P49662 (CASP4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	377 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. Cleaves caspase-1. Ref.11
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.11
Enzyme regulation	Inhibited by the effector protein NleF that is produced by pathogenic E.coli; this inhibits apoptosis. Ref.11
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. Ref.11
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

Keywords
Biological process	Apoptosis
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein Zymogen
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Traceable author statement Ref.3. Source: ProtInc induction of apoptosis Traceable author statement Ref.1. Source: ProtInc proteolysis Traceable author statement Ref.3. Source: ProtInc
Cellular_component	intracellular Inferred from electronic annotation. Source: InterPro
Molecular_function	cysteine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Propeptide	1 – ?80	80	Potential		PRO_0000004596
	Chain	?81 – 270	190	Caspase-4 subunit 1		PRO_0000004597
	Propeptide	271 – 289	19	Potential		PRO_0000004598
	Chain	290 – 377	88	Caspase-4 subunit 2		PRO_0000004599
Regions
	Domain	1 – 91	91	CARD
Sites
	Active site	210	1	By similarity
	Active site	258	1
Amino acid modifications
	Modified residue	83	1	Phosphoserine Ref.9 Ref.10
Natural variations
	Alternative sequence	1 – 56	56	Missing in isoform 2.		VSP_043495
	Natural variant	47	1	D → N. Corresponds to variant rs56226603 [ dbSNP | Ensembl ].		VAR_061081
	Natural variant	284	1	E → D. Corresponds to variant rs55901059 [ dbSNP | Ensembl ].		VAR_061082
Experimental info
	Mutagenesis	258	1	C → S: Loss of activity. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 1996. Version 1. Checksum: DC7CCEC6E9D483EB	FASTA	377	43,262
	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
	Isoform 2 [UniParc]. Checksum: 7336654FD603B65A	FASTA	321	36,705
	10 20 30 40 50 60 MADSMQEKQR MAGQMLLQTF FNIDQISPNK KAHPNMEAGP PESGESTDAL KLCPHEEFLR 70 80 90 100 110 120 LCKERAEEIY PIKERNNRTR LALIICNTEF DHLPPRNGAD FDITGMKELL EGLDYSVDVE 130 140 150 160 170 180 ENLTARDMES ALRAFATRPE HKSSDSTFLV LMSHGILEGI CGTVHDEKKP DVLLYDTIFQ 190 200 210 220 230 240 IFNNRNCLSL KDKPKVIIVQ ACRGANRGEL WVRDSPASLE VASSQSSENL EEDAVYKTHV 250 260 270 280 290 300 EKDFIAFCSS TPHNVSWRDS TMGSIFITQL ITCFQKYSWC CHLEEVFRKV QQSFETPRAK 310 320 AQMPTIERLS MTRYFYLFPG N

References

	« Hide 'large scale' referencesShow '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. , 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. , 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]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"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

NIEHS-SNPs

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.
IPI	IPI00027725. IPI00376080.
PIR	A57511.
RefSeq	NP_001216.1. NM_001225.3. NP_150649.1. NM_033306.2.
UniGene	Hs.138378.
3D structure databases
ProteinModelPortal	P49662.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-44806N.
IntAct	P49662. 3 interactions.
STRING	9606.ENSP00000388566.
Protein family/group databases
MEROPS	C14.007.
PTM databases
PhosphoSite	P49662.
Polymorphism databases
DMDM	1352420.
Proteomic databases
PaxDb	P49662.
PRIDE	P49662.
Protocols and materials databases
DNASU	837.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000393150; ENSP00000376857; ENSG00000196954. ENST00000444739; ENSP00000388566; ENSG00000196954.
GeneID	837.
KEGG	hsa:837.
UCSC	uc001pib.1. human.
Organism-specific databases
CTD	837.
GeneCards	GC11M104806.
HGNC	HGNC:1505. CASP4.
HPA	HPA027588.
MIM	602664. gene.
neXtProt	NX_P49662.
PharmGKB	PA26088.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG326166.
HOGENOM	HOG000234399.
HOVERGEN	HBG076981.
InParanoid	P49662.
KO	K04394.
OMA	AVYKTHV.
OrthoDB	EOG49W2FS.
PhylomeDB	P49662.
Enzyme and pathway databases
BRENDA	3.4.22.57. 2681.
Pathway_Interaction_DB	caspase_pathway. Caspase cascade in apoptosis.
Reactome	REACT_6900. Immune System.
SABIO-RK	P49662.
Gene expression databases
ArrayExpress	P49662.
Bgee	P49662.
CleanEx	HS_CASP4.
Genevestigator	P49662.
GermOnline	ENSG00000196954. Homo sapiens.
Family and domain databases
Gene3D	1.10.533.10. 1 hit.
InterPro	IPR001315. CARD. IPR017350. Caspase_IL-1_beta. IPR011029. DEATH-like_dom. 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	PF00619. CARD. 1 hit. PF00656. Peptidase_C14. 1 hit. [Graphical view]
PIRSF	PIRSF038001. Caspase_ICE. 1 hit.
PRINTS	PR00376. IL1BCENZYME.
SMART	SM00114. CARD. 1 hit. SM00115. CASc. 1 hit. [Graphical view]
SUPFAM	SSF47986. DEATH_like. 1 hit.
PROSITE	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]
ProtoNet	Search...
Other
BindingDB	P49662.
ChEMBL	CHEMBL2226.
GenomeRNAi	837.
NextBio	3484.
SOURCE	Search...

Entry information

Entry name

CASP4_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 128 of the entry and version 1 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.