ID CASPA_HUMAN Reviewed; 521 AA. AC Q92851; Q68HC0; Q6KF62; Q6KF63; Q8IUP5; Q8WYQ8; Q99845; Q9Y2U6; Q9Y2U7; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2001, sequence version 3. DT 27-MAR-2024, entry version 233. DE RecName: Full=Caspase-10; DE Short=CASP-10; DE EC=3.4.22.63 {ECO:0000269|PubMed:16916640}; 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; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), AND VARIANT ILE-479 (ISOFORM 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., Litwack G., RA Alnemri E.S.; RT "In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic RT 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 enzyme 2 RT (FLICE2), an ICE/Ced-3 homologue, is proximally involved in CD95- and p55- RT 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 VARIANT RP 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 isoforms RT of caspase-10."; RL J. Biol. Chem. 274:10301-10308(1999). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORMS A AND B), RP 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., Martindale D., RA Koop B.F., Scherer S.W., Nicholson D.W., Rouleau G.A., Ikeda J.-E., RA Hayden M.R.; RT "Cloning and characterization of three novel genes, ALS2CR1, ALS2CR2, and RT ALS2CR3, in the juvenile amyotrophic lateral sclerosis (ALS2) critical RT 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 (ISOFORM RP 6). RC TISSUE=Blood; RA Vonarbourg C., Fischer A., Rieux-Laucat F.; RT "A novel human caspase 10 isoform participating in Fas-induced apoptosis."; RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7), AND FUNCTION (ISOFORM 7). RX PubMed=17822854; DOI=10.1016/j.bbagen.2007.07.010; RA Wang H., Wang P., Sun X., Luo Y., Wang X., Ma D., Wu J.; RT "Cloning and characterization of a novel caspase-10 isoform that activates RT NF-kappa B activity."; RL Biochim. Biophys. Acta 1770:1528-1537(2007). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS CYS-239; ILE-410; SER-444; RP 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., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., 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., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., 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., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 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., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., 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 project: RT 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., Alnemri E.S.; RT "Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease RT Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like RT 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 CASP8, RP IDENTIFICATION IN A COMPLEX WITH FAS; FADD AND CASP8, AND MUTAGENESIS OF RP 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 FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=16916640; DOI=10.1016/j.molcel.2006.06.020; RA Denault J.B., Bekes M., Scott F.L., Sexton K.M., Bogyo M., Salvesen G.S.; RT "Engineered hybrid dimers: tracking the activation pathway of caspase-7."; RL Mol. Cell 23:523-533(2006). RN [16] RP INTERACTION WITH RIOK3. RX PubMed=19557502; DOI=10.1007/s11010-009-0180-8; RA Shan J., Wang P., Zhou J., Wu D., Shi H., Huo K.; RT "RIOK3 interacts with caspase-10 and negatively regulates the NF-kappaB RT signaling pathway."; RL Mol. Cell. Biochem. 