CASP4

Functionⁱ

Inflammatory caspase that acts as an essential effector of NLRP3 inflammasome-dependent CASP1 activation and IL1B and IL18 secretion in response to non-canonical activators, such as UVB radiation, cholera enterotoxin subunit B and cytosolic LPS (PubMed:23516580, PubMed:24879791, PubMed:25119034, PubMed:22246630, PubMed:26174085, PubMed:26173988, PubMed:26508369, PubMed:25964352).

Thiol protease that cleaves a tetrapeptide after an Asp residue at position P1 (PubMed:7797510, PubMed:23516580).

Independently of NLRP3 inflammasome and CASP1, promotes pyroptosis, through GSDMD cleavage and activation, followed by IL1A, IL18 and HMGB1 release in response to non-canonical inflammasome activators (PubMed:26375003, PubMed:32109412).

Plays a crucial role in the restriction of Salmonella typhimurium replication in colonic epithelial cells during infection: in later stages of the infection, LPS from cytosolic Salmonella triggers CASP4 activation, which catalyzes cleavage of GSDMD, resulting in pyroptosis of infected cells and their extrusion into the gut lumen, as well as in IL18 secretion (PubMed:25121752, PubMed:26375003, PubMed:25964352, PubMed:32109412).

Cleavage of GSDMD is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP4 that recognizes and binds the Gasdermin-D, C-terminal (GSDMD-CT) part (PubMed:32109412).

Pyroptosis limits bacterial replication, while cytokine secretion promotes the recruitment and activation of immune cells and triggers mucosal inflammation (PubMed:25121752, PubMed:26375003, PubMed:25964352).

Involved in LPS-induced IL6 secretion; this activity may not require caspase enzymatic activity (PubMed:26508369).

Involved in cell death induced by endoplasmic reticulum stress and by treatment with cytotoxic APP peptides found Alzheimer's patient brains (PubMed:15123740, PubMed:22246630, PubMed:23661706).

Activated by direct binding to LPS without the need of an upstream sensor (PubMed:25119034).

Does not directly process IL1B (PubMed:7743998, PubMed:7797510, PubMed:7797592).

During non-canonical inflammasome activation, cuts CGAS and may play a role in the regulation of antiviral innate immune activation (PubMed:28314590).

17 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-|-.
2 Publications
Manual assertion based on experiment inⁱ
- Ref.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), FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AUTOCATALYTIC CLEAVAGE AT ASP-289, BIOPHYSICOCHEMICAL PROPERTIES.
- Ref.20
  "The E. coli effector protein NleF is a caspase inhibitor."
  Blasche S., Mortl M., Steuber H., Siszler G., Nisa S., Schwarz F., Lavrik I., Gronewold T.M., Maskos K., Donnenberg M.S., Ullmann D., Uetz P., Kogl M.
  PLoS ONE 8:E58937-E58937(2013) [PubMed] [Europe PMC] [Abstract]
  Cited for: INTERACTION WITH E.COLI NLEF (MICROBIAL INFECTION), CATALYTIC ACTIVITY, FUNCTION, ACTIVITY REGULATION (MICROBIAL INFECTION).
EC:3.4.22.57

Activity regulationⁱ

Activated by homooligomerization induced by direct binding to cytosolic LPS, in a TLR4-independent manner (PubMed:25119034).1 Publication

Kineticsⁱ

Values obtained using the partial C-terminal enzyme sequence of 105-377.1 Publication

K_M=
681 µM for synthetic peptide acetyl-YVAD-p-nitroanilide
1 Publication
Manual assertion based on experiment inⁱ
Ref.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), FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AUTOCATALYTIC CLEAVAGE AT ASP-289, BIOPHYSICOCHEMICAL PROPERTIES.

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Active siteⁱ	210	By similarity		1
Active siteⁱ	258	4 Publications		1

GO - Molecular functionⁱ

Complete GO annotation on QuickGO ...

GO - Biological processⁱ

Complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Hydrolase, Protease, Thiol protease
Biological process	Immunity, Inflammatory response, Innate immunity, Necrosis

Enzyme and pathway databases

BRENDAⁱ	3.4.22.57, 2681
PathwayCommonsⁱ	P49662
Reactomeⁱ	R-HSA-168638, NOD1/2 Signaling Pathway R-HSA-5620971, Pyroptosis
SABIO-RKⁱ	P49662
SIGNORⁱ	P49662

Protein family/group databases

MEROPS protease database More...MEROPSⁱ	C14.007

MEROPSⁱ

C14.007

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Caspase-41 Publication (EC:3.4.22.572 Publications) Short name: CASP-41 Publication Alternative name(s): ICE and Ced-3 homolog 21 Publication Short name: ICH-21 Publication ICE(rel)-II1 Publication Mih11 Publication Protease TX1 Publication Cleaved into the following 2 chains: Caspase-4 subunit p10 Caspase-4 subunit p20
Gene namesⁱ	Name:CASP41 PublicationImported Synonyms:ICH21 Publication
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 11

Organism-specific databases

Human Gene Nomenclature Database More...HGNCⁱ	HGNC:1505, CASP4
MIMⁱ	602664, gene
neXtProtⁱ	NX_P49662
VEuPathDBⁱ	HostDB:ENSG00000196954

Keywords - Cellular componentⁱ

Cytoplasm, Endoplasmic reticulum, Inflammasome, Membrane, Mitochondrion, Secreted

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	258	C → A: Loss of enzymatic activity. Loss of LPS-induced pyroptosis. No effect on the interaction with LPS. Decrease in cell death induced by TMEM214 overexpression. Does not support IL1B and IL18 secretion following UVB irradiation. 4 Publications	1
Mutagenesisⁱ	258	C → S: Loss of autocatalysis. 1 Publication	1
Mutagenesisⁱ	267	W → L or N: Abolished interaction with Gasdermin-D (GSDMD) and ability to mediate its cleavage. 1 Publication	1
Mutagenesisⁱ	270	D → A: Abolished autoprocessing and ability to form a heterotetramer composed of Caspase-4 subunit p10 and Caspase-4 subunit p20, preventing ability to cleave GSDMD and induce pyroptosis. 1 Publication	1
Mutagenesisⁱ	291	V → N: Abolished interaction with Gasdermin-D (GSDMD) and ability to mediate its cleavage. 1 Publication	1

Organism-specific databases

DisGeNET More...DisGeNETⁱ	837
Open Targets More...OpenTargetsⁱ	ENSG00000196954
PharmGKBⁱ	PA26088

Miscellaneous databases

Pharosⁱ	P49662, Tchem

Pharosⁱ

P49662, Tchem

Chemistry databases

ChEMBLⁱ	CHEMBL2226
Drug and drug target database More...DrugBankⁱ	DB06255, Incadronic acid
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	1620

Genetic variation databases

BioMutaⁱ	CASP4
DMDMⁱ	1352420

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Length
PropeptideⁱPRO_0000004596	1 – ?80	Sequence analysisAdd BLAST	80
ChainⁱPRO_0000004597	?81 – 270	Caspase-4 subunit p101 PublicationAdd BLAST	190
PropeptideⁱPRO_0000004598	271 – 289	Sequence analysis1 PublicationAdd BLAST	19
ChainⁱPRO_0000004599	290 – 377	Caspase-4 subunit p201 PublicationAdd BLAST	88
Isoform 2 (identifier: P49662-2)
Initiator methionineⁱ		RemovedCombined sources

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	83	PhosphoserineCombined sources	1
Isoform 2 (identifier: P49662-2)
Modified residueⁱ	2	N-acetylalanineCombined sources	1

Post-translational modificationⁱ

In response to activation signals, including endoplasmic reticulum stress or treatment with amyloid-beta A4 protein fragments (such as amyloid-beta protein 40), undergoes autoproteolytic cleavage.4 Publications

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Siteⁱ	289 – 290	Cleavage; by autolysis1 Publication		2

Keywords - PTMⁱ

Acetylation, Phosphoprotein, Zymogen

Proteomic databases

EPDⁱ	P49662
jPOSTⁱ	P49662
MassIVEⁱ	P49662
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	P49662
PaxDbⁱ	P49662
PeptideAtlas More...PeptideAtlasⁱ	P49662
PRIDEⁱ	P49662
ProteomicsDBⁱ	56043 [P49662-1] 56044 [P49662-2]

PTM databases

iPTMnetⁱ	P49662
MetOSiteⁱ	P49662
PhosphoSitePlusⁱ	P49662

Expressionⁱ

Tissue specificityⁱ

Widely expressed, including in keratinocytes and colonic and small intestinal epithelial cells (at protein level). Not detected in brain.6 Publications

Inductionⁱ

In peripheral blood mononuclear cells and purified monocytes, up-regulated by bacterial lipopolysaccharides (LPS) and interferon-beta/IFNB1 at the mRNA level (PubMed:16893518, PubMed:24879791). However, this increase is not observed at the protein level, which remains constant in monocytes and other cell types following LPS treatment (PubMed:25121752) (PubMed:26508369). In monocyte-derived macrophages, some up-regulation at the protein level is observed following treatment with LPS and IFNB1 (PubMed:25964352). In SH-EP1 neuroblastoma cell line, up-regulated by NF-kappa-B RELA/p65 at both mRNA and protein levels.3 Publications

Gene expression databases

Bgeeⁱ	ENSG00000196954, Expressed in monocyte and 207 other tissues
ExpressionAtlasⁱ	P49662, baseline and differential
Genevisibleⁱ	P49662, HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	ENSG00000196954, Tissue enriched (blood)

HPAⁱ

ENSG00000196954, Tissue enriched (blood)

Interactionⁱ

Subunit structureⁱ

Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (Caspase-4 subunit p20) and a 10 kDa (Caspase-4 subunit p10) subunit (PubMed:32109412). Upon direct LPS-binding, forms large homooligomers, resulting in its activation (By similarity). These oligomers are often referred to as 'non-canonical inflammasomes' (PubMed:25119034). In its precursor form, interacts with TMEM214; this interaction is required for association with the endoplasmic reticulum membrane (PubMed:23661706).

Interacts with CASP1 (PubMed:22246630).

Interacts with NOD2 (PubMed:18511561).

Interacts with SERPINB1; this interaction regulates CASP4 activity (PubMed:30692621).

By similarity6 Publications

Caspase-4 subunit p20:

Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (Caspase-4 subunit p20) and a 10 kDa (Caspase-4 subunit p10) subunit.

1 Publication

Caspase-4 subunit p10:

Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (Caspase-4 subunit p20) and a 10 kDa (Caspase-4 subunit p10) subunit.

1 Publication

(Microbial infection) Interacts with NleF protein from pathogenic E.coli; this interaction leads to enzyme inhibition.

1 Publication

GO - Molecular functionⁱ

CARD domain binding
Source: UniProtKB
Inferred from physical interactionⁱ
- "Protective role of Cop in Rip2/caspase-1/caspase-4-mediated HeLa cell death."
  Wang X., Narayanan M., Bruey J.-M., Rigamonti D., Cattaneo E., Reed J.C., Friedlander R.M.
  Biochim. Biophys. Acta 1762:742-754(2006) [PubMed] [Europe PMC] [Abstract]

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGRIDⁱ	107287, 34 interactors
Database of interacting proteins More...DIPⁱ	DIP-44806N
IntActⁱ	P49662, 7 interactors
Molecular INTeraction database More...MINTⁱ	P49662
STRINGⁱ	9606.ENSP00000388566

Chemistry databases

BindingDBⁱ

P49662

Miscellaneous databases

RNActⁱ	P49662, protein

RNActⁱ

P49662, protein

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Helixⁱ	111 – 120	Combined sources	10
Helixⁱ	122 – 124	Combined sources	3
Turnⁱ	131 – 133	Combined sources	3
Beta strandⁱ	136 – 142	Combined sources	7
Beta strandⁱ	147 – 149	Combined sources	3
Helixⁱ	155 – 168	Combined sources	14
Beta strandⁱ	171 – 178	Combined sources	8
Helixⁱ	181 – 192	Combined sources	12
Helixⁱ	195 – 197	Combined sources	3
Beta strandⁱ	203 – 212	Combined sources	10
Beta strandⁱ	215 – 217	Combined sources	3
Beta strandⁱ	223 – 225	Combined sources	3
Beta strandⁱ	228 – 230	Combined sources	3
Helixⁱ	231 – 237	Combined sources	7
Turnⁱ	240 – 242	Combined sources	3
Helixⁱ	244 – 246	Combined sources	3
Beta strandⁱ	251 – 258	Combined sources	8
Beta strandⁱ	295 – 297	Combined sources	3
Beta strandⁱ	299 – 305	Combined sources	7
Helixⁱ	313 – 316	Combined sources	4
Helixⁱ	321 – 333	Combined sources	13
Turnⁱ	334 – 336	Combined sources	3
Helixⁱ	339 – 349	Combined sources	11
Turnⁱ	353 – 355	Combined sources	3
Helixⁱ	356 – 358	Combined sources	3
Beta strandⁱ	361 – 364	Combined sources	4
Beta strandⁱ	368 – 370	Combined sources	3

Show more details

3D structure databases

SMRⁱ	P49662
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	1 – 91	CARDPROSITE-ProRule annotationAdd BLAST		91

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	1 – 59	Required for LPS-bindingBy similarityAdd BLAST		59
Regionⁱ	84 – 104	DisorderedSequence analysisAdd BLAST		21

Domainⁱ

The CARD domain mediates LPS recognition and homooligomerization.1 Publication

Sequence similaritiesⁱ

Belongs to the peptidase C14A family.Curated

Phylogenomic databases

eggNOGⁱ	KOG3573, Eukaryota
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00940000161497
HOGENOMⁱ	CLU_036904_0_1_1
InParanoidⁱ	P49662
OMAⁱ	GICGTTH
Database of Orthologous Groups More...OrthoDBⁱ	1327703at2759
PhylomeDBⁱ	P49662
TreeFamⁱ	TF102023

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd00032, CASc, 1 hit
Gene3Dⁱ	1.10.533.10, 1 hit
InterProⁱ	View protein in InterPro IPR001315, CARD IPR029030, Caspase-like_dom_sf IPR033139, Caspase_cys_AS IPR016129, Caspase_his_AS IPR011029, DEATH-like_dom_sf IPR002398, Pept_C14 IPR002138, Pept_C14_p10 IPR001309, Pept_C14_p20 IPR015917, Pept_C14A
PANTHERⁱ	PTHR10454, PTHR10454, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00619, CARD, 1 hit
PRINTSⁱ	PR00376, IL1BCENZYME
SMARTⁱ	View protein in SMART SM00114, CARD, 1 hit SM00115, CASc, 1 hit
SUPFAMⁱ	SSF47986, SSF47986, 1 hit SSF52129, SSF52129, 1 hit
PROSITEⁱ	View protein in 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

Sequences (5+)ⁱ

Sequence statusⁱ: Complete.

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

This entry describes 5 isoformsⁱ produced by alternative splicing. Align Add to basket

This entry has 5 described isoforms and 2 potential isoforms that are computationally mapped.Show all Align All

Isoform 1 (identifier: P49662-1) [UniParc]FASTA Add to basket

Also known as: Alpha

This isoform has been chosen as the canonicalⁱ 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]FASTA Add to basket

Also known as: Gamma, mih1-beta

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

« Hide

        10         20         30         40         50
MADSMQEKQR MAGQMLLQTF FNIDQISPNK KAHPNMEAGP PESGESTDAL 
        60         70         80         90        100
KLCPHEEFLR LCKERAEEIY PIKERNNRTR LALIICNTEF DHLPPRNGAD 
       110        120        130        140        150
FDITGMKELL EGLDYSVDVE ENLTARDMES ALRAFATRPE HKSSDSTFLV 
       160        170        180        190        200
LMSHGILEGI CGTVHDEKKP DVLLYDTIFQ IFNNRNCLSL KDKPKVIIVQ 
       210        220        230        240        250
ACRGANRGEL WVRDSPASLE VASSQSSENL EEDAVYKTHV EKDFIAFCSS 
       260        270        280        290        300
TPHNVSWRDS TMGSIFITQL ITCFQKYSWC CHLEEVFRKV QQSFETPRAK 
       310        320 
AQMPTIERLS MTRYFYLFPG N

Show »

Length:321

Mass (Da):36,705

Checksum:ⁱ7336654FD603B65A

GO

Isoform 3 (identifier: P49662-3) [UniParc]FASTA Add to basket

Also known as: mih1-delta

The sequence of this isoform differs from the canonical sequence as follows:
88-116: AHPNMEAGPPESGESTDALKLCPHEEFLR → GDKLGHRGRNHNLCSAISCSSSEYGGWTT
117-377: Missing.

