ImmunoDeficiency Resource (IDR)

Names

HUGO name: CASP8

Alias(es):

Localization

Reference sequences

Chromosomal location

Maps

Markers

Variations / Mutations

• CASP8base; Mutation registry for Caspase 8 deficiency

Other gene-based resources

Description

Protein function:

Most upstream protease of the activation cascade of caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1a induced cell death. Binding to the adapter molecule fadd recruits it to either receptor. The resulting aggregate called death-inducing signaling complex (disc) performs CASP8 proteolytic activation. The active dimeric enzyme is then liberated from the disc and free to activate downstream apoptotic proteases. Proteolytic fragments of the n-terminal propeptide (termed cap3, cap5 and cap6) are likely retained in the disc. Cleaves and activates CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10. May participate in the GZMB apoptotic pathways. Cleaves ADPRT. Hydrolyzes the small-molecule substrate, ac-asp-glu-val-asp-|-amc. Likely target for the cowpox virus CRMA death inhibitory protein. Isoforms 5, 6, 7 and 8 lack the catalytic site and may interfere with the pro-apoptotic activity of the complex

Subunit:

Heterodimer of a 18 kDa (p18) and a 10 kDa (p10) subunit. Interacts with fadd, cflar and pea15. Isoform 9 interacts at the endoplasmic reticulum with a complex containing bcap31, bap29, bcl2 and/or bcl2l1.

Subcellular location:

Cytoplasmic

Post-translational modification:

Generation of the subunits requires association with the death-inducing signaling complex (disc), whereas additional processing is likely due to the autocatalytic activity of the activated protease. Gzmb and CASP10 can be involved in these processing events.

Alternative products:

Event=alternative splicing; named isoforms=9; name=1; synonyms=alpha-1; isoid=q14790-1; sequence=displayed; name=2; synonyms=alpha-2, mch5-beta; isoid=q14790-2; sequence=vsp_000810; name=3; synonyms=alpha-3; isoid=q14790-3; sequence=vsp_000813; name=4; synonyms=alpha-4; isoid=q14790-4; sequence=vsp_000809, vsp_000810; name=5; synonyms=beta-1; isoid=q14790-5; sequence=vsp_000814, vsp_000815; name=6; synonyms=beta-2; isoid=q14790-6; sequence=vsp_000811, vsp_000812; name=7; synonyms=beta-3, 8l; isoid=q14790-7; sequence=vsp_000816, vsp_000817; name=8; synonyms=beta-4; isoid=q14790-8; sequence=vsp_000810, vsp_000816, vsp_000817; name=9; synonyms=8l; isoid=q14790-9; sequence=vsp_000808;

Tissue specificity:

Isoforms 1, 5 and 7 are expressed in a wide variety of tissues. Highest expression in peripheral blood leukocytes, spleen, thymus, and liver. Barely detectable in brain, testis, and skeletal muscle.

Similarity:

Belongs to peptidase family C14.

Structures (PDB)

1F9E	Caspase-8 Specificity Probed At Subsite S4: Crystal Structure Of The Caspase-8-Z-Devd-Cho
1QDU	Crystal Structure Of The Complex Of Caspase-8 With The Tripeptide Ketone Inhibitor Zevd-Dcbmk
1QTN	Crystal Structure Of The Complex Of Caspase-8 With The Tetrapeptide Inhibitor Ace-Ietd-Aldehyde

Domains

DED 1 domain: 2-80

DED 2 domain: 100-177

Other features

Propeptide: 1-216

Caspase-8 subunit p18: 217-374

Propeptide: 375-384

Caspase-8 subunit p10: 385-479

Other related resourses:

Expression pattern for human

Tissue	Expression (%)	Clones
human placenta	8.44	2:7218
leukocyte	6.89	2:8838
sciatic nerve	6.07	1:5018
embryonal carcinoma	5.48	2:11109
mammary adenocarcinoma, cell line	5.31	3:17218
hypernephroma	5.26	1:5792
bone marrow	5.23	1:5829
moderately-differentiated adenocarcinoma	4.70	1:6478
mucoepidermoid carcinoma	4.58	1:6654
pre-eclamptic placenta	4.07	1:7480
human placenta	8.44	2:7218
leukocyte	6.89	2:8838
sciatic nerve	6.07	1:5018
embryonal carcinoma	5.48	2:11109
mammary adenocarcinoma, cell line	5.31	3:17218
hypernephroma	5.26	1:5792
bone marrow	5.23	1:5829
moderately-differentiated adenocarcinoma	4.70	1:6478
mucoepidermoid carcinoma	4.58	1:6654
pre-eclamptic placenta	4.07	1:7480

Animal models

Mouse

Rat