Q64537 (CPNS1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Calpain small subunit 1
Short name=CSS1

Alternative name(s):
Calcium-activated neutral proteinase small subunit
Short name=CANP small subunit
Calcium-dependent protease small subunit
Short name=CDPS
Calcium-dependent protease small subunit 1
Calpain regulatory subunit

Gene names

Name:	Capns1
Synonyms:	Capn4, Css1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	270 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Regulatory subunit of the calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction.
Subunit structure	Homodimer or heterodimer of a large (catalytic) and a small (regulatory) subunit. In presence of calcium, the heterodimer dissociates By similarity. Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8
Subcellular location	Cytoplasm. Cell membrane. Note: Translocates to the plasma membrane upon calcium binding By similarity. Allows the formation of the homodimer and also appears to mediate the contact between the large catalytic subunit and small regulatory subunit for the formation of the heterodimer.
Domain	The contact of the 5th EF-hand domain from each monomer allows the formation of the homodimer and also appears to mediate the contact between the large catalytic subunit and small regulatory subunit for the formation of the heterodimer. Ref.5 EF-hand domains are paired. EF-hand 1 is paired with EF-hand 2 and EF-hand 3 is paired with EF-hand 4. The fifth EF-hand domain, left unpaired, does not bind the calcium but is responsible of the dimerization by EF-embrace. The first four EF-hand domains bind calcium, however it is not sure if the binding of EF-hand 4 to calcium is physiologically relevant. Ref.5
Sequence similarities	Contains 5 EF-hand domains.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane
Domain	Repeat
Ligand	Calcium Metal-binding
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Inferred from mutant phenotype Ref.3. Source: RGD
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calcium ion binding Traceable author statement Ref.3. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 270

270

Calpain small subunit 1

PRO_0000073717

Regions

Domain

98 – 132

35

EF-hand 1; atypical

Domain

141 – 174

34

EF-hand 2

Domain

171 – 206

36

EF-hand 3

Domain

207 – 235

29

EF-hand 4

Domain

236 – 270

35

EF-hand 5

Calcium binding

110 – 121

12

1 Ref.7 Ref.8

Calcium binding

154 – 165

12

2 Ref.7 Ref.8

Calcium binding

184 – 195

12

3 Ref.7 Ref.8

Compositional bias

1 – 66

66

Gly-rich (hydrophobic)

Compositional bias

10 – 25

16

Poly-Gly

Compositional bias

37 – 58

22

Poly-Gly

Compositional bias

80 – 85

6

Poly-Pro

Sites

Metal binding

111

1

Calcium 1; via carbonyl oxygen

Metal binding

114

1

Calcium 1

Metal binding

116

1

Calcium 1; via carbonyl oxygen

Metal binding

121

1

Calcium 1

Metal binding

139

1

Calcium 4

Metal binding

154

1

Calcium 2

Metal binding

156

1

Calcium 2

Metal binding

158

1

Calcium 2; via carbonyl oxygen

Metal binding

160

1

Calcium 2; via carbonyl oxygen

Metal binding

165

1

Calcium 2

Metal binding

184

1

Calcium 3

Metal binding

186

1

Calcium 3

Metal binding

188

1

Calcium 3; via carbonyl oxygen

Metal binding

190

1

Calcium 3; via carbonyl oxygen

Metal binding

195

1

Calcium 3

Metal binding

227

1

Calcium 4

Amino acid modifications

Modified residue

1

1

N-acetylmethionine By similarity

Modified residue

181

1

N6-acetyllysine By similarity

Experimental info

Sequence conflict

87

1

S → M in AAA64828. Ref.3

Secondary structure

1

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270

Helix Strand Turn

Details...

Helix

98 – 111

14

Helix

112 – 114

3

Helix

119 – 132

14

Turn

134 – 136

3

Helix

143 – 153

11

Beta strand

158 – 161

4

Helix

163 – 183

21

Beta strand

188 – 191

4

Turn

193 – 195

3

Helix

196 – 202

7

Helix

209 – 219

11

Beta strand

224 – 226

3

Helix

228 – 243

16

Turn

248 – 251

4

Beta strand

253 – 258

6

Helix

260 – 268

9

Sequences

	Sequence		Length	Mass (Da)
	Q64537 [UniParc]. Last modified December 6, 2005. Version 3. Checksum: 63609614CD4D3EB7	FASTA	270	28,570
	10 20 30 40 50 60 MFLVNSFLKG GGGGGGGGGL GGGLGNVLGG LISGAAGGGG GGGGGGGMGL GGGGGGGGTA 70 80 90 100 110 120 MRILGGVISA ISEAAAQYNP EPPPPRSHYS NIEANESEEE RQFRKLFVQL AGDDMEVSAT 130 140 150 160 170 180 ELMNILNKVV TRHPDLKTDG FGIDTCRSMV AVMDSDTTGK LGFEEFKYLW NNIKKWQGIY 190 200 210 220 230 240 KRFDTDRSGT IGSNELPGAF EAAGFHLNQH IYSMIIRRYS DETGNMDFDN FISCLVRLDA 250 260 270 MFRAFRSLDK NGTGQIQVNI QEWLQLTMYS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[2]	"Primary sequences of rat mu-calpain large and small subunits are, respectively, moderately and highly similar to those of human." Sorimachi H., Amano S., Ishiura S., Suzuki K. Biochim. Biophys. Acta 1309:37-41(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 4-270.
[3]	"Active recombinant rat calpain II. Bacterially produced large and small subunits associate both in vivo and in vitro." Graham-Siegenthaler K., Gauthier S., Davies P.L., Elce J.S. J. Biol. Chem. 269:30457-30460(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 87-270, PARTIAL PROTEIN SEQUENCE, DOMAIN, SUBUNIT, X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 84-266.
[4]	"Structure of a calpain Ca(2+)-binding domain reveals a novel EF-hand and Ca(2+)-induced conformational changes." Blanchard H., Grochulski P., Li Y., Arthur J.S.C., Davies P.L., Elce J.S., Cygler M. Nat. Struct. Biol. 4:532-538(1997) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 98-270, SUBUNIT, DOMAIN.
[5]	"A second binding site revealed by C-terminal truncation of calpain small subunit, a penta-EF-hand protein." Leinala E.K., Arthur J.S., Grochulski P., Davies P.L., Elce J.S., Jia Z. Proteins 53:649-655(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 91-249, DOMAIN, SUBUNIT.
[6]	"Activation of calpain by Ca2+: roles of the large subunit N-terminal and domain III-IV linker peptides." Hosfield C.M., Elce J.S., Jia Z. J. Mol. Biol. 343:1049-1053(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.86 ANGSTROMS) OF 88-270, SUBUNIT.
[7]	"Calcium-bound structure of calpain and its mechanism of inhibition by calpastatin." Hanna R.A., Campbell R.L., Davies P.L. Nature 456:409-412(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 88-270 IN COMPLEX WITH CAPN2 AND CALPASTATIN, CALCIUM-BINDING SITES, SUBUNIT.
[8]	"Concerted multi-pronged attack by calpastatin to occlude the catalytic cleft of heterodimeric calpains." Moldoveanu T., Gehring K., Green D.R. Nature 456:404-408(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 88-270 IN COMPLEX WITH CAPN2 AND CALPASTATIN, CALCIUM-BINDING SITES, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

BC098068 mRNA. Translation: AAH98068.1.
U53859 mRNA. Translation: AAC53002.1.
U10861 mRNA. Translation: AAA64828.1.

IPI

IPI00213536.

PIR

A55143.

RefSeq

NP_058814.1. NM_017118.1.

UniGene

Rn.3430.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AJ5	X-ray	2.30	A/B	98-270	[»]
1DF0	X-ray	2.60	B	88-270	[»]
1DVI	X-ray	2.30	A/B	88-270	[»]
1NP8	X-ray	2.00	A/B	91-249	[»]
1U5I	X-ray	2.86	B	88-270	[»]
3BOW	X-ray	2.40	B	88-270	[»]
3DF0	X-ray	2.95	B	88-270	[»]

ProteinModelPortal

Q64537.

SMR

Q64537. Positions 95-270.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6140N.

IntAct

Q64537. 2 interactions.

MINT

MINT-112921.

Proteomic databases

PaxDb

Q64537.

PRIDE

Q64537.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

29156.

KEGG

rno:29156.

UCSC

RGD:2270. rat.

Organism-specific databases

CTD

826.

RGD

2270. Capns1.

Phylogenomic databases

eggNOG

NOG277774.

HOGENOM

HOG000063658.

HOVERGEN

HBG004492.

InParanoid

Q64537.

KO

K08583.

OrthoDB

EOG4W6NWR.

Gene expression databases

ArrayExpress

Q64537.

Genevestigator

Q64537.

Family and domain databases

Gene3D

1.10.238.10. 1 hit.

InterPro

IPR011992. EF-hand-like_dom.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
[Graphical view]

Pfam

PF13202. EF_hand_3. 1 hit.
[Graphical view]

SMART

SM00054. EFh. 3 hits.
[Graphical view]

PROSITE

PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 3 hits.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q64537.

ChEMBL

CHEMBL3756.

EvolutionaryTrace

Q64537.

NextBio

608179.

Entry information

Entry name

CPNS1_RAT

Accession

Primary (citable) accession number: Q64537
Secondary accession number(s): P97572, Q4V795

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	December 6, 2005
Last modified:	May 1, 2013
This is version 110 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program