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TCOF1
Identifikatori
Aliasi	TCOF1
Vanjski ID-jevi	OMIM: 606847 MGI: 892003 HomoloGene: 68049 GeneCards: TCOF1
Lokacija gena (čovjek)
Hrom.	Hromosom 5 (čovjek)
Kraj	150,400,308 bp
Lokacija gena (miš)
Hrom.	Hromosom 18 (miš)
Kraj	60,982,043 bp
Obrazac RNK ekspresije
	; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• GO:0001948, GO:0016582 vezivanje za proteine; • transporter activity; • vezivanje sa RNK; • RNA polymerase I core binding; • protein heterodimerization activity; • scaffold protein binding;
Ćelijska komponenta	• Jedarce; • jedro; • fibrillar center; • citosol;
Biološki proces	• skeletal system development; • regulation of translation; • neural crest formation; • neural crest cell development; • GO:0015915 transport; • nucleolar large rRNA transcription by RNA polymerase I;
	Izvori:Amigo / QuickGO
Ortolozi
	6949
	21453
	ENSG00000070814
	ENSMUSG00000024613
	Q13428
	O08784
NM_000356; NM_001008656; NM_001008657; NM_001135243; NM_001135244;
	NM_001135245; NM_001195141; NM_001371623
	NM_001198984; NM_011552
NP_000347; NP_001008657; NP_001128715; NP_001128716; NP_001128717;
	NP_001182070; NP_001358552
	NP_001185913; NP_035682
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Melasni ili slatki protein je protein koji je kod ljudi kodiran genom TCOF1 sa hromosoma 5.^[5]^[6]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 1.488 aminokiselina, a molekulska težina 152.106 Da.^[7]

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
MAEARKRREL	LPLIYHHLLR	AGYVRAAREV	KEQSGQKCFL	AQPVTLLDIY
THWQQTSELG	RKRKAEEDAA	LQAKKTRVSD	PISTSESSEE	EEEAEAETAK
ATPRLASTNS	SVLGADLPSS	MKEKAKAETE	KAGKTGNSMP	HPATGKTVAN
LLSGKSPRKS	AEPSANTTLV	SETEEEGSVP	AFGAAAKPGM	VSAGQADSSS
EDTSSSSDET	DVEGKPSVKP	AQVKASSVST	KESPARKAAP	APGKVGDVTP
QVKGGALPPA	KRAKKPEEES	ESSEEGSESE	EEAPAGTRSQ	VKASEKILQV
RAASAPAKGT	PGKGATPAPP	GKAGAVASQT	KAGKPEEDSE	SSSEESSDSE
EETPAAKALL	QAKASGKTSQ	VGAASAPAKE	SPRKGAAPAP	PGKTGPAVAK
AQAGKREEDS	QSSSEESDSE	EEAPAQAKPS	GKAPQVRAAS	APAKESPRKG
AAPAPPRKTG	PAAAQVQVGK	QEEDSRSSSE	ESDSDREALA	AMNAAQVKPL
GKSPQVKPAS	TMGMGPLGKG	AGPVPPGKVG	PATPSAQVGK	WEEDSESSSE
ESSDSSDGEV	PTAVAPAQEK	SLGNILQAKP	TSSPAKGPPQ	KAGPVAVQVK
AEKPMDNSES	SEESSDSADS	EEAPAAMTAA	QAKPALKIPQ	TKACPKKTNT
TASAKVAPVR	VGTQAPRKAG	TATSPAGSSP	AVAGGTQRPA	EDSSSSEESD
SEEEKTGLAV	TVGQAKSVGK	GLQVKAASVP	VKGSLGQGTA	PVLPGKTGPT
VTQVKAEKQE	DSESSEEESD	SEEAAASPAQ	VKTSVKKTQA	KANPAAARAP
SAKGTISAPG	KVVTAAAQAK	QRSPSKVKPP	VRNPQNSTVL	ARGPASVPSV
GKAVATAAQA	QTGPEEDSGS	SEEESDSEEE	AETLAQVKPS	GKTHQIRAAL
APAKESPRKG	AAPTPPGKTG	PSAAQAGKQD	DSGSSSEESD	SDGEAPAAVT
SAQVIKPPLI	FVDPNRSPAG	PAATPAQAQA	ASTPRKARAS	ESTARSSSSE
SEDEDVIPAT	QCLTPGIRTN	VVTMPTAHPR	IAPKASMAGA	SSSKESSRIS
DGKKQEGPAT	QVSKKNPASL	PLTQAALKVL	AQKASEAQPP	VARTQPSSGV
DSAVGTLPAT	SPQSTSVQAK	GTNKLRKPKL	PEVQQATKAP	ESSDDSEDSS
DSSSGSEEDG	EGPQGAKSAH	TLGPTPSRTE	TLVEETAAES	SEDDVVAPSQ
SLLSGYMTPG	LTPANSQASK	ATPKLDSSPS	VSSTLAAKDD	PDGKQEAKPQ
QAAGMLSPKT	GGKEAASGTT	PQKSRKPKKG	AGNPQASTLA	LQSNITQCLL
GQPWPLNEAQ	VQASVVKVLT	ELLEQERKKV	VDTTKESSRK	GWESRKRKLS
GDQPAARTPR	SKKKKKLGAG	EGGEASVSPE	KTSTTSKGKA	KRDKASGDVK
EKKGKGSLGS	QGAKDEPEEE	LQKGMGTVEG	GDQSNPKSKK	EKKKSDKRKK
DKEKKEKKKK	AKKASTKDSE	SPSQKKKKKK	KKTAEQTV

Funkcija

Ovaj gen kodira nukleolusni protein s domenom homologije LIS1. Protein je uključen u transkripciju gena ribosomske DNK, svojom interakcijom sa uzvodnim faktorom vezanja (UBF). Mutacije u ovom genu povezane su s Treacher Collinsov im sindrom, poremećajem koji uključuje abnormalni kraniofacijalni razvoj. Za ovaj gen pronađene su alternativno prerađene] varijante transkripta, koje kodiraju različite izoforme, ali samo su tri od njih do sada okarakterizirane.^[6]

TCOF1 je gen koji daje upute za izradu protein zvanog melasa.^[8] Ovaj protein je aktivan tokom ranog razvoja embriona u strukturama koje postaju kost i drugim tkivima na licu. Iako je precizna funkcija ovog proteina nepoznata, vjeruje se da on ima ključnu ulogu u razvoju kostiju lica i srodnih struktura.

Studije pokazuju da je uključen u proizvodnju molekule zvane ribosomska RNK (rRNK) unutar ćelija. Melasni ili slatki protein aktivan je u jedarcetu, koje je mala regija unutar jedra, gdje se proizvodi rRNK. Kao glavna komponenta ćelijske strukture koja se naziva ribosom, rRNK je bitna za sastavljanje proteina.

Osim u interakciji s UBF, bio je uključen u metilaciju prekursora zrele ribosomske RNK, interakcijom s nukleolusnim proteinom pNop56.^[9]

Gen TCOF1 nalazi se na dugom (q) kraku hromosoma 5, između pozicija 32 i 33.1, od bp 149,717.427 do bp 149,760.047.

Klinički značaj

Kod ljudi sa Treacher Collinsovim sindromom identificirano je više od 120 mutacija u genu TCOF. Većina ovih mutacija su insercije ili delecije malod broja gradivnih blokova DNK (bazni par) u TCOF1 genu. Mutacije TCOF1 dovode do proizvodnje abnormalno male, nefunkcionalne verzije proteina ili sprečavaju ćeliju da ga proizvodi . Nagađa se da njegov gubitak smanjuje proizvodnju rRNK u dijelovima embriona koji se razvijaju u kosti i tkiva lica. Nije poznato kako gubitak proteina uzrokuje specifične probleme s razvojem lica u Treacher Collinsovom sindromu. Naprimjer, mutacije u TCOF genu ovih osobaa često rezultiraju rascjepom nepca.^[10]

Modelni organizmi

Mutacije u ovom genu kod pasa jindo povezane su s uočenim kranijskim razlikama između pasa Jindo i boksera).^[11]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000070814 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000024613 - 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.
^ Jabs EW, Li X, Coss CA, Taylor EW, Meyers DA, Weber JL (Feb 1992). "Mapping the Treacher Collins syndrome locus to 5q31.3----q33.3". Genomics. 11 (1): 193–8. doi:10.1016/0888-7543(91)90118-X. PMID 1765376.
^ ^a ^b "Entrez Gene: TCOF1 Treacher Collins-Franceschetti syndrome 1".
^ "UniProt, Q13428" (jezik: engleski). Pristupljeno 18. 10. 2021.
^ Valdez BC, Henning D, So RB, Dixon J, Dixon MJ (2004). "The Treacher Collins syndrome (TCOF1) gene product is involved in ribosomal DNA gene transcription by interacting with upstream binding factor". Proc. Natl. Acad. Sci. U.S.A. 101 (29): 10709–14. doi:10.1073/pnas.0402492101. PMC 489999. PMID 15249688.
^ Gonzales B, Henning D, So RB, Dixon J, Dixon MJ, Valdez BC (2005). "The Treacher Collins syndrome (TCOF1) gene product is involved in pre-rRNA methylation". Hum Mol Genet. 14 (14): 2035–43. doi:10.1093/hmg/ddi208. PMID 15930015.
^ Dixon MJ, Marazita ML, Beaty TH, Murray JC (2011). "Cleft lip and palate: understanding genetic and environmental influences". Nature Reviews Genetics (12): 167-178.
^ Kim RN, Kim DS, Choi SH, et al. (2012). "Genome analysis of the domestic dog (korean jindo) by massively parallel sequencing". DNA Res. 19 (3): 275–88. doi:10.1093/dnares/dss011. PMC 3372376. PMID 22474061.

Dopunska literatura

Splendore A, Silva EO, Alonso LG, et al. (2000). "High mutation detection rate in TCOF1 among Treacher Collins syndrome patients reveals clustering of mutations and 16 novel pathogenic changes". Hum. Mutat. 16 (4): 315–22. doi:10.1002/1098-1004(200010)16:4<315::AID-HUMU4>3.0.CO;2-H. PMID 11013442.
Dixon MJ, Dixon J, Raskova D, et al. (1993). "Genetic and physical mapping of the Treacher Collins syndrome locus: refinement of the localization to chromosome 5q32-33.2". Hum. Mol. Genet. 1 (4): 249–53. doi:10.1093/hmg/1.4.249. PMID 1303194.
Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
Dixon MJ, Dixon J, Houseal T, et al. (1993). "Narrowing the position of the Treacher Collins syndrome locus to a small interval between three new microsatellite markers at 5q32-33.1". Am. J. Hum. Genet. 52 (5): 907–14. PMC 1682053. PMID 8488840.
Dixon, Jill; Edwards, Sara J.; Gladwin, Amanda J.; Dixon, Michael J.; Loftus, Stacie K.; Bonner, Cynthia A.; Koprivnikar, Kathryn; Wasmuth, John J. (1996). "Positional cloning of a gene involved in the pathogenesis of Treacher Collins syndrome. The Treacher Collins Syndrome Collaborative Group". Nat. Genet. 12 (2): 130–6. doi:10.1038/ng0296-130. PMID 8563749. S2CID 34312227.
Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
Edwards SJ, Gladwin AJ, Dixon MJ (1997). "The mutational spectrum in Treacher Collins syndrome reveals a predominance of mutations that create a premature-termination codon". Am. J. Hum. Genet. 60 (3): 515–24. PMC 1712503. PMID 9042910.
Dixon J, Edwards SJ, Anderson I, et al. (1997). "Identification of the complete coding sequence and genomic organization of the Treacher Collins syndrome gene". Genome Res. 7 (3): 223–34. doi:10.1101/gr.7.3.223. PMID 9074926.
Wise CA, Chiang LC, Paznekas WA, et al. (1997). "TCOF1 gene encodes a putative nucleolar phosphoprotein that exhibits mutations in Treacher Collins Syndrome throughout its coding region". Proc. Natl. Acad. Sci. U.S.A. 94 (7): 3110–5. doi:10.1073/pnas.94.7.3110. PMC 20330. PMID 9096354.
Paznekas WA, Zhang N, Gridley T, Jabs EW (1997). "Mouse TCOF1 is expressed widely, has motifs conserved in nucleolar phosphoproteins, and maps to chromosome 18". Biochem. Biophys. Res. Commun. 238 (1): 1–6. doi:10.1006/bbrc.1997.7229. PMID 9299440.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
Marsh KL, Dixon J, Dixon MJ (1998). "Mutations in the Treacher Collins syndrome gene lead to mislocalization of the nucleolar protein treacle". Hum. Mol. Genet. 7 (11): 1795–800. doi:10.1093/hmg/7.11.1795. PMID 9736782.
Winokur ST, Shiang R (1998). "The Treacher Collins syndrome (TCOF1) gene product, treacle, is targeted to the nucleolus by signals in its C-terminus". Hum. Mol. Genet. 7 (12): 1947–52. doi:10.1093/hmg/7.12.1947. PMID 9811939.
Jones NC, Farlie PG, Minichiello J, Newgreen DF (1999). "Detection of an appropriate kinase activity in branchial arches I and II that coincides with peak expression of the Treacher Collins syndrome gene product, treacle". Hum. Mol. Genet. 8 (12): 2239–45. doi:10.1093/hmg/8.12.2239. PMID 10545604.
Isaac C, Marsh KL, Paznekas WA, et al. (2000). "Characterization of the nucleolar gene product, treacle, in Treacher Collins syndrome". Mol. Biol. Cell. 11 (9): 3061–71. doi:10.1091/mbc.11.9.3061. PMC 14975. PMID 10982400.
Emes RD, Ponting CP (2002). "A new sequence motif linking lissencephaly, Treacher Collins and oral-facial-digital type 1 syndromes, microtubule dynamics and cell migration". Hum. Mol. Genet. 10 (24): 2813–20. doi:10.1093/hmg/10.24.2813. PMID 11734546.
Splendore A, Jabs EW, Passos-Bueno MR (2002). "Screening of TCOF1 in patients from different populations: confirmation of mutational hot spots and identification of a novel missense mutation that suggests an important functional domain in the protein treacle". J. Med. Genet. 39 (7): 493–5. doi:10.1136/jmg.39.7.493. PMC 1735178. PMID 12114482.
Ohta S, Shiomi Y, Sugimoto K, et al. (2002). "A proteomics approach to identify proliferating cell nuclear antigen (PCNA)-binding proteins in human cell lysates. Identification of the human CHL12/RFCs2-5 complex as a novel PCNA-binding protein". J. Biol. Chem. 277 (43): 40362–7. doi:10.1074/jbc.M206194200. PMID 12171929.

Vanjski linkovi

GeneReviews/NCBI/NIH/UW entry on Treacher Collins Syndrome or Mandibulofacial Dysostosis
GeneCard
TCOF1 protein, human na US National Library of Medicine Medical Subject Headings (MeSH)
TCOF1 lokacija ljudskog genoma UCSC Genome Browser.

TCOF1 detalji ljudskog genoma u UCSC Genome Browser.

Šablon:Jedro

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000070814 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000024613 - 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.

[pmid1765376-5] Jabs EW, Li X, Coss CA, Taylor EW, Meyers DA, Weber JL (Feb 1992). "Mapping the Treacher Collins syndrome locus to 5q31.3----q33.3". Genomics. 11 (1): 193–8. doi:10.1016/0888-7543(91)90118-X. PMID 1765376.

[entrez-6] "Entrez Gene: TCOF1 Treacher Collins-Franceschetti syndrome 1".

[UniProt-7] "UniProt, Q13428" (jezik: engleski). Pristupljeno 18. 10. 2021.

[8] Valdez BC, Henning D, So RB, Dixon J, Dixon MJ (2004). "The Treacher Collins syndrome (TCOF1) gene product is involved in ribosomal DNA gene transcription by interacting with upstream binding factor". Proc. Natl. Acad. Sci. U.S.A. 101 (29): 10709–14. doi:10.1073/pnas.0402492101. PMC 489999. PMID 15249688.

[9] Gonzales B, Henning D, So RB, Dixon J, Dixon MJ, Valdez BC (2005). "The Treacher Collins syndrome (TCOF1) gene product is involved in pre-rRNA methylation". Hum Mol Genet. 14 (14): 2035–43. doi:10.1093/hmg/ddi208. PMID 15930015.

[10] Dixon MJ, Marazita ML, Beaty TH, Murray JC (2011). "Cleft lip and palate: understanding genetic and environmental influences". Nature Reviews Genetics (12): 167-178.

[pmid.22474061-11] Kim RN, Kim DS, Choi SH, et al. (2012). "Genome analysis of the domestic dog (korean jindo) by massively parallel sequencing". DNA Res. 19 (3): 275–88. doi:10.1093/dnares/dss011. PMC 3372376. PMID 22474061.

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