Q14790

PTMD Annotation Information

※ Protein Information

Tag	Content
UniProt Accession	CASP8_HUMAN; Q14790;
Entrez ID	841
GenBank Protein ID	NM_001080124.1; NM_001080125.1; NM_001228.4; NM_033355.3; NM_033356.3; NM_033358.3; XM_005246886.1; XM_005246887.1; XM_005246888.1; XM_005246889.1; XM_005246890.3; XM_005246891.4; XM_005246892.1; XM_006712789.1; XM_006712790.3; XM_006712793.2;
GenBank Nucleotide ID	NP_001073593.1; NP_001073594.1; NP_001219.2; NP_203519.1; NP_203520.1; NP_203522.1; XP_005246943.1; XP_005246944.1; XP_005246945.1; XP_005246946.1; XP_005246947.1; XP_005246948.1; XP_005246949.1; XP_006712852.1; XP_006712853.1; XP_006712856.1;
Protein Name	Caspase-8 (CASP-8) (EC 3.4.22.61) (Apoptotic cysteine protease) (Apoptotic protease Mch-5) (CAP4) (FADD-homologous ICE/ced-3-like protease) (FADD-like ICE) (FLICE) (ICE-like apoptotic protease 5) (MORT1-associated ced-3 homolog) (MACH) [Cleaved into: Casp
Gene Name	CASP8; MCH5
Organism	Homo sapiens
NCBI Taxa ID	9606
Functional 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. Functional 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.
Sequence (Fasta)	MDFSRNLYDI GEQLDSEDLA SLKFLSLDYI PQRKQEPIKD ALMLFQRLQE KRMLEESNLS 60 FLKELLFRIN RLDLLITYLN TRKEEMEREL QTPGRAQISA YRVMLYQISE EVSRSELRSF 120 KFLLQEEISK CKLDDDMNLL DIFIEMEKRV ILGEGKLDIL KRVCAQINKS LLKIINDYEE 180 FSKERSSSLE GSPDEFSNGE ELCGVMTISD SPREQDSESQ TLDKVYQMKS KPRGYCLIIN 240 NHNFAKAREK VPKLHSIRDR NGTHLDAGAL TTTFEELHFE IKPHDDCTVE QIYEILKIYQ 300 LMDHSNMDCF ICCILSHGDK GIIYGTDGQE APIYELTSQF TGLKCPSLAG KPKVFFIQAC 360 QGDNYQKGIP VETDSEEQPY LEMDLSSPQT RYIPDEADFL LGMATVNNCV SYRNPAEGTW 420 YIQSLCQSLR ERCPRGDDIL TILTEVNYEV SNKDDKKNMG KQMPQPTFTL RKKLVFPSD 480 Fasta Sequence >Q14790\|CASP8; MCH5\|Homo sapiens (Human) MDFSRNLYDIGEQLDSEDLASLKFLSLDYIPQRKQEPIKDALMLFQRLQEKRMLEESNLSFLKELLFRINRLDLLITYLNTRKEEMERELQTPGRAQISAYRVMLYQISEEVSRSELRSFKFLLQEEISKCKLDDDMNLLDIFIEMEKRVILGEGKLDILKRVCAQINKSLLKIINDYEEFSKERSSSLEGSPDEFSNGEELCGVMTISDSPREQDSESQTLDKVYQMKSKPRGYCLIINNHNFAKAREKVPKLHSIRDRNGTHLDAGALTTTFEELHFEIKPHDDCTVEQIYEILKIYQLMDHSNMDCFICCILSHGDKGIIYGTDGQEAPIYELTSQFTGLKCPSLAGKPKVFFIQACQGDNYQKGIPVETDSEEQPYLEMDLSSPQTRYIPDEADFLLGMATVNNCVSYRNPAEGTWYIQSLCQSLRERCPRGDDILTILTEVNYEVSNKDDKKNMGKQMPQPTFTLRKKLVFPSD

※ PTM-Disease Association

Num	PTM	Disease	Cell Type	Type	PTM Site	PMID
1	Polyubiquitination	Breast cancer/tumor/carcinoma	MDA-MB-231 cell line	P		24287696
1	[Reference]: The HECTD3 E3 ubiquitin ligase facilitates cancer cell survival by promoting K63-linked polyubiquitination of caspase-8
2	Tyrosine Phosphorylation	Colon cancer/carcinoma		P	Y380	16619028
2	[Reference]: Tyr380 is phosphorylated also in human colon cancers where Src is aberrantly activated.
3	Serine Phosphorylation	Breast cancer/tumor/carcinoma		U	S387	20937773
3	[Reference]: In this study, we demonstrate that procaspase-8 is phosphorylated in mitotic cells by Cdk1/cyclin B1 on Ser-387, which is located at the N terminus of the catalytic subunit p10. This phosphorylation of procaspase-8 on Ser-387 occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes.?

