Full text data of CAPNS1
CAPNS1
(CAPN4, CAPNS)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Calpain small subunit 1; CSS1 (Calcium-activated neutral proteinase small subunit; CANP small subunit; Calcium-dependent protease small subunit; CDPS; Calcium-dependent protease small subunit 1; Calpain regulatory subunit)
Calpain small subunit 1; CSS1 (Calcium-activated neutral proteinase small subunit; CANP small subunit; Calcium-dependent protease small subunit; CDPS; Calcium-dependent protease small subunit 1; Calpain regulatory subunit)
UniProt
P04632
ID CPNS1_HUMAN Reviewed; 268 AA.
AC P04632; A8K0P1; Q8WTX3; Q96EW0;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
read moreDT 13-AUG-1987, sequence version 1.
DT 22-JAN-2014, entry version 157.
DE RecName: Full=Calpain small subunit 1;
DE Short=CSS1;
DE AltName: Full=Calcium-activated neutral proteinase small subunit;
DE Short=CANP small subunit;
DE AltName: Full=Calcium-dependent protease small subunit;
DE Short=CDPS;
DE AltName: Full=Calcium-dependent protease small subunit 1;
DE AltName: Full=Calpain regulatory subunit;
GN Name=CAPNS1; Synonyms=CAPN4, CAPNS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3016651;
RA Ohno S., Emori Y., Suzuki K.;
RT "Nucleotide sequence of a cDNA coding for the small subunit of human
RT calcium-dependent protease.";
RL Nucleic Acids Res. 14:5559-5559(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3024120; DOI=10.1093/nar/14.22.8805;
RA Miyake S., Emori Y., Suzuki K.;
RT "Gene organization of the small subunit of human calcium-activated
RT neutral protease.";
RL Nucleic Acids Res. 14:8805-8817(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-224.
RG NIEHS SNPs program;
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, Muscle, Pancreas, Skin, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 1-9; 61-84 AND 159-165, ACETYLATION AT MET-1, AND
RP MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (OCT-2004) to UniProtKB.
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-179, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
RX PubMed=10639123; DOI=10.1073/pnas.97.2.588;
RA Strobl S., Fernandez-Catalan C., Braun M., Huber R., Masumoto H.,
RA Nakagawa K., Irie A., Sorimachi H., Bourenkow G., Bartunik H.,
RA Suzuki K., Bode W.;
RT "The crystal structure of calcium-free human m-calpain suggests an
RT electrostatic switch mechanism for activation by calcium.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:588-592(2000).
CC -!- FUNCTION: Regulatory subunit of the calcium-regulated non-
CC lysosomal thiol-protease which catalyzes limited proteolysis of
CC substrates involved in cytoskeletal remodeling and signal
CC transduction.
CC -!- SUBUNIT: Homodimer or heterodimer of a large (catalytic) and a
CC small (regulatory) subunit. In presence of calcium, the
CC heterodimer dissociates (By similarity).
CC -!- INTERACTION:
CC P17655:CAPN2; NbExp=3; IntAct=EBI-711828, EBI-1028956;
CC P20936:RASA1; NbExp=3; IntAct=EBI-711828, EBI-1026476;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Cell membrane (By
CC similarity). Note=Translocates to the plasma membrane upon calcium
CC binding (By similarity).
CC -!- DOMAIN: The contact of the 5th EF-hand domain from each monomer
CC allows the formation of the homodimer and also appears to mediate
CC the contact between the large catalytic subunit and small
CC regulatory subunit for the formation of the heterodimer (By
CC similarity).
CC -!- DOMAIN: EF-hand domains are paired. EF-hand 1 is paired with EF-
CC hand 2 and EF-hand 3 is paired with EF-hand 4. The fifth EF-hand
CC domain, left unpaired, does not bind the calcium but is
CC responsible of the dimerization by EF-embrace. The first four EF-
CC hand domains bind calcium, however it is not sure if the binding
CC of EF-hand 4 to calcium is physiologically relevant.
CC -!- SIMILARITY: Contains 5 EF-hand domains.
CC -!- WEB RESOURCE: Name=CaBP; Note=Calpain;
CC URL="http://structbio.vanderbilt.edu/cabp_database/general/prot_pages/calpain.html";
CC -!- WEB RESOURCE: Name=Calpains homepage;
CC URL="http://ag.arizona.edu/calpains/";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/capns1/";
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DR EMBL; X04106; CAA27726.1; -; mRNA.
DR EMBL; M31511; AAA35646.1; -; Genomic_DNA.
DR EMBL; M31502; AAA35646.1; JOINED; Genomic_DNA.
DR EMBL; M31503; AAA35646.1; JOINED; Genomic_DNA.
DR EMBL; M31504; AAA35646.1; JOINED; Genomic_DNA.
DR EMBL; M31505; AAA35646.1; JOINED; Genomic_DNA.
DR EMBL; M31506; AAA35646.1; JOINED; Genomic_DNA.
DR EMBL; M31507; AAA35646.1; JOINED; Genomic_DNA.
DR EMBL; M31508; AAA35646.1; JOINED; Genomic_DNA.
DR EMBL; M31509; AAA35646.1; JOINED; Genomic_DNA.
DR EMBL; M31510; AAA35646.1; JOINED; Genomic_DNA.
DR EMBL; AK289606; BAF82295.1; -; mRNA.
DR EMBL; BT009775; AAP88777.1; -; mRNA.
DR EMBL; AY789642; AAV40829.1; -; Genomic_DNA.
DR EMBL; AD001527; AAB51183.1; -; Genomic_DNA.
DR EMBL; AC002984; AAB81546.1; -; Genomic_DNA.
DR EMBL; BC000592; AAH00592.1; -; mRNA.
DR EMBL; BC007779; AAH07779.1; -; mRNA.
DR EMBL; BC011903; AAH11903.1; -; mRNA.
DR EMBL; BC017308; AAH17308.1; -; mRNA.
DR EMBL; BC018931; AAH18931.1; -; mRNA.
DR EMBL; BC021933; AAH21933.1; -; mRNA.
DR EMBL; BC023643; AAH23643.1; -; mRNA.
DR EMBL; BC064998; AAH64998.1; -; mRNA.
DR PIR; A26107; CIHUL.
DR RefSeq; NP_001003962.1; NM_001003962.1.
DR RefSeq; NP_001740.1; NM_001749.2.
DR RefSeq; XP_005259352.1; XM_005259295.1.
DR RefSeq; XP_005259353.1; XM_005259296.1.
DR UniGene; Hs.515371; -.
DR PDB; 1KFU; X-ray; 2.50 A; S=85-268.
DR PDB; 1KFX; X-ray; 3.15 A; S=85-268.
DR PDBsum; 1KFU; -.
DR PDBsum; 1KFX; -.
DR ProteinModelPortal; P04632; -.
DR SMR; P04632; 85-268.
DR IntAct; P04632; 22.
DR MINT; MINT-5000880; -.
DR STRING; 9606.ENSP00000246533; -.
DR BindingDB; P04632; -.
DR ChEMBL; CHEMBL2111357; -.
DR PhosphoSite; P04632; -.
DR DMDM; 115612; -.
DR OGP; P04632; -.
DR REPRODUCTION-2DPAGE; IPI00025084; -.
DR SWISS-2DPAGE; P04632; -.
DR PaxDb; P04632; -.
DR PRIDE; P04632; -.
DR DNASU; 826; -.
DR Ensembl; ENST00000246533; ENSP00000246533; ENSG00000126247.
DR Ensembl; ENST00000587718; ENSP00000468041; ENSG00000126247.
DR Ensembl; ENST00000588815; ENSP00000464849; ENSG00000126247.
DR GeneID; 826; -.
DR KEGG; hsa:826; -.
DR UCSC; uc002odi.1; human.
DR CTD; 826; -.
DR GeneCards; GC19P036630; -.
DR HGNC; HGNC:1481; CAPNS1.
DR HPA; HPA006872; -.
DR MIM; 114170; gene.
DR neXtProt; NX_P04632; -.
DR PharmGKB; PA26067; -.
DR eggNOG; NOG277774; -.
DR HOGENOM; HOG000063658; -.
DR HOVERGEN; HBG004492; -.
DR InParanoid; P04632; -.
DR KO; K08583; -.
DR OrthoDB; EOG7RV9FM; -.
DR PhylomeDB; P04632; -.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR ChiTaRS; CAPNS1; human.
DR EvolutionaryTrace; P04632; -.
DR GeneWiki; CAPNS1; -.
DR GenomeRNAi; 826; -.
DR NextBio; 3398; -.
DR PRO; PR:P04632; -.
DR ArrayExpress; P04632; -.
DR Bgee; P04632; -.
DR CleanEx; HS_CAPNS1; -.
DR Genevestigator; P04632; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004198; F:calcium-dependent cysteine-type endopeptidase activity; TAS:ProtInc.
DR GO; GO:0008284; P:positive regulation of cell proliferation; TAS:ProtInc.
DR Gene3D; 1.10.238.10; -; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR Pfam; PF13405; EF-hand_6; 1.
DR SMART; SM00054; EFh; 3.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Calcium; Cell membrane; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Membrane; Metal-binding;
KW Polymorphism; Reference proteome; Repeat.
FT CHAIN 1 268 Calpain small subunit 1.
FT /FTId=PRO_0000073713.
FT DOMAIN 91 125 EF-hand 1; atypical.
FT DOMAIN 139 172 EF-hand 2.
FT DOMAIN 169 204 EF-hand 3.
FT DOMAIN 205 233 EF-hand 4.
FT DOMAIN 234 268 EF-hand 5.
FT CA_BIND 108 119 1 (By similarity).
FT CA_BIND 152 163 2 (By similarity).
