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(-) Description

Title :  STRUCTURE OF THE CAMP RESPONSIVE EXCHANGE FACTOR EPAC2 IN ITS AUTO-INHIBITED STATE
 
Authors :  H. Rehmann, A. Wittinghofer, J. L. Bos
Date :  08 Aug 05  (Deposition) - 02 Feb 06  (Release) - 24 Feb 09  (Revision)
Method :  X-RAY DIFFRACTION
Resolution :  2.70
Chains :  Asym./Biol. Unit :  E
Keywords :  Epac2, Camp-Gef2, Camp, Cyclic Nucleotide, Gef, Exchange Factor, Regulation, Auto-Inhibition, Cdc25 Homology Domain (Keyword Search: [Gene Ontology, PubMed, Web (Google))
 
Reference :  H. Rehmann, J. Das, P. Knipscheer, A. Wittinghofer, J. L. Bos
Structure Of The Cyclic-Amp Responsive Exchange Factor Epac2 In Its Auto-Inhibited State
Nature V. 439 625 2006
PubMed-ID: 16452984  |  Reference-DOI: 10.1038/NATURE04468
(for further references see the PDB file header)

(-) Compounds

Molecule 1 - RAP GUANINE NUCLEOTIDE EXCHANGE FACTOR 4
    ChainsE
    EngineeredYES
    Expression SystemESCHERICHIA COLI
    Expression System PlasmidPGEX4T
    Expression System StrainCK600K
    Expression System Taxid562
    Organism CommonMOUSE
    Organism ScientificMUS MUSCULUS
    Organism Taxid10090
    SynonymCAMP-REGULATED GUANINE NUCLEOTIDE EXCHANGE FACTOR II, CAMP-GEFII, EXCHANGE FACTOR DIRECTLY ACTIVATED BY CAMP 2, EPAC 2, CAMP-DEPENDENT RAP1 GUANINE-NUCLEOTIDE EXCHANGE FACTOR

 Structural Features

(-) Chains, Units

  1
Asymmetric/Biological Unit E

Summary Information (see also Sequences/Alignments below)

(-) Ligands, Modified Residues, Ions  (0, 0)

(no "Ligand,Modified Residues,Ions" information available for 2BYV)

(-) Sites  (0, 0)

(no "Site" information available for 2BYV)

(-) SS Bonds  (0, 0)

(no "SS Bond" information available for 2BYV)

(-) Cis Peptide Bonds  (1, 1)

Asymmetric/Biological Unit
No.Residues
1Pro E:160 -Pro E:161

 Sequence-Structure Mapping

(-) SAPs(SNPs)/Variants  (0, 0)

(no "SAP(SNP)/Variant" information available for 2BYV)

(-) PROSITE Motifs  (5, 6)

Asymmetric/Biological Unit (5, 6)
 PROSITEUniProtKBPDB
No.IDACDescriptionIDLocationCountLocation
1CNMP_BINDING_3PS50042 cAMP/cGMP binding motif profile.RPGF4_MOUSE43-146
356-457
  2E:43-146
E:338-439
2DEPPS50186 DEP domain profile.RPGF4_MOUSE216-291  1E:198-273
3RASGEF_NTERPS50212 Ras guanine-nucleotide exchange factors N-terminal domain profile.RPGF4_MOUSE496-634  1E:478-613
4RASGEF_CATPS50009 Ras guanine-nucleotide exchange factors catalytic domain profile.RPGF4_MOUSE772-1009  1E:754-991
5RASGEFPS00720 Ras Guanine-nucleotide exchange factors domain signature.RPGF4_MOUSE921-950  1E:903-932

(-) Exons   (0, 0)

(no "Exon" information available for 2BYV)

(-) Sequences/Alignments

Asymmetric/Biological Unit
   Reformat: Number of residues per line =  ('0' or empty: single-line sequence representation)
  Number of residues per labelling interval =   
  UniProt sequence: complete  aligned part    
   Show mapping: SCOP domains CATH domains Pfam domains Secondary structure (by author)
SAPs(SNPs) PROSITE motifs Exons
(details for a mapped element are shown in a popup box when the mouse pointer rests over it)
Chain E from PDB  Type:PROTEIN  Length:922
 aligned with RPGF4_MOUSE | Q9EQZ6 from UniProtKB/Swiss-Prot  Length:1011

