ARHGAP26 (GTPase activating protein for Rho associated with FAK)

2000-11-01   Stig Bojesen  , Arndt Borkhardt  

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

Atlas Image

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 IDLast YearTitleAuthors
    109086482000The 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 IDTranscript IDUniprot
    ENSG00000145819ENST00000274498Q9UNA1
    ENSG00000145819ENST00000418236H0Y835
    ENSG00000145819ENST00000419676H7C3P8
    ENSG00000145819ENST00000421521H7BZE1
    ENSG00000145819ENST00000424007H7C1J1
    ENSG00000145819ENST00000425417H7C205
    ENSG00000145819ENST00000443045H7BZZ0
    ENSG00000145819ENST00000443674H0Y4P9
    ENSG00000145819ENST00000451259C9J6V4
    ENSG00000145819ENST00000469131A0A2R8YDK5
    ENSG00000145819ENST00000475287A0A2R8Y5C0
    ENSG00000145819ENST00000642734A0A2R8YGB3
    ENSG00000145819ENST00000645722Q9UNA1
    ENSG00000145819ENST00000645722A0A0S2Z536

    Expression (GTEx)

    0
    5
    10
    15
    20
    25
    30
    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

    PathwaySourceExternal ID
    Signal TransductionREACTOMER-HSA-162582
    Signaling by Rho GTPasesREACTOMER-HSA-194315
    Rho GTPase cycleREACTOMER-HSA-194840

    Protein levels (Protein atlas)

    Not detected
    Low
    Medium
    High
    cerebral cortex
    cerebellum
    hippocampus
    caudate
    thyroid gland
    parathyroid gland
    adrenal gland
    nasopharynx
    bronchus
    lung
    oral mucosa
    salivary gland
    esophagus
    stomach 1
    stomach 2
    duodenum
    small intestine
    colon
    rectum
    liver
    gallbladder
    pancreas
    kidney
    urinary bladder
    testis
    seminal vesicle
    prostate
    vagina
    ovary
    fallopian tube
    endometrium 1
    endometrium 2
    cervix, uterine
    placenta
    breast
    heart muscle
    smooth muscle
    skeletal muscle
    soft tissue 1
    soft tissue 2
    adipose tissue
    skin 1
    skin 2
    appendix
    spleen
    lymph node
    tonsil
    bone marrow

    References

    Pubmed IDYearTitleCitations
    368494602023CEMIP, acting as a scaffold protein for bridging GRAF1 and MIB1, promotes colorectal cancer metastasis via activating CDC42/MAPK pathway.2
    380818472023GRAF1 integrates PINK1-Parkin signaling and actin dynamics to mediate cardiac mitochondrial homeostasis.4
    368494602023CEMIP, acting as a scaffold protein for bridging GRAF1 and MIB1, promotes colorectal cancer metastasis via activating CDC42/MAPK pathway.2
    380818472023GRAF1 integrates PINK1-Parkin signaling and actin dynamics to mediate cardiac mitochondrial homeostasis.4
    347168592022The role of GTPase-activating protein ARHGAP26 in human cancers.6
    351714502022Associations of ARHGAP26 Polymorphisms with Alzheimer's Disease and Cardiovascular Disease.3
    362925722022Missense Variants in GFRA1 and NPNT Are Associated with Congenital Anomalies of the Kidney and Urinary Tract.1
    347168592022The role of GTPase-activating protein ARHGAP26 in human cancers.6
    351714502022Associations of ARHGAP26 Polymorphisms with Alzheimer's Disease and Cardiovascular Disease.3
    362925722022Missense Variants in GFRA1 and NPNT Are Associated with Congenital Anomalies of the Kidney and Urinary Tract.1
    305923232019Hypoxia-induced ARHGAP26 deficiency inhibits the proliferation and migration of human ductus arteriosus smooth muscle cell through activating RhoA-ROCK-PTEN pathway.3
    307199982019Circular RNA ARHGAP26 is over-expressed and its downregulation inhibits cell proliferation and promotes cell apoptosis in gastric cancer cells.9
    310040812019SMURF1-mediated ubiquitination of ARHGAP26 promotes ovarian cancer cell invasion and migration.17
    305923232019Hypoxia-induced ARHGAP26 deficiency inhibits the proliferation and migration of human ductus arteriosus smooth muscle cell through activating RhoA-ROCK-PTEN pathway.3
    307199982019Circular RNA ARHGAP26 is over-expressed and its downregulation inhibits cell proliferation and promotes cell apoptosis in gastric cancer cells.9

    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/deep-insight-explorer/js/lib/favicon/favicon-32x32.png