FT CA_BIND 182 193 3 (By similarity).
FT COMPBIAS 1 66 Gly-rich (hydrophobic).
FT COMPBIAS 10 26 Poly-Gly.
FT COMPBIAS 35 56 Poly-Gly.
FT COMPBIAS 78 83 Poly-Pro.
FT METAL 109 109 Calcium 1; via carbonyl oxygen (By
FT similarity).
FT METAL 112 112 Calcium 1 (By similarity).
FT METAL 114 114 Calcium 1; via carbonyl oxygen (By
FT similarity).
FT METAL 119 119 Calcium 1 (By similarity).
FT METAL 137 137 Calcium 4 (By similarity).
FT METAL 152 152 Calcium 2 (By similarity).
FT METAL 154 154 Calcium 2 (By similarity).
FT METAL 156 156 Calcium 2; via carbonyl oxygen (By
FT similarity).
FT METAL 158 158 Calcium 2; via carbonyl oxygen (By
FT similarity).
FT METAL 163 163 Calcium 2 (By similarity).
FT METAL 182 182 Calcium 3 (By similarity).
FT METAL 184 184 Calcium 3 (By similarity).
FT METAL 186 186 Calcium 3; via carbonyl oxygen (By
FT similarity).
FT METAL 188 188 Calcium 3; via carbonyl oxygen (By
FT similarity).
FT METAL 193 193 Calcium 3 (By similarity).
FT METAL 225 225 Calcium 4 (By similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 179 179 N6-acetyllysine.
FT VARIANT 224 224 M -> V (in dbSNP:rs17878750).
FT /FTId=VAR_021089.
FT CONFLICT 5 5 N -> D (in Ref. 7; AAH64998).
FT CONFLICT 27 27 N -> G (in Ref. 7; AAH64998).
FT CONFLICT 34 34 S -> G (in Ref. 7; AAH64998).
FT CONFLICT 261 268 WLQLTMYS -> VRTPILGYGCLGGPHPSALHTSSELQSPS
FT SYFASRPWVRAKGLVLLGFPVLTLHPPLPSGCS (in
FT Ref. 7; AAH11903).
FT CONFLICT 267 267 Y -> F (in Ref. 7; AAH21933).
FT HELIX 96 108
FT TURN 109 111
FT HELIX 117 124
FT TURN 127 129
FT HELIX 141 151
FT STRAND 153 157
FT HELIX 162 180
FT STRAND 186 189
FT HELIX 191 193
FT HELIX 194 200
FT HELIX 207 217
FT TURN 220 222
FT HELIX 226 246
FT STRAND 252 256
FT HELIX 258 266
SQ SEQUENCE 268 AA; 28316 MW; 17B87A8E47A90632 CRC64;
MFLVNSFLKG GGGGGGGGGG LGGGLGNVLG GLISGAGGGG GGGGGGGGGG GGGGGGTAMR
ILGGVISAIS EAAAQYNPEP PPPRTHYSNI EANESEEVRQ FRRLFAQLAG DDMEVSATEL
MNILNKVVTR HPDLKTDGFG IDTCRSMVAV MDSDTTGKLG FEEFKYLWNN IKRWQAIYKQ
FDTDRSGTIC SSELPGAFEA AGFHLNEHLY NMIIRRYSDE SGNMDFDNFI SCLVRLDAMF
RAFKSLDKDG TGQIQVNIQE WLQLTMYS
//
ID CPNS1_HUMAN Reviewed; 268 AA.
AC P04632; A8K0P1; Q8WTX3; Q96EW0;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
read moreDT 13-AUG-1987, sequence version 1.
DT 22-JAN-2014, entry version 157.
DE RecName: Full=Calpain small subunit 1;
DE Short=CSS1;
DE AltName: Full=Calcium-activated neutral proteinase small subunit;
DE Short=CANP small subunit;
DE AltName: Full=Calcium-dependent protease small subunit;
DE Short=CDPS;
DE AltName: Full=Calcium-dependent protease small subunit 1;
DE AltName: Full=Calpain regulatory subunit;
GN Name=CAPNS1; Synonyms=CAPN4, CAPNS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3016651;
RA Ohno S., Emori Y., Suzuki K.;
RT "Nucleotide sequence of a cDNA coding for the small subunit of human
RT calcium-dependent protease.";
RL Nucleic Acids Res. 14:5559-5559(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3024120; DOI=10.1093/nar/14.22.8805;
RA Miyake S., Emori Y., Suzuki K.;
RT "Gene organization of the small subunit of human calcium-activated
RT neutral protease.";
RL Nucleic Acids Res. 14:8805-8817(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-224.
RG NIEHS SNPs program;
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, Muscle, Pancreas, Skin, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 1-9; 61-84 AND 159-165, ACETYLATION AT MET-1, AND
RP MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (OCT-2004) to UniProtKB.