    Alignment length:995
                                    24        34        44        54        64        74        84        94       104       114       124       134       144       154       164       174       184       194       204       214       224       234       244       254       264       274       284       294       304       314       324       334       344       354       364       374       384       394       404       414       424       434       444       454       464       474       484       494       504       514       524       534       544       554       564       574       584       594       604       614       624       634       644       654       664       674       684       694       704       714       724       734       744       754       764       774       784       794       804       814       824       834       844       854       864       874       884       894       904       914       924       934       944       954       964       974       984       994      1004     
         RPGF4_MOUSE     15 WIACLDKRPLERSSEDVDIIFTRLKGVKAFEKFHPNLLRQICLCGYYENLEKGITLFRQGDIGTNWYAVLAGSLDVKVSETSSHQDAVTICTLGIGTAFGESILDNTPRHATIVTRESSELLRIEQEDFKALWEKYRQYMAGLLAPPYGVMETGSNNDRIPDKENTPLIEPHVPLRPAHTITKVPSEKILRAGKILRIAILSRAPHMIRDRKYHLKTYRQCCVGTELVDWMIQQTSCVHSRTQAVGMWQVLLEDGVLNHVDQERHFQDKYLFYRFLDDEREDAPLPTEEEKKECDEELQDTMLLLSQMGPDAHMRMILRKPPGQRTVDDLEIIYDELLHIKALSHLSTTVKRELAGVLIFESHAKGGTVLFNQGEEGTSWYIILKGSVNVVIYGKGVVCTLHEGDDFGKLALVNDAPRAASIVLREDNCHFLRVDKEDFNRILRDVEANTVRLKEHDQDVLVLEKVPAGNRAANQGNSQPQQKYTVMSGTPEKILEHFLETIRLEPSLNEATDSVLNDFVMMHCVFMPNTQLCPALVAHYHAQPSQGTEQERMDYALNNKRRVIRLVLQWAAMYGDLLQEDDVAMAFLEEFYVSVSDDARMMAAFKEQLPELEKIVKQISEDAKAPQKKHKVLLQQFNTGDERAQKRQPIRGSDEVLFKVYCIDHTYTTIRVPVAASVKEVISAVADKLGSGEGLIIVKMNSGGEKVVLKSNDVSVFTTLTINGRLFACPREQFDSLTPLPEQEGPTTGTVGTFELMSSKDLAYQMTTYDWELFNCVHELELIYHTFGRHNFKKTTANLDLFLRRFNEIQFWVVTEVCLCSQLSKRVQLLKKFIKIAAHCKEYKNLNSFFAIVMGLSNVAVSRLALTWEKLPSKFKKFYAEFESLMDPSRNHRAYRLTAAKLEPPLIPFMPLLIKDMTFTHEGNKTFIDNLVNFEKMRMIANTARTVRYYRSQPFNPDAAQANKNHQDVRSYVRQLNVIDNQRTLSQMSHRLEPR 1009
               SCOP domains ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- SCOP domains
               CATH domains ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- CATH domains
               Pfam domains ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Pfam domains
         Sec.struct. author hhhhhhh.....hhhhhhhhhhhhhhhhhhh..hhhhhhhhhhhheeeee....eee.......eeeeeee..eeeee....hhhhheeeeee....eehhhhhhh.....eeee...eeeeeeehhhhhhhhhhhhhhhh...............--------------------------...hhhhhhhhhhhhhhhhhhhhhhheeeee..eeeeeeeehhhhhhhhhhh.....hhhhhhhhhhhhhhh..eee............eeee.hhh.......hhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhh.hhhhhhhhhhhhhhhhhhhhhhhh..hhhhhhhhh...eeeee.....eee.......eeeeeee..eeeee...eeeeee....ee.hhhhh.......eeee....eeeeeeehhhhhhhhhhhhh.eeeee....eeeeeee...------------...eeeeeehhhhhhhhhhhhh..hhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhh......hhhhhhhhhhhhhhhhhhhhhhhhhhhh.....hhhhhhhhhhhhhhhhhh...........hhhhhh..----------------------------.........eeeee.........eeeee...hhhhhhhhhhhhh........eee.....eee................eee.-------....hhhhhh......hhhhhhhhhhhhhhhhhhhhhhhh..hhhhhhhhhhhhhhh...hhhhhhhhhhhhhhhhhhhhhhhhh.hhhhhhhhhhhhhhhhhhhhhh.hhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhh.hhhhhhhhhhhhhh.......hhhhhhhhhhhhhhh........eehhhhhhhhhhhhhhhhhh..............hhhhhhhhhh.....hhhhhhhhhhhhh.. Sec.struct. author
                 SAPs(SNPs) ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- SAPs(SNPs)
