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FLASH GENE

Symbol

TIAM1

contributors: mct - updated : 31-05-2022

HGNC name	TIAM Rac1 associated GEF 1
HGNC id	11805

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	DDIDSDS developmental delay, intellectual disability, speech delay and seizures
Location	21q22.11      Physical location : 32.490.735 - 32.931.290
Synonym name	T-cell lymphoma invasion and metastasis 1
	human T-lymphoma invasion and metastasis inducing TIAM1 protein
Synonym symbol(s)	FLJ36302, TIAM-1

DNA

TYPE	functioning gene
STRUCTURE	440.67 kb     29 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003253 29 - 7308 NP_003244 - 1591 - 2010 20802514 NM_001353690 28 - 7255 NP_001340619 - 1591 - 2010 20802514 NM_001353688 30 - 7593 NP_001340617 - 1591 - 2010 20802514 NM_001353691 30 - 7404 NP_001340620 - 1591 - 2010 20802514 NM_001353692 28 - 7198 NP_001340621 - 1591 - 2010 20802514 NM_001353689 29 - 7375 NP_001340618 - 1591 - 2010 20802514 NM_001353687 27 - 7143 NP_001340616 - 1566 - 2010 20802514 NM_001353686 28 - 7143 NP_001340615 - 1566 - 2010 20802514 NM_001353694 28 - 7218 NP_001340623 - 1591 - 2010 20802514 NM_001353685 13 - 4152 NP_001340614 - 599 - 2010 20802514 NM_001353684 13 - 4227 NP_001340613 - 624 - 2010 20802514 NM_001353693 29 - 7647 NP_001340622 - 1591 - 2010 20802514

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Nervous brain       highly Homo sapiens   brain limbic system hippocampus dentate gyrus highly Homo sapiens Reproductive male system testis     highly

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal pleckstrin homology coiled-coiled extension (PHn-CC-Ex) and catalytic DBL homology domain (DH) modulating the activity of Rac1, RHO-like protein
	a DHR/PDZ (PSD95/disc large/ZO-1) domain
	C-terminal pleckstrin homology (DH-PHc) domain

HOMOLOGY

interspecies	homolog to murine T lymphoma invasion and metastasis inducing gene 1 (Tiam1)
	ortholog to drosophila Sif

Homologene

FAMILY

DBL-family guanine nucleotide exchange factor (GEF)

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
text	TIAM1 localises to centrosomes during S-phase, where it is required for the maintenance of normal centriole number

basic FUNCTION	putative GDP-GTP exchange factor, involved in neural cell development
	may function in cellular signaling by activation of a Rho-like GTPase that regulates the cytoskeletal organization
	playing an important role in invasion and metastasis of colorectal carcinoma and is a metastasis-related gene
	mediates neurite outgrowth induced by ephrin-B1 and EPHA2
	required for the activation of Rac1, actin polymerization, relocation of junctional associated proteins, and disruption of interendothelial junctions
	modulating the balance of Rho GTPase activities in the growth cone and, consequently, to control growth cone behavior
	required for chemokine- and S1P-induced Rac activation and subsequent cell migration
	implicated in tumor invasion and metastasis
	integrates signals from CADM1 to regulate the actin cytoskeleton through RAC activation, which may lead to tissue infiltration of leukemic cells in adult T-cell leukemia patients
	guanine exchange factor (GEF) for the Rho-family GTPase Rac1 that is crucial for the integrity of adherens junctions, tight junctions, and cell-matrix interactions
	mediator of NGF/NTRK1-dependent neurite elongation (mediates NTRK1 signaling and neurite outgrowth induced by NGF)
	implicated in multiple signaling pathways in epithelial tumor cells
	may have a role in modulating the effects of the tumor microenvironment on malignant cell invasion and metastasis
	is a metastasis-related gene, that may contribute to hepatocellular carcinoma invasion and metastasis
	TIAM1 plays a critical role in the development of glutamatergic perforant path-dentate gyrus synapses
	TIAM1 is a key regulator of dentate gyrus (DG) granule cell stabilization and function within hippocampal circuits
	promotes the formation and growth of spines and synapses by activating RAC1 signaling pathways that control the actin cytoskeleton

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	activator of Rho-like GTPases RAC
	SDC1 and CASPR4, are potential TIAM1 PDZ domain binding proteins
	interactions with different scaffold proteins activating different RAC1-dependent pathways by recruiting specific RAC1 effector proteins
	two TIAM1-interacting proteins in fibroblasts, insulin receptor substrate protein 53 kDa (BAIAP2) and PPP1R9B
	plays a role in clathrin-dependent endocytosis of EPHA8-ephrinA5 complexes
	interacting with ITGB2 (TCR-induced activation of ITGB2 involves signaling through TIAM1)
	GRIN2C and TIAM1 maturation genes are synergistically controlled by the activity-dependent induction of ETV1 and its phosphorylation by the BDNF signaling cascade
	RAC1 exchange factor TIAM1 participates in polarized cell migration with the PAR complex of PARD3, PARD6A, and PRKCI
	MAP1B-TIAM1 interaction, and pleckstrin homology (PH) domains in TIAM1 are responsible for MAP1B binding
	BAI1 interacts with PARD3/TIAM1 and recruits these proteins to synaptic sites
	RAB23 promotes squamous cell carcinoma cells migration and invasion by regulating ITGB1/TIAM1/RAC1 pathway
	TIAM1, and its cognate Rho-family G protein, RAC1, regulate interleukin (IL)17A transcription and autoimmunity
	SETDB1-TIAM1 compounds were involved in a novel pathway, which regulated epigenetic modification of gene expression in hepatocellular carcinoma (HCC)
	SH3GL3 stimulates cell migration by binding the Rac GEF TIAM1 leading to activation of small GTPase
	mediates RAC1 activation and contraction-induced glucose uptake in skeletal muscle cells
	regulates PLK4 levels through promoting BTRC-mediated degradation independently of RAC1 activation

cell & other

REGULATION

activated by

SIRT1, SIRT2, that positively regulate the levels of TIAM1, a Rac guanine nucleotide exchange factor (GEF)

Other	phosphorylated on Y384 by SRC (which is required for SRC-induced adherens junctions disassembly and cell migration, and creates a docking site on TIAM1 for GRB2)
	is auto-inhibited by its pleckstrin homology coiled-coil extension domain (

ASSOCIATED DISORDERS

corresponding disease(s)

DDIDSDS

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in colorectal cancer, especially in metastatic cases, associated with hypomethylation of promoter region in colorectal cancer tissues

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	prognostic marker for esophageal squamous cell carcinoma (ESCC)
	may be a prognostic factor for the treatment of thyroid cancers
	may be a useful biomarker for therapeutic strategy and control in hepatocellular carcinoma (HCC) treatment
Therapy target
	System Type Disorder Pubmed cancer     pharmacologic reversal of promoter hypomethylation may inhibit cell proliferation and migration immunology inflammatory   activation of a TIAM1-Rac1 signaling module, is a potential novel therapeutic target against increased vascular permeability associated with inflammatory diseases cancer endocrine thyroid potential therapeutic target for the treatment of thyroid cancers immunology autoimmune multiple sclerosis TIAM1/RAC1 may be a therapeutic target in multiple sclerosis

ANIMAL & CELL MODELS

mice lacking Tiam1 have simplified dendritic arbors, reduced dendritic spine density, and diminished excitatory synaptic transmission in the dentate gyrus