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Protein

Caspase-5

Gene

CASP5

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

Functioni

Mediator of programmed cell death (apoptosis). During non-canonical inflammasome activation, cuts MB21D1 and may play a role in the regulation of antiviral innate immune activation (PubMed:28314590).1 Publication

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-|-.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei267By similarity1
Active sitei3151

GO - Molecular functioni

GO - Biological processi

  • apoptotic process Source: ProtInc
  • cellular response to mechanical stimulus Source: UniProtKB
  • ectopic germ cell programmed cell death Source: Ensembl
  • positive regulation of interleukin-1 beta secretion Source: Ensembl
  • proteolysis Source: ProtInc
  • pyroptosis Source: Ensembl
  • regulation of apoptotic process Source: InterPro
  • regulation of inflammatory response Source: GO_Central
  • substantia nigra development Source: UniProtKB

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processApoptosis

Enzyme and pathway databases

BRENDAi3.4.22.58. 2681.
SABIO-RKiP51878.

Protein family/group databases

MEROPSiC14.008.

Names & Taxonomyi

Protein namesi
Recommended name:
Caspase-5 (EC:3.4.22.58)
Short name:
CASP-5
Alternative name(s):
ICE(rel)-III
Protease ICH-3
Protease TY
Cleaved into the following 2 chains:
Gene namesi
Name:CASP5
Synonyms:ICH3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:1506. CASP5.

Subcellular locationi

GO - Cellular componenti

  • neuronal cell body Source: Ensembl
  • neuron projection Source: Ensembl
  • NLRP1 inflammasome complex Source: UniProtKB

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi315C → A: Abolishes protease activity. 1 Publication1

Organism-specific databases

DisGeNETi838.
OpenTargetsiENSG00000137757.
PharmGKBiPA26089.

Chemistry databases

ChEMBLiCHEMBL3131.
GuidetoPHARMACOLOGYi1621.

Polymorphism and mutation databases

BioMutaiCASP5.
DMDMi294862523.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_00000046041 – 136Sequence analysisAdd BLAST136
ChainiPRO_0000004605137 – 327Caspase-5 subunit p20Add BLAST191
PropeptideiPRO_0000004606328 – 346Sequence analysisAdd BLAST19
ChainiPRO_0000004607347 – 434Caspase-5 subunit p10Add BLAST88

Post-translational modificationi

The two subunits are derived from the precursor sequence by an autocatalytic mechanism.

Keywords - PTMi

Zymogen

Proteomic databases

MaxQBiP51878.
PaxDbiP51878.
PeptideAtlasiP51878.
PRIDEiP51878.

PTM databases

iPTMnetiP51878.
PhosphoSitePlusiP51878.

Expressioni

Tissue specificityi

Expressed in barely detectable amounts in most tissues except brain, highest levels being found in lung, liver and skeletal muscle.

Inductioni

Up-regulated by bacterial lipopolysaccharides (LPS).1 Publication

Gene expression databases

BgeeiENSG00000137757.
CleanExiHS_CASP5.
ExpressionAtlasiP51878. baseline and differential.
GenevisibleiP51878. HS.

Organism-specific databases

HPAiHPA040937.

Interactioni

Subunit structurei

Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (p20) and a 10 kDa (p10) subunits. Interacts with MEFV.1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107288. 4 interactors.
DIPiDIP-40038N.
IntActiP51878. 1 interactor.
MINTiMINT-245149.
STRINGi9606.ENSP00000376849.

Chemistry databases

BindingDBiP51878.

Structurei

3D structure databases

ProteinModelPortaliP51878.
SMRiP51878.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini56 – 148CARDPROSITE-ProRule annotationAdd BLAST93

Sequence similaritiesi

Belongs to the peptidase C14A family.Curated

Phylogenomic databases

eggNOGiKOG3573. Eukaryota.
ENOG410ZQIE. LUCA.
GeneTreeiENSGT00760000118912.
HOVERGENiHBG076981.
InParanoidiP51878.
KOiK04395.
OMAiHDEIYPI.
OrthoDBiEOG091G07NO.
PhylomeDBiP51878.
TreeFamiTF102023.

