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TGFBR1

S Wikipedije, slobodne enciklopedije
(Preusmjereno sa TGF beta receptor 2)
TGFBR1
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

1B6C, 1IAS, 1PY5, 1RW8, 1VJY, 2L5S, 2PJY, 2WOT, 2WOU, 2X7O, 3FAA, 3GXL, 3HMM, 3KCF, 3KFD, 3TZM, 4X0M, 4X2J, 4X2K, 4X2N, 4X2G, 4X2F, 5E8W, 5E8X, 5E8U, 5E8T, 5E8S, 5E90, 5E8Z

Identifikatori
AliasiTGFBR1
Vanjski ID-jeviOMIM: 190181 MGI: 98728 HomoloGene: 3177 GeneCards: TGFBR1
Lokacija gena (čovjek)
Hromosom 9 (čovjek)
Hrom.Hromosom 9 (čovjek)[1]
Hromosom 9 (čovjek)
Genomska lokacija za TGFBR1
Genomska lokacija za TGFBR1
Bend9q22.33Početak99,104,038 bp[1]
Kraj99,154,192 bp[1]
Lokacija gena (miš)
Hromosom 4 (miš)
Hrom.Hromosom 4 (miš)[2]
Hromosom 4 (miš)
Genomska lokacija za TGFBR1
Genomska lokacija za TGFBR1
Bend4 B1|4 26.02 cMPočetak47,353,222 bp[2]
Kraj47,414,931 bp[2]
Ontologija gena
Molekularna funkcija type II transforming growth factor beta receptor binding
I-SMAD binding
transforming growth factor beta-activated receptor activity
kinase activity
signaling receptor binding
ATP binding
protein kinase activity
vezivanje iona metala
protein serine/threonine kinase activity
transforming growth factor beta receptor activity, type I
aktivnost sa transferazom
growth factor binding
transmembrane receptor protein serine/threonine kinase activity
GO:0001948, GO:0016582 vezivanje za proteine
SMAD binding
nucleotide binding
transforming growth factor beta binding
activin binding
Ćelijska komponenta endozom
membrana
bicellular tight junction
cell surface
Lipidni splav
integral component of membrane
receptor complex
ćelijska membrana
međućelijske veze
intracellular anatomical structure
intracellular membrane-bounded organelle
integral component of plasma membrane
activin receptor complex
jedro
Biološki proces skeletal system development
response to cholesterol
regulation of protein ubiquitination
post-embryonic development
protein phosphorylation
negative regulation of chondrocyte differentiation
mesenchymal cell differentiation
Angiogeneza
transforming growth factor beta receptor signaling pathway
positive regulation of filopodium assembly
extracellular structure organization
pharyngeal system development
GO:0097285 apoptoza
cellular response to transforming growth factor beta stimulus
pathway-restricted SMAD protein phosphorylation
positive regulation of protein kinase B signaling
GO:0009373 regulation of transcription, DNA-templated
Nefrogeneza
collagen fibril organization
thymus development
cell motility
negative regulation of extrinsic apoptotic signaling pathway
positive regulation of apoptotic signaling pathway
in utero embryonic development
negative regulation of transforming growth factor beta receptor signaling pathway
GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated
heart development
positive regulation of cell growth
parathyroid gland development
artery morphogenesis
blastocyst development
activin receptor signaling pathway
roof of mouth development
Ćelijska diferencijacija
male gonad development
Fosforilacija
skeletal system morphogenesis
Zarastanje rana
negative regulation of apoptotic process
epithelial to mesenchymal transition
Regulacija ekspresije gena
embryonic cranial skeleton morphogenesis
peptidyl-threonine phosphorylation
GO:0007243 intracellular signal transduction
positive regulation of endothelial cell proliferation
positive regulation of cell migration
regulation of epithelial to mesenchymal transition
positive regulation of pathway-restricted SMAD protein phosphorylation
endothelial cell activation
negative regulation of endothelial cell proliferation
transmembrane receptor protein serine/threonine kinase signaling pathway
lens development in camera-type eye
GO:0035404 peptidyl-serine phosphorylation
positive regulation of cell population proliferation
regulation of growth
neuron fate commitment
regulation of protein binding
endothelial cell migration
germ cell migration
positive regulation of SMAD protein signal transduction
cardiac epithelial to mesenchymal transition
GO:0072468 Transdukcija signala
anterior/posterior pattern specification
proepicardium development
ventricular trabecula myocardium morphogenesis
ventricular compact myocardium morphogenesis
positive regulation of epithelial to mesenchymal transition
protein deubiquitination
positive regulation of stress fiber assembly
regulation of cardiac muscle cell proliferation
ventricular septum morphogenesis
angiogenesis involved in coronary vascular morphogenesis
coronary artery morphogenesis
positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation
positive regulation of tight junction disassembly
epicardium morphogenesis
positive regulation of apoptotic process
GO:1901313 positive regulation of gene expression
pattern specification process
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_001130916
NM_001306210
NM_004612

