Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Caspase-6

Gene

CASP6

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

Functioni

Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves poly(ADP-ribose) polymerase in vitro, as well as lamins. Overexpression promotes programmed cell death.

Catalytic activityi

Strict requirement for Asp at position P1 and has a preferred cleavage sequence of Val-Glu-His-Asp-|-.

Enzyme regulationi

Activation is suppressed by phosphorylation at Ser-257.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei121By similarity1
Active sitei163By similarity1

GO - Molecular functioni

GO - Biological processi

  • apoptotic process Source: ProtInc
  • cellular component disassembly involved in execution phase of apoptosis Source: Reactome
  • epithelial cell differentiation Source: UniProtKB
  • proteolysis Source: UniProtKB
  • regulation of apoptotic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

BioCyciZFISH:HS06561-MONOMER.
BRENDAi3.4.22.59. 2681.
ReactomeiR-HSA-111465. Apoptotic cleavage of cellular proteins.
R-HSA-264870. Caspase-mediated cleavage of cytoskeletal proteins.
R-HSA-352238. Breakdown of the nuclear lamina.
R-HSA-6803207. TP53 Regulates Transcription of Caspase Activators and Caspases.
SIGNORiP55212.

Protein family/group databases

MEROPSiC14.005.

Names & Taxonomyi

Protein namesi
Recommended name:
Caspase-6 (EC:3.4.22.59)
Short name:
CASP-6
Alternative name(s):
Apoptotic protease Mch-2
Cleaved into the following 2 chains:
Gene namesi
Name:CASP6
Synonyms:MCH2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:1507. CASP6.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • cytosol Source: UniProtKB
  • nucleoplasm Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi257S → A: Suppression of caspase-6 activation. 1 Publication1

Organism-specific databases

DisGeNETi839.
OpenTargetsiENSG00000138794.
PharmGKBiPA26090.

Chemistry databases

ChEMBLiCHEMBL3308.
GuidetoPHARMACOLOGYi1622.

Polymorphism and mutation databases

BioMutaiCASP6.
DMDMi26006981.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_00000046081 – 23Add BLAST23
ChainiPRO_000000460924 – 179Caspase-6 subunit p18Add BLAST156
PropeptideiPRO_0000004610180 – 193Add BLAST14
ChainiPRO_0000004611194 – 293Caspase-6 subunit p11Add BLAST100

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei79PhosphoserineBy similarity1
Modified residuei257Phosphoserine; by NUAK11 Publication1

Post-translational modificationi

Cleavages by caspase-3, caspase-8 or -10 generate the two active subunits.

Keywords - PTMi

Phosphoprotein, Zymogen

Proteomic databases

EPDiP55212.
MaxQBiP55212.
PaxDbiP55212.
PeptideAtlasiP55212.
PRIDEiP55212.

2D gel databases

OGPiP55212.

PTM databases

iPTMnetiP55212.
PhosphoSitePlusiP55212.

Miscellaneous databases

PMAP-CutDBP55212.

Expressioni

Gene expression databases

BgeeiENSG00000138794.
CleanExiHS_CASP6.
ExpressionAtlasiP55212. baseline and differential.
GenevisibleiP55212. HS.

Organism-specific databases

HPAiCAB003775.
HPA011337.
HPA024303.

Interactioni

Subunit structurei

Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 18 kDa (p18) and a 11 kDa (p11) subunit. Interacts with BIRC6/bruce.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
itself6EBI-718729,EBI-718729
SATB1Q018262EBI-718729,EBI-743747

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi107289. 19 interactors.
DIPiDIP-44649N.
IntActiP55212. 15 interactors.
MINTiMINT-1374245.
STRINGi9606.ENSP00000265164.

Chemistry databases

BindingDBiP55212.

