RAPGEF4

Protein identityUniProt · HPA

UniProt accession

Q8WZA2

Gene

RAPGEF4

Ensembl

ENSG00000091428

Chromosome

2

Canonical length

1011 aa

Protein class

Predicted intracellular proteins

Subcellular location

Plasma membrane,Focal adhesion sites,Basal body,Cytosol,Mid piece

OverviewNCBI Gene

Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in Ras protein signal transduction; regulation of neurotransmitter receptor localization to postsynaptic specialization membrane; and regulation of postsynapse organization. Predicted to act upstream of or within with a positive effect on hormone secretion. Predicted to act upstream of or within adenylate cyclase-activating G protein-coupled receptor signaling pathway; regulation of exocytosis; and secretion by cell. Predicted to be located in membrane. Predicted to be active in several cellular components, including glutamatergic synapse; hippocampal mossy fiber to CA3 synapse; and postsynaptic density. Implicated in autistic disorder. [provided by Alliance of Genome Resources, Apr 2025]

Canonical amino-acid sequenceUniProt

1011 residues, UniProt reviewed canonical sequence.

>Q8WZA2|RAPGEF4
     1  MVAAHAAHSS SSAEWIACLD KRPLERSSED VDIIFTRLKE VKAFEKFHPN LLHQICLCGY
    61  YENLEKGITL FRQGDIGTNW YAVLAGSLDV KVSETSSHQD AVTICTLGIG TAFGESILDN
   121  TPRHATIVTR ESSELLRIEQ KDFKALWEKY RQYMAGLLAP PYGVMETGSN NDRIPDKENT
   181  PLIEPHVPLR PANTITKVPS EKILRAGKIL RNAILSRAPH MIRDRKYHLK TYRQCCVGTE
   241  LVDWMMQQTP CVHSRTQAVG MWQVLLEDGV LNHVDQEHHF QDKYLFYRFL DDEHEDAPLP
   301  TEEEKKECDE ELQDTMLLLS QMGPDAHMRM ILRKPPGQRT VDDLEIIYEE LLHIKALSHL
   361  STTVKRELAG VLIFESHAKG GTVLFNQGEE GTSWYIILKG SVNVVIYGKG VVCTLHEGDD
   421  FGKLALVNDA PRAASIVLRE DNCHFLRVDK EDFNRILRDV EANTVRLKEH DQDVLVLEKV
   481  PAGNRASNQG NSQPQQKYTV MSGTPEKILE HFLETIRLEA TLNEATDSVL NDFIMMHCVF
   541  MPNTQLCPAL VAHYHAQPSQ GTEQEKMDYA LNNKRRVIRL VLQWAAMYGD LLQEDDVSMA
   601  FLEEFYVSVS DDARMIAALK EQLPELEKIV KQISEDAKAP QKKHKVLLQQ FNTGDERAQK
   661  RQPIRGSDEV LFKVYCMDHT YTTIRVPVAT SVKEVISAVA DKLGSGEGLI IVKMSSGGEK
   721  VVLKPNDVSV FTTLTINGRL FACPREQFDS LTPLPEQEGP TVGTVGTFEL MSSKDLAYQM
   781  TIYDWELFNC VHELELIYHT FGRHNFKKTT ANLDLFLRRF NEIQFWVVTE ICLCSQLSKR
   841  VQLLKKFIKI AAHCKEYKNL NSFFAIVMGL SNVAVSRLAL TWEKLPSKFK KFYAEFESLM
   901  DPSRNHRAYR LTVAKLEPPL IPFMPLLIKD MTFTHEGNKT FIDNLVNFEK MRMIANTART
   961  VRYYRSQPFN PDAAQANKNH QDVRSYVRQL NVIDNQRTLS QMSHRLEPRR P

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against RAPGEF4 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

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.26

Highest tissue expression

272 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)

0.29

gnomAD pLI

0.99

gnomAD missense Z

1.83

DepMap mean gene effect

-0.08

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
• calcium-ion regulated exocytosis
• G protein-coupled receptor signaling pathway
• insulin secretion
• positive regulation of insulin secretion
• Ras protein signal transduction
• regulation of exocytosis
• regulation of synaptic vesicle cycle

Molecular functions

• cAMP binding
• guanyl-nucleotide exchange factor activity
• protein-macromolecule adaptor activity
• small GTPase binding

Cellular components

• cytosol
• hippocampal mossy fiber to CA3 synapse
• membrane
• 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

• Alternative promoter usage
• cAMP
• cAMP-binding
• Cytoplasm
• Exocytosis
• Guanine-nucleotide releasing factor
• Membrane
• Nucleotide-binding
• Repeat

InteractionsUniProt · HPA

Protein binding partners of RAPGEF4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• RIMS1
• RIMS2
• BMERB1