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ARF GTPase-activating protein GIT1; ARF GAP GIT1; G protein-coupled receptor kinase-interactor 1; GRK-interacting protein 1; cool-associated & tyrosine-phosphorylated protein 1; CAT-1; CAT1 (GIT1)
Function:
- GTPase-activating protein for the ADP ribosylation factor family
- may serve as a scaffold to bring together molecules to form signaling modules controlling vesicle trafficking, adhesion & cytoskeletal organization
- increases the speed of cell migration, & the size & rate of formation of protrusions, possibly by targeting PAK1 to adhesions & the leading edge of lamellipodia
- sequesters inactive non-Tyr-phosphorylated paxillin in cytoplasmic complexes
- phosphorylated on Tyr by PTK2 & SRC in growing fibroblasts
- Tyr-phosphorylation is increased following cell spreading on fibronectin, decreased in cells arrested in mitosis & increased in the ensuing G1 phase
- interacts with G protein-coupled receptor kinases: ADRBK1/GRK2, PPFIA1 & PPFIA4
- interacts with ARHGEF6/alpha-PIX, with ARHGEF7/beta-PIX, with PXN/paxillin & with PTK2/FAK
- component of cytoplasmic complexes, which also contain PXN, ARHGEF6 & PAK1
- interacts with TGFB1I1
- interacts with SCRIB
Structure:
- the paxillin-binding domain is masked in the full-length protein & is regulated by ARHGEF6 (putative)
- contains 3 ANK repeats
- contains 1 Arf-GAP domain
Compartment:
- cytoplasm
- cycles between at least 3 distinct intracellular compartments, including
a) focal adhesions
b) cytoplasmic complexes
c) membrane protrusions
- during cell migration, when cells detach, moves from the adhesions into the cytoplasmic complexes towards the leading edge, while, , while,
- when cells adhere, it is found in vinculin-containing adhesions
- recruitment to adhesions may be mediated by active Tyr-phosphorylated paxillin
Alternative splicing: named isoforms=2
Pathology:
- intron variant in GIT1 gene
- diminishes GIT1 protein expression
- associated with ADHD
General
ankyrin repeat domain protein (ANKRD)
ADP-ribosylation factor GTPase activating protein (ARF-GAP)
receptor
zinc finger protein
Properties
SIZE: entity length = 761 aa
MW = 84 kD
COMPARTMENT: cytoplasm
MOTIF: Arf-GAP domain
NAME: Arf-GAP domain
SITE: 1-124
MOTIF: Zn finger C4-type
SITE: 11-34
EFFECTOR-BOUND: Zn+2
ankyrin repeat
NAME: ankyrin repeat
SITE: 132-161
MOTIF: Ser phosphorylation site {S134}
ankyrin repeat
NAME: ankyrin repeat
SITE: 166-195
ankyrin repeat
NAME: ankyrin repeat
SITE: 199-228
MOTIF: Tyr phosphorylation site {Y224}
binding site
SITE: 251-415
FOR-BINDING-OF: focal adhesion kinase 1
MOTIF: binding site
SITE: 254-367
FOR-BINDING-OF: Rho guanine nucleotide exchange factor 6
Ser phosphorylation site {S361}
Ser phosphorylation site {S362}
Thr phosphorylation site {T364}
Ser phosphorylation site {S373}
Ser phosphorylation site {S375}
Tyr phosphorylation site {Y383}
Ser phosphorylation site {S385}
Ser phosphorylation site {S388}
Thr phosphorylation site {T392}
Ser phosphorylation site {S410}
Ser phosphorylation site {S508}
Tyr phosphorylation site {Y545}
Tyr phosphorylation site {Y554}
Ser phosphorylation site {S561}
Ser phosphorylation site {S592}
Ser phosphorylation site {S596}
Tyr phosphorylation site {Y598}
Thr phosphorylation site {T601}
PXN/TGFB1I1 interaction {637-761}
Database Correlations
OMIM 608434
UniProt Q9Y2X7
PFAM correlations
Entrez Gene 28964
Kegg hsa:28964
References
- UniProt :accession Q9Y2X7
- Won H et al.
GIT1 is associated with ADHD in humans and ADHD-like
behaviors in mice.
Nat Med 2011 May;17(5):566-72. Epub 2011 Apr 17
PMID: 21499268