ARHGAP26 (GTPase activating protein for Rho associated with FAK)

2000-11-01 Stig Bojesen , Arndt Borkhardt Affiliation

Dept. clinical biochemistry, Copenhagen Univeristy hospiatl, Rigshospitalet Blegdamsvej 9 DK-2100 Copenhagen, Denmark

Identity

HGNC

ARHGAP26

LOCATION

5q31.3

LOCUSID

23092

ALIAS

GRAF,GRAF1,OPHN1L,OPHN1L1

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

At least 24 exons.

Transcription

Two isoforms of 2277 bp (leukocytes) and 2442 bp (brain); transcripts of 4,4 and 9,5 kb.

Proteins

Description

Isoform A: 759 amino acids, 86 kDa; isoform B: 814 amino acids, 92 kDa.

Expression

Highly expressed in epithelial tissues i.e. pancreas islet beta-cells, testicles, prostate, mammary gland, GI glands, squamous layer of skin epithelium; highly expressed in nervous tissues including enteric ganglia; expressed in cardiomyocytes, erythropoiesis cells and liver.

Localisation

Mainly cytoplasmatic.

Function

Interacts with FAK and RhoA both in vivo and in vitro; acts as GTPase activating protein (GAP) for the active GTP-bound RhoA; negative regulator of RhoA.

Homology

Oligophrenin-1, Beta-chimerin, BCR.

Mutations

Germinal

Not known

Somatic

Deletion of four bases (251-254, A in ATG=nt1)

Insert 1158
GRAF-base 1144, 5 1 TA GAG ACA GGA TTT CAT CAT GTT GGC CAG GTT GGT TTT GAA
42 TTC CTG ACC TCA AGT GAT CCA CCT GCC TCG GCC TCC CAA AGT
84 GGT GGG ATT TTG G 3
......GRAF-base 1145

Insert 1299
GRAF-base 1285, 5 1 TC ATC GTT GTC ATA TAA ATC GGC GAG GTA ATA TTC CAT CAG
42 GTA GAC ATA CG 3
...GRAF-base 1286.Predicted STOP codon underlined.

Insert 2002
GRAF-base 1988 5 1 G GTT CAT GCG AGT TCA GCA AGC AGT TAC CAT GTC TAC GGC
41 ATG CCA GGA TAC TGT TGG GAA GGT AGT ATT CCG T 3
...GRAF-base 1989

Implicated in

Entity name

t(5;11)(q31;q23) / acute non lymphocytic leukemia --> KMT2A - ARHGAP26

Prognosis

Unknown; only a few cases

Hybrid gene

5 MLL 3 GRAF

Fusion protein

MLL-GRAF

Disease

Acute non lymphocytic leukemia and myelodysplastic syndrome with del(5q)

Prognosis

Unknown

Cytogenetics

del(5q)

Oncogenesis

Basically unknown; a bi-allelic loss of GRAF has been documented in three cases of AML.

Bibliography

Pubmed ID	Last Year	Title	Authors
10908648	2000	The human GRAF gene is fused to MLL in a unique t(5;11)(q31;q23) and both alleles are disrupted in three cases of myelodysplastic syndrome/acute myeloid leukemia with a deletion 5q.	Borkhardt A et al

Other Information

Locus ID:

NCBI: 23092
MIM: 605370
HGNC: 17073
Ensembl: ENSG00000145819

Variants:

dbSNP: 23092
ClinVar: 23092
TCGA: ENSG00000145819
COSMIC: ARHGAP26

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000145819	ENST00000274498	Q9UNA1
ENSG00000145819	ENST00000418236	H0Y835
ENSG00000145819	ENST00000419676	H7C3P8
ENSG00000145819	ENST00000421521	H7BZE1
ENSG00000145819	ENST00000424007	H7C1J1
ENSG00000145819	ENST00000425417	H7C205
ENSG00000145819	ENST00000443045	H7BZZ0
ENSG00000145819	ENST00000443674	H0Y4P9
ENSG00000145819	ENST00000451259	C9J6V4
ENSG00000145819	ENST00000469131	A0A2R8YDK5
ENSG00000145819	ENST00000475287	A0A2R8Y5C0
ENSG00000145819	ENST00000642734	A0A2R8YGB3
ENSG00000145819	ENST00000645722	Q9UNA1
ENSG00000145819	ENST00000645722	A0A0S2Z536

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Signal Transduction	REACTOME	R-HSA-162582
Signaling by Rho GTPases	REACTOME	R-HSA-194315
Rho GTPase cycle	REACTOME	R-HSA-194840

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
20379614	2010	Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.	62
21622574	2011	Skeletal muscle differentiation and fusion are regulated by the BAR-containing Rho-GTPase-activating protein (Rho-GAP), GRAF1.	35
24067935	2013	ADAR1 regulates ARHGAP26 gene expression through RNA editing by disrupting miR-30b-3p and miR-573 binding.	34
9858476	1999	Cytoskeletal changes induced by GRAF, the GTPase regulator associated with focal adhesion kinase, are mediated by Rho.	31
21965292	2011	The endocytic protein GRAF1 is directed to cell-matrix adhesion sites and regulates cell spreading.	27
26446261	2015	Endocytic membrane turnover at the leading edge is driven by a transient interaction between Cdc42 and GRAF1.	13
18929667	2009	Dissecting the thermodynamics of GAP-RhoA interactions.	9
20602808	2010	Decreased expression of GRAF1/OPHN-1-L in the X-linked alpha thalassemia mental retardation syndrome.	8
21074269	2011	Abnormal methylation of GRAF promoter Chinese patients with acute myeloid leukemia.	5
31004081	2019	SMURF1-mediated ubiquitination of ARHGAP26 promotes ovarian cancer cell invasion and migration.	3

Citation

Stig Bojesen ; Arndt Borkhardt

ARHGAP26 (GTPase activating protein for Rho associated with FAK)

Atlas Genet Cytogenet Oncol Haematol. 2000-11-01

Online version: http://atlasgeneticsoncology.org/gene/291/arhgap26-(gtpase-activating-protein-for-rho-associated-with-fak)