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.[4][5][6]

TIAM1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTIAM1, T-cell lymphoma invasion and metastasis-inducing protein 1, T-cell lymphoma invasion and metastasis 1
External IDsOMIM: 600687 MGI: 103306 HomoloGene: 2443 GeneCards: TIAM1
Orthologs
SpeciesHumanMouse
Entrez

7074

21844

Ensembl

ENSG00000156299

ENSMUSG00000002489

UniProt

Q13009

Q60610

RefSeq (mRNA)

NM_003253

NM_001145886
NM_001145887
NM_009384

RefSeq (protein)

n/a

Location (UCSC)n/aChr 16: 89.58 – 89.94 Mb
PubMed search[2][3]
Wikidata
View/Edit HumanView/Edit Mouse

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,[7] Myc,[8] RAC1[9][10] and PPP1R9B.[11]

Tiam1 interacts also with para-cingulin, that plays a role in recruiting Tiam1 to junctions and thus activate Rac1 at epithelial junctions.[12]

References

  1. GRCm38: Ensembl release 89: ENSMUSG00000002489 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Entrez Gene: TIAM1 T-cell lymphoma invasion and metastasis 1".
  5. Chen H, Antonarakis SE (Nov 1995). "Localization of a human homolog of the mouse Tiam-1 gene to chromosome 21q22.1". Genomics. 30 (1): 123–127. doi:10.1006/geno.1995.0025. PMID 8595894.
  6. Uhlenbrock K, Eberth A, Herbrand U, Daryab N, Stege P, Meier F, Friedl P, Collard JG, Ahmadian MR (Sep 2004). "The RacGEF Tiam1 inhibits migration and invasion of metastatic melanoma via a novel adhesive mechanism". Journal of Cell Science. 117 (Pt 20): 4863–4871. doi:10.1242/jcs.01367. PMID 15340013.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. Guillemot L, Paschoud S, Jond L, Foglia A, Citi S (Oct 2008). "Paracingulin regulates the activity of Rac1 and RhoA GTPases by recruiting Tiam1 and GEF-H1 to epithelial junctions". Molecular Biology of the Cell. 19 (10): 4442–4453. doi:10.1091/mbc.E08-06-0558. PMC 2555940. PMID 18653465.

Further reading

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