                PROSITE (1) ----------------------------CNMP_BINDING_3  PDB: E:43-146 UniProt: 43-146                                                           ---------------------------------------------------------------------DEP  PDB: E:198-273 UniProt: 216-291                                        ----------------------------------------------------------------CNMP_BINDING_3  PDB: E:338-439 UniProt: 356-457                                                       --------------------------------------RASGEF_NTER  PDB: E:478-613 UniProt: 496-634                                                                                               -----------------------------------------------------------------------------------------------------------------------------------------RASGEF_CAT  PDB: E:754-991 UniProt: 772-1009                                                                                                                                                                                                   PROSITE (1)
                PROSITE (2) ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------RASGEF  PDB: E:903-932        ----------------------------------------------------------- PROSITE (2)
                 Transcript ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Transcript
                2byv E   15 WIACLDKRPLERSSEDVDIIFTRLKGVKAFEKFHPNLLRQICLCGYYENLEKGITLFRQGDIGTNWYAVLAGSLDVKVSETSSHQDAVTICTLGIGTAFGESILDNTPRHATIVTRESSELLRIEQEDFKALWEKYRQYMAGLLAPPYGVMETGSN--------------------------NVPSEKILRAGKILRIAILSRAPHMIRDRKYHLKTYRQCCVGTELVDWMIQQTSCVHSRTQAVGMWQVLLEDGVLNHVDQERHFQDKYLFYRFLDDEREDAPLPTEEEKKECDEELQDTMLLLSQMGPDAHMRMILRKPPGQRTVDDLEIIYDELLHIKALSHLSTTVKRELAGVLIFESHAKGGTVLFNQGEEGTSWYIILKGSVNVVIYGKGVVCTLHEGDDFGKLALVNDAPRAASIVLREDNCHFLRVDKEDFNRILRDVEANTVRLKEHDQDVLVLEKVPA------------QQKYTVMSGTPEKILEHFLETIRLEPSLNEATDSVLNDFVMMHCVFMPNTQLCPALVAHYHAQPSQGTEQERMDYALNNKRRVIRLVLQWAAMYGDLLQEDDVAMAFLEEFYVSVSDDARMMAAFKEQLPELEKIVK----------------------------KRQPIRGSDEVLFKVYCIDHTYTTIRVPVAASVKEVISAVADKLGSGEGLIIVKMNSGGEKVVLKSNDVSVFTTLTINGRLFA-------SLTPLPEQEGPTTGTVGTFELMSSKDLAYQMTTYDWELFNCVHELELIYHTFGRHNFKKTTANLDLFLRRFNEIQFWVVTEVCLCSQLSKRVQLLKKFIKIAAHCKEYKNLNSFFAIVMGLSNVAVSRLALTWEKLPSKFKKFYAEFESLMDPSRNHRAYRLTAAKLEPPLIPFMPLLIKDMTFTHEGNKTFIDNLVNFEKMRMIANTARTVRYYRSQPFNPDAAQANKNHQDVRSYVRQLNVIDNQRTLSQMSHRLEPR  991
                                    24        34        44        54        64        74        84        94       104       114       124       134       144       154       164     |   -         -         -  |    186       196       206       216       226       236       246       256       266       276       286       296       306       316       326       336       346       356       366       376       386       396       406       416       426       436       446       456       | -         -|      486       496       506       516       526       536       546       556       566       576       586       596       606      |  -         -         -     | 646       656       666       676       686       696       706       716       | -     | 736       746       756       766       776       786       796       806       816       826       836       846       856       866       876       886       896       906       916       926       936       946       956       966       976       986     
                                                                                                                                                                                     170                        179                                                                                                                                                                                                                                                                                          464          477                                                                                                                                     613                          642                                                                               724     732                                                                                                                                                                                                                                                                   