332:113-120(2009). RN [17] RP VARIANT ALPS2A PHE-285, VARIANT ILE-410, AND ALTERNATIVE SPLICING (ISOFORMS RP 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 and RT dendritic cell apoptosis in autoimmune lymphoproliferative syndrome type RT II."; RL Cell 98:47-58(1999). RN [18] 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., Lee J.H., RA Park J.Y., Jang J.J., Kim C.W., Kim S.H., Lee J.Y., Yoo N.J., Lee S.H.; RT "Inactivating mutations of CASP10 gene in non-Hodgkin lymphomas."; RL Blood 99:4094-4099(2002). RN [19] 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., Kim Y.S., RA 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 [20] RP VARIANTS LEU-406; ILE-410 AND CYS-446, AND CHARACTERIZATION OF VARIANTS RP LEU-406; ILE-410 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 [21] 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., Prieto V.G., RA 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 [22] 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 [23] 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). RN [24] RP VARIANT LEU-406. RX PubMed=27378136; DOI=10.1016/j.imlet.2016.07.001; RA Tripodi S.I., Mazza C., Moratto D., Ramenghi U., Caorsi R., Gattorno M., RA Badolato R.; RT "Atypical presentation of autoimmune lymphoproliferative syndrome due to RT CASP10 mutation."; RL Immunol. Lett. 177:22-24(2016). RN [25] RP VARIANT LEU-406. RX PubMed=27535533; DOI=10.1038/nature19057; RG Exome Aggregation Consortium; RA Lek M., Karczewski K.J., Minikel E.V., Samocha K.E., Banks E., Fennell T., RA O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B., Tukiainen T., RA Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K., Zhao F., Zou J., RA Pierce-Hoffman E., Berghout J., Cooper D.N., Deflaux N., DePristo M., RA Do R., Flannick J., Fromer M., Gauthier L., Goldstein J., Gupta N., RA Howrigan D., Kiezun A., Kurki M.I., Moonshine A.L., Natarajan P., RA Orozco L., Peloso G.M., Poplin R., Rivas M.A., Ruano-Rubio V., Rose S.A., RA Ruderfer D.M., Shakir K., Stenson P.D., Stevens C., Thomas B.P., Tiao G., RA Tusie-Luna M.T., Weisburd B., Won H.H., Yu D., Altshuler D.M., RA Ardissino D., Boehnke M., Danesh J., Donnelly S., Elosua R., Florez J.C., RA Gabriel S.B., Getz G., Glatt S.J., Hultman C.M., Kathiresan S., Laakso M., RA McCarroll S., McCarthy M.I., McGovern D., McPherson R., Neale B.M., RA Palotie A., Purcell S.M., Saleheen D., Scharf J.M., Sklar P., RA Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C., Wilson J.G., RA Daly M.J., MacArthur D.G.; RT "Analysis of protein-coding genetic variation in 60,706 humans."; RL Nature 536:285-291(2016). CC -!- FUNCTION: Involved in the activation cascade of caspases responsible CC for apoptosis execution. Recruited to both Fas- and TNFR-1 receptors in CC a FADD dependent manner. May participate in the granzyme B apoptotic CC pathways. Cleaves and activates effector caspases CASP3, CASP4, CASP6, CC CASP7, CASP8 and CASP9. Hydrolyzes the small- molecule substrates, Tyr- CC Val-Ala-Asp-|-AMC and Asp-Glu-Val-Asp-|-AMC. CC {ECO:0000269|PubMed:11717445, ECO:0000269|PubMed:16916640}. CC -!