ID   CPNS1_RAT               Reviewed;         270 AA.
AC   Q64537; P97572; Q4V795;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   06-DEC-2005, sequence version 3.
DT   24-JAN-2024, entry version 176.
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, Css1;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Placenta;
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 project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 4-270.
RX   PubMed=8950173; DOI=10.1016/s0167-4781(96)00135-2;
RA   Sorimachi H., Amano S., Ishiura S., Suzuki K.;
RT   "Primary sequences of rat mu-calpain large and small subunits are,
RT   respectively, moderately and highly similar to those of human.";
RL   Biochim. Biophys. Acta 1309:37-41(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 87-270, PARTIAL PROTEIN SEQUENCE, DOMAIN,
RP   SUBUNIT, AND X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 84-266.
RX   PubMed=7982961; DOI=10.1016/s0021-9258(18)43835-5;
RA   Graham-Siegenthaler K., Gauthier S., Davies P.L., Elce J.S.;
RT   "Active recombinant rat calpain II. Bacterially produced large and small
RT   subunits associate both in vivo and in vitro.";
RL   J. Biol. Chem. 269:30457-30460(1994).
RN   [4]
RP   X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 98-270 IN COMPLEX WITH CALCIUM,
RP   SUBUNIT, AND DOMAIN.
RX   PubMed=9228945; DOI=10.1038/nsb0797-532;
RA   Blanchard H., Grochulski P., Li Y., Arthur J.S.C., Davies P.L., Elce J.S.,
RA   Cygler M.;
RT   "Structure of a calpain Ca(2+)-binding domain reveals a novel EF-hand and
RT   Ca(2+)-induced conformational changes.";
RL   Nat. Struct. Biol. 4:532-538(1997).
RN   [5]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 91-249, DOMAIN, AND SUBUNIT.
RX   PubMed=14579356; DOI=10.1002/prot.10453;
RA   Leinala E.K., Arthur J.S., Grochulski P., Davies P.L., Elce J.S., Jia Z.;
RT   "A second binding site revealed by C-terminal truncation of calpain small
RT   subunit, a penta-EF-hand protein.";
RL   Proteins 53:649-655(2003).
RN   [6]
RP   X-RAY CRYSTALLOGRAPHY (2.86 ANGSTROMS) OF 88-270, AND SUBUNIT.
RX   PubMed=15476820; DOI=10.1016/j.jmb.2004.08.073;
RA   Hosfield C.M., Elce J.S., Jia Z.;
RT   "Activation of calpain by Ca2+: roles of the large subunit N-terminal and
RT   domain III-IV linker peptides.";
RL   J. Mol. Biol. 343:1049-1053(2004).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 88-270 IN COMPLEX WITH CAPN2 AND
RP   CALPASTATIN, CALCIUM-BINDING SITES, AND SUBUNIT.
RX   PubMed=19020623; DOI=10.1038/nature07451;
RA   Hanna R.A., Campbell R.L., Davies P.L.;
RT   "Calcium-bound structure of calpain and its mechanism of inhibition by
RT   calpastatin.";
RL   Nature 456:409-412(2008).
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 88-270 IN COMPLEX WITH CAPN2 AND
RP   CALPASTATIN, CALCIUM-BINDING SITES, AND SUBUNIT.
RX   PubMed=19020622; DOI=10.1038/nature07353;
RA   Moldoveanu T., Gehring K., Green D.R.;
RT   "Concerted multi-pronged attack by calpastatin to occlude the catalytic
RT   cleft of heterodimeric calpains.";
RL   Nature 456:404-408(2008).
CC   -!- FUNCTION: Regulatory subunit of the calcium-regulated non-lysosomal
CC       thiol-protease which catalyzes limited proteolysis of substrates
CC       involved in cytoskeletal remodeling and signal transduction. Essential
CC       for embryonic development (By similarity).
CC       {ECO:0000250|UniProtKB:O88456}.
CC   -!- SUBUNIT: Homodimer or heterodimer of a large (catalytic) and a small
CC       (regulatory) subunit. In presence of calcium, the heterodimer
CC       dissociates (By similarity). {ECO:0000250}.
CC   -!- INTERACTION:
CC       Q64537; Q07009: Capn2; NbExp=8; IntAct=EBI-918712, EBI-1040438;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Note=Translocates to
CC       the plasma membrane upon calcium binding (By similarity). Allows the
CC       formation of the homodimer and also appears to mediate the contact
CC       between the large catalytic subunit and small regulatory subunit for
CC       the formation of the heterodimer. {ECO:0000250}.
