| UniProt ID | CASP8_HUMAN | |
|---|---|---|
| UniProt AC | Q14790 | |
| Protein Name | Caspase-8 | |
| Gene Name | CASP8 | |
| Organism | Homo sapiens (Human). | |
| Sequence Length | 479 | |
| Subcellular Localization | Cytoplasm. | |
| Protein Description | 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. Isoform 5, isoform 6, isoform 7 and isoform 8 lack the catalytic site and may interfere with the pro-apoptotic activity of the complex.. | |
| Protein Sequence | MDFSRNLYDIGEQLDSEDLASLKFLSLDYIPQRKQEPIKDALMLFQRLQEKRMLEESNLSFLKELLFRINRLDLLITYLNTRKEEMERELQTPGRAQISAYRVMLYQISEEVSRSELRSFKFLLQEEISKCKLDDDMNLLDIFIEMEKRVILGEGKLDILKRVCAQINKSLLKIINDYEEFSKERSSSLEGSPDEFSNGEELCGVMTISDSPREQDSESQTLDKVYQMKSKPRGYCLIINNHNFAKAREKVPKLHSIRDRNGTHLDAGALTTTFEELHFEIKPHDDCTVEQIYEILKIYQLMDHSNMDCFICCILSHGDKGIIYGTDGQEAPIYELTSQFTGLKCPSLAGKPKVFFIQACQGDNYQKGIPVETDSEEQPYLEMDLSSPQTRYIPDEADFLLGMATVNNCVSYRNPAEGTWYIQSLCQSLRERCPRGDDILTILTEVNYEVSNKDDKKNMGKQMPQPTFTLRKKLVFPSD | |
| Overview of Protein Modification Sites with Functional and Structural Information | ||
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* ASA = Accessible Surface Area
| Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
|---|---|---|---|---|---|
| 8 | Phosphorylation | MDFSRNLYDIGEQLD CCCCCCHHCHHHHCC | 14.73 | - | |
| 16 | Phosphorylation | DIGEQLDSEDLASLK CHHHHCCHHHHHHCH | 41.42 | 27251275 | |
| 21 | Phosphorylation | LDSEDLASLKFLSLD CCHHHHHHCHHHCCC | 39.11 | 27067055 | |
| 23 | Ubiquitination | SEDLASLKFLSLDYI HHHHHHCHHHCCCCC | 41.59 | - | |
| 26 | Phosphorylation | LASLKFLSLDYIPQR HHHCHHHCCCCCCHH | 23.48 | 27067055 | |
| 34 | Ubiquitination | LDYIPQRKQEPIKDA CCCCCHHCCCCHHHH | 54.49 | - | |
| 39 | Ubiquitination | QRKQEPIKDALMLFQ HHCCCCHHHHHHHHH | 47.89 | - | |
| 52 (in isoform 9) | Phosphorylation | - | 33.88 | 25159151 | |
| 60 | Phosphorylation | MLEESNLSFLKELLF CHHHCCCHHHHHHHH | 32.55 | 24719451 | |
| 63 (in isoform 6) | Ubiquitination | - | 44.28 | 21906983 | |
| 63 (in isoform 5) | Ubiquitination | - | 44.28 | 21906983 | |
| 63 (in isoform 4) | Ubiquitination | - | 44.28 | 21906983 | |
| 63 (in isoform 3) | Ubiquitination | - | 44.28 | 21906983 | |
| 63 (in isoform 2) | Ubiquitination | - | 44.28 | 21906983 | |
| 63 (in isoform 1) | Ubiquitination | - | 44.28 | 21906983 | |
| 63 (in isoform 7) | Ubiquitination | - | 44.28 | 21906983 | |
| 63 (in isoform 8) | Ubiquitination | - | 44.28 | 21906983 | |
| 63 | Ubiquitination | ESNLSFLKELLFRIN HCCCHHHHHHHHHHH | 44.28 | 21906983 | |
| 113 | Phosphorylation | YQISEEVSRSELRSF HHHCCCCCHHHHHHH | 33.11 | - | |
| 121 | Ubiquitination | RSELRSFKFLLQEEI HHHHHHHHHHHHHHH | 36.03 | - | |
| 122 (in isoform 9) | Ubiquitination | - | 8.51 | 21906983 | |