Family and domain databases

CDDicd00032. CASc. 1 hit.
InterProiView protein in InterPro
IPR001315. CARD.
IPR029030. Caspase-like_dom.
IPR033139. Caspase_cys_AS.
IPR016129. Caspase_his_AS.
IPR011029. DEATH-like_dom.
IPR002138. Pept_C14_p10.
IPR001309. Pept_C14_p20.
IPR015917. Pept_C14A.
PfamiView protein in Pfam
PF00619. CARD. 1 hit.
PRINTSiPR00376. IL1BCENZYME.
SMARTiView protein in SMART
SM00114. CARD. 1 hit.
SM00115. CASc. 1 hit.
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF52129. SSF52129. 1 hit.
PROSITEiView 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 (6)i

Sequence statusi: Complete.

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

This entry describes 6 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

Isoform 1 (identifier: P51878-1) [UniParc]FASTAAdd to basket
Also known as: caspase-5/a

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
MAEDSGKKKR RKNFEAMFKG ILQSGLDNFV INHMLKNNVA GQTSIQTLVP
60 70 80 90 100
NTDQKSTSVK KDNHKKKTVK MLEYLGKDVL HGVFNYLAKH DVLTLKEEEK
110 120 130 140 150
KKYYDTKIED KALILVDSLR KNRVAHQMFT QTLLNMDQKI TSVKPLLQIE
160 170 180 190 200
AGPPESAEST NILKLCPREE FLRLCKKNHD EIYPIKKRED RRRLALIICN
210 220 230 240 250
TKFDHLPARN GAHYDIVGMK RLLQGLGYTV VDEKNLTARD MESVLRAFAA
260 270 280 290 300
RPEHKSSDST FLVLMSHGIL EGICGTAHKK KKPDVLLYDT IFQIFNNRNC
310 320 330 340 350
LSLKDKPKVI IVQACRGEKH GELWVRDSPA SLALISSQSS ENLEADSVCK
360 370 380 390 400
IHEEKDFIAF CSSTPHNVSW RDRTRGSIFI TELITCFQKY SCCCHLMEIF
410 420 430
RKVQKSFEVP QAKAQMPTIE RATLTRDFYL FPGN
Note: Most abundant isoform.
Length:434
Mass (Da):49,736
Last modified:April 20, 2010 - v3
Checksum:iC5257C2BF15EB6D5
GO
Isoform 2 (identifier: P51878-2) [UniParc]FASTAAdd to basket
Also known as: Caspase-5/b

The sequence of this isoform differs from the canonical sequence as follows:
     5-62: Missing.

Note: Most abundant isoform.
Show »
Length:376
Mass (Da):43,261
Checksum:i7D3035A84418FE31
GO
Isoform 3 (identifier: P51878-3) [UniParc]FASTAAdd to basket
Also known as: Caspase-5/c

The sequence of this isoform differs from the canonical sequence as follows:
     1-145: MAEDSGKKKR...MDQKITSVKP → MAA

Show »
Length:292
Mass (Da):33,304
Checksum:iFD1D1199CB76E857
GO
Isoform 4 (identifier: P51878-4) [UniParc]FASTAAdd to basket
Also known as: Caspase-5/e

The sequence of this isoform differs from the canonical sequence as follows:
     5-62: Missing.
     145-166: PLLQIEAGPPESAESTNILKLC → HLSNKKERGPQTPGSHHMQYKV
     167-434: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:108
Mass (Da):12,694
Checksum:i2A441B191C453A3C
GO
Isoform 5 (identifier: P51878-5) [UniParc]FASTAAdd to basket
Also known as: Caspase-5/f

The sequence of this isoform differs from the canonical sequence as follows:
     1-2: MA → MAAVPRVEGVFIFLI

Show »
Length:447
Mass (Da):51,177
Checksum:i39D5955FA0419B68
GO
Isoform 6 (identifier: P51878-6) [UniParc]FASTAAdd to basket
Also known as: Caspase-5-S

The sequence of this isoform differs from the canonical sequence as follows:
     1-70: Missing.