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-179, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
RX PubMed=10639123; DOI=10.1073/pnas.97.2.588;
RA Strobl S., Fernandez-Catalan C., Braun M., Huber R., Masumoto H.,
RA Nakagawa K., Irie A., Sorimachi H., Bourenkow G., Bartunik H.,
RA Suzuki K., Bode W.;
RT "The crystal structure of calcium-free human m-calpain suggests an
RT electrostatic switch mechanism for activation by calcium.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:588-592(2000).
CC -!- FUNCTION: Regulatory subunit of the calcium-regulated non-
CC lysosomal thiol-protease which catalyzes limited proteolysis of
CC substrates involved in cytoskeletal remodeling and signal
CC transduction.
CC -!- SUBUNIT: Homodimer or heterodimer of a large (catalytic) and a
CC small (regulatory) subunit. In presence of calcium, the
CC heterodimer dissociates (By similarity).
CC -!- INTERACTION:
CC P17655:CAPN2; NbExp=3; IntAct=EBI-711828, EBI-1028956;
CC P20936:RASA1; NbExp=3; IntAct=EBI-711828, EBI-1026476;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Cell membrane (By
CC similarity). Note=Translocates to the plasma membrane upon calcium
CC binding (By similarity).
CC -!- DOMAIN: The contact of the 5th EF-hand domain from each monomer
CC allows the formation of the homodimer and also appears to mediate
CC the contact between the large catalytic subunit and small
CC regulatory subunit for the formation of the heterodimer (By
CC similarity).
CC -!- DOMAIN: EF-hand domains are paired. EF-hand 1 is paired with EF-
CC hand 2 and EF-hand 3 is paired with EF-hand 4. The fifth EF-hand
CC domain, left unpaired, does not bind the calcium but is
CC responsible of the dimerization by EF-embrace. The first four EF-
CC hand domains bind calcium, however it is not sure if the binding
CC of EF-hand 4 to calcium is physiologically relevant.
CC -!- SIMILARITY: Contains 5 EF-hand domains.
CC -!- WEB RESOURCE: Name=CaBP; Note=Calpain;
CC URL="http://structbio.vanderbilt.edu/cabp_database/general/prot_pages/calpain.html";
CC -!- WEB RESOURCE: Name=Calpains homepage;
CC URL="http://ag.arizona.edu/calpains/";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/capns1/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; X04106; CAA27726.1; -; mRNA.
DR EMBL; M31511; AAA35646.1; -; Genomic_DNA.
DR EMBL; M31502; AAA35646.1; JOINED; Genomic_DNA.
DR EMBL; M31503; AAA35646.1; JOINED; Genomic_DNA.
DR EMBL; M31504; AAA35646.1; JOINED; Genomic_DNA.
DR EMBL; M31505; AAA35646.1; JOINED; Genomic_DNA.
DR EMBL; M31506; AAA35646.1; JOINED; Genomic_DNA.
DR EMBL; M31507; AAA35646.1; JOINED; Genomic_DNA.
DR EMBL; M31508; AAA35646.1; JOINED; Genomic_DNA.
DR EMBL; M31509; AAA35646.1; JOINED; Genomic_DNA.
DR EMBL; M31510; AAA35646.1; JOINED; Genomic_DNA.
DR EMBL; AK289606; BAF82295.1; -; mRNA.
DR EMBL; BT009775; AAP88777.1; -; mRNA.
DR EMBL; AY789642; AAV40829.1; -; Genomic_DNA.
DR EMBL; AD001527; AAB51183.1; -; Genomic_DNA.
DR EMBL; AC002984; AAB81546.1; -; Genomic_DNA.
DR EMBL; BC000592; AAH00592.1; -; mRNA.
DR EMBL; BC007779; AAH07779.1; -; mRNA.
DR EMBL; BC011903; AAH11903.1; -; mRNA.
DR EMBL; BC017308; AAH17308.1; -; mRNA.
DR EMBL; BC018931; AAH18931.1; -; mRNA.
DR EMBL; BC021933; AAH21933.1; -; mRNA.
DR EMBL; BC023643; AAH23643.1; -; mRNA.
DR EMBL; BC064998; AAH64998.1; -; mRNA.
DR PIR; A26107; CIHUL.
DR RefSeq; NP_001003962.1; NM_001003962.1.
DR RefSeq; NP_001740.1; NM_001749.2.
DR RefSeq; XP_005259352.1; XM_005259295.1.
DR RefSeq; XP_005259353.1; XM_005259296.1.
DR UniGene; Hs.515371; -.
DR PDB; 1KFU; X-ray; 2.50 A; S=85-268.
DR PDB; 1KFX; X-ray; 3.15 A; S=85-268.
DR PDBsum; 1KFU; -.
DR PDBsum; 1KFX; -.
DR ProteinModelPortal; P04632; -.
DR SMR; P04632; 85-268.
DR IntAct; P04632; 22.
DR MINT; MINT-5000880; -.
