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Q92851

- CASPA_HUMAN

UniProt

Q92851 - CASPA_HUMAN

Protein

Caspase-10

Gene

CASP10

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 160 (01 Oct 2014)
      Sequence version 3 (11 Jan 2001)
      Previous versions | rss
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    Functioni

    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.1 Publication
    Isoform C is proteolytically inactive.1 Publication

    Catalytic activityi

    Strict requirement for Asp at position P1 and has a preferred cleavage sequence of Leu-Gln-Thr-Asp-|-Gly.

    Enzyme regulationi

    Negatively regulated by RFFL through proteasomal degradation.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei358 – 3581By similarity
    Active sitei401 – 4011By similarity

    GO - Molecular functioni

    1. cysteine-type endopeptidase activity Source: ProtInc
    2. cysteine-type endopeptidase activity involved in apoptotic signaling pathway Source: UniProtKB
    3. death effector domain binding Source: UniProtKB
    4. protein binding Source: IntAct
    5. ubiquitin protein ligase binding Source: UniProtKB

    GO - Biological processi

    1. apoptotic process Source: RefGenome
    2. apoptotic signaling pathway Source: Reactome
    3. innate immune response Source: Reactome
    4. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
    5. regulation of apoptotic process Source: InterPro

    Keywords - Molecular functioni

    Hydrolase, Protease, Thiol protease

    Keywords - Biological processi

    Apoptosis

    Enzyme and pathway databases

    BRENDAi3.4.22.63. 2681.
    ReactomeiREACT_25039. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
    REACT_402. TRAIL signaling.
    REACT_900. FasL/ CD95L signaling.

    Protein family/group databases

    MEROPSiC14.011.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Caspase-10 (EC:3.4.22.63)
    Short name:
    CASP-10
    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:
    Gene namesi
    Name:CASP10
    Synonyms:MCH4
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:1500. CASP10.

    Subcellular locationi

    GO - Cellular componenti

    1. CD95 death-inducing signaling complex Source: UniProtKB
    2. cytoplasm Source: RefGenome
    3. cytosol Source: Reactome
    4. plasma membrane Source: Reactome
    5. ripoptosome Source: UniProtKB

    Pathology & Biotechi

    Involvement in diseasei

    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.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti285 – 2851L → F in ALPS2A. 1 Publication
    Corresponds to variant rs17860403 [ dbSNP | Ensembl ].
    VAR_014071
    Natural varianti406 – 4061I → L in ALPS2A; the mutant protein has defective apoptosis and exerts a dominant-negative effect when cotransfected with the wild-type protein. 1 Publication
    Corresponds to variant rs80358239 [ dbSNP | Ensembl ].
    VAR_037429
    Natural varianti446 – 4461Y → C Associated with ALPS2A; does not interfere with apoptosis in a dominant negative manner. 1 Publication
    Corresponds to variant rs17860405 [ dbSNP | Ensembl ].
    VAR_037431
    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.1 Publication
    Note: The gene represented in this entry is involved in disease pathogenesis.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti414 – 4141A → V in NHL; somatic mutation. 1 Publication
    Corresponds to variant rs28936699 [ dbSNP | Ensembl ].
    VAR_037430
    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.1 Publication
    Note: The gene represented in this entry is involved in disease pathogenesis.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti147 – 1471M → T in GASC; somatic mutation; impairs CASP10-mediated apoptosis. 1 Publication
    Corresponds to variant rs121909776 [ dbSNP | Ensembl ].
    VAR_037428

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi401 – 4011C → A: Abolishes proteolytic activity. 1 Publication

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi603909. phenotype.
    605027. phenotype.
    613659. phenotype.
    Orphaneti3261. Autoimmune lymphoproliferative syndrome.
    PharmGKBiPA26084.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Propeptidei1 – 219219PRO_0000004644Add
    BLAST
    Chaini220 – 415196Caspase-10 subunit p23/17PRO_0000004645Add
    BLAST
    Chaini416 – 521106Caspase-10 subunit p12PRO_0000004646Add
    BLAST

    Post-translational modificationi

    Cleavage by granzyme B and autocatalytic activity generate the two active subunits.

    Keywords - PTMi

    Zymogen

    Proteomic databases

    MaxQBiQ92851.
    PaxDbiQ92851.
    PRIDEiQ92851.

    PTM databases

    PhosphoSiteiQ92851.

    Miscellaneous databases

    PMAP-CutDBQ8IUP5.

