SOX10 Identifikatori Aliasi SOX10 Vanjski ID-jevi OMIM : 602229 MGI : 98358 HomoloGene : 5055 GeneCards : SOX10 Ontologija gena Molekularna funkcija • GO:0001105 transcription coactivator activity • transcription factor binding • chromatin binding • GO:0001948, GO:0016582 vezivanje za proteine • vezivanje identičnih proteina • promoter-specific chromatin binding • vezivanje sa DNK • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding Ćelijska komponenta • citoplazma • nukleoplazma • jedro • Hromatin • mitohondrija • mitochondrial outer membrane • membrana • extrinsic component of mitochondrial outer membrane Biološki proces • GO:0009373 regulation of transcription, DNA-templated • GO:0044324, GO:0003256, GO:1901213, GO:0046019, GO:0046020, GO:1900094, GO:0061216, GO:0060994, GO:1902064, GO:0003258, GO:0072212 regulation of transcription by RNA polymerase II • anatomical structure morphogenesis • transcription, DNA-templated • stem cell differentiation • GO:0045996 negative regulation of transcription, DNA-templated • transcription elongation from RNA polymerase II promoter • negative regulation of Schwann cell proliferation • GO:1901313 positive regulation of gene expression • positive regulation of myelination • cellular response to progesterone stimulus • GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated • oligodendrocyte development • central nervous system myelination • oligodendrocyte differentiation • in utero embryonic development • neural crest cell migration • morphogenesis of an epithelium • positive regulation of neuroblast proliferation • central nervous system development • peripheral nervous system development • positive regulation of gliogenesis • Ćelijska diferencijacija • melanocyte differentiation • lacrimal gland development • negative regulation of apoptotic process • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II • cell maturation • enteric nervous system development • digestive tract morphogenesis • developmental growth • morphogenesis of a branching epithelium • negative regulation of canonical Wnt signaling pathway Izvori:Amigo / QuickGO
Ortolozi Vrste Čovjek Miš Entrez Ensembl UniProt RefSeq (mRNK) RefSeq (bjelančevina) Lokacija (UCSC) Chr 22: 37.97 – 37.99 Mb Chr 15: 79.04 – 79.05 Mb PubMed pretraga[ 3] [ 4] Wikipodaci
Transkripcijski faktor SOX-10 jest protein koji je kod ljudi kodiran genom SOX10 sa hromosoma 22 .[ 5] [ 6] [ 7] [ 8]
Dužina polipeptidnog lanca je 466 aminokiselina , a molekulska težina 49.911 Da .[ 8]
10 20 30 40 50
MAEEQDLSEV ELSPVGSEEP RCLSPGSAPS LGPDGGGGGS GLRASPGPGE
LGKVKKEQQD GEADDDKFPV CIREAVSQVL SGYDWTLVPM PVRVNGASKS
KPHVKRPMNA FMVWAQAARR KLADQYPHLH NAELSKTLGK LWRLLNESDK
RPFIEEAERL RMQHKKDHPD YKYQPRRRKN GKAAQGEAEC PGGEAEQGGT
AAIQAHYKSA HLDHRHPGEG SPMSDGNPEH PSGQSHGPPT PPTTPKTELQ
SGKADPKRDG RSMGEGGKPH IDFGNVDIGE ISHEVMSNME TFDVAELDQY
LPPNGHPGHV SSYSAAGYGL GSALAVASGH SAWISKPPGV ALPTVSPPGV
DAKAQVKTET AGPQGPPHYT DQPSTSQIAY TSLSLPHYGS AFPSISRPQF
DYSDHQPSGP YYGHSGQASG LYSAFSYMGP SQRPLYTAIS DPSPSGPQSH
SPTHWEQPVY TTLSRP
Ovaj gen kodira člana porodice SOX (srodne SRY -u HMG-kutije ) porodice faktora transkripcije uključenih u regulaciju i razvoja embriona i određivanje ćelijske sudbine. Kodirani protein djeluje kao transkripcijski aktivator nakon formiranja proteinskog kompleksa s drugim proteinima. Ovaj protein djeluje kao nukleocitoplazmatski šatl-protein i važan je za razvoj nervnog grebena i perifernog nervnog sistema .[ 8]
U melanocitnim ćelijama, postoje dokazi da ekspresija gena SOX10 može biti regulirana transkripcijskim faktorom povezanim sa mikroftalmijom (MITF).[ 9]
Mutacije ovog gena povezane su sa Waardenburg-Shahovim sindromom [ 8] i uveinim melanomom .[ 10]
SOX10 se koristi kao imunohistohemijski marker, jer je pozitivan na:[ 11]
Melanom , iako dezmoplazik+jski melanomi mogu biti samo fokusno pozitivni.
Nevus
Imunohistohemijski nalaz SOX10 u
dermnom nevusu ima pozitivno obojene ćelije nevusa (strelice)
folikulima dlake][].
Imunohistohemijska obrada SOX10 olakšava prikaz
lentigo maligna , kao povećanog broja melanocita duž
stratum basale i jedarnog
plejomorfizma . Promjene su kontinuirane sa resekcijskom marginom (obilježeno žutom bojom, lijevo), što daje dijagnozu neradikalno uklonjenog
lentigo maligna .
Interakcija između SOX10 i PAX3 proučavana je najbolje kod pacijenata sa Waardenburgovim sindromom , autosomno dominantnim poremećajem koji je podijeljen u četiri različita tipa, na osnovu mutacije u dodatnim genima. Smatra se da su interakcije SOX10 i PAX3 regulatori drugih gena uključenih u simptome Waardenburgovog sindroma, posebno MITF , koji utiče na razvoj melanocita , kao i formiranje nervnog grebena . Ekspresija MITF može se transaktivirati pomoću SOX10 i PAX3, da bi imao aditivni efekt.[ 12] [ 13] Dva gena imaju međusomno bliska vezujuća mjesta na uzvodnom pojačivaču gena c-RET .[ 14] Također se smatra da SOX10 cilja na dopahrom-tautomerazu preko sinergijske interakcije sa MITF -om, što onda rezultira drugim promjenama melanocita .[ 15]
SOX10 može uticati na stvaranje transkripcije mijelinskih proteina putem njegove interakcije sa proteinima kao što su OLIG1 i EGR2 ,[ 16] [ 17] što je važno za funkcionalnost neurona . Identificirani su i ostali kofaktori , kao što su SP1 , OCT6 , NMI , FOXD3 i SOX2 .[ 18]
Interakcija između SOX10 i NMI javljaju se koeksprimirano u glijinim ćelijamama , gliomima i kičmenoj moždini i pokazalo se da modulira transkripcijsku aktivnost SOX10.[ 19]
^ a b c GRCh38: Ensembl release 89: ENSG00000100146 - Ensembl , maj 2017
^ a b c GRCm38: Ensembl release 89: ENSMUSG00000033006 - 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 .
^ Pingault V, Bondurand N, Kuhlbrodt K, Goerich DE, Préhu MO, Puliti A, Herbarth B, Hermans-Borgmeyer I, Legius E, Matthijs G, Amiel J, Lyonnet S, Ceccherini I, Romeo G, Smith JC, Read AP, Wegner M, Goossens M (Feb 1998). "SOX10 mutations in patients with Waardenburg-Hirschsprung disease". Nature Genetics . 18 (2): 171–3. doi :10.1038/ng0298-171 . PMID 9462749 . S2CID 2327032 .
^ Bondurand N, Kuhlbrodt K, Pingault V, Enderich J, Sajus M, Tommerup N, Warburg M, Hennekam RC, Read AP, Wegner M, Goossens M (Sep 1999). "A molecular analysis of the yemenite deaf-blind hypopigmentation syndrome: SOX10 dysfunction causes different neurocristopathies" . Human Molecular Genetics . 8 (9): 1785–9. doi :10.1093/hmg/8.9.1785 . PMID 10441344 .
^ Huber WE, Price ER, Widlund HR, Du J, Davis IJ, Wegner M, Fisher DE (Nov 2003). "A tissue-restricted cAMP transcriptional response: SOX10 modulates alpha-melanocyte-stimulating hormone-triggered expression of microphthalmia-associated transcription factor in melanocytes" . The Journal of Biological Chemistry . 278 (46): 45224–30. doi :10.1074/jbc.M309036200 . PMID 12944398 .