| 130 | Ubiquitination | LLQEEISKCKLDDDM HHHHHHHCCCCCCCC | 40.84 | - | |
| 148 | Ubiquitination | DIFIEMEKRVILGEG HHHHHHHCCEEECCC | 51.13 | 20972266 | |
| 148 (in isoform 5) | Ubiquitination | - | 51.13 | 21906983 | |
| 156 | Acetylation | RVILGEGKLDILKRV CEEECCCHHHHHHHH | 38.39 | 132805 | |
| 156 | Ubiquitination | RVILGEGKLDILKRV CEEECCCHHHHHHHH | 38.39 | - | |
| 161 | Ubiquitination | EGKLDILKRVCAQIN CCHHHHHHHHHHHHH | 43.02 | - | |
| 169 | Acetylation | RVCAQINKSLLKIIN HHHHHHHHHHHHHHH | 44.07 | 26051181 | |
| 169 | Ubiquitination | RVCAQINKSLLKIIN HHHHHHHHHHHHHHH | 44.07 | - | |
| 170 | Phosphorylation | VCAQINKSLLKIIND HHHHHHHHHHHHHHC | 34.15 | 24719451 | |
| 173 | Ubiquitination | QINKSLLKIINDYEE HHHHHHHHHHHCHHH | 47.00 | - | |
| 178 | Phosphorylation | LLKIINDYEEFSKER HHHHHHCHHHHHHHH | 16.93 | - | |
| 180 (in isoform 9) | Ubiquitination | - | 49.33 | - | |
| 183 | Ubiquitination | NDYEEFSKERSSSLE HCHHHHHHHHHHCCC | 63.57 | - | |
| 186 | Phosphorylation | EEFSKERSSSLEGSP HHHHHHHHHCCCCCC | 25.93 | 27251275 | |
| 187 | Phosphorylation | EFSKERSSSLEGSPD HHHHHHHHCCCCCCC | 45.20 | 27251275 | |
| 188 | Phosphorylation | FSKERSSSLEGSPDE HHHHHHHCCCCCCCC | 31.52 | 27251275 | |
| 189 (in isoform 9) | Ubiquitination | - | 10.50 | - | |
| 192 | Phosphorylation | RSSSLEGSPDEFSNG HHHCCCCCCCCCCCC | 21.58 | 27251275 | |
| 194 (in isoform 2) | Phosphorylation | - | 71.87 | 25159151 | |
| 194 (in isoform 8) | Phosphorylation | - | 71.87 | 25159151 | |
| 196 (in isoform 8) | Phosphorylation | - | 10.03 | 25159151 | |
| 196 (in isoform 2) | Phosphorylation | - | 10.03 | 25159151 | |
| 207 | Phosphorylation | EELCGVMTISDSPRE CEEEEEEEECCCCCC | 18.21 | 26074081 | |
| 209 | Phosphorylation | LCGVMTISDSPREQD EEEEEEECCCCCCCC | 23.91 | 26074081 | |
| 211 | Phosphorylation | GVMTISDSPREQDSE EEEEECCCCCCCCCC | 21.04 | 21815630 | |
| 215 (in isoform 9) | Ubiquitination | - | 61.89 | - | |
| 217 | Phosphorylation | DSPREQDSESQTLDK CCCCCCCCCCCHHHH | 38.55 | 20068231 | |
| 219 | Phosphorylation | PREQDSESQTLDKVY CCCCCCCCCHHHHHH | 32.20 | 17525332 | |
| 220 (in isoform 9) | Ubiquitination | - | 41.87 | - | |
| 221 | Phosphorylation | EQDSESQTLDKVYQM CCCCCCCHHHHHHHC | 46.32 | 20068231 | |
| 224 | Ubiquitination | SESQTLDKVYQMKSK CCCCHHHHHHHCCCC | 46.05 | - | |
| 224 | Acetylation | SESQTLDKVYQMKSK CCCCHHHHHHHCCCC | 46.05 | - | |
| 226 | Phosphorylation | SQTLDKVYQMKSKPR CCHHHHHHHCCCCCC | 14.50 | 20068231 | |
| 226 (in isoform 4) | Phosphorylation | - | 14.50 | 25159151 | |
| 228 (in isoform 4) | Phosphorylation | - | 2.64 | 25159151 | |
| 228 (in isoform 9) | Ubiquitination | - | 2.64 | - | |
| 229 | Ubiquitination | LDKVYQMKSKPRGYC HHHHHHCCCCCCCEE | 39.54 | - | |
