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Reviewed, UniProtKB/Swiss-Prot P42575 (CASP2_HUMAN)

Last modified July 7, 2009. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Caspase-2
      Short name=CASP-2
    EC=3.4.22.55
Alternative name(s):
    ICH-1 protease
    Neural precursor cell expressed developmentally down-regulated protein 2
      Short name=NEDD-2
Cleaved into the following 3 chains:
    1- Recommended name:
            Caspase-2 subunit p18
    2- Recommended name:
            Caspase-2 subunit p13
    3- Recommended name:
            Caspase-2 subunit p12
Gene names
Name: CASP2
Synonyms: ICH1, NEDD2
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length452 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. Might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival.

Catalytic activity

Strict requirement for an Asp residue at P1, with 316-asp being essential for proteolytic activity and has a preferred cleavage sequence of Val-Asp-Val-Ala-Asp-|-.

Subunit structure

Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a p18 subunit and a p12 subunit. Interacts with LRDD. Ref.10 Ref.11 Ref.12

Tissue specificity

Expressed at higher levels in the embryonic lung, liver and kidney than in the heart and brain. In adults, higher level expression is seen in the placenta, lung, kidney, and pancreas than in the heart, brain, liver and skeletal muscle.

Post-translational modification

The mature protease can process its own propeptide, but not that of other caspases.

Sequence similarities

Belongs to the peptidase C14A family.

Contains 1 CARD domain.

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Isoforms differ in the N- and C-termini.
Isoform ICH-1L (identifier: P42575-1)

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.
Note: Acts as a positive regulator of apoptosis.
Isoform ICH-1S (identifier: P42575-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-31: Missing.
     323-452: DETDRGVDQQ...LYLFPGHPPT → GGAIGSLGHLLLFTAATASLAL
Note: Acts as a negative regulator of apoptosis.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Propeptide1 – 169169
PRO_0000004541
Chain170 – 325156Caspase-2 subunit p18
PRO_0000004542
Propeptide326 – 3338
PRO_0000004543
Chain334 – 452119Caspase-2 subunit p13
PRO_0000004544
Chain348 – 452105Caspase-2 subunit p12
PRO_0000004545

Regions

Domain32 – 12089CARD

Sites

Active site2771 By similarity
Active site3201 By similarity

Natural variations

Alternative sequence1 – 3131Missing in isoform ICH-1S.
VSP_000801
Alternative sequence323 – 452130DETDR…GHPPT → GGAIGSLGHLLLFTAATASL AL in isoform ICH-1S.
VSP_000802
Natural variant1051A → G: dbSNP rs4647298.
VAR_055621
Natural variant1721V → L: dbSNP rs4647297. Ref.3 Ref.5 Ref.6
VAR_016334
Natural variant1781P → A: dbSNP rs4647298. Ref.3
VAR_016335
Natural variant4411R → G: dbSNP rs4647338. Ref.3
VAR_016336

Experimental info

Mutagenesis3201C → S: Loss of function.
Mutagenesis3691A → T: Loss of function.
Sequence conflict107 – 1082RE → HS in AAK00300. Ref.7
Sequence conflict309 – 32214QNKPK…QACRG → EEVTSLSILSAFVT in BAD92877. Ref.8

Secondary structure

............................................. 452
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform ICH-1L [UniParc].

Last modified December 6, 2005. Version 2.
Checksum: 6EF0ED05EF808385

FASTA45250,685
        10         20         30         40         50         60 
MAAPSAGSWS TFQHKELMAA DRGRRILGVC GMHPHHQETL KKNRVVLAKQ LLLSELLEHL 

        70         80         90        100        110        120 
LEKDIITLEM RELIQAKVGS FSQNVELLNL LPKRGPQAFD AFCEALRETK QGHLEDMLLT 

       130        140        150        160        170        180 
TLSGLQHVLP PLSCDYDLSL PFPVCESCPL YKKLRLSTDT VEHSLDNKDG PVCLQVKPCT 

       190        200        210        220        230        240 
PEFYQTHFQL AYRLQSRPRG LALVLSNVHF TGEKELEFRS GGDVDHSTLV TLFKLLGYDV 

       250        260        270        280        290        300 
HVLCDQTAQE MQEKLQNFAQ LPAHRVTDSC IVALLSHGVE GAIYGVDGKL LQLQEVFQLF 

       310        320        330        340        350        360 
DNANCPSLQN KPKMFFIQAC RGDETDRGVD QQDGKNHAGS PGCEESDAGK EKLPKMRLPT 

       370        380        390        400        410        420 
RSDMICGYAC LKGTAAMRNT KRGSWYIEAL AQVFSERACD MHVADMLVKV NALIKDREGY 

       430        440        450 
APGTEFHRCK EMSEYCSTLC RHLYLFPGHP PT 

« Hide

Isoform ICH-1S.

Checksum: FA1E307A41B8299E
Show »

FASTA31334,923

References

« Hide 'large scale' references
[1]"Ich-1, an Ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death."
Wang L., Miura M., Bergeron L., Zhu H., Yuan J.
Cell 78:739-750(1994) [PubMed: 8087842] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ICH-1S), NUCLEOTIDE SEQUENCE [MRNA] OF 14-452 (ISOFORM ICH-1L).
Tissue: Fetal brain.
[2]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ICH-1S).
[3]NIEHS SNPs program
Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-172; ALA-178 AND GLY-441.
[4]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed: 12853948] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ICH-1L), VARIANT LEU-172.
Tissue: Skin.
[6]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 18-452 (ISOFORM 1), VARIANT LEU-172.
[7]"Identification of a caspase-2 isoform that behaves as an endogenous inhibitor of the caspase cascade."
Droin N., Beauchemin M., Solary E., Bertrand R.
Cancer Res. 60:7039-7047(2000) [PubMed: 11156409] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 32-108 (ISOFORMS 1/2).
[8]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 194-452.
Tissue: Spleen.
[9]"The Caenorhabditis elegans cell-death protein CED-3 is a cysteine protease with substrate specificities similar to those of the human CPP32 protease."
Xue D., Shaham S., Horvitz H.R.
Genes Dev. 10:1073-1083(1996) [PubMed: 8654923] [Abstract]
Cited for: CLEAVAGE SITES.
[10]"The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress."
Tinel A., Tschopp J.
Science 304:843-846(2004) [PubMed: 15073321] [Abstract]
Cited for: INTERACTION WITH LRDD.
[11]"Functional connection between p53 and caspase-2 is essential for apoptosis induced by DNA damage."
Vakifahmetoglu H., Olsson M., Orrenius S., Zhivotovsky B.
Oncogene 25:5683-5692(2006) [PubMed: 16652156] [Abstract]
Cited for: INTERACTION WITH LRDD.
[12]"Crystal structure of caspase-2, apical initiator of the intrinsic apoptotic pathway."
Schweizer A., Briand C., Grutter M.G.
J. Biol. Chem. 278:42441-42447(2003) [PubMed: 12920126] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 167-452 IN COMPLEX WITH INHIBITOR, SUBUNIT, DISULFIDE BOND.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

U13021 mRNA. Translation: AAA58959.1. Different initiation.
U13022 mRNA. Translation: AAA58960.1.
CR541748 mRNA. Translation: CAG46548.1.
AY219042 Genomic DNA. Translation: AAO25653.1. Different initiation.
AC073342 Genomic DNA. Translation: AAP22346.1. Different initiation.
AC073342 Genomic DNA. Translation: AAP22347.1.
AC073342 Genomic DNA. Translation: AAP22349.1. Different initiation.
BC002427 mRNA. Translation: AAH02427.2.
BT007240 mRNA. Translation: AAP35904.1.
AF314175 mRNA. Translation: AAK00300.1.
AB209640 mRNA. Translation: BAD92877.1. Different initiation.
IPIIPI00216410.
IPI00291570.
PIRA54821.
RefSeqNP_116764.2.
UniGeneHs.368982

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1PYOX-ray1.65A/C167-333[»]
B/D348-452[»]
2P2CX-ray3.24A/C/E/G/I/K167-333[»]
B/D/F/H/J/L348-452[»]
ModBaseSearch...

Protein-protein interaction databases

IntActP42575. 4 interactions.

Protein family/group databases

MEROPSC14.006.

PTM databases

PhosphoSiteP42575.

Proteomic databases

PeptideAtlasP42575.
PRIDEP42575.

Genome annotation databases

EnsemblENSG00000106144. Homo sapiens. [Contig view]
GeneID835.
KEGGhsa:835.
UCSCuc003wco.1. human.

Organism-specific databases

GeneCardsGC07P142695.
H-InvDBHIX0007169.
HGNCHGNC:1503. CASP2.
HPACAB012175.
MIM600639. gene.
PharmGKBPA26086.
GenAtlasSearch...

Phylogenomic databases

HOVERGENP42575.
OMAP42575. FRLFDNA.

Enzyme and pathway databases

BRENDA3.4.22.55. 247.
Pathway_Interaction_DBcaspase_pathway. Caspase cascade in apoptosis.
hivnefpathway. HIV-1 Nef: Negative effector of Fas and TNF-alpha.
ReactomeREACT_11061. Signalling by NGF.

Gene expression databases

ArrayExpressP42575.
BgeeP42575.
CleanExHS_CASP2.
GermOnlineENSG00000106144. Homo sapiens.

Family and domain databases

InterProIPR001315. CARD.
IPR017350. Caspase_IL-1_beta.
IPR011029. DEATH-like.
IPR011600. Pept_C14_cat.
IPR001309. Pept_C14_ICE_p20.
IPR016129. Pept_C14_ICE_p20_AS.
IPR002138. Pept_C14_p10.
IPR002398. Pept_C14_p45.
IPR015917. Pept_C14_p45_core.
[Graphical view]
Gene3DG3DSA:1.10.533.10. DEATH_like. 1 hit.
PANTHERPTHR10454. Pept_C14_p45. 1 hit.
PfamPF00619. CARD. 1 hit.
PF00656. Peptidase_C14. 1 hit.
[Graphical view]
PIRSFPIRSF038001. Caspase_ICE. 1 hit.
PRINTSPR00376. IL1BCENZYME.
SMARTSM00114. CARD. 1 hit.
SM00115. CASc. 1 hit.
[Graphical view]
PROSITEPS50209. CARD. 1 hit.
PS01122. CASPASE_CYS. 1 hit.
PS01121. CASPASE_HIS. 1 hit.
PS50207. CASPASE_P10. 1 hit.
PS50208. CASPASE_P20. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio3472.
PMAP-CutDBP42575.
SOURCESearch...

Entry information

Entry nameCASP2_HUMAN
AccessionPrimary (citable) accession number: P42575
Secondary accession number(s): P42576 expand/collapse secondary AC list , Q59F21, Q7KZL6, Q86UJ3, Q9BUP7, Q9BZK9
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: December 6, 2005
Last modified: July 7, 2009
This is version 99 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents