ID NFL_HUMAN Reviewed; 543 AA. AC P07196; B9ZVN2; Q16154; Q8IU72; DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 27-MAR-2024, entry version 239. DE RecName: Full=Neurofilament light polypeptide; DE Short=NF-L; DE AltName: Full=68 kDa neurofilament protein; DE AltName: Full=Neurofilament triplet L protein; GN Name=NEFL; Synonyms=NF68, NFL; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3034332; DOI=10.1016/0167-4781(87)90041-8; RA Julien J.-P., Grosveld F., Yazdanbaksh K., Flavell D., Meijer D., RA Mushynski W.; RT "The structure of a human neurofilament gene (NF-L): a unique exon-intron RT organization in the intermediate filament gene family."; RL Biochim. Biophys. Acta 909:10-20(1987). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=12432080; DOI=10.1242/jcs.00148; RA Perez-Olle R., Leung C.L., Liem R.K.; RT "Effects of Charcot-Marie-Tooth-linked mutations of the neurofilament light RT subunit on intermediate filament formation."; RL J. Cell Sci. 115:4937-4946(2002). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., RA Platzer M., Shimizu N., Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-11. RX PubMed=8180132; RA Pospelov V.A., Pospelova T.V., Julien J.-P.; RT "AP-1 and Krox-24 transcription factors activate the neurofilament light RT gene promoter in P19 embryonal carcinoma cells."; RL Cell Growth Differ. 5:187-196(1994). RN [7] RP PROTEIN SEQUENCE OF 38-54; 213-224; 340-353; 380-390 AND 422-437, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Fetal brain cortex; RA Lubec G., Chen W.-Q., Sun Y.; RL Submitted (DEC-2008) to UniProtKB. RN [8] RP PROTEIN SEQUENCE OF 468-473. RC TISSUE=Brain; RX PubMed=6135695; DOI=10.1093/jb/93.3.825; RA Nomata Y., Watanabe T., Wada H.; RT "Highly acidic proteins from human brain: purification and properties of RT Glu-50 protein."; RL J. Biochem. 93:825-831(1983). RN [9] RP PHOSPHORYLATION BY PKN1. RX PubMed=8621664; DOI=10.1074/jbc.271.16.9816; RA Mukai H., Toshimori M., Shibata H., Kitagawa M., Shimakawa M., Miyahara M., RA Sunakawa H., Ono Y.; RT "PKN associates and phosphorylates the head-rod domain of neurofilament RT protein."; RL J. Biol. Chem. 271:9816-9822(1996). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [12] RP VARIANT CMT2E PRO-332. RX PubMed=10841809; DOI=10.1086/302962; RA Mersiyanova I.V., Perepelov A.V., Polyakov A.V., Sitnikov V.F., RA Dadali E.L., Oparin R.B., Petrin A.N., Evgrafov O.V.; RT "A new variant of Charcot-Marie-Tooth disease type 2 is probably the result RT of a mutation in the neurofilament-light gene."; RL Am. J. Hum. Genet. 67:37-46(2000). RN [13] RP VARIANT CMT2E ARG-8. RX PubMed=11220745; RX DOI=10.1002/1531-8249(20010201)49:2<245::aid-ana45>3.0.co;2-a; RA De Jonghe P., Mersivanova I., Nelis E., Del Favero J., Martin J.-J., RA Van Broeckhoven C., Evgrafov O., Timmerman V.; RT "Further evidence that neurofilament light chain gene mutations can cause RT Charcot-Marie-Tooth disease type 2E."; RL Ann. Neurol. 49:245-249(2001). RN [14] RP VARIANT CMT2E SER-22. RX PubMed=12481988; DOI=10.1007/s10048-002-0138-4; RA Georgiou D.-M., Zidar J., Korosec M., Middleton L.T., Kyriakides T., RA Christodoulou K.; RT "A novel NF-L mutation Pro22Ser is associated with CMT2 in a large RT Slovenian family."; RL Neurogenetics 4:93-96(2002). RN [15] RP VARIANTS CMT1F ARG-8; LEU-8; GLN-8; LYS-90; SER-98 AND GLU-527 DEL, AND RP VARIANTS LYS-7 AND ASN-468. RX PubMed=12566280; DOI=10.1093/brain/awg059; RA Jordanova A., De Jonghe P., Boerkoel C.F., Takashima H., De Vriendt E., RA Ceuterick C., Martin J.-J., Butler I.J., Mancias P., Papasozomenos S.C., RA Terespolsky D., Potocki L., Brown C.W., Shy M., Rita D.A., Tournev I., RA Kremensky I., Lupski J.R., Timmerman V.; RT "Mutations in the neurofilament light chain gene (NEFL) cause early onset RT severe Charcot-Marie-Tooth disease."; RL Brain 126:590-597(2003). RN [16] RP VARIANT CMT2E PRO-336, AND VARIANT CMT1F LYS-396. RX PubMed=15241803; DOI=10.1002/humu.9261; RA Choi B.-O., Lee M.S., Shin S.H., Hwang J.H., Choi K.-G., Kim W.-K., RA Sunwoo I.N., Kim N.K., Chung K.W.; RT "Mutational analysis of PMP22, MPZ, GJB1, EGR2 and NEFL in Korean Charcot- RT Marie-Tooth neuropathy patients."; RL Hum. Mutat. 24:185-186(2004). RN [17] RP VARIANT CMTDIG LYS-396. RX PubMed=14733962; DOI=10.1016/j.nmd.2003.10.003; RA Zuechner S., Vorgerd M., Sindern E., Schroeder J.M.; RT "The novel neurofilament light (NEFL) mutation Glu397Lys is associated with RT a clinically and morphologically heterogeneous type of Charcot-Marie-Tooth RT neuropathy."; RL Neuromuscul. Disord. 14:147-157(2004). RN [18] RP VARIANTS MET-213 AND ASN-468, VARIANTS CMT2E SER-22; PRO-268 AND RP 322-CYS--ASN-326 DEL, AND VARIANT CMTDIG LYS-396. RX PubMed=17052987; DOI=10.1093/brain/awl284; RA Fabrizi G.M., Cavallaro T., Angiari C., Cabrini I., Taioli F., Malerba G., RA Bertolasi L., Rizzuto N.; RT "Charcot-Marie-Tooth disease type 2E, a disorder of the cytoskeleton."; RL Brain 130:394-403(2007). RN [19] RP VARIANTS CMT2E ARG-8; SER-22 AND LYS-396. RX PubMed=22206013; DOI=10.1371/journal.pone.0029393; RA Lin K.P., Soong B.W., Yang C.C., Huang L.W., Chang M.H., Lee I.H., RA Antonellis A., Lee Y.C.; RT "The mutational spectrum in a cohort of Charcot-Marie-Tooth disease type 2 RT among the Han Chinese in Taiwan."; RL PLoS ONE 6:E29393-E29393(2011). RN [20] RP VARIANT CMTDIG LYS-396, AND INVOLVEMENT IN CMTDIG. RX PubMed=25877835; DOI=10.1007/s00415-015-7709-4; RA Berciano J., Garcia A., Peeters K., Gallardo E., De Vriendt E., RA Pelayo-Negro A.L., Infante J., Jordanova A.; RT "NEFL E396K mutation is associated with a novel dominant intermediate RT Charcot-Marie-Tooth disease phenotype."; RL J. Neurol. 262:1289-1300(2015). RN [21] RP VARIANTS CMT2E CYS-265; PRO-268; PRO-336 AND LEU-440. RX PubMed=25802885; DOI=10.1002/mgg3.126; RA Drew A.P., Zhu D., Kidambi A., Ly C., Tey S., Brewer M.H., Ahmad-Annuar A., RA Nicholson G.A., Kennerson M.L.; RT "Improved inherited peripheral neuropathy genetic diagnosis by whole-exome RT sequencing."; RL Mol. Genet. Genomic Med. 3:143-154(2015). RN [22] RP VARIANT CMTDIG SER-98, AND INVOLVEMENT IN CMTDIG. RX PubMed=26645395; DOI=10.1007/s00415-015-7985-z; RA Berciano J., Peeters K., Garcia A., Lopez-Alburquerque T., Gallardo E., RA Hernandez-Fabian A., Pelayo-Negro A.L., De Vriendt E., Infante J., RA Jordanova A.; RT "NEFL N98S mutation: another cause of dominant intermediate Charcot-Marie- RT Tooth disease with heterogeneous early-onset phenotype."; RL J. Neurol. 263:361-369(2016). CC -!- FUNCTION: Neurofilaments usually contain three intermediate filament CC proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of CC neuronal caliber. May additionally cooperate with the neuronal CC intermediate filament proteins PRPH and INA to form neuronal CC filamentous networks (By similarity). {ECO:0000250|UniProtKB:P08551}. CC -!- SUBUNIT: Forms homodimers (in vitro) (By similarity). Forms CC heterodimers with NEFH or NEFM; which can further hetero-oligomerize CC (in vitro) (By similarity). Forms heterodimers with INA (in vitro) (By CC similarity). Interacts with ARHGEF28. Interacts with TRIM2. CC {ECO:0000250, ECO:0000250|UniProtKB:P19527}. CC -!