CC   -!- DOMAIN: The contact of the 5th EF-hand domain from each monomer allows
CC       the formation of the homodimer and also appears to mediate the contact
CC       between the large catalytic subunit and small regulatory subunit for
CC       the formation of the heterodimer.
CC   -!- DOMAIN: EF-hand domains are paired. EF-hand 1 is paired with EF-hand 2
CC       and EF-hand 3 is paired with EF-hand 4. The fifth EF-hand domain, left
CC       unpaired, does not bind the calcium but is responsible of the
CC       dimerization by EF-embrace. The first four EF-hand domains bind
CC       calcium, however it is not sure if the binding of EF-hand 4 to calcium
CC       is physiologically relevant.
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DR   EMBL; BC098068; AAH98068.1; -; mRNA.
DR   EMBL; U53859; AAC53002.1; -; mRNA.
DR   EMBL; U10861; AAA64828.1; -; mRNA.
DR   PIR; A55143; A55143.
DR   RefSeq; NP_058814.1; NM_017118.1.
DR   RefSeq; XP_017445520.1; XM_017590031.1.
DR   PDB; 1AJ5; X-ray; 2.30 A; A/B=98-270.
DR   PDB; 1DF0; X-ray; 2.60 A; B=88-270.
DR   PDB; 1DVI; X-ray; 2.30 A; A/B=88-270.
DR   PDB; 1NP8; X-ray; 2.00 A; A/B=91-249.
DR   PDB; 1QXP; X-ray; 2.80 A; A/B=88-270.
DR   PDB; 1U5I; X-ray; 2.86 A; B=88-270.
DR   PDB; 3BOW; X-ray; 2.40 A; B=88-270.
DR   PDB; 3DF0; X-ray; 2.95 A; B=87-270.
DR   PDBsum; 1AJ5; -.
DR   PDBsum; 1DF0; -.
DR   PDBsum; 1DVI; -.
DR   PDBsum; 1NP8; -.
DR   PDBsum; 1QXP; -.
DR   PDBsum; 1U5I; -.
DR   PDBsum; 3BOW; -.
DR   PDBsum; 3DF0; -.
DR   AlphaFoldDB; Q64537; -.
DR   SMR; Q64537; -.
DR   DIP; DIP-6140N; -.
DR   IntAct; Q64537; 4.
DR   MINT; Q64537; -.
DR   STRING; 10116.ENSRNOP00000064489; -.
DR   iPTMnet; Q64537; -.
DR   PhosphoSitePlus; Q64537; -.
DR   jPOST; Q64537; -.
DR   PaxDb; 10116-ENSRNOP00000064489; -.
DR   Ensembl; ENSRNOT00055057849; ENSRNOP00055047732; ENSRNOG00055033452.
DR   Ensembl; ENSRNOT00060050154; ENSRNOP00060041793; ENSRNOG00060028834.
DR   Ensembl; ENSRNOT00065058591; ENSRNOP00065048239; ENSRNOG00065034103.
DR   GeneID; 29156; -.
DR   KEGG; rno:29156; -.
DR   UCSC; RGD:2270; rat.
DR   AGR; RGD:2270; -.
DR   CTD; 826; -.
DR   RGD; 2270; Capns1.
DR   eggNOG; KOG0037; Eukaryota.
DR   InParanoid; Q64537; -.
DR   OrthoDB; 4075143at2759; -.
DR   PhylomeDB; Q64537; -.
DR   BRENDA; 3.4.22.B24; 5301.
DR   Reactome; R-RNO-1474228; Degradation of the extracellular matrix.
DR   EvolutionaryTrace; Q64537; -.
DR   PRO; PR:Q64537; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0110158; C:calpain complex; ISO:RGD.
DR   GO; GO:0005829; C:cytosol; ISO:RGD.
DR   GO; GO:0016020; C:membrane; ISO:RGD.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005509; F:calcium ion binding; TAS:RGD.
DR   GO; GO:0004198; F:calcium-dependent cysteine-type endopeptidase activity; ISO:RGD.
DR   GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR   GO; GO:0030163; P:protein catabolic process; IMP:RGD.
DR   CDD; cd16188; EFh_PEF_CPNS1_2; 1.
DR   Gene3D; 1.10.238.10; EF-hand; 1.
