P04632 (CPNS1_HUMAN) 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, CAPNS

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	268 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.
Subcellular location	Cytoplasm By similarity. Cell membrane By similarity. Note: Translocates to the plasma membrane upon calcium binding By similarity.
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 By similarity. 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.
Sequence similarities	Contains 5 EF-hand domains.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	Calcium Metal-binding
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	positive regulation of cell proliferation Traceable author statement PubMed 8702541. Source: ProtInc
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: InterPro calcium-dependent cysteine-type endopeptidase activity Traceable author statement PubMed 8702541. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CAPN2	P17655	2	EBI-711828,EBI-1028956

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 268

268

Calpain small subunit 1

PRO_0000073713

Regions

Domain

91 – 125

35

EF-hand 1; atypical

Domain

139 – 172

34

EF-hand 2

Domain

169 – 204

36

EF-hand 3

Domain

205 – 233

29

EF-hand 4

Domain

234 – 268

35

EF-hand 5

Calcium binding

108 – 119

12

1 By similarity

Calcium binding

152 – 163

12

2 By similarity

Calcium binding

182 – 193

12

3 By similarity

Compositional bias

1 – 66

66

Gly-rich (hydrophobic)

Compositional bias

10 – 26

17

Poly-Gly

Compositional bias

35 – 56

22

Poly-Gly

Compositional bias

78 – 83

6

Poly-Pro

Sites

Metal binding

109

1

Calcium 1; via carbonyl oxygen By similarity

Metal binding

112

1

Calcium 1 By similarity

Metal binding

114

1

Calcium 1; via carbonyl oxygen By similarity

Metal binding

119

1

Calcium 1 By similarity

Metal binding

137

1

Calcium 4 By similarity

Metal binding

152

1

Calcium 2 By similarity

Metal binding

154

1

Calcium 2 By similarity

Metal binding

156

1

Calcium 2; via carbonyl oxygen By similarity

Metal binding

158

1

Calcium 2; via carbonyl oxygen By similarity

Metal binding

163

1

Calcium 2 By similarity

Metal binding

182

1

Calcium 3 By similarity

Metal binding

184

1

Calcium 3 By similarity

Metal binding

186

1

Calcium 3; via carbonyl oxygen By similarity

Metal binding

188

1

Calcium 3; via carbonyl oxygen By similarity

Metal binding

193

1

Calcium 3 By similarity

Metal binding

225

1

Calcium 4 By similarity

Amino acid modifications

Modified residue

1

1

N-acetylmethionine Ref.8

Modified residue

179

1

N6-acetyllysine Ref.9

Natural variations

Natural variant

224

1

M → V. Ref.5
Corresponds to variant rs17878750 [ dbSNP | Ensembl ].

VAR_021089

Experimental info

Sequence conflict

5

1

N → D in AAH64998. Ref.7

Sequence conflict

27

1

N → G in AAH64998. Ref.7

Sequence conflict

34

1

S → G in AAH64998. Ref.7

Sequence conflict

261 – 268

8

WLQLTMYS → VRTPILGYGCLGGPHPSALH TSSELQSPSSYFASRPWVRA KGLVLLGFPVLTLHPPLPSG CS in AAH11903. Ref.7

Sequence conflict

267

1

Y → F in AAH21933. Ref.7

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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.

.

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268

Helix Strand Turn

Details...

Helix

96 – 108

13

Turn

109 – 111

3

Helix

117 – 124

8

Turn

127 – 129

3

Helix

141 – 151

11

Beta strand

153 – 157

5

Helix

162 – 180

19

Beta strand

186 – 189

4

Helix

191 – 193

3

Helix

194 – 200

7

Helix

207 – 217

11

Turn

220 – 222

3

Helix

226 – 246

21

Beta strand

252 – 256

5

Helix

258 – 266

9

Sequences

	Sequence		Length	Mass (Da)
	P04632 [UniParc]. Last modified August 13, 1987. Version 1. Checksum: 17B87A8E47A90632	FASTA	268	28,316
	10 20 30 40 50 60 MFLVNSFLKG GGGGGGGGGG LGGGLGNVLG GLISGAGGGG GGGGGGGGGG GGGGGGTAMR 70 80 90 100 110 120 ILGGVISAIS EAAAQYNPEP PPPRTHYSNI EANESEEVRQ FRRLFAQLAG DDMEVSATEL 130 140 150 160 170 180 MNILNKVVTR HPDLKTDGFG IDTCRSMVAV MDSDTTGKLG FEEFKYLWNN IKRWQAIYKQ 190 200 210 220 230 240 FDTDRSGTIC SSELPGAFEA AGFHLNEHLY NMIIRRYSDE SGNMDFDNFI SCLVRLDAMF 250 260 RAFKSLDKDG TGQIQVNIQE WLQLTMYS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of a cDNA coding for the small subunit of human calcium-dependent protease." Ohno S., Emori Y., Suzuki K. Nucleic Acids Res. 14:5559-5559(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Gene organization of the small subunit of human calcium-activated neutral protease." Miyake S., Emori Y., Suzuki K. Nucleic Acids Res. 14:8805-8817(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	NIEHS SNPs program Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-224.
[6]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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: Lung, Muscle, Pancreas, Skin and Uterus.
[8]	Bienvenut W.V. Submitted (OCT-2004) to UniProtKB Cited for: PROTEIN SEQUENCE OF 1-9; 61-84 AND 159-165, ACETYLATION AT MET-1, MASS SPECTROMETRY. Tissue: B-cell lymphoma.
[9]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-179, MASS SPECTROMETRY.
[10]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
+	Additional computationally mapped references.

Web resources

CaBP

Calpain

Calpains homepage

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X04106 mRNA. Translation: CAA27726.1.
M31511 , M31502, M31503, M31504, M31505, M31506, M31507, M31508, M31509, M31510 Genomic DNA. Translation: AAA35646.1.
AK289606 mRNA. Translation: BAF82295.1.
BT009775 mRNA. Translation: AAP88777.1.
AY789642 Genomic DNA. Translation: AAV40829.1.
AD001527 Genomic DNA. Translation: AAB51183.1.
AC002984 Genomic DNA. Translation: AAB81546.1.
BC000592 mRNA. Translation: AAH00592.1.
BC007779 mRNA. Translation: AAH07779.1.
BC011903 mRNA. Translation: AAH11903.1.
BC017308 mRNA. Translation: AAH17308.1.
BC018931 mRNA. Translation: AAH18931.1.
BC021933 mRNA. Translation: AAH21933.1.
BC023643 mRNA. Translation: AAH23643.1.
BC064998 mRNA. Translation: AAH64998.1.

IPI

IPI00025084.

PIR

CIHUL. A26107.

RefSeq

NP_001003962.1. NM_001003962.1.
NP_001740.1. NM_001749.2.

UniGene

Hs.515371.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1KFU	X-ray	2.50	S	85-268	[»]
1KFX	X-ray	3.15	S	85-268	[»]

ProteinModelPortal

P04632.

ModBase

Search...

Protein-protein interaction databases

IntAct

P04632. 20 interactions.

MINT

MINT-5000880.

STRING

9606.ENSP00000246533.

PTM databases

PhosphoSite

P04632.

Polymorphism databases

DMDM

115612.

2D gel databases

OGP

P04632.

REPRODUCTION-2DPAGE

IPI00025084.

SWISS-2DPAGE

P04632.

Proteomic databases

PaxDb

P04632.

PRIDE

P04632.

Protocols and materials databases

DNASU

826.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000246533; ENSP00000246533; ENSG00000126247.
ENST00000587718; ENSP00000468041; ENSG00000126247.
ENST00000588815; ENSP00000464849; ENSG00000126247.

GeneID

826.

KEGG

hsa:826.

UCSC

uc002odi.1. human.

Organism-specific databases

CTD

826.

GeneCards

GC19P036630.

HGNC

HGNC:1481. CAPNS1.

HPA

HPA006872.

MIM

114170. gene.

neXtProt

NX_P04632.

PharmGKB

PA26067.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG277774.

HOGENOM

HOG000063658.

HOVERGEN

HBG004492.

InParanoid

P04632.

KO

K08583.

OMA

RRYSDEG.

OrthoDB

EOG4W6NWR.

PhylomeDB

P04632.

Gene expression databases

Bgee

P04632.

CleanEx

HS_CAPNS1.

Genevestigator

P04632.

GermOnline

ENSG00000126247. Homo sapiens.

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

PF13405. EF_hand_4. 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

P04632.

ChEMBL

CHEMBL4962.

ChiTaRS

CAPNS1. human.

EvolutionaryTrace

P04632.

GenomeRNAi

826.

NextBio

3398.

SOURCE

Search...

Entry information

Entry name

CPNS1_HUMAN

Accession

Primary (citable) accession number: P04632
Secondary accession number(s): A8K0P1, Q8WTX3, Q96EW0

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	August 13, 1987
Last modified:	May 1, 2013
This is version 151 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.