- INTERACTION: CC P07196; P20933: AGA; NbExp=3; IntAct=EBI-475646, EBI-1223922; CC P07196; P13928: ANXA8; NbExp=3; IntAct=EBI-475646, EBI-2556915; CC P07196; Q9NP61: ARFGAP3; NbExp=3; IntAct=EBI-475646, EBI-2875816; CC P07196; Q9Y575-3: ASB3; NbExp=3; IntAct=EBI-475646, EBI-14199987; CC P07196; P21281: ATP6V1B2; NbExp=3; IntAct=EBI-475646, EBI-4290814; CC P07196; O95817: BAG3; NbExp=3; IntAct=EBI-475646, EBI-747185; CC P07196; Q8IXM2: BAP18; NbExp=3; IntAct=EBI-475646, EBI-4280811; CC P07196; Q96LL4: C8orf48; NbExp=3; IntAct=EBI-475646, EBI-751596; CC P07196; Q8N5S9-2: CAMKK1; NbExp=3; IntAct=EBI-475646, EBI-25850646; CC P07196; Q8IYE1: CCDC13; NbExp=3; IntAct=EBI-475646, EBI-10961312; CC P07196; P0C7W6: CCDC172; NbExp=3; IntAct=EBI-475646, EBI-2548868; CC P07196; A0A1B0GWI1: CCDC196; NbExp=3; IntAct=EBI-475646, EBI-10181422; CC P07196; Q6P2R3: CEP57L1; NbExp=3; IntAct=EBI-475646, EBI-12696312; CC P07196; Q494V2-2: CFAP100; NbExp=3; IntAct=EBI-475646, EBI-11953200; CC P07196; Q9Y240: CLEC11A; NbExp=3; IntAct=EBI-475646, EBI-3957044; CC P07196; Q8IUI8: CRLF3; NbExp=3; IntAct=EBI-475646, EBI-2872414; CC P07196; Q7L576: CYFIP1; NbExp=3; IntAct=EBI-475646, EBI-1048143; CC P07196; Q5TAQ9-2: DCAF8; NbExp=3; IntAct=EBI-475646, EBI-25842815; CC P07196; P17661: DES; NbExp=7; IntAct=EBI-475646, EBI-1055572; CC P07196; P63172: DYNLT1; NbExp=3; IntAct=EBI-475646, EBI-1176455; CC P07196; Q6UXG2-3: ELAPOR1; NbExp=3; IntAct=EBI-475646, EBI-12920100; CC P07196; Q9H6S3: EPS8L2; NbExp=3; IntAct=EBI-475646, EBI-3940939; CC P07196; Q99504: EYA3; NbExp=3; IntAct=EBI-475646, EBI-9089567; CC P07196; Q6P587-2: FAHD1; NbExp=3; IntAct=EBI-475646, EBI-12902289; CC P07196; Q8IZU1: FAM9A; NbExp=3; IntAct=EBI-475646, EBI-8468186; CC P07196; Q8TC84: FANK1; NbExp=3; IntAct=EBI-475646, EBI-21975404; CC P07196; Q53R41: FASTKD1; NbExp=3; IntAct=EBI-475646, EBI-3957005; CC P07196; Q7L622: G2E3; NbExp=3; IntAct=EBI-475646, EBI-751757; CC P07196; P14136: GFAP; NbExp=9; IntAct=EBI-475646, EBI-744302; CC P07196; Q9NXC2: GFOD1; NbExp=3; IntAct=EBI-475646, EBI-8799578; CC P07196; Q08379: GOLGA2; NbExp=3; IntAct=EBI-475646, EBI-618309; CC P07196; Q9BQQ3: GORASP1; NbExp=3; IntAct=EBI-475646, EBI-2561458; CC P07196; A0A024R8L2: hCG_1987119; NbExp=3; IntAct=EBI-475646, EBI-14103818; CC P07196; Q14005-2: IL16; NbExp=3; IntAct=EBI-475646, EBI-17178971; CC P07196; Q6ZU52: KIAA0408; NbExp=3; IntAct=EBI-475646, EBI-739493; CC P07196; Q9BVG8-5: KIFC3; NbExp=3; IntAct=EBI-475646, EBI-14069005; CC P07196; Q6P597-2: KLC3; NbExp=3; IntAct=EBI-475646, EBI-11033402; CC P07196; P13646: KRT13; NbExp=3; IntAct=EBI-475646, EBI-1223876; CC P07196; P19012: KRT15; NbExp=3; IntAct=EBI-475646, EBI-739566; CC P07196; P05783: KRT18; NbExp=3; IntAct=EBI-475646, EBI-297888; CC P07196; P08727: KRT19; NbExp=3; IntAct=EBI-475646, EBI-742756; CC P07196; Q14525: KRT33B; NbExp=3; IntAct=EBI-475646, EBI-1049638; CC P07196; Q8IUC2: KRTAP8-1; NbExp=3; IntAct=EBI-475646, EBI-10261141; CC P07196; Q14847-2: LASP1; NbExp=3; IntAct=EBI-475646, EBI-9088686; CC P07196; A2RU56: LOC401296; NbExp=3; IntAct=EBI-475646, EBI-9088215; CC P07196; Q9NS73-5: MBIP; NbExp=3; IntAct=EBI-475646, EBI-10182361; CC P07196; P51608: MECP2; NbExp=3; IntAct=EBI-475646, EBI-1189067; CC P07196; Q15049: MLC1; NbExp=3; IntAct=EBI-475646, EBI-8475277; CC P07196; Q8IXL7-2: MSRB3; NbExp=3; IntAct=EBI-475646, EBI-10699187; CC P07196; Q13614: MTMR2; NbExp=2; IntAct=EBI-475646, EBI-475631; CC P07196; Q99608: NDN; NbExp=4; IntAct=EBI-475646, EBI-718177; CC P07196; O76041: NEBL; NbExp=3; IntAct=EBI-475646, EBI-2880203; CC P07196; P07197: NEFM; NbExp=4; IntAct=EBI-475646, EBI-1105035; CC P07196; Q9HC98-4: NEK6; NbExp=3; IntAct=EBI-475646, EBI-11750983; CC P07196; Q9Y5B8: NME7; NbExp=3; IntAct=EBI-475646, EBI-744782; CC P07196; Q6X4W1-6: NSMF; NbExp=3; IntAct=EBI-475646, EBI-25842707; CC P07196; Q7Z417: NUFIP2; NbExp=3; IntAct=EBI-475646, EBI-1210753; CC P07196; O43482: OIP5; NbExp=3; IntAct=EBI-475646, EBI-536879; CC P07196; Q9P286: PAK5; NbExp=3; IntAct=EBI-475646, EBI-741896; CC P07196; Q9BRX2: PELO; NbExp=3; IntAct=EBI-475646, EBI-1043580; CC P07196; Q96LB9: PGLYRP3; NbExp=3; IntAct=EBI-475646, EBI-12339509; CC P07196; Q16512: PKN1; NbExp=3; IntAct=EBI-475646, EBI-602382; CC P07196; Q6NYC8: PPP1R18; NbExp=3; IntAct=EBI-475646, EBI-2557469; CC P07196; Q8NI37: PPTC7; NbExp=3; IntAct=EBI-475646, EBI-9089276; CC P07196; Q9Y5P3: RAI2; NbExp=3; IntAct=EBI-475646, EBI-746228; CC