Structurei

Secondary structure

1293
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi41 – 43Combined sources3
Beta strandi46 – 51Combined sources6
Helixi57 – 59Combined sources3
Helixi67 – 80Combined sources14
Beta strandi84 – 90Combined sources7
Helixi93 – 105Combined sources13
Beta strandi114 – 120Combined sources7
Beta strandi122 – 124Combined sources3
Beta strandi126 – 128Combined sources3
Beta strandi130 – 135Combined sources6
Helixi136 – 141Combined sources6
Turni145 – 147Combined sources3
Helixi149 – 151Combined sources3
Beta strandi156 – 162Combined sources7
Beta strandi165 – 167Combined sources3
Beta strandi190 – 194Combined sources5
Beta strandi197 – 199Combined sources3
Turni202 – 205Combined sources4
Beta strandi206 – 212Combined sources7
Beta strandi219 – 221Combined sources3
Turni222 – 224Combined sources3
Helixi227 – 239Combined sources13
Turni240 – 242Combined sources3
Helixi245 – 258Combined sources14
Beta strandi263 – 265Combined sources3
Helixi267 – 269Combined sources3
Beta strandi271 – 273Combined sources3
Beta strandi277 – 280Combined sources4
Beta strandi283 – 285Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1MI9model-A34-175[»]
B198-290[»]
2WDPX-ray1.95A/B/C/D1-293[»]
3K7EX-ray3.00A/B/C/D24-293[»]
3NKFX-ray2.90A/B/C/D24-293[»]
3NR2X-ray2.90A/B24-293[»]
3OD5X-ray1.60A/B24-293[»]
3P45X-ray2.53A/C/E/G/I/K/M/O1-179[»]
B/D/F/H/J/L/N/P193-293[»]
3P4UX-ray1.90A/C23-179[»]
B/D193-293[»]
3QNWX-ray2.65A/C/E/G24-179[»]
B/D/F/H194-293[»]
3S70X-ray1.62A/C24-293[»]
3S8EX-ray2.88A/B/C/D/E/F/G/H24-293[»]
3V6LX-ray2.20A/B21-293[»]
3V6MX-ray2.69A/B/C/D/F/G/I/J24-293[»]
4EJFX-ray2.65A/B/C/D24-293[»]
4FXOX-ray2.85A/B/C/D1-293[»]
4HVAX-ray2.07A/B24-293[»]
4IYRX-ray2.70A/B1-293[»]
4N5DX-ray2.06A/B24-293[»]
4N6GX-ray2.14A/B24-293[»]
4N7JX-ray1.67A/B24-293[»]
4N7MX-ray2.12A/B24-293[»]
4NBKX-ray1.94A/B24-293[»]
4NBLX-ray1.76A/B24-293[»]
4NBNX-ray1.75A/B24-293[»]
ProteinModelPortaliP55212.
SMRiP55212.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP55212.

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase C14A family.Curated

Phylogenomic databases

eggNOGiKOG3573. Eukaryota.
ENOG410ZQIE. LUCA.
GeneTreeiENSGT00760000118912.
HOGENOMiHOG000231878.
HOVERGENiHBG050802.
InParanoidiP55212.
KOiK04396.
OMAiGNQHDVP.
OrthoDBiEOG091G05YD.
PhylomeDBiP55212.
TreeFamiTF102023.

Family and domain databases

CDDicd00032. CASc. 1 hit.
Gene3Di3.40.50.1460. 1 hit.
InterProiIPR029030. Caspase-like_dom.
IPR033139. Caspase_cys_AS.
IPR016129. Caspase_his_AS.
IPR002138. Pept_C14_p10.
IPR001309. Pept_C14_p20.
IPR015917. Pept_C14A.
[Graphical view]
PRINTSiPR00376. IL1BCENZYME.
SMARTiSM00115. CASc. 1 hit.
[Graphical view]
SUPFAMiSSF52129. SSF52129. 1 hit.
PROSITEiPS01122. CASPASE_CYS. 1 hit.
PS01121. CASPASE_HIS. 1 hit.
PS50207. CASPASE_P10. 1 hit.
PS50208. CASPASE_P20. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Alpha (identifier: P55212-1) [UniParc]FASTAAdd to basket

