RAPGEF3

Protein identityUniProt · HPA

UniProt accession

O95398

Gene

RAPGEF3

Ensembl

ENSG00000079337

Chromosome

12

Canonical length

923 aa

Protein class

Predicted intracellular proteins

Subcellular location

Endoplasmic reticulum,Cytosol

OverviewNCBI Gene

Enables guanyl-nucleotide exchange factor activity and protein domain specific binding activity. Involved in several processes, including Rap protein signal transduction; cellular response to cAMP; and regulation of syncytium formation by plasma membrane fusion. Located in several cellular components, including filopodium; lamellipodium; and microvillus. Implicated in nicotine dependence. Biomarker of congestive heart failure. [provided by Alliance of Genome Resources, Jul 2025]

Canonical amino-acid sequenceUniProt

923 residues, UniProt reviewed canonical sequence.

>O95398|RAPGEF3
     1  MKVGWPGESC WQVGLAVEDS PALGAPRVGA LPDVVPEGTL LNMVLRRMHR PRSCSYQLLL
    61  EHQRPSCIQG LRWTPLTNSE ESLDFSESLE QASTERVLRA GRQLHRHLLA TCPNLIRDRK
   121  YHLRLYRQCC SGRELVDGIL ALGLGVHSRS QVVGICQVLL DEGALCHVKH DWAFQDRDAQ
   181  FYRFPGPEPE PVRTHEMEEE LAEAVALLSQ RGPDALLTVA LRKPPGQRTD EELDLIFEEL
   241  LHIKAVAHLS NSVKRELAAV LLFEPHSKAG TVLFSQGDKG TSWYIIWKGS VNVVTHGKGL
   301  VTTLHEGDDF GQLALVNDAP RAATIILRED NCHFLRVDKQ DFNRIIKDVE AKTMRLEEHG
   361  KVVLVLERAS QGAGPSRPPT PGRNRYTVMS GTPEKILELL LEAMGPDSSA HDPTETFLSD
   421  FLLTHRVFMP SAQLCAALLH HFHVEPAGGS EQERSTYVCN KRQQILRLVS QWVALYGSML
   481  HTDPVATSFL QKLSDLVGRD TRLSNLLREQ WPERRRCHRL ENGCGNASPQ MKARNLPVWL
   541  PNQDEPLPGS SCAIQVGDKV PYDICRPDHS VLTLQLPVTA SVREVMAALA QEDGWTKGQV
   601  LVKVNSAGDA IGLQPDARGV ATSLGLNERL FVVNPQEVHE LIPHPDQLGP TVGSAEGLDL
   661  VSAKDLAGQL TDHDWSLFNS IHQVELIHYV LGPQHLRDVT TANLERFMRR FNELQYWVAT
   721  ELCLCPVPGP RAQLLRKFIK LAAHLKEQKN LNSFFAVMFG LSNSAISRLA HTWERLPHKV
   781  RKLYSALERL LDPSWNHRVY RLALAKLSPP VIPFMPLLLK DMTFIHEGNH TLVENLINFE
   841  KMRMMARAAR MLHHCRSHNP VPLSPLRSRV SHLHEDSQVA RISTCSEQSL STRSPASTWA
   901  YVQQLKVIDN QRELSRLSRE LEP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against RAPGEF3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.31

Highest tissue expression

42 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.95

gnomAD pLI

0

gnomAD missense Z

0.87

DepMap mean gene effect

0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adaptive immune response
• adenylate cyclase-activating G protein-coupled receptor signaling pathway
• angiogenesis
• associative learning
• cellular response to cAMP
• establishment of endothelial barrier
• intracellular signal transduction
• positive regulation of angiogenesis
• positive regulation of GTPase activity
• positive regulation of insulin secretion
• positive regulation of protein export from nucleus
• positive regulation of stress fiber assembly
• positive regulation of syncytium formation by plasma membrane fusion
• Rap protein signal transduction
• Ras protein signal transduction
• regulation of actin cytoskeleton organization
• regulation of angiogenesis
• regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• signal transduction
• negative regulation of syncytium formation by plasma membrane fusion

Molecular functions

• cAMP binding
• guanyl-nucleotide exchange factor activity
• protein domain specific binding

Cellular components

• endomembrane system
• extracellular exosome
• filopodium
• lamellipodium
• membrane
• microvillus
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• DEP domain
• Cyclic nucleotide-binding domain
• Ras-like guanine nucleotide exchange factor, N-terminal
• Ras guanine-nucleotide exchange factors catalytic domain
• Ras-like guanine nucleotide exchange factor
• RmlC-like jelly roll fold
• Cyclic nucleotide-binding domain superfamily
• Ras guanine-nucleotide exchange factor, conserved site
• Ras guanine nucleotide exchange factor domain superfamily
• Ubiquitin-like domain superfamily
• Winged helix-like DNA-binding domain superfamily
• Winged helix DNA-binding domain superfamily
• Ras guanine-nucleotide exchange factor, catalytic domain superfamily
• Cyclic nucleotide-binding domain
• Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP)
• RasGEF domain
• RasGEF N-terminal motif

KeywordsUniProt

• Angiogenesis
• cAMP
• cAMP-binding
• Guanine-nucleotide releasing factor
• Membrane
• Nucleotide-binding
• Phosphoprotein

InteractionsUniProt · HPA

Protein binding partners of RAPGEF3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• PDE3B
• PIK3R6