associated RING proteins results in RT sensitization to death ligands and inhibition of tumor cell growth."; RL Proc. Natl. Acad. Sci. U.S.A. 101:6170-6175(2004). RN [15] RP VARIANT ALPS2A PHE-285, VARIANT ILE-410, AND ALTERNATIVE SPLICING RP (ISOFORMS B AND D). RX PubMed=10412980; DOI=10.1016/S0092-8674(00)80605-4; RA Wang J., Zheng L., Lobito A., Chan F.K., Dale J., Sneller M., Yao X., RA Puck J.M., Straus S.E., Lenardo M.J.; RT "Inherited human caspase 10 mutations underlie defective lymphocyte RT and dendritic cell apoptosis in autoimmune lymphoproliferative RT syndrome type II."; RL Cell 98:47-58(1999). RN [16] RP VARIANT NHL VAL-414. RX PubMed=12010812; DOI=10.1182/blood.V99.11.4094; RA Shin M.S., Kim H.S., Kang C.S., Park W.S., Kim S.Y., Lee S.N., RA Lee J.H., Park J.Y., Jang J.J., Kim C.W., Kim S.H., Lee J.Y., RA Yoo N.J., Lee S.H.; RT "Inactivating mutations of CASP10 gene in non-Hodgkin lymphomas."; RL Blood 99:4094-4099(2002). RN [17] RP VARIANT GASC THR-147, AND CHARACTERIZATION OF VARIANT GASC THR-147. RX PubMed=11973654; DOI=10.1038/sj.onc.1205394; RA Park W.S., Lee J.H., Shin M.S., Park J.Y., Kim H.S., Lee J.H., RA Kim Y.S., Lee S.N., Xiao W., Park C.H., Lee S.H., Yoo N.J., Lee J.Y.; RT "Inactivating mutations of the caspase-10 gene in gastric cancer."; RL Oncogene 21:2919-2925(2002). RN [18] RP VARIANT ALPS2A LEU-406, VARIANTS ILE-410 AND CYS-446, CHARACTERIZATION RP OF VARIANTS ALPS2A LEU-406, AND CHARACTERIZATION OF VARIANTS ILE-410 RP AND CYS-446. RX PubMed=16446975; DOI=10.1007/s00439-006-0138-9; RA Zhu S., Hsu A.P., Vacek M.M., Zheng L., Schaeffer A.A., Dale J.K., RA Davis J., Fischer R.E., Straus S.E., Boruchov D., Saulsbury F.T., RA Lenardo M.J., Puck J.M.; RT "Genetic alterations in caspase-10 may be causative or protective in RT autoimmune lymphoproliferative syndrome."; RL Hum. Genet. 119:284-294(2006). RN [19] RP VARIANT ILE-522 (ISOFORM D), AND RISK FACTOR FOR CUTANEOUS MELANOMA. RX PubMed=18563783; DOI=10.1002/humu.20803; RA Li C., Zhao H., Hu Z., Liu Z., Wang L.-E., Gershenwald J.E., RA Prieto V.G., Lee J.E., Duvic M., Grimm E.A., Wei Q.; RT "Genetic variants and haplotypes of the caspase-8 and caspase-10 genes RT contribute to susceptibility to cutaneous melanoma."; RL Hum. Mutat. 29:1443-1451(2008). RN [20] RP VARIANTS CYS-21 AND PRO-285. RX PubMed=19900088; DOI=10.1080/00313020903041143; RA Kim M.S., Oh J.E., Min C.K., Lee S., Chung N.G., Yoo N.J., Lee S.H.; RT "Mutational analysis of CASP10 gene in acute leukaemias and multiple RT myelomas."; RL Pathology 41:484-487(2009). RN [21] RP VARIANT THR-14. RX PubMed=20025484; DOI=10.3109/00313020903434371; RA Oh J.E., Kim M.S., Ahn C.H., Kim S.S., Han J.Y., Lee S.H., Yoo N.J.; RT "Mutational analysis of CASP10 gene in colon, breast, lung and RT hepatocellular carcinomas."; RL Pathology 42:73-76(2010). CC -!