DR STRING; 9606.ENSP00000246533; -.
DR BindingDB; P04632; -.
DR ChEMBL; CHEMBL2111357; -.
DR PhosphoSite; P04632; -.
DR DMDM; 115612; -.
DR OGP; P04632; -.
DR REPRODUCTION-2DPAGE; IPI00025084; -.
DR SWISS-2DPAGE; P04632; -.
DR PaxDb; P04632; -.
DR PRIDE; P04632; -.
DR DNASU; 826; -.
DR Ensembl; ENST00000246533; ENSP00000246533; ENSG00000126247.
DR Ensembl; ENST00000587718; ENSP00000468041; ENSG00000126247.
DR Ensembl; ENST00000588815; ENSP00000464849; ENSG00000126247.
DR GeneID; 826; -.
DR KEGG; hsa:826; -.
DR UCSC; uc002odi.1; human.
DR CTD; 826; -.
DR GeneCards; GC19P036630; -.
DR HGNC; HGNC:1481; CAPNS1.
DR HPA; HPA006872; -.
DR MIM; 114170; gene.
DR neXtProt; NX_P04632; -.
DR PharmGKB; PA26067; -.
DR eggNOG; NOG277774; -.
DR HOGENOM; HOG000063658; -.
DR HOVERGEN; HBG004492; -.
DR InParanoid; P04632; -.
DR KO; K08583; -.
DR OrthoDB; EOG7RV9FM; -.
DR PhylomeDB; P04632; -.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR ChiTaRS; CAPNS1; human.
DR EvolutionaryTrace; P04632; -.
DR GeneWiki; CAPNS1; -.
DR GenomeRNAi; 826; -.
DR NextBio; 3398; -.
DR PRO; PR:P04632; -.
DR ArrayExpress; P04632; -.
DR Bgee; P04632; -.
DR CleanEx; HS_CAPNS1; -.
DR Genevestigator; P04632; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004198; F:calcium-dependent cysteine-type endopeptidase activity; TAS:ProtInc.
DR GO; GO:0008284; P:positive regulation of cell proliferation; TAS:ProtInc.
DR Gene3D; 1.10.238.10; -; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR Pfam; PF13405; EF-hand_6; 1.
DR SMART; SM00054; EFh; 3.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Calcium; Cell membrane; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Membrane; Metal-binding;
KW Polymorphism; Reference proteome; Repeat.
FT CHAIN 1 268 Calpain small subunit 1.
FT /FTId=PRO_0000073713.
FT DOMAIN 91 125 EF-hand 1; atypical.
FT DOMAIN 139 172 EF-hand 2.
FT DOMAIN 169 204 EF-hand 3.
FT DOMAIN 205 233 EF-hand 4.
FT DOMAIN 234 268 EF-hand 5.
FT CA_BIND 108 119 1 (By similarity).
FT CA_BIND 152 163 2 (By similarity).
FT CA_BIND 182 193 3 (By similarity).
FT COMPBIAS 1 66 Gly-rich (hydrophobic).
FT COMPBIAS 10 26 Poly-Gly.
FT COMPBIAS 35 56 Poly-Gly.
FT COMPBIAS 78 83 Poly-Pro.
FT METAL 109 109 Calcium 1; via carbonyl oxygen (By
FT similarity).
FT METAL 112 112 Calcium 1 (By similarity).
FT METAL 114 114 Calcium 1; via carbonyl oxygen (By
FT similarity).
FT METAL 119 119 Calcium 1 (By similarity).
FT METAL 137 137 Calcium 4 (By similarity).
FT METAL 152 152 Calcium 2 (By similarity).
FT METAL 154 154 Calcium 2 (By similarity).
FT METAL 156 156 Calcium 2; via carbonyl oxygen (By
FT similarity).
FT METAL 158 158 Calcium 2; via carbonyl oxygen (By
FT similarity).
FT METAL 163 163 Calcium 2 (By similarity).
FT METAL 182 182 Calcium 3 (By similarity).
FT METAL 184 184 Calcium 3 (By similarity).
FT METAL 186 186 Calcium 3; via carbonyl oxygen (By
FT similarity).
FT METAL 188 188 Calcium 3; via carbonyl oxygen (By
FT similarity).
FT METAL 193 193 Calcium 3 (By similarity).
FT METAL 225 225 Calcium 4 (By similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 179 179 N6-acetyllysine.
FT VARIANT 224 224 M -> V (in dbSNP:rs17878750).
FT /FTId=VAR_021089.
FT CONFLICT 5 5 N -> D (in Ref. 7; AAH64998).
FT CONFLICT 27 27 N -> G (in Ref. 7; AAH64998).
FT CONFLICT 34 34 S -> G (in Ref. 7; AAH64998).
FT CONFLICT 261 268 WLQLTMYS -> VRTPILGYGCLGGPHPSALHTSSELQSPS
FT SYFASRPWVRAKGLVLLGFPVLTLHPPLPSGCS (in
FT Ref. 7; AAH11903).