| 230 | Phosphorylation | DKVYQMKSKPRGYCL HHHHHCCCCCCCEEE | 42.42 | 20068231 | |
| 235 | Phosphorylation | MKSKPRGYCLIINNH CCCCCCCEEEEECCC | 5.83 | - | |
| 242 (in isoform 9) | Ubiquitination | - | 26.71 | - | |
| 253 | Ubiquitination | KAREKVPKLHSIRDR HHHHHCCCHHHCCCC | 62.92 | - | |
| 263 | Phosphorylation | SIRDRNGTHLDAGAL HCCCCCCCCCCCCCE | 23.86 | 21183680 | |
| 272 | Phosphorylation | LDAGALTTTFEELHF CCCCCEECCHHHHCC | 30.27 | 20068231 | |
| 273 | Phosphorylation | DAGALTTTFEELHFE CCCCEECCHHHHCCC | 24.66 | 20068231 | |
| 283 (in isoform 9) | Ubiquitination | - | 41.63 | - | |
| 305 | Phosphorylation | IYQLMDHSNMDCFIC HHHHHCCCCCCEEEE | 29.59 | - | |
| 334 | Phosphorylation | DGQEAPIYELTSQFT CCCCCCEEECCCCCC | 12.11 | 15592455 | |
| 344 | Ubiquitination | TSQFTGLKCPSLAGK CCCCCCCCCHHHCCC | 45.50 | - | |
| 347 | Phosphorylation | FTGLKCPSLAGKPKV CCCCCCHHHCCCCEE | 40.08 | 14970175 | |
| 351 | Ubiquitination | KCPSLAGKPKVFFIQ CCHHHCCCCEEEEEE | 35.74 | - | |
| 353 | Ubiquitination | PSLAGKPKVFFIQAC HHHCCCCEEEEEEEC | 55.98 | - | |
| 373 | Phosphorylation | QKGIPVETDSEEQPY CCCCCCCCCCCCCCC | 45.09 | 30576142 | |
| 375 | Phosphorylation | GIPVETDSEEQPYLE CCCCCCCCCCCCCEE | 50.91 | 30576142 | |
| 377 (in isoform 3) | Ubiquitination | - | 61.89 | 21906983 | |
| 380 | Phosphorylation | TDSEEQPYLEMDLSS CCCCCCCCEEEECCC | 18.26 | 28796482 | |
| 386 | Phosphorylation | PYLEMDLSSPQTRYI CCEEEECCCCCCCCC | 35.39 | 29978859 | |
| 387 | Phosphorylation | YLEMDLSSPQTRYIP CEEEECCCCCCCCCC | 28.46 | 11917123 | |
| 390 | Phosphorylation | MDLSSPQTRYIPDEA EECCCCCCCCCCCHH | 28.91 | 29523821 | |
| 403 (in isoform 9) | Ubiquitination | - | 2.59 | - | |
| 410 (in isoform 9) | Ubiquitination | - | 6.48 | - | |
| 446 (in isoform 2) | Ubiquitination | - | 8.56 | 21906983 | |
| 448 | Phosphorylation | TILTEVNYEVSNKDD HHHHHHCCCCCCCHH | 23.92 | 18083107 | |
| 461 | Ubiquitination | DDKKNMGKQMPQPTF HHHHCCCCCCCCCCE | 32.43 | 2190698 | |
| 461 (in isoform 1) | Ubiquitination | - | 32.43 | 21906983 | |
| 469 | Phosphorylation | QMPQPTFTLRKKLVF CCCCCCEEEEECCCC | 28.29 | 24719451 | |
| 473 | Ubiquitination | PTFTLRKKLVFPSD- CCEEEEECCCCCCC- | 43.37 | - | |
| 478 (in isoform 4) | Ubiquitination | - | 44.48 | 21906983 | |
| 520 (in isoform 9) | Ubiquitination | - | 21906983 | ||
| 531 (in isoform 9) | Ubiquitination | - | - | ||
| 532 (in isoform 9) | Ubiquitination | - | - |
| Modified Location | Modified Residue | Modification | Type of Upstream Proteins | Gene Name of Upstream Proteins | UniProt AC of Upstream Proteins | Sources |
|---|---|---|---|---|---|---|
| 263 | T | Phosphorylation | Kinase | RPS6KA3 | P51812 | GPS |
| 273 | T | Phosphorylation | Kinase | PLK3 | Q9H4B4 | PSP |