^ a b c d "Entrez Gene: SOX10 SRY (sex determining region Y)-box 10" .
^ Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (Dec 2008). "Novel MITF targets identified using a two-step DNA microarray strategy" . Pigment Cell & Melanoma Research . 21 (6): 665–76. doi :10.1111/j.1755-148X.2008.00505.x . PMID 19067971 .
^ Das D, Kaur I, Ali MJ, Biswas NK, Das S, Kumar S, Honavar SG, Maitra A, Chakrabarti S, Majumder PP (Jul 2014). "Exome sequencing reveals the likely involvement of SOX10 in uveal melanoma". Optometry and Vision Science . 91 (7): e185–92. doi :10.1097/OPX.0000000000000309 . PMID 24927141 . S2CID 24239911 .
^ Nat Pernick. "Stains - SOX10" . Pathology Outlines . Topic Completed: 1 February 2014. Revised: 20 September 2019
^ Potterf SB, Furumura M, Dunn KJ, Arnheiter H, Pavan WJ (July 2000). "Transcription factor hierarchy in Waardenburg syndrome: regulation of MITF expression by SOX10 and PAX3". Hum. Genet . 107 (1): 1–6. doi :10.1007/s004390000328 . PMID 10982026 . S2CID 24931810 .
^ Bondurand N, Pingault V, Goerich DE, Lemort N, Le Caignec C, Wegner M, Goossens M (August 2000). "Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome" . Hum. Mol. Genet . 9 (13): 1907–17. doi :10.1093/hmg/9.13.1907 . PMID 10942418 .
^ Lang D, Epstein JA (April 2003). "Sox10 and Pax3 physically interact to mediate activation of a conserved c-RET enhancer" . Hum. Mol. Genet . 12 (8): 937–45. doi :10.1093/hmg/ddg107 . PMID 12668617 .
^ Ludwig A, Rehberg S, Wegner, M (January 2004). "Melanocyte-specific expression of dopachrome tautomerase is dependent on synergistic gene activation by the Sox10 and Mitf transcription factors" . FEBS Letters . 556 (1–3): 236–44. doi :10.1016/s0014-5793(03)01446-7 . PMID 14706856 . S2CID 8245142 .
^ Li H, Lu Y, Smith HK, Richardson W (December 2007). "Olig1 and Sox10 Interact Synergistically to Drive Myelin Basic Protein Transcription in Oligodendrocytes" . The Journal of Neuroscience . 27 (52): 14375–82. doi :10.1523/jneurosci.4456-07.2007 . PMC 6329447 . PMID 18160645 .
^ LeBlanc S, Ward R, Svaren, J (May 2007). "Neuropathy-Associated Egr2 Mutants Disrupt Cooperative Activation of Myelin Protein Zero by Egr2 and Sox10" . Mol. Cell. Biol . 27 (9): 3521–29. doi :10.1128/mcb.01689-06 . PMC 1899967 . PMID 17325040 .
^ Bondurand N, Sham MH (October 2013). "The role of SOX10 during enteric nervous system development" . Dev. Biol . 382 (1): 330–43. doi :10.1016/j.ydbio.2013.04.024 . PMID 23644063 .
^ Schlierf B, Lang S, Kosian T, Werner T, Wegner M (November 2011). "The high-mobility group transcription factor Sox10 interacts with the N-myc-interacting protein Nmi". J. Mol. Biol . 353 (5): 1033–42. doi :10.1016/j.jmb.2005.09.013 . PMID 16214168 .
Jacobs JM, Wilson J (1992). "An unusual demyelinating neuropathy in a patient with Waardenburg's syndrome" . Acta Neuropathol . 83 (6): 670–4. doi :10.1007/BF00299420 . PMID 1636383 . S2CID 35774306 .
Southard-Smith EM, Kos L, Pavan WJ (1998). "Sox10 mutation disrupts neural crest development in Dom Hirschsprung mouse model" . Nat. Genet . 18 (1): 60–4. doi :10.1038/ng0198-60 . PMID 9425902 . S2CID 25574343 .
Kuhlbrodt K, Schmidt C, Sock E, Pingault V, Bondurand N, Goossens M, Wegner M (1998). "Functional analysis of Sox10 mutations found in human Waardenburg-Hirschsprung patients" . J. Biol. Chem . 273 (36): 23033–8. doi :10.1074/jbc.273.36.23033 . PMID 9722528 .
Pusch C, Hustert E, Pfeifer D, Südbeck P, Kist R, Roe B, Wang Z, Balling R, Blin N, Scherer G (1998). "The SOX10/Sox10 gene from human and mouse: sequence, expression, and transactivation by the encoded HMG domain transcription factor". Hum. Genet . 103 (2): 115–23. doi :10.1007/s004390050793 . PMID 9760192 . S2CID 20623767 .
Inoue K, Tanabe Y, Lupski JR (1999). "Myelin deficiencies in both the central and the peripheral nervous systems associated with a SOX10 mutation" . Ann. Neurol . 46 (3): 313–8. doi :10.1002/1531-8249(199909)46:3<313::AID-ANA6>3.0.CO;2-7 . PMID 10482261 .
Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP (1999). "The DNA sequence of human chromosome 22" . Nature . 402 (6761): 489–95. Bibcode :1999Natur.402..489D . doi :10.1038/990031 . PMID 10591208 .
Touraine RL, Attié-Bitach T, Manceau E, Korsch E, Sarda P, Pingault V, Encha-Razavi F, Pelet A, Augé J, Nivelon-Chevallier A, Holschneider AM, Munnes M, Doerfler W, Goossens M, Munnich A, Vekemans M, Lyonnet S (2000). "Neurological phenotype in Waardenburg syndrome type 4 correlates with novel SOX10 truncating mutations and expression in developing brain" . Am. J. Hum. Genet . 66 (5): 1496–503. doi :10.1086/302895 . PMC 1378013 . PMID 10762540 .
Bondurand N, Pingault V, Goerich DE, Lemort N, Sock E, Le Caignec C, Wegner M, Goossens M (2000). "Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome" . Hum. Mol. Genet . 9 (13): 1907–17. doi :10.1093/hmg/9.13.1907 . PMID 10942418 .
Smit DJ, Smith AG, Parsons PG, Muscat GE, Sturm RA (2000). "Domains of Brn-2 that mediate homodimerization and interaction with general and melanocytic transcription factors" . Eur. J. Biochem . 267 (21): 6413–22. doi :10.1046/j.1432-1327.2000.01737.x . PMID 11029584 .
Sham MH, Lui VC, Chen BL, Fu M, Tam PK (2001). "Novel mutations of SOX10 suggest a dominant negative role in Waardenburg-Shah syndrome" . J. Med. Genet . 38 (9): 30e–30. doi :10.1136/jmg.38.9.e30 . PMC 1734934 . PMID 11546831 .
Rehberg S, Lischka P, Glaser G, Stamminger T, Wegner M, Rosorius O (2002). "Sox10 is an active nucleocytoplasmic shuttle protein, and shuttling is crucial for Sox10-mediated transactivation" . Mol. Cell. Biol . 22 (16): 5826–34. doi :10.1128/MCB.22.16.5826-5834.2002 . PMC 133963 . PMID 12138193 .
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Lang D, Epstein JA (2003). "Sox10 and Pax3 physically interact to mediate activation of a conserved c-RET enhancer" . Hum. Mol. Genet . 12 (8): 937–45. doi :10.1093/hmg/ddg107 . PMID 12668617 .
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Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država , koji je u javnom vlasništvu .
(1) Basic domains
(1.1) Osnovni leucine zipper (bZIP )(1.2) Basic helix-loop-helix (bHLH )
Group A Group B Grupa C bHLH-PAS Grupa D Grupa E Grupa F bHLH-COE
(1.3) bHLH-ZIP (1.4) NF-1 (1.5) RF-X (1.6) Basic helix-span-helix (bHSH)
(2) Cinkov prst DNA-binding domains
(2.1) Nuclear receptor (Cys4 )
potporodica 1 potporodica 2 potporodica 3 potporodica 4 potporodica 5 potporodica 6 potporodica 0
(2.2) Other Cys4 (2.3) Cys2 His2 (2.4) Cys6 (2.5) Alternating composition (2.6) WRKY
(4) β-Scaffold factors with minor groove contacts
(0) Other transcription factors