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O14815 (CAN9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 121. 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·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Calpain-9

EC=3.4.22.-
Alternative name(s):
Digestive tract-specific calpain
New calpain 4
Short name=nCL-4
Protein CG36
Gene names
Name:CAPN9
Synonyms:NCL4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length690 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Calcium-regulated non-lysosomal thiol-protease.

Catalytic activity

Broad endopeptidase specificity.

Tissue specificity

Expressed predominantly in stomach.

Induction

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

Sequence similarities

Belongs to the peptidase C2 family.

Contains 1 calpain catalytic domain.

Contains 3 EF-hand domains.

Ontologies

Keywords
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
   LigandCalcium
Metal-binding
   Molecular functionHydrolase
Protease
Thiol protease
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdigestion

Traceable author statement Ref.1. Source: ProtInc

proteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentintracellular

Inferred from electronic annotation. Source: InterPro

   Molecular_functioncalcium ion binding

Traceable author statement Ref.1. Source: ProtInc

calcium-dependent cysteine-type endopeptidase activity

Traceable author statement. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O14815-1)

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 2 (identifier: O14815-2)

Also known as: CG36;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 690690Calpain-9
PRO_0000207722

Regions

Domain42 – 337296Calpain catalytic
Domain518 – 55235EF-hand 1
Domain561 – 59434EF-hand 2
Domain591 – 62636EF-hand 3
Calcium binding574 – 585121 Potential
Calcium binding604 – 615122 Potential
Region338 – 521184Domain III
Region522 – 690169Domain IV

Sites

Active site971 Ref.5
Active site2541 Ref.5
Active site2781 Ref.5
Metal binding811Calcium 1; via carbonyl oxygen
Metal binding831Calcium 1; via carbonyl oxygen
Metal binding881Calcium 1
Metal binding1671Calcium 1
Metal binding2841Calcium 2
Metal binding2911Calcium 2
Metal binding3121Calcium 2; via carbonyl oxygen
Metal binding3141Calcium 2
Metal binding3161Calcium 2; via carbonyl oxygen

Natural variations

Alternative sequence292 – 31827SSPEW…DGEFW → R in isoform 2.
VSP_007553
Natural variant1021A → V. Ref.3
Corresponds to variant rs12562749 [ dbSNP | Ensembl ].
VAR_022188
Natural variant1221S → R. Ref.3
Corresponds to variant rs28359608 [ dbSNP | Ensembl ].
VAR_022189
Natural variant1641D → N. Ref.3
Corresponds to variant rs28359632 [ dbSNP | Ensembl ].
VAR_022190
Natural variant2341I → T. Ref.3
Corresponds to variant rs28359644 [ dbSNP | Ensembl ].
VAR_022191
Natural variant2391A → T. Ref.3
Corresponds to variant rs28359647 [ dbSNP | Ensembl ].
VAR_022192
Natural variant2771R → W. Ref.3
Corresponds to variant rs28359655 [ dbSNP | Ensembl ].
VAR_022193
Natural variant3221K → Q. Ref.3
Corresponds to variant rs1933631 [ dbSNP | Ensembl ].
VAR_022194
Natural variant3271H → Q. Ref.3
Corresponds to variant rs28359684 [ dbSNP | Ensembl ].
VAR_022195
Natural variant3421E → K. Ref.3
Corresponds to variant rs16852652 [ dbSNP | Ensembl ].
VAR_022196
Natural variant4581R → W. Ref.3
Corresponds to variant rs28359688 [ dbSNP | Ensembl ].
VAR_022197
Natural variant5221R → W. Ref.3
Corresponds to variant rs12731961 [ dbSNP | Ensembl ].
VAR_022198
Natural variant6111M → I. Ref.3
Corresponds to variant rs16852683 [ dbSNP | Ensembl ].
VAR_022199

Secondary structure

............................................................ 690
Helix Strand Turn

Details...

Sequences

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

Last modified January 1, 1998. Version 1.
Checksum: 02176C04BE1E5C23

FASTA69079,097
        10         20         30         40         50         60 
MPYLYRAPGP QAHPVPKDAR ITHSSGQSFE QMRQECLQRG TLFEDADFPA SNSSLFYSER 

        70         80         90        100        110        120 
PQIPFVWKRP GEIVKNPEFI LGGATRTDIC QGELGDCWLL AAIASLTLNQ KALARVIPQD 

       130        140        150        160        170        180 
QSFGPGYAGI FHFQFWQHSE WLDVVIDDRL PTFRDRLVFL HSADHNEFWS ALLEKAYAKL 

       190        200        210        220        230        240 
NGSYEALKGG SAIEAMEDFT GGVAETFQTK EAPENFYEIL EKALKRGSLL GCFIDTRSAA 

       250        260        270        280        290        300 
ESEARTPFGL IKGHAYSVTG IDQVSFRGQR IELIRIRNPW GQVEWNGSWS DSSPEWRSVG 

       310        320        330        340        350        360 
PAEQKRLCHT ALDDGEFWMA FKDFKAHFDK VEICNLTPDA LEEDAIHKWE VTVHQGSWVR 

       370        380        390        400        410        420 
GSTAGGCRNF LDTFWTNPQI KLSLTEKDEG QEECSFLVAL MQKDRRKLKR FGANVLTIGY 

       430        440        450        460        470        480 
AIYECPDKDE HLNKDFFRYH ASRARSKTFI NLREVSDRFK LPPGEYILIP STFEPHQEAD 

       490        500        510        520        530        540 
FCLRIFSEKK AITRDMDGNV DIDLPEPPKP TPPDQETEEE QRFRALFEQV AGEDMEVTAE 

       550        560        570        580        590        600 
ELEYVLNAVL QKKKDIKFKK LSLISCKNII SLMDTSGNGK LEFDEFKVFW DKLKQWINLF 

       610        620        630        640        650        660 
LRFDADKSGT MSTYELRTAL KAAGFQLSSH LLQLIVLRYA DEELQLDFDD FLNCLVRLEN 

       670        680        690 
ASRVFQALST KNKEFIHLNI NEFIHLTMNI 

« Hide

Isoform 2 (CG36) [UniParc].

Checksum: 8D0524E4A476159D
Show »

FASTA66476,168

References

« Hide 'large scale' references
[1]"Molecular cloning and characterization of a novel tissue-specific calpain predominantly expressed in the digestive tract."
Lee H.-J., Sorimachi H., Jeong S.-Y., Ishiura S., Suzuki K.
Biol. Chem. 379:175-183(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Stomach.
[2]"Isolation of two novel genes, down-regulated in gastric cancer."
Yoshikawa Y., Mukai H., Hino F., Asada K., Kato I.
Jpn. J. Cancer Res. 91:459-463(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]NIEHS SNPs program
Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-102; ARG-122; ASN-164; THR-234; THR-239; TRP-277; GLN-322; GLN-327; LYS-342; TRP-458; TRP-522 AND ILE-611.
[4]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The crystal structures of human calpains 1 and 9 imply diverse mechanisms of action and auto-inhibition."
Davis T.L., Walker J.R., Finerty P.J. Jr., Mackenzie F., Newman E.M., Dhe-Paganon S.
J. Mol. Biol. 366:216-229(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.31 ANGSTROMS) OF 28-347, ACTIVE SITE, CALCIUM-BINDING SITES.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_006606.1. NM_006615.2.
NP_057536.1. NM_016452.1.
UniGeneHs.498021.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ZIVX-ray2.31A28-347[»]
2P0RX-ray2.50A/B10-340[»]
ProteinModelPortalO14815.
SMRO14815. Positions 19-688.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000271971.

Protein family/group databases

MEROPSC02.006.

PTM databases

PhosphoSiteO14815.

Proteomic databases

PaxDbO14815.
PRIDEO14815.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000271971; ENSP00000271971; ENSG00000135773. [O14815-1]
ENST00000354537; ENSP00000346538; ENSG00000135773. [O14815-2]
GeneID10753.
KEGGhsa:10753.
UCSCuc001htz.1. human. [O14815-1]
uc001hua.1. human. [O14815-2]

Organism-specific databases

CTD10753.
GeneCardsGC01P230883.
HGNCHGNC:1486. CAPN9.
HPACAB033483.
HPA020398.
MIM606401. gene.
neXtProtNX_O14815.
PharmGKBPA26066.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG327523.
HOGENOMHOG000232035.
HOVERGENHBG012645.
InParanoidO14815.
KOK08578.
OMAFFRYHAS.
OrthoDBEOG7RV9FM.
PhylomeDBO14815.
TreeFamTF314748.

Gene expression databases

ArrayExpressO14815.
BgeeO14815.
CleanExHS_CAPN9.
GenevestigatorO14815.

Family and domain databases

Gene3D1.10.238.10. 1 hit.
InterProIPR022684. Calpain_cysteine_protease.
IPR022682. Calpain_domain_III.
IPR022683. Calpain_III.
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]
PfamPF01067. Calpain_III. 1 hit.
PF13405. EF-hand_6. 1 hit.
PF00648. Peptidase_C2. 1 hit.
[Graphical view]
PRINTSPR00704. CALPAIN.
SMARTSM00720. calpain_III. 1 hit.
SM00230. CysPc. 1 hit.
SM00054. EFh. 2 hits.
[Graphical view]
SUPFAMSSF49758. SSF49758. 1 hit.
PROSITEPS50203. CALPAIN_CAT. 1 hit.
PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 3 hits.
PS00139. THIOL_PROTEASE_CYS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO14815.
GeneWikiCAPN9.
GenomeRNAi10753.
NextBio40837.
PROO14815.
SOURCESearch...

Entry information

Entry nameCAN9_HUMAN
AccessionPrimary (citable) accession number: O14815
Secondary accession number(s): B1APS1, B1AQI0, Q9NS74
Entry history
Integrated into UniProtKB/Swiss-Prot: June 16, 2003
Last sequence update: January 1, 1998
Last modified: March 19, 2014
This is version 121 of the entry and version 1 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 1

Human chromosome 1: entries, gene names and cross-references to MIM