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
  • focal adhesions
  • cytoplasmic complexes
  • 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

More general terms

• ADP-ribosylation factor GTPase activating protein (ARF-GAP)
• zinc finger protein
• receptor
• ankyrin repeat domain protein (ANKRD)

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=28964
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:28964
• OMIM: https://mirror.omim.org/entry/608434
• UniProt: http://www.uniprot.org/uniprot/Q9Y2X7.html