GDF6

GDF6
Identifikatori
Aliasi	GDF6
Vanjski ID-jevi	OMIM: 601147 MGI: 95689 HomoloGene: 40883 GeneCards: GDF6
Lokacija gena (čovjek)
Hrom.	Hromosom 8 (čovjek)
Kraj	96,160,806 bp
Lokacija gena (miš)
Hrom.	Hromosom 4 (miš)
Kraj	9,862,345 bp
Ontologija gena
Molekularna funkcija	• cytokine activity; • protein homodimerization activity; • transforming growth factor beta receptor binding; • growth factor activity; • GO:0001948, GO:0016582 vezivanje za proteine;
Ćelijska komponenta	• extracellular region; • Vanćelijsko;
Biološki proces	• regulation of apoptotic process; • GO:0097285 apoptoza; • pathway-restricted SMAD protein phosphorylation; • retinal cell apoptotic process; • regulation of MAPK cascade; • cell development; • positive regulation of pathway-restricted SMAD protein phosphorylation; • BMP signaling pathway; • GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated; • multicellular organism development; • positive regulation of chondrocyte differentiation; • positive regulation of neuron differentiation; • activin receptor signaling pathway; • SMAD protein signal transduction; • positive regulation of p38MAPK cascade; • fat cell differentiation; • regulation of signaling receptor activity;
	Izvori:Amigo / QuickGO
Ortolozi
	392255
	242316
	ENSG00000156466
	ENSMUSG00000051279
	Q6KF10
	P43028
	NM_001001557
	NM_013526
	NP_001001557
	NP_038554
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Faktor diferencijacije rasta 6 (GDF6) je protein koji je kod ljudi kodiran genom GDF6.^[5]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 455 aminokiselina, а molekulska težina 50.662 Da.^[6]

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
MDTPRVLLSA	VFLISFLWDL	PGFQQASISS	SSSSAELGST	KGMRSRKEGK
MQRAPRDSDA	GREGQEPQPR	PQDEPRAQQP	RAQEPPGRGP	RVVPHEYMLS
IYRTYSIAEK	LGINASFFQS	SKSANTITSF	VDRGLDDLSH	TPLRRQKYLF
DVSMLSDKEE	LVGAELRLFR	QAPSAPWGPP	AGPLHVQLFP	CLSPLLLDAR
TLDPQGAPPA	GWEVFDVWQG	LRHQPWKQLC	LELRAAWGEL	DAGEAEARAR
GPQQPPPPDL	RSLGFGRRVR	PPQERALLVV	FTRSQRKNLF	AEMREQLGSA
EAAGPGAGAE	GSWPPPSGAP	DARPWLPSPG	RRRRRTAFAS	RHGKRHGKKS
RLRCSKKPLH	VNFKELGWDD	WIIAPLEYEA	YHCEGVCDFP	LRSHLEPTNH
AIIQTLMNSM	DPGSTPPSCC	VPTKLTPISI	LYIDAGNNVV	YKQYEDMVVE
SCGCR

Funkcija

GDF6 pripada natporodici transformirajućeg faktora rasta beta i može regulirati obrasce ektoderma, interakcijom s koštano-morfogenetskim faktorima,^[7] i kontrolom razvoja očiju.^[8]^[9]

Faktor diferencijacije rasta 6 (GDF6) je regulatorni protein povezan s rastom i diferencijacijom embriona u razvoju. GDF6 je kodiran genom GDF6. Član je superporodice transformirajućeg faktora rasta beta, koja je skupina proteina uključenih u ranu regulaciju ćelijskog rasta i razvoja . Pokazalo se da GDF6 ima važnu ulogu u oblikovanju epiderme^[10] i formiranju kostiju i zglobova.^[11] GDF6 inducira gene povezane s razvojem epiderme i može se direktno vezati za nogin, gen koji kontrolira razvoj neurona, kako bi blokirao njegov učinak.^[10] GDF6 stupa u interakciju s morfogenetskim proteinom kosti (BMP) za formiranje heterodimera koji mogu djelovati na regulaciju neuronske indukcije i uzorkovanja embriona u razvoju.^[10] Razvijanjem GDF6 "nokaut"-modela, naučnici su potisnuli ekspresiju GDF6 u embrionima miševa u razvoju. Ovim eksperimentom su uspjeli izravno povezati GDF6 s nekoliko poremećaja lobanje i kičmenih pršljenova, poput skolioza i hondrodisplazije, tipa Grebe.^[11]

Klinički značaj

GDF6 se periodično pojačava i specifično eksprimira u 80% melanoma. Pacijenti s manje GDF6 imali su manji rizik od metastaza i veće šanse za preživljavanje. Budući da je ekspresija GDF6 vrlo niska ili se ne može otkriti u većini zdravih tkiva odraslih osoba, njena inhibicija se može koristiti za liječenje ove smrtonosne bolesti.^[12]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000156466 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000051279 - 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.
^ Davidson AJ, Postlethwait JH, Yan YL, Beier DR, van Doren C, Foernzler D, Celeste AJ, Crosier KE, Crosier PS (februar 1999). "Isolation of zebrafish gdf7 and comparative genetic mapping of genes belonging to the growth/differentiation factor 5, 6, 7 subgroup of the TGF-beta superfamily". Genome Res. 9 (2): 121–9. doi:10.1101/gr.9.2.121 (neaktivno 31. 5. 2021). PMID 10022976.CS1 održavanje: DOI nije aktivan od 2021 (link)
^ "UniProt, Q6KF10" (jezik: engleski). Pristupljeno 18. 9. 2021.
^ Chang C, Hemmati-Brivanlou A (1999). "Xenopus GDF6, a new antagonist of noggin and a partner of BMPs". Development. 126 (15): 3347–57. doi:10.1242/dev.126.15.3347. PMID 10393114.
^ Asai-Coakwell M, French C, Berry K, Ye M, Koss R, Somerville M, Mueller R, van Heyningen V, Waskiewicz A, Lehmann O (2007). "GDF6, a Novel Locus for a Spectrum of Ocular Developmental Anomalies". Am J Hum Genet. 80 (2): 306–15. doi:10.1086/511280. PMC 1785352. PMID 17236135.
^ Hanel M, Hensey C (2006). "Eye and neural defects associated with loss of GDF6". BMC Dev Biol. 6: 43. doi:10.1186/1471-213X-6-43. PMC 1609107. PMID 17010201.
^ ^a ^b ^c Chang C, Hemmati-Brivanlou A (august 1999). "Xenopus GDF6, a new antagonist of noggin and a partner of BMPs". Development. 126 (15): 3347–57. doi:10.1242/dev.126.15.3347. PMID 10393114.
^ ^a ^b Settle SH, Rountree RB, Sinha A, Thacker A, Higgins K, Kingsley DM (februar 2003). "Multiple joint and skeletal patterning defects caused by single and double mutations in the mouse Gdf6 and Gdf5 genes". Dev. Biol. 254 (1): 116–30. doi:10.1016/S0012-1606(02)00022-2. PMID 12606286.
^ Venkatesan AM, Vyas R, Gramann AK, Dresser K, Gujja S, Bhatnagar S, Chhangawala S, Gomes CB, Xi HS, Lian CG, Houvras Y, Edwards YJ, Deng A, Green M, Ceol CJ (2017). "Ligand-activated BMP signaling inhibits cell differentiation and death to promote melanoma". The Journal of Clinical Investigation. 128 (1): 294–308. doi:10.1172/JCI92513. PMC 5749509. PMID 29202482.

Dopunska literatura

Chiquet BT, Hashmi SS, Henry R, et al. (2009). "Genomic screening identifies novel linkages and provides further evidence for a role of MYH9 in nonsyndromic cleft lip and palate". Eur. J. Hum. Genet. 17 (2): 195–204. doi:10.1038/ejhg.2008.149. PMC 2874967. PMID 18716610.
Mazerbourg S, Sangkuhl K, Luo CW, et al. (2005). "Identification of receptors and signaling pathways for orphan bone morphogenetic protein/growth differentiation factor ligands based on genomic analyses". J. Biol. Chem. 280 (37): 32122–32. doi:10.1074/jbc.M504629200. PMID 16049014. S2CID 23693180.
Storm EE, Huynh TV, Copeland NG, et al. (1994). "Limb alterations in brachypodism mice due to mutations in a new member of the TGF beta-superfamily". Nature. 368 (6472): 639–43. Bibcode:1994Natur.368..639S. doi:10.1038/368639a0. PMID 8145850. S2CID 31921634.
Zhang X, Li S, Xiao X, et al. (2009). "Mutational screening of 10 genes in Chinese patients with microphthalmia and/or coloboma". Mol. Vis. 15: 2911–8. PMC 2802294. PMID 20057906.
Erlacher L, McCartney J, Piek E, et al. (1998). "Cartilage-derived morphogenetic proteins and osteogenic protein-1 differentially regulate osteogenesis". J. Bone Miner. Res. 13 (3): 383–92. doi:10.1359/jbmr.1998.13.3.383. PMID 9525338. S2CID 25307046.
Tassabehji M, Fang ZM, Hilton EN, et al. (2008). "Mutations in GDF6 are associated with vertebral segmentation defects in Klippel-Feil syndrome". Hum. Mutat. 29 (8): 1017–27. doi:10.1002/humu.20741. PMID 18425797. S2CID 5276691.
Wolfman NM, Hattersley G, Cox K, et al. (1997). "Ectopic induction of tendon and ligament in rats by growth and differentiation factors 5, 6, and 7, members of the TGF-beta gene family". J. Clin. Invest. 100 (2): 321–30. doi:10.1172/JCI119537. PMC 508194. PMID 9218508.
Tomaski SM, Zalzal GH (1999). "In vitro regulation of expression of cartilage-derived morphogenetic proteins by growth hormone and insulinlike growth factor 1 in the bovine cricoid chondrocyte". Arch. Otolaryngol. Head Neck Surg. 125 (8): 901–6. doi:10.1001/archotol.125.8.901. PMID 10448738.
Asai-Coakwell M, French CR, Ye M, et al. (2009). "Incomplete penetrance and phenotypic variability characterize Gdf6-attributable oculo-skeletal phenotypes". Hum. Mol. Genet. 18 (6): 1110–21. doi:10.1093/hmg/ddp008. PMID 19129173.
Bobacz K, Gruber R, Soleiman A, et al. (2002). "Cartilage-derived morphogenetic protein-1 and -2 are endogenously expressed in healthy and osteoarthritic human articular chondrocytes and stimulate matrix synthesis". Osteoarthr. Cartil. 10 (5): 394–401. doi:10.1053/joca.2002.0522. PMID 12027540.
Gajavelli S, Wood PM, Pennica D, et al. (2004). "BMP signaling initiates a neural crest differentiation program in embryonic rat CNS stem cells". Exp. Neurol. 188 (2): 205–23. doi:10.1016/j.expneurol.2004.03.026. PMID 15246821. S2CID 27002904.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Chang SC, Hoang B, Thomas JT, et al. (1994). "Cartilage-derived morphogenetic proteins. New members of the transforming growth factor-beta superfamily predominantly expressed in long bones during human embryonic development". J. Biol. Chem. 269 (45): 28227–34. doi:10.1016/S0021-9258(18)46918-9. PMID 7961761.
Reddi AH (1995). "Cartilage morphogenesis: role of bone and cartilage morphogenetic proteins, homeobox genes and extracellular matrix". Matrix Biol. 14 (8): 599–606. doi:10.1016/S0945-053X(05)80024-1. PMID 9057810.
Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Shen B, Bhargav D, Wei A, et al. (2009). "BMP-13 Emerges as a Potential Inhibitor of Bone Formation". Int. J. Biol. Sci. 5 (2): 192–200. doi:10.7150/ijbs.5.192. PMC 2646266. PMID 19240811.

