TIAM1

TIAM1
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2D8I, 3KZD, 3KZE, 4GVC, 4GVD, 4K2O, 4K2P, 4NXP, 4NXQ, 4NXR
Identifikatori
Aliasi	TIAM1
Vanjski ID-jevi	OMIM: 600687 MGI: 103306 HomoloGene: 2443 GeneCards: TIAM1
Lokacija gena (miš)
Hrom.	Hromosom 16 (miš)
Kraj	89,940,657 bp
Obrazac RNK ekspresije
	; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• microtubule binding; • kinase binding; • GO:0001948, GO:0016582 vezivanje za proteine; • lipid binding; • guanyl-nucleotide exchange factor activity; • receptor tyrosine kinase binding;
Ćelijska komponenta	• citoplazma; • citosol; • membrana; • cell-cell junction; • cell-cell contact zone; • extrinsic component of cytoplasmic side of plasma membrane; • ćelijska membrana; • dendritična kičma; • axonal growth cone; • sinapsa; • main axon; • ruffle membrane; • međućelijske veze; • neuronal cell body; • somatodendritic compartment; • Mikrotubula; • jedro; • GO:0097483, GO:0097481 postsynaptic density; • glutamatergic synapse; • extrinsic component of postsynaptic density membrane;
Biološki proces	• protein localization to membrane; • GO:0097285 apoptoza; • regulation of insulin secretion involved in cellular response to glucose stimulus; • GO:0007243 intracellular signal transduction; • GO:0032861, GO:0032862, GO:0032856 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; • Ćelijska migracija; • positive regulation of dendritic spine morphogenesis; • GO:0072468 Transdukcija signala; • 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;
	Izvori:Amigo / QuickGO
Ortolozi
	7074
	21844
	ENSG00000156299
	ENSMUSG00000002489
	Q13009
	Q60610
	NM_003253
	NM_001145886; NM_001145887; NM_009384
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
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

T-ćelijski invazijski limfomski i metastazno inducirani protein 1 jest protein koji je kod ljudi kodiran genom TIAM1 sa hromosoma 21.^[4]^[5]^[6]

