ARHGEF3
Rho guanine nucleotide exchange factor 3
Also known as: ARHG3_HUMAN, DKFZP434F2429, GEF3, STA3, XPLN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q9NR81
- Gene
- ARHGEF3
- Ensembl
- ENSG00000163947
- Chromosome
- 3
- Canonical length
- 526 aa
- Protein class
- Predicted intracellular proteins
- Subcellular location
- Cytosol
OverviewNCBI Gene
Rho-like GTPases are involved in a variety of cellular processes, and they are activated by binding GTP and inactivated by conversion of GTP to GDP by their intrinsic GTPase activity. Guanine nucleotide exchange factors (GEFs) accelerate the GTPase activity of Rho GTPases by catalyzing their release of bound GDP. This gene encodes a guanine nucleotide exchange factor, which specifically activates two members of the Rho GTPase family: RHOA and RHOB, both of which have a role in bone cell biology. It has been identified that genetic variation in this gene plays a role in the determination of bone mineral density (BMD), indicating the implication of this gene in postmenopausal osteoporosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
526 residues, UniProt reviewed canonical sequence.
>Q9NR81|ARHGEF3
1 MVAKDYPFYL TVKRANCSLE LPPASGPAKD AEEPSNKRVK PLSRVTSLAN LIPPVKATPL
61 KRFSQTLQRS ISFRSESRPD ILAPRPWSRN AAPSSTKRRD SKLWSETFDV CVNQMLTSKE
121 IKRQEAIFEL SQGEEDLIED LKLAKKAYHD PMLKLSIMTE QELNQIFGTL DSLIPLHEEL
181 LSQLRDVRKP DGSTEHVGPI LVGWLPCLSS YDSYCSNQVA AKALLDHKKQ DHRVQDFLQR
241 CLESPFSRKL DLWNFLDIPR SRLVKYPLLL REILRHTPND NPDQQHLEEA INIIQGIVAE
301 INTKTGESEC RYYKERLLYL EEGQKDSLID SSRVLCCHGE LKNNRGVKLH VFLFQEVLVI
361 TRAVTHNEQL CYQLYRQPIP VKDLLLEDLQ DGEVRLGGSL RGAFSNNERI KNFFRVSFKN
421 GSQSQTHSLQ ANDTFNKQQW LNCIRQAKET VLCAAGQAGV LDSEGSFLNP TTGSRELQGE
481 TKLEQMDQSD SESDCSMDTS EVSLDCERME QTDSSCGNSR HGESNVLocalizationUniProt · AlphaFold · HPA
Whether an antibody against ARHGEF3 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)
- 0.41
- Highest tissue expression
- 49 nTPM
Expression across tissuesHPA
Tissue
- parathyroid gland: 49 nTPM
- adrenal gland: 41 nTPM
- endometrium: 36 nTPM
- thymus: 34 nTPM
- smooth muscle: 32 nTPM
- choroid plexus: 31 nTPM
Single-cell type
- podocytes: 1,580 nCPM
- sertoli cells: 857 nCPM
- choroid plexus epithelial cells: 754 nCPM
- distal convoluted tubule cells: 607 nCPM
- renal connecting tubule cells: 559 nCPM
- adrenal cortex cells: 500 nCPM
Immune cell
- gdT-cell: 96 nTPM
- memory CD8 T-cell: 85 nTPM
- total PBMC: 76 nTPM
- memory CD4 T-cell: 74 nTPM
- naive CD8 T-cell: 74 nTPM
- MAIT T-cell: 73 nTPM
Brain region
- choroid plexus: 71 nTPM
- hippocampal formation: 60 nTPM
- cerebral cortex: 41 nTPM
- cerebellum: 35 nTPM
- basal ganglia: 31 nTPM
- white matter: 31 nTPM
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)
- 0.52
- gnomAD pLI
- 0
- gnomAD missense Z
- 2.08
- DepMap mean gene effect
- 0
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- positive regulation of Rho protein signal transduction
- regulation of small GTPase mediated signal transduction
- Rho protein signal transduction
Molecular functions
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Dbl homology domain
- Guanine-nucleotide dissociation stimulator, CDC24, conserved site
- Pleckstrin homology domain
- PH-like domain superfamily
- Dbl homology (DH) domain superfamily
- Endocytic & GEF Adapter
- SOS1/NGEF-like, PH domain
- RhoGEF domain
- SOS1/NGEF-like PH domain
- Rho guanine nucleotide exchange factor 3, PH domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of ARHGEF3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads ARHGEF3 as an antibody target. Whether an autoantibody or antibody against ARHGEF3 could matter depends on whether native ARHGEF3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
ARHGEF3 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label ARHGEF3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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