Nukleolin jest protein koji je kod ljudi kodiran genom NCL sa hromosoma 2.[5][6]

Nukleolin
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

2FC8, 2FC9, 2KRR

Identifikatori
AliasiNCL
Vanjski ID-jeviOMIM: 164035 MGI: 97286 HomoloGene: 136488 GeneCards: NCL
Lokacija gena (čovjek)
Hromosom 2 (čovjek)
Hrom.Hromosom 2 (čovjek)[1]
Hromosom 2 (čovjek)
Genomska lokacija za Nukleolin
Genomska lokacija za Nukleolin
Bend2q37.1Početak231,453,531 bp[1]
Kraj231,483,641 bp[1]
Lokacija gena (miš)
Hromosom 1 (miš)
Hrom.Hromosom 1 (miš)[2]
Hromosom 1 (miš)
Genomska lokacija za Nukleolin
Genomska lokacija za Nukleolin
Bend1 C5|1 43.94 cMPočetak86,272,441 bp[2]
Kraj86,287,122 bp[2]
Obrazac RNK ekspresije
Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija vezivanje sa DNK
telomeric DNA binding
protein C-terminus binding
GO:0001948, GO:0016582 vezivanje za proteine
vezivanje sa RNK
vezivanje identičnih proteina
nucleic acid binding
DNA topoisomerase binding
mRNA 5'-UTR binding
Ćelijska komponenta citoplazma
membrana
nukleoplazma
cell cortex
Jedarce
cytoplasmic ribonucleoprotein granule
Egzosom
jedro
ribonukleoprotein
Biološki proces positive regulation of transcription of nucleolar large rRNA by RNA polymerase I
Angiogeneza
GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II
cellular response to epidermal growth factor stimulus
negative regulation of translation
cellular response to leukemia inhibitory factor
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_005381

NM_010880

RefSeq (bjelančevina)

NP_005372

NP_035010

Lokacija (UCSC)Chr 2: 231.45 – 231.48 MbChr 1: 86.27 – 86.29 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Amiokiselininska sekvenca

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Dužina polipeptidnog lanca je 710 aminokiselina, a molekulska težina 76.614 Da.[7]

1020304050
MVKLAKAGKNQGDPKKMAPPPKEVEEDSEDEEMSEDEEDDSSGEEVVIPQ
KKGKKAAATSAKKVVVSPTKKVAVATPAKKAAVTPGKKAAATPAKKTVTP
AKAVTTPGKKGATPGKALVATPGKKGAAIPAKGAKNGKNAKKEDSDEEED
DDSEEDEEDDEDEDEDEDEIEPAAMKAAAAAPASEDEDDEDDEDDEDDDD
DEEDDSEEEAMETTPAKGKKAAKVVPVKAKNVAEDEDEEEDDEDEDDDDD
EDDEDDDDEDDEEEEEEEEEEPVKEAPGKRKKEMAKQKAAPEAKKQKVEG
TEPTTAFNLFVGNLNFNKSAPELKTGISDVFAKNDLAVVDVRIGMTRKFG
YVDFESAEDLEKALELTGLKVFGNEIKLEKPKGKDSKKERDARTLLAKNL
PYKVTQDELKEVFEDAAEIRLVSKDGKSKGIAYIEFKTEADAEKTFEEKQ
GTEIDGRSISLYYTGEKGQNQDYRGGKNSTWSGESKTLVLSNLSYSATEE
TLQEVFEKATFIKVPQNQNGKSKGYAFIEFASFEDAKEALNSCNKREIEG
RAIRLELQGPRGSPNARSQPSKTLFVKGLSEDTTEETLKESFDGSVRARI
VTDRETGSSKGFGFVDFNSEEDAKAAKEAMEDGEIDGNKVTLDWAKPKGE
GGFGGRGGGRGGFGGRGGGRGGRGGFGGRGRGGFGGRGGFRGGRGGGGDH
KPQGKKTKFE

Ljudski NCL gen nalazi se na hromosomu 2 i sastoji se od 14 egzon asa 13 introna i prostire se na približno 11 kb. Intron 11 gena NCL kodira malu nukleolusnu RNK, označenu kao U20.[8]

Funkcija

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Nukleolin je glavni nukleolusni protein rastućih eukariotskih ćelija. Utvrđeno je da je povezan s unutarjedarčanim hromatinom i preribosomnim česticama. Inducira dekondenzaciju hromatina, vezivanjem za histon H1. Smatra se da ima ulogu u transkripciji pre-rRNK i sastavljanju ribosoma. Može imati ulogu u procesu transkripcijske elongacije. Veže RNK-oligonukleotide sa 5'-UUAGGG-3' ponavljanjima čvršće od telomernih jednolančanih DNK 5'-TTAGGG-3' ponavljanja.

Nukleolin također može da deluje kao koaktivator transkripcije sa faktorom transkripcije II uzvodnog promotora kokošijeg ovalbumina (COUP-TFII).[9]

Klinički značaj

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Midkin i plejotrofin se vezuju za nukleolin na površini ćelije kao receptora niskog afiniteta. Ovo vezivanje može inhibirati infekciju HI V-om.[10][11]

Nukleolin na površini ćelije je receptor za respiratorni sincicijski virus (RSV), fuzijski protein.[12] Interference with the nucleolin - RSV fusion protein interaction has been shown to be therapeutic against RSV infection in cell cultures and animal models.[13][14][15][16]

Interakcije

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Pokazalo se da nukleolin međuragira sa:

Reference

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000115053 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026234 - 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.
  5. ^ Srivastava M, McBride OW, Fleming PJ, Pollard HB, Burns AL (Sep 1990). "Genomic organization and chromosomal localization of the human nucleolin gene". The Journal of Biological Chemistry. 265 (25): 14922–31. doi:10.1016/S0021-9258(18)77205-0. PMID 2394707.
  6. ^ Erard MS, Belenguer P, Caizergues-Ferrer M, Pantaloni A, Amalric F (Aug 1988). "A major nucleolar protein, nucleolin, induces chromatin decondensation by binding to histone H1". European Journal of Biochemistry. 175 (3): 525–30. doi:10.1111/j.1432-1033.1988.tb14224.x. PMID 3409881.
  7. ^ "UniProt, P19338" (jezik: engleski). Pristupljeno 18. 11. 2021.
  8. ^ "Entrez Gene: NCL nucleolin".
  9. ^ Litchfield LM, Riggs KA, Hockenberry AM, Oliver LD, Barnhart KG, Cai J, Pierce WM, Ivanova MM, Bates PJ, Appana SN, Datta S, Kulesza P, McBryan J, Young LS, Klinge CM (maj 2012). "Identification and characterization of nucleolin as a COUP-TFII coactivator of retinoic acid receptor β transcription in breast cancer cells". PLOS ONE. 7 (5): e38278. Bibcode:2012PLoSO...738278L. doi:10.1371/journal.pone.0038278. PMC 3365040. PMID 22693611.
  10. ^ Said EA, Krust B, Nisole S, Svab J, Briand JP, Hovanessian AG (Oct 2002). "The anti-HIV cytokine midkine binds the cell surface-expressed nucleolin as a low affinity receptor". The Journal of Biological Chemistry. 277 (40): 37492–502. doi:10.1074/jbc.M201194200. PMID 12147681. S2CID 41621217.
  11. ^ Said EA, Courty J, Svab J, Delbé J, Krust B, Hovanessian AG (Sep 2005). "Pleiotrophin inhibits HIV infection by binding the cell surface-expressed nucleolin". The FEBS Journal. 272 (18): 4646–59. doi:10.1111/j.1742-4658.2005.04870.x. PMID 16156786. S2CID 21153881.
  12. ^ Tayyari F, Marchant D, Moraes TJ, Duan W, Mastrangelo P, Hegele RG (Sep 2011). "Identification of nucleolin as a cellular receptor for human respiratory syncytial virus". Nature Medicine. 17 (9): 1132–5. doi:10.1038/nm.2444. PMID 21841784. S2CID 205388029.
  13. ^ Bilawchuk LM, Griffiths CD, Jensen LD, Elawar F, Marchant DJ (Aug 2017). "The Susceptibilities of Respiratory Syncytial Virus to Nucleolin Receptor Blocking and Antibody Neutralization are Dependent upon the Method of Virus Purification". Viruses. 9 (8): 207. doi:10.3390/v9080207. PMC 5580464. PMID 28771197.
  14. ^ Mastrangelo P, Hegele RG (Nov 2012). "The RSV fusion receptor: not what everyone expected it to be". Microbes and Infection / Institut Pasteur. 14 (13): 1205–10. doi:10.1016/j.micinf.2012.07.015. PMID 22884716.
  15. ^ Mastrangelo P, Hegele RG (Mar 2013). "RSV fusion: time for a new model". Viruses. 5 (3): 873–85. doi:10.3390/v5030873. PMC 3705301. PMID 23518574.
  16. ^ Shakeri A, Mastrangelo P, Griffin JK, Moraes TJ, Hegele RG (Nov 2014). "Respiratory syncytial virus receptor expression in the mouse and viral tropism". Histology and Histopathology. 30 (30): 401–411. doi:10.14670/HH-30.401. PMID 25374027.
  17. ^ Li D, Dobrowolska G, Krebs EG (Jun 1996). "The physical association of casein kinase 2 with nucleolin". The Journal of Biological Chemistry. 271 (26): 15662–8. doi:10.1074/jbc.271.26.15662. PMID 8663258. S2CID 10750338.
  18. ^ Dubois T, Zemlickova E, Howell S, Aitken A (Feb 2003). "Centaurin-alpha 1 associates in vitro and in vivo with nucleolin". Biochemical and Biophysical Research Communications. 301 (2): 502–8. doi:10.1016/s0006-291x(02)03010-3. PMID 12565890.
  19. ^ Tominaga K, Srikantan S, Lee EK, Subaran SS, Martindale JL, Abdelmohsen K, Gorospe M (Oct 2011). "Competitive regulation of nucleolin expression by HuR and miR-494". Molecular and Cellular Biology. 31 (20): 4219–31. doi:10.1128/MCB.05955-11. PMC 3187287. PMID 21859890.
  20. ^ Li YP, Busch RK, Valdez BC, Busch H (Apr 1996). "C23 interacts with B23, a putative nucleolar-localization-signal-binding protein". European Journal of Biochemistry. 237 (1): 153–8. doi:10.1111/j.1432-1033.1996.0153n.x. PMID 8620867.
  21. ^ Daniely Y, Dimitrova DD, Borowiec JA (Aug 2002). "Stress-dependent nucleolin mobilization mediated by p53-nucleolin complex formation". Molecular and Cellular Biology. 22 (16): 6014–22. doi:10.1128/mcb.22.16.6014-6022.2002. PMC 133981. PMID 12138209.
  22. ^ Morimoto H, Okamura H, Haneji T (Sep 2002). "Interaction of protein phosphatase 1 delta with nucleolin in human osteoblastic cells". The Journal of Histochemistry and Cytochemistry. 50 (9): 1187–93. doi:10.1177/002215540205000905. PMID 12185196. S2CID 24950287.
  23. ^ Sakaguchi M, Miyazaki M, Takaishi M, Sakaguchi Y, Makino E, Kataoka N, Yamada H, Namba M, Huh NH (Nov 2003). "S100C/A11 is a key mediator of Ca(2+)-induced growth inhibition of human epidermal keratinocytes". The Journal of Cell Biology. 163 (4): 825–35. doi:10.1083/jcb.200304017. PMC 2173690. PMID 14623863.
  24. ^ Fouraux MA, Bouvet P, Verkaart S, van Venrooij WJ, Pruijn GJ (Jul 2002). "Nucleolin associates with a subset of the human Ro ribonucleoprotein complexes". Journal of Molecular Biology. 320 (3): 475–88. doi:10.1016/s0022-2836(02)00518-1. PMID 12096904.
  25. ^ Haluska P, Saleem A, Edwards TK, Rubin EH (Apr 1998). "Interaction between the N-terminus of human topoisomerase I and SV40 large T antigen". Nucleic Acids Research. 26 (7): 1841–7. doi:10.1093/nar/26.7.1841. PMC 147454. PMID 9512561.
  26. ^ Bharti AK, Olson MO, Kufe DW, Rubin EH (Jan 1996). "Identification of a nucleolin binding site in human topoisomerase I". The Journal of Biological Chemistry. 271 (4): 1993–7. doi:10.1074/jbc.271.4.1993. PMID 8567649. S2CID 25059254.
  27. ^ Khurts S, Masutomi K, Delgermaa L, Arai K, Oishi N, Mizuno H, Hayashi N, Hahn WC, Murakami S (Dec 2004). "Nucleolin interacts with telomerase". The Journal of Biological Chemistry. 279 (49): 51508–15. doi:10.1074/jbc.M407643200. PMID 15371412. S2CID 41394148.

Dopunska literatura

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Vanjski linkovi

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