- FUNCTION: Involved in the activation cascade of caspases CC responsible for apoptosis execution. Recruited to both Fas- and CC TNFR-1 receptors in a FADD dependent manner. May participate in CC the granzyme B apoptotic pathways. Cleaves and activates caspase- CC 3, -4, -6, -7, -8, and -9. Hydrolyzes the small- molecule CC substrates, Tyr-Val-Ala-Asp-|-AMC and Asp-Glu-Val-Asp-|-AMC. CC {ECO:0000269|PubMed:11717445}. CC -!- FUNCTION: Isoform C is proteolytically inactive. CC {ECO:0000269|PubMed:11717445}. CC -!- CATALYTIC ACTIVITY: Strict requirement for Asp at position P1 and CC has a preferred cleavage sequence of Leu-Gln-Thr-Asp-|-Gly. CC -!- SUBUNIT: Heterotetramer that consists of two anti-parallel CC arranged heterodimers, each one formed by a 23/17 kDa (p23/17) CC (depending on the splicing events) and a 12 kDa (p12) subunit (By CC similarity). Self-associates. Interacts with FADD and CASP8. Found CC in a Fas signaling complex consisting of FAS, FADD, CASP8 and CC CASP10. Interacts with RFFL and RNF34; negatively regulate CASP10 CC through proteasomal degradation. {ECO:0000250, CC ECO:0000269|PubMed:11717445, ECO:0000269|PubMed:15069192}. CC -!- INTERACTION: CC Q14790:CASP8; NbExp=3; IntAct=EBI-495095, EBI-78060; CC O15519:CFLAR; NbExp=3; IntAct=EBI-495095, EBI-514941; CC O14730:RIOK3; NbExp=4; IntAct=EBI-495095, EBI-1047061; CC Q13546:RIPK1; NbExp=2; IntAct=EBI-495095, EBI-358507; CC P98170:XIAP; NbExp=3; IntAct=EBI-495095, EBI-517127; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=7; CC Name=A; Synonyms=10-A; CC IsoId=Q92851-1; Sequence=Displayed; CC Name=B; Synonyms=10-B, 10-S; CC IsoId=Q92851-2; Sequence=VSP_000819, VSP_000820; CC Note=May be produced at very low levels due to a premature stop CC codon in the mRNA, leading to nonsense-mediated mRNA decay. CC Variant in position: 479:L->I (in dbSNP:rs13006529).; CC Name=D; Synonyms=10-D, 10-L; CC IsoId=Q92851-4; Sequence=VSP_000820; CC Note=Variant in position: 522:L->I (not associated with CC significantly altered cutaneous melanoma risk, CC dbSNP:rs13006529).; CC Name=C; Synonyms=10-C; CC IsoId=Q92851-3; Sequence=VSP_000821, VSP_000822; CC Note=May be produced at very low levels due to a premature stop CC codon in the mRNA, leading to nonsense-mediated mRNA decay.; CC Name=5; CC IsoId=Q92851-5; Sequence=VSP_000819; CC Name=6; CC IsoId=Q92851-6; Sequence=VSP_037229, VSP_000820; CC Note=Variant in position: 455:L->I (in dbSNP:rs13006529).; CC Name=7; CC IsoId=Q92851-7; Sequence=VSP_053333, VSP_053334; CC -!- TISSUE SPECIFICITY: Detectable in most tissues. Lowest expression CC is seen in brain, kidney, prostate, testis and colon. CC -!- PTM: Cleavage by granzyme B and autocatalytic activity generate CC the two active subunits. CC -!