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
MSSASGLRRG HPAGGEENMT ETDAFYKREM FDPAEKYKMD HRRRGIALIF
60 70 80 90 100
NHERFFWHLT LPERRGTCAD RDNLTRRFSD LGFEVKCFND LKAEELLLKI
110 120 130 140 150
HEVSTVSHAD ADCFVCVFLS HGEGNHIYAY DAKIEIQTLT GLFKGDKCHS
160 170 180 190 200
LVGKPKIFII QACRGNQHDV PVIPLDVVDN QTEKLDTNIT EVDAASVYTL
210 220 230 240 250
PAGADFLMCY SVAEGYYSHR ETVNGSWYIQ DLCEMLGKYG SSLEFTELLT
260 270 280 290
LVNRKVSQRR VDFCKDPSAI GKKQVPCFAS MLTKKLHFFP KSN
Length:293
Mass (Da):33,310
Last modified:November 28, 2002 - v2
Checksum:i0738AE4F9791EBD7
GO
Isoform Beta (identifier: P55212-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     14-102: Missing.

Show »
Length:204
Mass (Da):22,574
Checksum:i9DCC10C99F81D912
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti66G → R in AAC50168 (PubMed:7796396).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02924235E → K.Corresponds to variant rs11574697dbSNPEnsembl.1
Natural variantiVAR_016130109A → T.Corresponds to variant rs5030674dbSNPEnsembl.1
Natural variantiVAR_020126182T → S.1 PublicationCorresponds to variant rs5030593dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00080514 – 102Missing in isoform Beta. 1 PublicationAdd BLAST89

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U20536 mRNA. Translation: AAC50168.1.
U20537 mRNA. Translation: AAC50169.1.
AY254046 Genomic DNA. Translation: AAO63494.1.
BC000305 mRNA. Translation: AAH00305.1.
BC004460 mRNA. Translation: AAH04460.1.
CCDSiCCDS3684.1. [P55212-1]
CCDS3685.1. [P55212-2]
RefSeqiNP_001217.2. NM_001226.3. [P55212-1]
NP_116787.1. NM_032992.2. [P55212-2]
UniGeneiHs.654616.

Genome annotation databases

EnsembliENST00000265164; ENSP00000265164; ENSG00000138794. [P55212-1]
ENST00000352981; ENSP00000285333; ENSG00000138794. [P55212-2]
GeneIDi839.
KEGGihsa:839.
UCSCiuc003hzn.2. human. [P55212-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U20536 mRNA. Translation: AAC50168.1.
U20537 mRNA. Translation: AAC50169.1.
AY254046 Genomic DNA. Translation: AAO63494.1.
BC000305 mRNA. Translation: AAH00305.1.
BC004460 mRNA. Translation: AAH04460.1.
CCDSiCCDS3684.1. [P55212-1]
CCDS3685.1. [P55212-2]
RefSeqiNP_001217.2. NM_001226.3. [P55212-1]
NP_116787.1. NM_032992.2. [P55212-2]
UniGeneiHs.654616.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1MI9model-A34-175[»]
B198-290[»]
2WDPX-ray1.95A/B/C/D1-293[»]
3K7EX-ray3.00A/B/C/D24-293[»]
3NKFX-ray2.90A/B/C/D24-293[»]
3NR2X-ray2.90A/B24-293[»]
3OD5X-ray1.60A/B24-293[»]
3P45X-ray2.53A/C/E/G/I/K/M/O1-179[»]
B/D/F/H/J/L/N/P193-293[»]
3P4UX-ray1.90A/C23-179[»]
B/D193-293[»]
3QNWX-ray2.65A/C/E/G24-179[»]
B/D/F/H194-293[»]
3S70X-ray1.62A/C24-293[»]
3S8EX-ray2.88A/B/C/D/E/F/G/H24-293[»]
3V6LX-ray2.20A/B21-293[»]
3V6MX-ray2.69A/B/C/D/F/G/I/J24-293[»]
4EJFX-ray2.65A/B/C/D24-293[»]
4FXOX-ray2.85A/B/C/D1-293[»]
4HVAX-ray2.07A/B24-293[»]
4IYRX-ray2.70A/B1-293[»]
4N5DX-ray2.06A/B24-293[»]
4N6GX-ray2.14A/B24-293[»]
4N7JX-ray1.67A/B24-293[»]
4N7MX-ray2.12A/B24-293[»]
4NBKX-ray1.94A/B24-293[»]
4NBLX-ray1.76A/B24-293[»]
4NBNX-ray1.75A/B24-293[»]
ProteinModelPortaliP55212.
SMRiP55212.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107289. 19 interactors.
DIPiDIP-44649N.
IntActiP55212. 15 interactors.
MINTiMINT-1374245.
STRINGi9606.ENSP00000265164.

