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0CAN1_HUMAN*   SwissProt (?) | Description Local Annotation Link Reference
General Information
NameCAPN1
DescriptionCalpain-1 catalytic subunit (ec 3.4.22.52) (calpain-1 large subunit) (calcium-activated neutral proteinase 1) (canp 1) (calpain mu-type) (mucanp) (micromolar-calpain).
SpeciesHomo sapiens (NCBI taxonomy ID: 9606)
GO0008284 positive regulation of cell proliferation (TAS)
Domain Architecture (Details)
InterPro domains unassigned to SynO:
Peptidases are grouped into clans and families. Clans are groups of families for which there is evidence of common ancestry. Families are grouped by their catalytic type.he first character representing the catalytic type: A.spartic; C.ysteine; G.lutamic acid; M.etallo; S.erine; T.hreonine; and U.nknown. A clan that contains families of more than one type is described as being of type P. The serine.hreonine and cysteine peptidases utilise the catalytic part of an amino acid as a nucleophile and form an acyl intermediate - these peptidases can also readily act as transferases. In the case of aspartic.lutamic and metallopeptidases.he nucleophile is an activated water molecule. Cysteine peptidases have characteristic molecular topologies.hich can be seen not only in their three-dimensional structures.ut commonly also in the two-dimensional structures. The peptidase domain is responsible for peptide bond hydrolysis; in Merops this is termed the peptidase unit. These are peptidases in which the nucleophile is the sulphydryl group of a cysteine residue. Cysteine proteases are divided into clans (proteins which are evolutionary related).nd further sub-divided into families.n the basis of the architecture of their catalytic dyad or triad : Clan CA contains the families of papain (C1).alpain (C2).treptopain (C10) and the ubiquitin-specific peptidases (C12.19).s well as many families of viral cysteine endopeptidases. Clan CD contains the families of clostripain (C11).ingipain R (C25).egumain (C13).aspase-1 (C14) and separin (C50). These enzymes have specificities dominated by the interactions of the S1 subsite. Clan CE contains the families of adenain (C5) from adenoviruses.he eukaryotic Ulp1 protease (C48) and the bacterial YopJ proteases (C55). Clan CF contains only pyroglutamyl peptidase I (C15). Clan PA contains the picornains (C3).hich have probably evolved from serine peptidases and which form the majority of enzymes in this clan. Clans PB and CH contain the autolytic cysteine peptidases. This group of cysteine peptidases belong to the MEROPS peptidase family C2 (calpain family.lan CA). A type example is calpain.hich is an intracellular protease involved in many important cellular functions that are regulated by calcium . The protein is a complex of 2polypeptide chains (light and heavy).ith three known forms in mammals. a highly calcium-sensitive (i.e..icro-molar range) form known as mu-calpain.u-CANP or calpain I; a form sensitive to calcium in the milli-molar range.nown as m-calpain.-CANP or calpain II; and a third form.nown as p94.hich is found in skeletal muscle only . All forms have identical light but different heavy chains. Both mu- and m-calpain are heterodimers containing an identical 28-kDa subunit and an 80-kDa subunit that shares 55-65% sequence homology between the two proteases . The crystallographic structure of m-calpain reveals six "domains" in the 80-kDa subunit: A 19-amino acid NH2-terminal sequence;Active site domain IIa;Active site domain IIb. Domain 2 showslow levels of sequence similarity to papain; although the catalytic His hasnot been located by biochemical means.t is likely that calpain and papainare related . Domain III;An 18-amino acid extended sequence linking domain III to domain IV;Domain IV.hich resembles the penta EF-hand family of polypeptides.inds calcium and regulates activity . />. Ca2+-binding causes a rearrangement of the protein backbone.he net effect of which is that a Trp side chain.hich acts as a wedge between catalytic domains IIa and IIb in the apo state.oves away from the active site cleft allowing for the proper formation of the catalytic triad . Calpain-like mRNAs have been identified in other organisms including bacteria.ut the molecules encoded by these mRNAs have not been isolated.o little is known about their properties. How calpain activity is regulated in these organisms cells is still unclear In metazoans.he activity of calpain is controlled by a single proteinase inhibitor.alpastatin (). The calpastatin gene can produce eight or more calpastatin polypeptides ranging from 17 to 85 kDa by use of different promoters and alternative splicing events. The physiological significance of these different calpastatins is unclear.lthough all bind to three different places on the calpain molecule; binding to at least two of the sites is Ca2+ dependent. The calpains ostensibly participate in a variety of cellular processes including remodelling of cytoskeletal/membrane attachments.ifferent signal transduction pathways.nd apoptosis. Deregulated calpain activity following loss of Ca2+ homeostasis results in tissue damage in response to events such as myocardial infarcts.troke.nd brain trauma .
  IPR001300:Peptidase C2, calpain
Many calcium-binding proteins belong to the same evolutionary family and share a type of calcium-binding domain known as the EF-hand. This type of domain consists of a twelve residue loop flanked on both side by a twelve residue alpha-helical domain. In an EF-hand loop the calcium ion is coordinated in a pentagonal bipyramidal configuration. The six residues involved in the binding are in positions 1.... and 12; these residues are denoted by X...Y.X and -Z. The invariant Glu or Asp at position 12 provides two oxygens for liganding Ca (bidentate ligand).
