NEFL

NEFL
Identifikatori
Aliasi	NEFL
Vanjski ID-jevi	OMIM: 162280 MGI: 97313 HomoloGene: 4487 GeneCards: NEFL
Lokacija gena (čovjek)
Hrom.	Hromosom 8 (čovjek)
Kraj	24,956,721 bp
Lokacija gena (miš)
Hrom.	Hromosom 14 (miš)
Kraj	68,326,544 bp
Obrazac RNK ekspresije
	; ; ; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• protein-macromolecule adaptor activity; • structural molecule activity; • structural constituent of cytoskeleton; • protein C-terminus binding; • GO:0001948, GO:0016582 vezivanje za proteine; • vezivanje identičnih proteina; • protein heterodimerization activity; • protein domain specific binding; • phospholipase binding; • structural constituent of postsynaptic intermediate filament cytoskeleton;
Ćelijska komponenta	• citoplazma; • citosol; • neurofilament; • growth cone; • myelin sheath; • TSC1-TSC2 complex; • Akson; • neuron projection; • Intermedijarni filament; • axon cytoplasm; • Nervno-mišićna veza; • Schaffer collateral - CA1 synapse; • cholinergic synapse; • postsynaptic intermediate filament cytoskeleton; • presynaptic intermediate filament cytoskeleton;
Biološki proces	• GO:1904089 negative regulation of neuron apoptotic process; • retrograde axonal transport; • intermediate filament organization; • response to sodium arsenite; • neuron projection morphogenesis; • protein polymerization; • intermediate filament bundle assembly; • neuromuscular process controlling balance; • neurofilament bundle assembly; • response to corticosterone; • response to peptide hormone; • response to organic substance; • positive regulation of axonogenesis; • MAPK cascade; • anterograde axonal transport; • axonal transport of mitochondrion; • regulation of axon diameter; • peripheral nervous system axon regeneration; • locomotion; • response to acrylamide; • spinal cord development; • cerebral cortex development; • intermediate filament polymerization or depolymerization; • neurofilament cytoskeleton organization; • hippocampus development; • response to toxic substance; • microtubule cytoskeleton organization; • axon development; • synapse maturation; • postsynaptic intermediate filament cytoskeleton organization; • regulation of NMDA receptor activity;
	Izvori:Amigo / QuickGO
Ortolozi
	4747
	18039
	ENSG00000277586
	ENSMUSG00000022055
	P07196
	P08551
	NM_006158
	NM_010910
	NP_006149
	NP_035040
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Neurofilamentni lahki polipeptid, znan i kao neurofilamentni lahki lanac, je neurofilamentni protein koji je kod ljudi kodiran genom NEFL.^[5]^[6]

Aminokiselinska sekvenca uredi

Dužina polipeptidnog lanca je 543 aminokiseline, а molekulska težina 61.517 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
MSSFSYEPYY	STSYKRRYVE	TPRVHISSVR	SGYSTARSAY	SSYSAPVSSS
LSVRRSYSSS	SGSLMPSLEN	LDLSQVAAIS	NDLKSIRTQE	KAQLQDLNDR
FASFIERVHE	LEQQNKVLEA	ELLVLRQKHS	EPSRFRALYE	QEIRDLRLAA
EDATNEKQAL	QGEREGLEET	LRNLQARYEE	EVLSREDAEG	RLMEARKGAD
EAALARAELE	KRIDSLMDEI	SFLKKVHEEE	IAELQAQIQY	AQISVEMDVT
KPDLSAALKD	IRAQYEKLAA	KNMQNAEEWF	KSRFTVLTES	AAKNTDAVRA
AKDEVSESRR	LLKAKTLEIE	ACRGMNEALE	KQLQELEDKQ	NADISAMQDT
INKLENELRT	TKSEMARYLK	EYQDLLNVKM	ALDIEIAAYR	KLLEGEETRL
SFTSVGSITS	GYSQSSQVFG	RSAYGGLQTS	SYLMSTRSFP	SYYTSHVQEE
QIEVEETIEA	AKAEEAKDEP	PSEGEAEEEE	KDKEEAEEEE	AAEEEEAAKE
ESEEAKEEEE	GGEGEEGEET	KEAEEEEKKV	EGAGEEQAAK	KKD

Funkcija uredi

Lahki lanac neurofilamenta je biomarker koji se može mjeriti imunološkim testovima u moždanokičmenoj tekućini i plazmi i odražava aksonsko oštećenje u raznim neurološkim poremećajima.^[8]^[9] To je upotrebljiv marker za prećenje bolesti kao što je amiotrofna lateralna skleroza,^[10] multipla skleroza^[11] i Alzheimerova bolest,^[12]^[13] a od nedavno i Huntingtonova bolest.^[14] Veći broj povezan je s povećanjem mortaliteta.^[15]

Povezan je s Charcot-Marie-Toothovim bolestima 1F i 2E.^[5]

Interakcije uredi

Lahki neurofilamentni polipeptid je pokazao interakcije sa:

Reference uredi

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000277586 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000022055 - 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.
^ ^a ^b Miltenberger-Miltenyi G, Janecke AR, Wanschitz JV, Timmerman V, Windpassinger C, Auer-Grumbach M, Löscher WN (juli 2007). "Clinical and electrophysiological features in Charcot-Marie-Tooth disease with mutations in the NEFL gene". Archives of Neurology. 64 (7): 966–70. doi:10.1001/archneur.64.7.966. PMID 17620486.
^ "Entrez Gene: NEFL neurofilament, light polypeptide 68kDa".
^ "UniProt, P07196" (jezik: англ.). Pristupljeno 20. 9. 2021.CS1 održavanje: nepoznati jezik (link)
^ Khalil M, Teunissen CE, Otto M, Piehl F, Sormani MP, Gattringer T, Barro C, Kappos L, Comabella M, Fazekas F, Petzold A, Blennow K, Zetterberg H, Kuhle J (oktobar 2018). "Neurofilaments as biomarkers in neurological disorders" (PDF). Nature Reviews. Neurology. 14 (10): 577–589. doi:10.1038/s41582-018-0058-z. PMID 30171200. S2CID 52140127. neuroaxonal damage is the pathological substrate of permanent disability in various neurological disorders. ... Here, we review what is known about the structure and function of neurofilaments, discuss analytical aspects and knowledge of age-dependent normal ranges of neurofilaments and provide a comprehensive overview of studies on neurofilament light chain as a marker of axonal injury in different neurological disorders, including multiple sclerosis, neurodegenerative dementia, stroke, traumatic brain injury, amyotrophic lateral sclerosis and Parkinson disease.
^ Thompson AB, Mead SH (decembar 2018). "Review: Fluid biomarkers in the human prion diseases" (PDF). Molecular and Cellular Neurosciences. 97: 81–92. doi:10.1016/j.mcn.2018.12.003. PMID 30529227. S2CID 54437514. The very rapid neurodegeneration of prion disease results in strong signals from surrogate protein markers in the blood that reflect neuronal, axonal, synaptic or glial pathology in the brain: notably the tau and neurofilament light chain proteins.
^ Xu Z, Henderson RD, David M, McCombe PA (2016). "Neurofilaments as Biomarkers for Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis". PLOS ONE. 11 (10): e0164625. Bibcode:2016PLoSO..1164625X. doi:10.1371/journal.pone.0164625. PMC 5061412. PMID 27732645. NF heavy and light chain levels have potential use as a marker of neural degeneration in ALS, but are not specific for the disease, and are more likely to be used as measures of disease progression.
^ Cai L, Huang J (2018). "Neurofilament light chain as a biological marker for multiple sclerosis: a meta-analysis study". Neuropsychiatric Disease and Treatment. 14: 2241–2254. doi:10.2147/NDT.S173280. PMC 6126505. PMID 30214214. NFL chain has significantly increased in MS patients, which substantially strengthens the clinical evidence of the NFL in MS. The NFL may be used as a prognostic biomarker to monitor disease progression, disease activity, and treatment efficacy in the future.
^ Zetterberg, Henrik (6. 2. 2019). "Biomarkers for Alzheimer's disease beyond amyloid and tau" (PDF). Nature Medicine. 25 (2): 201–203. doi:10.1038/s41591-019-0348-z. PMID 30728536. S2CID 59607046.
^ Preische O, Schultz SA, Apel A, et al. (2019). "Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease". Nature Medicine. 25 (2): 277–283. doi:10.1038/s41591-018-0304-3. PMC 6367005. PMID 30664784.
^ Niemelä V, Landtblom AM, Blennow K, Sundblom J (27. 2. 2017). "Tau or neurofilament light-Which is the more suitable biomarker for Huntington's disease?". PLOS ONE. 12 (2): e0172762. Bibcode:2017PLoSO..1272762N. doi:10.1371/journal.pone.0172762. PMC 5328385. PMID 28241046.
^ "A neuronal blood marker is associated with mortality in old age". Pristupljeno 11. 2. 2021.
^ Frappier T, Stetzkowski-Marden F, Pradel LA (april 1991). "Interaction domains of neurofilament light chain and brain spectrin". The Biochemical Journal. 275 ( Pt 2) (2): 521–7. doi:10.1042/bj2750521. PMC 1150082. PMID 1902666.
^ Mukai H, Toshimori M, Shibata H, Kitagawa M, Shimakawa M, Miyahara M, Sunakawa H, Ono Y (april 1996). "PKN associates and phosphorylates the head-rod domain of neurofilament protein". The Journal of Biological Chemistry. 271 (16): 9816–22. doi:10.1074/jbc.271.16.9816. PMID 8621664.
^ Haddad LA, Smith N, Bowser M, Niida Y, Murthy V, Gonzalez-Agosti C, Ramesh V (novembar 2002). "The TSC1 tumor suppressor hamartin interacts with neurofilament-L and possibly functions as a novel integrator of the neuronal cytoskeleton". The Journal of Biological Chemistry. 277 (46): 44180–6. doi:10.1074/jbc.M207211200. PMID 12226091.

Dopunska literatura uredi

Hirokawa N, Takeda S (oktobar 1998). "Gene targeting studies begin to reveal the function of neurofilament proteins". The Journal of Cell Biology. 143 (1): 1–4. doi:10.1083/jcb.143.1.1. PMC 2132816. PMID 9763415.
Beaudet L, Charron G, Julien JP (maj 1992). "Origin of the two mRNA species for the human neurofilament light gene". Biochemistry and Cell Biology. 70 (5): 279–84. doi:10.1139/o92-044. PMID 1497855.
Frappier T, Stetzkowski-Marden F, Pradel LA (april 1991). "Interaction domains of neurofilament light chain and brain spectrin". The Biochemical Journal. 275 ( Pt 2) (Pt 2): 521–7. doi:10.1042/bj2750521. PMC 1150082. PMID 1902666.
Chin SS, Liem RK (decembar 1989). "Expression of rat neurofilament proteins NF-L and NF-M in transfected non-neuronal cells". European Journal of Cell Biology. 50 (2): 475–90. PMID 2516804.
Julien JP, Grosveld F, Yazdanbaksh K, Flavell D, Meijer D, Mushynski W (juni 1987). "The structure of a human neurofilament gene (NF-L): a unique exon-intron organization in the intermediate filament gene family". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 909 (1): 10–20. doi:10.1016/0167-4781(87)90041-8. hdl:1765/2408. PMID 3034332.
Hurst J, Flavell D, Julien JP, Meijer D, Mushynski W, Grosveld F (1987). "The human neurofilament gene (NEFL) is located on the short arm of chromosome 8". Cytogenetics and Cell Genetics. 45 (1): 30–2. doi:10.1159/000132421. hdl:1765/2414. PMID 3036423.
Frappier T, Regnouf F, Pradel LA (decembar 1987). "Binding of brain spectrin to the 70-kDa neurofilament subunit protein". European Journal of Biochemistry. 169 (3): 651–7. doi:10.1111/j.1432-1033.1987.tb13657.x. PMID 3121319.
Nomata Y, Watanabe T, Wada H (mart 1983). "Highly acidic proteins from human brain: purification and properties of Glu-50 protein". Journal of Biochemistry. 93 (3): 825–31. doi:10.1093/jb/93.3.825. PMID 6135695.
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.
Pospelov VA, Pospelova TV, Julien JP (februar 1994). "AP-1 and Krox-24 transcription factors activate the neurofilament light gene promoter in P19 embryonal carcinoma cells". Cell Growth & Differentiation. 5 (2): 187–96. PMID 8180132.
Dong DL, Xu ZS, Chevrier MR, Cotter RJ, Cleveland DW, Hart GW (august 1993). "Glycosylation of mammalian neurofilaments. Localization of multiple O-linked N-acetylglucosamine moieties on neurofilament polypeptides L and M". The Journal of Biological Chemistry. 268 (22): 16679–87. doi:10.1016/S0021-9258(19)85471-6. PMID 8344946.
Charron G, Guy LG, Bazinet M, Julien JP (decembar 1995). "Multiple neuron-specific enhancers in the gene coding for the human neurofilament light chain". The Journal of Biological Chemistry. 270 (51): 30604–10. doi:10.1074/jbc.270.51.30604. PMID 8530496.
Mukai H, Toshimori M, Shibata H, Kitagawa M, Shimakawa M, Miyahara M, Sunakawa H, Ono Y (april 1996). "PKN associates and phosphorylates the head-rod domain of neurofilament protein". The Journal of Biological Chemistry. 271 (16): 9816–22. doi:10.1074/jbc.271.16.9816. PMID 8621664.
Rosengren LE, Karlsson JE, Karlsson JO, Persson LI, Wikkelsø C (novembar 1996). "Patients with amyotrophic lateral sclerosis and other neurodegenerative diseases have increased levels of neurofilament protein in CSF". Journal of Neurochemistry. 67 (5): 2013–8. doi:10.1046/j.1471-4159.1996.67052013.x. PMID 8863508. S2CID 36897027.
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.
Athlan ES, Mushynski WE (decembar 1997). "Heterodimeric associations between neuronal intermediate filament proteins". The Journal of Biological Chemistry. 272 (49): 31073–8. doi:10.1074/jbc.272.49.31073. PMID 9388258.
Ehlers MD, Fung ET, O'Brien RJ, Huganir RL (januar 1998). "Splice variant-specific interaction of the NMDA receptor subunit NR1 with neuronal intermediate filaments". The Journal of Neuroscience. 18 (2): 720–30. doi:10.1523/JNEUROSCI.18-02-00720.1998. PMC 6792537. PMID 9425014.
Mersiyanova IV, Perepelov AV, Polyakov AV, Sitnikov VF, Dadali EL, Oparin RB, Petrin AN, Evgrafov OV (juli 2000). "A new variant of Charcot-Marie-Tooth disease type 2 is probably the result of a mutation in the neurofilament-light gene". American Journal of Human Genetics. 67 (1): 37–46. doi:10.1086/302962. PMC 1287099. PMID 10841809.
De Jonghe P, Mersivanova I, Nelis E, Del Favero J, Martin JJ, Van Broeckhoven C, Evgrafov O, Timmerman V (februar 2001). "Further evidence that neurofilament light chain gene mutations can cause Charcot-Marie-Tooth disease type 2E". Annals of Neurology. 49 (2): 245–9. doi:10.1002/1531-8249(20010201)49:2<245::AID-ANA45>3.0.CO;2-A. PMID 11220745.

Vanjski linkovi uredi

Bird TD (26. 3. 2015). "Charcot-Marie-Tooth Neuropathy Type 1". u Pagon RA, Bird TD, Dolan CR, et al. (ured.). GeneReviews. Seattle WA: University of Washington, Seattle. NBK1205.
Bird TD (30. 1. 2014). Charcot-Marie-Tooth Neuropathy Type 2. PMID 20301462. NBK1285. In GeneReviews
De Jonghe P, Jordanova AK (27. 10. 2011). Charcot-Marie-Tooth Neuropathy Type 2E/1F. NBK1187. In GeneReviews

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000277586 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000022055 - 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.

[pmid17620486-5] Miltenberger-Miltenyi G, Janecke AR, Wanschitz JV, Timmerman V, Windpassinger C, Auer-Grumbach M, Löscher WN (juli 2007). "Clinical and electrophysiological features in Charcot-Marie-Tooth disease with mutations in the NEFL gene". Archives of Neurology. 64 (7): 966–70. doi:10.1001/archneur.64.7.966. PMID 17620486.

[entrez-6] "Entrez Gene: NEFL neurofilament, light polypeptide 68kDa".

[UniProt-7] "UniProt, P07196" (jezik: англ.). Pristupljeno 20. 9. 2021.CS1 održavanje: nepoznati jezik (link)

[Neurofilament_biomarkers-8] Khalil M, Teunissen CE, Otto M, Piehl F, Sormani MP, Gattringer T, Barro C, Kappos L, Comabella M, Fazekas F, Petzold A, Blennow K, Zetterberg H, Kuhle J (oktobar 2018). "Neurofilaments as biomarkers in neurological disorders" (PDF). Nature Reviews. Neurology. 14 (10): 577–589. doi:10.1038/s41582-018-0058-z. PMID 30171200. S2CID 52140127. neuroaxonal damage is the pathological substrate of permanent disability in various neurological disorders. ... Here, we review what is known about the structure and function of neurofilaments, discuss analytical aspects and knowledge of age-dependent normal ranges of neurofilaments and provide a comprehensive overview of studies on neurofilament light chain as a marker of axonal injury in different neurological disorders, including multiple sclerosis, neurodegenerative dementia, stroke, traumatic brain injury, amyotrophic lateral sclerosis and Parkinson disease.

[Prion_neurodegeneration_biomarkers-9] Thompson AB, Mead SH (decembar 2018). "Review: Fluid biomarkers in the human prion diseases" (PDF). Molecular and Cellular Neurosciences. 97: 81–92. doi:10.1016/j.mcn.2018.12.003. PMID 30529227. S2CID 54437514. The very rapid neurodegeneration of prion disease results in strong signals from surrogate protein markers in the blood that reflect neuronal, axonal, synaptic or glial pathology in the brain: notably the tau and neurofilament light chain proteins.

[ALS_systematic_review_and_meta-analysis-10] Xu Z, Henderson RD, David M, McCombe PA (2016). "Neurofilaments as Biomarkers for Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis". PLOS ONE. 11 (10): e0164625. Bibcode:2016PLoSO..1164625X. doi:10.1371/journal.pone.0164625. PMC 5061412. PMID 27732645. NF heavy and light chain levels have potential use as a marker of neural degeneration in ALS, but are not specific for the disease, and are more likely to be used as measures of disease progression.

[MS_Meta-analysis-11] Cai L, Huang J (2018). "Neurofilament light chain as a biological marker for multiple sclerosis: a meta-analysis study". Neuropsychiatric Disease and Treatment. 14: 2241–2254. doi:10.2147/NDT.S173280. PMC 6126505. PMID 30214214. NFL chain has significantly increased in MS patients, which substantially strengthens the clinical evidence of the NFL in MS. The NFL may be used as a prognostic biomarker to monitor disease progression, disease activity, and treatment efficacy in the future.

[12] Zetterberg, Henrik (6. 2. 2019). "Biomarkers for Alzheimer's disease beyond amyloid and tau" (PDF). Nature Medicine. 25 (2): 201–203. doi:10.1038/s41591-019-0348-z. PMID 30728536. S2CID 59607046.

[13] Preische O, Schultz SA, Apel A, et al. (2019). "Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease". Nature Medicine. 25 (2): 277–283. doi:10.1038/s41591-018-0304-3. PMC 6367005. PMID 30664784.

[14] Niemelä V, Landtblom AM, Blennow K, Sundblom J (27. 2. 2017). "Tau or neurofilament light-Which is the more suitable biomarker for Huntington's disease?". PLOS ONE. 12 (2): e0172762. Bibcode:2017PLoSO..1272762N. doi:10.1371/journal.pone.0172762. PMC 5328385. PMID 28241046.

[MyUser_Https:_February_11_2021c-15] "A neuronal blood marker is associated with mortality in old age". Pristupljeno 11. 2. 2021.

[pmid1902666-16] Frappier T, Stetzkowski-Marden F, Pradel LA (april 1991). "Interaction domains of neurofilament light chain and brain spectrin". The Biochemical Journal. 275 ( Pt 2) (2): 521–7. doi:10.1042/bj2750521. PMC 1150082. PMID 1902666.

[pmid8621664-17] Mukai H, Toshimori M, Shibata H, Kitagawa M, Shimakawa M, Miyahara M, Sunakawa H, Ono Y (april 1996). "PKN associates and phosphorylates the head-rod domain of neurofilament protein". The Journal of Biological Chemistry. 271 (16): 9816–22. doi:10.1074/jbc.271.16.9816. PMID 8621664.

[pmid12226091-18] Haddad LA, Smith N, Bowser M, Niida Y, Murthy V, Gonzalez-Agosti C, Ramesh V (novembar 2002). "The TSC1 tumor suppressor hamartin interacts with neurofilament-L and possibly functions as a novel integrator of the neuronal cytoskeleton". The Journal of Biological Chemistry. 277 (46): 44180–6. doi:10.1074/jbc.M207211200. PMID 12226091.

[5]

[6]

[1]

[2]

[3]

[4]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]

[18]