- DISEASE: Autoimmune lymphoproliferative syndrome 2A (ALPS2A) CC [MIM:603909]: A disorder of apoptosis that manifests in early CC childhood and results in the accumulation of autoreactive CC lymphocytes. It is characterized by non-malignant lymphadenopathy CC with hepatosplenomegaly, and autoimmune hemolytic anemia, CC thrombocytopenia and neutropenia. {ECO:0000269|PubMed:10412980, CC ECO:0000269|PubMed:16446975}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Familial non-Hodgkin lymphoma (NHL) [MIM:605027]: Cancer CC that starts in cells of the lymph system, which is part of the CC body's immune system. NHLs can occur at any age and are often CC marked by enlarged lymph nodes, fever and weight loss. CC {ECO:0000269|PubMed:12010812}. Note=The gene represented in this CC entry is involved in disease pathogenesis. CC -!- DISEASE: Gastric cancer (GASC) [MIM:613659]: A malignant disease CC which starts in the stomach, can spread to the esophagus or the CC small intestine, and can extend through the stomach wall to nearby CC lymph nodes and organs. It also can metastasize to other parts of CC the body. The term gastric cancer or gastric carcinoma refers to CC adenocarcinoma of the stomach that accounts for most of all CC gastric malignant tumors. Two main histologic types are CC recognized, diffuse type and intestinal type carcinomas. Diffuse CC tumors are poorly differentiated infiltrating lesions, resulting CC in thickening of the stomach. In contrast, intestinal tumors are CC usually exophytic, often ulcerating, and associated with CC intestinal metaplasia of the stomach, most often observed in CC sporadic disease. {ECO:0000269|PubMed:11973654}. Note=The gene CC represented in this entry is involved in disease pathogenesis. CC -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000305}. CC -!- SIMILARITY: Contains 2 DED (death effector) domains. CC {ECO:0000255|PROSITE-ProRule:PRU00065}. CC -!- WEB RESOURCE: Name=CASP10base; Note=CASP10 mutation db; CC URL="http://structure.bmc.lu.se/idbase/CASP10base/"; CC -!- WEB RESOURCE: Name=Autoimmune Lymphoproliferative Syndrome CC Database (ALPSbase); Note=Caspase-10 mutations causing ALPS type CC II; CC URL="http://research.nhgri.nih.gov/ALPS/alpsII_mut.shtml"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/casp10/"; 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; U60519; AAC50644.1; -; mRNA. DR EMBL; U86214; AAB46730.1; -; mRNA. DR EMBL; AF111344; AAD28402.1; -; mRNA. DR EMBL; AF111345; AAD28403.1; -; mRNA. DR EMBL; AB038979; BAB32553.1; -; Genomic_DNA. DR EMBL; AB038979; BAB32554.1; -; Genomic_DNA. DR EMBL; AJ487678; CAD32371.1; -; mRNA. DR EMBL; AJ487679; CAD32372.1; -; mRNA. DR EMBL; AY690601; AAU00989.1; -; mRNA. DR EMBL; EF050529; ABJ53426.1; -; Genomic_DNA. DR EMBL; AC007283; AAY24291.1; -; Genomic_DNA. DR EMBL; CH471063; EAW70248.1; -; Genomic_DNA. DR EMBL; CH471063; EAW70249.1; -; Genomic_DNA. DR EMBL; BC042844; AAH42844.1; -; mRNA. DR CCDS; CCDS2338.1; -. [Q92851-1] DR