RAPGEF5

Protein identityUniProt · HPA

UniProt accession

Q92565

Gene

RAPGEF5

Ensembl

ENSG00000136237

Chromosome

7

Canonical length

580 aa

Protein class

Plasma proteins, Predicted intracellular proteins, RAS pathway related proteins

Subcellular location

Nucleoplasm,Nuclear bodies

OverviewNCBI Gene

Members of the RAS (see HRAS; MIM 190020) subfamily of GTPases function in signal transduction as GTP/GDP-regulated switches that cycle between inactive GDP- and active GTP-bound states. Guanine nucleotide exchange factors (GEFs), such as RAPGEF5, serve as RAS activators by promoting acquisition of GTP to maintain the active GTP-bound state and are the key link between cell surface receptors and RAS activation (Rebhun et al., 2000 [PubMed 10934204]).[supplied by OMIM, Mar 2008]

Canonical amino-acid sequenceUniProt

580 residues, UniProt reviewed canonical sequence.

>Q92565|RAPGEF5
     1  MGSSRLRVFD PHLERKDSAA ALSDRELPLP TFDVPYFKYI DEEDEDDEWS SRSQSSTEDD
    61  SVDSLLSDRY VVVSGTPEKI LEHLLNDLHL EEVQDKETET LLDDFLLTYT VFMTTDDLCQ
   121  ALLRHYSAKK YQGKEENSDV PRRKRKVLHL VSQWIALYKD WLPEDEHSKM FLKTIYRNVL
   181  DDVYEYPILE KELKEFQKIL GMHRRHTVDE YSPQKKNKAL FHQFSLKENW LQHRGTVTET
   241  EEIFCHVYIT EHSYVSVKAK VSSIAQEILK VVAEKIQYAE EDLALVAITF SGEKHELQPN
   301  DLVISKSLEA SGRIYVYRKD LADTLNPFAE NEESQQRSMR ILGMNTWDLA LELMNFDWSL
   361  FNSIHEQELI YFTFSRQGSG EHTANLSLLL QRCNEVQLWV ATEILLCSQL GKRVQLVKKF
   421  IKIAAHCKAQ RNLNSFFAIV MGLNTASVSR LSQTWEKIPG KFKKLFSELE SLTDPSLNHK
   481  AYRDAFKKMK PPKIPFMPLL LKDVTFIHEG NKTFLDNLVN FEKLHMIADT VRTLRHCRTN
   541  QFGDLSPKEH QELKSYVNHL YVIDSQQALF ELSHRIEPRV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against RAPGEF5 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)

0.31

Highest tissue expression

365 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about RAPGEF5.

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 110 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Dilated cardiomyopathy 1A

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)

0.31

gnomAD pLI

0.98

gnomAD missense Z

1.64

DepMap mean gene effect

0.1

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• nervous system development
• Ras protein signal transduction
• small GTPase-mediated signal transduction

Molecular functions

• GTP-dependent protein binding
• guanyl-nucleotide exchange factor activity

Cellular components

• nuclear body
• nucleoplasm
• nucleus
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Ras-like guanine nucleotide exchange factor, N-terminal
• Ras guanine-nucleotide exchange factors catalytic domain
• Ras-like guanine nucleotide exchange factor
• Ras guanine-nucleotide exchange factor, conserved site
• Ras guanine nucleotide exchange factor domain superfamily
• Ubiquitin-like domain superfamily
• Ras guanine-nucleotide exchange factor, catalytic domain superfamily
• RasGEF domain
• RasGEF N-terminal motif

KeywordsUniProt

• Guanine-nucleotide releasing factor
• Nucleus