FT CONFLICT 267 267 Y -> F (in Ref. 7; AAH21933).
FT HELIX 96 108
FT TURN 109 111
FT HELIX 117 124
FT TURN 127 129
FT HELIX 141 151
FT STRAND 153 157
FT HELIX 162 180
FT STRAND 186 189
FT HELIX 191 193
FT HELIX 194 200
FT HELIX 207 217
FT TURN 220 222
FT HELIX 226 246
FT STRAND 252 256
FT HELIX 258 266
SQ SEQUENCE 268 AA; 28316 MW; 17B87A8E47A90632 CRC64;
MFLVNSFLKG GGGGGGGGGG LGGGLGNVLG GLISGAGGGG GGGGGGGGGG GGGGGGTAMR
ILGGVISAIS EAAAQYNPEP PPPRTHYSNI EANESEEVRQ FRRLFAQLAG DDMEVSATEL
MNILNKVVTR HPDLKTDGFG IDTCRSMVAV MDSDTTGKLG FEEFKYLWNN IKRWQAIYKQ
FDTDRSGTIC SSELPGAFEA AGFHLNEHLY NMIIRRYSDE SGNMDFDNFI SCLVRLDAMF
RAFKSLDKDG TGQIQVNIQE WLQLTMYS
//
MIM
114170
*RECORD*
*FIELD* NO
114170
*FIELD* TI
*114170 CALPAIN, SMALL SUBUNIT 1; CAPNS1
;;CALPAIN 4; CAPN4;;
CANPS;;
CALCIUM-DEPENDENT PROTEASE, SMALL SUBUNIT; CDPS
read more*FIELD* TX
DESCRIPTION
Calcium-dependent cysteine proteinases, or calpains (EC 3.4.22.17), are
widely distributed in mammalian cells. There are 2 distinct molecular
forms, calpains I and II, which differ in the quantity of calcium
required. Both calpains I and II are heterodimeric; each is composed of
1 heavy (about 80 kD), CAPN1 (114220) and CAPN2 (114230), respectively,
and 1 shared light (about 30 kD) subunit, CAPNS1. The heavy subunit has
a catalytic function, and the light subunit is regulatory.
CLONING
Ohno et al. (1986) gave the nucleotide sequence for a nearly full-length
cDNA coding for the small subunit of human calcium-dependent protease. A
human spleen cDNA library was the source. The human protein has 268
amino acids.
GENE FUNCTION
Using cell biologic, pharmacologic, and genetic methods,
Chandramohanadas et al. (2009) found that the apicomplexan parasites
Plasmodium falciparum and Toxoplasma gondii, the causative agents of
malaria and toxoplasmosis, respectively, used host cell calpains to
facilitate parasite egress. Immunodepletion and inhibition experiments
showed that calpain-1 was required for escape of P. falciparum from
human erythrocytes. Similarly, elimination of both calpain-1 and
calpain-2 via small interfering RNA against the common regulatory
subunit CAPNS1 in human osteosarcoma cells or deletion of Capns1 in
mouse embryonic fibroblasts blocked egress of T. gondii.
Chandramohanadas et al. (2009) concluded that P. falciparum and T.
gondii both exploit host cell calpains to facilitate escape from
intracellular parasitophorous vacuoles and/or the host plasma membrane,
a process required for parasite proliferation.
BIOCHEMICAL FEATURES
- Crystal Structure
Blanchard et al. (1997) reported the crystal structure of the
Ca(2+)-binding domain (domain VI) of rat Capns1 at 2.3-angstrom
resolution, both with and without bound Ca(2+). Monomers of domain VI
formed dimers with or without Ca(2+). The domain VI monomer was compact,
predominantly alpha helical, and incorporated 5 EF-hand supersecondary
structural elements. Only EF1, EF2, and EF3 were able to bind Ca(2+) at
physiologic Ca(2+) concentrations, and EF1 showed a novel Ca(2+)
coordination pattern.
MAPPING
By a combination of spot blot hybridization with sorted chromosomes and
of Southern hybridization with human-mouse cell hybrid DNAs, using in
each case a cDNA probe, Ohno et al. (1990) assigned the CANPS gene to
chromosome 19.
ANIMAL MODEL
Using targeted disruption of the mouse Capn4 gene and casein zymography
analysis, Arthur et al. (2000) demonstrated that wildtype and
heterozygote embryonic stem cell lysates maintained mu- and m-calpain
(i.e., calpain I and II) activities, whereas mutant homozygote embryonic
stem cell lysates did not. Immunoblot analysis showed that the m-calpain
large subunit was lost in Capn4 -/- cells. Growth of fibroblasts from
day 9.5 Capn4 -/- embryos was indistinguishable from those of wildtype
and heterozygous mice. At day 10.5, Capn4 -/- mice had a normal
cardiovascular system except for apparent defects in the development of
heart chambers and the vessels leading to and from the heart. After day
11.5, the accumulation of nucleated erythroid cells correlated with the
death of all Capn4 -/- embryos. Although unable to determine a
physiologic function for calpain, Arthur et al. (2000) concluded that
calpain is essential for life.
