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P49662

- CASP4_HUMAN

UniProt

P49662 - CASP4_HUMAN

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Protein

Caspase-4

Gene

CASP4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Involved in the activation cascade of caspases responsible for apoptosis execution. Involved in ER-stress induced apoptosis. Cleaves caspase-1.2 Publications

Catalytic activityi

Strict requirement for Asp at the P1 position. It has a preferred cleavage sequence of Tyr-Val-Ala-Asp-|- but also cleaves at Asp-Glu-Val-Asp-|-.1 Publication

Enzyme regulationi

Inhibited by the effector protein NleF that is produced by pathogenic E.coli; this inhibits apoptosis.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei210 – 2101By similarity
Active sitei258 – 2581

GO - Molecular functioni

  1. cysteine-type endopeptidase activity Source: RefGenome

GO - Biological processi

  1. apoptotic process Source: ProtInc
  2. execution phase of apoptosis Source: RefGenome
  3. proteolysis Source: ProtInc
  4. regulation of apoptotic process Source: InterPro
  5. regulation of inflammatory response Source: RefGenome
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

BRENDAi3.4.22.57. 2681.
ReactomeiREACT_75776. NOD1/2 Signaling Pathway.
SABIO-RKP49662.

Protein family/group databases

MEROPSiC14.007.

Names & Taxonomyi

Protein namesi
Recommended name:
Caspase-4 (EC:3.4.22.57)
Short name:
CASP-4
Alternative name(s):
ICE(rel)-II
Protease ICH-2
Protease TX
Cleaved into the following 2 chains:
Gene namesi
Name:CASP4
Synonyms:ICH2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 11

Organism-specific databases

HGNCiHGNC:1505. CASP4.

Subcellular locationi

GO - Cellular componenti

  1. AIM2 inflammasome complex Source: RefGenome
  2. cytoplasm Source: RefGenome
  3. endoplasmic reticulum Source: UniProtKB-KW
  4. IPAF inflammasome complex Source: RefGenome
  5. membrane Source: UniProtKB-KW
  6. mitochondrion Source: UniProtKB-KW
  7. NLRP3 inflammasome complex Source: RefGenome
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Mitochondrion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi258 – 2581C → S: Loss of activity. 1 Publication

Organism-specific databases

PharmGKBiPA26088.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Propeptidei1 – ?8080Sequence AnalysisPRO_0000004596Add
BLAST
Chaini?81 – 270190Caspase-4 subunit 1PRO_0000004597Add
BLAST
Propeptidei271 – 28919Sequence AnalysisPRO_0000004598Add
BLAST
Chaini290 – 37788Caspase-4 subunit 2PRO_0000004599Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei83 – 831Phosphoserine2 Publications

Post-translational modificationi

The two subunits are derived from the precursor sequence by an autocatalytic mechanism or by cleavage by Caspase-8.

Keywords - PTMi

Phosphoprotein, Zymogen

Proteomic databases

MaxQBiP49662.
PaxDbiP49662.
PRIDEiP49662.

PTM databases

PhosphoSiteiP49662.

Expressioni

Tissue specificityi

Widely expressed, with highest levels in spleen and lung. Moderate expression in heart and liver, low expression in skeletal muscle, kidney and testis. Not found in the brain.

Gene expression databases

BgeeiP49662.
CleanExiHS_CASP4.
ExpressionAtlasiP49662. baseline and differential.
GenevestigatoriP49662.

Organism-specific databases

HPAiHPA027588.

Interactioni

Subunit structurei

Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a small and a large subunit (By similarity). Interacts with NleF from pathogenic E.coli. Interacts with TMEM214, the interaction is required for ER membrane localization.By similarity2 Publications

Protein-protein interaction databases

BioGridi107287. 32 interactions.
DIPiDIP-44806N.
IntActiP49662. 3 interactions.
MINTiMINT-1533864.
STRINGi9606.ENSP00000388566.

Structurei

3D structure databases

ProteinModelPortaliP49662.
SMRiP49662. Positions 99-377.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 9191CARDPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the peptidase C14A family.Curated
Contains 1 CARD domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG326166.
GeneTreeiENSGT00760000118912.
HOGENOMiHOG000234399.
HOVERGENiHBG076981.
InParanoidiP49662.
KOiK04394.
OMAiRAKAQMP.
OrthoDBiEOG7FXZZ6.
PhylomeDBiP49662.
TreeFamiTF102023.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
3.40.50.1460. 1 hit.
InterProiIPR001315. CARD.
IPR029030. Caspase-like_dom.
IPR017350. Caspase_ICE-type.
IPR011029. DEATH-like_dom.
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]
PfamiPF00619. CARD. 1 hit.
PF00656. Peptidase_C14. 1 hit.
[Graphical view]
PIRSFiPIRSF038001. Caspase_ICE. 1 hit.
PRINTSiPR00376. IL1BCENZYME.
SMARTiSM00114. CARD. 1 hit.
SM00115. CASc. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiPS50209. CARD. 1 hit.
PS01122. CASPASE_CYS. 1 hit.
PS01121. CASPASE_HIS. 1 hit.
PS50207. CASPASE_P10. 1 hit.
PS50208. CASPASE_P20. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P49662-1) [UniParc]FASTAAdd to Basket

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

        10         20         30         40         50
MAEGNHRKKP LKVLESLGKD FLTGVLDNLV EQNVLNWKEE EKKKYYDAKT
60 70 80 90 100
EDKVRVMADS MQEKQRMAGQ MLLQTFFNID QISPNKKAHP NMEAGPPESG
110 120 130 140 150
ESTDALKLCP HEEFLRLCKE RAEEIYPIKE RNNRTRLALI ICNTEFDHLP
160 170 180 190 200
PRNGADFDIT GMKELLEGLD YSVDVEENLT ARDMESALRA FATRPEHKSS
210 220 230 240 250
DSTFLVLMSH GILEGICGTV HDEKKPDVLL YDTIFQIFNN RNCLSLKDKP
260 270 280 290 300
KVIIVQACRG ANRGELWVRD SPASLEVASS QSSENLEEDA VYKTHVEKDF
310 320 330 340 350
IAFCSSTPHN VSWRDSTMGS IFITQLITCF QKYSWCCHLE EVFRKVQQSF
360 370
ETPRAKAQMP TIERLSMTRY FYLFPGN
Length:377
Mass (Da):43,262
Last modified:February 1, 1996 - v1
Checksum:iDC7CCEC6E9D483EB
GO
Isoform 2 (identifier: P49662-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-56: Missing.

Show »
Length:321
Mass (Da):36,705
Checksum:i7336654FD603B65A
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti47 – 471D → N.
Corresponds to variant rs56226603 [ dbSNP | Ensembl ].
VAR_061081
Natural varianti284 – 2841E → D.
Corresponds to variant rs55901059 [ dbSNP | Ensembl ].
VAR_061082

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5656Missing in isoform 2. 1 PublicationVSP_043495Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z48810 mRNA. Translation: CAA88750.1.
U28014 mRNA. Translation: AAA75171.1.
U25804 mRNA. Translation: AAA86890.1.
U28976 mRNA. Translation: AAC99850.1.
U28978 mRNA. Translation: AAC99852.1.
EF636667 Genomic DNA. Translation: ABR09278.1.
AP001153 Genomic DNA. No translation available.
AP002004 Genomic DNA. No translation available.
CH471065 Genomic DNA. Translation: EAW67051.1.
CH471065 Genomic DNA. Translation: EAW67052.1.
BC017839 mRNA. Translation: AAH17839.1.
CCDSiCCDS41704.1. [P49662-2]
CCDS8327.1. [P49662-1]
PIRiA57511.
RefSeqiNP_001216.1. NM_001225.3. [P49662-1]
NP_150649.1. NM_033306.2. [P49662-2]
UniGeneiHs.138378.

Genome annotation databases

EnsembliENST00000393150; ENSP00000376857; ENSG00000196954. [P49662-2]
ENST00000444739; ENSP00000388566; ENSG00000196954. [P49662-1]
GeneIDi837.
KEGGihsa:837.
UCSCiuc001pib.1. human. [P49662-1]

Polymorphism databases

DMDMi1352420.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z48810 mRNA. Translation: CAA88750.1 .
U28014 mRNA. Translation: AAA75171.1 .
U25804 mRNA. Translation: AAA86890.1 .
U28976 mRNA. Translation: AAC99850.1 .
U28978 mRNA. Translation: AAC99852.1 .
EF636667 Genomic DNA. Translation: ABR09278.1 .
AP001153 Genomic DNA. No translation available.
AP002004 Genomic DNA. No translation available.
CH471065 Genomic DNA. Translation: EAW67051.1 .
CH471065 Genomic DNA. Translation: EAW67052.1 .
BC017839 mRNA. Translation: AAH17839.1 .
CCDSi CCDS41704.1. [P49662-2 ]
CCDS8327.1. [P49662-1 ]
PIRi A57511.
RefSeqi NP_001216.1. NM_001225.3. [P49662-1 ]
NP_150649.1. NM_033306.2. [P49662-2 ]
UniGenei Hs.138378.

3D structure databases

ProteinModelPortali P49662.
SMRi P49662. Positions 99-377.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 107287. 32 interactions.
DIPi DIP-44806N.
IntActi P49662. 3 interactions.
MINTi MINT-1533864.
STRINGi 9606.ENSP00000388566.

Chemistry

BindingDBi P49662.
ChEMBLi CHEMBL2226.

Protein family/group databases

MEROPSi C14.007.

PTM databases

PhosphoSitei P49662.

Polymorphism databases

DMDMi 1352420.

Proteomic databases

MaxQBi P49662.
PaxDbi P49662.
PRIDEi P49662.