CCDS; CCDS2339.1; -. [Q92851-2] DR CCDS; CCDS2340.1; -. [Q92851-4] DR CCDS; CCDS56159.1; -. [Q92851-6] DR CCDS; CCDS56160.1; -. [Q92851-5] DR CCDS; CCDS77506.1; -. [Q92851-7] DR RefSeq; NP_001193453.1; NM_001206524.1. [Q92851-6] DR RefSeq; NP_001193471.1; NM_001206542.1. [Q92851-5] DR RefSeq; NP_001221.2; NM_001230.4. [Q92851-2] DR RefSeq; NP_001293012.1; NM_001306083.1. [Q92851-7] DR RefSeq; NP_116756.2; NM_032974.4. [Q92851-1] DR RefSeq; NP_116758.1; NM_032976.3. [Q92851-3] DR RefSeq; NP_116759.2; NM_032977.3. [Q92851-4] DR UniGene; Hs.5353; -. DR ProteinModelPortal; Q92851; -. DR SMR; Q92851; 20-189, 273-499. DR BioGrid; 107293; 91. DR IntAct; Q92851; 22. DR MINT; MINT-201954; -. DR STRING; 9606.ENSP00000286186; -. DR BindingDB; Q92851; -. DR ChEMBL; CHEMBL5037; -. DR MEROPS; C14.011; -. DR PhosphoSite; Q92851; -. DR BioMuta; CASP10; -. DR DMDM; 12644463; -. DR MaxQB; Q92851; -. DR PaxDb; Q92851; -. DR PRIDE; Q92851; -. DR Ensembl; ENST00000272879; ENSP00000272879; ENSG00000003400. [Q92851-1] DR Ensembl; ENST00000286186; ENSP00000286186; ENSG00000003400. [Q92851-4] DR Ensembl; ENST00000313728; ENSP00000314599; ENSG00000003400. [Q92851-6] DR Ensembl; ENST00000346817; ENSP00000237865; ENSG00000003400. [Q92851-2] DR Ensembl; ENST00000360132; ENSP00000353250; ENSG00000003400. [Q92851-3] DR Ensembl; ENST00000374650; ENSP00000363781; ENSG00000003400. [Q92851-7] DR Ensembl; ENST00000448480; ENSP00000396835; ENSG00000003400. [Q92851-5] DR GeneID; 843; -. DR KEGG; hsa:843; -. DR UCSC; uc002uxi.1; human. DR UCSC; uc002uxj.1; human. [Q92851-4] DR UCSC; uc002uxk.1; human. [Q92851-2] DR UCSC; uc002uxl.2; human. [Q92851-1] DR UCSC; uc002uxm.2; human. [Q92851-5] DR UCSC; uc010fta.1; human. [Q92851-6] DR UCSC; uc010ftb.2; human. [Q92851-3] DR CTD; 843; -. DR GeneCards; CASP10; -. DR GeneReviews; CASP10; -. DR HGNC; HGNC:1500; CASP10. DR HPA; CAB003780; -. DR HPA; HPA017059; -. DR MIM; 601762; gene. DR MIM; 603909; phenotype. DR MIM; 605027; phenotype. DR MIM; 613659; phenotype. DR neXtProt; NX_Q92851; -. DR Orphanet; 3261; Autoimmune lymphoproliferative syndrome. DR PharmGKB; PA26084; -. DR eggNOG; KOG3573; Eukaryota. DR eggNOG; ENOG410ZQIE; LUCA. DR GeneTree; ENSGT00760000118912; -. DR HOGENOM; HOG000140947; -. DR HOVERGEN; HBG050803; -. DR InParanoid; Q92851; -. DR KO; K04400; -. DR OMA; GHADGDC; -. DR OrthoDB; EOG7CRTQM; -. DR PhylomeDB; Q92851; -. DR TreeFam; TF102023; -. DR BRENDA; 3.4.22.63; 2681. DR Reactome; R-HSA-75157; FasL/ CD95L signaling. DR Reactome; R-HSA-75158; TRAIL signaling. DR Reactome; R-HSA-933543; NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10. DR ChiTaRS; CASP10; human. DR GeneWiki; Caspase_10; -. DR GenomeRNAi; 843; -. DR NextBio; 3530; -. DR PMAP-CutDB; Q8IUP5; -. DR PRO; PR:Q92851; -. DR Proteomes; UP000005640; Chromosome 2. DR Bgee; Q92851; -. DR CleanEx; HS_CASP10; -. DR