    Expressioni

    Tissue specificityi

    Detectable in most tissues. Lowest expression is seen in brain, kidney, prostate, testis and colon.

    Gene expression databases

    ArrayExpressiQ92851.
    BgeeiQ92851.
    CleanExiHS_CASP10.
    GenevestigatoriQ92851.

    Organism-specific databases

    HPAiCAB003780.
    HPA017059.

    Interactioni

    Subunit structurei

    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. Interacts with RFFL.By similarity2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CASP8Q147903EBI-495095,EBI-78060
    CFLARO155193EBI-495095,EBI-514941
    RIOK3O147304EBI-495095,EBI-1047061
    RIPK1Q135462EBI-495095,EBI-358507

    Protein-protein interaction databases

    BioGridi107293. 88 interactions.
    IntActiQ92851. 21 interactions.
    MINTiMINT-201954.
    STRINGi9606.ENSP00000286186.

    Structurei

    3D structure databases

    ProteinModelPortaliQ92851.
    SMRiQ92851. Positions 273-499.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini19 – 9779DED 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini114 – 18774DED 2PROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the peptidase C14A family.Curated
    Contains 2 DED (death effector) domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiNOG303276.
    HOVERGENiHBG050803.
    KOiK04400.
    OMAiEANIEKW.
    OrthoDBiEOG7CRTQM.
    PhylomeDBiQ92851.
    TreeFamiTF102023.

    Family and domain databases

    Gene3Di1.10.533.10. 2 hits.
    3.40.50.1460. 1 hit.
    InterProiIPR029030. Caspase-like_dom.
    IPR011029. DEATH-like_dom.
    IPR001875. DED.
    IPR011600. Pept_C14_caspase.
    IPR001309. Pept_C14_ICE_p20.
    IPR016129. Pept_C14_ICE_p20_AS.
    IPR002138. Pept_C14_p10.
    IPR015917. Pept_C14A_p45_core.
    [Graphical view]
    PfamiPF01335. DED. 2 hits.
    PF00656. Peptidase_C14. 1 hit.
    [Graphical view]
    PRINTSiPR00376. IL1BCENZYME.
    SMARTiSM00115. CASc. 1 hit.
    SM00031. DED. 2 hits.
    [Graphical view]
    SUPFAMiSSF47986. SSF47986. 2 hits.
    PROSITEiPS01122. 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]

    Sequences (7)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 7 isoformsi produced by alternative splicing. Align

    Isoform A (identifier: Q92851-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MKSQGQHWYS SSDKNCKVSF REKLLIIDSN LGVQDVENLK FLCIGLVPNK    50
    KLEKSSSASD VFEHLLAEDL LSEEDPFFLA ELLYIIRQKK LLQHLNCTKE 100
    EVERLLPTRQ RVSLFRNLLY ELSEGIDSEN LKDMIFLLKD SLPKTEMTSL 150
    SFLAFLEKQG KIDEDNLTCL EDLCKTVVPK LLRNIEKYKR EKAIQIVTPP 200
    VDKEAESYQG EEELVSQTDV KTFLEALPQE SWQNKHAGSN GNRATNGAPS 250
    LVSRGMQGAS ANTLNSETST KRAAVYRMNR NHRGLCVIVN NHSFTSLKDR 300
    QGTHKDAEIL SHVFQWLGFT VHIHNNVTKV EMEMVLQKQK CNPAHADGDC 350
    FVFCILTHGR FGAVYSSDEA LIPIREIMSH FTALQCPRLA EKPKLFFIQA 400
    CQGEEIQPSV SIEADALNPE QAPTSLQDSI PAEADFLLGL ATVPGYVSFR 450
    HVEEGSWYIQ SLCNHLKKLV PRMLKFLEKT MEIRGRKRTV WGAKQISATS 500
    LPTAISAQTP RPPMRRWSSV S 521
    Length:521
    Mass (Da):58,951
    Last modified:January 11, 2001 - v3
    Checksum:i840348AE602B8243
    GO
    Isoform B (identifier: Q92851-2) [UniParc]FASTAAdd to Basket

    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.

    Show »
    Length:479
    Mass (Da):54,566
    Checksum:i1467FD7A4EE003FF
    GO
    Isoform D (identifier: Q92851-4) [UniParc]FASTAAdd to Basket

    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

    Show »
    Length:522
    Mass (Da):58,994
    Checksum:i34847E07B3DFA688
    GO
    Isoform C (identifier: Q92851-3) [UniParc]FASTAAdd to Basket

    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.

