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0RPGF2_HUMAN*   SwissProt (?) | Description Local Annotation Link Reference
General Information
NameRAPGEF2
DescriptionRap guanine nucleotide exchange factor 2 (pdz domain containing guanine nucleotide exchange factor 1) (pdz-gef1) (ra-gef).
SpeciesHomo sapiens (NCBI taxonomy ID: 9606)
GO0005887 integral to plasma membrane (NAS)
0016020 membrane (IDA)
0005509 calcium ion binding (NAS)
0019992 diacylglycerol binding (NAS)
0005515 protein binding (IDA)
0046582 Rap GTPase activator activity (IDA)
0017034 Rap guanyl-nucleotide exchange factor activity (IDA)
0004871 signal transducer activity (TAS)
0019933 cAMP-mediated signaling (NAS)
0000165 MAPKKK cascade (NAS)
0007264 small GTPase mediated signal transduction (TAS)

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Domain Architecture (Details)
InterPro domains unassigned to SynO:
This domain is found in several guanine nucleotide exchange factors for Ras-like small GTPases.nd liesN-terminal to the RasGef (Cdc25-like) domain. Proteins belonging to this family include guanine nucleotidedissociation stimulator.hich stimulates the dissociation of GDP from the Ras-related RalA and RalBGTPases and allows GTP binding and activation of the GTPases; GTPase-activating protein (GAP) for Rho1and Rho2.hich is involved in the control of cellular morphogenesis; and the yeast cell division controlprotein.hich promotes the exchange of Ras-bound GDP by GTP and controls the level of cAMP whenthe cell division cycle is triggered. Also included is the son of sevenless protein.hich promotes theexchange of Ras-bound GDP by GTP during neuronal development.
  IPR000651:Guanine nucleotide exchange factor for Ras-like GTPases, N-terminal
Proteins with this domain are mostly RasGTP effectors and include guanine-nucleotide releasing factor in mammals . This factor stimulates the dissociation of GDP from the Ras-related RALA and RALB GTPases which allows GTP binding and activation of the GTPases. It interacts and acts as an effector molecule for R-ras.-Ras and Rap .The domain is also present in a number of other proteins among them the sexual differentiation protein in yeast that is essential for mating and meiosis and yeast adenylate cyclase. These proteins contain repeated leucine-rich (LRR) segments.
  IPR000159:RA
PDZ domains are found in diverse signaling proteins in bacteria.easts.lants.nsects and vertebrates . PDZ domains can occur in one or multiple copies and are nearly always found in cytoplasmic proteins. They bind either the carboxyl-terminal sequences of proteins or internal peptide sequences . In most cases.nteraction between a PDZ domain and its target is constitutive.ith a binding affinity of 1 to 10 ┬ÁM. However.gonist-dependent activation of cell surface receptors is sometimes required to promote interaction with a PDZ protein. PDZ domain proteins are frequently associated with the plasma membrane. compartment where high concentrations of phosphatidylinositol 4.-bisphosphate (PIP2) are found. Direct interaction between PIP2 and a subset of class II PDZ domains (syntenin.ASK.iam-1) has been demonstrated. PDZ domains consist of 80 to 90 amino acids comprising six beta-strands (betaA to betaF) and two alpha-helices. and B.ompactly arranged in a globular structure. Peptide binding of the ligand takes place in an elongated surface groove as an antiparallel beta-strand interacts with the betaB strand and the B helix. The structure of PDZ domains allows binding to a free carboxylate group at the end of a peptide through a carboxylate-binding loop between the betaA and betaB strands.
  IPR001478:PDZ/DHR/GLGF
Proteins that bind cyclic nucleotides (cAMP or cGMP) share a structural domain of about 120 residues . The best studied of these proteins is the prokaryotic catabolite gene activator (alsoknown as the cAMP receptor protein) (gene crp) where such a domain is known to be composed of three alpha-helices anda distinctive eight-stranded.ntiparallel beta-barrel structure. There are six invariant amino acids in this domain.hree of which are glycine residues that are thought to be essential for maintenance of the structural integrity ofthe beta-barrel. cAMP- and cGMP-dependent protein kinases (cAPK and cGPK) contain two tandem copies of the cyclicnucleotide-binding domain. The cAPKs are composed of two different subunits. catalytic chain and a regulatory chain.hich contains both copies of the domain. The cGPKs are single chain enzymes that include the two copies of the domainin their N-terminal section. Vertebrate cyclic nucleotide-gated ion-channels also contain this domain. Two suchcations channels have been fully characterized.ne is found in rod cells where it plays a role in visual signaltransduction.
  IPR000595:Cyclic nucleotide-binding
Ras proteins are membrane-associated molecular switches that bind GTP and GDP and slowly hydrolyze GTP to GDP . The balance between the GTP bound (active) and GDP bound (inactive) states is regulated by the opposite action of proteins activating the GTPase activity and that of proteins which promote the loss of bound GDP and the uptake of fresh GTP . The latter proteins are known as guanine-nucleotide dissociation stimulators (GDSs) (or also as guanine-nucleotide releasing (or exchange) factors (GRFs)). Proteins that act as GDS can be classified into at least two families.n the basis of sequence similarities.he CDC24 family (see ) and the CDC25 family.The size of the proteins of the CDC25 family range from 309 residues (LTE1) to 1596 residues (sos). The sequence similarity shared by all these proteins is limited to a region of about 250 amino acids generally located in their C-terminal section (currently the only exceptions are sos and ralGDS where this domain makes up the central part of the protein). This domain has been shown.n CDC25 an SCD25.o be essential for the activity of these proteins.
  IPR001895:Guanine-nucleotide dissociation stimulator CDC25
Small GTPases of the Ras family alternate between 2 conformations induced by the binding of either GTP or GDP. Guanine nucleotide exchange factors (GEFs) induce the dissociation of GDP to allow association of the more abundant GTP. The Ras-like family of small GTPases includes.mong others.as.ap1.-ras.nd Ral. The family is characterized by similarities in the effector domain. The Ras GTPase Rap1 is activated rapidly in response to activation of a variety of receptors. Rap1 activation is mediated by several second messengers.ncluding calcium.iacylglycerol.nd cAMP. GEFs have been identified that mediate these effects. One such GEF is Epac.n exchange protein directly activated by cAMP.hich represents a novel cAMP-induced.rotein kinase A-independent pathway .The SSF signature in this entry is currently under review. Please be aware that some of the protein hits may be false positives.
  IPR008937:Ras guanine nucleotide exchange factor
IPR001895:RasGEF 
Evalue:-99.698970004336 
Location:713-950IPR000651:RasGEFN 
Evalue:-30.8860566476932 
Location:267-380IPR000159:RA 
Evalue:-21.698970004336 
Location:606-692IPR001478:PDZ 
Evalue:-14.7447274948967 
Location:395-467IPR000595:cNMP 
Evalue:-14.6197887582884 
Location:135-253IPR008937:Ras_GEF 
Evalue:0 
Location:972-1030
SequencesProtein: RPGF2_HUMAN (1499 aa)
mRNA: AB002311
Local Annotation
Synapse Ontology
Calcium release from RyR (Ryanodine Receptor) in the SR (Sarcoplasmic Reticulum) is activated by the calcium induced-calcium-release
sdb:0325 RyR-CICR  (Evidence:keywords)
KO assignmentK08018
  Level 3 annotation:
    Rap guanine nucleotide exchange factor (GEF) 2
  Level 2 annotation:
    MAPK signaling pathway
Loci Structure (Details)Loci index, Chromosomal location, Length, Possible relational loci clusterExon1: 41 residues, 160408695-160408817Exon2: 46 residues, 160444943-160445075Exon3: 61 residues, 160455192-160455370Exon4: 47 residues, 160462948-160463085Exon5: 55 residues, 160464060-160464219Exon6: 53 residues, 160470459-160470612Exon7: 57 residues, 160470935-160471100Exon8: 38 residues, 160472032-160472140Exon9: 70 residues, 160472231-160472435Exon10: 38 residues, 160472527-160472636Exon11: 84 residues, 160473052-160473299Exon12: 54 residues, 160478912-160479070Exon13: 82 residues, 160479715-160479956Exon14: 130 residues, 160482165-160482549Exon15: 72 residues, 160483580-160483792Exon16: 43 residues, 160483882-160484006Exon17: 10 residues, 160484637-160484661Exon18: 76 residues, 160485707-160485931Exon19: 72 residues, 160487390-160487600Exon20: 53 residues, 160490738-160490891Exon21: 77 residues, 160493286-160493512Exon22: 188 residues, 160494088-160494648Exon23: 104 residues, 160496454-160496760Exon24: 680 residues, 160498715-160500749Exon25: 2 residues, -Jump to RPGF2_HUMAN  
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