« Hide

        10         20         30         40         50
MAEGNHRKKP LKVLESLGKD FLTGVLDNLV EQNVLNWKEE EKKKYYDAKT 
        60         70         80         90        100
EDKVRVMADS MQEKQRMAGQ MLLQTFFNID QISPNKKGDK LGHRGRNHNL 
       110 
CSAISCSSSE YGGWTT

Note: May be due to competing acceptor splice site. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.Curated

Show »

Length:116

Mass (Da):13,264

Checksum:ⁱFD9ED1FF1DF981D3

GO

Isoform 4 (identifier: P49662-4) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
261-263: ANR → GEC
264-377: Missing.

« 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 
KVIIVQACRG GEC

Show »

Length:263

Mass (Da):30,000

Checksum:ⁱFED10278B701F0F0

GO

Isoform 5 (identifier: P49662-5) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
125-157: IYPIKERNNRTRLALIICNTEFDHLPPRNGADF → VLCYLYEIEKKEEISLLSFSAPFLTALNDWGWG
158-377: Missing.

« 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 RAEEVLCYLY EIEKKEEISL LSFSAPFLTA 

LNDWGWG

Show »

Length:157

Mass (Da):18,111

Checksum:ⁱ65936259DD31435E

GO

Computationally mapped potential isoform sequencesⁱ

There are 2 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

Entry	Entry name	Protein names	Gene names	Length	Annotation

E9PMT1	E9PMT1_HUMAN	Caspase-4 Caspase-4	CASP4	147	Annotation score:
H0YD34	H0YD34_HUMAN	Caspase-4 Caspase-4	CASP4	72	Annotation score:

Sequence cautionⁱ

Isoform 2:

The sequence AAC99851 differs from that shown. Reason: Frameshift.Curated

The sequence AAC99854 differs from that shown. Reason: Erroneous translation. Erroneous CDS prediction.Curated

The sequence EAW67050 differs from that shown. Reason: Erroneous gene model prediction.Curated

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_061081	47	D → N. Corresponds to variant dbSNP:rs56226603EnsemblClinVar.	1
Natural variantⁱVAR_075654	134	R → C1 PublicationCorresponds to variant dbSNP:rs181090259Ensembl.	1
Natural variantⁱVAR_061082	284	E → D. Corresponds to variant dbSNP:rs55901059EnsemblClinVar.	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Length
Alternative sequenceⁱVSP_043495	1 – 56	Missing in isoform 2. 1 PublicationAdd BLAST	56
Alternative sequenceⁱVSP_058177	88 – 116	AHPNM…EEFLR → GDKLGHRGRNHNLCSAISCS SSEYGGWTT in isoform 3. 1 PublicationAdd BLAST	29
Alternative sequenceⁱVSP_058178	117 – 377	Missing in isoform 3. 1 PublicationAdd BLAST	261
Alternative sequenceⁱVSP_058179	125 – 157	IYPIK…NGADF → VLCYLYEIEKKEEISLLSFS APFLTALNDWGWG in isoform 5. 1 PublicationAdd BLAST	33
Alternative sequenceⁱVSP_058180	158 – 377	Missing in isoform 5. 1 PublicationAdd BLAST	220
Alternative sequenceⁱVSP_058181	261 – 263	ANR → GEC in isoform 4. 2 Publications	3
Alternative sequenceⁱVSP_058182	264 – 377	Missing in isoform 4. 2 PublicationsAdd BLAST	114

