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P55212 (CASP6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 155. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Caspase-6

Short name=CASP-6
EC=3.4.22.59
Alternative name(s):
Apoptotic protease Mch-2

Cleaved into the following 2 chains:

  1. Caspase-6 subunit p18
  2. Caspase-6 subunit p11
Gene names
Name:CASP6
Synonyms:MCH2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length293 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 activity

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

Enzyme regulation

Activation is suppressed by phosphorylation at Ser-257. Ref.6

Subunit structure

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. Ref.5

Subcellular location

Cytoplasm.

Post-translational modification

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

Sequence similarities

Belongs to the peptidase C14A family.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

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

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Alpha (identifier: P55212-1)

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.
Isoform Beta (identifier: P55212-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Propeptide1 – 2323
PRO_0000004608
Chain24 – 179156Caspase-6 subunit p18
PRO_0000004609
Propeptide180 – 19314
PRO_0000004610
Chain194 – 293100Caspase-6 subunit p11
PRO_0000004611

Sites

Active site1211 By similarity
Active site1631 By similarity

Amino acid modifications

Modified residue2571Phosphoserine; by NUAK1 Ref.6

Natural variations

Alternative sequence14 – 10289Missing in isoform Beta.
VSP_000805
Natural variant351E → K.
Corresponds to variant rs11574697 [ dbSNP | Ensembl ].
VAR_029242
Natural variant1091A → T.
Corresponds to variant rs5030674 [ dbSNP | Ensembl ].
VAR_016130
Natural variant1821T → S. Ref.2
Corresponds to variant rs5030593 [ dbSNP | Ensembl ].
VAR_020126

Experimental info

Mutagenesis2571S → A: Suppression of caspase-6 activation. Ref.6
Sequence conflict661G → R in AAC50168. Ref.1

Secondary structure

....................................................... 293
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Alpha [UniParc].

Last modified November 28, 2002. Version 2.
Checksum: 0738AE4F9791EBD7

FASTA29333,310
        10         20         30         40         50         60 
MSSASGLRRG HPAGGEENMT ETDAFYKREM FDPAEKYKMD HRRRGIALIF NHERFFWHLT 

        70         80         90        100        110        120 
LPERRGTCAD RDNLTRRFSD LGFEVKCFND LKAEELLLKI HEVSTVSHAD ADCFVCVFLS 

       130        140        150        160        170        180 
HGEGNHIYAY DAKIEIQTLT GLFKGDKCHS LVGKPKIFII QACRGNQHDV PVIPLDVVDN 

       190        200        210        220        230        240 
QTEKLDTNIT EVDAASVYTL PAGADFLMCY SVAEGYYSHR ETVNGSWYIQ DLCEMLGKYG 

       250        260        270        280        290 
SSLEFTELLT LVNRKVSQRR VDFCKDPSAI GKKQVPCFAS MLTKKLHFFP KSN 

« Hide

Isoform Beta [UniParc].

Checksum: 9DCC10C99F81D912
Show »

FASTA20422,574

References

« Hide 'large scale' references
[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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001217.2. NM_001226.3.
NP_116787.1. NM_032992.2.
UniGeneHs.654616.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalP55212.
SMRP55212. Positions 31-292.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107289. 17 interactions.
DIPDIP-44649N.
IntActP55212. 10 interactions.
MINTMINT-1374245.
STRING9606.ENSP00000265164.

Chemistry

BindingDBP55212.
ChEMBLCHEMBL3308.
GuidetoPHARMACOLOGY1622.

Protein family/group databases

MEROPSC14.005.

PTM databases

PhosphoSiteP55212.

Polymorphism databases

DMDM26006981.

2D gel databases

OGPP55212.

Proteomic databases

PaxDbP55212.
PeptideAtlasP55212.
PRIDEP55212.

Protocols and materials databases

DNASU839.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265164; ENSP00000265164; ENSG00000138794. [P55212-1]
ENST00000352981; ENSP00000285333; ENSG00000138794. [P55212-2]
GeneID839.
KEGGhsa:839.
UCSCuc003hzn.1. human. [P55212-1]
uc003hzo.1. human. [P55212-2]

Organism-specific databases

CTD839.
GeneCardsGC04M110609.
HGNCHGNC:1507. CASP6.
HPACAB003775.
HPA011337.
HPA024303.
MIM601532. gene.
neXtProtNX_P55212.
PharmGKBPA26090.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG278720.
HOGENOMHOG000231878.
HOVERGENHBG050802.
InParanoidP55212.
KOK04396.
OMADFCKDPS.
OrthoDBEOG7TTQ7K.
PhylomeDBP55212.
TreeFamTF102023.

Enzyme and pathway databases

BRENDA3.4.22.59. 2681.
ReactomeREACT_578. Apoptosis.

Gene expression databases

ArrayExpressP55212.
BgeeP55212.
CleanExHS_CASP6.
GenevestigatorP55212.

Family and domain databases

InterProIPR011600. 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]
PfamPF00656. Peptidase_C14. 1 hit.
[Graphical view]
PRINTSPR00376. IL1BCENZYME.
SMARTSM00115. CASc. 1 hit.
[Graphical view]
PROSITEPS01122. CASPASE_CYS. 1 hit.
PS01121. CASPASE_HIS. 1 hit.
PS50207. CASPASE_P10. 1 hit.
PS50208. CASPASE_P20. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCASP6. human.
EvolutionaryTraceP55212.
GeneWikiCaspase_6.
GenomeRNAi839.
NextBio3494.
PMAP-CutDBP55212.
PROP55212.
SOURCESearch...

Entry information

Entry nameCASP6_HUMAN
AccessionPrimary (citable) accession number: P55212
Secondary accession number(s): Q9BQE7
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: November 28, 2002
Last modified: April 16, 2014
This is version 155 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM