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Protein

Caspase-2

Gene

CASP2

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

Catalytic activityi

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-|-.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei277By similarity1
Active sitei320By similarity1

GO - Molecular functioni

  • cysteine-type endopeptidase activity Source: UniProtKB
  • cysteine-type endopeptidase activity involved in execution phase of apoptosis Source: GO_Central
  • enzyme binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • protein domain specific binding Source: BHF-UCL

GO - Biological processi

  • aging Source: Ensembl
  • apoptotic process Source: UniProtKB
  • apoptotic signaling pathway Source: UniProtKB
  • brain development Source: Ensembl
  • cellular response to mechanical stimulus Source: UniProtKB
  • DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Source: UniProtKB
  • ectopic germ cell programmed cell death Source: Ensembl
  • execution phase of apoptosis Source: UniProtKB
  • extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
  • intrinsic apoptotic signaling pathway in response to DNA damage Source: UniProtKB
  • luteolysis Source: Ensembl
  • negative regulation of apoptotic process Source: UniProtKB
  • neural retina development Source: Ensembl
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of apoptotic signaling pathway Source: Ensembl
  • positive regulation of neuron apoptotic process Source: Ensembl
  • protein processing Source: BHF-UCL
  • regulation of apoptotic process Source: Reactome

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processApoptosis

Enzyme and pathway databases

BRENDAi3.4.22.55 2681
ReactomeiR-HSA-168638 NOD1/2 Signaling Pathway
R-HSA-205025 NADE modulates death signalling
R-HSA-6803207 TP53 Regulates Transcription of Caspase Activators and Caspases
SIGNORiP42575

Protein family/group databases

MEROPSiC14.006

Names & Taxonomyi

Protein namesi
Recommended name:
Caspase-2 (EC:3.4.22.55)
Short name:
CASP-2
Alternative name(s):
Neural precursor cell expressed developmentally down-regulated protein 2
Short name:
NEDD-2
Protease ICH-1
Cleaved into the following 3 chains:
Gene namesi
Name:CASP2
Synonyms:ICH1, NEDD2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000106144.19
HGNCiHGNC:1503 CASP2
MIMi600639 gene
neXtProtiNX_P42575

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi320C → S: Loss of function. 1
Mutagenesisi369A → T: Loss of function. 1

Organism-specific databases

DisGeNETi835
OpenTargetsiENSG00000106144
PharmGKBiPA26086

Chemistry databases

ChEMBLiCHEMBL4884
GuidetoPHARMACOLOGYi1618

Polymorphism and mutation databases

BioMutaiCASP2
DMDMi83300977

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
PropeptideiPRO_00000045412 – 169Add BLAST168
ChainiPRO_0000004542170 – 325Caspase-2 subunit p18Add BLAST156
PropeptideiPRO_0000004543326 – 3338
ChainiPRO_0000004544334 – 452Caspase-2 subunit p13Add BLAST119
ChainiPRO_0000004545348 – 452Caspase-2 subunit p12Add BLAST105

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei157PhosphoserineCombined sources1
Modified residuei340PhosphoserineCombined sources1

Post-translational modificationi

The mature protease can process its own propeptide, but not that of other caspases.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, Zymogen

Proteomic databases

EPDiP42575
MaxQBiP42575
PaxDbiP42575
PeptideAtlasiP42575
PRIDEiP42575
ProteomicsDBi55519
55520 [P42575-2]

PTM databases

iPTMnetiP42575
PhosphoSitePlusiP42575

Miscellaneous databases

PMAP-CutDBiP42575

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiENSG00000106144
CleanExiHS_CASP2
ExpressionAtlasiP42575 baseline and differential
GenevisibleiP42575 HS

Organism-specific databases

HPAiCAB012175
HPA050678

Interactioni

Subunit structurei

Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a p18 subunit and a p12 subunit. Interacts with LRDD. Interacts with NOL3 (via CARD domain); inhibits CASP2 activity in a phosphorylation-dependent manner.By similarity4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • protein domain specific binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi107285, 33 interactors
CORUMiP42575
IntActiP42575, 12 interactors
MINTiP42575
STRINGi9606.ENSP00000312664

