FLT1

FLT1
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	1FLT, 1QSV, 1QSZ, 1QTY, 1RV6, 2XAC, 3HNG, 4CKV, 4CL7, 5EX3
Identifikatori
Aliasi	FLT1
Vanjski ID-jevi	OMIM: 165070 MGI: 95558 HomoloGene: 134179 GeneCards: FLT1
Lokacija gena (čovjek)
Hrom.	Hromosom 13 (čovjek)
Kraj	28,495,145 bp
Lokacija gena (miš)
Hrom.	Hromosom 5 (miš)
Kraj	147,662,821 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• vascular endothelial growth factor-activated receptor activity; • aktivnost sa transferazom; • nucleotide binding; • protein kinase activity; • placental growth factor-activated receptor activity; • kinase activity; • GO:0001948, GO:0016582 vezivanje za proteine; • transmembrane receptor protein tyrosine kinase activity; • protein tyrosine kinase activity; • ATP binding; • growth factor binding; • vascular endothelial growth factor binding;
Ćelijska komponenta	• citoplazma; • integral component of membrane; • endozom; • focal adhesion; • membrana; • receptor complex; • integral component of plasma membrane; • extracellular region; • Vanćelijsko; • ćelijska membrana; • actin cytoskeleton;
Biološki proces	• positive regulation of vascular endothelial growth factor receptor signaling pathway; • Ćelijska diferencijacija; • blood vessel morphogenesis; • vascular endothelial growth factor receptor-1 signaling pathway; • positive regulation of MAP kinase activity; • monocyte chemotaxis; • positive regulation of phospholipase C activity; • transmembrane receptor protein tyrosine kinase signaling pathway; • vascular endothelial growth factor signaling pathway; • Fosforilacija; • positive regulation of angiogenesis; • positive regulation of phosphatidylinositol 3-kinase activity; • multicellular organism development; • Hemotaksija; • protein phosphorylation; • vascular endothelial growth factor receptor signaling pathway; • embryonic morphogenesis; • Angiogeneza; • protein autophosphorylation; • positive regulation of phosphatidylinositol 3-kinase signaling; • peptidyl-tyrosine phosphorylation; • cellular response to vascular endothelial growth factor stimulus; • Ćelijska migracija; • positive regulation of MAPK cascade; • positive regulation of cell population proliferation; • positive regulation of cell migration; • sprouting angiogenesis; • positive regulation of ERK1 and ERK2 cascade; • negative regulation of vascular endothelial cell proliferation;
	Izvori:Amigo / QuickGO
Ortolozi
	2321
	14254
	ENSG00000102755
	ENSMUSG00000029648
	P17948
	P35969
	NM_001159920; NM_001160030; NM_001160031; NM_002019
	NM_010228; NM_001363135
	NP_001153392; NP_001153502; NP_001153503; NP_002010
	NP_034358; NP_001350064
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Receptor 1 vaskularnog endotelnog faktora rasta je protein koji je kod ljudi kodiran genom FLT1.^[5]

Aminokiselinska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 1.338 aminokiselina, a molekulska težina 150 769 Da .^[6]

Simboli

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
MVSYWDTGVL	LCALLSCLLL	TGSSSGSKLK	DPELSLKGTQ	HIMQAGQTLH
LQCRGEAAHK	WSLPEMVSKE	SERLSITKSA	CGRNGKQFCS	TLTLNTAQAN
HTGFYSCKYL	AVPTSKKKET	ESAIYIFISD	TGRPFVEMYS	EIPEIIHMTE
GRELVIPCRV	TSPNITVTLK	KFPLDTLIPD	GKRIIWDSRK	GFIISNATYK
EIGLLTCEAT	VNGHLYKTNY	LTHRQTNTII	DVQISTPRPV	KLLRGHTLVL
NCTATTPLNT	RVQMTWSYPD	EKNKRASVRR	RIDQSNSHAN	IFYSVLTIDK
MQNKDKGLYT	CRVRSGPSFK	SVNTSVHIYD	KAFITVKHRK	QQVLETVAGK
RSYRLSMKVK	AFPSPEVVWL	KDGLPATEKS	ARYLTRGYSL	IIKDVTEEDA
GNYTILLSIK	QSNVFKNLTA	TLIVNVKPQI	YEKAVSSFPD	PALYPLGSRQ
ILTCTAYGIP	QPTIKWFWHP	CNHNHSEARC	DFCSNNEESF	ILDADSNMGN
RIESITQRMA	IIEGKNKMAS	TLVVADSRIS	GIYICIASNK	VGTVGRNISF
YITDVPNGFH	VNLEKMPTEG	EDLKLSCTVN	KFLYRDVTWI	LLRTVNNRTM
HYSISKQKMA	ITKEHSITLN	LTIMNVSLQD	SGTYACRARN	VYTGEEILQK
KEITIRDQEA	PYLLRNLSDH	TVAISSSTTL	DCHANGVPEP	QITWFKNNHK
IQQEPGIILG	PGSSTLFIER	VTEEDEGVYH	CKATNQKGSV	ESSAYLTVQG
TSDKSNLELI	TLTCTCVAAT	LFWLLLTLFI	RKMKRSSSEI	KTDYLSIIMD
PDEVPLDEQC	ERLPYDASKW	EFARERLKLG	KSLGRGAFGK	VVQASAFGIK
KSPTCRTVAV	KMLKEGATAS	EYKALMTELK	ILTHIGHHLN	VVNLLGACTK
QGGPLMVIVE	YCKYGNLSNY	LKSKRDLFFL	NKDAALHMEP	KKEKMEPGLE
QGKKPRLDSV	TSSESFASSG	FQEDKSLSDV	EEEEDSDGFY	KEPITMEDLI
SYSFQVARGM	EFLSSRKCIH	RDLAARNILL	SENNVVKICD	FGLARDIYKN
PDYVRKGDTR	LPLKWMAPES	IFDKIYSTKS	DVWSYGVLLW	EIFSLGGSPY
PGVQMDEDFC	SRLREGMRMR	APEYSTPEIY	QIMLDCWHRD	PKERPRFAEL
VEKLGDLLQA	NVQQDGKDYI	PINAILTGNS	GFTYSTPAFS	EDFFKESISA
PKFNSGSSDD	VRYVNAFKFM	SLERIKTFEE	LLPNATSMFD	DYQGDSSTLL
ASPMLKRFTW	TDSKPKASLK	IDLRVTSKSK	ESGLSDVSRP	SFCHSSCGHV
SEGKRRFTYD	HAELERKIAC	CSPPPDYNSV	VLYSTPPI

Funkcija[uredi | uredi izvor]

Onkogen FLT pripada porodici src gena i srodan je onkogenu ROS (MIM 165020). Kao i drugi članovi ove porodice, pokazuje aktivnost tirozinske protein-kinaze, koja je važna za kontrolu proliferacije i diferencijacije ćelija. Struktura sekvence gena FLT nalikuje strukturi gena FMS (MIM 164770); stoga, Yoshida et al. (1987) predložili su naziv FLT kao akronim za FMS-sličnu tirozin-kinazu.^[7]

Nedavno je otkriveno da je ablacija VEGFR1 hemijskim i genetičkim putem povećala pretvorbu bijelog masnog tkiva u tamno masno tkivo, kao i povećala smeđu masnu angiogenezu kod miševa.^[8]

Utvrđeno je da funkcionalne genetičke varijacije u FLT1 (rs9582036) utiču na preživljavanje karcinom pluća ne-malih ćelija.^[9]

Interakcije[uredi | uredi izvor]

Pokazano je da FLT1 stupa u interakcije sa PLCG1 ^[10] i VEGF-B.^[11]^[12]

Također pogledajte[uredi | uredi izvor]

VEGF receptori

Reference[uredi | uredi izvor]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000102755 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000029648 - 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.
^ Shibuya M, Yamaguchi S, Yamane A, Ikeda T, Tojo A, Matsushime H, Sato M (april 1990). "Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family". Oncogene. 5 (4): 519–24. PMID 2158038.
^ "UniProt, P17948". Pristupljeno 11. 9. 2017.
^ "Entrez Gene: FLT1 fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)".
^ Seki T, Hosaka K, Fischer C, Lim S, Andersson P, Abe M, Iwamoto H, Gao Y, Wang X, Fong GH, Cao Y (februar 2018). "Ablation of endothelial VEGFR1 improves metabolic dysfunction by inducing adipose tissue browning". The Journal of Experimental Medicine. 215 (2): 611–626. doi:10.1084/jem.20171012. PMC 5789413. PMID 29305395.
^ Glubb DM, Paré-Brunet L, Jantus-Lewintre E, Jiang C, Crona D, Etheridge AS, Mirza O, Zhang W, Seiser EL, Rzyman W, Jassem J, Auman T, Hirsch FR, Owzar K, Camps C, Dziadziuszko R, Innocenti F (juli 2015). "Functional FLT1 Genetic Variation is a Prognostic Factor for Recurrence in Stage I-III Non-Small-Cell Lung Cancer". Journal of Thoracic Oncology. 10 (7): 1067–75. doi:10.1097/JTO.0000000000000549. PMC 4494119. PMID 26134224.
^ Cunningham SA, Arrate MP, Brock TA, Waxham MN (novembar 1997). "Interactions of FLT-1 and KDR with phospholipase C gamma: identification of the phosphotyrosine binding sites". Biochemical and Biophysical Research Communications. 240 (3): 635–9. doi:10.1006/bbrc.1997.7719. PMID 9398617.
^ Olofsson B, Korpelainen E, Pepper MS, Mandriota SJ, Aase K, Kumar V, Gunji Y, Jeltsch MM, Shibuya M, Alitalo K, Eriksson U (septembar 1998). "Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells". Proceedings of the National Academy of Sciences of the United States of America. 95 (20): 11709–14. doi:10.1073/pnas.95.20.11709. PMC 21705. PMID 9751730.
^ Makinen T, Olofsson B, Karpanen T, Hellman U, Soker S, Klagsbrun M, Eriksson U, Alitalo K (juli 1999). "Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1". The Journal of Biological Chemistry. 274 (30): 21217–22. doi:10.1074/jbc.274.30.21217. PMID 10409677.

Dopunska literatura[uredi | uredi izvor]

Petrova TV, Makinen T, Alitalo K (novembar 1999). "Signaling via vascular endothelial growth factor receptors". Experimental Cell Research. 253 (1): 117–30. doi:10.1006/excr.1999.4707. PMID 10579917.
Sato Y, Kanno S, Oda N, Abe M, Ito M, Shitara K, Shibuya M (maj 2000). "Properties of two VEGF receptors, Flt-1 and KDR, in signal transduction". Annals of the New York Academy of Sciences. 902 (1): 201–5, discussion 205–7. doi:10.1111/j.1749-6632.2000.tb06314.x. PMID 10865839.
Boyd AW, Lackmann M (decembar 2001). "Signals from Eph and ephrin proteins: a developmental tool kit". Science's STKE. 2001 (112): re20. doi:10.1126/stke.2001.112.re20. PMID 11741094.
Luttun A, Tjwa M, Carmeliet P (decembar 2002). "Placental growth factor (PlGF) and its receptor Flt-1 (VEGFR-1): novel therapeutic targets for angiogenic disorders". Annals of the New York Academy of Sciences. 979: 80–93. doi:10.1111/j.1749-6632.2002.tb04870.x. PMID 12543719.
Maynard SE, Venkatesha S, Thadhani R, Karumanchi SA (maj 2005). "Soluble Fms-like tyrosine kinase 1 and endothelial dysfunction in the pathogenesis of preeclampsia". Pediatric Research. 57 (5 Pt 2): 1R–7R. doi:10.1203/01.PDR.0000159567.85157.B7. PMID 15817508.
Shibuya M (2007). "Vascular endothelial growth factor receptor-1 (VEGFR-1/Flt-1): a dual regulator for angiogenesis". Angiogenesis. 9 (4): 225–30, discussion 231. doi:10.1007/s10456-006-9055-8. PMID 17109193.
Widmer M, Villar J, Benigni A, Conde-Agudelo A, Karumanchi SA, Lindheimer M (januar 2007). "Mapping the theories of preeclampsia and the role of angiogenic factors: a systematic review". Obstetrics and Gynecology. 109 (1): 168–80. doi:10.1097/01.AOG.0000249609.04831.7c. PMID 17197602.
López-Novoa JM (mart 2007). "Soluble endoglin is an accurate predictor and a pathogenic molecule in pre-eclampsia". Nephrology, Dialysis, Transplantation. 22 (3): 712–4. doi:10.1093/ndt/gfl768. PMID 17210583.
Poesen K, Lambrechts D, Van Damme P, Dhondt J, Bender F, Frank N, Bogaert E, Claes B, Heylen L, Verheyen A, Raes K, Tjwa M, Eriksson U, Shibuya M, Nuydens R, Van Den Bosch L, Meert T, D'Hooge R, Sendtner M, Robberecht W, Carmeliet P (oktobar 2008). "Novel role for vascular endothelial growth factor (VEGF) receptor-1 and its ligand VEGF-B in motor neuron degeneration". The Journal of Neuroscience. 28 (42): 10451–9. doi:10.1523/JNEUROSCI.1092-08.2008. PMID 18923022.
Joukov V, Kaipainen A, Jeltsch M, Pajusola K, Olofsson B, Kumar V, Eriksson U, Alitalo K (novembar 1997). "Vascular endothelial growth factors VEGF-B and VEGF-C". Journal of Cellular Physiology. 173 (2): 211–5. doi:10.1002/(SICI)1097-4652(199711)173:2<211::AID-JCP23>3.0.CO;2-H. PMID 9365524.
Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, MacDonald DD, Jin DK, Shido K, Kerns SA, Zhu Z, Hicklin D, Wu Y, Port JL, Altorki N, Port ER, Ruggero D, Shmelkov SV, Jensen KK, Rafii S, Lyden D (decembar 2005). "VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche". Nature. 438 (7069): 820–7. doi:10.1038/nature04186. PMC 2945882. PMID 16341007.

Vanjski linkovi[uredi | uredi izvor]

Portal Biologija

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000102755 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000029648 - 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.

[pmid2158038-5] Shibuya M, Yamaguchi S, Yamane A, Ikeda T, Tojo A, Matsushime H, Sato M (april 1990). "Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family". Oncogene. 5 (4): 519–24. PMID 2158038.

[UniProt-6] "UniProt, P17948". Pristupljeno 11. 9. 2017.

[7] "Entrez Gene: FLT1 fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)".

[8] Seki T, Hosaka K, Fischer C, Lim S, Andersson P, Abe M, Iwamoto H, Gao Y, Wang X, Fong GH, Cao Y (februar 2018). "Ablation of endothelial VEGFR1 improves metabolic dysfunction by inducing adipose tissue browning". The Journal of Experimental Medicine. 215 (2): 611–626. doi:10.1084/jem.20171012. PMC 5789413. PMID 29305395.

[9] Glubb DM, Paré-Brunet L, Jantus-Lewintre E, Jiang C, Crona D, Etheridge AS, Mirza O, Zhang W, Seiser EL, Rzyman W, Jassem J, Auman T, Hirsch FR, Owzar K, Camps C, Dziadziuszko R, Innocenti F (juli 2015). "Functional FLT1 Genetic Variation is a Prognostic Factor for Recurrence in Stage I-III Non-Small-Cell Lung Cancer". Journal of Thoracic Oncology. 10 (7): 1067–75. doi:10.1097/JTO.0000000000000549. PMC 4494119. PMID 26134224.

[pmid9398617-10] Cunningham SA, Arrate MP, Brock TA, Waxham MN (novembar 1997). "Interactions of FLT-1 and KDR with phospholipase C gamma: identification of the phosphotyrosine binding sites". Biochemical and Biophysical Research Communications. 240 (3): 635–9. doi:10.1006/bbrc.1997.7719. PMID 9398617.

[pmid9751730-11] Olofsson B, Korpelainen E, Pepper MS, Mandriota SJ, Aase K, Kumar V, Gunji Y, Jeltsch MM, Shibuya M, Alitalo K, Eriksson U (septembar 1998). "Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells". Proceedings of the National Academy of Sciences of the United States of America. 95 (20): 11709–14. doi:10.1073/pnas.95.20.11709. PMC 21705. PMID 9751730.

[pmid10409677-12] Makinen T, Olofsson B, Karpanen T, Hellman U, Soker S, Klagsbrun M, Eriksson U, Alitalo K (juli 1999). "Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1". The Journal of Biological Chemistry. 274 (30): 21217–22. doi:10.1074/jbc.274.30.21217. PMID 10409677.

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p r u Enzimi
Teme	Aktivno mjesto Alosterna regulacija Difuzijski limitirani enzim EC broj Enzimska kataliza Inhibicija enzimskih reakcija Kinetika enzima Koenzim Kooperativnost Lineweaver–Burkov dijagram Michaelis–Mentenova kinetika Mjesto vezanja Spisak enzima
Tipovi	EC1 Oksidoreduktaze/spisak EC2 Transferaze/spisak EC3 Hidrolaze/spisak EC4 Lijaze/spisak EC5 Izomeraze/spisak EC6 Ligaze/spisak