DR   InterPro; IPR011992; EF-hand-dom_pair.
DR   InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR   InterPro; IPR002048; EF_hand_dom.
DR   PANTHER; PTHR46735:SF1; CALPAIN SMALL SUBUNIT 1; 1.
DR   PANTHER; PTHR46735; CALPAIN, SMALL SUBUNIT 1 A-RELATED; 1.
DR   Pfam; PF13833; EF-hand_8; 1.
DR   SUPFAM; SSF47473; EF-hand; 1.
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; Cytoplasm;
KW   Direct protein sequencing; Membrane; Metal-binding; Phosphoprotein;
KW   Reference proteome; Repeat.
FT   CHAIN           1..270
FT                   /note="Calpain small subunit 1"
FT                   /id="PRO_0000073717"
FT   DOMAIN          98..132
FT                   /note="EF-hand 1; atypical"
FT                   /evidence="ECO:0000305"
FT   DOMAIN          141..174
FT                   /note="EF-hand 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   DOMAIN          171..206
FT                   /note="EF-hand 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   DOMAIN          207..235
FT                   /note="EF-hand 4"
FT                   /evidence="ECO:0000305"
FT   DOMAIN          236..270
FT                   /note="EF-hand 5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         111
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:19020622,
FT                   ECO:0000269|PubMed:19020623, ECO:0000269|PubMed:9228945,
FT                   ECO:0007744|PDB:1DVI, ECO:0007744|PDB:3BOW,
FT                   ECO:0007744|PDB:3DF0"
FT   BINDING         114
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:19020622,
FT                   ECO:0000269|PubMed:19020623, ECO:0000269|PubMed:9228945,
FT                   ECO:0007744|PDB:1DVI, ECO:0007744|PDB:3BOW,
FT                   ECO:0007744|PDB:3DF0"
FT   BINDING         116
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:19020622,
FT                   ECO:0000269|PubMed:19020623, ECO:0000269|PubMed:9228945,
FT                   ECO:0007744|PDB:1DVI, ECO:0007744|PDB:3BOW,
FT                   ECO:0007744|PDB:3DF0"
FT   BINDING         121
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:19020622,
FT                   ECO:0000269|PubMed:19020623, ECO:0000269|PubMed:9228945,
FT                   ECO:0007744|PDB:1DVI, ECO:0007744|PDB:3BOW,
FT                   ECO:0007744|PDB:3DF0"
FT   BINDING         139
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000269|PubMed:19020622,
FT                   ECO:0000269|PubMed:19020623, ECO:0000269|PubMed:9228945,
FT                   ECO:0007744|PDB:1DVI, ECO:0007744|PDB:3BOW,
FT                   ECO:0007744|PDB:3DF0"
FT   BINDING         154
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT                   ECO:0000269|PubMed:19020622, ECO:0000269|PubMed:19020623,
FT                   ECO:0000269|PubMed:9228945, ECO:0007744|PDB:1DVI,
FT                   ECO:0007744|PDB:3BOW, ECO:0007744|PDB:3DF0"
FT   BINDING         156
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT                   ECO:0000269|PubMed:19020622, ECO:0000269|PubMed:19020623,
FT                   ECO:0000269|PubMed:9228945, ECO:0007744|PDB:1DVI,
FT                   ECO:0007744|PDB:3BOW, ECO:0007744|PDB:3DF0"
FT   BINDING         158
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT                   ECO:0000269|PubMed:19020622, ECO:0000269|PubMed:19020623,
FT                   ECO:0000269|PubMed:9228945, ECO:0007744|PDB:1DVI,
FT                   ECO:0007744|PDB:3BOW, ECO:0007744|PDB:3DF0"
FT   BINDING         160
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT                   ECO:0000269|PubMed:19020622, ECO:0000269|PubMed:19020623,
FT                   ECO:0000269|PubMed:9228945, ECO:0007744|PDB:1DVI,
FT                   ECO:0007744|PDB:3BOW, ECO:0007744|PDB:3DF0"
FT   BINDING         165
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT                   ECO:0000269|PubMed:19020622, ECO:0000269|PubMed:19020623,
