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P07196 (NFL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 159. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Neurofilament light polypeptide

Short name=NF-L
Alternative name(s):
68 kDa neurofilament protein
Neurofilament triplet L protein
Gene names
Name:NEFL
Synonyms:NF68, NFL
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length543 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Neurofilaments usually contain three intermediate filament proteins: L, M, and H which are involved in the maintenance of neuronal caliber.

Subunit structure

Interacts with ARHGEF28 By similarity. Interacts with TRIM2 By similarity.

Domain

The extra mass and high charge density that distinguish the neurofilament proteins from all other intermediate filament proteins are due to the tailpiece extensions. This region may form a charged scaffolding structure suitable for interaction with other neuronal components or ions.

Post-translational modification

O-glycosylated By similarity.

Phosphorylated in the head and rod regions by the PKC kinase PKN1, leading to the inhibition of polymerization. Ref.9

Ubiquitinated in the presence of TRIM2 and UBE2D1 By similarity.

Involvement in disease

Charcot-Marie-Tooth disease 1F (CMT1F) [MIM:607734]: A dominant demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. CMT1F is characterized by onset in infancy or childhood (range 1 to 13 years).
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15 Ref.16 Ref.17

Charcot-Marie-Tooth disease 2E (CMT2E) [MIM:607684]: A dominant axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. Nerve conduction velocities are normal or slightly reduced.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12 Ref.13 Ref.14 Ref.16 Ref.18

Miscellaneous

NF-L is the most abundant of the three neurofilament proteins and, like the other nonepithelial intermediate filament proteins, it can form homopolymeric 10-nm filaments.

Sequence similarities

Belongs to the intermediate filament family.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MTMR2Q136142EBI-475646,EBI-475631

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 543542Neurofilament light polypeptide
PRO_0000063787

Regions

Region2 – 9291Head
Region93 – 396304Rod
Region93 – 12432Coil 1A
Region125 – 13713Linker 1
Region138 – 23497Coil 1B
Region235 – 25218Linker 12
Region253 – 27119Coil 2A
Region272 – 2809Linker 2
Region281 – 396116Coil 2B
Region381 – 39111Epitope; recognized by IF-specific monoclonal antibody
Region397 – 543147Tail
Region397 – 44347Tail, subdomain A
Region444 – 543100Tail, subdomain B (acidic)

Amino acid modifications

Modified residue21N-acetylserine Ref.11
Modified residue431Phosphotyrosine By similarity
Modified residue561Phosphoserine By similarity
Modified residue671Phosphoserine By similarity
Modified residue4721Phosphoserine By similarity
Glycosylation211O-linked (GlcNAc) By similarity
Glycosylation271O-linked (GlcNAc) By similarity

Natural variations

Natural variant71E → K in a Charcot-Marie-Tooth disease patient. Ref.15
Corresponds to variant rs57848467 [ dbSNP | Ensembl ].
VAR_016017
Natural variant81P → L in CMT1F. Ref.15
VAR_016018
Natural variant81P → Q in CMT1F. Ref.15
VAR_016019
Natural variant81P → R in CMT2E and CMT1F; severely reduced nerve conduction velocities in some patients. Ref.13 Ref.15 Ref.18
Corresponds to variant rs60261494 [ dbSNP | Ensembl ].
VAR_016020
Natural variant221P → S in CMT2E. Ref.14 Ref.18
Corresponds to variant rs28928910 [ dbSNP | Ensembl ].
VAR_016021
Natural variant901E → K in CMT1F. Ref.15
Corresponds to variant rs58332872 [ dbSNP | Ensembl ].
VAR_016022
Natural variant981N → S in CMT1F. Ref.15
Corresponds to variant rs58982919 [ dbSNP | Ensembl ].
VAR_016023
Natural variant3321Q → P in CMT2E. Ref.12
Corresponds to variant rs59443585 [ dbSNP | Ensembl ].
VAR_009703
Natural variant3361L → P in CMT2E. Ref.16
VAR_021613
Natural variant3961E → K in CMT1F and CMT2E. Ref.16 Ref.17 Ref.18
VAR_021614
Natural variant4681D → N. Ref.15
Corresponds to variant rs57153321 [ dbSNP | Ensembl ].
VAR_016024
Natural variant5271Missing in CMT1F. Ref.15
VAR_016025

Experimental info

Sequence conflict281Missing in CAA29097. Ref.1
Sequence conflict1551N → TN Ref.1
Sequence conflict1611Q → R in CAA29097. Ref.1
Sequence conflict1651E → EE in CAA29097. Ref.1
Sequence conflict1951A → R in CAA29097. Ref.1
Sequence conflict4521I → T in CAA29097. Ref.1
Sequence conflict4611A → S in CAA29097. Ref.1
Sequence conflict4721S → D AA sequence Ref.8

