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P49662 (CASP4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Caspase-4

Short name=CASP-4
EC=3.4.22.57
Alternative name(s):
ICE(rel)-II
Protease ICH-2
Protease TX

Cleaved into the following 2 chains:

  1. Caspase-4 subunit 1
  2. Caspase-4 subunit 2
Gene names
Name:CASP4
Synonyms:ICH2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length377 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in the activation cascade of caspases responsible for apoptosis execution. Involved in ER-stress induced apoptosis. Cleaves caspase-1. Ref.9 Ref.14

Catalytic activity

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-|-. Ref.14

Enzyme regulation

Inhibited by the effector protein NleF that is produced by pathogenic E.coli; this inhibits apoptosis. Ref.14

Subunit structure

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. Ref.13 Ref.14

Subcellular location

Endoplasmic reticulum membrane. Mitochondrion Ref.9 Ref.13.

Tissue specificity

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.

Post-translational modification

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

Sequence similarities

Belongs to the peptidase C14A family.

Contains 1 CARD domain.

Ontologies

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P49662-1)

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 2 (identifier: P49662-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Propeptide1 – ?8080 Potential
PRO_0000004596
Chain?81 – 270190Caspase-4 subunit 1
PRO_0000004597
Propeptide271 – 28919 Potential
PRO_0000004598
Chain290 – 37788Caspase-4 subunit 2
PRO_0000004599

Regions

Domain1 – 9191CARD

Sites

Active site2101 By similarity
Active site2581

Amino acid modifications

Modified residue831Phosphoserine Ref.10 Ref.11

Natural variations

Alternative sequence1 – 5656Missing in isoform 2.
VSP_043495
Natural variant471D → N.
Corresponds to variant rs56226603 [ dbSNP | Ensembl ].
VAR_061081
Natural variant2841E → D.
Corresponds to variant rs55901059 [ dbSNP | Ensembl ].
VAR_061082

Experimental info

Mutagenesis2581C → S: Loss of activity. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 1, 1996. Version 1.
Checksum: DC7CCEC6E9D483EB

FASTA37743,262
        10         20         30         40         50         60 
MAEGNHRKKP LKVLESLGKD FLTGVLDNLV EQNVLNWKEE EKKKYYDAKT EDKVRVMADS 

        70         80         90        100        110        120 
MQEKQRMAGQ MLLQTFFNID QISPNKKAHP NMEAGPPESG ESTDALKLCP HEEFLRLCKE 

       130        140        150        160        170        180 
RAEEIYPIKE RNNRTRLALI ICNTEFDHLP PRNGADFDIT GMKELLEGLD YSVDVEENLT 

       190        200        210        220        230        240 
ARDMESALRA FATRPEHKSS DSTFLVLMSH GILEGICGTV HDEKKPDVLL YDTIFQIFNN 

       250        260        270        280        290        300 
RNCLSLKDKP KVIIVQACRG ANRGELWVRD SPASLEVASS QSSENLEEDA VYKTHVEKDF 

       310        320        330        340        350        360 
IAFCSSTPHN VSWRDSTMGS IFITQLITCF QKYSWCCHLE EVFRKVQQSF ETPRAKAQMP 

       370 
TIERLSMTRY FYLFPGN 

« Hide

Isoform 2 [UniParc].

Checksum: 7336654FD603B65A
Show »

FASTA32136,705

References

« Hide 'large scale' references
[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]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton 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. expand/collapse author list , 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].
[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]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
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]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA57511.
RefSeqNP_001216.1. NM_001225.3.
NP_150649.1. NM_033306.2.
UniGeneHs.138378.

3D structure databases

ProteinModelPortalP49662.
SMRP49662. Positions 2-89, 99-377.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107287. 32 interactions.
DIPDIP-44806N.
IntActP49662. 3 interactions.
MINTMINT-1533864.
STRING9606.ENSP00000388566.

Chemistry

BindingDBP49662.
ChEMBLCHEMBL2226.

Protein family/group databases

MEROPSC14.007.

PTM databases

PhosphoSiteP49662.

Polymorphism databases

DMDM1352420.

Proteomic databases

PaxDbP49662.
PRIDEP49662.

Protocols and materials databases

DNASU837.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000393150; ENSP00000376857; ENSG00000196954. [P49662-2]
ENST00000444739; ENSP00000388566; ENSG00000196954. [P49662-1]
GeneID837.
KEGGhsa:837.
UCSCuc001pib.1. human. [P49662-1]

Organism-specific databases

CTD837.
GeneCardsGC11M104806.
HGNCHGNC:1505. CASP4.
HPAHPA027588.
MIM602664. gene.
neXtProtNX_P49662.
PharmGKBPA26088.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG326166.
HOGENOMHOG000234399.
HOVERGENHBG076981.
InParanoidP49662.
KOK04394.
OMARAKAQMP.
OrthoDBEOG7FXZZ6.
PhylomeDBP49662.
TreeFamTF102023.

Enzyme and pathway databases

BRENDA3.4.22.57. 2681.
ReactomeREACT_6900. Immune System.
SABIO-RKP49662.

Gene expression databases

ArrayExpressP49662.
BgeeP49662.
CleanExHS_CASP4.
GenevestigatorP49662.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
InterProIPR001315. CARD.
IPR017350. Caspase_IL-1_beta.
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]
PfamPF00619. CARD. 1 hit.
PF00656. Peptidase_C14. 1 hit.
[Graphical view]
PIRSFPIRSF038001. Caspase_ICE. 1 hit.
PRINTSPR00376. IL1BCENZYME.
SMARTSM00114. CARD. 1 hit.
SM00115. CASc. 1 hit.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
PROSITEPS50209. 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]
ProtoNetSearch...

Other

GenomeRNAi837.
NextBio3484.
PROP49662.
SOURCESearch...

Entry information

Entry nameCASP4_HUMAN
AccessionPrimary (citable) accession number: P49662
Secondary accession number(s): A2NHL8, A2NHM0
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: March 19, 2014
This is version 137 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM