Q92851 (CASPA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Caspase-10
Short name=CASP-10
EC=3.4.22.63

Alternative name(s):
Apoptotic protease Mch-4
FAS-associated death domain protein interleukin-1B-converting enzyme 2
Short name=FLICE2
ICE-like apoptotic protease 4

Cleaved into the following 2 chains:

1. Caspase-10 subunit p23/17
2. Caspase-10 subunit p12

Gene names

Name:	CASP10
Synonyms:	MCH4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	521 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved 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. Ref.11 Isoform C is proteolytically inactive. Ref.11
Catalytic activity	Strict requirement for Asp at position P1 and has a preferred cleavage sequence of Leu-Gln-Thr-Asp-|-Gly.
Subunit structure	Heterotetramer 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. Ref.11
Tissue specificity	Detectable in most tissues. Lowest expression is seen in brain, kidney, prostate, testis and colon.
Post-translational modification	Cleavage by granzyme B and autocatalytic activity generate the two active subunits. Phosphorylated upon DNA damage, probably by ATM or ATR.
Involvement in disease	Autoimmune 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13 Ref.16 Familial 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. Note: The gene represented in this entry is involved in disease pathogenesis. Ref.14 Gastric 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. Note: The gene represented in this entry is involved in disease pathogenesis. Ref.15
Sequence similarities	Belongs to the peptidase C14A family. Contains 2 DED (death effector) domains.

Ontologies

Keywords
Biological process	Apoptosis
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Repeat
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein Zymogen
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Traceable author statement. Source: Reactome induction of apoptosis Traceable author statement Ref.13. Source: ProtInc innate immune response Traceable author statement. Source: Reactome positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from mutant phenotype PubMed 12884866. Source: UniProtKB proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome plasma membrane Traceable author statement. Source: Reactome
Molecular_function	cysteine-type endopeptidase activity Traceable author statement Ref.13Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CASP8	Q14790	5	EBI-495095,EBI-78060
RIOK3	O14730	4	EBI-495095,EBI-1047061
RIPK1	Q13546	2	EBI-495095,EBI-358507

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]

Isoform A (identifier: Q92851-1)

Also known as: 10-A;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform B (identifier: Q92851-2)

Also known as: 10-B; 10-S;

The sequence of this isoform differs from the canonical sequence as follows:
     229-271: Missing.
     473-521: MLKFLEKTME...PPMRRWSSVS → HEDILSILTA...FPVPLDALSL

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoform D (identifier: Q92851-4)

Also known as: 10-D; 10-L;

The sequence of this isoform differs from the canonical sequence as follows:
     473-521: MLKFLEKTME...PPMRRWSSVS → HEDILSILTA...FPVPLDALSL

Isoform C (identifier: Q92851-3)

Also known as: 10-C;

The sequence of this isoform differs from the canonical sequence as follows:
     241-273: GNRATNGAPSLVSRGMQGASANTLNSETSTKRA → EGSCVQDESEPQRPLCHCQQPQLYLPEGQTRNP
     274-521: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoform 5 (identifier: Q92851-5)

The sequence of this isoform differs from the canonical sequence as follows:
     229-271: Missing.

Isoform 6 (identifier: Q92851-6)

The sequence of this isoform differs from the canonical sequence as follows:
     241-307: Missing.
     473-521: MLKFLEKTME...PPMRRWSSVS → HEDILSILTA...FPVPLDALSL

