Q9Z1C8

SS
Gene name
Rapgef3 (Epac, Epac1)
Protein name
Rap guanine nucleotide exchange factor 3
Names
Exchange factor directly activated by cAMP 1 , Exchange protein directly activated by cAMP 1 , EPAC 1 , cAMP-regulated guanine nucleotide exchange factor I , cAMP-GEFI
Species
Rattus norvegicus (Rat)
KEGG Pathway
rno:59326
EC number
Protein Class

Descriptions

Epac1 (RAPGEF3) is a guanine nucleotide exchange factor (GEF) for the small G protein Rap and is directly activated by cyclic AMP (cAMP). Epac1 contains a regulatory region with a cAMP-binding domain (CBD), a Dishev-elled, Egl-10, Pleckstrin (DEP) domain, and a catalytic region for GEF activity. Upon cAMP binding, Epac1 undergoes a conformational change that allows the interaction of its GEF domain with Rap, resulting in Rap activation and subsequent downstream effects, including integrin-mediated cell adhesion and cell-cell junction formation. cAMP also induces the translocation of Epac1 toward the plasma membrane (PM), which is requisite for cAMP-induced Rap activation at the PM and enhances Rap-mediated cell adhesion. In the autoinhibited state, the catalytic site is sterically covered by the N-terminal regulatory region, which occludes the Rap binding site. The autoinhibition is released by a conformational change induced by the binding of cAMP.

Autoinhibitory domains (AIDs)

245-364 (CBD) SS

Target domain

661-926 (GEF catalytic domain)

Relief mechanism

Ligand binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for Q9Z1C8

Entry ID Method Resolution Chain Position Source
AF-Q9Z1C8-F1 Predicted AlphaFoldDB

No variants for Q9Z1C8

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q9Z1C8

No associated diseases with Q9Z1C8

5 regional properties for Q9Z1C8

Type Name Position InterPro Accession
domain DEP domain 111 - 186 IPR000591
domain Cyclic nucleotide-binding domain 245 - 364 IPR000595
domain Ras-like guanine nucleotide exchange factor, N-terminal 383 - 521 IPR000651
domain Ras guanine-nucleotide exchange factors catalytic domain 661 - 926 IPR001895
conserved_site Ras guanine-nucleotide exchange factor, conserved site 815 - 844 IPR019804

Functions

Description
EC Number
Subcellular Localization
  • Cytoplasm
  • Membrane ; Peripheral membrane protein
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

14 GO annotations of cellular component

Name Definition
apical part of cell The region of a polarized cell that forms a tip or is distal to a base. For example, in a polarized epithelial cell, the apical region has an exposed surface and lies opposite to the basal lamina that separates the epithelium from other tissue.
axon terminus Terminal inflated portion of the axon, containing the specialized apparatus necessary to release neurotransmitters. The axon terminus is considered to be the whole region of thickening and the terminal button is a specialized region of it.
basal plasma membrane The region of the plasma membrane located at the basal end of the cell. Often used in reference to animal polarized epithelial membranes, where the basal membrane is the part attached to the extracellular matrix, or in plant cells, where the basal membrane is defined with respect to the zygotic axis.
basolateral part of cell The region of a cell situated by the cell sides which interface adjacent cells and near the base. Often used in reference to animal polarized epithelial cells.
brush border membrane The portion of the plasma membrane surrounding the brush border.
filopodium Thin, stiff, actin-based protrusion extended by the leading edge of a motile cell such as a crawling fibroblast or amoeba, or an axonal or dendritic growth cone, or a dendritic shaft.
growth cone The migrating motile tip of a growing neuron projection, where actin accumulates, and the actin cytoskeleton is the most dynamic.
lamellipodium A thin sheetlike process extended by the leading edge of a migrating cell or extending cell process; contains a dense meshwork of actin filaments.
microvillus Thin cylindrical membrane-covered projections on the surface of an animal cell containing a core bundle of actin filaments. Present in especially large numbers on the absorptive surface of intestinal cells.
neuronal cell body The portion of a neuron that includes the nucleus, but excludes cell projections such as axons and dendrites.
perinuclear region of cytoplasm Cytoplasm situated near, or occurring around, the nucleus.
photoreceptor cell terminal bouton A specialized region of the axon terminus portion of a photoreceptor cell axon. A photoreceptor cell is a neuron specialized to detect and transduce light.
ribbon synapse Type of synapse characterized by an electron-dense ribbon, lamella (bar) or spherical body in the presynaptic process cytoplasm.
rod bipolar cell terminal bouton A specialized region of the axon terminus portion of a rod bipolar axon. A rod bipolar cell is a neuron found in the retina and having connections with rod photoreceptor cells and neurons in the inner plexiform layer.

4 GO annotations of molecular function

Name Definition
cAMP binding Binding to cAMP, the nucleotide cyclic AMP (adenosine 3',5'-cyclophosphate).
guanyl-nucleotide exchange factor activity Stimulates the exchange of GDP to GTP on a signaling GTPase, changing its conformation to its active form. Guanine nucleotide exchange factors (GEFs) act by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP), which is more abundant in the cell under normal cellular physiological conditions.
protein domain specific binding Binding to a specific domain of a protein.
transmembrane transporter binding Binding to a transmembrane transporter, a protein or protein complex that enables the transfer of a substance, usually a specific substance or a group of related substances, from one side of a membrane to the other.

32 GO annotations of biological process

Name Definition
angiogenesis Blood vessel formation when new vessels emerge from the proliferation of pre-existing blood vessels.
artery development The progression of the artery over time, from its initial formation to the mature structure. An artery is a blood vessel that carries blood away from the heart to a capillary bed.
associative learning Learning by associating a stimulus (the cause) with a particular outcome (the effect).
cellular response to cAMP Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cAMP (cyclic AMP, adenosine 3',5'-cyclophosphate) stimulus.
cellular response to L-dopa Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a L-dopa stimulus.
cellular response to organic cyclic compound Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an organic cyclic compound stimulus.
cellular response to transforming growth factor beta stimulus Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a transforming growth factor beta stimulus.
cellular response to xenobiotic stimulus Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a xenobiotic, a compound foreign to the organism exposed to it. It may be synthesized by another organism (like ampicilin) or it can be a synthetic chemical.
dorsal root ganglion development The process whose specific outcome is the progression of a dorsal root ganglion over time, from its formation to the mature structure.
establishment of endothelial barrier The establishment of a barrier between endothelial cell layers, such as those in the brain, lung or intestine, to exert specific and selective control over the passage of water and solutes, thus allowing formation and maintenance of compartments that differ in fluid and solute composition.
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.
liver regeneration The regrowth of lost or destroyed liver.
negative regulation of cardiac muscle cell apoptotic process Any process that decreases the rate or extent of cardiac cell apoptotic process, a form of programmed cell death induced by external or internal signals that trigger the activity of proteolytic caspases whose actions dismantle a cardiac muscle cell and result in its death.
negative regulation of collagen biosynthetic process Any process that stops, prevents, or reduces the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of collagen, any of a group of fibrous proteins of very high tensile strength that form the main component of connective tissue in animals.
negative regulation of syncytium formation by plasma membrane fusion Any process that decreases the frequency, rate or extent of the formation of a syncytium, a mass of cytoplasm containing several nuclei enclosed within a single plasma membrane, by the fusion of the plasma membranes of two or more individual cells.
positive regulation of angiogenesis Any process that activates or increases angiogenesis.
positive regulation of calcium ion transmembrane transport Any process that activates or increases the frequency, rate or extent of calcium ion transmembrane transport.
positive regulation of cell size Any process that increases cell size.
positive regulation of GTPase activity Any process that activates or increases the activity of a GTPase.
positive regulation of protein export from nucleus Any process that activates or increases the frequency, rate or extent of directed movement of proteins from the nucleus into the cytoplasm.
positive regulation of protein phosphorylation Any process that activates or increases the frequency, rate or extent of addition of phosphate groups to amino acids within a protein.
positive regulation of smooth muscle cell migration Any process that activates, maintains or increases the frequency, rate or extent of smooth muscle cell migration.
positive regulation of stress fiber assembly Any process that activates or increases the frequency, rate or extent of the assembly of a stress fiber, a bundle of microfilaments and other proteins found in fibroblasts.
positive regulation of syncytium formation by plasma membrane fusion Any process that increases the frequency, rate or extent of the formation of a syncytium, a mass of cytoplasm containing several nuclei enclosed within a single plasma membrane, by the fusion of the plasma membranes of two or more individual cells.
positive regulation of transcription by RNA polymerase II Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
Rap protein signal transduction The series of molecular signals within the cell that are mediated by a member of the Rap family of proteins switching to a GTP-bound active state.
Ras protein signal transduction The series of molecular signals within the cell that are mediated by a member of the Ras superfamily of proteins switching to a GTP-bound active state.
regulation of actin cytoskeleton organization Any process that modulates the frequency, rate or extent of the formation, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments and their associated proteins.
regulation of angiogenesis Any process that modulates the frequency, rate or extent of angiogenesis.
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction Any process that modulates the frequency, rate or extent of protein kinase B signaling, a series of reactions mediated by the intracellular serine/threonine kinase protein kinase B.
response to nicotine Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a nicotine stimulus.
spinal cord development The process whose specific outcome is the progression of the spinal cord over time, from its formation to the mature structure. The spinal cord primarily conducts sensory and motor nerve impulses between the brain and the peripheral nervous tissues.

8 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q8WZA2 RAPGEF4 Rap guanine nucleotide exchange factor 4 Homo sapiens (Human) SS
O95398 RAPGEF3 Rap guanine nucleotide exchange factor 3 Homo sapiens (Human) EV
Q9EQZ6 Rapgef4 Rap guanine nucleotide exchange factor 4 Mus musculus (Mouse) EV
Q8VCC8 Rapgef3 Rap guanine nucleotide exchange factor 3 Mus musculus (Mouse) SS
Q03386 Ralgds Ral guanine nucleotide dissociation stimulator Rattus norvegicus (Rat) PR
Q9R1K8 Rasgrp1 RAS guanyl-releasing protein 1 Rattus norvegicus (Rat) SS
Q8R5I4 Rasgrp4 RAS guanyl-releasing protein 4 Rattus norvegicus (Rat) SS
P0C643 Rasgrp2 RAS guanyl-releasing protein 2 Rattus norvegicus (Rat) SS
10 20 30 40 50 60
MKVSWPGENH WQVGPAVVES PAVGAPQVGG LPDVVPEGTL LNMVLKRMHR PRCCSYQLVF
70 80 90 100 110 120
EHRRPSCIQG LRWTPLTNSE GSLDFRVSLE QATTEHVHKA GKLLYRHLLA TYPTLIRDRK
130 140 150 160 170 180
YHLRLHRQCC SGRELVDGIL ALGLGVHSRS QAVGICQVLL DEGALCHVKH DWTFQDRDAQ
190 200 210 220 230 240
FYRFPGPEPQ PAGTHDVEEE LVEAMALLSQ RGPDALLTVA LRKSPGQRTD EELDLIFEEL
250 260 270 280 290 300
VHIKAVAHLS NSVKRELAAV LLFEPHSKAG TVLFSQGDKG TSWYIIWKGS VNVVTRGKGL
310 320 330 340 350 360
VTTLHEGDDF GQLALVNDAP RAATIILREN NCHFLRVDKQ DFNRIIKDVE AKTMRLEEHG
370 380 390 400 410 420
KVVLVLERTS QGAGPSRPPT PGRNRYTVMS GTPEKILELL LEAMRPDSSA HDPTETFLSD
430 440 450 460 470 480
FLLTHSVFMP CTQLFAALLH HFHVEPSEPA GGSEQERSTY ICNKRQQILR LVSRWVALYS
490 500 510 520 530 540
PMLRSDPVAT SFLQKLSDLV SRDTRLSNLL REQYPERRRH HRLENGCGNV SPQTKARNAP
550 560 570 580 590 600
VWFPNHEEPL PSSAGAIRVG DKVPYDICRP DHSVLTLHLP VTASVREVMA ALAHEDHWTK
610 620 630 640 650 660
GQVLVKVNSA GDVVGLQPDA RGVATSLGLN ERIFVVDPQE VHELTPHPEQ LGPTLGSSEM
670 680 690 700 710 720
LDLVSAKDLA GQLTEHDWNL FNRIHQVELI HYVLGPQHLR DVTTANLERF MRRFNELQYW
730 740 750 760 770 780
VATELCLCPV PGPRAQLLRK FIKLAAHLKE QKNLNSFFAV MFGLSNSAIS RLAHTWERLP
790 800 810 820 830 840
HKVRKLYSAL ERLLDPSWNH RVYRLALTKL SPPVIPFMPL LLKDMTFIHE GNHTLVENLI
850 860 870 880 890 900
NFEKMRMMAR AVRMLHHCRS HSTAPLSPLR SRVSHIHEDS QASRISTCSE QSLSTRSPAS
910 920
TWAYVQQLKV IDNQRELSRL SRELEP