Protocols and materials databases

DNASUi 837.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000393150 ; ENSP00000376857 ; ENSG00000196954 . [P49662-2 ]
ENST00000444739 ; ENSP00000388566 ; ENSG00000196954 . [P49662-1 ]
GeneIDi 837.
KEGGi hsa:837.
UCSCi uc001pib.1. human. [P49662-1 ]

Organism-specific databases

CTDi 837.
GeneCardsi GC11M104806.
HGNCi HGNC:1505. CASP4.
HPAi HPA027588.
MIMi 602664. gene.
neXtProti NX_P49662.
PharmGKBi PA26088.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG326166.
GeneTreei ENSGT00760000118912.
HOGENOMi HOG000234399.
HOVERGENi HBG076981.
InParanoidi P49662.
KOi K04394.
OMAi RAKAQMP.
OrthoDBi EOG7FXZZ6.
PhylomeDBi P49662.
TreeFami TF102023.

Enzyme and pathway databases

BRENDAi 3.4.22.57. 2681.
Reactomei REACT_75776. NOD1/2 Signaling Pathway.
SABIO-RK P49662.

Miscellaneous databases

ChiTaRSi CASP4. human.
GenomeRNAii 837.
NextBioi 3484.
PROi P49662.
SOURCEi Search...

Gene expression databases

Bgeei P49662.
CleanExi HS_CASP4.
ExpressionAtlasi P49662. baseline and differential.
Genevestigatori P49662.

Family and domain databases

Gene3Di 1.10.533.10. 1 hit.
3.40.50.1460. 1 hit.
InterProi IPR001315. CARD.
IPR029030. Caspase-like_dom.
IPR017350. Caspase_ICE-type.
IPR011029. DEATH-like_dom.
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 PF00619. CARD. 1 hit.
PF00656. Peptidase_C14. 1 hit.
[Graphical view ]
PIRSFi PIRSF038001. Caspase_ICE. 1 hit.
PRINTSi PR00376. IL1BCENZYME.
SMARTi SM00114. CARD. 1 hit.
SM00115. CASc. 1 hit.
[Graphical view ]
SUPFAMi SSF47986. SSF47986. 1 hit.
PROSITEi PS50209. CARD. 1 hit.
PS01122. CASPASE_CYS. 1 hit.
PS01121. CASPASE_HIS. 1 hit.
PS50207. CASPASE_P10. 1 hit.
PS50208. CASPASE_P20. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "A novel human protease similar to the interleukin-1 beta converting enzyme induces apoptosis in transfected cells."
    Faucheu C., Diu A., Chan A.W.E., Blanchet A.-M., Miossec C., Herve F., Collard-Dutilleul V., Gu Y., Aldape R.A., Lippke J.A., Rocher C., Su M.S.-S., Livingston D.J., Hercend T., Lalanne J.-L.
    EMBO J. 14:1914-1922(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF CYS-258, 3D-STRUCTURE MODELING.
    Tissue: Placenta.
  2. "Molecular cloning and pro-apoptotic activity of ICErelII and ICErelIII, members of the ICE/CED-3 family of cysteine proteases."
    Munday N.A., Vaillancourt J.P., Ali A., Casano F.J., Miller D.K., Molineaux S.M., Yamin T.-T., Yu V.L., Nicholson D.W.
    J. Biol. Chem. 270:15870-15876(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  3. "Identification and characterization of ICH-2, a novel member of the interleukin-1 beta-converting enzyme family of cysteine proteases."
    Kamens J., Paskind M., Hugunin M., Talanian R.V., Allen H., Banach D., Bump N.J., Hackett M.C., Johnston C.G., Li P., Mankovich J.A., Terranova M., Ghayur T.
    J. Biol. Chem. 270:15250-15256(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION.
    Tissue: Thymus.
  4. "Cloning of human ICE homolog Mih1."
    Fernandes-Alnemri T., Litwack G., Alnemri E.S.
    Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
  5. NIEHS SNPs program
    Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. "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 1).
    Tissue: Testis.
  9. "Involvement of caspase-4 in endoplasmic reticulum stress-induced apoptosis and Abeta-induced cell death."
    Hitomi J., Katayama T., Eguchi Y., Kudo T., Taniguchi M., Koyama Y., Manabe T., Yamagishi S., Bando Y., Imaizumi K., Tsujimoto Y., Tohyama M.
    J. Cell Biol. 165:347-356(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  10. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  11. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  12. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  13. "Transmembrane protein 214 (TMEM214) mediates endoplasmic reticulum stress-induced caspase 4 enzyme activation and apoptosis."
    Li C., Wei J., Li Y., He X., Zhou Q., Yan J., Zhang J., Liu Y., Liu Y., Shu H.B.
    J. Biol. Chem. 288:17908-17917(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH TMEM214.
  14. "The E.coli effector protein NleF is a caspase inhibitor."
    Blasche S., Moertl M., Steuber H., Siszler G., Nisa S., Schwarz F., Lavrik I., Gronewold T.M.A., Maskos K., Donnenberg M.S., Ullmann D., Uetz P., Koegl M.
    PLoS ONE 0:0-0(2013)
    Cited for: INTERACTION WITH E.COLI NLEF, CATALYTIC ACTIVITY, FUNCTION, ENZYME REGULATION.

Entry informationi

Entry nameiCASP4_HUMAN
AccessioniPrimary (citable) accession number: P49662
Secondary accession number(s): A2NHL8, A2NHM0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: November 26, 2014
This is version 144 of the entry and version 1 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, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: 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