T-lymphoma invasion & metastasis-inducing protein 2 (TIAM-2, SIF & TIAM1-like exchange factor, TIAM2, KIAA2016, STEF)
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Function
- modulates the activity of RHO-like proteins & connects extracellular signals to cytoskeletal activities
- acts as a GDP-dissociation stimulator protein that stimulates the GDP-GTP exchange activity of RHO-like GTPases & activates them
- mediates extracellular laminin signals to activate Rac1, contributing to neurite growth
- involved in lamellipodial formation & advancement of the growth cone of embryonic hippocampal neurons
- promotes migration of neurons in the cerebral cortex
- when overexpressed, induces membrane ruffling accompanied by the accumulation of actin filaments along the altered plasma membrane (putative)
- activates specifically RAC1, but not CDC42 & RHOA
- interacts with MAP1A, MAP1B, PARP1 & YWHAE
- phosphorylated on serine & threonine residues
- phosphorylated on Thr-1648 by Rho-kinase
- phosphorylation by Rho-kinase inhibits its guanine nucleotide exchange activity, its interaction with MAP1A, MAP1B, PARP1 & YWHAE & reduces its ability to promote neurite growth (putative)
Structure
- PH 1 domain & amino acids 621-782 (a region called TSS; otherwise known as CC-Ex) are necessary for membrane localization
- PH 1 & TSS domains are necessary for Rac1 activity
- PH 2 domain is engaged in the enhancement of catalytic activity of the adjacent DH domain
- PH 1, TSS & DH domains are necessary to induce neurite-like structure
- belongs to the TIAM family
- contains 1 DH (DBL-homology) domain
- contains 1 PDZ (DHR) domain
- contains 2 PH domains
- contains 1 RBD (Ras-binding) domain
Compartment
- cytoplasm (putative)
- cell projection, lamellipodium (putative), filopodium
- growth cone
- localizes to the plasma membrane in neurites (putative)
Alternative splicing
named isoforms=5
Expression
- expressed in the occipital, frontal & temporal lobes, cerebellum, putamen & testis