    Show »
    Length:273
    Mass (Da):31,419
    Checksum:i1146630514EE38DC
    GO
    Isoform 5 (identifier: Q92851-5) [UniParc]FASTAAdd to Basket

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

    Show »
    Length:478
    Mass (Da):54,523
    Checksum:iE78035535F8EF57B
    GO
    Isoform 6 (identifier: Q92851-6) [UniParc]FASTAAdd to Basket

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

    Show »
    Length:455
    Mass (Da):51,785
    Checksum:i89037FC3EC173616
    GO
    Isoform 7 (identifier: Q92851-7) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         229-247: QESWQNKHAGSNGNRATNG → EGVFVFLNEGDRGNSPDDL
         248-521: Missing.

    Show »
    Length:247
    Mass (Da):28,364
    Checksum:i52370B5AD12C4DCF
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti68 – 681E → G in AAB46730. (PubMed:9045686)Curated
    Sequence conflicti268 – 2681T → A in AAD28403. (PubMed:10187817)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti14 – 141K → T Found in a colon cancer sample; somatic mutation. 1 Publication
    VAR_065233
    Natural varianti21 – 211R → C Found in a multiple myeloma sample; somatic mutation. 1 Publication
    VAR_065234
    Natural varianti147 – 1471M → T in GASC; somatic mutation; impairs CASP10-mediated apoptosis. 1 Publication
    Corresponds to variant rs121909776 [ dbSNP | Ensembl ].
    VAR_037428
    Natural varianti239 – 2391S → C.
    Corresponds to variant rs41473647 [ dbSNP | Ensembl ].
    VAR_055361
    Natural varianti285 – 2851L → F in ALPS2A. 1 Publication
    Corresponds to variant rs17860403 [ dbSNP | Ensembl ].
    VAR_014071
    Natural varianti285 – 2851L → P Found in a T-acute lymphoblastic leukemia sample; somatic mutation. 1 Publication
    VAR_065235
    Natural varianti406 – 4061I → L in ALPS2A; the mutant protein has defective apoptosis and exerts a dominant-negative effect when cotransfected with the wild-type protein. 1 Publication
    Corresponds to variant rs80358239 [ dbSNP | Ensembl ].
    VAR_037429
    Natural varianti410 – 4101V → I Does not interfere with apoptosis in a dominant negative manner. 3 Publications
    Corresponds to variant rs13010627 [ dbSNP | Ensembl ].
    VAR_014072
    Natural varianti414 – 4141A → V in NHL; somatic mutation. 1 Publication
    Corresponds to variant rs28936699 [ dbSNP | Ensembl ].
    VAR_037430
    Natural varianti444 – 4441P → S.
    Corresponds to variant rs41513147 [ dbSNP | Ensembl ].
    VAR_055362
    Natural varianti446 – 4461Y → C Associated with ALPS2A; does not interfere with apoptosis in a dominant negative manner. 1 Publication
    Corresponds to variant rs17860405 [ dbSNP | Ensembl ].
    VAR_037431
    Isoform 6 (identifier: Q92851-6)
    Natural varianti455 – 4551L → I.
    Corresponds to variant rs13006529 [ dbSNP | Ensembl ].
    Isoform B (identifier: Q92851-2)
    Natural varianti479 – 4791L → I.
    Corresponds to variant rs13006529 [ dbSNP | Ensembl ].
    Isoform D (identifier: Q92851-4)
    Natural varianti522 – 5221L → I Not associated with significantly altered cutaneous melanoma risk.
    Corresponds to variant rs13006529 [ dbSNP | Ensembl ].