- FUNCTION: Isoform 7 can enhance NF-kappaB activity but promotes only CC slight apoptosis. {ECO:0000269|PubMed:17822854}. CC -!- FUNCTION: Isoform C is proteolytically inactive. CC {ECO:0000269|PubMed:11717445}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Strict requirement for Asp at position P1 and has a preferred CC cleavage sequence of Leu-Gln-Thr-Asp-|-Gly.; EC=3.4.22.63; CC Evidence={ECO:0000269|PubMed:16916640}; CC -!- SUBUNIT: Heterotetramer that consists of two anti-parallel arranged CC heterodimers, each one formed by a 23/17 kDa (p23/17) (depending on the CC splicing events) and a 12 kDa (p12) subunit (By similarity). Self- CC associates. Interacts with FADD and CASP8. Found in a Fas signaling CC complex consisting of FAS, FADD, CASP8 and CASP10. Interacts with RFFL CC and RNF34; negatively regulate CASP10 through proteasomal degradation. CC Interacts with RIOK3. {ECO:0000250, ECO:0000269|PubMed:11717445, CC ECO:0000269|PubMed:15069192, ECO:0000269|PubMed:19557502}. CC -!- INTERACTION: CC Q92851; Q14790: CASP8; NbExp=3; IntAct=EBI-495095, EBI-78060; CC Q92851; O15519: CFLAR; NbExp=3; IntAct=EBI-495095, EBI-514941; CC Q92851; O14730: RIOK3; NbExp=6; IntAct=EBI-495095, EBI-1047061; CC Q92851; Q13546: RIPK1; NbExp=2; IntAct=EBI-495095, EBI-358507; CC Q92851; P98170: XIAP; NbExp=3; IntAct=EBI-495095, EBI-517127; CC Q92851-4; PRO_0000004678 [O15519]: CFLAR; NbExp=3; IntAct=EBI-6621134, EBI-4478097; CC Q92851-4; P98170: XIAP; NbExp=3; IntAct=EBI-6621134, EBI-517127; CC Q92851-7; O14730: RIOK3; NbExp=3; IntAct=EBI-12737837, EBI-1047061; 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 Name=D; Synonyms=10-D, 10-L; CC IsoId=Q92851-4; Sequence=VSP_000820; CC Name=C; Synonyms=10-C; CC IsoId=Q92851-3; Sequence=VSP_000821, VSP_000822; CC Name=5; CC IsoId=Q92851-5; Sequence=VSP_000819; CC Name=6; CC IsoId=Q92851-6; Sequence=VSP_037229, VSP_000820; CC Name=7; Synonyms=10-G, 10g; CC IsoId=Q92851-7; Sequence=VSP_053333, VSP_053334; CC -!- TISSUE SPECIFICITY: Detectable in most tissues. Lowest expression is CC seen in brain, kidney, prostate, testis and colon. CC -!- PTM: Cleavage by granzyme B and autocatalytic activity generate the two CC active subunits. CC -!- DISEASE: Autoimmune lymphoproliferative syndrome 2A (ALPS2A) CC [MIM:603909]: A disorder of apoptosis that manifests in early childhood CC and results in the accumulation of autoreactive lymphocytes. It is CC characterized by non-malignant lymphadenopathy with hepatosplenomegaly, CC and autoimmune hemolytic anemia, thrombocytopenia and neutropenia. CC {ECO:0000269|PubMed:10412980}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Familial non-Hodgkin lymphoma (NHL) [MIM:605027]: Cancer that CC starts in cells of the lymph system, which is part of the body's immune CC system. NHLs can occur at any age and are often marked by enlarged CC lymph nodes, fever and weight loss. {ECO:0000269|PubMed:12010812}. CC Note=The gene represented in this entry is involved in disease CC pathogenesis. CC -!- DISEASE: Gastric cancer (GASC) [MIM:613659]: A malignant disease which CC starts in the stomach, can spread to the esophagus or the small CC intestine, and can extend through the stomach wall to nearby lymph CC nodes and organs. It also can metastasize to other parts of the body. CC The term gastric cancer or gastric carcinoma refers to adenocarcinoma CC of the stomach that accounts for most of all gastric malignant tumors. CC Two main histologic types are recognized, diffuse type and intestinal CC type carcinomas. Diffuse tumors are poorly differentiated infiltrating CC lesions, resulting in thickening of the stomach. In contrast, CC intestinal tumors are usually exophytic, often ulcerating, and CC associated with intestinal metaplasia of the stomach, most often CC observed in sporadic disease. {ECO:0000269|PubMed:11973654}. Note=The CC gene represented in this entry is involved in disease pathogenesis. CC -!- MISCELLANEOUS: [Isoform B]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform C]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000305}. 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 Database CC (ALPSbase); Note=Caspase-10 mutations causing ALPS type II; CC URL="https://www.niaid.nih.gov/diseases-conditions/autoimmune-lymphoproliferative-syndrome-alps"; 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 AlphaFoldDB; Q92851; -. DR SMR; Q92851; -. DR BioGRID; 107293; 95. DR CORUM; Q92851; -. DR IntAct; Q92851; 24. DR MINT; Q92851; -. DR STRING; 9606.ENSP00000286186; -. DR BindingDB; Q92851; -. DR ChEMBL; CHEMBL5037; -. DR MEROPS; C14.011; -. DR iPTMnet; Q92851; -. DR PhosphoSitePlus; Q92851; -. DR BioMuta; CASP10; -. DR DMDM; 12644463; -. DR CPTAC; CPTAC-1039; -. DR EPD; Q92851; -. DR jPOST; Q92851; -. DR MassIVE; Q92851; -. DR MaxQB; Q92851; -. DR PaxDb; 9606-ENSP00000286186; -. DR PeptideAtlas; Q92851; -. DR ProteomicsDB; 66146; -. DR ProteomicsDB; 75543; -. [Q92851-1] DR ProteomicsDB; 75544; -. [Q92851-2] DR ProteomicsDB; 75545; -. [Q92851-3] DR ProteomicsDB; 75546; -. [Q92851-4] DR ProteomicsDB; 75547; -. [Q92851-5] DR ProteomicsDB; 75548; -. [Q92851-6] DR Pumba; Q92851; -. DR Antibodypedia; 1700; 701 antibodies from 46 providers. DR DNASU; 843; -. DR Ensembl; ENST00000272879.9; ENSP00000272879.5; ENSG00000003400.16. [Q92851-1] DR Ensembl; ENST00000286186.11; ENSP00000286186.6; ENSG00000003400.16. [Q92851-4] DR Ensembl; ENST00000313728.12; ENSP00000314599.7; ENSG00000003400.16. [Q92851-6] DR Ensembl; ENST00000346817.10; ENSP00000237865.7; ENSG00000003400.16. [Q92851-2] DR Ensembl; ENST00000374650.8; ENSP00000363781.3; ENSG00000003400.16. [Q92851-7] DR Ensembl; ENST00000448480.1; ENSP00000396835.1; ENSG00000003400.16. [Q92851-5] DR Ensembl; ENST00000492363.6; ENSP00000512459.1; ENSG00000003400.16. [Q92851-3] DR GeneID; 843; -. DR KEGG; hsa:843; -. DR MANE-Select; ENST00000286186.11; ENSP00000286186.6; NM_032977.4; NP_116759.2. [Q92851-4] DR UCSC; uc002uxi.2; human. [Q92851-1] DR AGR; HGNC:1500; -. DR CTD; 843; -. DR DisGeNET; 843; -. DR GeneCards; CASP10; -. DR GeneReviews; CASP10; -. DR HGNC; HGNC:1500; CASP10. DR HPA; ENSG00000003400; Low tissue specificity. DR MalaCards; CASP10; -. DR MIM; 601762; gene. DR MIM; 603909; phenotype. DR MIM; 605027; phenotype. DR MIM; 613659; phenotype. DR neXtProt; NX_Q92851; -. DR OpenTargets; ENSG00000003400; -. DR Orphanet; 3261; Autoimmune lymphoproliferative syndrome. DR PharmGKB; PA26084; -. DR VEuPathDB; HostDB:ENSG00000003400; -. DR eggNOG; KOG3573; Eukaryota. DR GeneTree; ENSGT00940000160994; -. DR HOGENOM; CLU_088972_0_0_1; -. DR InParanoid; Q92851; -. DR OMA; CRDCISH; -. DR OrthoDB; 2873736at2759; -. DR PhylomeDB; Q92851; -. DR TreeFam; TF102023; -. DR BioCyc; MetaCyc:HS00093-MONOMER; -. DR BRENDA; 3.4.22.63; 2681. DR PathwayCommons; Q92851; -. DR Reactome; R-HSA-6803207; TP53 Regulates Transcription of Caspase Activators and Caspases. 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 SignaLink; Q92851; -. DR SIGNOR; Q92851; -. DR BioGRID-ORCS; 843; 6 hits in 1156 CRISPR screens. DR ChiTaRS; CASP10; human. DR GeneWiki; Caspase_10; -. DR GenomeRNAi; 843; -. DR Pharos; Q92851; Tchem. DR PRO; PR:Q92851; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q92851; Protein. DR Bgee; ENSG00000003400; Expressed in colonic epithelium and 126 other cell types or tissues. DR ExpressionAtlas; Q92851; baseline and differential. 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; IDA:UniProtKB. DR GO; GO:0097153; F:cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB. 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:0006915; P:apoptotic process; TAS:ProtInc. DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IBA:GO_Central. DR GO; GO:0030225; P:macrophage differentiation; IBA:GO_Central. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IMP:UniProtKB. DR GO; GO:0051604; P:protein maturation; IDA:UniProt. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro. DR CDD; cd00032; CASc; 1. DR CDD; cd08341; DED_Caspase_10_r1; 1. DR CDD; cd08814; DED_Caspase_10_r2; 1. DR Gene3D; 3.40.50.1460; -; 1. DR Gene3D; 1.10.533.10; Death Domain, Fas; 2. DR InterPro; IPR035701; CASP10_DED2. DR InterPro; IPR029030; Caspase-like_dom_sf. DR InterPro; IPR033139; Caspase_cys_AS. DR InterPro; IPR016129; Caspase_his_AS. DR InterPro; IPR011029; DEATH-like_dom_sf. DR InterPro; IPR001875; DED_dom. DR InterPro; IPR011600; Pept_C14_caspase. DR InterPro; IPR002138; Pept_C14_p10. DR InterPro; IPR001309; Pept_C14_p20. DR InterPro; IPR015917; Pept_C14A. DR PANTHER; PTHR48169:SF5; CASPASE 10; 1. DR PANTHER; PTHR48169; DED DOMAIN-CONTAINING PROTEIN; 1. 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; SSF52129; Caspase-like; 1. DR SUPFAM; SSF47986; DEATH domain; 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. DR Genevisible; Q92851; HS. PE 1: Evidence at protein level; KW Alternative splicing; Apoptosis; Direct protein sequencing; KW Disease variant; Hydrolase; Protease; Reference proteome; Repeat; KW Thiol protease; Zymogen. FT PROPEP 1..219 FT /id="PRO_0000004644" FT CHAIN 220..415 FT /note="Caspase-10 subunit p23/17" FT /id="PRO_0000004645" FT CHAIN 416..521 FT /note="Caspase-10 subunit p12" FT /id="PRO_0000004646" FT DOMAIN 19..97 FT /note="DED 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00065" FT DOMAIN 114..187 FT /note="DED 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00065" FT REGION 231..269 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 358 FT /evidence="ECO:0000250" FT ACT_SITE 401 FT /evidence="ECO:0000250" FT VAR_SEQ 229..271 FT /note="Missing (in isoform B and isoform 5)" FT /evidence="ECO:0000303|PubMed:8755496, ECO:0000303|Ref.5" FT /id="VSP_000819" FT VAR_SEQ 229..247 FT /note="QESWQNKHAGSNGNRATNG -> EGVFVFLNEGDRGNSPDDL (in FT isoform 7)" FT /evidence="ECO:0000303|PubMed:17822854" FT /id="VSP_053333" FT VAR_SEQ 241..307 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|Ref.5" FT /id="VSP_037229" FT