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Protein

Caspase-5

Gene

CASP5

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

Functioni

Mediator of programmed cell death (apoptosis). During non-canonical inflammasome activation, cuts CGAS 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

  • cysteine-type endopeptidase activity Source: UniProtKB
  • cysteine-type endopeptidase activity involved in apoptotic process Source: GO_Central
  • cysteine-type peptidase activity Source: ProtInc

GO - Biological processi

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

EuPathDBiHostDB:ENSG00000137757.10
HGNCiHGNC:1506 CASP5
MIMi602665 gene
neXtProtiNX_P51878

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

EPDiP51878
MaxQBiP51878
PaxDbiP51878
PeptideAtlasiP51878
PRIDEiP51878
ProteomicsDBi56442
56443 [P51878-2]
56444 [P51878-3]
56445 [P51878-4]
56446 [P51878-5]
56447 [P51878-6]

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 Expressed in 92 organ(s), highest expression level in blood
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

Protein-protein interaction databases

BioGridi107288, 4 interactors
CORUMiP51878
DIPiDIP-40038N
IntActiP51878, 2 interactors
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
GeneTreeiENSGT00910000144131
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_sf
IPR033139 Caspase_cys_AS
IPR016129 Caspase_his_AS
IPR011029 DEATH-like_dom_sf
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

This entry has 6 described isoforms and 2 potential isoforms that are computationally mapped.iShow all

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H7C0P5H7C0P5_HUMAN
Caspase-5
CASP5
117Annotation score:
C9JF14C9JF14_HUMAN
Caspase-5
CASP5
165Annotation score:

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

Cross-referencesi

Web resourcesi

NIEHS-SNPs

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

3D structure databases

ProteinModelPortaliP51878
SMRiP51878
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107288, 4 interactors
CORUMiP51878
DIPiDIP-40038N
IntActiP51878, 2 interactors
STRINGi9606.ENSP00000376849

Chemistry databases

BindingDBiP51878
ChEMBLiCHEMBL3131
GuidetoPHARMACOLOGYi1621

Protein family/group databases

MEROPSiC14.008

PTM databases

iPTMnetiP51878
PhosphoSitePlusiP51878

Polymorphism and mutation databases

BioMutaiCASP5
DMDMi294862523

Proteomic databases

EPDiP51878
MaxQBiP51878
PaxDbiP51878
PeptideAtlasiP51878
PRIDEiP51878
ProteomicsDBi56442
56443 [P51878-2]
56444 [P51878-3]
56445 [P51878-4]
56446 [P51878-5]
56447 [P51878-6]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi838
DisGeNETi838
EuPathDBiHostDB:ENSG00000137757.10
GeneCardsiCASP5
HGNCiHGNC:1506 CASP5
HPAiHPA040937
MIMi602665 gene
neXtProtiNX_P51878
OpenTargetsiENSG00000137757
PharmGKBiPA26089
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3573 Eukaryota
ENOG410ZQIE LUCA
GeneTreeiENSGT00910000144131
HOVERGENiHBG076981
InParanoidiP51878
KOiK04395
OMAiHDEIYPI
OrthoDBiEOG091G07NO
PhylomeDBiP51878
TreeFamiTF102023

Enzyme and pathway databases

BRENDAi3.4.22.58 2681
SABIO-RKiP51878

Miscellaneous databases

ChiTaRSiCASP5 human
GenomeRNAii838
PROiPR:P51878
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000137757 Expressed in 92 organ(s), highest expression level in blood
CleanExiHS_CASP5
ExpressionAtlasiP51878 baseline and differential
GenevisibleiP51878 HS

Family and domain databases

CDDicd00032 CASc, 1 hit
InterProiView protein in InterPro
IPR001315 CARD
IPR029030 Caspase-like_dom_sf
IPR033139 Caspase_cys_AS
IPR016129 Caspase_his_AS
IPR011029 DEATH-like_dom_sf
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
ProtoNetiSearch...

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: September 12, 2018
This is version 171 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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