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei229 – 27143Missing in isoform B and isoform 5. 2 PublicationsVSP_000819Add
    BLAST
    Alternative sequencei229 – 24719QESWQ…RATNG → EGVFVFLNEGDRGNSPDDL in isoform 7. 1 PublicationVSP_053333Add
    BLAST
    Alternative sequencei241 – 30767Missing in isoform 6. 1 PublicationVSP_037229Add
    BLAST
    Alternative sequencei241 – 27333GNRAT…STKRA → EGSCVQDESEPQRPLCHCQQ PQLYLPEGQTRNP in isoform C. 1 PublicationVSP_000821Add
    BLAST
    Alternative sequencei248 – 521274Missing in isoform 7. 1 PublicationVSP_053334Add
    BLAST
    Alternative sequencei274 – 521248Missing in isoform C. 1 PublicationVSP_000822Add
    BLAST
    Alternative sequencei473 – 52149MLKFL…WSSVS → HEDILSILTAVNDDVSRRVD KQGTKKQMPQPAFTLRKKLV FPVPLDALSL in isoform B, isoform D and isoform 6. 4 PublicationsVSP_000820Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    AY690601 mRNA. Translation: AAU00989.1.
    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.
    CCDSiCCDS2338.1. [Q92851-1]
    CCDS2339.1. [Q92851-2]
    CCDS2340.1. [Q92851-4]
    CCDS56159.1. [Q92851-6]
    CCDS56160.1. [Q92851-5]
    RefSeqiNP_001193453.1. NM_001206524.1. [Q92851-6]
    NP_001193471.1. NM_001206542.1. [Q92851-5]
    NP_001221.2. NM_001230.4. [Q92851-2]
    NP_116756.2. NM_032974.4. [Q92851-1]
    NP_116758.1. NM_032976.3. [Q92851-3]
    NP_116759.2. NM_032977.3. [Q92851-4]
    XP_005246967.1. XM_005246910.1. [Q92851-3]
    XP_005246968.1. XM_005246911.1. [Q92851-7]
    UniGeneiHs.5353.

    Genome annotation databases

    EnsembliENST00000272879; ENSP00000272879; ENSG00000003400. [Q92851-1]
    ENST00000286186; ENSP00000286186; ENSG00000003400. [Q92851-4]
    ENST00000313728; ENSP00000314599; ENSG00000003400. [Q92851-6]
    ENST00000346817; ENSP00000237865; ENSG00000003400. [Q92851-2]
    ENST00000360132; ENSP00000353250; ENSG00000003400. [Q92851-3]
    ENST00000374650; ENSP00000363781; ENSG00000003400. [Q92851-7]
    ENST00000448480; ENSP00000396835; ENSG00000003400. [Q92851-5]
    GeneIDi843.
    KEGGihsa:843.
    UCSCiuc002uxj.1. human. [Q92851-4]
    uc002uxk.1. human. [Q92851-2]
    uc002uxl.2. human. [Q92851-1]
    uc002uxm.2. human. [Q92851-5]
    uc010fta.1. human. [Q92851-6]
    uc010ftb.2. human. [Q92851-3]

    Polymorphism databases

    DMDMi12644463.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    CASP10base

    CASP10 mutation db

    Autoimmune Lymphoproliferative Syndrome Database (ALPSbase)

    Caspase-10 mutations causing ALPS type II

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    AY690601 mRNA. Translation: AAU00989.1 .
    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 .
    CCDSi CCDS2338.1. [Q92851-1 ]
    CCDS2339.1. [Q92851-2 ]
    CCDS2340.1. [Q92851-4 ]
    CCDS56159.1. [Q92851-6 ]
    CCDS56160.1. [Q92851-5 ]
    RefSeqi NP_001193453.1. NM_001206524.1. [Q92851-6 ]
    NP_001193471.1. NM_001206542.1. [Q92851-5 ]
    NP_001221.2. NM_001230.4. [Q92851-2 ]
    NP_116756.2. NM_032974.4. [Q92851-1 ]
    NP_116758.1. NM_032976.3. [Q92851-3 ]
    NP_116759.2. NM_032977.3. [Q92851-4 ]
    XP_005246967.1. XM_005246910.1. [Q92851-3 ]
    XP_005246968.1. XM_005246911.1. [Q92851-7 ]
    UniGenei Hs.5353.

    3D structure databases

    ProteinModelPortali Q92851.
    SMRi Q92851. Positions 273-499.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107293. 88 interactions.
    IntActi Q92851. 21 interactions.
    MINTi MINT-201954.
    STRINGi 9606.ENSP00000286186.

    Chemistry

    BindingDBi Q92851.
    ChEMBLi CHEMBL5037.

    Protein family/group databases

    MEROPSi C14.011.

    PTM databases

    PhosphoSitei Q92851.

    Polymorphism databases

    DMDMi 12644463.

