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O14815

- CAN9_HUMAN

UniProt

O14815 - CAN9_HUMAN

Protein

Calpain-9

Gene

CAPN9

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 126 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      Previous versions | rss
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    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

    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

    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

    ArrayExpressiO14815.
    BgeeiO14815.
    CleanExiHS_CAPN9.
    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 – 3810
    Beta strandi46 – 483
    Helixi52 – 543
    Beta strandi57 – 593
    Beta strandi66 – 683
    Helixi70 – 723
    Beta strandi74 – 763
    Beta strandi78 – 803
    Helixi86 – 883
    Beta strandi93 – 953
    Helixi98 – 10710
    Helixi110 – 1167
    Beta strandi129 – 1368
    Beta strandi138 – 14710
    Beta strandi150 – 16112
    Helixi169 – 18113
    Helixi185 – 1873
    Beta strandi188 – 1903
    Helixi192 – 2009
    Beta strandi205 – 2084
    Helixi209 – 2113
    Helixi216 – 22611
    Beta strandi229 – 2335
    Helixi239 – 2413
    Beta strandi256 – 26611
    Beta strandi269 – 2779
    Helixi294 – 2985
    Helixi301 – 3066
    Beta strandi313 – 3208
    Helixi321 – 3277
    Beta strandi330 – 3345

    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.
    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

    MPYLYRAPGP QAHPVPKDAR ITHSSGQSFE QMRQECLQRG TLFEDADFPA    50
    SNSSLFYSER PQIPFVWKRP GEIVKNPEFI LGGATRTDIC QGELGDCWLL 100
    AAIASLTLNQ KALARVIPQD QSFGPGYAGI FHFQFWQHSE WLDVVIDDRL 150
    PTFRDRLVFL HSADHNEFWS ALLEKAYAKL NGSYEALKGG SAIEAMEDFT 200
    GGVAETFQTK EAPENFYEIL EKALKRGSLL GCFIDTRSAA ESEARTPFGL 250
    IKGHAYSVTG IDQVSFRGQR IELIRIRNPW GQVEWNGSWS DSSPEWRSVG 300
    PAEQKRLCHT ALDDGEFWMA FKDFKAHFDK VEICNLTPDA LEEDAIHKWE 350
    VTVHQGSWVR GSTAGGCRNF LDTFWTNPQI KLSLTEKDEG QEECSFLVAL 400
    MQKDRRKLKR FGANVLTIGY AIYECPDKDE HLNKDFFRYH ASRARSKTFI 450
    NLREVSDRFK LPPGEYILIP STFEPHQEAD FCLRIFSEKK AITRDMDGNV 500
    DIDLPEPPKP TPPDQETEEE QRFRALFEQV AGEDMEVTAE ELEYVLNAVL 550
    QKKKDIKFKK LSLISCKNII SLMDTSGNGK LEFDEFKVFW DKLKQWINLF 600
    LRFDADKSGT MSTYELRTAL KAAGFQLSSH LLQLIVLRYA DEELQLDFDD 650
    FLNCLVRLEN ASRVFQALST KNKEFIHLNI NEFIHLTMNI 690
    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.
    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

    ArrayExpressi O14815.
    Bgeei O14815.
    CleanExi HS_CAPN9.
    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

    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 1, 2014
    This is version 126 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