NM_009370
NM_001312868
NM_001312869

RefSeq (bjelančevina)

NP_001124388
NP_001293139
NP_004603

NP_001299797
NP_001299798
NP_033396

Lokacija (UCSC)Chr 9: 99.1 – 99.15 MbChr 4: 47.35 – 47.41 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Beta receptor I transformirajućeg faktora rasta (aktivinski receptor A tipa sličnog kunazi II, 53kDa) je membranski vezani TGF-beta receptorski protein porodice receptora TGF-beta za superporodicu signalnih liganda TGF-beta. TGFBR1 je njegov ljudski gen.

Aminokiselinska sekvenca

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Dužina polipeptidnog lanca je 503 aminokiseline, а molekulska težina Da. 55 960[5]

1020304050
MEAAVAAPRPRLLLLVLAAAAAAAAALLPGATALQCFCHLCTKDNFTCVT
DGLCFVSVTETTDKVIHNSMCIAEIDLIPRDRPFVCAPSSKTGSVTTTYC
CNQDHCNKIELPTTVKSSPGLGPVELAAVIAGPVCFVCISLMLMVYICHN
RTVIHHRVPNEEDPSLDRPFISEGTTLKDLIYDMTTSGSGSGLPLLVQRT
IARTIVLQESIGKGRFGEVWRGKWRGEEVAVKIFSSREERSWFREAEIYQ
TVMLRHENILGFIAADNKDNGTWTQLWLVSDYHEHGSLFDYLNRYTVTVE
GMIKLALSTASGLAHLHMEIVGTQGKPAIAHRDLKSKNILVKKNGTCCIA
DLGLAVRHDSATDTIDIAPNHRVGTKRYMAPEVLDDSINMKHFESFKRAD
IYAMGLVFWEIARRCSIGGIHEDYQLPYYDLVPSDPSVEEMRKVVCEQKL
RPNIPNRWQSCEALRVMAKIMRECWYANGAARLTALRIKKTLSQLSQQEG
IKM

Funkcija

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Protein kodiran ovim genom formira heteromerni kompleks sa tipom II TGF-β receptora kada je vezan za TGF-β, transducirajući signal TGF-β sa ćelijske površine na citoplazmu. Kodirani protein je serin/treonin protein kinaza. Mutacije u ovom genu povezane su s sindromom Loeys – Dietzove aortne aneurizme (LDS, LDAS).[6]

Interakcije

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Pokazalo se da TGF beta receptor 1 stupa u interakciju skako slijedi:

Inhibitori

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Studije na životinjama

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Defekti se primjećuju kada je gen TGFBR-1 ili nokautiran ili kada je konstitutivno aktivan mutant TGFBR-1 (koji je aktivan u prisustvu ili odsustvu liganda)

U mišjim nokaut TGFBR-1 modelima, ženke bile su sterilne. Razvili su oviduktne divertikule i neispravan glatki mišić maternice, što znači da su slojevi glatkih mišića maternice bili slabo formirani. Oviduktni divertikule su male, ispupčene vrećice smještene na jajovodu, koji je cijev koja prenosi jajnu ćeliju iz jajnika u maternicu. Ova deformacija jajovoda nastala je obostrano i rezultirala je smanjenim razvojem embriona i njegovim otežanim prolaskom u maternicu. Ovulacija i oplodnja su se još dogoađale u nokautima, ali ostaci embriona pronađeni su u ovim oviduktnim divertikulama.[25]