   Legend:   → Mismatch (orange background)
  - → Gap (green background, '-', border residues have a numbering label)
    → Modified Residue (blue background, lower-case, 'x' indicates undefined single-letter code, labelled with number + name)
  x → Chemical Group (purple background, 'x', labelled with number + name, e.g. ACE or NH2)
  extra numbering lines below/above indicate numbering irregularities and modified residue names etc., number ends below/above '|'

 Classification and Annotation

(-) SCOP Domains  (0, 0)

(no "SCOP Domain" information available for 2BYV)

(-) CATH Domains  (0, 0)

(no "CATH Domain" information available for 2BYV)

(-) Pfam Domains  (0, 0)

(no "Pfam Domain" information available for 2BYV)

(-) Gene Ontology  (17, 17)

Asymmetric/Biological Unit(hide GO term definitions)
Chain E   (RPGF4_MOUSE | Q9EQZ6)
molecular function
    GO:0017016    Ras GTPase binding    Interacting selectively and non-covalently with any member of the Ras superfamily of monomeric GTPases.
    GO:0005088    Ras guanyl-nucleotide exchange factor activity    Stimulates the exchange of guanyl nucleotides associated with a GTPase of the Ras superfamily. Under normal cellular physiological conditions, the concentration of GTP is higher than that of GDP, favoring the replacement of GDP by GTP in association with the GTPase.
    GO:0030552    cAMP binding    Interacting selectively and non-covalently with cAMP, the nucleotide cyclic AMP (adenosine 3',5'-cyclophosphate).
    GO:0005085    guanyl-nucleotide exchange factor activity    Stimulates the exchange of guanyl nucleotides associated with a GTPase. Under normal cellular physiological conditions, the concentration of GTP is higher than that of GDP, favoring the replacement of GDP by GTP in association with the GTPase.
    GO:0000166    nucleotide binding    Interacting selectively and non-covalently with a nucleotide, any compound consisting of a nucleoside that is esterified with (ortho)phosphate or an oligophosphate at any hydroxyl group on the ribose or deoxyribose.
    GO:0005515    protein binding    Interacting selectively and non-covalently with any protein or protein complex (a complex of two or more proteins that may include other nonprotein molecules).
biological process
    GO:0019933    cAMP-mediated signaling    Any intracellular signal transduction in which the signal is passed on within the cell via cyclic AMP (cAMP). Includes production of cAMP, and downstream effectors that further transmit the signal within the cell.
    GO:0017156    calcium ion regulated exocytosis    The release of intracellular molecules (e.g. hormones, matrix proteins) contained within a membrane-bounded vesicle by fusion of the vesicle with the plasma membrane of a cell, induced by a rise in cytosolic calcium-ion levels.
    GO:0006887    exocytosis    A process of secretion by a cell that results in the release of intracellular molecules (e.g. hormones, matrix proteins) contained within a membrane-bounded vesicle. Exocytosis can occur either by full fusion, when the vesicle collapses into the plasma membrane, or by a kiss-and-run mechanism that involves the formation of a transient contact, a pore, between a granule (for exemple of chromaffin cells) and the plasma membrane. The latter process most of the time leads to only partial secretion of the granule content. Exocytosis begins with steps that prepare vesicles for fusion with the membrane (tethering and docking) and ends when molecules are secreted from the cell.
    GO:0030073    insulin secretion    The regulated release of proinsulin from secretory granules (B granules) in the B cells of the pancreas; accompanied by cleavage of proinsulin to form mature insulin.
    GO:0035556    intracellular signal transduction    The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
    GO:0043547    positive regulation of GTPase activity    Any process that activates or increases the activity of a GTPase.
    GO:0017157    regulation of exocytosis    Any process that modulates the frequency, rate or extent of exocytosis.
    GO:0007264    small GTPase mediated signal transduction    Any series of molecular signals in which a small monomeric GTPase relays one or more of the signals.
cellular component
    GO:0005737    cytoplasm    All of the contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
    GO:0005829    cytosol    The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
    GO:0016020    membrane    A lipid bilayer along with all the proteins and protein complexes embedded in it an attached to it.

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 Related Entries

(-) Entries Sharing at Least One Protein Chain (UniProt ID)

UniProtKB/Swiss-Prot
        RPGF4_MOUSE | Q9EQZ61o7f 3cf6 4f7z 4mgi 4mgk 4mgy 4mgz 4mh0

(-) Related Entries Specified in the PDB File

1o7f CRYSTAL STRUCTURE OF THE REGULATORY DOMAIN OF EPAC2