※ Disease Cross-ref Annotation

Database	Annotation
Cancer Gene Census	hepatocellular, oral squamous cell, breast
CTD (Curated) (count: 23) (view all)	MESH:D000230 ; Adenocarcinoma MESH:D056735 ; Autoimmune Lymphoproliferative Syndrome MESH:D001943 ; Breast Neoplasms MESH:D006528 ; Carcinoma, Hepatocellular MESH:C535575 ; Carcinoma, squamous cell of head and neck MESH:D002543 ; Cerebral Hemorrhage MESH:D015179 ; Colorectal Neoplasms MESH:D017449 ; Dermatitis, Allergic Contact MESH:D003877 ; Dermatitis, Contact MESH:D003924 ; Diabetes Mellitus, Type 2 MESH:D004487 ; Edema MESH:D004938 ; Esophageal Neoplasms MESH:D008175 ; Lung Neoplasms MESH:D008545 ; Melanoma MESH:D015428 ; Myocardial Reperfusion Injury MESH:D013226 ; Status Epilepticus MESH:D002289 ; Carcinoma, Non-Small-Cell Lung MESH:D030361 ; Papillomavirus Infections MESH:D054198 ; Precursor Cell Lymphoblastic Leukemia-Lymphoma MESH:D015427 ; Reperfusion Injury MESH:D012878 ; Skin Neoplasms MESH:D013274 ; Stomach Neoplasms MESH:D002583 ; Uterine Cervical Neoplasms
HGMD (count: 3)	CD072346; Cancer, reduced risk, association with; Small deletions CM023571; Caspase 8 deficiency; Missense/nonsense CM043455; Breast cancer, reduced risk, association with; Missense/nonsense
GWASdb (count: 15) (view all)	rs2037815; Multiple complex diseases; Null rs3769825; Chronic lymphocytic leukemia; chronic lymphocytic leukemia rs35665714; Insulin resistance; type 2 diabetes mellitus rs6712381; Insulin resistance; type 2 diabetes mellitus rs3769823; post-traumatic stress disorder; post-traumatic stress disorder rs3769823; Schizophrenia; schizophrenia rs4381764; Type 2 diabetes and other traits; type 2 diabetes mellitus rs10084352; Insulin resistance; type 2 diabetes mellitus rs10931936; Melanoma; skin melanoma rs10931936; Esophageal cancer (squamous cell); esophageal cancer rs11681399; Telomere length; Null rs10804111; Esophageal cancer (squamous cell); esophageal cancer rs3769818; Esophageal cancer (squamous cell); esophageal cancer rs3769818; post-traumatic stress disorder; post-traumatic stress disorder rs3769818; Schizophrenia; schizophrenia

※ PTM Sites

PTM	Modification Sites
Phosphorylation (count: 18) (view all)	113 YQISEEVSRSELRSF dbPAF 209 LCGVMTISDSPREQD dbPAF 211 GVMTISDSPREQDSE dbPAF 217 DSPREQDSESQTLDK dbPAF 219 PREQDSESQTLDKVY dbPAF 230 DKVYQMKSKPRGYCL dbPAF 235 MKSKPRGYCLIINNH dbPAF 263 SIRDRNGTHLDAGAL dbPAF 272 LDAGALTTTFEELHF dbPAF 273 DAGALTTTFEELHFE dbPAF 305 IYQLMDHSNMDCFIC dbPAF 334 DGQEAPIYELTSQFT dbPAF 347 FTGLKCPSLAGKPKV dbPAF 373 QKGIPVETDSEEQPY dbPAF 375 GIPVETDSEEQPYLE dbPAF 380 TDSEEQPYLEMDLSS dbPAF 387 YLEMDLSSPQTRYIP dbPAF 448 TILTEVNYEVSNKDD dbPAF
Acetylation (count: 1)	169 RVCAQINKSLLKIIN PLMD
Ubiquitination (count: 15) (view all)	121 RSELRSFKFLLQEEI PLMD 130 LLQEEISKCKLDDDM PLMD 148 DIFIEMEKRVILGEG PLMD 156 RVILGEGKLDILKRV PLMD 161 EGKLDILKRVCAQIN PLMD 169 RVCAQINKSLLKIIN PLMD 183 NDYEEFSKERSSSLE PLMD 224 SESQTLDKVYQMKSK PLMD 344 TSQFTGLKCPSLAGK PLMD 351 KCPSLAGKPKVFFIQ PLMD 367 CQGDNYQKGIPVETD PLMD 461 DDKKNMGKQMPQPTF PLMD 472 QPTFTLRKKLVFPSD PLMD 473 PTFTLRKKLVFPSD* PLMD 63 ESNLSFLKELLFRIN PLMD
Glycation (count: 1)	148 DIFIEMEKRVILGEG PLMD

※ Protein-Protein Interaction

Network

Interaction

A

B

Source

O14727	Q14790	HPRD
O14920	Q14790	HPRD
O15111	Q14790	HPRD
O15519	Q14790	HPRD; IntAct
P06400	Q14790	HPRD
P10275	Q14790	HPRD; MINT
P10415	Q14790	HPRD; IntAct
P19525	Q14790	HPRD
P25445	Q14790	IntAct;HPRD; IntAct; MINT
P27361	Q14790	HPRD; MINT
P28482	Q14790	HPRD; MINT
P35222	Q14790	HPRD
P46527	Q14790	HPRD
P49768	Q14790	HPRD
Q12933	Q14790	HPRD; IntAct
Q13546	Q14790	HPRD; IntAct
Q14790	Q15121	HPRD