Chemistry databases

BindingDBiP42575

Structurei

Secondary structure

1452
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi181 – 187Combined sources7
Helixi188 – 190Combined sources3
Beta strandi197 – 206Combined sources10
Beta strandi212 – 214Combined sources3
Helixi222 – 235Combined sources14
Beta strandi238 – 245Combined sources8
Helixi248 – 259Combined sources12
Helixi262 – 265Combined sources4
Beta strandi267 – 276Combined sources10
Beta strandi282 – 284Combined sources3
Beta strandi290 – 292Combined sources3
Helixi293 – 299Combined sources7
Turni302 – 304Combined sources3
Helixi306 – 308Combined sources3
Beta strandi313 – 319Combined sources7
Beta strandi321 – 324Combined sources4
Beta strandi363 – 370Combined sources8
Beta strandi377 – 379Combined sources3
Turni380 – 382Combined sources3
Helixi385 – 397Combined sources13
Turni398 – 400Combined sources3
Helixi403 – 415Combined sources13
Turni425 – 428Combined sources4
Beta strandi434 – 437Combined sources4
Beta strandi440 – 442Combined sources3

3D structure databases

ProteinModelPortaliP42575
SMRiP42575
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP42575

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini32 – 121CARDPROSITE-ProRule annotationAdd BLAST90

Sequence similaritiesi

Belongs to the peptidase C14A family.Curated

Phylogenomic databases

eggNOGiKOG3573 Eukaryota
ENOG410ZQIE LUCA
GeneTreeiENSGT00760000118912
HOVERGENiHBG103962
InParanoidiP42575
KOiK02186
OMAiVMVLMTH
OrthoDBiEOG091G05YD
PhylomeDBiP42575
TreeFamiTF102023

Family and domain databases

CDDicd00032 CASc, 1 hit
InterProiView protein in InterPro
IPR001315 CARD
IPR029030 Caspase-like_dom_sf
IPR035702 Caspase_2
IPR033139 Caspase_cys_AS
IPR016129 Caspase_his_AS
IPR011029 DEATH-like_dom_sf
IPR002138 Pept_C14_p10
IPR001309 Pept_C14_p20
IPR015917 Pept_C14A
PANTHERiPTHR10454:SF151 PTHR10454:SF151, 1 hit
PfamiView protein in Pfam
PF00619 CARD, 1 hit
PRINTSiPR00376 IL1BCENZYME
SMARTiView protein in SMART
SM00114 CARD, 1 hit
SM00115 CASc, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
SSF52129 SSF52129, 1 hit
PROSITEiView protein in PROSITE
PS50209 CARD, 1 hit
PS01122 CASPASE_CYS, 1 hit
PS01121 CASPASE_HIS, 1 hit
PS50207 CASPASE_P10, 1 hit
PS50208 CASPASE_P20, 1 hit

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Isoforms differ in the N- and C-termini.
Isoform 1 (identifier: P42575-1) [UniParc]FASTAAdd to basket
Also known as: ICH-1L

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
MAAPSAGSWS TFQHKELMAA DRGRRILGVC GMHPHHQETL KKNRVVLAKQ
60 70 80 90 100
LLLSELLEHL LEKDIITLEM RELIQAKVGS FSQNVELLNL LPKRGPQAFD
110 120 130 140 150
AFCEALRETK QGHLEDMLLT TLSGLQHVLP PLSCDYDLSL PFPVCESCPL
160 170 180 190 200
YKKLRLSTDT VEHSLDNKDG PVCLQVKPCT PEFYQTHFQL AYRLQSRPRG
210 220 230 240 250
LALVLSNVHF TGEKELEFRS GGDVDHSTLV TLFKLLGYDV HVLCDQTAQE
260 270 280 290 300
MQEKLQNFAQ LPAHRVTDSC IVALLSHGVE GAIYGVDGKL LQLQEVFQLF
310 320 330 340 350
DNANCPSLQN KPKMFFIQAC RGDETDRGVD QQDGKNHAGS PGCEESDAGK
360 370 380 390 400
EKLPKMRLPT RSDMICGYAC LKGTAAMRNT KRGSWYIEAL AQVFSERACD
410 420 430 440 450
MHVADMLVKV NALIKDREGY APGTEFHRCK EMSEYCSTLC RHLYLFPGHP

PT
Note: Acts as a positive regulator of apoptosis.
Length:452
Mass (Da):50,685
Last modified:December 6, 2005 - v2
Checksum:i6EF0ED05EF808385
GO
Isoform 2 (identifier: P42575-2) [UniParc]FASTAAdd to basket
Also known as: ICH-1S

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.
Show »
Length:313
Mass (Da):34,923
Checksum:iFA1E307A41B8299E
GO
Isoform 3 (identifier: P42575-3) [UniParc]FASTAAdd to basket
Also known as: Casp-2L-Pro

The sequence of this isoform differs from the canonical sequence as follows:
     1-17: Missing.
     107-108: RE → HS
     109-452: Missing.

Note: May function as an endogenous apoptosis inhibitor that antagonizes caspase activation and cell death.
Show »
Length:91
Mass (Da):10,309
Checksum:iE80E3D9233686A98
GO

Sequence cautioni

The sequence AAA58959 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAO25653 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAP22346 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAP22349 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAD92877 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti309 – 322QNKPK…QACRG → EEVTSLSILSAFVT in BAD92877 (Ref. 10) CuratedAdd BLAST14

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_055621105A → G. Corresponds to variant dbSNP:rs4647298Ensembl.1
Natural variantiVAR_016334172V → L3 PublicationsCorresponds to variant dbSNP:rs4647297Ensembl.1
Natural variantiVAR_016335178P → A1 PublicationCorresponds to variant dbSNP:rs4647298Ensembl.1
Natural variantiVAR_016336441R → G1 PublicationCorresponds to variant dbSNP:rs4647338Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0008011 – 31Missing in isoform 2. 2 PublicationsAdd BLAST31
Alternative sequenceiVSP_0462801 – 17Missing in isoform 3. 1 PublicationAdd BLAST17
Alternative sequenceiVSP_046281107 – 108RE → HS in isoform 3. 1 Publication2
Alternative sequenceiVSP_046282109 – 452Missing in isoform 3. 1 PublicationAdd BLAST344
Alternative sequenceiVSP_000802323 – 452DETDR…GHPPT → GGAIGSLGHLLLFTAATASL AL in isoform 2. 2 PublicationsAdd BLAST130

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U13021 mRNA Translation: AAA58959.1 Different initiation.
U13022 mRNA Translation: AAA58960.1
AF314174 mRNA Translation: AAK00299.1
AF314175 mRNA Translation: AAK00300.1
CR541748 mRNA Translation: CAG46548.1
AK291274 mRNA Translation: BAF83963.1
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: AAP22348.1
AC073342 Genomic DNA Translation: AAP22349.1 Different initiation.
CH471198 Genomic DNA Translation: EAW51863.1
CH471198 Genomic DNA Translation: EAW51867.1
CH471198 Genomic DNA Translation: EAW51870.1
BC002427 mRNA Translation: AAH02427.2
BT007240 mRNA Translation: AAP35904.1
AB209640 mRNA Translation: BAD92877.1 Different initiation.
CCDSiCCDS5879.1 [P42575-1]
PIRiA54821
RefSeqiNP_001215.1, NM_001224.4
NP_116764.2, NM_032982.3 [P42575-1]
NP_116765.2, NM_032983.3
UniGeneiHs.368982

Genome annotation databases

EnsembliENST00000310447; ENSP00000312664; ENSG00000106144 [P42575-1]
GeneIDi835
KEGGihsa:835
UCSCiuc003wco.3 human [P42575-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCASP2_HUMAN
AccessioniPrimary (citable) accession number: P42575
Secondary accession number(s): A8K5F9
, D3DXD6, E9PDN0, P42576, Q59F21, Q7KZL6, Q86UJ3, Q9BUP7, Q9BZK9, Q9BZL0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: December 6, 2005
Last modified: July 18, 2018
This is version 191 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 7
    Human chromosome 7: 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

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