VAR_SEQ 241..273 FT /note="GNRATNGAPSLVSRGMQGASANTLNSETSTKRA -> EGSCVQDESEPQRPL FT CHCQQPQLYLPEGQTRNP (in isoform C)" FT /evidence="ECO:0000303|PubMed:10187817" FT /id="VSP_000821" FT VAR_SEQ 248..521 FT /note="Missing (in isoform 7)" FT /evidence="ECO:0000303|PubMed:17822854" FT /id="VSP_053334" FT VAR_SEQ 274..521 FT /note="Missing (in isoform C)" FT /evidence="ECO:0000303|PubMed:10187817" FT /id="VSP_000822" FT VAR_SEQ 473..521 FT /note="MLKFLEKTMEIRGRKRTVWGAKQISATSLPTAISAQTPRPPMRRWSSVS -> FT HEDILSILTAVNDDVSRRVDKQGTKKQMPQPAFTLRKKLVFPVPLDALSL (in FT isoform B, isoform D and isoform 6)" FT /evidence="ECO:0000303|PubMed:10187817, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:8755496, FT ECO:0000303|Ref.5" FT /id="VSP_000820" FT VARIANT 14 FT /note="K -> T (found in a colon cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:20025484" FT /id="VAR_065233" FT VARIANT 21 FT /note="R -> C (found in a multiple myeloma sample; somatic FT mutation; dbSNP:rs559979934)" FT /evidence="ECO:0000269|PubMed:19900088" FT /id="VAR_065234" FT VARIANT 147 FT /note="M -> T (in GASC; somatic mutation; impairs FT CASP10-mediated apoptosis; dbSNP:rs121909776)" FT /evidence="ECO:0000269|PubMed:11973654" FT /id="VAR_037428" FT VARIANT 239 FT /note="S -> C (in dbSNP:rs41473647)" FT /id="VAR_055361" FT VARIANT 285 FT /note="L -> F (in ALPS2A; dbSNP:rs17860403)" FT /evidence="ECO:0000269|PubMed:10412980" FT /id="VAR_014071" FT VARIANT 285 FT /note="L -> P (found in a T-acute lymphoblastic leukemia FT sample; somatic mutation)" FT /evidence="ECO:0000269|PubMed:19900088" FT /id="VAR_065235" FT VARIANT 406 FT /note="I -> L (the mutant protein has defective apoptosis FT and exerts a dominant-negative effect when cotransfected FT with the wild-type protein; dbSNP:rs80358239)" FT /evidence="ECO:0000269|PubMed:16446975, FT ECO:0000269|PubMed:27378136, ECO:0000269|PubMed:27535533" FT /id="VAR_037429" FT VARIANT 410 FT /note="V -> I (does not interfere with apoptosis in a FT dominant negative manner; dbSNP:rs13010627)" FT /evidence="ECO:0000269|PubMed:10187817, FT ECO:0000269|PubMed:10412980, ECO:0000269|PubMed:16446975" FT /id="VAR_014072" FT VARIANT 414 FT /note="A -> V (in NHL; somatic mutation; dbSNP:rs28936699)" FT /evidence="ECO:0000269|PubMed:12010812" FT /id="VAR_037430" FT VARIANT 444 FT /note="P -> S (in dbSNP:rs41513147)" FT /id="VAR_055362" FT VARIANT 446 FT /note="Y -> C (risk factor for ALPS2A; does not interfere FT with apoptosis in a dominant negative manner; FT dbSNP:rs17860405)" FT /evidence="ECO:0000269|PubMed:16446975" FT /id="VAR_037431" FT MUTAGEN 401 FT /note="C->A: Abolishes proteolytic activity." FT /evidence="ECO:0000269|PubMed:11717445" FT CONFLICT 68 FT /note="E -> G (in Ref. 2; AAB46730)" FT /evidence="ECO:0000305" FT CONFLICT 268 FT /note="T -> A (in Ref. 3; AAD28403)" FT /evidence="ECO:0000305" FT VARIANT Q92851-2:479 FT /note="L -> I (in dbSNP:rs13006529)" FT /evidence="ECO:0000269|PubMed:11161814, FT ECO:0000269|PubMed:8755496" FT /id="VAR_082802" FT VARIANT Q92851-4:522 FT /note="L -> I (in dbSNP:rs13006529)" FT /evidence="ECO:0000305" FT /id="VAR_082803" FT VARIANT Q92851-6:455 FT /note="L -> I (in dbSNP:rs13006529)" FT /evidence="ECO:0000305" FT /id="VAR_082804" 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 //