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Protein

Caspase-6

Gene

CASP6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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-|-.

Activity 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

  • cysteine-type endopeptidase activity Source: Reactome
  • cysteine-type endopeptidase activity involved in execution phase of apoptosis Source: CAFA
  • cysteine-type peptidase activity Source: ProtInc
  • identical protein binding Source: IntAct

GO - Biological processi

  • apoptotic process Source: ProtInc
  • cellular response to staurosporine Source: CAFA
  • epithelial cell differentiation Source: UniProtKB
  • execution phase of apoptosis Source: Reactome
  • proteolysis Source: UniProtKB
  • regulation of apoptotic process Source: Reactome

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processApoptosis

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000138794.9
HGNCiHGNC:1507 CASP6
MIMi601532 gene
neXtProtiNX_P55212

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

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
ProteomicsDBi56817
56818 [P55212-2]

2D gel databases

OGPiP55212

PTM databases

iPTMnetiP55212
PhosphoSitePlusiP55212

Miscellaneous databases

PMAP-CutDBiP55212

Expressioni

Gene expression databases

BgeeiENSG00000138794 Expressed in 197 organ(s), highest expression level in intestine
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107289, 20 interactors
DIPiDIP-44649N
ELMiP55212
IntActiP55212, 18 interactors
MINTiP55212
STRINGi9606.ENSP00000265164

Chemistry databases

BindingDBiP55212

Structurei

Secondary structure

1293
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
OMAiDPAEKYK
OrthoDBiEOG091G05YD
PhylomeDBiP55212
TreeFamiTF102023

Family and domain databases

CDDicd00032 CASc, 1 hit
InterProiView protein in InterPro
IPR029030 Caspase-like_dom_sf
IPR037554 Caspase_6
IPR033139 Caspase_cys_AS
IPR016129 Caspase_his_AS
IPR002138 Pept_C14_p10
IPR001309 Pept_C14_p20
IPR015917 Pept_C14A
PANTHERiPTHR10454:SF164 PTHR10454:SF164, 1 hit
PRINTSiPR00376 IL1BCENZYME
SMARTiView protein in SMART
SM00115 CASc, 1 hit
SUPFAMiSSF52129 SSF52129, 1 hit
PROSITEiView protein in PROSITE
PS01122 CASPASE_CYS, 1 hit
PS01121 CASPASE_HIS, 1 hit
PS50207 CASPASE_P10, 1 hit
PS50208 CASPASE_P20, 1 hit

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

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RHU3D6RHU3_HUMAN
Caspase-6
CASP6
143Annotation score:
D6RBM3D6RBM3_HUMAN
Caspase-6
CASP6
80Annotation score:

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 dbSNP:rs11574697Ensembl.1
Natural variantiVAR_016130109A → T. Corresponds to variant dbSNP:rs5030674Ensembl.1
Natural variantiVAR_020126182T → S1 PublicationCorresponds to variant dbSNP:rs5030593Ensembl.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

Similar proteinsi

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, 20 interactors
DIPiDIP-44649N
ELMiP55212
IntActiP55212, 18 interactors
MINTiP55212
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
ProteomicsDBi56817
56818 [P55212-2]

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
EuPathDBiHostDB:ENSG00000138794.9
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
OMAiDPAEKYK
OrthoDBiEOG091G05YD
PhylomeDBiP55212
TreeFamiTF102023

Enzyme and pathway databases

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-CutDBiP55212
PROiPR:P55212
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000138794 Expressed in 197 organ(s), highest expression level in intestine
CleanExiHS_CASP6
ExpressionAtlasiP55212 baseline and differential
GenevisibleiP55212 HS

Family and domain databases

CDDicd00032 CASc, 1 hit
InterProiView protein in InterPro
IPR029030 Caspase-like_dom_sf
IPR037554 Caspase_6
IPR033139 Caspase_cys_AS
IPR016129 Caspase_his_AS
IPR002138 Pept_C14_p10
IPR001309 Pept_C14_p20
IPR015917 Pept_C14A
PANTHERiPTHR10454:SF164 PTHR10454:SF164, 1 hit
PRINTSiPR00376 IL1BCENZYME
SMARTiView protein in SMART
SM00115 CASc, 1 hit
SUPFAMiSSF52129 SSF52129, 1 hit
PROSITEiView protein in PROSITE
PS01122 CASPASE_CYS, 1 hit
PS01121 CASPASE_HIS, 1 hit
PS50207 CASPASE_P10, 1 hit
PS50208 CASPASE_P20, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCASP6_HUMAN
AccessioniPrimary (citable) accession number: P55212
Secondary accession number(s): Q9BQE7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: November 28, 2002
Last modified: September 12, 2018
This is version 197 of the entry and version 2 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

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. Peptidase families
    Classification of peptidase families and list of entries
  4. SIMILARITY comments
    Index of protein domains and families
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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