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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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei121 – 1211By similarity
Active sitei163 – 1631By similarity

GO - Molecular functioni

  1. cysteine-type endopeptidase activity Source: GO_Central
  2. cysteine-type peptidase activity Source: ProtInc
  3. identical protein binding Source: IntAct

GO - Biological processi

  1. apoptotic process Source: GO_Central
  2. cellular component disassembly involved in execution phase of apoptosis Source: Reactome
  3. epithelial cell differentiation Source: UniProtKB
  4. proteolysis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

BRENDAi3.4.22.59. 2681.
ReactomeiREACT_107. Apoptotic cleavage of cellular proteins.
REACT_13472. Breakdown of the nuclear lamina.
REACT_13541. Caspase-mediated cleavage of cytoskeletal proteins.

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
ProteomesiUP000005640: Chromosome 4

Organism-specific databases

HGNCiHGNC:1507. CASP6.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: HPA
  2. cytosol Source: UniProtKB
  3. nucleoplasm Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi257 – 2571S → A: Suppression of caspase-6 activation. 1 Publication

Organism-specific databases

PharmGKBiPA26090.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Propeptidei1 – 2323PRO_0000004608Add
BLAST
Chaini24 – 179156Caspase-6 subunit p18PRO_0000004609Add
BLAST
Propeptidei180 – 19314PRO_0000004610Add
BLAST
Chaini194 – 293100Caspase-6 subunit p11PRO_0000004611Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei257 – 2571Phosphoserine; by NUAK11 Publication

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein, Zymogen

Proteomic databases

MaxQBiP55212.
PaxDbiP55212.
PeptideAtlasiP55212.
PRIDEiP55212.

2D gel databases

OGPiP55212.

PTM databases

PhosphoSiteiP55212.

Miscellaneous databases

PMAP-CutDBP55212.

Expressioni

Gene expression databases

BgeeiP55212.
CleanExiHS_CASP6.
ExpressionAtlasiP55212. baseline and differential.
GenevestigatoriP55212.

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
itself3EBI-718729,EBI-718729
SATB1Q018262EBI-718729,EBI-743747

Protein-protein interaction databases

BioGridi107289. 19 interactions.
DIPiDIP-44649N.
IntActiP55212. 12 interactions.
MINTiMINT-1374245.
STRINGi9606.ENSP00000265164.

Structurei

Secondary structure

1
293
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi41 – 433Combined sources
Beta strandi46 – 516Combined sources
Helixi57 – 593Combined sources
Helixi67 – 8014Combined sources
Beta strandi84 – 907Combined sources
Helixi93 – 10513Combined sources
Beta strandi114 – 1207Combined sources
Beta strandi122 – 1243Combined sources
Beta strandi126 – 1283Combined sources
Beta strandi130 – 1356Combined sources
Helixi136 – 1416Combined sources
Turni145 – 1473Combined sources
Helixi149 – 1513Combined sources
Beta strandi156 – 1627Combined sources
Beta strandi165 – 1673Combined sources
Beta strandi190 – 1945Combined sources
Beta strandi197 – 1993Combined sources
Turni202 – 2054Combined sources
Beta strandi206 – 2127Combined sources
Beta strandi219 – 2213Combined sources
Turni222 – 2243Combined sources
Helixi227 – 23913Combined sources
Turni240 – 2423Combined sources
Helixi245 – 25814Combined sources
Beta strandi263 – 2653Combined sources
Helixi267 – 2693Combined sources
Beta strandi271 – 2733Combined sources
Beta strandi277 – 2804Combined sources
Beta strandi283 – 2853Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 25-292.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP55212.

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase C14A family.Curated

Phylogenomic databases

eggNOGiNOG278720.
GeneTreeiENSGT00760000118912.
HOGENOMiHOG000231878.
HOVERGENiHBG050802.
InParanoidiP55212.
KOiK04396.
OMAiDFCKDPS.
OrthoDBiEOG7TTQ7K.
PhylomeDBiP55212.
TreeFamiTF102023.

Family and domain databases

Gene3Di3.40.50.1460. 1 hit.
InterProiIPR029030. Caspase-like_dom.
IPR011600. Pept_C14_caspase.
IPR001309. Pept_C14_ICE_p20.
IPR016129. Pept_C14_ICE_p20_AS.
IPR002138. Pept_C14_p10.
IPR015917. Pept_C14A_p45_core.
[Graphical view]
PfamiPF00656. Peptidase_C14. 1 hit.
[Graphical view]
PRINTSiPR00376. IL1BCENZYME.
SMARTiSM00115. CASc. 1 hit.
[Graphical view]
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. Align

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti66 – 661G → R in AAC50168. (PubMed:7796396)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti35 – 351E → K.
Corresponds to variant rs11574697 [ dbSNP | Ensembl ].
VAR_029242
Natural varianti109 – 1091A → T.
Corresponds to variant rs5030674 [ dbSNP | Ensembl ].
VAR_016130
Natural varianti182 – 1821T → S.1 Publication
Corresponds to variant rs5030593 [ dbSNP | Ensembl ].
VAR_020126

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei14 – 10289Missing in isoform Beta. 1 PublicationVSP_000805Add
BLAST

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.1. human. [P55212-1]
uc003hzo.1. human. [P55212-2]

Polymorphism databases

DMDMi26006981.

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
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. Positions 25-292.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107289. 19 interactions.
DIPiDIP-44649N.
IntActiP55212. 12 interactions.
MINTiMINT-1374245.
STRINGi9606.ENSP00000265164.

Chemistry

BindingDBiP55212.
ChEMBLiCHEMBL3308.
GuidetoPHARMACOLOGYi1622.

Protein family/group databases

MEROPSiC14.005.

PTM databases

PhosphoSiteiP55212.

Polymorphism databases

DMDMi26006981.

2D gel databases

OGPiP55212.

Proteomic databases

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.1. human. [P55212-1]
uc003hzo.1. human. [P55212-2]

Organism-specific databases

CTDi839.
GeneCardsiGC04M110609.
HGNCiHGNC:1507. CASP6.
HPAiCAB003775.
HPA011337.
HPA024303.
MIMi601532. gene.
neXtProtiNX_P55212.
PharmGKBiPA26090.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG278720.
GeneTreeiENSGT00760000118912.
HOGENOMiHOG000231878.
HOVERGENiHBG050802.
InParanoidiP55212.
KOiK04396.
OMAiDFCKDPS.
OrthoDBiEOG7TTQ7K.
PhylomeDBiP55212.
TreeFamiTF102023.

Enzyme and pathway databases

BRENDAi3.4.22.59. 2681.
ReactomeiREACT_107. Apoptotic cleavage of cellular proteins.
REACT_13472. Breakdown of the nuclear lamina.
REACT_13541. Caspase-mediated cleavage of cytoskeletal proteins.

Miscellaneous databases

ChiTaRSiCASP6. human.
EvolutionaryTraceiP55212.
GeneWikiiCaspase_6.
GenomeRNAii839.
NextBioi3494.
PMAP-CutDBP55212.
PROiP55212.
SOURCEiSearch...

Gene expression databases

BgeeiP55212.
CleanExiHS_CASP6.
ExpressionAtlasiP55212. baseline and differential.
GenevestigatoriP55212.

Family and domain databases

Gene3Di3.40.50.1460. 1 hit.
InterProiIPR029030. Caspase-like_dom.
IPR011600. Pept_C14_caspase.
IPR001309. Pept_C14_ICE_p20.
IPR016129. Pept_C14_ICE_p20_AS.
IPR002138. Pept_C14_p10.
IPR015917. Pept_C14A_p45_core.
[Graphical view]
PfamiPF00656. Peptidase_C14. 1 hit.
[Graphical view]
PRINTSiPR00376. IL1BCENZYME.
SMARTiSM00115. CASc. 1 hit.
[Graphical view]
PROSITEiPS01122. CASPASE_CYS. 1 hit.
PS01121. CASPASE_HIS. 1 hit.
PS50207. CASPASE_P10. 1 hit.
PS50208. CASPASE_P20. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family."
    Fernandes-Alnemri T., Litwack G., Alnemri E.S.
    Cancer Res. 55:2737-2742(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA).
    Tissue: T-cell.
  2. NIEHS SNPs program
    Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-182.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA).
    Tissue: Lung.
  4. "The Ced-3/interleukin 1beta converting enzyme-like homolog Mch6 and the lamin-cleaving enzyme Mch2alpha are substrates for the apoptotic mediator CPP32."
    Srinivasula S.M., Fernandes-Alnemri T., Zangrilli J., Robertson N., Armstrong R.C., Wang L., Trapani J.A., Tomaselli K.J., Litwack G., Alnemri E.S.
    J. Biol. Chem. 271:27099-27106(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING.
    Tissue: Lymphocyte.
  5. "Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin ligase."
    Bartke T., Pohl C., Pyrowolakis G., Jentsch S.
    Mol. Cell 14:801-811(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH BIRC6/BRUCE.
  6. "Regulation of caspase-6 and FLIP by the AMPK family member ARK5."
    Suzuki A., Kusakai G., Kishimoto A., Shimojo Y., Miyamoto S., Ogura T., Ochiai A., Esumi H.
    Oncogene 23:7067-7075(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: ENZYME REGULATION, PHOSPHORYLATION AT SER-257, MUTAGENESIS OF SER-257.
  7. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

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: February 4, 2015
This is version 163 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

External Data

Dasty 3

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 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.