Sequences

Sequence LengthMass (Da)Tools
P07196 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 98C1712D8ACFF33A

FASTA54361,517
        10         20         30         40         50         60 
MSSFSYEPYY STSYKRRYVE TPRVHISSVR SGYSTARSAY SSYSAPVSSS LSVRRSYSSS 

        70         80         90        100        110        120 
SGSLMPSLEN LDLSQVAAIS NDLKSIRTQE KAQLQDLNDR FASFIERVHE LEQQNKVLEA 

       130        140        150        160        170        180 
ELLVLRQKHS EPSRFRALYE QEIRDLRLAA EDATNEKQAL QGEREGLEET LRNLQARYEE 

       190        200        210        220        230        240 
EVLSREDAEG RLMEARKGAD EAALARAELE KRIDSLMDEI SFLKKVHEEE IAELQAQIQY 

       250        260        270        280        290        300 
AQISVEMDVT KPDLSAALKD IRAQYEKLAA KNMQNAEEWF KSRFTVLTES AAKNTDAVRA 

       310        320        330        340        350        360 
AKDEVSESRR LLKAKTLEIE ACRGMNEALE KQLQELEDKQ NADISAMQDT INKLENELRT 

       370        380        390        400        410        420 
TKSEMARYLK EYQDLLNVKM ALDIEIAAYR KLLEGEETRL SFTSVGSITS GYSQSSQVFG 

       430        440        450        460        470        480 
RSAYGGLQTS SYLMSTRSFP SYYTSHVQEE QIEVEETIEA AKAEEAKDEP PSEGEAEEEE 

       490        500        510        520        530        540 
KDKEEAEEEE AAEEEEAAKE ESEEAKEEEE GGEGEEGEET KEAEEEEKKV EGAGEEQAAK 


KKD 

« Hide

References

« Hide 'large scale' references
[1]"The structure of a human neurofilament gene (NF-L): a unique exon-intron organization in the intermediate filament gene family."
Julien J.-P., Grosveld F., Yazdanbaksh K., Flavell D., Meijer D., Mushynski W.
Biochim. Biophys. Acta 909:10-20(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Effects of Charcot-Marie-Tooth-linked mutations of the neurofilament light subunit on intermediate filament formation."
Perez-Olle R., Leung C.L., Liem R.K.
J. Cell Sci. 115:4937-4946(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"DNA sequence and analysis of human chromosome 8."
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. expand/collapse author list , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[6]"AP-1 and Krox-24 transcription factors activate the neurofilament light gene promoter in P19 embryonal carcinoma cells."
Pospelov V.A., Pospelova T.V., Julien J.-P.
Cell Growth Differ. 5:187-196(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-11.
[7]Lubec G., Chen W.-Q., Sun Y.
Submitted (DEC-2008) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 38-54; 213-224; 340-353; 380-390 AND 422-437, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Fetal brain cortex.
[8]"Highly acidic proteins from human brain: purification and properties of Glu-50 protein."
Nomata Y., Watanabe T., Wada H.
J. Biochem. 93:825-831(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 468-473.
Tissue: Brain.
[9]"PKN associates and phosphorylates the head-rod domain of neurofilament protein."
Mukai H., Toshimori M., Shibata H., Kitagawa M., Shimakawa M., Miyahara M., Sunakawa H., Ono Y.
J. Biol. Chem. 271:9816-9822(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY PKN1.
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[12]"A new variant of Charcot-Marie-Tooth disease type 2 is probably the result of a mutation in the neurofilament-light gene."
Mersiyanova I.V., Perepelov A.V., Polyakov A.V., Sitnikov V.F., Dadali E.L., Oparin R.B., Petrin A.N., Evgrafov O.V.
Am. J. Hum. Genet. 67:37-46(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CMT2E PRO-332.
[13]"Further evidence that neurofilament light chain gene mutations can cause Charcot-Marie-Tooth disease type 2E."
De Jonghe P., Mersivanova I., Nelis E., Del Favero J., Martin J.-J., Van Broeckhoven C., Evgrafov O., Timmerman V.
Ann. Neurol. 49:245-249(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CMT2E ARG-8.
[14]"A novel NF-L mutation Pro22Ser is associated with CMT2 in a large Slovenian family."
Georgiou D.-M., Zidar J., Korosec M., Middleton L.T., Kyriakides T., Christodoulou K.
Neurogenetics 4:93-96(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CMT2E SER-22.
[15]"Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot-Marie-Tooth disease."
Jordanova A., De Jonghe P., Boerkoel C.F., Takashima H., De Vriendt E., Ceuterick C., Martin J.-J., Butler I.J., Mancias P., Papasozomenos S.C., Terespolsky D., Potocki L., Brown C.W., Shy M., Rita D.A., Tournev I., Kremensky I., Lupski J.R., Timmerman V.
Brain 126:590-597(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CMT1F ARG-8; LEU-8; GLN-8; LYS-90; SER-98 AND GLU-527 DEL, VARIANTS LYS-7 AND ASN-468.
[16]"Mutational analysis of PMP22, MPZ, GJB1, EGR2 and NEFL in Korean Charcot-Marie-Tooth neuropathy patients."
Choi B.-O., Lee M.S., Shin S.H., Hwang J.H., Choi K.-G., Kim W.-K., Sunwoo I.N., Kim N.K., Chung K.W.
Hum. Mutat. 24:185-186(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CMT2E PRO-336, VARIANT CMT1F LYS-396.
[17]"The novel neurofilament light (NEFL) mutation Glu397Lys is associated with a clinically and morphologically heterogeneous type of Charcot-Marie-Tooth neuropathy."
Zuechner S., Vorgerd M., Sindern E., Schroeder J.M.
Neuromuscul. Disord. 14:147-157(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CMT1F LYS-396.
[18]"The mutational spectrum in a cohort of Charcot-Marie-Tooth disease type 2 among the Han Chinese in Taiwan."
Lin K.P., Soong B.W., Yang C.C., Huang L.W., Chang M.H., Lee I.H., Antonellis A., Lee Y.C.
PLoS ONE 6:E29393-E29393(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CMT2E ARG-8; SER-22 AND LYS-396.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X05608 Genomic DNA. Translation: CAA29097.1.
AY156690 mRNA. Translation: AAN74826.1.
AC107373 Genomic DNA. No translation available.
CH471080 Genomic DNA. Translation: EAW63598.1.
CH471080 Genomic DNA. Translation: EAW63599.1.
CH471080 Genomic DNA. Translation: EAW63600.1.
BC039237 mRNA. Translation: AAH39237.1.
S70309 Genomic DNA. Translation: AAD14057.1.
PIRS07144.
RefSeqNP_006149.2. NM_006158.4.
UniGeneHs.521461.

