CASPA_HUMAN
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 03-AUG-2022, entry version 224.
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; 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 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 [16]
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 [17]
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 [18]
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 [19]
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 [20]
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 [21]
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 [22]
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 [23]
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 [24]
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 caspase-3, -4, -6, -7, -8, and -9.
CC Hydrolyzes the small- molecule substrates, Tyr-Val-Ala-Asp-|-AMC and
CC Asp-Glu-Val-Asp-|-AMC. {ECO:0000269|PubMed:11717445}.
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 -!- 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/";
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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; 93.
DR CORUM; Q92851; -.
DR IntAct; Q92851; 23.
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; Q92851; -.
DR PeptideAtlas; Q92851; -.
DR PRIDE; 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 Antibodypedia; 1700; 614 antibodies from 46 providers.
DR DNASU; 843; -.
DR Ensembl; ENST00000272879.9; ENSP00000272879.5; ENSG00000003400.15. [Q92851-1]
DR Ensembl; ENST00000286186.11; ENSP00000286186.6; ENSG00000003400.15. [Q92851-4]
DR Ensembl; ENST00000313728.11; ENSP00000314599.7; ENSG00000003400.15. [Q92851-6]
DR Ensembl; ENST00000346817.9; ENSP00000237865.7; ENSG00000003400.15. [Q92851-2]
DR Ensembl; ENST00000360132.7; ENSP00000353250.3; ENSG00000003400.15. [Q92851-3]
DR Ensembl; ENST00000374650.7; ENSP00000363781.3; ENSG00000003400.15. [Q92851-7]
DR Ensembl; ENST00000448480.1; ENSP00000396835.1; ENSG00000003400.15. [Q92851-5]
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 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; VPNLMRK; -.
DR PhylomeDB; Q92851; -.
DR TreeFam; TF102023; -.
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; 5 hits in 1078 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 124 other tissues.
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; IDA:UniProtKB.
DR GO; GO:0097153; F:cysteine-type endopeptidase activity involved in apoptotic process; IBA:GO_Central.
DR GO; GO:0097199; F:cysteine-type endopeptidase activity involved in apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0097200; F:cysteine-type endopeptidase activity involved in execution phase of apoptosis; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
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 Gene3D; 1.10.533.10; -; 2.
DR InterPro; IPR029030; Caspase-like_dom_sf.
DR InterPro; IPR035701; Caspase_10.
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; IPR002398; Pept_C14.
DR InterPro; IPR002138; Pept_C14_p10.
DR InterPro; IPR001309; Pept_C14_p20.
DR InterPro; IPR015917; Pept_C14A.
DR PANTHER; PTHR10454; PTHR10454; 1.
DR PANTHER; PTHR10454:SF26; PTHR10454:SF26; 1.
DR Pfam; PF01335; DED; 2.
DR PRINTS; PR00376; IL1BCENZYME.
DR SMART; SM00115; CASc; 1.
DR SMART; SM00031; DED; 2.
DR SUPFAM; SSF47986; SSF47986; 2.
DR SUPFAM; SSF52129; SSF52129; 1.
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; 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 CASP10-
FT 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 (associated with 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 (not associated with significantly altered
FT cutaneous melanoma risk; 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