| 305 | S | Phosphorylation | Kinase | PLK1 | P53350 | PSP |
| 347 | S | Phosphorylation | Kinase | MAPK14 | Q16539 | GPS |
| 380 | Y | Phosphorylation | Kinase | LYN | P07948 | PSP |
| 380 | Y | Phosphorylation | Kinase | SRC | P12931 | PSP |
| 387 | S | Phosphorylation | Kinase | CDK1 | P06493 | Uniprot |
| 387 | S | Phosphorylation | Kinase | MAPK1 | P28482 | GPS |
| 387 | S | Phosphorylation | Kinase | MAPK3 | P27361 | GPS |
| 397 | Y | Phosphorylation | Kinase | SRC | P12931 | PSP |
| 448 | Y | Phosphorylation | Kinase | LYN | P07948 | PSP |
| - | K | Ubiquitination | E3 ubiquitin ligase | RNF34 | Q969K3 | PMID:15069192 |
| - | K | Ubiquitination | E3 ubiquitin ligase | BIRC3 | Q13489 | PMID:22199232 |
| - | K | Ubiquitination | E3 ubiquitin ligase | BIRC2 | Q13490 | PMID:22199232 |
| - | K | Ubiquitination | E3 ubiquitin ligase | RFFL | Q8WZ73 | PMID:15069192 |
| - | K | Ubiquitination | E3 ubiquitin ligase | XIAP | P98170 | PMID:22199232 |
| - | K | Ubiquitination | E3 ubiquitin ligase | HECTD3 | Q5T447 | PMID:24287696 |
| Modified Location | Modified Residue | Modification | Function | Reference |
|---|---|---|---|---|
| 387 | S | Phosphorylation |
| 20937773 |
* Distance = the distance between SAP position and PTM sites.
| Modified Location | Modification | Variant Position (Distance <= 10) |
Residue Change | SAP | Related Disease | Reference |
|---|---|---|---|---|---|---|
Oops, there are no SNP-PTM records of CASP8_HUMAN !! | ||||||
| Kegg Disease | ||||||
|---|---|---|---|---|---|---|
| There are no disease associations of PTM sites. | ||||||
| OMIM Disease | ||||||
| 607271 | Caspase-8 deficiency (CASP8D) | |||||
| Kegg Drug | ||||||
| There are no disease associations of PTM sites. | ||||||
| DrugBank | ||||||
| There are no disease associations of PTM sites. | ||||||
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| Phosphorylation | |
| Reference | PubMed |
| "Cdk1/cyclin B1 controls Fas-mediated apoptosis by regulating caspase-8 activity."; Matthess Y., Raab M., Sanhaji M., Lavrik I.N., Strebhardt K.; Mol. Cell. Biol. 30:5726-5740(2010). Cited for: PHOSPHORYLATION AT SER-387 BY CDK1. | |
| "ATM and ATR substrate analysis reveals extensive protein networksresponsive to DNA damage."; Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.; Science 316:1160-1166(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-219, AND MASSSPECTROMETRY. | |
| "Immunoaffinity profiling of tyrosine phosphorylation in cancercells."; Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,Zha X.-M., Polakiewicz R.D., Comb M.J.; Nat. Biotechnol. 23:94-101(2005). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-334, AND MASSSPECTROMETRY. | |
