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O14815

- CAN9_HUMAN

UniProt

O14815 - CAN9_HUMAN

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Protein

Calpain-9

Gene

CAPN9

Organism
Homo sapiens (Human)
Status
Reviewed - 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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi81 – 811Calcium 1; via carbonyl oxygen
Metal bindingi83 – 831Calcium 1; via carbonyl oxygen
Metal bindingi88 – 881Calcium 1
Active sitei97 – 9711 Publication
Metal bindingi167 – 1671Calcium 1
Active sitei254 – 25411 Publication
Active sitei278 – 27811 Publication
Metal bindingi284 – 2841Calcium 2
Metal bindingi291 – 2911Calcium 2
Metal bindingi312 – 3121Calcium 2; via carbonyl oxygen
Metal bindingi314 – 3141Calcium 2
Metal bindingi316 – 3161Calcium 2; via carbonyl oxygen

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi574 – 585121PROSITE-ProRule annotationAdd
BLAST
Calcium bindingi604 – 615122PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. calcium-dependent cysteine-type endopeptidase activity Source: RefGenome
  2. calcium ion binding Source: ProtInc

GO - Biological processi

  1. digestion Source: ProtInc
  2. proteolysis Source: RefGenome
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Ligandi

Calcium, Metal-binding

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
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:1486. CAPN9.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: RefGenome
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA26066.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 690690Calpain-9PRO_0000207722Add
BLAST

Proteomic databases

PaxDbiO14815.
PRIDEiO14815.

PTM databases

PhosphoSiteiO14815.

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

BgeeiO14815.
CleanExiHS_CAPN9.
ExpressionAtlasiO14815. baseline and differential.
GenevestigatoriO14815.

Organism-specific databases

HPAiCAB033483.
HPA020398.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000271971.

Structurei

Secondary structure

1
690
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi29 – 3810Combined sources
Beta strandi46 – 483Combined sources
Helixi52 – 543Combined sources
Beta strandi57 – 593Combined sources
Beta strandi66 – 683Combined sources
Helixi70 – 723Combined sources
Beta strandi74 – 763Combined sources
Beta strandi78 – 803Combined sources
Helixi86 – 883Combined sources
Beta strandi93 – 953Combined sources
Helixi98 – 10710Combined sources
Helixi110 – 1167Combined sources
Beta strandi129 – 1368Combined sources
Beta strandi138 – 14710Combined sources
Beta strandi150 – 16112Combined sources
Helixi169 – 18113Combined sources
Helixi185 – 1873Combined sources
Beta strandi188 – 1903Combined sources
Helixi192 – 2009Combined sources
Beta strandi205 – 2084Combined sources
Helixi209 – 2113Combined sources
Helixi216 – 22611Combined sources
Beta strandi229 – 2335Combined sources
Helixi239 – 2413Combined sources
Beta strandi256 – 26611Combined sources
Beta strandi269 – 2779Combined sources
Helixi294 – 2985Combined sources
Helixi301 – 3066Combined sources
Beta strandi313 – 3208Combined sources
Helixi321 – 3277Combined sources
Beta strandi330 – 3345Combined sources

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1ZIVX-ray2.31A28-347[»]
2P0RX-ray2.50A/B10-340[»]
ProteinModelPortaliO14815.
SMRiO14815. Positions 19-688.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO14815.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini42 – 337296Calpain catalyticPROSITE-ProRule annotationAdd
BLAST
Domaini518 – 55235EF-hand 1PROSITE-ProRule annotationAdd
BLAST
Domaini561 – 59434EF-hand 2PROSITE-ProRule annotationAdd
BLAST
Domaini591 – 62636EF-hand 3PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni338 – 521184Domain IIIAdd
BLAST
Regioni522 – 690169Domain IVAdd
BLAST

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

eggNOGiNOG327523.
GeneTreeiENSGT00760000118971.
HOGENOMiHOG000232035.
HOVERGENiHBG012645.
InParanoidiO14815.
KOiK08578.
OMAiEQKRLCH.
OrthoDBiEOG7RV9FM.
PhylomeDBiO14815.
TreeFamiTF314748.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR022684. 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:SF136. PTHR10183:SF136. 1 hit.
PfamiPF01067. Calpain_III. 1 hit.
PF13405. EF-hand_6. 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]
SUPFAMiSSF49758. 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. Align

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti102 – 1021A → V.1 Publication
Corresponds to variant rs12562749 [ dbSNP | Ensembl ].
VAR_022188
Natural varianti122 – 1221S → R.1 Publication
Corresponds to variant rs28359608 [ dbSNP | Ensembl ].
VAR_022189
Natural varianti164 – 1641D → N.1 Publication
Corresponds to variant rs28359632 [ dbSNP | Ensembl ].
VAR_022190
Natural varianti234 – 2341I → T.1 Publication
Corresponds to variant rs28359644 [ dbSNP | Ensembl ].
VAR_022191
Natural varianti239 – 2391A → T.1 Publication
Corresponds to variant rs28359647 [ dbSNP | Ensembl ].
VAR_022192
Natural varianti277 – 2771R → W.1 Publication
Corresponds to variant rs28359655 [ dbSNP | Ensembl ].
VAR_022193
Natural varianti322 – 3221K → Q.1 Publication
Corresponds to variant rs1933631 [ dbSNP | Ensembl ].
VAR_022194
Natural varianti327 – 3271H → Q.1 Publication
Corresponds to variant rs28359684 [ dbSNP | Ensembl ].
VAR_022195
Natural varianti342 – 3421E → K.1 Publication
Corresponds to variant rs16852652 [ dbSNP | Ensembl ].
VAR_022196
Natural varianti458 – 4581R → W.1 Publication
Corresponds to variant rs28359688 [ dbSNP | Ensembl ].
VAR_022197
Natural varianti522 – 5221R → W.1 Publication
Corresponds to variant rs12731961 [ dbSNP | Ensembl ].
VAR_022198
Natural varianti611 – 6111M → I.1 Publication
Corresponds to variant rs16852683 [ dbSNP | Ensembl ].
VAR_022199

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei292 – 31827SSPEW…DGEFW → R in isoform 2. 1 PublicationVSP_007553Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_006606.1. NM_006615.2. [O14815-1]
NP_057536.1. NM_016452.1. [O14815-2]
UniGeneiHs.498021.

Genome annotation databases

EnsembliENST00000271971; ENSP00000271971; ENSG00000135773. [O14815-1]
ENST00000354537; ENSP00000346538; ENSG00000135773. [O14815-2]
GeneIDi10753.
KEGGihsa:10753.
UCSCiuc001htz.1. human. [O14815-1]
uc001hua.1. human. [O14815-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
CCDSi CCDS1586.1. [O14815-1 ]
CCDS31053.1. [O14815-2 ]
RefSeqi NP_006606.1. NM_006615.2. [O14815-1 ]
NP_057536.1. NM_016452.1. [O14815-2 ]
UniGenei Hs.498021.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1ZIV X-ray 2.31 A 28-347 [» ]
2P0R X-ray 2.50 A/B 10-340 [» ]
ProteinModelPortali O14815.
SMRi O14815. Positions 19-688.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9606.ENSP00000271971.

Protein family/group databases

MEROPSi C02.006.

PTM databases

PhosphoSitei O14815.

Proteomic databases

PaxDbi O14815.
PRIDEi O14815.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000271971 ; ENSP00000271971 ; ENSG00000135773 . [O14815-1 ]
ENST00000354537 ; ENSP00000346538 ; ENSG00000135773 . [O14815-2 ]
GeneIDi 10753.
KEGGi hsa:10753.
UCSCi uc001htz.1. human. [O14815-1 ]
uc001hua.1. human. [O14815-2 ]

Organism-specific databases

CTDi 10753.
GeneCardsi GC01P230883.
HGNCi HGNC:1486. CAPN9.
HPAi CAB033483.
HPA020398.
MIMi 606401. gene.
neXtProti NX_O14815.
PharmGKBi PA26066.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG327523.
GeneTreei ENSGT00760000118971.
HOGENOMi HOG000232035.
HOVERGENi HBG012645.
InParanoidi O14815.
KOi K08578.
OMAi EQKRLCH.
OrthoDBi EOG7RV9FM.
PhylomeDBi O14815.
TreeFami TF314748.

Miscellaneous databases

EvolutionaryTracei O14815.
GeneWikii CAPN9.
GenomeRNAii 10753.
NextBioi 40837.
PROi O14815.
SOURCEi Search...

Gene expression databases

Bgeei O14815.
CleanExi HS_CAPN9.
ExpressionAtlasi O14815. baseline and differential.
Genevestigatori O14815.

Family and domain databases

Gene3Di 1.10.238.10. 1 hit.
InterProi 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 ]
PANTHERi PTHR10183:SF136. PTHR10183:SF136. 1 hit.
Pfami PF01067. Calpain_III. 1 hit.
PF13405. EF-hand_6. 1 hit.
PF00648. Peptidase_C2. 1 hit.
[Graphical view ]
PRINTSi PR00704. CALPAIN.
SMARTi SM00720. calpain_III. 1 hit.
SM00230. CysPc. 1 hit.
SM00054. EFh. 2 hits.
[Graphical view ]
SUPFAMi SSF49758. SSF49758. 1 hit.
PROSITEi PS50203. CALPAIN_CAT. 1 hit.
PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 3 hits.
PS00139. THIOL_PROTEASE_CYS. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.

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: October 29, 2014
This is version 127 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

External Data

Dasty 3