Reviewed, UniProtKB/Swiss-Prot P17655 (CAN2_HUMAN)

Names and origin

Protein names

Recommended name:
    Calpain-2 catalytic subunit
    EC=3.4.22.53
Alternative name(s):
    Calpain-2 large subunit
    Calcium-activated neutral proteinase 2
      Short name=CANP 2
    Calpain M-type
    M-calpain
    Millimolar-calpain
    Calpain large polypeptide L2

Gene names

Name:	CAPN2
Synonyms:	CANPL2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	700 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Calcium-regulated non-lysosomal thiol-protease which catalyze limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction.
Catalytic activity	Broad endopeptidase specificity.
Cofactor	Binds 3 calcium ions.
Enzyme regulation	Activated by 200-1000 micromolar concentrations of calcium and inhibited by calpastatin.
Subunit structure	Forms a heterodimer with a small (regulatory) subunit (CAPNS1).
Subcellular location	Cytoplasm. Cell membrane. Note: Translocates to the plasma membrane upon Ca2+ binding.
Tissue specificity	Ubiquitous.
Sequence similarities	Belongs to the peptidase C2 family. Contains 1 calpain catalytic domain. Contains 3 EF-hand domains.
Sequence caution	The sequence AAH07686.1 differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Potential poly-A sequence. The sequence AAH11828.1 differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Potential poly-A sequence.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	Calcium
Molecular function	Hydrolase Protease Thiol protease
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW calcium-dependent cysteine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro protein binding Ref.9 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CAPNS1	P04632	1	EBI-1028956,EBI-711828

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.7

Propeptide

2 – 19

18

Anchors to the small subunit Potential

PRO_0000026487

Chain

20 – 700

681

Calpain-2 catalytic subunit

PRO_0000026488

Regions

Domain

45 – 344

300

Calpain catalytic

Domain

572 – 605

34

EF-hand 1

Domain

602 – 637

36

EF-hand 2

Domain

667 – 700

34

EF-hand 3

Calcium binding

585 – 596

12

1

Calcium binding

615 – 626

12

2

Region

345 – 514

170

Domain III

Region

515 – 529

15

Linker

Region

530 – 700

171

Domain IV

Sites

Active site

105

1

By similarity

Active site

262

1

By similarity

Active site

286

1

By similarity

Natural variations

Natural variant

22

1

E → D: dbSNP rs25655.

VAR_014435

Natural variant

68

1

S → G: dbSNP rs2230083. Ref.3 Ref.6

VAR_021404

Natural variant

476

1

K → R: dbSNP rs9804140. Ref.3

VAR_021405

Natural variant

521

1

E → Q Ref.3

VAR_021406

Natural variant

568

1

K → Q: dbSNP rs17599. Ref.3

VAR_014436

Natural variant

677

1

K → Q Ref.3

VAR_021407

Experimental info

Sequence conflict

73 – 74

2

IE → MR in AAA35645. Ref.1

Sequence conflict

256

1

Q → K in AAF99682. Ref.2

Sequence conflict

300

1

N → S in AAF99682. Ref.2

Sequence conflict

436

1

V → N in AC099065. Ref.4

Sequence conflict

438

1

E → D in AC099065. Ref.4

Sequence conflict

534

1

F → V in AAA35645. Ref.1

Sequence conflict

534

1

F → V in AAF99682. Ref.2

Secondary structure

1

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700

Helix Strand Turn

Details...

Helix

4 – 16

13

Turn

17 – 19

3

Helix

27 – 29

3

Helix

32 – 42

11

Helix

55 – 58

4

Beta strand

74 – 76

3

Helix

78 – 81

4

Helix

94 – 96

3

Helix

105 – 115

11

Helix

118 – 124

7

Beta strand

136 – 144

9

Beta strand

146 – 155

10

Beta strand

158 – 161

4

Beta strand

164 – 167

4

Helix

177 – 189

13

Beta strand

190 – 192

3

Helix

193 – 195

3

Beta strand

196 – 199

4

Turn

204 – 206

3

Helix

207 – 209

3

Beta strand

212 – 216

5

Helix

224 – 233

10

Beta strand

237 – 241

5

Helix

247 – 249

3

Beta strand

259 – 261

3

Beta strand

264 – 274

11

Beta strand

277 – 285

9

Helix

302 – 306

5

Helix

309 – 315

7

Beta strand

321 – 327

7

Helix

328 – 334

7

Beta strand

336 – 341

6

Helix

344 – 346

3

Beta strand

347 – 349

3

Beta strand

363 – 365

3

Turn

367 – 370

4

Turn

378 – 380

3

Helix

381 – 383

3

Beta strand

388 – 390

3

Beta strand

400 – 402

3

Beta strand

406 – 413

8

Beta strand

420 – 425

6

Beta strand

429 – 435

7

Turn

442 – 444

3

Helix

450 – 455

6

Beta strand

466 – 471

6

Beta strand

474 – 476

3

Beta strand

479 – 492

14

Beta strand

495 – 505

11

Beta strand

527 – 530

4

Helix

533 – 541

9

Beta strand

542 – 546

5

Helix

550 – 560

11

Turn

561 – 564

4

Helix

574 – 582

9

Beta strand

586 – 588

3

Beta strand

590 – 592

3

Helix

595 – 612

18

Beta strand

622 – 624

3

Helix

627 – 630

4

Turn

631 – 635

5

Helix

640 – 650

11

Beta strand

655 – 657

3

Helix

659 – 679

21

Beta strand

687 – 690

4

Helix

691 – 698

8

Sequences

	Sequence		Length	Mass (Da)
	P17655-1 [UniParc]. Last modified January 23, 2007. Version 5. Checksum: 8D105821A4374FB2	FASTA	700	80,009
	10 20 30 40 50 60 MAGIAAKLAK DREAAEGLGS HERAIKYLNQ DYEALRNECL EAGTLFQDPS FPAIPSALGF 70 80 90 100 110 120 KELGPYSSKT RGIEWKRPTE ICADPQFIIG GATRTDICQG ALGDCWLLAA IASLTLNEEI 130 140 150 160 170 180 LARVVPLNQS FQENYAGIFH FQFWQYGEWV EVVVDDRLPT KDGELLFVHS AEGSEFWSAL 190 200 210 220 230 240 LEKAYAKING CYEALSGGAT TEGFEDFTGG IAEWYELKKP PPNLFKIIQK ALQKGSLLGC 250 260 270 280 290 300 SIDITSAADS EAITFQKLVK GHAYSVTGAE EVESNGSLQK LIRIRNPWGE VEWTGRWNDN 310 320 330 340 350 360 CPSWNTIDPE ERERLTRRHE DGEFWMSFSD FLRHYSRLEI CNLTPDTLTS DTYKKWKLTK 370 380 390 400 410 420 MDGNWRRGST AGGCRNYPNT FWMNPQYLIK LEEEDEDEED GESGCTFLVG LIQKHRRRQR 430 440 450 460 470 480 KMGEDMHTIG FGIYEVPEEL SGQTNIHLSK NFFLTNRARE RSDTFINLRE VLNRFKLPPG 490 500 510 520 530 540 EYILVPSTFE PNKDGDFCIR VFSEKKADYQ AVDDEIEANL EEFDISEDDI DDGFRRLFAQ 550 560 570 580 590 600 LAGEDAEISA FELQTILRRV LAKRQDIKSD GFSIETCKIM VDMLDSDGSG KLGLKEFYIL 610 620 630 640 650 660 WTKIQKYQKI YREIDVDRSG TMNSYEMRKA LEEAGFKMPC QLHQVIVARF ADDQLIIDFD 670 680 690 700 NFVRCLVRLE TLFKIFKQLD PENTGTIELD LISWLCFSVL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of the cDNA for the large subunit of the high-Ca2+-requiring form of human Ca2+-activated neutral protease." Imajoh S., Aoki K., Ohno S., Emori Y., Kawasaki H., Sugihara H., Suzuki K. Biochemistry 27:8122-8128(1988) [PubMed: 2852952] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"cDNA cloning by amplification of circularized first strand cDNAs reveals non-IRE-regulated iron-responsive mRNAs." Ye Z., Connor J.R. Biochem. Biophys. Res. Commun. 275:223-227(2000) [PubMed: 10944468] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Astrocytoma.
[3]	NIEHS SNPs program Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLY-68; ARG-476; GLN-521; GLN-568 AND GLN-677.
[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: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ASP-22.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas, Placenta and Skin.
[6]	"Tandemly reiterated negative enhancer-like elements regulate transcription of a human gene for the large subunit of calcium-dependent protease." Hata A., Ohno S., Akita Y., Suzuki K. J. Biol. Chem. 264:6404-6411(1989) [PubMed: 2539381] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-79, VARIANT GLY-68. Tissue: Lymph node.
[7]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-12. Tissue: Platelet.
[8]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[9]	"The crystal structure of calcium-free human m-calpain suggests an electrostatic switch mechanism for activation by calcium." Strobl S., Fernandez-Catalan C., Braun M., Huber R., Masumoto H., Nakagawa K., Irie A., Sorimachi H., Bourenkow G., Bartunik H., Suzuki K., Bode W. Proc. Natl. Acad. Sci. U.S.A. 97:588-592(2000) [PubMed: 10639123] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

M23254 mRNA. Translation: AAA35645.1.
AF261089 mRNA. Translation: AAF99682.1.
AY835586 Genomic DNA. Translation: AAV80421.1.
AC099065 Genomic DNA. No translation available.
BC007686 mRNA. Translation: AAH07686.1. Sequence problems.
BC011828 mRNA. Translation: AAH11828.1. Sequence problems.
BC021303 mRNA. Translation: AAH21303.1.
J04700 Genomic DNA. Translation: AAA52760.1.

IPI

IPI00289758.

PIR

CIHUH2. S10590.

RefSeq

NP_001739.2.

UniGene

Hs.350899

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1KFU	X-ray	2.50	L	2-700	[»]
1KFX	X-ray	3.15	L	2-700	[»]
2NQA	X-ray	2.20	A/B	26-346	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P17655. 1 interaction.

Protein family/group databases

MEROPS

C02.002.

PTM databases

PhosphoSite

P17655.

Proteomic databases

PeptideAtlas

P17655.

PRIDE

P17655.

Genome annotation databases

Ensembl

ENSG00000162909. Homo sapiens. [Contig view]

GeneID

824.

KEGG

hsa:824.

Organism-specific databases

GeneCards

GC01P221966.

HGNC

HGNC:1479. CAPN2.

MIM

114230. gene.

PharmGKB

PA26060.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P17655.

Enzyme and pathway databases

BRENDA

3.4.22.53. 247.

Gene expression databases

ArrayExpress

P17655.

Bgee

P17655.

CleanEx

HS_CAPN2.

GermOnline

ENSG00000162909. Homo sapiens.

Family and domain databases

InterPro

IPR011992. EF-Hand_type.
IPR018247. EF_HAND_1.
IPR018249. EF_HAND_2.
IPR002048. EF_hand_Ca_bd.
IPR000169. Pept_cys_AS.
IPR001300. Peptidase_C2.
[Graphical view]

Gene3D

G3DSA:1.10.238.10. EF-Hand_type. 1 hit.

Pfam

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

PRINTS

PR00704. CALPAIN.

SMART

SM00720. calpain_III. 1 hit.
SM00230. CysPc. 1 hit.
SM00054. EFh. 3 hits.
[Graphical view]

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 Resources

NextBio

3374.

SOURCE

Search...

Entry information

Entry name

CAN2_HUMAN

Accession

Primary (citable) accession number: P17655
Secondary accession number(s): A6NDG7 , Q16738, Q6PJT3, Q8WU26, Q9HBB1

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 129 of the entry and version 5 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)