CFAP298

CFAP298
Identifikatori
Aliasi	CFAP298
Vanjski ID-jevi	OMIM: 615494 MGI: 1915251 HomoloGene: 10941 GeneCards: CFAP298
Lokacija gena (miš)
Hrom.	Hromosom 16 (miš)
Kraj	90,732,002 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• GO:0001948, GO:0016582 vezivanje za proteine;
Ćelijska komponenta	• citosol; • citoplazma; • jedro; • citoskelet; • Treplja; • projekcija ćelije;
Biološki proces	• cell projection morphogenesis; • regulation of cilium movement; • cilium assembly;
	Izvori:Amigo / QuickGO
Ortolozi
	56683
	68001
	ENSG00000159079
	ENSMUSG00000022972
	P57076
	Q8BL95
	NM_017835; NM_021254
	NM_026502
	NP_067077; NP_001337263; NP_001337264; NP_001337265; NP_001337266
	NP_080778
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Cilijski i flagelno vezani protein 298 jest protein koji je kod ljudi kodiran genom CFAP298 sa hromosoma 21. Zanimljiv je i zbog povezanosti s raznim bolestima. Utvrđen je u visokim razinama u koštanoj srži pacijenata s negativnom prognozom akutne mijeloidne leukemije i abnormalnim kariotipom.^[4]^[5]^[6] Muški pacijenti s Alzheimerovom bolešću pokazali su smanjenje ekspresije CFAP298 u njihovim krvnim ćelijama.^[7]^[8] Gen CFAP298 nalazi se unutar kritične regije za Downov sindrom.^[9] Nema jasnih paraloga kod ljudi, ali gen ima homologe široko kozervirane među životinjama, gljivama i algama.

Gen

CFAP298 je gen na hromosomu 21, na sekvenci 21q22.1. Ukupno je pronađeno trinaest varijanti transkripta, ali samo jedanaest onih koji kodiraju proteine.^[10] Najčešći oblik CFAP298 iRNK ima 1.427 baznih parova, raspoređenih u sedam egzona. Njegovi najbliži susjedi na hromosomu su TCP10L, EVA1C, LOC100506185, OR7E23P i SYNJ1.

Ekspresija gena

Primarna sekvenca CFAP298 nalazi se u velikim količinama u većini tkiva. Neka od njih sa značajno manjom ekspresijom su ganglije, srce i jetra.^[11] Sumnja se da se CFAP298 nalazi u mozgu rano u razvoju zbog dva aheatno-štitna kompleksna homologna mjesta vezivanja faktora transkripcije koja se nalaze u promotoru.^[12]

Protein

Primarna sekvenca CFAP298 sastoji se od 290 aminokiselina mase 33.093 kDa. Izoelektrična tačka je 7,283, ali se smanjuje na 5,86 ako je potpuno fosforiliran.^[13] Masena spektroskopija|Masenom spektroskopijom]] pronađeno je nekoliko posttranslacijskih modifikacija: pet mjesta fosforilacije, jedno mjesto metiliranja, jedno mjesto ubikvitinacije i jedno acetilacijsko mjesto.^[13] Većina ovih modifikacija dešava se u drugoj polovini proteina.

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 290 aminokiselina, a molekulska težina 33 224 Da.^[5]

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
MVLLHVKRGD	ESQFLLQAPG	STELEELTVQ	VARVYNGRLK	VQRLCSEMEE
LAEHGIFLPP	NMQGLTDDQI	EELKLKDEWG	EKCVPSGGAV	FKKDDIGRRN
GQAPNEKMKQ	VLKKTIEEAK	AIISKKQVEA	GVCVTMEMVK	DALDQLRGAV
MIVYPMGLPP	YDPIRMEFEN	KEDLSGTQAG	LNVIKEAEAQ	LWWAAKELRR
TKKLSDYVGK	NEKTKIIAKI	QQRGQGAPAR	EPIISSEEQK	QLMLYYHRRQ
EELKRLEEND	DDAYLNSPWA	DNTALKRHFH	GVKDIKWRPR