Vanjski linkovi

Šablon:Signalizacija TGF-beta

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000156466 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000051279 - 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.

[pmid10022976-5] Davidson AJ, Postlethwait JH, Yan YL, Beier DR, van Doren C, Foernzler D, Celeste AJ, Crosier KE, Crosier PS (februar 1999). "Isolation of zebrafish gdf7 and comparative genetic mapping of genes belonging to the growth/differentiation factor 5, 6, 7 subgroup of the TGF-beta superfamily". Genome Res. 9 (2): 121–9. doi:10.1101/gr.9.2.121 (neaktivno 31. 5. 2021). PMID 10022976.CS1 održavanje: DOI nije aktivan od 2021 (link)

[UniProt-6] "UniProt, Q6KF10" (jezik: engleski). Pristupljeno 18. 9. 2021.

[7] Chang C, Hemmati-Brivanlou A (1999). "Xenopus GDF6, a new antagonist of noggin and a partner of BMPs". Development. 126 (15): 3347–57. doi:10.1242/dev.126.15.3347. PMID 10393114.

[8] Asai-Coakwell M, French C, Berry K, Ye M, Koss R, Somerville M, Mueller R, van Heyningen V, Waskiewicz A, Lehmann O (2007). "GDF6, a Novel Locus for a Spectrum of Ocular Developmental Anomalies". Am J Hum Genet. 80 (2): 306–15. doi:10.1086/511280. PMC 1785352. PMID 17236135.

[9] Hanel M, Hensey C (2006). "Eye and neural defects associated with loss of GDF6". BMC Dev Biol. 6: 43. doi:10.1186/1471-213X-6-43. PMC 1609107. PMID 17010201.

[Chang_1999-10] Chang C, Hemmati-Brivanlou A (august 1999). "Xenopus GDF6, a new antagonist of noggin and a partner of BMPs". Development. 126 (15): 3347–57. doi:10.1242/dev.126.15.3347. PMID 10393114.

[Settle_2003-11] Settle SH, Rountree RB, Sinha A, Thacker A, Higgins K, Kingsley DM (februar 2003). "Multiple joint and skeletal patterning defects caused by single and double mutations in the mouse Gdf6 and Gdf5 genes". Dev. Biol. 254 (1): 116–30. doi:10.1016/S0012-1606(02)00022-2. PMID 12606286.

[pmid29202482-12] Venkatesan AM, Vyas R, Gramann AK, Dresser K, Gujja S, Bhatnagar S, Chhangawala S, Gomes CB, Xi HS, Lian CG, Houvras Y, Edwards YJ, Deng A, Green M, Ceol CJ (2017). "Ligand-activated BMP signaling inhibits cell differentiation and death to promote melanoma". The Journal of Clinical Investigation. 128 (1): 294–308. doi:10.1172/JCI92513. PMC 5749509. PMID 29202482.

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