ExpressionAtlas; Q92851; baseline and differential. DR Genevisible; Q92851; HS. DR GO; GO:0031265; C:CD95 death-inducing signaling complex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0097342; C:ripoptosome; IDA:UniProtKB. DR GO; GO:0004197; F:cysteine-type endopeptidase activity; TAS:ProtInc. DR GO; GO:0097199; F:cysteine-type endopeptidase activity involved in apoptotic signaling pathway; IMP:UniProtKB. DR GO; GO:0035877; F:death effector domain binding; IPI:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IBA:GO_Central. DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc. DR GO; GO:0097190; P:apoptotic signaling pathway; TAS:Reactome. DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:Reactome. DR GO; GO:0045087; P:innate immune response; TAS:Reactome. DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB. DR Gene3D; 1.10.533.10; -; 2. DR Gene3D; 3.40.50.1460; -; 1. DR InterPro; IPR029030; Caspase-like_dom. DR InterPro; IPR011029; DEATH-like_dom. DR InterPro; IPR001875; DED_dom. DR InterPro; IPR011600; Pept_C14_caspase. DR InterPro; IPR001309; Pept_C14_ICE_p20. DR InterPro; IPR016129; Pept_C14_ICE_p20_AS. DR InterPro; IPR002138; Pept_C14_p10. DR InterPro; IPR015917; Pept_C14A_p45_core. DR Pfam; PF01335; DED; 2. DR Pfam; PF00656; Peptidase_C14; 1. DR PRINTS; PR00376; IL1BCENZYME. DR SMART; SM00115; CASc; 1. DR SMART; SM00031; DED; 2. DR SUPFAM; SSF47986; SSF47986; 2. DR PROSITE; PS01122; CASPASE_CYS; 1. DR PROSITE; PS01121; CASPASE_HIS; 1. DR PROSITE; PS50207; CASPASE_P10; 1. DR PROSITE; PS50208; CASPASE_P20; 1. DR PROSITE; PS50168; DED; 2. PE 1: Evidence at protein level; KW Alternative splicing; Apoptosis; Complete proteome; KW Direct protein sequencing; Disease mutation; Hydrolase; Polymorphism; KW Protease; Reference proteome; Repeat; Thiol protease; Zymogen. FT PROPEP 1 219 FT /FTId=PRO_0000004644. FT CHAIN 220 415 Caspase-10 subunit p23/17. FT /FTId=PRO_0000004645. FT CHAIN 416 521 Caspase-10 subunit p12. FT /FTId=PRO_0000004646. FT DOMAIN 19 97 DED 1. {ECO:0000255|PROSITE- FT ProRule:PRU00065}. FT DOMAIN 114 187 DED 2. {ECO:0000255|PROSITE- FT ProRule:PRU00065}. FT ACT_SITE 358 358 {ECO:0000250}. FT ACT_SITE 401 401 {ECO:0000250}. FT VAR_SEQ 229 271 Missing (in isoform B and isoform 5). FT {ECO:0000303|PubMed:8755496, FT ECO:0000303|Ref.5}. FT /FTId=VSP_000819. FT VAR_SEQ 229 247 QESWQNKHAGSNGNRATNG -> EGVFVFLNEGDRGNSPDD FT L (in isoform 7). {ECO:0000303|Ref.6}. FT /FTId=VSP_053333. FT VAR_SEQ 241 307 Missing (in isoform 6). FT {ECO:0000303|Ref.5}. FT /FTId=VSP_037229. FT VAR_SEQ 241 273 GNRATNGAPSLVSRGMQGASANTLNSETSTKRA -> EGSC FT VQDESEPQRPLCHCQQPQLYLPEGQTRNP (in isoform FT C). {ECO:0000303|PubMed:10187817}. FT /FTId=VSP_000821. FT VAR_SEQ 248 521 Missing (in isoform 7). FT {ECO:0000303|Ref.6}. FT /FTId=VSP_053334. FT VAR_SEQ 274 521 Missing (in isoform C). FT {ECO:0000303|PubMed:10187817}. FT /FTId=VSP_000822. FT VAR_SEQ 473 521 MLKFLEKTMEIRGRKRTVWGAKQISATSLPTAISAQTPRPP FT MRRWSSVS -> HEDILSILTAVNDDVSRRVDKQGTKKQMP FT QPAFTLRKKLVFPVPLDALSL (in isoform B, FT isoform D and isoform 6). FT {ECO:0000303|PubMed:10187817, FT ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:8755496, FT ECO:0000303|Ref.5}. FT /FTId=VSP_000820. FT VARIANT 14 14 K -> T (found in a colon cancer sample; FT somatic mutation). FT {ECO:0000269|PubMed:20025484}. FT /FTId=VAR_065233. FT VARIANT 21 21 R -> C (found in a multiple myeloma FT sample; somatic mutation). FT {ECO:0000269|PubMed:19900088}. FT /FTId=VAR_065234. FT VARIANT 147 147 M -> T (in GASC; somatic mutation; FT impairs CASP10-mediated apoptosis; FT dbSNP:rs121909776). FT {ECO:0000269|PubMed:11973654}. FT /FTId=VAR_037428. FT VARIANT 239 239 S -> C (in dbSNP:rs41473647). FT /FTId=VAR_055361. FT VARIANT 285 285 L -> F (in ALPS2A; dbSNP:rs17860403). FT {ECO:0000269|PubMed:10412980}. FT /FTId=VAR_014071. FT VARIANT 285 285 L -> P (found in a T-acute lymphoblastic FT leukemia sample; somatic mutation). FT {ECO:0000269|PubMed:19900088}. FT /FTId=VAR_065235. FT VARIANT 406 406 I -> L (in ALPS2A; the mutant protein has FT defective apoptosis and exerts a FT dominant-negative effect when FT cotransfected with the wild-type protein; FT dbSNP:rs80358239). FT {ECO:0000269|PubMed:16446975}. FT /FTId=VAR_037429. FT VARIANT 410 410 V -> I (does not interfere with apoptosis FT in a dominant negative manner; FT dbSNP:rs13010627). FT {ECO:0000269|PubMed:10187817, FT ECO:0000269|PubMed:10412980, FT ECO:0000269|PubMed:16446975}. FT /FTId=VAR_014072. FT VARIANT 414 414 A -> V (in NHL; somatic mutation; FT dbSNP:rs28936699). FT {ECO:0000269|PubMed:12010812}. FT /FTId=VAR_037430. FT VARIANT 444 444 P -> S (in dbSNP:rs41513147). FT /FTId=VAR_055362. FT VARIANT 446 446 Y -> C (associated with ALPS2A; does not FT interfere with apoptosis in a dominant FT negative manner; dbSNP:rs17860405). FT {ECO:0000269|PubMed:16446975}. FT /FTId=VAR_037431. FT MUTAGEN 401 401 C->A: Abolishes proteolytic activity. FT {ECO:0000269|PubMed:11717445}. FT CONFLICT 68 68 E -> G (in Ref. 2; AAB46730). FT {ECO:0000305}. FT CONFLICT 268 268 T -> A (in Ref. 3; AAD28403). FT {ECO:0000305}. SQ SEQUENCE 521 AA; 58951 MW; 840348AE602B8243 CRC64; MKSQGQHWYS SSDKNCKVSF REKLLIIDSN LGVQDVENLK FLCIGLVPNK KLEKSSSASD VFEHLLAEDL LSEEDPFFLA ELLYIIRQKK LLQHLNCTKE EVERLLPTRQ RVSLFRNLLY ELSEGIDSEN LKDMIFLLKD SLPKTEMTSL SFLAFLEKQG KIDEDNLTCL EDLCKTVVPK LLRNIEKYKR EKAIQIVTPP VDKEAESYQG EEELVSQTDV KTFLEALPQE SWQNKHAGSN GNRATNGAPS LVSRGMQGAS ANTLNSETST KRAAVYRMNR NHRGLCVIVN NHSFTSLKDR QGTHKDAEIL SHVFQWLGFT VHIHNNVTKV EMEMVLQKQK CNPAHADGDC FVFCILTHGR FGAVYSSDEA LIPIREIMSH FTALQCPRLA EKPKLFFIQA CQGEEIQPSV SIEADALNPE QAPTSLQDSI PAEADFLLGL ATVPGYVSFR HVEEGSWYIQ SLCNHLKKLV PRMLKFLEKT MEIRGRKRTV WGAKQISATS LPTAISAQTP RPPMRRWSSV S //