T-cell lymphoma invasion and metastasis-inducing protein 1

Rho guanine nucleotide exchange factor TIAM1 is a protein that in humans is encoded by the TIAM1 gene.

TIAM1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2D8I, 3KZD, 3KZE, 4GVC, 4GVD, 4K2O, 4K2P, 4NXP, 4NXQ, 4NXR
Identifiers
Aliases	TIAM1, T-cell lymphoma invasion and metastasis-inducing protein 1, T-cell lymphoma invasion and metastasis 1
External IDs	OMIM: 600687; MGI: 103306; HomoloGene: 2443; GeneCards: TIAM1; OMA:TIAM1 - orthologs
Gene location (Mouse) Chr. Chromosome 16 (mouse) Band 16 C3.3|16 51.5 cM Start 89,583,999 bp End 89,940,657 bp
RNA expression pattern Bgee Human Mouse (ortholog) n/a Top expressed in zygote primary oocyte secondary oocyte olfactory tubercle lobe of cerebellum medial geniculate nucleus lateral geniculate nucleus cerebellar vermis medial dorsal nucleus piriform cortex BioGPS More reference expression data
Gene ontology Molecular function microtubule binding kinase binding protein binding lipid binding guanyl-nucleotide exchange factor activity receptor tyrosine kinase binding Cellular component cytoplasm cytosol membrane cell-cell junction cell-cell contact zone extrinsic component of cytoplasmic side of plasma membrane plasma membrane dendritic spine axonal growth cone synapse main axon ruffle membrane cell junction soma somatodendritic compartment microtubule nucleus postsynaptic density glutamatergic synapse extrinsic component of postsynaptic density membrane Biological process protein localization to membrane apoptotic process regulation of insulin secretion involved in cellular response to glucose stimulus intracellular signal transduction activation of GTPase activity positive regulation of JUN kinase activity ephrin receptor signaling pathway cardiac muscle hypertrophy regulation of non-canonical Wnt signaling pathway positive regulation of axonogenesis neuron projection extension Wnt signaling pathway, planar cell polarity pathway regulation of dopaminergic neuron differentiation regulation of ERK1 and ERK2 cascade positive regulation of neuron projection development positive regulation of apoptotic process positive regulation of Schwann cell chemotaxis positive regulation of protein binding cell-matrix adhesion Rac protein signal transduction regulation of Rho protein signal transduction regulation of small GTPase mediated signal transduction cell migration positive regulation of dendritic spine morphogenesis signal transduction response to cocaine positive regulation of cell population proliferation positive regulation of cell migration NMDA selective glutamate receptor signaling pathway regulation of modification of postsynaptic actin cytoskeleton regulation of epithelial to mesenchymal transition positive regulation of epithelial to mesenchymal transition G protein-coupled receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7074 21844 Ensembl ENSG00000156299 ENSMUSG00000002489 UniProt Q13009 Q60610 RefSeq (mRNA) NM_003253 NM_001145886 NM_001145887 NM_009384 RefSeq (protein) NP_003244 NP_001340613 NP_001340614 NP_001340615 NP_001340616 NP_001340617 NP_001340618 NP_001340619 NP_001340620 NP_001340621 NP_001340622 NP_001340623 n/a Location (UCSC) n/a Chr 16: 89.58 – 89.94 Mb PubMed search
Wikidata
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Structure

TIAM1 is tightly associate with BAIAP2 as a subunit. It contains one DH (DBL-homology) domain, one PDZ domain, two PH domains and one Ras-binding RBD domain.

Function

TIAM1 modulates the activity of Rho GTP-binding proteins and connects extracellular signals to cytoskeletal activities. In addition, TIAM1 activates Rac1, CDC42, and to a lesser extent RhoA.

Clinical significance

TIAM1 is found in virtually all tumor cell lines examined including B- and T-lymphomas, neuroblastomas, melanomas and carcinomas.

Interactions

T-cell lymphoma invasion and metastasis-inducing protein 1 has been shown to interact with ANK1, Myc, RAC1 and PPP1R9B.

Tiam1 interacts also with para-cingulin, that plays a role in recruiting Tiam1 to junctions and thus activate Rac1 at epithelial junctions.