FT                   ECO:0000269|PubMed:9228945, ECO:0007744|PDB:1DVI,
FT                   ECO:0007744|PDB:3BOW, ECO:0007744|PDB:3DF0"
FT   BINDING         184
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT                   ECO:0000269|PubMed:19020622, ECO:0000269|PubMed:19020623,
FT                   ECO:0000269|PubMed:9228945, ECO:0007744|PDB:1DVI,
FT                   ECO:0007744|PDB:3BOW, ECO:0007744|PDB:3DF0"
FT   BINDING         186
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT                   ECO:0000269|PubMed:19020622, ECO:0000269|PubMed:19020623,
FT                   ECO:0000269|PubMed:9228945, ECO:0007744|PDB:1DVI,
FT                   ECO:0007744|PDB:3BOW, ECO:0007744|PDB:3DF0"
FT   BINDING         188
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT                   ECO:0000269|PubMed:19020622, ECO:0000269|PubMed:19020623,
FT                   ECO:0000269|PubMed:9228945, ECO:0007744|PDB:1DVI,
FT                   ECO:0007744|PDB:3BOW, ECO:0007744|PDB:3DF0"
FT   BINDING         190
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT                   ECO:0000269|PubMed:19020622, ECO:0000269|PubMed:19020623,
FT                   ECO:0000269|PubMed:9228945, ECO:0007744|PDB:1DVI,
FT                   ECO:0007744|PDB:3BOW, ECO:0007744|PDB:3DF0"
FT   BINDING         195
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT                   ECO:0000269|PubMed:19020622, ECO:0000269|PubMed:19020623,
FT                   ECO:0000269|PubMed:9228945, ECO:0007744|PDB:1DVI,
FT                   ECO:0007744|PDB:3BOW, ECO:0007744|PDB:3DF0"
FT   BINDING         227
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000269|PubMed:19020622,
FT                   ECO:0000269|PubMed:19020623, ECO:0000269|PubMed:9228945,
FT                   ECO:0007744|PDB:1DVI, ECO:0007744|PDB:3BOW,
FT                   ECO:0007744|PDB:3DF0"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0000250|UniProtKB:P04632"
FT   MOD_RES         6
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P04632"
FT   MOD_RES         181
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P04632"
FT   CONFLICT        87
FT                   /note="S -> M (in Ref. 3; AAA64828)"
FT                   /evidence="ECO:0000305"
FT   HELIX           98..111
FT                   /evidence="ECO:0007829|PDB:1NP8"
FT   HELIX           112..114
FT                   /evidence="ECO:0007829|PDB:1NP8"
FT   HELIX           119..132
FT                   /evidence="ECO:0007829|PDB:1NP8"
FT   TURN            134..136
FT                   /evidence="ECO:0007829|PDB:1AJ5"
FT   HELIX           143..153
FT                   /evidence="ECO:0007829|PDB:1NP8"
FT   STRAND          158..161
FT                   /evidence="ECO:0007829|PDB:1NP8"
FT   HELIX           163..183
FT                   /evidence="ECO:0007829|PDB:1NP8"
FT   STRAND          188..191
FT                   /evidence="ECO:0007829|PDB:1NP8"
FT   TURN            193..195
FT                   /evidence="ECO:0007829|PDB:1NP8"
FT   HELIX           196..202
FT                   /evidence="ECO:0007829|PDB:1NP8"
FT   HELIX           209..219
FT                   /evidence="ECO:0007829|PDB:1NP8"
FT   STRAND          224..226
FT                   /evidence="ECO:0007829|PDB:1DVI"
FT   HELIX           228..243
FT                   /evidence="ECO:0007829|PDB:1NP8"
FT   TURN            248..251
FT                   /evidence="ECO:0007829|PDB:1DF0"
FT   STRAND          253..258
FT                   /evidence="ECO:0007829|PDB:1DVI"
FT   HELIX           260..268
FT                   /evidence="ECO:0007829|PDB:1AJ5"
SQ   SEQUENCE   270 AA;  28570 MW;  63609614CD4D3EB7 CRC64;
     MFLVNSFLKG GGGGGGGGGL GGGLGNVLGG LISGAAGGGG GGGGGGGMGL GGGGGGGGTA
     MRILGGVISA ISEAAAQYNP EPPPPRSHYS NIEANESEEE RQFRKLFVQL AGDDMEVSAT
     ELMNILNKVV TRHPDLKTDG FGIDTCRSMV AVMDSDTTGK LGFEEFKYLW NNIKKWQGIY
     KRFDTDRSGT IGSNELPGAF EAAGFHLNQH IYSMIIRRYS DETGNMDFDN FISCLVRLDA
     MFRAFRSLDK NGTGQIQVNI QEWLQLTMYS
//