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

TIAM1
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

2D8I, 3KZD, 3KZE, 4GVC, 4GVD, 4K2O, 4K2P, 4NXP, 4NXQ, 4NXR

Identifikatori
AliasiTIAM1
Vanjski ID-jeviOMIM: 600687 MGI: 103306 HomoloGene: 2443 GeneCards: TIAM1
Lokacija gena (miš)
Hromosom 16 (miš)
Hrom.Hromosom 16 (miš)[1]
Hromosom 16 (miš)
Genomska lokacija za TIAM1
Genomska lokacija za TIAM1
Bend16 C3.3|16 51.5 cMPočetak89,583,999 bp[1]
Kraj89,940,657 bp[1]
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
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_003253

NM_001145886
NM_001145887
NM_009384

RefSeq (bjelančevina)
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

Lokacija (UCSC)n/aChr 16: 89.58 – 89.94 Mb
PubMed pretraga[2][3]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Aminokiselinska sekvenca

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

1020304050
MGNAESQHVEHEFYGEKHASLGRKHTSRSLRLSHKTRRTRHASSGKVIHR
NSEVSTRSSSTPSIPQSLAENGLEPFSQDGTLEDFGSPIWVDRVDMGLRP
VSYTDSSVTPSVDSSIVLTAASVQSMPDTEESRLYGDDATYLAEGGRRQH
SYTSNGPTFMETASFKKKRSKSADIWREDSLEFSLSDLSQEHLTSNEEIL
GSAEEKDCEEARGMETRASPRQLSTCQRANSLGDLYAQKNSGVTANGGPG
SKFAGYCRNLVSDIPNLANHKMPPAAAEETPPYSNYNTLPCRKSHCLSEG
ATNPQISHSNSMQGRRAKTTQDVNAGEGSEFADSGIEGATTDTDLLSRRS
NATNSSYSPTTGRAFVGSDSGSSSTGDAARQGVYENFRRELEMSTTNSES
LEEAGSAHSDEQSSGTLSSPGQSDILLTAAQGTVRKAGALAVKNFLVHKK
NKKVESATRRKWKHYWVSLKGCTLFFYESDGRSGIDHNSIPKHAVWVENS
IVQAVPEHPKKDFVFCLSNSLGDAFLFQTTSQTELENWITAIHSACATAV
ARHHHKEDTLRLLKSEIKKLEQKIDMDEKMKKMGEMQLSSVTDSKKKKTI
LDQIFVWEQNLEQFQMDLFRFRCYLASLQGGELPNPKRLLAFASRPTKVA
MGRLGIFSVSSFHALVAARTGETGVRRRTQAMSRSASKRRSRFSSLWGLD
TTSKKKQGRPSINQVFGEGTEAVKKSLEGIFDDIVPDGKREKEVVLPNVH
QHNPDCDIWVHEYFTPSWFCLPNNQPALTVVRPGDTARDTLELICKTHQL
DHSAHYLRLKFLIENKMQLYVPQPEEDIYELLYKEIEICPKVTQSIHIEK
SDTAADTYGFSLSSVEEDGIRRLYVNSVKETGLASKKGLKAGDEILEINN
RAADALNSSMLKDFLSQPSLGLLVRTYPELEEGVELLESPPHRVDGPADL
GESPLAFLTSNPGHSLCSEQGSSAETAPEETEGPDLESSDETDHSSKSTE
QVAAFCRSLHEMNPSDQSPSPQDSTGPQLATMRQLSDADKLRKVICELLE
TERTYVKDLNCLMERYLKPLQKETFLTQDELDVLFGNLTEMVEFQVEFLK
TLEDGVRLVPDLEKLEKVDQFKKVLFSLGGSFLYYADRFKLYSAFCASHT
KVPKVLVKAKTDTAFKAFLDAQNPKQQHSSTLESYLIKPIQRILKYPLLL
RELFALTDAESEEHYHLDVAIKTMNKVASHINEMQKIHEEFGAVFDQLIA
EQTGEKKEVADLSMGDLLLHTTVIWLNPPASLGKWKKEPELAAFVFKTAV
VLVYKDGSKQKKKLVGSHRLSIYEDWDPFRFRHMIPTEALQVRALASADA
EANAVCEIVHVKSESEGRPERVFHLCCSSPESRKDFLKAVHSILRDKHRR
QLLKTESLPSSQQYVPFGGKRLCALKGARPAMSRAVSAPSKSLGRRRRRL
ARNRFTIDSDAVSASSPEKESQQPPGGGDTDRWVEEQFDLAQYEEQDDIK
ETDILSDDDEFCESVKGASVDRDLQERLQATSISQRERGRKTLDSHASRM
AQLKKQAALSGINGGLESASEEVIWVRREDFAPSRKLNTEI

Struktura

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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

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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

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

Interakcije

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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

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  1. ^ a b c 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".
  5. ^ 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.
  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.

Dopunska literatura

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Vanjski linkovi

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