Kod mišjih TGFBR-1 nock-in modela u kojima je konstitutivno aktivni gen TGFBR-1 uvjetno induciran, prekomjerna aktivacija receptora TGFBR-1 dovodi do neplodnosti, smanjenja broja žlijezda materice i hipermišićavih maternica (povećanje količina glatkih mišića u maternici).[26]

Ovi eksperimenti pokazuju da receptor TGFB-1 ima kritičnu ulogu u funkciji ženskog reproduktivnog trakta. Oni također pokazuju da genetičke mutacije u genu TGFBR-1 mogu dovesti do problema s plodnošću kod žena.

Reference

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000106799 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000007613 - Ensembl, maj 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "UniProt, P36897". Pristupljeno 12. 9. 2021.
  6. ^ "Entrez Gene: TGFBR1 transforming growth factor, beta receptor I (activin A receptor type II-like kinase, 53kDa)".
  7. ^ a b Razani B, Zhang XL, Bitzer M, von Gersdorff G, Böttinger EP, Lisanti MP (mart 2001). "Caveolin-1 regulates transforming growth factor (TGF)-beta/SMAD signaling through an interaction with the TGF-beta type I receptor". The Journal of Biological Chemistry. 276 (9): 6727–38. doi:10.1074/jbc.M008340200. PMID 11102446.
  8. ^ Guerrero-Esteo M, Sanchez-Elsner T, Letamendia A, Bernabeu C (august 2002). "Extracellular and cytoplasmic domains of endoglin interact with the transforming growth factor-beta receptors I and II". The Journal of Biological Chemistry. 277 (32): 29197–209. doi:10.1074/jbc.M111991200. PMID 12015308.
  9. ^ Barbara NP, Wrana JL, Letarte M (januar 1999). "Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-beta superfamily". The Journal of Biological Chemistry. 274 (2): 584–94. doi:10.1074/jbc.274.2.584. PMID 9872992.
  10. ^ Wang T, Donahoe PK, Zervos AS (juli 1994). "Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12". Science. 265 (5172): 674–6. doi:10.1126/science.7518616. PMID 7518616.
  11. ^ Liu F, Ventura F, Doody J, Massagué J (juli 1995). "Human type II receptor for bone morphogenic proteins (BMPs): extension of the two-kinase receptor model to the BMPs". Molecular and Cellular Biology. 15 (7): 3479–86. doi:10.1128/mcb.15.7.3479. PMC 230584. PMID 7791754.
  12. ^ Kawabata M, Imamura T, Miyazono K, Engel ME, Moses HL (decembar 1995). "Interaction of the transforming growth factor-beta type I receptor with farnesyl-protein transferase-alpha". The Journal of Biological Chemistry. 270 (50): 29628–31. doi:10.1074/jbc.270.50.29628. PMID 8530343.
  13. ^ Wrighton KH, Lin X, Feng XH (juli 2008). "Critical regulation of TGFbeta signaling by Hsp90". Proceedings of the National Academy of Sciences of the United States of America. 105 (27): 9244–9. doi:10.1073/pnas.0800163105. PMC 2453700. PMID 18591668.
  14. ^ Mochizuki T, Miyazaki H, Hara T, Furuya T, Imamura T, Watabe T, Miyazono K (juli 2004). "Roles for the MH2 domain of Smad7 in the specific inhibition of transforming growth factor-beta superfamily signaling". The Journal of Biological Chemistry. 279 (30): 31568–74. doi:10.1074/jbc.M313977200. PMID 15148321.
  15. ^ Asano Y, Ihn H, Yamane K, Kubo M, Tamaki K (januar 2004). "Impaired Smad7-Smurf-mediated negative regulation of TGF-beta signaling in scleroderma fibroblasts". The Journal of Clinical Investigation. 113 (2): 253–64. doi:10.1172/JCI16269. PMC 310747. PMID 14722617.
