O14815 (CAN9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	CAPN9
Synonyms:	NCL4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	690 AA.
Sequence status	Complete.
Protein existence	Evidence 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 diversity	Alternative splicing Polymorphism
Domain	Repeat
Ligand	Calcium Metal-binding
Molecular function	Hydrolase Protease Thiol protease
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	digestion Traceable author statement Ref.1. Source: ProtInc proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	intracellular Inferred from electronic annotation. Source: InterPro
Molecular_function	calcium ion binding Traceable author statement Ref.1. Source: ProtInc calcium-dependent cysteine-type endopeptidase activity Traceable author statement Ref.1. 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 690

690

Calpain-9

PRO_0000207722

Regions

Domain

42 – 337

296

Calpain catalytic

Domain

518 – 552

35

EF-hand 1

Domain

561 – 594

34

EF-hand 2

Domain

591 – 626

36

EF-hand 3

Calcium binding

574 – 585

12

1 Potential

Calcium binding

604 – 615

12

2 Potential

Region

338 – 521

184

Domain III

Region

522 – 690

169

Domain IV

Sites

Active site

97

1

Ref.5

Active site

254

1

Ref.5

Active site

278

1

Ref.5

Metal binding

81

1

Calcium 1; via carbonyl oxygen

Metal binding

83

1

Calcium 1; via carbonyl oxygen

Metal binding

88

1

Calcium 1

Metal binding

167

1

Calcium 1

Metal binding

284

1

Calcium 2

Metal binding

291

1

Calcium 2

Metal binding

312

1

Calcium 2; via carbonyl oxygen

Metal binding

314

1

Calcium 2

Metal binding

316

1

Calcium 2; via carbonyl oxygen

Natural variations

Alternative sequence

292 – 318

27

SSPEW…DGEFW → R in isoform 2.

VSP_007553

Natural variant

102

1

A → V. Ref.3
Corresponds to variant rs12562749 [ dbSNP | Ensembl ].

VAR_022188

Natural variant

122

1

S → R. Ref.3
Corresponds to variant rs28359608 [ dbSNP | Ensembl ].

VAR_022189

Natural variant

164

1

D → N. Ref.3
Corresponds to variant rs28359632 [ dbSNP | Ensembl ].

VAR_022190

Natural variant

234

1

I → T. Ref.3
Corresponds to variant rs28359644 [ dbSNP | Ensembl ].

VAR_022191

Natural variant

239

1

A → T. Ref.3
Corresponds to variant rs28359647 [ dbSNP | Ensembl ].

VAR_022192

Natural variant

277

1

R → W. Ref.3
Corresponds to variant rs28359655 [ dbSNP | Ensembl ].

VAR_022193

Natural variant

322

1

K → Q. Ref.3
Corresponds to variant rs1933631 [ dbSNP | Ensembl ].

VAR_022194

Natural variant

327

1

H → Q. Ref.3
Corresponds to variant rs28359684 [ dbSNP | Ensembl ].

VAR_022195

Natural variant

342

1

E → K. Ref.3
Corresponds to variant rs16852652 [ dbSNP | Ensembl ].

VAR_022196

Natural variant

458

1

R → W. Ref.3
Corresponds to variant rs28359688 [ dbSNP | Ensembl ].

VAR_022197

Natural variant

522

1

R → W. Ref.3
Corresponds to variant rs12731961 [ dbSNP | Ensembl ].

VAR_022198

Natural variant

611

1

M → I. Ref.3
Corresponds to variant rs16852683 [ dbSNP | Ensembl ].

VAR_022199

Secondary structure

1

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690

Helix Strand Turn

Details...

Helix

29 – 38

10

Beta strand

46 – 48

3

Helix

52 – 54

3

Beta strand

57 – 59

3

Beta strand

66 – 68

3

Helix

70 – 72

3

Beta strand

74 – 76

3

Beta strand

78 – 80

3

Helix

86 – 88

3

Beta strand

93 – 95

3

Helix

98 – 107

10

Helix

110 – 116

7

Beta strand

129 – 136

8

Beta strand

138 – 147

10

Beta strand

150 – 161

12

Helix

169 – 181

13

Helix

185 – 187

3

Beta strand

188 – 190

3

Helix

192 – 200

9

Beta strand

205 – 208

4

Helix

209 – 211

3

Helix

216 – 226

11

Beta strand

229 – 233

5

Helix

239 – 241

3

Beta strand

256 – 266

11

Beta strand

269 – 277

9

Helix

294 – 298

5

Helix

301 – 306

6

Beta strand

313 – 320

8

Helix

321 – 327

7

Beta strand

330 – 334

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 02176C04BE1E5C23	FASTA	690	79,097
	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
	Isoform 2 (CG36) [UniParc]. Checksum: 8D0524E4A476159D	FASTA	664	76,168
	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 DRMAFKDFKA 310 320 330 340 350 360 HFDKVEICNL TPDALEEDAI HKWEVTVHQG SWVRGSTAGG CRNFLDTFWT NPQIKLSLTE 370 380 390 400 410 420 KDEGQEECSF LVALMQKDRR KLKRFGANVL TIGYAIYECP DKDEHLNKDF FRYHASRARS 430 440 450 460 470 480 KTFINLREVS DRFKLPPGEY ILIPSTFEPH QEADFCLRIF SEKKAITRDM DGNVDIDLPE 490 500 510 520 530 540 PPKPTPPDQE TEEEQRFRAL FEQVAGEDME VTAEELEYVL NAVLQKKKDI KFKKLSLISC 550 560 570 580 590 600 KNIISLMDTS GNGKLEFDEF KVFWDKLKQW INLFLRFDAD KSGTMSTYEL RTALKAAGFQ 610 620 630 640 650 660 LSSHLLQLIV LRYADEELQL DFDDFLNCLV RLENASRVFQ ALSTKNKEFI HLNINEFIHL TMNI

References

	« Hide 'large scale' referencesShow '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. , 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

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF022799 mRNA. Translation: AAB80762.1.
AB038463 mRNA. Translation: BAA92137.1.
AY874864 Genomic DNA. Translation: AAW49735.1.
AL591291, AL512328 Genomic DNA. Translation: CAI17215.1.
AL591291, AL512328 Genomic DNA. Translation: CAI17214.1.

IPI

IPI00009063.
IPI00016919.

RefSeq

NP_006606.1. NM_006615.2.
NP_057536.1. NM_016452.1.

UniGene

Hs.498021.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ZIV	X-ray	2.31	A	28-347	[»]
2P0R	X-ray	2.50	A/B	10-340	[»]

ProteinModelPortal

O14815.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000271971.

Protein family/group databases

MEROPS

C02.006.

PTM databases

PhosphoSite

O14815.

Proteomic databases

PaxDb

O14815.

PRIDE

O14815.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000271971; ENSP00000271971; ENSG00000135773.
ENST00000354537; ENSP00000346538; ENSG00000135773.

GeneID

10753.

KEGG

hsa:10753.

UCSC

uc001htz.1. human.
uc001hua.1. human.

Organism-specific databases

CTD

10753.

GeneCards

GC01P230883.

HGNC

HGNC:1486. CAPN9.

HPA

CAB033483.
HPA020398.

MIM

606401. gene.

neXtProt

NX_O14815.

PharmGKB

PA26066.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG327523.

HOGENOM

HOG000232035.

HOVERGEN

HBG012645.

InParanoid

O14815.

KO

K08578.

OMA

FFRYHAS.

OrthoDB

EOG41ZF9D.

PhylomeDB

O14815.

Gene expression databases

ArrayExpress

O14815.

Bgee

O14815.

CleanEx

HS_CAPN9.

Genevestigator

O14815.

GermOnline

ENSG00000135773. Homo sapiens.

Family and domain databases

Gene3D

1.10.238.10. 1 hit.

InterPro

IPR022684. Calpain_cysteine_protease.
IPR022682. Calpain_domain_III.
IPR022683. Calpain_III.
IPR011992. EF-hand-like_dom.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR000169. Pept_cys_AS.
IPR001300. Peptidase_C2_calpain_cat.
[Graphical view]

Pfam

PF01067. Calpain_III. 1 hit.
PF13405. EF_hand_4. 1 hit.
PF00648. Peptidase_C2. 1 hit.
[Graphical view]

PRINTS

PR00704. CALPAIN.

SMART

SM00720. calpain_III. 1 hit.
SM00230. CysPc. 1 hit.
SM00054. EFh. 2 hits.
[Graphical view]

SUPFAM

SSF49758. Peptidase_C2. 1 hit.

PROSITE

PS50203. CALPAIN_CAT. 1 hit.
PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 3 hits.
PS00640. THIOL_PROTEASE_ASN. False negative.
PS00139. THIOL_PROTEASE_CYS. 1 hit.
PS00639. THIOL_PROTEASE_HIS. False negative.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O14815.

GenomeRNAi

10753.

NextBio

40837.

SOURCE

Search...

Entry information

Entry name

CAN9_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.