P07196; Q96PK6: RBM14; NbExp=3; IntAct=EBI-475646, EBI-954272; CC P07196; Q9P2K3-2: RCOR3; NbExp=3; IntAct=EBI-475646, EBI-1504830; CC P07196; Q8TCX5: RHPN1; NbExp=3; IntAct=EBI-475646, EBI-746325; CC P07196; Q8N488: RYBP; NbExp=3; IntAct=EBI-475646, EBI-752324; CC P07196; P25815: S100P; NbExp=3; IntAct=EBI-475646, EBI-743700; CC P07196; P12757: SKIL; NbExp=6; IntAct=EBI-475646, EBI-2902468; CC P07196; Q8NB12: SMYD1; NbExp=3; IntAct=EBI-475646, EBI-8463848; CC P07196; Q13573: SNW1; NbExp=3; IntAct=EBI-475646, EBI-632715; CC P07196; Q99932-2: SPAG8; NbExp=3; IntAct=EBI-475646, EBI-11959123; CC P07196; Q8N865: SPMIP4; NbExp=3; IntAct=EBI-475646, EBI-10174456; CC P07196; Q9H7C4: SYNC; NbExp=3; IntAct=EBI-475646, EBI-11285923; CC P07196; Q9BQG1: SYT3; NbExp=3; IntAct=EBI-475646, EBI-17284568; CC P07196; Q86TJ2-3: TADA2B; NbExp=3; IntAct=EBI-475646, EBI-18173581; CC P07196; Q5VWN6: TASOR2; NbExp=3; IntAct=EBI-475646, EBI-745958; CC P07196; Q8TDR4: TCP10L; NbExp=3; IntAct=EBI-475646, EBI-3923210; CC P07196; Q13569: TDG; NbExp=3; IntAct=EBI-475646, EBI-348333; CC P07196; P54274: TERF1; NbExp=2; IntAct=EBI-475646, EBI-710997; CC P07196; Q5W5X9-3: TTC23; NbExp=3; IntAct=EBI-475646, EBI-9090990; CC P07196; Q9UGJ1-2: TUBGCP4; NbExp=3; IntAct=EBI-475646, EBI-10964469; CC P07196; Q5VYS8-5: TUT7; NbExp=3; IntAct=EBI-475646, EBI-9088812; CC P07196; O75604: USP2; NbExp=3; IntAct=EBI-475646, EBI-743272; CC P07196; P45880: VDAC2; NbExp=3; IntAct=EBI-475646, EBI-354022; CC P07196; P08670: VIM; NbExp=3; IntAct=EBI-475646, EBI-353844; CC P07196; P58304: VSX2; NbExp=3; IntAct=EBI-475646, EBI-6427899; CC P07196; Q53FD0-2: ZC2HC1C; NbExp=3; IntAct=EBI-475646, EBI-14104088; CC P07196; Q15776: ZKSCAN8; NbExp=3; IntAct=EBI-475646, EBI-2602314; CC P07196; Q9UJW8-4: ZNF180; NbExp=3; IntAct=EBI-475646, EBI-12055755; CC P07196; Q9NR11-2: ZNF302; NbExp=3; IntAct=EBI-475646, EBI-12988373; CC P07196; Q9C0F3: ZNF436; NbExp=3; IntAct=EBI-475646, EBI-8489702; CC P07196; Q96MN9-2: ZNF488; NbExp=3; IntAct=EBI-475646, EBI-25831733; CC P07196; Q68EA5: ZNF57; NbExp=3; IntAct=EBI-475646, EBI-8490788; CC P07196; Q7Z3I7: ZNF572; NbExp=3; IntAct=EBI-475646, EBI-10172590; CC P07196; Q96N77-2: ZNF641; NbExp=3; IntAct=EBI-475646, EBI-12939666; CC P07196; Q3KNS6-3: ZNF829; NbExp=3; IntAct=EBI-475646, EBI-18036029; CC P07196; O15535: ZSCAN9; NbExp=3; IntAct=EBI-475646, EBI-751531; CC P07196; Q86V28; NbExp=3; IntAct=EBI-475646, EBI-10259496; CC P07196; P14079: tax; Xeno; NbExp=4; IntAct=EBI-475646, EBI-9675698; CC -!- SUBCELLULAR LOCATION: Cell projection, axon CC {ECO:0000250|UniProtKB:P08551}. Cytoplasm, cytoskeleton CC {ECO:0000250|UniProtKB:P08551}. CC -!- DOMAIN: The extra mass and high charge density that distinguish the CC neurofilament proteins from all other intermediate filament proteins CC are due to the tailpiece extensions. This region may form a charged CC scaffolding structure suitable for interaction with other neuronal CC components or ions. CC -!- PTM: O-glycosylated. {ECO:0000250}. CC -!- PTM: Phosphorylated in the head and rod regions by the PKC kinase PKN1, CC leading to the inhibition of polymerization. CC {ECO:0000269|PubMed:8621664}. CC -!- PTM: Ubiquitinated in the presence of TRIM2 and UBE2D1. {ECO:0000250}. CC -!- DISEASE: Charcot-Marie-Tooth disease, demyelinating, 1F (CMT1F) CC [MIM:607734]: A dominant demyelinating form of Charcot-Marie-Tooth CC disease, a disorder of the peripheral nervous system, characterized by CC progressive weakness and atrophy, initially of the peroneal muscles and CC later of the distal muscles of the arms. Charcot-Marie-Tooth disease is CC classified in two main groups on the basis of electrophysiologic CC properties and histopathology: primary peripheral demyelinating CC neuropathies (designated CMT1 when they are dominantly inherited) and CC primary peripheral axonal