    Proteomic databases

    MaxQBi Q92851.
    PaxDbi Q92851.
    PRIDEi Q92851.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000272879 ; ENSP00000272879 ; ENSG00000003400 . [Q92851-1 ]
    ENST00000286186 ; ENSP00000286186 ; ENSG00000003400 . [Q92851-4 ]
    ENST00000313728 ; ENSP00000314599 ; ENSG00000003400 . [Q92851-6 ]
    ENST00000346817 ; ENSP00000237865 ; ENSG00000003400 . [Q92851-2 ]
    ENST00000360132 ; ENSP00000353250 ; ENSG00000003400 . [Q92851-3 ]
    ENST00000374650 ; ENSP00000363781 ; ENSG00000003400 . [Q92851-7 ]
    ENST00000448480 ; ENSP00000396835 ; ENSG00000003400 . [Q92851-5 ]
    GeneIDi 843.
    KEGGi hsa:843.
    UCSCi uc002uxj.1. human. [Q92851-4 ]
    uc002uxk.1. human. [Q92851-2 ]
    uc002uxl.2. human. [Q92851-1 ]
    uc002uxm.2. human. [Q92851-5 ]
    uc010fta.1. human. [Q92851-6 ]
    uc010ftb.2. human. [Q92851-3 ]

    Organism-specific databases

    CTDi 843.
    GeneCardsi GC02P202047.
    GeneReviewsi CASP10.
    HGNCi HGNC:1500. CASP10.
    HPAi CAB003780.
    HPA017059.
    MIMi 601762. gene.
    603909. phenotype.
    605027. phenotype.
    613659. phenotype.
    neXtProti NX_Q92851.
    Orphaneti 3261. Autoimmune lymphoproliferative syndrome.
    PharmGKBi PA26084.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG303276.
    HOVERGENi HBG050803.
    KOi K04400.
    OMAi EANIEKW.
    OrthoDBi EOG7CRTQM.
    PhylomeDBi Q92851.
    TreeFami TF102023.

    Enzyme and pathway databases

    BRENDAi 3.4.22.63. 2681.
    Reactomei REACT_25039. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
    REACT_402. TRAIL signaling.
    REACT_900. FasL/ CD95L signaling.

    Miscellaneous databases

    ChiTaRSi CASP10. human.
    GeneWikii Caspase_10.
    GenomeRNAii 843.
    NextBioi 3530.
    PMAP-CutDB Q8IUP5.
    PROi Q92851.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q92851.
    Bgeei Q92851.
    CleanExi HS_CASP10.
    Genevestigatori Q92851.

    Family and domain databases

    Gene3Di 1.10.533.10. 2 hits.
    3.40.50.1460. 1 hit.
    InterProi IPR029030. Caspase-like_dom.
    IPR011029. DEATH-like_dom.
    IPR001875. DED.
    IPR011600. Pept_C14_caspase.
    IPR001309. Pept_C14_ICE_p20.
    IPR016129. Pept_C14_ICE_p20_AS.
    IPR002138. Pept_C14_p10.
    IPR015917. Pept_C14A_p45_core.
    [Graphical view ]
    Pfami PF01335. DED. 2 hits.
    PF00656. Peptidase_C14. 1 hit.
    [Graphical view ]
    PRINTSi PR00376. IL1BCENZYME.
    SMARTi SM00115. CASc. 1 hit.
    SM00031. DED. 2 hits.
    [Graphical view ]
    SUPFAMi SSF47986. SSF47986. 2 hits.
    PROSITEi 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 ]
    ProtoNeti Search...

    Publicationsi

    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. "Three novel isoforms of caspase family that are deficient of conservative CASP domain."
      Wang P.Z.
      Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7).
    7. 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).
    8. "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].
    9. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    10. "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.
    11. "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.
    12. "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.
    13. Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
    14. "Suppression of caspase-8- and -10-associated RING proteins results in sensitization to death ligands and inhibition of tumor cell growth."
      McDonald E.R. III, El-Deiry W.S.
      Proc. Natl. Acad. Sci. U.S.A. 101:6170-6175(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH RFFL, ENZYME REGULATION.
    15. "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: VARIANT ALPS2A PHE-285, VARIANT ILE-410, ALTERNATIVE SPLICING (ISOFORMS B AND D).
    16. Cited for: VARIANT NHL VAL-414.
    17. Cited for: VARIANT GASC THR-147, CHARACTERIZATION OF VARIANT GASC THR-147.
    18. "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.
    19. "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.
    20. "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.
    21. "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.

    Entry informationi

    Entry nameiCASPA_HUMAN
    AccessioniPrimary (citable) accession number: Q92851
    Secondary accession number(s): Q68HC0
    , Q6KF62, Q6KF63, Q8IUP5, Q8WYQ8, Q99845, Q9Y2U6, Q9Y2U7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: January 11, 2001
    Last modified: October 1, 2014
    This is version 160 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny 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.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. Peptidase families
      Classification of peptidase families and list of entries
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3