*FIELD* SA
Sakihama et al. (1985)
*FIELD* RF
1. Arthur, J. S. C.; Elce, J. S.; Hegadorn, C.; Williams, K.; Greer,
P. A.: Disruption of the murine calpain small subunit gene, Capn4:
calpain is essential for embryonic development but not for cell growth
and division. Molec. Cell. Biol. 20: 4474-4481, 2000.
2. Blanchard, H.; Grochulski, P.; Li, Y.; Arthur, J. S. C.; Davies,
P. L.; Elce, J. S.; Cygler, M.: Structure of a calpain Ca(2+)-binding
domain reveals a novel EF-hand and Ca(2+)-induced conformational changes. Nature
Struct. Biol. 4: 532-538, 1997.
3. Chandramohanadas, R.; Davis, P. H.; Beiting, D. P.; Harbut, M.
B.; Darling, C.; Velmourougane, G.; Lee, M. Y.; Greer, P. A.; Roos,
D. S.; Greenbaum, D. C.: Apicomplexan parasites co-opt host calpains
to facilitate their escape from infected cells. Science 324: 794-797,
2009.
4. Ohno, S.; Emori, Y.; Suzuki, K.: Nucleotide sequence of a cDNA
coding for the small subunit of human calcium-dependent protease. Nucleic
Acids Res. 14: 5559 only, 1986.
5. Ohno, S.; Minoshima, S.; Kudoh, J.; Fukuyama, R.; Shimizu, Y.;
Ohmi-Imajoh, S.; Shimizu, N.; Suzuki, K.: Four genes for the calpain
family locate on four distinct human chromosomes. Cytogenet. Cell
Genet. 53: 225-229, 1990.
6. Sakihama, T.; Kakidani, H.; Zenita, K.; Yumoto, N.; Kikuchi, T.;
Sasaki, T.; Kannagi, R.; Nakanishi, S.; Ohmori, M.; Takio, K.; Titani,
K.; Murachi, T.: A putative Ca(2+)-binding protein: structure of
the light subunit of porcine calpain elucidated by molecular cloning
and protein sequence analysis. Proc. Nat. Acad. Sci. 82: 6075-6079,
1985.
*FIELD* CN
Paul J. Converse - updated: 07/07/2009
Ada Hamosh - updated: 3/11/2009
Patricia A. Hartz - updated: 11/22/2005
Paul J. Converse - updated: 9/11/2000
*FIELD* CD
Victor A. McKusick: 10/16/1986
*FIELD* ED
mgross: 07/07/2009
alopez: 3/16/2009
terry: 3/11/2009
mgross: 12/2/2005
terry: 11/22/2005
carol: 8/21/2001
mgross: 9/11/2000
psherman: 4/10/2000
carol: 8/18/1998
supermim: 3/16/1992
carol: 4/29/1991
supermim: 3/20/1990
carol: 12/19/1989
ddp: 10/27/1989
*RECORD*
*FIELD* NO
114170
*FIELD* TI
*114170 CALPAIN, SMALL SUBUNIT 1; CAPNS1
;;CALPAIN 4; CAPN4;;
CANPS;;
CALCIUM-DEPENDENT PROTEASE, SMALL SUBUNIT; CDPS
read more*FIELD* TX
DESCRIPTION
Calcium-dependent cysteine proteinases, or calpains (EC 3.4.22.17), are
widely distributed in mammalian cells. There are 2 distinct molecular
forms, calpains I and II, which differ in the quantity of calcium
required. Both calpains I and II are heterodimeric; each is composed of
1 heavy (about 80 kD), CAPN1 (114220) and CAPN2 (114230), respectively,
and 1 shared light (about 30 kD) subunit, CAPNS1. The heavy subunit has
a catalytic function, and the light subunit is regulatory.
CLONING
Ohno et al. (1986) gave the nucleotide sequence for a nearly full-length
cDNA coding for the small subunit of human calcium-dependent protease. A
human spleen cDNA library was the source. The human protein has 268
amino acids.
GENE FUNCTION
Using cell biologic, pharmacologic, and genetic methods,
Chandramohanadas et al. (2009) found that the apicomplexan parasites
Plasmodium falciparum and Toxoplasma gondii, the causative agents of
malaria and toxoplasmosis, respectively, used host cell calpains to
facilitate parasite egress. Immunodepletion and inhibition experiments
showed that calpain-1 was required for escape of P. falciparum from
human erythrocytes. Similarly, elimination of both calpain-1 and
calpain-2 via small interfering RNA against the common regulatory
subunit CAPNS1 in human osteosarcoma cells or deletion of Capns1 in
mouse embryonic fibroblasts blocked egress of T. gondii.