neuropathies (CMT2). Demyelinating CC neuropathies are characterized by severely reduced nerve conduction CC velocities (less than 38 m/sec), segmental demyelination and CC remyelination with onion bulb formations on nerve biopsy, slowly CC progressive distal muscle atrophy and weakness, absent deep tendon CC reflexes, and hollow feet. CMT1F is characterized by onset in infancy CC or childhood (range 1 to 13 years). {ECO:0000269|PubMed:12566280, CC ECO:0000269|PubMed:15241803}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Charcot-Marie-Tooth disease, axonal, 2E (CMT2E) [MIM:607684]: CC A dominant axonal form of Charcot-Marie-Tooth disease, a disorder of CC the peripheral nervous system, characterized by progressive weakness CC and atrophy, initially of the peroneal muscles and later of the distal CC muscles of the arms. Charcot-Marie-Tooth disease is classified in two CC main groups on the basis of electrophysiologic properties and CC histopathology: primary peripheral demyelinating neuropathies CC (designated CMT1 when they are dominantly inherited) and primary CC peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group CC are characterized by signs of axonal degeneration in the absence of CC obvious myelin alterations, normal or slightly reduced nerve conduction CC velocities, and progressive distal muscle weakness and atrophy. CC {ECO:0000269|PubMed:10841809, ECO:0000269|PubMed:11220745, CC ECO:0000269|PubMed:12481988, ECO:0000269|PubMed:15241803, CC ECO:0000269|PubMed:17052987, ECO:0000269|PubMed:22206013, CC ECO:0000269|PubMed:25802885}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Charcot-Marie-Tooth disease, dominant intermediate G (CMTDIG) CC [MIM:617882]: An autosomal dominant, intermediate form of Charcot- CC Marie-Tooth disease, a disorder of the peripheral nervous system, CC characterized by progressive weakness and atrophy, initially of the CC peroneal muscles and later of the distal muscles of the arms. Dominant CC intermediate forms are characterized by clinical and pathologic CC features intermediate between demyelinating and axonal peripheral CC neuropathies, and motor median nerve conduction velocities ranging from CC 25 to 45 m/sec. CMTDIG is phenotypically variable. Most affected CC individuals have onset in the first or second decades of slowly CC progressive distal motor weakness and atrophy, resulting in gait CC instability and distal upper limb impairment, as well as distal sensory CC impairment. {ECO:0000269|PubMed:14733962, ECO:0000269|PubMed:17052987, CC ECO:0000269|PubMed:25877835, ECO:0000269|PubMed:26645395}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: NF-L is the most abundant of the three neurofilament CC proteins and, like the other nonepithelial intermediate filament CC proteins, it can form homomeric 10-nm filaments. CC -!- SIMILARITY: Belongs to the intermediate filament family. CC {ECO:0000255|PROSITE-ProRule:PRU01188}. CC -!- WEB RESOURCE: Name=Inherited peripheral neuropathies mutation db; CC URL="https://uantwerpen.vib.be/CMTMutations"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X05608; CAA29097.1; -; Genomic_DNA. DR EMBL; AY156690; AAN74826.1; -; mRNA. DR EMBL; AC107373; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471080; EAW63598.1; -; Genomic_DNA. DR EMBL; CH471080; EAW63599.1; -; Genomic_DNA. DR EMBL; CH471080; EAW63600.1; -; Genomic_DNA. DR EMBL; BC039237; AAH39237.1; -; mRNA. DR EMBL; S70309; AAD14057.1; -; Genomic_DNA. DR CCDS; CCDS75712.1; -. DR PIR; S07144; S07144. DR RefSeq; NP_006149.2; NM_006158.4. DR AlphaFoldDB; P07196; -. DR SMR; P07196; -. DR BioGRID; 110822; 134. DR IntAct; P07196; 153. DR MINT; P07196; -. DR STRING; 9606.ENSP00000482169; -. DR GlyCosmos; P07196; 22 sites, 1 glycan. DR GlyGen; P07196; 24 sites, 1 O-linked glycan (21 sites). DR iPTMnet; P07196; -. DR PhosphoSitePlus; P07196; -. DR SwissPalm; P07196; -. DR BioMuta; NEFL; -. DR DMDM; 62511894; -. DR EPD; P07196; -. DR jPOST; P07196; -. DR MassIVE; P07196; -. DR MaxQB; P07196; -. DR PaxDb; 9606-ENSP00000482169; -. DR PeptideAtlas; P07196; -. DR ProteomicsDB; 51961; -. DR Pumba; P07196; -. DR ABCD; P07196; 1 sequenced antibody. DR Antibodypedia; 73404; 1319 antibodies from 42 providers. DR DNASU; 4747; -. DR Ensembl; ENST00000610854.2; ENSP00000482169.2; ENSG00000277586.4. DR GeneID; 4747; -. DR KEGG; hsa:4747; -. DR MANE-Select; ENST00000610854.2; ENSP00000482169.2; NM_006158.5; NP_006149.2. DR UCSC; uc033bfe.2; human. DR AGR; HGNC:7739; -. DR CTD; 4747; -. DR DisGeNET; 4747; -. DR GeneCards; NEFL; -. DR GeneReviews; NEFL; -. DR HGNC; HGNC:7739; NEFL. DR HPA; ENSG00000277586; Group enriched (brain, retina). DR MalaCards; NEFL; -. DR MIM; 162280; gene. DR MIM; 607684; phenotype. DR MIM; 607734; phenotype. DR MIM; 617882; phenotype. DR neXtProt; NX_P07196; -. DR OpenTargets; ENSG00000277586; -. DR Orphanet; 99939; Autosomal dominant Charcot-Marie-Tooth disease type 2E. DR Orphanet; 101085; Charcot-Marie-Tooth disease type 1F. DR Orphanet; 228374; Charcot-Marie-Tooth disease type 2B5. DR PharmGKB; PA31542; -. DR VEuPathDB; HostDB:ENSG00000277586; -. DR eggNOG; ENOG502QSXY; Eukaryota. DR GeneTree; ENSGT00940000156208; -. DR HOGENOM; CLU_012560_7_3_1; -. DR InParanoid; P07196; -. DR OMA; EATHEKQ; -. DR OrthoDB; 4640531at2759; -. DR PhylomeDB; P07196; -. DR PathwayCommons; P07196; -. DR Reactome; R-HSA-438066; Unblocking of NMDA receptors, glutamate binding and activation. DR Reactome; R-HSA-442982; Ras activation upon Ca2+ influx through NMDA receptor. DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. DR Reactome; R-HSA-9609736; Assembly and cell surface presentation of NMDA receptors. DR Reactome; R-HSA-9617324; Negative regulation of NMDA receptor-mediated neuronal transmission. DR Reactome; R-HSA-9620244; Long-term potentiation. DR SignaLink; P07196; -. DR SIGNOR; P07196; -. DR BioGRID-ORCS; 4747; 11 hits in 259 CRISPR screens. DR ChiTaRS; NEFL; human. DR GeneWiki; NEFL; -. DR GenomeRNAi; 4747; -. DR Pharos; P07196; Tbio. DR PRO; PR:P07196; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; P07196; Protein. DR Bgee; ENSG00000277586; Expressed in dorsal root ganglion and 159 other cell types or tissues. DR GO; GO:0030424; C:axon; IDA:UniProtKB. DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC. DR GO; GO:0098981; C:cholinergic synapse; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; ISS:BHF-UCL. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0030426; C:growth cone; IEA:Ensembl. DR GO; GO:0005882; C:intermediate filament; IBA:GO_Central. DR GO; GO:0005883; C:neurofilament; IDA:UniProtKB. DR GO; GO:0031594; C:neuromuscular junction; IEA:Ensembl. DR GO; GO:0099160; C:postsynaptic intermediate filament cytoskeleton; IBA:GO_Central. DR GO; GO:0099182; C:presynaptic intermediate filament cytoskeleton; IEA:Ensembl. DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB. DR GO; GO:0043274; F:phospholipase binding; IEA:Ensembl. DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl. DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl. DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISS:BHF-UCL. DR GO; GO:0005200; F:structural constituent of cytoskeleton; IDA:UniProtKB. DR GO; GO:0099184; F:structural constituent of postsynaptic intermediate filament cytoskeleton; IBA:GO_Central. DR GO; GO:0008089; P:anterograde axonal transport; IMP:UniProtKB. DR GO; GO:0019896; P:axonal transport of mitochondrion; IMP:UniProtKB. DR GO; GO:0007409; P:axonogenesis; IEA:Ensembl. DR GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl. DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl. DR GO; GO:0045109; P:intermediate filament organization; IMP:UniProtKB. DR GO; GO:0045105; P:intermediate filament polymerization or