Note: Produced by alternative initiation at Met-71 of isoform 1.
Show »
Length:364
Mass (Da):41,851
Checksum:i64533BAB7E528B37
GO

Sequence cautioni

The sequence AAA75172 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH74994 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAI13407 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence ABF47103 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAG59257 differs from that shown. Reason: Frameshift at position 10.Curated
The sequence CAA64450 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04721619K → N1 PublicationCorresponds to variant dbSNP:rs45483102Ensembl.1
Natural variantiVAR_04721726L → W. Corresponds to variant dbSNP:rs1792778Ensembl.1
Natural variantiVAR_02440329F → L2 PublicationsCorresponds to variant dbSNP:rs3181320Ensembl.1
Natural variantiVAR_05448075L → R1 PublicationCorresponds to variant dbSNP:rs45585331Ensembl.1
Natural variantiVAR_047218106T → A7 PublicationsCorresponds to variant dbSNP:rs507879Ensembl.1
Natural variantiVAR_024404168R → H2 PublicationsCorresponds to variant dbSNP:rs3181179Ensembl.1
Natural variantiVAR_024405217V → L2 PublicationsCorresponds to variant dbSNP:rs3181326Ensembl.1
Natural variantiVAR_054481298R → H1 PublicationCorresponds to variant dbSNP:rs45464699Ensembl.1
Natural variantiVAR_047219334L → V4 PublicationsCorresponds to variant dbSNP:rs523104Ensembl.1
Natural variantiVAR_047220353E → K1 PublicationCorresponds to variant dbSNP:rs45619739Ensembl.1
Natural variantiVAR_054482382E → Q1 PublicationCorresponds to variant dbSNP:rs45458695Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0389901 – 145MAEDS…TSVKP → MAA in isoform 3. 1 PublicationAdd BLAST145
Alternative sequenceiVSP_0389911 – 70Missing in isoform 6. CuratedAdd BLAST70
Alternative sequenceiVSP_0389921 – 2MA → MAAVPRVEGVFIFLI in isoform 5. 1 Publication2
Alternative sequenceiVSP_0389935 – 62Missing in isoform 2 and isoform 4. 2 PublicationsAdd BLAST58
Alternative sequenceiVSP_038994145 – 166PLLQI…ILKLC → HLSNKKERGPQTPGSHHMQY KV in isoform 4. 1 PublicationAdd BLAST22
Alternative sequenceiVSP_038995167 – 434Missing in isoform 4. 1 PublicationAdd BLAST268

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ228672 mRNA. Translation: ABB58698.1.
DQ228673 mRNA. Translation: ABB58699.1.
DQ228674 mRNA. Translation: ABB58700.1.
DQ228676 mRNA. Translation: ABB58702.1.
DQ228677 mRNA. Translation: ABB58703.1.
AK296660 mRNA. Translation: BAG59257.1. Frameshift.
AP001153 Genomic DNA. No translation available.
U28015 mRNA. Translation: AAA75172.1. Different initiation.
BC074994 mRNA. Translation: AAH74994.1. Different initiation.
BC113406 mRNA. Translation: AAI13407.1. Different initiation.
X94993 mRNA. Translation: CAA64450.1. Different initiation.
DQ508420 Genomic DNA. Translation: ABF47103.1. Different initiation.
CH471065 Genomic DNA. Translation: EAW67054.1.
CCDSiCCDS44718.1. [P51878-3]
CCDS44719.1. [P51878-2]
CCDS44720.1. [P51878-5]
CCDS8328.2. [P51878-1]
PIRiB57511.
RefSeqiNP_001129581.1. NM_001136109.1. [P51878-2]
NP_001129582.1. NM_001136110.1. [P51878-3]
NP_001129584.1. NM_001136112.1. [P51878-5]
NP_004338.3. NM_004347.3. [P51878-1]
UniGeneiHs.213327.

Genome annotation databases

EnsembliENST00000260315; ENSP00000260315; ENSG00000137757. [P51878-1]
ENST00000393141; ENSP00000376849; ENSG00000137757. [P51878-5]
ENST00000418434; ENSP00000398130; ENSG00000137757. [P51878-3]
ENST00000444749; ENSP00000388365; ENSG00000137757. [P51878-2]
ENST00000456200; ENSP00000408455; ENSG00000137757. [P51878-4]
ENST00000526056; ENSP00000436877; ENSG00000137757. [P51878-5]
ENST00000531367; ENSP00000434471; ENSG00000137757. [P51878-3]
GeneIDi838.
KEGGihsa:838.
UCSCiuc010ruz.1. human. [P51878-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing, Polymorphism

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiCASP5_HUMAN
AccessioniPrimary (citable) accession number: P51878
Secondary accession number(s): B4DKP5
, Q0QVY7, Q0QVY8, Q0QVZ0, Q0QVZ1, Q0QVZ2, Q14DD6, Q1HBJ3, Q6DJV7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: April 20, 2010
Last modified: July 5, 2017
This is version 163 of the entry and version 3 of the sequence. See 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