Struktura

Većina proteina sastoji se od domena DUF2870. Ovaj domen se prvenstveno nalazi u homolozima CFAP298, ali i u drugim nekarakterističnim proteinima^[14] i sadrži većinu mjesta koje se mijenjaju nakon translacije. Predviđeno je da se protein sastoji uglavnom od alfa-heliksa i da mu nedostajei beta-listovi.^[15]

Lokalizacija

Pokazalo se da se CFAP298 nalazi u citosolu i nukleusu,^[16] ali je predviđeno, iako sa manjom snagom, da se nalazi i na citoskeletu, peroksisomima i mitohondrijama.^[17]

Interakcije

Pomoću masene spektrometrije, nađene su interakcije sa SUMO2,^[18] identificirane su proteinske posttranslacijske modifikacije nalik ubikvitinu i ubikvitinu C^[19]. Preko dvo-hibridnih eksperimenta, otkrivena je interakcija sa MAPK6, kinaznim proteinom.^[20]

Nedavne studije

Studija na zebricama pokazala je da se CFAP298 nalazi u visokim koncentracijama u Kupfferovim vezikulama i da je unutarćelijski lokaliziran na baznom tijelu cilija.^[21] Zebricim mutant u homologu CFAP298 ima defekte u pokretljivosti cilija.^[21] Osim toga, pokretne cilije kod mutanata zebrice i ksenopusa CFAP298 su nepokretne i pogrešno polarizirane, što sugerira da CFAP298 igra ulogu u polaritetu ravnih ćelija kao i u polaritetu motki.^[22]

Reference

^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000022972 - 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.
^ Bullinger L, Döhner K, Bair E, Fröhling S, Schlenk RF, Tibshirani R, et al. (april 2004). "Use of gene-expression profiling to identify prognostic subclasses in adult acute myeloid leukemia". The New England Journal of Medicine. 350 (16): 1605–16. doi:10.1056/NEJMoa031046. PMID 15084693. S2CID 13205096.
^ ^a ^b Greiner J, Schmitt M, Li L, Giannopoulos K, Bosch K, Schmitt A, et al. (decembar 2006). "Expression of tumor-associated antigens in acute myeloid leukemia: Implications for specific immunotherapeutic approaches". Blood. 108 (13): 4109–17. doi:10.1182/blood-2006-01-023127. PMID 16931630. S2CID 15937337.
^ Bullinger L, Ehrich M, Döhner K, Schlenk RF, Döhner H, Nelson MR, van den Boom D (januar 2010). "Quantitative DNA methylation predicts survival in adult acute myeloid leukemia". Blood. 115 (3): 636–42. doi:10.1182/blood-2009-03-211003. PMID 19903898. S2CID 13349367.
^ Maes OC, Xu S, Yu B, Chertkow HM, Wang E, Schipper HM (decembar 2007). "Transcriptional profiling of Alzheimer blood mononuclear cells by microarray". Neurobiology of Aging. 28 (12): 1795–809. doi:10.1016/j.neurobiolaging.2006.08.004. PMID 16979800. S2CID 8185187.
^ Maes OC, Schipper HM, Chertkow HM, Wang E (juni 2009). "Methodology for discovery of Alzheimer's disease blood-based biomarkers". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 64 (6): 636–45. doi:10.1093/gerona/glp045. PMID 19366883.
^ Moncaster JA, Pineda R, Moir RD, Lu S, Burton MA, Ghosh JG, et al. (maj 2010). "Alzheimer's disease amyloid-beta links lens and brain pathology in Down syndrome". PLOS ONE. 5 (5): e10659. Bibcode:2010PLoSO...510659M. doi:10.1371/journal.pone.0010659. PMC 2873949. PMID 20502642.
^ Ensembl http://ensembl.org
^ C21orf59 GDS596 GEOprofil
^ "Genomatix". Arhivirano s originala, 2. 12. 2021. Pristupljeno 15. 2. 2022.
^ ^a ^b "Cilia- and flagella-associated protein 298". Phosphosite.
^ Conserved Domains
^ SDSC PELE
^ Hu YH, Warnatz HJ, Vanhecke D, Wagner F, Fiebitz A, Thamm S, et al. (juni 2006). "Cell array-based intracellular localization screening reveals novel functional features of human chromosome 21 proteins". BMC Genomics. 7: 155. doi:10.1186/1471-2164-7-155. PMC 1526728. PMID 16780588.
^ "PsortII".
^ Golebiowski F, Matic I, Tatham MH, Cole C, Yin Y, Nakamura A, et al. (maj 2009). "System-wide changes to SUMO modifications in response to heat shock". Science Signaling. 2 (72): ra24. doi:10.1126/scisignal.2000282. PMID 19471022. S2CID 33450256.
^ Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, et al. (oktobar 2011). "Systematic and quantitative assessment of the ubiquitin-modified proteome". Molecular Cell. 44 (2): 325–40. doi:10.1016/j.molcel.2011.08.025. PMC 3200427. PMID 21906983.
^ Vinayagam A, Stelzl U, Foulle R, Plassmann S, Zenkner M, Timm J, et al. (septembar 2011). "A directed protein interaction network for investigating intracellular signal transduction". Science Signaling. 4 (189): rs8. doi:10.1126/scisignal.2001699. PMID 21900206. S2CID 7418133.
^ ^a ^b Schottenfeld, Jodi (2008). The role of PKD2 and C21ORF59 in patterning the left-right axis of the zebrafish embryo (Thesis). OCLC 236339661. Gale A195982386.
^ Jaffe KM, Grimes DT, Schottenfeld-Roames J, Werner ME, Ku TS, Kim SK, et al. (mart 2016). "c21orf59/kurly Controls Both Cilia Motility and Polarization". Cell Reports. 14 (8): 1841–9. doi:10.1016/j.celrep.2016.01.069. PMC 4775428. PMID 26904945.

Dopunska literatura

Denoeud F, Kapranov P, Ucla C, Frankish A, Castelo R, Drenkow J, et al. (juni 2007). "Prominent use of distal 5' transcription start sites and discovery of a large number of additional exons in ENCODE regions". Genome Research. 17 (6): 746–59. doi:10.1101/gr.5660607. PMC 1891335. PMID 17567994.
Hu YH, Warnatz HJ, Vanhecke D, Wagner F, Fiebitz A, Thamm S, et al. (juni 2006). "Cell array-based intracellular localization screening reveals novel functional features of human chromosome 21 proteins". BMC Genomics. 7: 155. doi:10.1186/1471-2164-7-155. PMC 1526728. PMID 16780588.
Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, et al. (januar 2005). "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells". Nature Biotechnology. 23 (1): 94–101. doi:10.1038/nbt1046. PMID 15592455. S2CID 7200157.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (oktobar 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.
Maruyama K, Sugano S (januar 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.

Vanjski linkovi

Lokacija ljudskog genoma CFAP298 i stranica sa detaljima o genu CFAP298 u UCSC Genome Browseru.

[refGRCm38Ensembl-1] GRCm38: Ensembl release 89: ENSMUSG00000022972 - Ensembl, maj 2017

[2] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[3] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid15084693-4] Bullinger L, Döhner K, Bair E, Fröhling S, Schlenk RF, Tibshirani R, et al. (april 2004). "Use of gene-expression profiling to identify prognostic subclasses in adult acute myeloid leukemia". The New England Journal of Medicine. 350 (16): 1605–16. doi:10.1056/NEJMoa031046. PMID 15084693. S2CID 13205096.