Chandramohanadas et al. (2009) concluded that P. falciparum and T.
gondii both exploit host cell calpains to facilitate escape from
intracellular parasitophorous vacuoles and/or the host plasma membrane,
a process required for parasite proliferation.
BIOCHEMICAL FEATURES
- Crystal Structure
Blanchard et al. (1997) reported the crystal structure of the
Ca(2+)-binding domain (domain VI) of rat Capns1 at 2.3-angstrom
resolution, both with and without bound Ca(2+). Monomers of domain VI
formed dimers with or without Ca(2+). The domain VI monomer was compact,
predominantly alpha helical, and incorporated 5 EF-hand supersecondary
structural elements. Only EF1, EF2, and EF3 were able to bind Ca(2+) at
physiologic Ca(2+) concentrations, and EF1 showed a novel Ca(2+)
coordination pattern.
MAPPING
By a combination of spot blot hybridization with sorted chromosomes and
of Southern hybridization with human-mouse cell hybrid DNAs, using in
each case a cDNA probe, Ohno et al. (1990) assigned the CANPS gene to
chromosome 19.
ANIMAL MODEL
Using targeted disruption of the mouse Capn4 gene and casein zymography
analysis, Arthur et al. (2000) demonstrated that wildtype and
heterozygote embryonic stem cell lysates maintained mu- and m-calpain
(i.e., calpain I and II) activities, whereas mutant homozygote embryonic
stem cell lysates did not. Immunoblot analysis showed that the m-calpain
large subunit was lost in Capn4 -/- cells. Growth of fibroblasts from
day 9.5 Capn4 -/- embryos was indistinguishable from those of wildtype
and heterozygous mice. At day 10.5, Capn4 -/- mice had a normal
cardiovascular system except for apparent defects in the development of
heart chambers and the vessels leading to and from the heart. After day
11.5, the accumulation of nucleated erythroid cells correlated with the
death of all Capn4 -/- embryos. Although unable to determine a
physiologic function for calpain, Arthur et al. (2000) concluded that
calpain is essential for life.
*FIELD* SA
Sakihama et al. (1985)
*FIELD* RF
1. Arthur, J. S. C.; Elce, J. S.; Hegadorn, C.; Williams, K.; Greer,
P. A.: Disruption of the murine calpain small subunit gene, Capn4:
calpain is essential for embryonic development but not for cell growth
and division. Molec. Cell. Biol. 20: 4474-4481, 2000.
2. Blanchard, H.; Grochulski, P.; Li, Y.; Arthur, J. S. C.; Davies,
P. L.; Elce, J. S.; Cygler, M.: Structure of a calpain Ca(2+)-binding
domain reveals a novel EF-hand and Ca(2+)-induced conformational changes. Nature
Struct. Biol. 4: 532-538, 1997.
3. Chandramohanadas, R.; Davis, P. H.; Beiting, D. P.; Harbut, M.
B.; Darling, C.; Velmourougane, G.; Lee, M. Y.; Greer, P. A.; Roos,
D. S.; Greenbaum, D. C.: Apicomplexan parasites co-opt host calpains
to facilitate their escape from infected cells. Science 324: 794-797,
2009.
4. Ohno, S.; Emori, Y.; Suzuki, K.: Nucleotide sequence of a cDNA
coding for the small subunit of human calcium-dependent protease. Nucleic
Acids Res. 14: 5559 only, 1986.
5. Ohno, S.; Minoshima, S.; Kudoh, J.; Fukuyama, R.; Shimizu, Y.;
Ohmi-Imajoh, S.; Shimizu, N.; Suzuki, K.: Four genes for the calpain
family locate on four distinct human chromosomes. Cytogenet. Cell
Genet. 53: 225-229, 1990.
6. Sakihama, T.; Kakidani, H.; Zenita, K.; Yumoto, N.; Kikuchi, T.;
Sasaki, T.; Kannagi, R.; Nakanishi, S.; Ohmori, M.; Takio, K.; Titani,
K.; Murachi, T.: A putative Ca(2+)-binding protein: structure of
the light subunit of porcine calpain elucidated by molecular cloning
and protein sequence analysis. Proc. Nat. Acad. Sci. 82: 6075-6079,
1985.
*FIELD* CN
Paul J. Converse - updated: 07/07/2009
Ada Hamosh - updated: 3/11/2009
Patricia A. Hartz - updated: 11/22/2005
Paul J. Converse - updated: 9/11/2000
*FIELD* CD
Victor A. McKusick: 10/16/1986
*FIELD* ED
mgross: 07/07/2009
alopez: 3/16/2009
terry: 3/11/2009
mgross: 12/2/2005
terry: 11/22/2005
carol: 8/21/2001
mgross: 9/11/2000
psherman: 4/10/2000
carol: 8/18/1998
supermim: 3/16/1992
carol: 4/29/1991
supermim: 3/20/1990
carol: 12/19/1989
ddp: 10/27/1989