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 U28977 mRNA Translation: AAC99851.1 Frameshift. U28978 mRNA Translation: AAC99852.1 U28979 mRNA Translation: AAC99853.1 U28979 mRNA Translation: AAC99854.1 Sequence problems. AK057094 mRNA Translation: BAG51861.1 AK296081 mRNA Translation: BAG58837.1 AK304222 mRNA Translation: BAG65094.1 EF636667 Genomic DNA Translation: ABR09278.1 AP001153 Genomic DNA No translation available. AP002004 Genomic DNA No translation available. CH471065 Genomic DNA Translation: EAW67050.1 Sequence problems. CH471065 Genomic DNA Translation: EAW67051.1 CH471065 Genomic DNA Translation: EAW67052.1 BC017839 mRNA Translation: AAH17839.1 AL050391 mRNA Translation: CAB43686.2
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS41704.1 [P49662-2] CCDS8327.1 [P49662-1]
PIRⁱ	A57511
NCBI Reference Sequences More...RefSeqⁱ	NP_001216.1, NM_001225.3 [P49662-1] NP_150649.1, NM_033306.2 [P49662-2] XP_011541321.1, XM_011543019.1 XP_016873886.1, XM_017018397.1

Genome annotation databases

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

Keywords - Coding sequence diversityⁱ

Alternative splicing

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
P49662	Caspase-4 (Fragment)		HUMAN		147	UniRef100_P49662
Isoform 2 of Caspase-4		HUMAN		321
Caspase-4 isoform alpha (Fragment)		HUMAN		31
+1

Protein	Similar proteins		Species	Score	Length	Source
P49662	Caspase-4 (Fragment)		HUMAN		147	UniRef90_P49662
CASP4 isoform 2		PONAB		377
Caspase 4		GORGO		377
Uncharacterized protein		CHLSB		377
caspase-4		SAPAP		377
+37

Protein	Similar proteins		Species	Score	Length	Source
P49662	Caspase-4 (Fragment)		HUMAN		147	UniRef50_P49662
Uncharacterized protein		PONAB		377
Caspase 4		CERAT		377
Caspase 4		PANTR		377
Caspase-4		PAPAN		377
+55
P49662-4	Caspase-13-like		MARMO		297	UniRef50_P49662-4
+3

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 U28977 mRNA Translation: AAC99851.1 Frameshift. U28978 mRNA Translation: AAC99852.1 U28979 mRNA Translation: AAC99853.1 U28979 mRNA Translation: AAC99854.1 Sequence problems. AK057094 mRNA Translation: BAG51861.1 AK296081 mRNA Translation: BAG58837.1 AK304222 mRNA Translation: BAG65094.1 EF636667 Genomic DNA Translation: ABR09278.1 AP001153 Genomic DNA No translation available. AP002004 Genomic DNA No translation available. CH471065 Genomic DNA Translation: EAW67050.1 Sequence problems. CH471065 Genomic DNA Translation: EAW67051.1 CH471065 Genomic DNA Translation: EAW67052.1 BC017839 mRNA Translation: AAH17839.1 AL050391 mRNA Translation: CAB43686.2
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] XP_011541321.1, XM_011543019.1 XP_016873886.1, XM_017018397.1

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	6KMZ	X-ray	3.61	A/B/C/D	105-377	[»]
	6NRY	X-ray	2.18	A	92-377	[»]
SMRⁱ	P49662
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Protein-protein interaction databases

BioGRIDⁱ	107287, 34 interactors
DIPⁱ	DIP-44806N
IntActⁱ	P49662, 7 interactors
MINTⁱ	P49662
STRINGⁱ	9606.ENSP00000388566

Chemistry databases

BindingDBⁱ	P49662
ChEMBLⁱ	CHEMBL2226
DrugBankⁱ	DB06255, Incadronic acid
GuidetoPHARMACOLOGYⁱ	1620

Protein family/group databases

MEROPSⁱ	C14.007

MEROPSⁱ

C14.007

PTM databases

iPTMnetⁱ	P49662
MetOSiteⁱ	P49662
PhosphoSitePlusⁱ	P49662

Genetic variation databases

BioMutaⁱ	CASP4
DMDMⁱ	1352420

Proteomic databases

EPDⁱ	P49662
jPOSTⁱ	P49662
MassIVEⁱ	P49662
MaxQBⁱ	P49662
PaxDbⁱ	P49662
PeptideAtlasⁱ	P49662
PRIDEⁱ	P49662
ProteomicsDBⁱ	56043 [P49662-1] 56044 [P49662-2]