[pmid16931630-5] Greiner J, Schmitt M, Li L, Giannopoulos K, Bosch K, Schmitt A, et al. (decembar 2006). "Expression of tumor-associated antigens in acute myeloid leukemia: Implications for specific immunotherapeutic approaches". Blood. 108 (13): 4109–17. doi:10.1182/blood-2006-01-023127. PMID 16931630. S2CID 15937337.

[pmid19903898-6] Bullinger L, Ehrich M, Döhner K, Schlenk RF, Döhner H, Nelson MR, van den Boom D (januar 2010). "Quantitative DNA methylation predicts survival in adult acute myeloid leukemia". Blood. 115 (3): 636–42. doi:10.1182/blood-2009-03-211003. PMID 19903898. S2CID 13349367.

[pmid16979800-7] Maes OC, Xu S, Yu B, Chertkow HM, Wang E, Schipper HM (decembar 2007). "Transcriptional profiling of Alzheimer blood mononuclear cells by microarray". Neurobiology of Aging. 28 (12): 1795–809. doi:10.1016/j.neurobiolaging.2006.08.004. PMID 16979800. S2CID 8185187.

[pmid19366883-8] Maes OC, Schipper HM, Chertkow HM, Wang E (juni 2009). "Methodology for discovery of Alzheimer's disease blood-based biomarkers". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 64 (6): 636–45. doi:10.1093/gerona/glp045. PMID 19366883.

[pmid20502642-9] Moncaster JA, Pineda R, Moir RD, Lu S, Burton MA, Ghosh JG, et al. (maj 2010). "Alzheimer's disease amyloid-beta links lens and brain pathology in Down syndrome". PLOS ONE. 5 (5): e10659. Bibcode:2010PLoSO...510659M. doi:10.1371/journal.pone.0010659. PMC 2873949. PMID 20502642.

[10] Ensembl http://ensembl.org

[11] C21orf59 GDS596 GEOprofil

[12] "Genomatix". Arhivirano s originala, 2. 12. 2021. Pristupljeno 15. 2. 2022.

[phos-13] "Cilia- and flagella-associated protein 298". Phosphosite.

[14] Conserved Domains

[15] SDSC PELE

[pmid16780588-16] Hu YH, Warnatz HJ, Vanhecke D, Wagner F, Fiebitz A, Thamm S, et al. (juni 2006). "Cell array-based intracellular localization screening reveals novel functional features of human chromosome 21 proteins". BMC Genomics. 7: 155. doi:10.1186/1471-2164-7-155. PMC 1526728. PMID 16780588.

[17] "PsortII".

[pmid19471022-18] Golebiowski F, Matic I, Tatham MH, Cole C, Yin Y, Nakamura A, et al. (maj 2009). "System-wide changes to SUMO modifications in response to heat shock". Science Signaling. 2 (72): ra24. doi:10.1126/scisignal.2000282. PMID 19471022. S2CID 33450256.

[pmid21906983-19] Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, et al. (oktobar 2011). "Systematic and quantitative assessment of the ubiquitin-modified proteome". Molecular Cell. 44 (2): 325–40. doi:10.1016/j.molcel.2011.08.025. PMC 3200427. PMID 21906983.

[pmid21900206-20] Vinayagam A, Stelzl U, Foulle R, Plassmann S, Zenkner M, Timm J, et al. (septembar 2011). "A directed protein interaction network for investigating intracellular signal transduction". Science Signaling. 4 (189): rs8. doi:10.1126/scisignal.2001699. PMID 21900206. S2CID 7418133.

[Dis-21] Schottenfeld, Jodi (2008). The role of PKD2 and C21ORF59 in patterning the left-right axis of the zebrafish embryo (Thesis). OCLC 236339661. Gale A195982386.

[22] Jaffe KM, Grimes DT, Schottenfeld-Roames J, Werner ME, Ku TS, Kim SK, et al. (mart 2016). "c21orf59/kurly Controls Both Cilia Motility and Polarization". Cell Reports. 14 (8): 1841–9. doi:10.1016/j.celrep.2016.01.069. PMC 4775428. PMID 26904945.

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