depolymerization; IEA:Ensembl. DR GO; GO:0040011; P:locomotion; IEA:Ensembl. DR GO; GO:0000226; P:microtubule cytoskeleton organization; IEA:Ensembl. DR GO; GO:0097049; P:motor neuron apoptotic process; IEA:Ensembl. DR GO; GO:2000672; P:negative regulation of motor neuron apoptotic process; IEA:Ensembl. DR GO; GO:0033693; P:neurofilament bundle assembly; IDA:UniProtKB. DR GO; GO:0060052; P:neurofilament cytoskeleton organization; IEA:Ensembl. DR GO; GO:0050885; P:neuromuscular process controlling balance; IEA:Ensembl. DR GO; GO:0014012; P:peripheral nervous system axon regeneration; IEA:Ensembl. DR GO; GO:0050772; P:positive regulation of axonogenesis; IEA:Ensembl. DR GO; GO:0099170; P:postsynaptic modulation of chemical synaptic transmission; IEA:Ensembl. DR GO; GO:0051258; P:protein polymerization; IEA:Ensembl. DR GO; GO:0031133; P:regulation of axon diameter; IEA:Ensembl. DR GO; GO:0090128; P:regulation of synapse maturation; IEA:Ensembl. DR GO; GO:1903937; P:response to acrylamide; IEA:Ensembl. DR GO; GO:0051412; P:response to corticosterone; IEA:Ensembl. DR GO; GO:0043434; P:response to peptide hormone; IEA:Ensembl. DR GO; GO:1903935; P:response to sodium arsenite; IEA:Ensembl. DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl. DR GO; GO:0008090; P:retrograde axonal transport; IMP:UniProtKB. DR GO; GO:0021510; P:spinal cord development; IEA:Ensembl. DR Gene3D; 1.20.5.170; -; 1. DR Gene3D; 1.20.5.500; Single helix bin; 1. DR Gene3D; 1.20.5.1160; Vasodilator-stimulated phosphoprotein; 1. DR InterPro; IPR018039; IF_conserved. DR InterPro; IPR039008; IF_rod_dom. DR InterPro; IPR006821; Intermed_filament_DNA-bd. DR PANTHER; PTHR45652; GLIAL FIBRILLARY ACIDIC PROTEIN; 1. DR PANTHER; PTHR45652:SF8; NEUROFILAMENT LIGHT POLYPEPTIDE; 1. DR Pfam; PF00038; Filament; 1. DR Pfam; PF04732; Filament_head; 1. DR SMART; SM01391; Filament; 1. DR SUPFAM; SSF64593; Intermediate filament protein, coiled coil region; 2. DR PROSITE; PS00226; IF_ROD_1; 1. DR PROSITE; PS51842; IF_ROD_2; 1. DR UCD-2DPAGE; P07196; -. DR Genevisible; P07196; HS. PE 1: Evidence at protein level; KW Acetylation; Cell projection; Charcot-Marie-Tooth disease; Coiled coil; KW Cytoplasm; Cytoskeleton; Direct protein sequencing; Disease variant; KW Glycoprotein; Intermediate filament; Methylation; Neurodegeneration; KW Neuropathy; Phosphoprotein; Reference proteome; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:22223895" FT CHAIN 2..543 FT /note="Neurofilament light polypeptide" FT /id="PRO_0000063787" FT DOMAIN 90..400 FT /note="IF rod" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01188" FT REGION 2..92 FT /note="Head" FT REGION 93..124 FT /note="Coil 1A" FT REGION 125..137 FT /note="Linker 1" FT REGION 138..234 FT /note="Coil 1B" FT REGION 235..252 FT /note="Linker 12" FT REGION 253..271 FT /note="Coil 2A" FT REGION 272..280 FT /note="Linker 2" FT REGION 281..396 FT /note="Coil 2B" FT REGION 381..391 FT /note="Epitope; recognized by IF-specific monoclonal FT antibody" FT REGION 397..543 FT /note="Tail" FT REGION 397..443 FT /note="Tail, subdomain A" FT REGION 444..543 FT /note="Tail, subdomain B (acidic)" FT REGION 462..543 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 470..522 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 523..543 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0007744|PubMed:22223895" FT MOD_RES 23 FT /note="Asymmetric dimethylarginine; alternate" FT /evidence="ECO:0000250|UniProtKB:P08551" FT MOD_RES 23 FT /note="Omega-N-methylarginine; alternate" FT /evidence="ECO:0000250|UniProtKB:P08551" FT MOD_RES 30 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:P08551" FT MOD_RES 43 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P08551" FT MOD_RES 56 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P02548" FT MOD_RES 67 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P02548" FT