Protocols and materials databases

Antibodypediaⁱ	18094, 743 antibodies
The DNASU plasmid repository More...DNASUⁱ	837

Genome annotation databases

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

Organism-specific databases

CTDⁱ	837
DisGeNETⁱ	837
GeneCardsⁱ	CASP4
HGNCⁱ	HGNC:1505, CASP4
HPAⁱ	ENSG00000196954, Tissue enriched (blood)
MIMⁱ	602664, gene
neXtProtⁱ	NX_P49662
OpenTargetsⁱ	ENSG00000196954
PharmGKBⁱ	PA26088
VEuPathDBⁱ	HostDB:ENSG00000196954
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG3573, Eukaryota
GeneTreeⁱ	ENSGT00940000161497
HOGENOMⁱ	CLU_036904_0_1_1
InParanoidⁱ	P49662
OMAⁱ	GICGTTH
OrthoDBⁱ	1327703at2759
PhylomeDBⁱ	P49662
TreeFamⁱ	TF102023

Enzyme and pathway databases

BRENDAⁱ	3.4.22.57, 2681
PathwayCommonsⁱ	P49662
Reactomeⁱ	R-HSA-168638, NOD1/2 Signaling Pathway R-HSA-5620971, Pyroptosis
SABIO-RKⁱ	P49662
SIGNORⁱ	P49662

Miscellaneous databases

BioGRID-ORCSⁱ	837, 9 hits in 1014 CRISPR screens
ChiTaRSⁱ	CASP4, human
GenomeRNAiⁱ	837
Pharosⁱ	P49662, Tchem
Protein Ontology More...PROⁱ	PR:P49662
RNActⁱ	P49662, protein
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000196954, Expressed in monocyte and 207 other tissues
ExpressionAtlasⁱ	P49662, baseline and differential
Genevisibleⁱ	P49662, HS

Family and domain databases

CDDⁱ	cd00032, CASc, 1 hit
Gene3Dⁱ	1.10.533.10, 1 hit
InterProⁱ	View protein in InterPro IPR001315, CARD IPR029030, Caspase-like_dom_sf IPR033139, Caspase_cys_AS IPR016129, Caspase_his_AS IPR011029, DEATH-like_dom_sf IPR002398, Pept_C14 IPR002138, Pept_C14_p10 IPR001309, Pept_C14_p20 IPR015917, Pept_C14A
PANTHERⁱ	PTHR10454, PTHR10454, 1 hit
Pfamⁱ	View protein in Pfam PF00619, CARD, 1 hit
PRINTSⁱ	PR00376, IL1BCENZYME
SMARTⁱ	View protein in SMART SM00114, CARD, 1 hit SM00115, CASc, 1 hit
SUPFAMⁱ	SSF47986, SSF47986, 1 hit SSF52129, SSF52129, 1 hit
PROSITEⁱ	View protein in 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
MobiDBⁱ	Search...

Entry informationⁱ

Entry nameⁱ	CASP4_HUMAN
Accessionⁱ	P49662Primary (citable) accession number: P49662 Secondary accession number(s): A2NHL8 Q9UG96
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
	Last sequence update:	February 1, 1996
	Last modified:	September 29, 2021
	This is version 203 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	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.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Reference proteome

Documents

Peptidase families
Classification of peptidase families and list of entries
Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM
Human entries with genetic variants
List of human entries with genetic variants
Human variants curated from literature reports
Index of human variants curated from literature reports
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PDB cross-references
Index of Protein Data Bank (PDB) cross-references
SIMILARITY comments
Index of protein domains and families

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UniProtKB - P49662 (CASP4_HUMAN)

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Caspase-4

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<p>This subsection of the 'Sequence' section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

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Keywords - Coding sequence diversityi

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Functionⁱ

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Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Sequence cautionⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Web resourcesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