Reviewed, UniProtKB/Swiss-Prot P49662 (CASP4_HUMAN)

Names and origin

Protein names

Recommended name:
    Caspase-4
      Short name=CASP-4
    EC=3.4.22.57
Alternative name(s):
    Protease ICH-2
    Protease TX
    ICE(rel)-II
Cleaved into the following 2 chains:
    1- Recommended name:
            Caspase-4 subunit 1
    2- Recommended name:
            Caspase-4 subunit 2

Gene names

Name:	CASP4
Synonyms:	ICH2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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.
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-|-.
Subunit structure	Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a small and a large subunit By similarity.
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	Polymorphism
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein Zymogen
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	apoptosis Ref.3 Traceable author statement. Source: ProtInc induction of apoptosis Ref.1 Traceable author statement. Source: ProtInc proteolysis Ref.3 Traceable author statement. Source: ProtInc
Cellular component	intracellular Inferred from electronic annotation. Source: InterPro
Molecular function	cysteine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDK2	P24941	1	EBI-1057327,EBI-375096
CTNNBIP1	Q9NSA3	1	EBI-1057327,EBI-747082
EIF2S3	P41091	1	EBI-1057327,EBI-1054228
GSN	P06396	1	EBI-1057327,EBI-351506
HEATR2	Q86Y56	1	EBI-1057327,EBI-719966
HIGD1A	Q9Y241	1	EBI-1057327,EBI-1051940
KIAA0776	O94874	1	EBI-1057327,EBI-1048088
MSH6	P52701	1	EBI-1057327,EBI-395529
MTHFD1L	Q6UB35	1	EBI-1057327,EBI-1046835
MYCBPAP	Q8TBZ2	1	EBI-1057327,EBI-1391585
NUP93	Q8N1F7	1	EBI-1057327,EBI-1042703
PSMB1	P20618	1	EBI-1057327,EBI-372273
SLC25A22	Q9H936	1	EBI-1057327,EBI-1050588
SMC1A	Q14683	1	EBI-1057327,EBI-80690
SMC2	O95347	1	EBI-1057327,EBI-355822
SMC3	Q9UQE7	1	EBI-1057327,EBI-80718
SRPRB	Q9Y5M8	1	EBI-1057327,EBI-355393
USP9X	Q93008	1	EBI-1057327,EBI-302524
VDAC3	Q9Y277	1	EBI-1057327,EBI-354196

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.5
Natural variations
	Natural variant	47	1	D → N: dbSNP rs56226603.		VAR_061081
	Natural variant	284	1	E → D: dbSNP rs55901059.		VAR_061082
Experimental info
	Mutagenesis	258	1	C → S: Loss of activity. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P49662-1 [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

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: 7743998] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], 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: 7797592] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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: 7797510] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION. Tissue: Thymus.
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[5]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z48810 mRNA. Translation: CAA88750.1. U28014 mRNA. Translation: AAA75171.1. U25804 mRNA. Translation: AAA86890.1. BC017839 mRNA. Translation: AAH17839.1.
IPI	IPI00027725.
PIR	A57511.
RefSeq	NP_001216.1.
UniGene	Hs.138378
3D structure databases
SMR	P49662. Positions 7-80, 97-270, 123-376, 290-377.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-44806N.
IntAct	P49662. 37 interactions.
STRING	P49662.
Protein family/group databases
MEROPS	C14.007.
PTM databases
PhosphoSite	P49662.
Proteomic databases
PRIDE	P49662.
Genome annotation databases
Ensembl	ENST00000444739; ENSP00000388566; ENSG00000196954; Homo sapiens. [Genome view]
GeneID	837.
KEGG	hsa:837.
UCSC	uc001pid.1. human.
Organism-specific databases
CTD	837.
GeneCards	GC11M104318.
H-InvDB	HIX0010073.
HGNC	HGNC:1505. CASP4.
MIM	602664. gene.
PharmGKB	PA26088.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG505276.
HOVERGEN	P49662.
InParanoid	P49662.
OMA	VYKTHVE.
PhylomeDB	P49662.
Enzyme and pathway databases
BRENDA	3.4.22.57. 247.
Pathway_Interaction_DB	caspase_pathway. Caspase cascade in apoptosis.
Gene expression databases
ArrayExpress	P49662.
Bgee	P49662.
CleanEx	HS_CASP4.
Genevestigator	P49662.
GermOnline	ENSG00000196954. Homo sapiens.
Family and domain databases
InterPro	IPR001315. CARD. IPR017350. Caspase_IL-1_beta. IPR011029. DEATH-like. 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]
Gene3D	G3DSA:1.10.533.10. DEATH_like. 1 hit.
PANTHER	PTHR10454. Pept_C14_p45. 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]
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 Resources
NextBio	3484.
SOURCE	Search...

Entry information

Entry name

CASP4_HUMAN

Accession

Primary (citable) accession number: P49662

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	January 19, 2010
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.