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Propeptide	1 – 219	219			PRO_0000004644
	Chain	220 – 415	196	Caspase-10 subunit p23/17		PRO_0000004645
	Chain	416 – 521	106	Caspase-10 subunit p12		PRO_0000004646
Regions
	Domain	19 – 97	79	DED 1
	Domain	114 – 187	74	DED 2
Sites
	Active site	358	1	By similarity
	Active site	401	1	By similarity
Natural variations
	Alternative sequence	229 – 271	43	Missing in isoform B and isoform 5.		VSP_000819
	Alternative sequence	241 – 307	67	Missing in isoform 6.		VSP_037229
	Alternative sequence	241 – 273	33	GNRAT…STKRA → EGSCVQDESEPQRPLCHCQQ PQLYLPEGQTRNP in isoform C.		VSP_000821
	Alternative sequence	274 – 521	248	Missing in isoform C.		VSP_000822
	Alternative sequence	473 – 521	49	MLKFL…WSSVS → HEDILSILTAVNDDVSRRVD KQGTKKQMPQPAFTLRKKLV FPVPLDALSL in isoform B, isoform D and isoform 6.		VSP_000820
	Natural variant	14	1	K → T Found in a colon cancer sample; somatic mutation. Ref.19		VAR_065233
	Natural variant	21	1	R → C Found in a multiple myeloma sample; somatic mutation. Ref.18		VAR_065234
	Natural variant	147	1	M → T in GASC; somatic mutation; impairs CASP10-mediated apoptosis. Ref.15		VAR_037428
	Natural variant	239	1	S → C. Ref.6 Corresponds to variant rs41473647 [ dbSNP | Ensembl ].		VAR_055361
	Natural variant	285	1	L → F in ALPS2A. Ref.13 Corresponds to variant rs17860403 [ dbSNP | Ensembl ].		VAR_014071
	Natural variant	285	1	L → P Found in a T-acute lymphoblastic leukemia sample; somatic mutation. Ref.18		VAR_065235
	Natural variant	406	1	I → L in ALPS2A; the mutant protein has defective apoptosis and exerts a dominant-negative effect when cotransfected with the wild-type protein. Ref.16		VAR_037429
	Natural variant	410	1	V → I Does not interfere with apoptosis in a dominant negative manner. Ref.3 Ref.6 Ref.13 Ref.16 Corresponds to variant rs13010627 [ dbSNP | Ensembl ].		VAR_014072
	Natural variant	414	1	A → V in NHL; somatic mutation. Ref.14 Corresponds to variant rs28936699 [ dbSNP | Ensembl ].		VAR_037430
	Natural variant	444	1	P → S. Ref.6 Corresponds to variant rs41513147 [ dbSNP | Ensembl ].		VAR_055362
	Natural variant	446	1	Y → C Associated with ALPS2A; does not interfere with apoptosis in a dominant negative manner. Ref.6 Ref.16 Corresponds to variant rs17860405 [ dbSNP | Ensembl ].		VAR_037431
Isoform B:
	Natural variant	479	1	L → I. Corresponds to variant rs13006529 [ dbSNP | Ensembl ].
Isoform D:
	Natural variant	522	1	L → I Not associated with significantly altered cutaneous melanoma risk. Corresponds to variant rs13006529 [ dbSNP | Ensembl ].
Isoform 6:
	Natural variant	455	1	L → I. Corresponds to variant rs13006529 [ dbSNP | Ensembl ].
Experimental info
	Mutagenesis	401	1	C → A: Abolishes proteolytic activity. Ref.11
	Sequence conflict	68	1	E → G in AAB46730. Ref.2
	Sequence conflict	268	1	T → A in AAD28403. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform A (10-A) [UniParc]. Last modified January 11, 2001. Version 3. Checksum: 840348AE602B8243	FASTA	521	58,951
	10 20 30 40 50 60 MKSQGQHWYS SSDKNCKVSF REKLLIIDSN LGVQDVENLK FLCIGLVPNK KLEKSSSASD 70 80 90 100 110 120 VFEHLLAEDL LSEEDPFFLA ELLYIIRQKK LLQHLNCTKE EVERLLPTRQ RVSLFRNLLY 130 140 150 160 170 180 ELSEGIDSEN LKDMIFLLKD SLPKTEMTSL SFLAFLEKQG KIDEDNLTCL EDLCKTVVPK 190 200 210 220 230 240 LLRNIEKYKR EKAIQIVTPP VDKEAESYQG EEELVSQTDV KTFLEALPQE SWQNKHAGSN 250 260 270 280 290 300 GNRATNGAPS LVSRGMQGAS ANTLNSETST KRAAVYRMNR NHRGLCVIVN NHSFTSLKDR 310 320 330 340 350 360 QGTHKDAEIL SHVFQWLGFT VHIHNNVTKV EMEMVLQKQK CNPAHADGDC FVFCILTHGR 370 380 390 400 410 420 FGAVYSSDEA LIPIREIMSH FTALQCPRLA EKPKLFFIQA CQGEEIQPSV SIEADALNPE 430 440 450 460 470 480 QAPTSLQDSI PAEADFLLGL ATVPGYVSFR HVEEGSWYIQ SLCNHLKKLV PRMLKFLEKT 490 500 510 520 MEIRGRKRTV WGAKQISATS LPTAISAQTP RPPMRRWSSV S
	Isoform B (10-B) (10-S) [UniParc]. Checksum: 1467FD7A4EE003FF	FASTA	479	54,566
	10 20 30 40 50 60 MKSQGQHWYS SSDKNCKVSF REKLLIIDSN LGVQDVENLK FLCIGLVPNK KLEKSSSASD 70 80 90 100 110 120 VFEHLLAEDL LSEEDPFFLA ELLYIIRQKK LLQHLNCTKE EVERLLPTRQ RVSLFRNLLY 130 140 150 160 170 180 ELSEGIDSEN LKDMIFLLKD SLPKTEMTSL SFLAFLEKQG KIDEDNLTCL EDLCKTVVPK 190 200 210 220 230 240 LLRNIEKYKR EKAIQIVTPP VDKEAESYQG EEELVSQTDV KTFLEALPRA AVYRMNRNHR 250 260 270 280 290 300 GLCVIVNNHS FTSLKDRQGT HKDAEILSHV FQWLGFTVHI HNNVTKVEME MVLQKQKCNP 310 320 330 340 350 360 AHADGDCFVF CILTHGRFGA VYSSDEALIP IREIMSHFTA LQCPRLAEKP KLFFIQACQG 370 380 390 400 410 420 EEIQPSVSIE ADALNPEQAP TSLQDSIPAE ADFLLGLATV PGYVSFRHVE EGSWYIQSLC 430 440 450 460 470 NHLKKLVPRH EDILSILTAV NDDVSRRVDK QGTKKQMPQP AFTLRKKLVF PVPLDALSL
	Isoform D (10-D) (10-L) [UniParc]. Checksum: 34847E07B3DFA688	FASTA	522	58,994
	10 20 30 40 50 60 MKSQGQHWYS SSDKNCKVSF REKLLIIDSN LGVQDVENLK FLCIGLVPNK KLEKSSSASD 70 80 90 100 110 120 VFEHLLAEDL LSEEDPFFLA ELLYIIRQKK LLQHLNCTKE EVERLLPTRQ RVSLFRNLLY 130 140 150 160 170 180 ELSEGIDSEN LKDMIFLLKD SLPKTEMTSL SFLAFLEKQG KIDEDNLTCL EDLCKTVVPK 190 200 210 220 230 240 LLRNIEKYKR EKAIQIVTPP VDKEAESYQG EEELVSQTDV KTFLEALPQE SWQNKHAGSN 250 260 270 280 290 300 GNRATNGAPS LVSRGMQGAS ANTLNSETST KRAAVYRMNR NHRGLCVIVN NHSFTSLKDR 310 320 330 340 350 360 QGTHKDAEIL SHVFQWLGFT VHIHNNVTKV EMEMVLQKQK CNPAHADGDC FVFCILTHGR 370 380 390 400 410 420 FGAVYSSDEA LIPIREIMSH FTALQCPRLA EKPKLFFIQA CQGEEIQPSV SIEADALNPE 430 440 450 460 470 480 QAPTSLQDSI PAEADFLLGL ATVPGYVSFR HVEEGSWYIQ SLCNHLKKLV PRHEDILSIL 490 500 510 520 TAVNDDVSRR VDKQGTKKQM PQPAFTLRKK LVFPVPLDAL SL
	Isoform C (10-C) [UniParc]. Checksum: 1146630514EE38DC	FASTA	273	31,419
	10 20 30 40 50 60 MKSQGQHWYS SSDKNCKVSF REKLLIIDSN LGVQDVENLK FLCIGLVPNK KLEKSSSASD 70 80 90 100 110 120 VFEHLLAEDL LSEEDPFFLA ELLYIIRQKK LLQHLNCTKE EVERLLPTRQ RVSLFRNLLY 130 140 150 160 170 180 ELSEGIDSEN LKDMIFLLKD SLPKTEMTSL SFLAFLEKQG KIDEDNLTCL EDLCKTVVPK 190 200 210 220 230 240 LLRNIEKYKR EKAIQIVTPP VDKEAESYQG EEELVSQTDV KTFLEALPQE SWQNKHAGSN 250 260 270 EGSCVQDESE PQRPLCHCQQ PQLYLPEGQT RNP
	Isoform 5 [UniParc]. Checksum: E78035535F8EF57B	FASTA	478	54,523
	10 20 30 40 50 60 MKSQGQHWYS SSDKNCKVSF REKLLIIDSN LGVQDVENLK FLCIGLVPNK KLEKSSSASD 70 80 90 100 110 120 VFEHLLAEDL LSEEDPFFLA ELLYIIRQKK LLQHLNCTKE EVERLLPTRQ RVSLFRNLLY 130 140 150 160 170 180 ELSEGIDSEN LKDMIFLLKD SLPKTEMTSL SFLAFLEKQG KIDEDNLTCL EDLCKTVVPK 190 200 210 220 230 240 LLRNIEKYKR EKAIQIVTPP VDKEAESYQG EEELVSQTDV KTFLEALPRA AVYRMNRNHR 250 260 270 280 290 300 GLCVIVNNHS FTSLKDRQGT HKDAEILSHV FQWLGFTVHI HNNVTKVEME MVLQKQKCNP 310 320 330 340 350 360 AHADGDCFVF CILTHGRFGA VYSSDEALIP IREIMSHFTA LQCPRLAEKP KLFFIQACQG 370 380 390 400 410 420 EEIQPSVSIE ADALNPEQAP TSLQDSIPAE ADFLLGLATV PGYVSFRHVE EGSWYIQSLC 430 440 450 460 470 NHLKKLVPRM LKFLEKTMEI RGRKRTVWGA KQISATSLPT AISAQTPRPP MRRWSSVS
	Isoform 6 [UniParc]. Checksum: 89037FC3EC173616	FASTA	455	51,785
	10 20 30 40 50 60 MKSQGQHWYS SSDKNCKVSF REKLLIIDSN LGVQDVENLK FLCIGLVPNK KLEKSSSASD 70 80 90 100 110 120 VFEHLLAEDL LSEEDPFFLA ELLYIIRQKK LLQHLNCTKE EVERLLPTRQ RVSLFRNLLY 130 140 150 160 170 180 ELSEGIDSEN LKDMIFLLKD SLPKTEMTSL SFLAFLEKQG KIDEDNLTCL EDLCKTVVPK 190 200 210 220 230 240 LLRNIEKYKR EKAIQIVTPP VDKEAESYQG EEELVSQTDV KTFLEALPQE SWQNKHAGSN 250 260 270 280 290 300 EILSHVFQWL GFTVHIHNNV TKVEMEMVLQ KQKCNPAHAD GDCFVFCILT HGRFGAVYSS 310 320 330 340 350 360 DEALIPIREI MSHFTALQCP RLAEKPKLFF IQACQGEEIQ PSVSIEADAL NPEQAPTSLQ 370 380 390 400 410 420 DSIPAEADFL LGLATVPGYV SFRHVEEGSW YIQSLCNHLK KLVPRHEDIL SILTAVNDDV 430 440 450 SRRVDKQGTK KQMPQPAFTL RKKLVFPVPL DALSL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic cysteine protease containing two FADD-like domains." Fernandes-Alnemri T., Armstrong R.C., Krebs J.F., Srinivasula S.M., Wang L., Bullrich F., Fritz L.C., Trapani J.A., Tomaselli K.J., Litwack G., Alnemri E.S. Proc. Natl. Acad. Sci. U.S.A. 93:7464-7469(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), VARIANT ILE-479 (ISOFORM B). Tissue: T-cell.
[2]	"Fas-associated death domain protein interleukin-1beta-converting enzyme 2 (FLICE2), an ICE/Ced-3 homologue, is proximally involved in CD95- and p55-mediated death signaling." Vincenz C., Dixit V.M. J. Biol. Chem. 272:6578-6583(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
[3]	"Molecular cloning and characterization of two novel pro-apoptotic isoforms of caspase-10." Ng P.W., Porter A.G., Janicke R.U. J. Biol. Chem. 274:10301-10308(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS C AND D), VARIANT ILE-410, VARIANT ILE-522 (ISOFORM D). Tissue: Spleen and Thymus.
[4]	"Cloning and characterization of three novel genes, ALS2CR1, ALS2CR2, and ALS2CR3, in the juvenile amyotrophic lateral sclerosis (ALS2) critical region at chromosome 2q33-q34: candidate genes for ALS2." Hadano S., Yanagisawa Y., Skaug J., Fichter K., Nasir J., Martindale D., Koop B.F., Scherer S.W., Nicholson D.W., Rouleau G.A., Ikeda J.-E., Hayden M.R. Genomics 71:200-213(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORMS A AND B), VARIANT ILE-479 (ISOFORM B).
[5]	"A novel human caspase 10 isoform participating in Fas-induced apoptosis." Vonarbourg C., Fischer A., Rieux-Laucat F. Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5 AND 6), VARIANT ILE-455 (ISOFORM 6). Tissue: Blood.
[6]	NIEHS SNPs program Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CYS-239; ILE-410; SER-444; CYS-446 AND ILE-522 (ISOFORM 2).
[7]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM D). Tissue: Brain.
[10]	"Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases." Srinivasula S.M., Ahmad M., Fernandes-Alnemri T., Litwack G., Alnemri E.S. Proc. Natl. Acad. Sci. U.S.A. 93:14486-14491(1996) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, PROTEOLYTIC PROCESSING.
[11]	"Caspase-10 is an initiator caspase in death receptor signaling." Wang J., Chun H.J., Wong W., Spencer D.M., Lenardo M.J. Proc. Natl. Acad. Sci. U.S.A. 98:13884-13888(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SELF-ASSOCIATION, INTERACTION WITH FADD, INTERACTION WITH CASP8, IDENTIFICATION IN A COMPLEX WITH FAS; FADD AND CASP8, MUTAGENESIS OF CYS-401.
[12]	"An unappreciated role for RNA surveillance." Hillman R.T., Green R.E., Brenner S.E. Genome Biol. 5:R8.1-R8.16(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[13]	"Inherited human caspase 10 mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome type II." Wang J., Zheng L., Lobito A., Chan F.K., Dale J., Sneller M., Yao X., Puck J.M., Straus S.E., Lenardo M.J. Cell 98:47-58(1999) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING (ISOFORMS B AND D), VARIANT ALPS2A PHE-285, VARIANT ILE-410.
[14]	"Inactivating mutations of CASP10 gene in non-Hodgkin lymphomas." Shin M.S., Kim H.S., Kang C.S., Park W.S., Kim S.Y., Lee S.N., Lee J.H., Park J.Y., Jang J.J., Kim C.W., Kim S.H., Lee J.Y., Yoo N.J., Lee S.H. Blood 99:4094-4099(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT NHL VAL-414.
[15]	"Inactivating mutations of the caspase-10 gene in gastric cancer." Park W.S., Lee J.H., Shin M.S., Park J.Y., Kim H.S., Lee J.H., Kim Y.S., Lee S.N., Xiao W., Park C.H., Lee S.H., Yoo N.J., Lee J.Y. Oncogene 21:2919-2925(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GASC THR-147, CHARACTERIZATION OF VARIANT GASC THR-147.
[16]	"Genetic alterations in caspase-10 may be causative or protective in autoimmune lymphoproliferative syndrome." Zhu S., Hsu A.P., Vacek M.M., Zheng L., Schaeffer A.A., Dale J.K., Davis J., Fischer R.E., Straus S.E., Boruchov D., Saulsbury F.T., Lenardo M.J., Puck J.M. Hum. Genet. 119:284-294(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ALPS2A LEU-406, VARIANTS ILE-410 AND CYS-446, CHARACTERIZATION OF VARIANTS ALPS2A LEU-406, CHARACTERIZATION OF VARIANTS ILE-410 AND CYS-446.
[17]	"Genetic variants and haplotypes of the caspase-8 and caspase-10 genes contribute to susceptibility to cutaneous melanoma." Li C., Zhao H., Hu Z., Liu Z., Wang L.-E., Gershenwald J.E., Prieto V.G., Lee J.E., Duvic M., Grimm E.A., Wei Q. Hum. Mutat. 29:1443-1451(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ILE-522 (ISOFORM D), RISK FACTOR FOR CUTANEOUS MELANOMA.
[18]	"Mutational analysis of CASP10 gene in acute leukaemias and multiple myelomas." Kim M.S., Oh J.E., Min C.K., Lee S., Chung N.G., Yoo N.J., Lee S.H. Pathology 41:484-487(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CYS-21 AND PRO-285.
[19]	"Mutational analysis of CASP10 gene in colon, breast, lung and hepatocellular carcinomas." Oh J.E., Kim M.S., Ahn C.H., Kim S.S., Han J.Y., Lee S.H., Yoo N.J. Pathology 42:73-76(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT THR-14.
+	Additional computationally mapped references.

Web resources

CASP10base

CASP10 mutation db

Autoimmune Lymphoproliferative Syndrome Database (ALPSbase)

Caspase-10 mutations causing ALPS type II

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	U60519 mRNA. Translation: AAC50644.1. U86214 mRNA. Translation: AAB46730.1. AF111344 mRNA. Translation: AAD28402.1. AF111345 mRNA. Translation: AAD28403.1. AB038979 Genomic DNA. Translation: BAB32553.1. AB038979 Genomic DNA. Translation: BAB32554.1. AJ487678 mRNA. Translation: CAD32371.1. AJ487679 mRNA. Translation: CAD32372.1. EF050529 Genomic DNA. Translation: ABJ53426.1. AC007283 Genomic DNA. Translation: AAY24291.1. CH471063 Genomic DNA. Translation: EAW70248.1. CH471063 Genomic DNA. Translation: EAW70249.1. BC042844 mRNA. Translation: AAH42844.1.
IPI	IPI00216197. IPI00290791. IPI00334756. IPI00433086. IPI00433087. IPI00868860.
RefSeq	NP_001193453.1. NM_001206524.1. NP_001193471.1. NM_001206542.1. NP_001221.2. NM_001230.4. NP_116756.2. NM_032974.4. NP_116758.1. NM_032976.3. NP_116759.2. NM_032977.3.
UniGene	Hs.5353.
3D structure databases
ProteinModelPortal	Q92851.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q92851. 18 interactions.
MINT	MINT-201954.
STRING	9606.ENSP00000286186.
Protein family/group databases
MEROPS	C14.011.
PTM databases
PhosphoSite	Q92851.
Polymorphism databases
DMDM	12644463.
Proteomic databases
PaxDb	Q92851.
PRIDE	Q92851.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000272879; ENSP00000272879; ENSG00000003400. ENST00000286186; ENSP00000286186; ENSG00000003400. ENST00000313728; ENSP00000314599; ENSG00000003400. ENST00000346817; ENSP00000237865; ENSG00000003400. ENST00000360132; ENSP00000353250; ENSG00000003400. ENST00000448480; ENSP00000396835; ENSG00000003400.
GeneID	843.
KEGG	hsa:843.
UCSC	uc002uxj.1. human. uc002uxk.1. human. uc002uxl.2. human. uc002uxm.2. human. uc010fta.1. human. uc010ftb.2. human.
Organism-specific databases
CTD	843.
GeneCards	GC02P202047.
HGNC	HGNC:1500. CASP10.
HPA	CAB003780. HPA017059.
MIM	601762. gene. 603909. phenotype. 605027. phenotype. 613659. phenotype.
neXtProt	NX_Q92851.
Orphanet	3261. Autoimmune lymphoproliferative syndrome.
PharmGKB	PA26084.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG303276.
HOVERGEN	HBG050803.
KO	K04400.
OMA	QGTKKQM.
Enzyme and pathway databases
BRENDA	3.4.22.63. 2681.
Pathway_Interaction_DB	caspase_pathway. Caspase cascade in apoptosis. faspathway. FAS signaling pathway (CD95). trail_pathway. TRAIL signaling pathway.
Reactome	REACT_578. Apoptosis. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q92851.
Bgee	Q92851.
CleanEx	HS_CASP10.
Genevestigator	Q92851.
GermOnline	ENSG00000003400. Homo sapiens.
Family and domain databases
Gene3D	1.10.533.10. 2 hits.
InterPro	IPR011029. DEATH-like_dom. IPR001875. DED. IPR011600. Pept_C14_cat. IPR001309. Pept_C14_ICE_p20. IPR016129. Pept_C14_ICE_p20_AS. IPR002138. Pept_C14_p10. IPR002398. Pept_C14_p45. IPR015917. Pept_C14_p45_core. [Graphical view]
PANTHER	PTHR10454. PTHR10454. 1 hit.
Pfam	PF01335. DED. 2 hits. PF00656. Peptidase_C14. 1 hit. [Graphical view]
PRINTS	PR00376. IL1BCENZYME.
SMART	SM00115. CASc. 1 hit. SM00031. DED. 2 hits. [Graphical view]
SUPFAM	SSF47986. DEATH_like. 2 hits.
PROSITE	PS01122. CASPASE_CYS. 1 hit. PS01121. CASPASE_HIS. 1 hit. PS50207. CASPASE_P10. 1 hit. PS50208. CASPASE_P20. 1 hit. PS50168. DED. 2 hits. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q92851.
ChEMBL	CHEMBL5037.
ChiTaRS	CASP10. human.
GenomeRNAi	843.
NextBio	3530.
PMAP-CutDB	Q8IUP5.
SOURCE	Search...

Entry information

Entry name

CASPA_HUMAN

Accession

Primary (citable) accession number: Q92851
Secondary accession number(s): Q6KF62 , Q6KF63, Q8IUP5, Q8WYQ8, Q99845, Q9Y2U6, Q9Y2U7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	January 11, 2001
Last modified:	May 1, 2013
This is version 144 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.