  16. ^ Koinuma D, Shinozaki M, Komuro A, Goto K, Saitoh M, Hanyu A, Ebina M, Nukiwa T, Miyazawa K, Imamura T, Miyazono K (decembar 2003). "Arkadia amplifies TGF-beta superfamily signalling through degradation of Smad7". The EMBO Journal. 22 (24): 6458–70. doi:10.1093/emboj/cdg632. PMC 291827. PMID 14657019.
  17. ^ Kavsak P, Rasmussen RK, Causing CG, Bonni S, Zhu H, Thomsen GH, Wrana JL (decembar 2000). "Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation". Molecular Cell. 6 (6): 1365–75. doi:10.1016/s1097-2765(00)00134-9. PMID 11163210.
  18. ^ Hayashi H, Abdollah S, Qiu Y, Cai J, Xu YY, Grinnell BW, Richardson MA, Topper JN, Gimbrone MA, Wrana JL, Falb D (juni 1997). "The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling". Cell. 89 (7): 1165–73. doi:10.1016/s0092-8674(00)80303-7. PMID 9215638. S2CID 16552782.
  19. ^ a b Datta PK, Moses HL (maj 2000). "STRAP and Smad7 synergize in the inhibition of transforming growth factor beta signaling". Molecular and Cellular Biology. 20 (9): 3157–67. doi:10.1128/mcb.20.9.3157-3167.2000. PMC 85610. PMID 10757800.
  20. ^ Griswold-Prenner I, Kamibayashi C, Maruoka EM, Mumby MC, Derynck R (novembar 1998). "Physical and functional interactions between type I transforming growth factor beta receptors and Balpha, a WD-40 repeat subunit of phosphatase 2A". Molecular and Cellular Biology. 18 (11): 6595–604. doi:10.1128/mcb.18.11.6595. PMC 109244. PMID 9774674.
  21. ^ Datta PK, Chytil A, Gorska AE, Moses HL (decembar 1998). "Identification of STRAP, a novel WD domain protein in transforming growth factor-beta signaling". The Journal of Biological Chemistry. 273 (52): 34671–4. doi:10.1074/jbc.273.52.34671. PMID 9856985.
  22. ^ Ebner R, Chen RH, Lawler S, Zioncheck T, Derynck R (novembar 1993). "Determination of type I receptor specificity by the type II receptors for TGF-beta or activin". Science. 262 (5135): 900–2. doi:10.1126/science.8235612. PMID 8235612.
  23. ^ Oh SP, Seki T, Goss KA, Imamura T, Yi Y, Donahoe PK, Li L, Miyazono K, ten Dijke P, Kim S, Li E (mart 2000). "Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis". Proceedings of the National Academy of Sciences of the United States of America. 97 (6): 2626–31. doi:10.1073/pnas.97.6.2626. PMC 15979. PMID 10716993.
  24. ^ Kawabata M, Chytil A, Moses HL (mart 1995). "Cloning of a novel type II serine/threonine kinase receptor through interaction with the type I transforming growth factor-beta receptor". The Journal of Biological Chemistry. 270 (10): 5625–30. doi:10.1074/jbc.270.10.5625. PMID 7890683.
  25. ^ Li Q, Agno JE, Edson MA, Nagaraja AK, Nagashima T, Matzuk MM (oktobar 2011). "Transforming growth factor β receptor type 1 is essential for female reproductive tract integrity and function". PLOS Genetics. 7 (10): e1002320. doi:10.1371/journal.pgen.1002320. PMC 3197682. PMID 22028666.
  26. ^ Gao Y, Duran S, Lydon JP, DeMayo FJ, Burghardt RC, Bayless KJ, Bartholin L, Li Q (februar 2015). "Constitutive activation of transforming growth factor Beta receptor 1 in the mouse uterus impairs uterine morphology and function". Biology of Reproduction. 92 (2): 34. doi:10.1095/biolreprod.114.125146. PMC 4435420. PMID 25505200.

Dopunska literatura

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Vanjski linkovi

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