Aminokiselinska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 1.591 aminokiselina, a molekulska težina 177.508 Da.^[5]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MGNAESQHVE	HEFYGEKHAS	LGRKHTSRSL	RLSHKTRRTR	HASSGKVIHR
NSEVSTRSSS	TPSIPQSLAE	NGLEPFSQDG	TLEDFGSPIW	VDRVDMGLRP
VSYTDSSVTP	SVDSSIVLTA	ASVQSMPDTE	ESRLYGDDAT	YLAEGGRRQH
SYTSNGPTFM	ETASFKKKRS	KSADIWREDS	LEFSLSDLSQ	EHLTSNEEIL
GSAEEKDCEE	ARGMETRASP	RQLSTCQRAN	SLGDLYAQKN	SGVTANGGPG
SKFAGYCRNL	VSDIPNLANH	KMPPAAAEET	PPYSNYNTLP	CRKSHCLSEG
ATNPQISHSN	SMQGRRAKTT	QDVNAGEGSE	FADSGIEGAT	TDTDLLSRRS
NATNSSYSPT	TGRAFVGSDS	GSSSTGDAAR	QGVYENFRRE	LEMSTTNSES
LEEAGSAHSD	EQSSGTLSSP	GQSDILLTAA	QGTVRKAGAL	AVKNFLVHKK
NKKVESATRR	KWKHYWVSLK	GCTLFFYESD	GRSGIDHNSI	PKHAVWVENS
IVQAVPEHPK	KDFVFCLSNS	LGDAFLFQTT	SQTELENWIT	AIHSACATAV
ARHHHKEDTL	RLLKSEIKKL	EQKIDMDEKM	KKMGEMQLSS	VTDSKKKKTI
LDQIFVWEQN	LEQFQMDLFR	FRCYLASLQG	GELPNPKRLL	AFASRPTKVA
MGRLGIFSVS	SFHALVAART	GETGVRRRTQ	AMSRSASKRR	SRFSSLWGLD
TTSKKKQGRP	SINQVFGEGT	EAVKKSLEGI	FDDIVPDGKR	EKEVVLPNVH
QHNPDCDIWV	HEYFTPSWFC	LPNNQPALTV	VRPGDTARDT	LELICKTHQL
DHSAHYLRLK	FLIENKMQLY	VPQPEEDIYE	LLYKEIEICP	KVTQSIHIEK
SDTAADTYGF	SLSSVEEDGI	RRLYVNSVKE	TGLASKKGLK	AGDEILEINN
RAADALNSSM	LKDFLSQPSL	GLLVRTYPEL	EEGVELLESP	PHRVDGPADL
GESPLAFLTS	NPGHSLCSEQ	GSSAETAPEE	TEGPDLESSD	ETDHSSKSTE
QVAAFCRSLH	EMNPSDQSPS	PQDSTGPQLA	TMRQLSDADK	LRKVICELLE
TERTYVKDLN	CLMERYLKPL	QKETFLTQDE	LDVLFGNLTE	MVEFQVEFLK
TLEDGVRLVP	DLEKLEKVDQ	FKKVLFSLGG	SFLYYADRFK	LYSAFCASHT
KVPKVLVKAK	TDTAFKAFLD	AQNPKQQHSS	TLESYLIKPI	QRILKYPLLL
RELFALTDAE	SEEHYHLDVA	IKTMNKVASH	INEMQKIHEE	FGAVFDQLIA
EQTGEKKEVA	DLSMGDLLLH	TTVIWLNPPA	SLGKWKKEPE	LAAFVFKTAV
VLVYKDGSKQ	KKKLVGSHRL	SIYEDWDPFR	FRHMIPTEAL	QVRALASADA
EANAVCEIVH	VKSESEGRPE	RVFHLCCSSP	ESRKDFLKAV	HSILRDKHRR
QLLKTESLPS	SQQYVPFGGK	RLCALKGARP	AMSRAVSAPS	KSLGRRRRRL
ARNRFTIDSD	AVSASSPEKE	SQQPPGGGDT	DRWVEEQFDL	AQYEEQDDIK
ETDILSDDDE	FCESVKGASV	DRDLQERLQA	TSISQRERGR	KTLDSHASRM
AQLKKQAALS	GINGGLESAS	EEVIWVRRED	FAPSRKLNTE	I

Struktura[uredi | uredi izvor]

TIAM1 je usko povezan sa BAIAP2, kao podjedinicom. Sadrži jedan DH (DBL-homologija) domen, jedan PDZ domen, dva PH-domena i jedan Ras-vezujući RBD-domen.

Funkcija[uredi | uredi izvor]

TIAM1 modulira aktivnost Rho GTP-vezujućih proteina i povezuje vanćelijske signale sa aktivnostima citoskeleta. Osim toga, TIAM1 aktivira Rac1, CDC42 i u manjoj mjeri RhoA.

Klinički značaj[uredi | uredi izvor]

TIAM1 se nalazi u gotovo svim pregledanim tumorskim ćelijskim linijama, uključujući B– i T-limfom, neuroblastom, melanom i karcinome.

Interakcije[uredi | uredi izvor]

Pokazalo se da invazija limfoma T-ćelija i protein 1 koji indukuje metastaze reaguju sa ANK1,^[7] Myc,^[8] RAC1^[9]^[10] i PPP1R9B.^[11]

Tiam1 također stupa u interakciju s paracingulinom, koji ima ulogu u regrutovanju Tiam1 u spojeve i tako aktivira Rac1 na epitelnim spojevima.^[12]

Reference[uredi | uredi izvor]

^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000002489 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: TIAM1 T-cell lymphoma invasion and metastasis 1".
^ ^a ^b 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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 (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.
^ 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.

Dopunska literatura[uredi | uredi izvor]

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.
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.

Vanjski linkovi[uredi | uredi izvor]

[refGRCm38Ensembl-1] GRCm38: Ensembl release 89: ENSMUSG00000002489 - Ensembl, maj 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".

[pmid8595894-5] 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.

[pmid15340013-6] 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.

[pmid10893266-7] 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.

[pmid12446731-8] 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.

[pmid11130063-9] 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.

[pmid11595749-10] 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.

[pmid12531897-11] 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.

[pmid18653465-12] 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.

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