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Protein

Calpain-9

Gene

CAPN9

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Calcium-regulated non-lysosomal thiol-protease.

Catalytic activityi

Broad endopeptidase specificity.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi81Calcium 1; via carbonyl oxygen1
Metal bindingi83Calcium 1; via carbonyl oxygen1
Metal bindingi88Calcium 11
Active sitei971 Publication1
Metal bindingi167Calcium 11
Active sitei2541 Publication1
Active sitei2781 Publication1
Metal bindingi284Calcium 21
Metal bindingi291Calcium 21
Metal bindingi312Calcium 2; via carbonyl oxygen1
Metal bindingi314Calcium 21
Metal bindingi316Calcium 2; via carbonyl oxygen1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi574 – 5851PROSITE-ProRule annotationAdd BLAST12
Calcium bindingi604 – 6152PROSITE-ProRule annotationAdd BLAST12

GO - Molecular functioni

  • calcium-dependent cysteine-type endopeptidase activity Source: ProtInc
  • calcium ion binding Source: ProtInc

GO - Biological processi

  • digestion Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

BRENDAi3.4.22.B29. 2681.
ReactomeiR-HSA-1474228. Degradation of the extracellular matrix.

Protein family/group databases

MEROPSiC02.006.

Names & Taxonomyi

Protein namesi
Recommended name:
Calpain-9 (EC:3.4.22.-)
Alternative name(s):
Digestive tract-specific calpain
New calpain 4
Short name:
nCL-4
Protein CG36
Gene namesi
Name:CAPN9
Synonyms:NCL4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:1486. CAPN9.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

DisGeNETi10753.
OpenTargetsiENSG00000135773.
PharmGKBiPA26066.

Polymorphism and mutation databases

BioMutaiCAPN9.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002077221 – 690Calpain-9Add BLAST690

Proteomic databases

PaxDbiO14815.
PeptideAtlasiO14815.
PRIDEiO14815.

PTM databases

iPTMnetiO14815.
PhosphoSitePlusiO14815.

Expressioni

Tissue specificityi

Expressed predominantly in stomach.

Inductioni

Down-regulated in gastric cancer tissue and in gastric cell lines of differentiated and poorly differentiated types.

Gene expression databases

BgeeiENSG00000135773.
CleanExiHS_CAPN9.
ExpressionAtlasiO14815. baseline and differential.
GenevisibleiO14815. HS.

Organism-specific databases

HPAiCAB033483.
HPA020398.

Interactioni

Protein-protein interaction databases

BioGridi115976. 2 interactors.
STRINGi9606.ENSP00000271971.

Structurei

Secondary structure

1690
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi29 – 38Combined sources10
Beta strandi46 – 48Combined sources3
Helixi52 – 54Combined sources3
Beta strandi57 – 59Combined sources3
Beta strandi66 – 68Combined sources3
Helixi70 – 72Combined sources3
Beta strandi74 – 76Combined sources3
Beta strandi78 – 80Combined sources3
Helixi86 – 88Combined sources3
Beta strandi93 – 95Combined sources3
Helixi98 – 107Combined sources10
Helixi110 – 116Combined sources7
Beta strandi129 – 136Combined sources8
Beta strandi138 – 147Combined sources10
Beta strandi150 – 161Combined sources12
Helixi169 – 181Combined sources13
Helixi185 – 187Combined sources3
Beta strandi188 – 190Combined sources3
Helixi192 – 200Combined sources9
Beta strandi205 – 208Combined sources4
Helixi209 – 211Combined sources3
Helixi216 – 226Combined sources11
Beta strandi229 – 233Combined sources5
Helixi239 – 241Combined sources3
Beta strandi256 – 266Combined sources11
Beta strandi269 – 277Combined sources9
Helixi294 – 298Combined sources5
Helixi301 – 306Combined sources6
Beta strandi313 – 320Combined sources8
Helixi321 – 327Combined sources7
Beta strandi330 – 334Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ZIVX-ray2.31A28-347[»]
2P0RX-ray2.50A/B10-340[»]
ProteinModelPortaliO14815.
SMRiO14815.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO14815.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini42 – 337Calpain catalyticPROSITE-ProRule annotationAdd BLAST296
Domaini518 – 552EF-hand 1PROSITE-ProRule annotationAdd BLAST35
Domaini561 – 594EF-hand 2PROSITE-ProRule annotationAdd BLAST34
Domaini591 – 626EF-hand 3PROSITE-ProRule annotationAdd BLAST36

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni338 – 521Domain IIIAdd BLAST184
Regioni522 – 690Domain IVAdd BLAST169

Sequence similaritiesi

Belongs to the peptidase C2 family.Curated
Contains 1 calpain catalytic domain.PROSITE-ProRule annotation
Contains 3 EF-hand domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0045. Eukaryota.
ENOG410XP0B. LUCA.
GeneTreeiENSGT00760000118971.
HOGENOMiHOG000232035.
HOVERGENiHBG012645.
InParanoidiO14815.
KOiK08578.
OMAiHEIAENP.
OrthoDBiEOG091G049E.
PhylomeDBiO14815.
TreeFamiTF314748.

Family and domain databases

CDDicd00214. Calpain_III. 1 hit.
cd00044. CysPc. 1 hit.
cd00051. EFh. 1 hit.
Gene3Di1.10.238.10. 1 hit.
InterProiIPR033883. C2_III.
IPR022684. Calpain_cysteine_protease.
IPR022682. Calpain_domain_III.
IPR022683. Calpain_III.
IPR029542. CAPN9.
IPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR000169. Pept_cys_AS.
IPR001300. Peptidase_C2_calpain_cat.
[Graphical view]
PANTHERiPTHR10183:SF311. PTHR10183:SF311. 1 hit.
PfamiPF01067. Calpain_III. 1 hit.
PF13833. EF-hand_8. 1 hit.
PF00648. Peptidase_C2. 1 hit.
[Graphical view]
PRINTSiPR00704. CALPAIN.
SMARTiSM00720. calpain_III. 1 hit.
SM00230. CysPc. 1 hit.
SM00054. EFh. 2 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
SSF49758. SSF49758. 1 hit.
PROSITEiPS50203. CALPAIN_CAT. 1 hit.
PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 3 hits.
PS00139. THIOL_PROTEASE_CYS. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O14815-1) [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
MPYLYRAPGP QAHPVPKDAR ITHSSGQSFE QMRQECLQRG TLFEDADFPA
60 70 80 90 100
SNSSLFYSER PQIPFVWKRP GEIVKNPEFI LGGATRTDIC QGELGDCWLL
110 120 130 140 150
AAIASLTLNQ KALARVIPQD QSFGPGYAGI FHFQFWQHSE WLDVVIDDRL
160 170 180 190 200
PTFRDRLVFL HSADHNEFWS ALLEKAYAKL NGSYEALKGG SAIEAMEDFT
210 220 230 240 250
GGVAETFQTK EAPENFYEIL EKALKRGSLL GCFIDTRSAA ESEARTPFGL
260 270 280 290 300
IKGHAYSVTG IDQVSFRGQR IELIRIRNPW GQVEWNGSWS DSSPEWRSVG
310 320 330 340 350
PAEQKRLCHT ALDDGEFWMA FKDFKAHFDK VEICNLTPDA LEEDAIHKWE
360 370 380 390 400
VTVHQGSWVR GSTAGGCRNF LDTFWTNPQI KLSLTEKDEG QEECSFLVAL
410 420 430 440 450
MQKDRRKLKR FGANVLTIGY AIYECPDKDE HLNKDFFRYH ASRARSKTFI
460 470 480 490 500
NLREVSDRFK LPPGEYILIP STFEPHQEAD FCLRIFSEKK AITRDMDGNV
510 520 530 540 550
DIDLPEPPKP TPPDQETEEE QRFRALFEQV AGEDMEVTAE ELEYVLNAVL
560 570 580 590 600
QKKKDIKFKK LSLISCKNII SLMDTSGNGK LEFDEFKVFW DKLKQWINLF
610 620 630 640 650
LRFDADKSGT MSTYELRTAL KAAGFQLSSH LLQLIVLRYA DEELQLDFDD
660 670 680 690
FLNCLVRLEN ASRVFQALST KNKEFIHLNI NEFIHLTMNI
Length:690
Mass (Da):79,097
Last modified:January 1, 1998 - v1
Checksum:i02176C04BE1E5C23
GO
Isoform 2 (identifier: O14815-2) [UniParc]FASTAAdd to basket
Also known as: CG36

The sequence of this isoform differs from the canonical sequence as follows:
     292-318: SSPEWRSVGPAEQKRLCHTALDDGEFW → R

Show »
Length:664
Mass (Da):76,168
Checksum:i8D0524E4A476159D
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_022188102A → V.1 PublicationCorresponds to variant rs12562749dbSNPEnsembl.1
Natural variantiVAR_022189122S → R.1 PublicationCorresponds to variant rs28359608dbSNPEnsembl.1
Natural variantiVAR_022190164D → N.1 PublicationCorresponds to variant rs28359632dbSNPEnsembl.1
Natural variantiVAR_022191234I → T.1 PublicationCorresponds to variant rs28359644dbSNPEnsembl.1
Natural variantiVAR_022192239A → T.1 PublicationCorresponds to variant rs28359647dbSNPEnsembl.1
Natural variantiVAR_022193277R → W.1 PublicationCorresponds to variant rs28359655dbSNPEnsembl.1
Natural variantiVAR_022194322K → Q.1 PublicationCorresponds to variant rs1933631dbSNPEnsembl.1
Natural variantiVAR_022195327H → Q.1 PublicationCorresponds to variant rs28359684dbSNPEnsembl.1
Natural variantiVAR_022196342E → K.1 PublicationCorresponds to variant rs16852652dbSNPEnsembl.1
Natural variantiVAR_022197458R → W.1 PublicationCorresponds to variant rs28359688dbSNPEnsembl.1
Natural variantiVAR_022198522R → W.1 PublicationCorresponds to variant rs12731961dbSNPEnsembl.1
Natural variantiVAR_022199611M → I.1 PublicationCorresponds to variant rs16852683dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_007553292 – 318SSPEW…DGEFW → R in isoform 2. 1 PublicationAdd BLAST27

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF022799 mRNA. Translation: AAB80762.1.
AB038463 mRNA. Translation: BAA92137.1.
AY874864 Genomic DNA. Translation: AAW49735.1.
AL512328 Genomic DNA. No translation available.
FO393421 Genomic DNA. No translation available.
CCDSiCCDS1586.1. [O14815-1]
CCDS31053.1. [O14815-2]
RefSeqiNP_001306605.1. NM_001319676.1.
NP_006606.1. NM_006615.2. [O14815-1]
NP_057536.1. NM_016452.2. [O14815-2]
UniGeneiHs.498021.

Genome annotation databases

EnsembliENST00000271971; ENSP00000271971; ENSG00000135773. [O14815-1]
ENST00000354537; ENSP00000346538; ENSG00000135773. [O14815-2]
GeneIDi10753.
KEGGihsa:10753.
UCSCiuc001htz.2. human. [O14815-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF022799 mRNA. Translation: AAB80762.1.
AB038463 mRNA. Translation: BAA92137.1.
AY874864 Genomic DNA. Translation: AAW49735.1.
AL512328 Genomic DNA. No translation available.
FO393421 Genomic DNA. No translation available.
CCDSiCCDS1586.1. [O14815-1]
CCDS31053.1. [O14815-2]
RefSeqiNP_001306605.1. NM_001319676.1.
NP_006606.1. NM_006615.2. [O14815-1]
NP_057536.1. NM_016452.2. [O14815-2]
UniGeneiHs.498021.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ZIVX-ray2.31A28-347[»]
2P0RX-ray2.50A/B10-340[»]
ProteinModelPortaliO14815.
SMRiO14815.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115976. 2 interactors.
STRINGi9606.ENSP00000271971.

Protein family/group databases

MEROPSiC02.006.

PTM databases

iPTMnetiO14815.
PhosphoSitePlusiO14815.

Polymorphism and mutation databases

BioMutaiCAPN9.

Proteomic databases

PaxDbiO14815.
PeptideAtlasiO14815.
PRIDEiO14815.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000271971; ENSP00000271971; ENSG00000135773. [O14815-1]
ENST00000354537; ENSP00000346538; ENSG00000135773. [O14815-2]
GeneIDi10753.
KEGGihsa:10753.
UCSCiuc001htz.2. human. [O14815-1]

Organism-specific databases

CTDi10753.
DisGeNETi10753.
GeneCardsiCAPN9.
HGNCiHGNC:1486. CAPN9.
HPAiCAB033483.
HPA020398.
MIMi606401. gene.
neXtProtiNX_O14815.
OpenTargetsiENSG00000135773.
PharmGKBiPA26066.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0045. Eukaryota.
ENOG410XP0B. LUCA.
GeneTreeiENSGT00760000118971.
HOGENOMiHOG000232035.
HOVERGENiHBG012645.
InParanoidiO14815.
KOiK08578.
OMAiHEIAENP.
OrthoDBiEOG091G049E.
PhylomeDBiO14815.
TreeFamiTF314748.

Enzyme and pathway databases

BRENDAi3.4.22.B29. 2681.
ReactomeiR-HSA-1474228. Degradation of the extracellular matrix.

Miscellaneous databases

EvolutionaryTraceiO14815.
GeneWikiiCAPN9.
GenomeRNAii10753.
PROiO14815.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000135773.
CleanExiHS_CAPN9.
ExpressionAtlasiO14815. baseline and differential.
GenevisibleiO14815. HS.

Family and domain databases

CDDicd00214. Calpain_III. 1 hit.
cd00044. CysPc. 1 hit.
cd00051. EFh. 1 hit.
Gene3Di1.10.238.10. 1 hit.
InterProiIPR033883. C2_III.
IPR022684. Calpain_cysteine_protease.
IPR022682. Calpain_domain_III.
IPR022683. Calpain_III.
IPR029542. CAPN9.
IPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR000169. Pept_cys_AS.
IPR001300. Peptidase_C2_calpain_cat.
[Graphical view]
PANTHERiPTHR10183:SF311. PTHR10183:SF311. 1 hit.
PfamiPF01067. Calpain_III. 1 hit.
PF13833. EF-hand_8. 1 hit.
PF00648. Peptidase_C2. 1 hit.
[Graphical view]
PRINTSiPR00704. CALPAIN.
SMARTiSM00720. calpain_III. 1 hit.
SM00230. CysPc. 1 hit.
SM00054. EFh. 2 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
SSF49758. SSF49758. 1 hit.
PROSITEiPS50203. CALPAIN_CAT. 1 hit.
PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 3 hits.
PS00139. THIOL_PROTEASE_CYS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCAN9_HUMAN
AccessioniPrimary (citable) accession number: O14815
Secondary accession number(s): B1APS1, B1AQI0, Q9NS74
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 16, 2003
Last sequence update: January 1, 1998
Last modified: November 30, 2016
This is version 149 of the entry and version 1 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 1
    Human chromosome 1: 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

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 one 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.