MGP Database

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MGP000421

UniProt Annotations

Entry Information
Gene Namecaspase 10, apoptosis-related cysteine peptidase
Protein EntryCASPA_HUMAN
UniProt IDQ92851
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=7; Name=A; Synonyms=10-A; IsoId=Q92851-1; Sequence=Displayed; Name=B; Synonyms=10-B, 10-S; IsoId=Q92851-2; Sequence=VSP_000819, VSP_000820; Note=May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. Variant in position: 479:L->I (in dbSNP:rs13006529).; Name=D; Synonyms=10-D, 10-L; IsoId=Q92851-4; Sequence=VSP_000820; Note=Variant in position: 522:L->I (not associated with significantly altered cutaneous melanoma risk, dbSNP:rs13006529).; Name=C; Synonyms=10-C; IsoId=Q92851-3; Sequence=VSP_000821, VSP_000822; Note=May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.; Name=5; IsoId=Q92851-5; Sequence=VSP_000819; Name=6; IsoId=Q92851-6; Sequence=VSP_037229, VSP_000820; Note=Variant in position: 455:L->I (in dbSNP:rs13006529).; Name=7; IsoId=Q92851-7; Sequence=VSP_053333, VSP_053334;
Catalytic ActivityStrict requirement for Asp at position P1 and has a preferred cleavage sequence of Leu-Gln-Thr-Asp-|-Gly.
DiseaseAutoimmune lymphoproliferative syndrome 2A (ALPS2A) [MIM:603909]: A disorder of apoptosis that manifests in early childhood and results in the accumulation of autoreactive lymphocytes. It is characterized by non-malignant lymphadenopathy with hepatosplenomegaly, and autoimmune hemolytic anemia, thrombocytopenia and neutropenia. {ECO:0000269|PubMed:10412980, ECO:0000269|PubMed:16446975}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseFamilial non-Hodgkin lymphoma (NHL) [MIM:605027]: Cancer that starts in cells of the lymph system, which is part of the body's immune system. NHLs can occur at any age and are often marked by enlarged lymph nodes, fever and weight loss. {ECO:0000269|PubMed:12010812}. Note=The gene represented in this entry is involved in disease pathogenesis.
DiseaseGastric cancer (GASC) [MIM:613659]: A malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease. {ECO:0000269|PubMed:11973654}. Note=The gene represented in this entry is involved in disease pathogenesis.
FunctionInvolved in the activation cascade of caspases responsible for apoptosis execution. Recruited to both Fas- and TNFR-1 receptors in a FADD dependent manner. May participate in the granzyme B apoptotic pathways. Cleaves and activates caspase- 3, -4, -6, -7, -8, and -9. Hydrolyzes the small- molecule substrates, Tyr-Val-Ala-Asp-|-AMC and Asp-Glu-Val-Asp-|-AMC. {ECO:0000269|PubMed:11717445}.
FunctionIsoform C is proteolytically inactive. {ECO:0000269|PubMed:11717445}.
InteractionQ14790:CASP8; NbExp=3; IntAct=EBI-495095, EBI-78060; O15519:CFLAR; NbExp=3; IntAct=EBI-495095, EBI-514941; O14730:RIOK3; NbExp=4; IntAct=EBI-495095, EBI-1047061; Q13546:RIPK1; NbExp=2; IntAct=EBI-495095, EBI-358507;
PtmCleavage by granzyme B and autocatalytic activity generate the two active subunits.
SimilarityBelongs to the peptidase C14A family. {ECO:0000305}.
SimilarityContains 2 DED (death effector) domains. {ECO:0000255|PROSITE-ProRule:PRU00065}.
SubunitHeterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 23/17 kDa (p23/17) (depending on the splicing events) and a 12 kDa (p12) subunit (By similarity). Self-associates. Interacts with FADD and CASP8. Found in a Fas signaling complex consisting of FAS, FADD, CASP8 and CASP10. Interacts with RFFL and RNF34; negatively regulate CASP10 through proteasomal degradation. {ECO:0000250, ECO:0000269|PubMed:11717445, ECO:0000269|PubMed:15069192}.
Tissue SpecificityDetectable in most tissues. Lowest expression is seen in brain, kidney, prostate, testis and colon.
Web ResourceName=Autoimmune Lymphoproliferative Syndrome Database (ALPSbase); Note=Caspase-10 mutations causing ALPS type II; URL="http://research.nhgri.nih.gov/ALPS/alpsII_mut.shtml";
Web ResourceName=CASP10base; Note=CASP10 mutation db; URL="http://structure.bmc.lu.se/idbase/CASP10base/";
Web ResourceName=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/casp10/";
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