  IPR002048:Calcium-binding EF-hand
This domain consists of a duplication of two EF-hand units.here each unit is composed of two helices connected by a twelve-residue calcium-binding loop. The calcium ion in the EF-hand loop is coordinated in a pentagonal bipyramidal configuration. Many calcium-binding proteins contain an EF-hand type calcium-binding domain . These include: calbindin D9K.100 proteins such as calcyclin.olcalcin phl p 7 (a calcium-binding pollen allergen).steonectin.arvalbumin.almodulin family of proteins (troponin C.altractin.dc4p.yosin essential chain.alcineurin.ecoverin.eurocalcin).lasmodial-specific CaII-binding protein Cbp40.enta-EF-Hand proteins (sorcin.rancalcin.alpain).s well as multidomain proteins such as phosphoinositide-specific phospholipase C.ystrophin.b1 and alpha-actinin. The fold consists of four helices and an open array of two hairpins.
  IPR011992:EF-Hand type
IPR001300:Peptidase_C2 
Evalue:-241.309799194336 
Location:55-354IPR001300:Calpain_III 
Evalue:-112.481483459473 
Location:365-522IPR002048:efhand 
Evalue:-2.17392516136169 
Location:589-617IPR002048:efhand 
Evalue:-1.65757727622986 
Location:619-647IPR002048:EF_HAND_2 
Evalue:0 
Location:680-714IPR002048:EF_HAND_2 
Evalue:0 
Location:558-576IPR000169:THIOL_PROTEASE_HIS 
Evalue:0 
Location:0-0
SequencesProtein: CAN1_HUMAN (714 aa)
mRNA: NM_005186
Local Annotation
Synapse Ontology
A process that increases long-term neuronal synaptic plasticity, the ability of neuronal synapses to change long-term as circumstances require. Long-term neuronal synaptic plasticity generally involves increase or decrease in actual synapse numbers.
sdb:0039 positive regulation of long-term neuronal synaptic plasticity  (Evidence:keywords)
KO assignmentK01367
  Level 3 annotation:
    calpain-1
  Level 2 annotation:
    Apoptosis
    Focal adhesion
K03853
  Level 3 annotation:
    calpain-2
  Level 2 annotation:
    Apoptosis
Loci Structure (Details)Loci index, Chromosomal location, Length, Possible relational loci clusterExon1: 48 residues, 64705918-64706060Exon2: 91 residues, 64706747-64707015Exon3: 25 residues, 64707174-64707244Exon4: 41 residues, 64707520-64707639Exon5: 46 residues, 64709963-64710097Exon6: 58 residues, 64710216-64710385Exon7: 30 residues, 64711261-64711345Exon8: 30 residues, 64712001-64712087Exon9: 27 residues, 64712460-64712535Exon10: 55 residues, 64712632-64712793Exon11: 60 residues, 64728729-64728905Exon12: 6 residues, 64729756-64729768Exon13: 72 residues, 64730509-64730721Exon14: 15 residues, 64730826-64730866Exon15: 24 residues, 64732101-64732167Exon16: 21 residues, 64732251-64732309Exon17: 23 residues, 64733369-64733434Exon18: 25 residues, 64733895-64733964Exon19: 28 residues, 64734064-64734143Exon20: 41 residues, 64734382-64734499Exon21: 21 residues, 64734860-64734919Exon22: 250 residues, 64735306-64736052Exon23: 2 residues, -Jump to CAN1_HUMAN  
Tune and view alternative isoforms
Loci Cluster (Details)Loci: 2672 63498654-63500590 ~-2K 6992(COX8A)(+)Loci: 2673 63758841-63762834 ~-4K 7008(VEGFB)(+)Loci: 2674 63775570-63791969 ~-16K 7011(PLCB3)(+)Loci: 2675 63883200-63896262 ~-13K 7031(RPS6KA4)(+)Loci: 3958 64130223-64247236 ~-117K 7042(NRXN2)(-)Loci: 3959 64376783-64402767 ~-26K 7059(EHD1)(-)Loci: 2676 64551485-64564618 ~-13K 7071(SNX15)(+)Loci: 2677 64635935-64640274 ~-4K 7081(TM7SF2)(+)Loci: 2678 64705918-64736052 ~-30K 7088(CAPN1)(+)Loci: 2679 65049159-65062750 ~-14K 7102(+)Loci: 3960 65121802-65138296 ~-16K 7115(MAP3K11)(-)Loci: 3961 65407787-65412586 ~-5K 7136(FIBP)(-)Loci: 3962 65416267-65424573 ~-8K 7139(FOSL1)(-)Loci: 2680 65594399-65768789 ~-174K 7153(PACS1)(+)Loci: 2681 65792680-65801537 ~-9K 7155(RAB1B)(+)Loci: 2682 65815916-65820707 ~-5K 7159(+)Loci: 3963 65856117-65860576 ~-4K 7162(RIN1)(-)Loci: 2683 66140672-66151387 ~-11K 7189(RBM14)(+)Loci: 2684 66162753-66170514 ~-8K 7192(RBM4)(+)Loci: 3964 66209298-66245446 ~-36K 7194(SPTBN2)(-)Loci: 3965 66372572-66478456 ~-106K 7198(PC)(-)Loci: 2685 66547466-66574905 ~-27K 7200(SYT12)(+)Loci: 2686 66580896-66596059 ~-15K 7201(RHOD)(+)Loci: 3966 66922227-66925952 ~-4K 7219(PPP1CA)(-)Loci: 2687 66979393-66983261 ~-4K 7229(CABP4)(+)Loci: 2688 67130982-67136581 ~-6K 7239(NDUFV1)(+)Loci: 2689 67554684-67560690 ~-6K 7248(NDUFS8)(+)Loci: 2690 67836710-67973317 ~-137K 7259(LRP5)(+)Loci: 2671 63412650-63433621 ~-21K 6988(MARK2)(+)Link out to UCSC