Further reading

• Habets GG, van der Kammen RA, Stam JC, Michiels F, Collard JG (Apr 1995). "Sequence of the human invasion-inducing TIAM1 gene, its conservation in evolution and its expression in tumor cell lines of different tissue origin". Oncogene. 10 (7): 1371–1376. PMID 7731688.
• Habets GG, van der Kammen RA, Jenkins NA, Gilbert DJ, Copeland NG, Hagemeijer A, Collard JG (1995). "The invasion-inducing TIAM1 gene maps to human chromosome band 21q22 and mouse chromosome 16". Cytogenetics and Cell Genetics. 70 (1–2): 48–51. doi:10.1159/000133989. PMID 7736788. S2CID 46831770.
• Michiels F, Habets GG, Stam JC, van der Kammen RA, Collard JG (May 1995). "A role for Rac in Tiam1-induced membrane ruffling and invasion". Nature. 375 (6529): 338–340. Bibcode:1995Natur.375..338M. doi:10.1038/375338a0. PMID 7753201. S2CID 4251212.
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (Apr 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry. 236 (1): 107–113. doi:10.1006/abio.1996.0138. PMID 8619474.
• Michiels F, Stam JC, Hordijk PL, van der Kammen RA, Ruuls-Van Stalle L, Feltkamp CA, Collard JG (Apr 1997). "Regulated membrane localization of Tiam1, mediated by the NH2-terminal pleckstrin homology domain, is required for Rac-dependent membrane ruffling and C-Jun NH2-terminal kinase activation". The Journal of Cell Biology. 137 (2): 387–398. doi:10.1083/jcb.137.2.387. PMC 2139766. PMID 9128250.
• Fleming IN, Elliott CM, Buchanan FG, Downes CP, Exton JH (Apr 1999). "Ca2+/calmodulin-dependent protein kinase II regulates Tiam1 by reversible protein phosphorylation". The Journal of Biological Chemistry. 274 (18): 12753–12758. doi:10.1074/jbc.274.18.12753. PMID 10212259.
• Bourguignon LY, Zhu H, Shao L, Chen YW (Jan 2000). "CD44 interaction with tiam1 promotes Rac1 signaling and hyaluronic acid-mediated breast tumor cell migration". The Journal of Biological Chemistry. 275 (3): 1829–1838. doi:10.1074/jbc.275.3.1829. PMID 10636882.
• Crompton AM, Foley LH, Wood A, Roscoe W, Stokoe D, McCormick F, Symons M, Bollag G (Aug 2000). "Regulation of Tiam1 nucleotide exchange activity by pleckstrin domain binding ligands". The Journal of Biological Chemistry. 275 (33): 25751–25759. doi:10.1074/jbc.M002050200. PMID 10835422.
• Bourguignon LY, Zhu H, Shao L, Chen YW (Jul 2000). "Ankyrin-Tiam1 interaction promotes Rac1 signaling and metastatic breast tumor cell invasion and migration". The Journal of Cell Biology. 150 (1): 177–191. doi:10.1083/jcb.150.1.177. PMC 2185563. PMID 10893266.
• Worthylake DK, Rossman KL, Sondek J (Dec 2000). "Crystal structure of Rac1 in complex with the guanine nucleotide exchange region of Tiam1". Nature. 408 (6813): 682–688. Bibcode:2000Natur.408..682W. doi:10.1038/35047014. PMID 11130063. S2CID 4429919.
• Otsuki Y, Tanaka M, Yoshii S, Kawazoe N, Nakaya K, Sugimura H (Apr 2001). "Tumor metastasis suppressor nm23H1 regulates Rac1 GTPase by interaction with Tiam1". Proceedings of the National Academy of Sciences of the United States of America. 98 (8): 4385–4390. Bibcode:2001PNAS...98.4385O. doi:10.1073/pnas.071411598. PMC 31844. PMID 11274357.
• Gao Y, Xing J, Streuli M, Leto TL, Zheng Y (Dec 2001). "Trp(56) of rac1 specifies interaction with a subset of guanine nucleotide exchange factors". The Journal of Biological Chemistry. 276 (50): 47530–47541. doi:10.1074/jbc.M108865200. PMID 11595749.
• Buchsbaum RJ, Connolly BA, Feig LA (Jun 2002). "Interaction of Rac exchange factors Tiam1 and Ras-GRF1 with a scaffold for the p38 mitogen-activated protein kinase cascade". Molecular and Cellular Biology. 22 (12): 4073–4085. doi:10.1128/MCB.22.12.4073-4085.2002. PMC 133864. PMID 12024021.
• Lambert JM, Lambert QT, Reuther GW, Malliri A, Siderovski DP, Sondek J, Collard JG, Der CJ (Aug 2002). "Tiam1 mediates Ras activation of Rac by a PI(3)K-independent mechanism". Nature Cell Biology. 4 (8): 621–625. doi:10.1038/ncb833. PMID 12134164. S2CID 21639425.
• Wennerberg K, Ellerbroek SM, Liu RY, Karnoub AE, Burridge K, Der CJ (Dec 2002). "RhoG signals in parallel with Rac1 and Cdc42". The Journal of Biological Chemistry. 277 (49): 47810–47817. doi:10.1074/jbc.M203816200. PMID 12376551.
• Otsuki Y, Tanaka M, Kamo T, Kitanaka C, Kuchino Y, Sugimura H (Feb 2003). "Guanine nucleotide exchange factor, Tiam1, directly binds to c-Myc and interferes with c-Myc-mediated apoptosis in rat-1 fibroblasts". The Journal of Biological Chemistry. 278 (7): 5132–5140. doi:10.1074/jbc.M206733200. PMID 12446731.
• Buchsbaum RJ, Connolly BA, Feig LA (May 2003). "Regulation of p70 S6 kinase by complex formation between the Rac guanine nucleotide exchange factor (Rac-GEF) Tiam1 and the scaffold spinophilin". The Journal of Biological Chemistry. 278 (21): 18833–18841. doi:10.1074/jbc.M207876200. PMID 12531897.