MOD_RES 103 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19527" FT MOD_RES 472 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P02548" FT MOD_RES 502 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P19527" FT MOD_RES 520 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P19527" FT CARBOHYD 21 FT /note="O-linked (GlcNAc) threonine" FT /evidence="ECO:0000250" FT CARBOHYD 27 FT /note="O-linked (GlcNAc) serine" FT /evidence="ECO:0000250" FT VARIANT 7 FT /note="E -> K (in a Charcot-Marie-Tooth disease patient; FT dbSNP:rs57848467)" FT /evidence="ECO:0000269|PubMed:12566280" FT /id="VAR_016017" FT VARIANT 8 FT /note="P -> L (in CMT1F; dbSNP:rs61491953)" FT /evidence="ECO:0000269|PubMed:12566280" FT /id="VAR_016018" FT VARIANT 8 FT /note="P -> Q (in CMT1F; dbSNP:rs61491953)" FT /evidence="ECO:0000269|PubMed:12566280" FT /id="VAR_016019" FT VARIANT 8 FT /note="P -> R (in CMT2E and CMT1F; dbSNP:rs61491953)" FT /evidence="ECO:0000269|PubMed:11220745, FT ECO:0000269|PubMed:12566280, ECO:0000269|PubMed:22206013" FT /id="VAR_016020" FT VARIANT 22 FT /note="P -> S (in CMT2E; dbSNP:rs28928910)" FT /evidence="ECO:0000269|PubMed:12481988, FT ECO:0000269|PubMed:17052987, ECO:0000269|PubMed:22206013" FT /id="VAR_016021" FT VARIANT 90 FT /note="E -> K (in CMT1F; dbSNP:rs58332872)" FT /evidence="ECO:0000269|PubMed:12566280" FT /id="VAR_016022" FT VARIANT 98 FT /note="N -> S (in CMT1F and CMTDIG; dbSNP:rs58982919)" FT /evidence="ECO:0000269|PubMed:12566280, FT ECO:0000269|PubMed:26645395" FT /id="VAR_016023" FT VARIANT 213 FT /note="I -> M (in dbSNP:rs62636522)" FT /evidence="ECO:0000269|PubMed:17052987" FT /id="VAR_081565" FT VARIANT 265 FT /note="Y -> C (in CMT2E; uncertain significance; FT dbSNP:rs587777880)" FT /evidence="ECO:0000269|PubMed:25802885" FT /id="VAR_081566" FT VARIANT 268 FT /note="L -> P (in CMT2E; dbSNP:rs62636502)" FT /evidence="ECO:0000269|PubMed:17052987, FT ECO:0000269|PubMed:25802885" FT /id="VAR_081567" FT VARIANT 322..326 FT /note="Missing (in CMT2E; uncertain significance)" FT /evidence="ECO:0000269|PubMed:17052987" FT /id="VAR_081568" FT VARIANT 332 FT /note="Q -> P (in CMT2E; dbSNP:rs59443585)" FT /evidence="ECO:0000269|PubMed:10841809" FT /id="VAR_009703" FT VARIANT 336 FT /note="L -> P (in CMT2E; uncertain significance; FT dbSNP:rs587777881)" FT /evidence="ECO:0000269|PubMed:15241803, FT ECO:0000269|PubMed:25802885" FT /id="VAR_021613" FT VARIANT 396 FT /note="E -> K (in CMTDIG and CMT2E; dbSNP:rs62636503)" FT /evidence="ECO:0000269|PubMed:14733962, FT ECO:0000269|PubMed:15241803, ECO:0000269|PubMed:17052987, FT ECO:0000269|PubMed:22206013, ECO:0000269|PubMed:25877835" FT /id="VAR_021614" FT VARIANT 440 FT /note="P -> L (in CMT2E; uncertain significance; FT dbSNP:rs587777882)" FT /evidence="ECO:0000269|PubMed:25802885" FT /id="VAR_081569" FT VARIANT 468 FT /note="D -> N (in dbSNP:rs57153321)" FT /evidence="ECO:0000269|PubMed:12566280, FT ECO:0000269|PubMed:17052987" FT /id="VAR_016024" FT VARIANT 527 FT /note="Missing (in CMT1F; dbSNP:rs3832558)" FT /evidence="ECO:0000269|PubMed:12566280" FT /id="VAR_016025" FT CONFLICT 28 FT /note="Missing (in Ref. 1; CAA29097)" FT /evidence="ECO:0000305" FT CONFLICT 155 FT /note="N -> TN (in Ref. 1)" FT /evidence="ECO:0000305" FT CONFLICT 161 FT /note="Q -> R (in Ref. 1; CAA29097)" FT /evidence="ECO:0000305" FT CONFLICT 165 FT /note="E -> EE (in Ref. 1; CAA29097)" FT /evidence="ECO:0000305" FT CONFLICT 195 FT /note="A -> R (in Ref. 1; CAA29097)" FT /evidence="ECO:0000305" FT CONFLICT 452 FT /note="I -> T (in Ref. 1; CAA29097)" FT /evidence="ECO:0000305" FT CONFLICT 461 FT /note="A -> S (in Ref. 1; CAA29097)" FT /evidence="ECO:0000305" FT CONFLICT 472 FT /note="S -> D (in Ref. 8; AA sequence)" FT /evidence="ECO:0000305" SQ SEQUENCE 543 AA; 61517 MW; 98C1712D8ACFF33A CRC64; 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 //