Chemistry databases

BindingDBiP55212.
ChEMBLiCHEMBL3308.
GuidetoPHARMACOLOGYi1622.

Protein family/group databases

MEROPSiC14.005.

PTM databases

iPTMnetiP55212.
PhosphoSitePlusiP55212.

Polymorphism and mutation databases

BioMutaiCASP6.
DMDMi26006981.

2D gel databases

OGPiP55212.

Proteomic databases

EPDiP55212.
MaxQBiP55212.
PaxDbiP55212.
PeptideAtlasiP55212.
PRIDEiP55212.

Protocols and materials databases

DNASUi839.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265164; ENSP00000265164; ENSG00000138794. [P55212-1]
ENST00000352981; ENSP00000285333; ENSG00000138794. [P55212-2]
GeneIDi839.
KEGGihsa:839.
UCSCiuc003hzn.2. human. [P55212-1]

Organism-specific databases

CTDi839.
DisGeNETi839.
GeneCardsiCASP6.
HGNCiHGNC:1507. CASP6.
HPAiCAB003775.
HPA011337.
HPA024303.
MIMi601532. gene.
neXtProtiNX_P55212.
OpenTargetsiENSG00000138794.
PharmGKBiPA26090.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3573. Eukaryota.
ENOG410ZQIE. LUCA.
GeneTreeiENSGT00760000118912.
HOGENOMiHOG000231878.
HOVERGENiHBG050802.
InParanoidiP55212.
KOiK04396.
OMAiGNQHDVP.
OrthoDBiEOG091G05YD.
PhylomeDBiP55212.
TreeFamiTF102023.

Enzyme and pathway databases

BioCyciZFISH:HS06561-MONOMER.
BRENDAi3.4.22.59. 2681.
ReactomeiR-HSA-111465. Apoptotic cleavage of cellular proteins.
R-HSA-264870. Caspase-mediated cleavage of cytoskeletal proteins.
R-HSA-352238. Breakdown of the nuclear lamina.
R-HSA-6803207. TP53 Regulates Transcription of Caspase Activators and Caspases.
SIGNORiP55212.

Miscellaneous databases

ChiTaRSiCASP6. human.
EvolutionaryTraceiP55212.
GeneWikiiCaspase_6.
GenomeRNAii839.
PMAP-CutDBP55212.
PROiP55212.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000138794.
CleanExiHS_CASP6.
ExpressionAtlasiP55212. baseline and differential.
GenevisibleiP55212. HS.

Family and domain databases

CDDicd00032. CASc. 1 hit.
Gene3Di3.40.50.1460. 1 hit.
InterProiIPR029030. Caspase-like_dom.
IPR033139. Caspase_cys_AS.
IPR016129. Caspase_his_AS.
IPR002138. Pept_C14_p10.
IPR001309. Pept_C14_p20.
IPR015917. Pept_C14A.
[Graphical view]
PRINTSiPR00376. IL1BCENZYME.
SMARTiSM00115. CASc. 1 hit.
[Graphical view]
SUPFAMiSSF52129. SSF52129. 1 hit.
PROSITEiPS01122. CASPASE_CYS. 1 hit.
PS01121. CASPASE_HIS. 1 hit.
PS50207. CASPASE_P10. 1 hit.
PS50208. CASPASE_P20. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCASP6_HUMAN
AccessioniPrimary (citable) accession number: P55212
Secondary accession number(s): Q9BQE7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: November 28, 2002
Last modified: November 30, 2016
This is version 181 of the entry and version 2 of the sequence. [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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

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.