3D structure databases

ProteinModelPortalP07196.
SMRP07196. Positions 87-238, 252-321, 326-395.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110822. 18 interactions.
IntActP07196. 14 interactions.
MINTMINT-1370620.
STRING9606.ENSP00000221169.

PTM databases

PhosphoSiteP07196.

Polymorphism databases

DMDM62511894.

2D gel databases

UCD-2DPAGEP07196.

Proteomic databases

PaxDbP07196.
PRIDEP07196.

Protocols and materials databases

DNASU4747.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID4747.
KEGGhsa:4747.
UCSCuc003xee.4. human.

Organism-specific databases

CTD4747.
GeneCardsGC08M024808.
HGNCHGNC:7739. NEFL.
MIM162280. gene.
607684. phenotype.
607734. phenotype.
neXtProtNX_P07196.
Orphanet99939. Autosomal dominant Charcot-Marie-Tooth disease type 2E.
101085. Charcot-Marie-Tooth disease type 1F.
228374. Severe early-onset axonal neuropathy due to NEFL deficiency.
PharmGKBPA31542.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG145720.
HOVERGENHBG013015.
InParanoidP07196.
KOK04572.
PhylomeDBP07196.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.

Gene expression databases

CleanExHS_NEFL.
GenevestigatorP07196.

Family and domain databases

InterProIPR001664. IF.
IPR006821. Intermed_filament_DNA-bd.
IPR018039. Intermediate_filament_CS.
IPR027692. NF-L.
[Graphical view]
PANTHERPTHR23239. PTHR23239. 1 hit.
PTHR23239:SF22. PTHR23239:SF22. 1 hit.
PfamPF00038. Filament. 1 hit.
PF04732. Filament_head. 1 hit.
[Graphical view]
PROSITEPS00226. IF. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNEFL. human.
GeneWikiNEFL.
GenomeRNAi4747.
NextBio18298.
PROP07196.
SOURCESearch...

Entry information

Entry nameNFL_HUMAN
AccessionPrimary (citable) accession number: P07196
Secondary accession number(s): B9ZVN2, Q16154, Q8IU72
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 159 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM