Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Neurofilament light polypeptide

Gene

NEFL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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

GO - Molecular functioni

  • identical protein binding Source: UniProtKB
  • protein binding, bridging Source: BHF-UCL
  • protein C-terminus binding Source: UniProtKB
  • Ras guanyl-nucleotide exchange factor activity Source: Reactome
  • structural constituent of cytoskeleton Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000104725-MONOMER.
ReactomeiR-HSA-438066. Unblocking of NMDA receptor, glutamate binding and activation.
R-HSA-442729. CREB phosphorylation through the activation of CaMKII.
R-HSA-442982. Ras activation uopn Ca2+ infux through NMDA receptor.
R-HSA-5673001. RAF/MAP kinase cascade.

Names & Taxonomyi

Protein namesi
Recommended name:
Neurofilament light polypeptide
Short name:
NF-L
Alternative name(s):
68 kDa neurofilament protein
Neurofilament triplet L protein
Gene namesi
Name:NEFL
Synonyms:NF68, NFL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:7739. NEFL.

Subcellular locationi

GO - Cellular componenti

  • axon Source: UniProtKB
  • axon cytoplasm Source: GOC
  • cytoplasm Source: BHF-UCL
  • cytosol Source: Reactome
  • growth cone Source: Ensembl
  • myelin sheath Source: Ensembl
  • neurofilament Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Intermediate filament

Pathology & Biotechi

Involvement in diseasei

Charcot-Marie-Tooth disease 1F (CMT1F)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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).
See also OMIM:607734
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0160188P → L in CMT1F. 1 PublicationCorresponds to variant rs61491953dbSNPEnsembl.1
Natural variantiVAR_0160198P → Q in CMT1F. 1 PublicationCorresponds to variant rs61491953dbSNPEnsembl.1
Natural variantiVAR_0160208P → R in CMT2E and CMT1F. 3 PublicationsCorresponds to variant rs60261494dbSNPEnsembl.1
Natural variantiVAR_01602290E → K in CMT1F. 1 PublicationCorresponds to variant rs58332872dbSNPEnsembl.1
Natural variantiVAR_01602398N → S in CMT1F. 1 PublicationCorresponds to variant rs58982919dbSNPEnsembl.1
Natural variantiVAR_021614396E → K in CMT1F and CMT2E. 3 PublicationsCorresponds to variant rs62636503dbSNPEnsembl.1
Natural variantiVAR_016025527Missing in CMT1F. 1 Publication1
Charcot-Marie-Tooth disease 2E (CMT2E)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:607684
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0160208P → R in CMT2E and CMT1F. 3 PublicationsCorresponds to variant rs60261494dbSNPEnsembl.1
Natural variantiVAR_01602122P → S in CMT2E. 2 PublicationsCorresponds to variant rs28928910dbSNPEnsembl.1
Natural variantiVAR_009703332Q → P in CMT2E. 1 PublicationCorresponds to variant rs59443585dbSNPEnsembl.1
Natural variantiVAR_021613336L → P in CMT2E. 1 PublicationCorresponds to variant rs587777881dbSNPEnsembl.1
Natural variantiVAR_021614396E → K in CMT1F and CMT2E. 3 PublicationsCorresponds to variant rs62636503dbSNPEnsembl.1

Keywords - Diseasei

Charcot-Marie-Tooth disease, Disease mutation, Neurodegeneration, Neuropathy

Organism-specific databases

DisGeNETi4747.
MalaCardsiNEFL.
MIMi607684. phenotype.
607734. phenotype.
OpenTargetsiENSG00000277586.
Orphaneti99939. 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.
PharmGKBiPA31542.

Polymorphism and mutation databases

DMDMi62511894.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000637872 – 543Neurofilament light polypeptideAdd BLAST542

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Glycosylationi21O-linked (GlcNAc)By similarity1
Modified residuei23Asymmetric dimethylarginine; alternateBy similarity1
Modified residuei23Omega-N-methylarginine; alternateBy similarity1
Glycosylationi27O-linked (GlcNAc)By similarity1
Modified residuei30Omega-N-methylarginineBy similarity1
Modified residuei43PhosphotyrosineBy similarity1
Modified residuei56PhosphoserineBy similarity1
Modified residuei67PhosphoserineBy similarity1
Modified residuei103PhosphoserineBy similarity1
Modified residuei472PhosphoserineBy similarity1
Modified residuei502PhosphoserineBy similarity1
Modified residuei520PhosphothreonineBy similarity1

Post-translational modificationi

O-glycosylated.By similarity
Phosphorylated in the head and rod regions by the PKC kinase PKN1, leading to the inhibition of polymerization.1 Publication
Ubiquitinated in the presence of TRIM2 and UBE2D1.By similarity

Keywords - PTMi

Acetylation, Glycoprotein, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP07196.
MaxQBiP07196.
PeptideAtlasiP07196.
PRIDEiP07196.

2D gel databases

UCD-2DPAGEP07196.

PTM databases

iPTMnetiP07196.
PhosphoSitePlusiP07196.
SwissPalmiP07196.

Expressioni

Gene expression databases

CleanExiHS_NEFL.
ExpressionAtlasiP07196. baseline and differential.
GenevisibleiP07196. HS.

Organism-specific databases

HPAiHPA014850.

Interactioni

Subunit structurei

Interacts with ARHGEF28. Interacts with TRIM2.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
APPP050672EBI-475646,EBI-77613
DESP176613EBI-475646,EBI-1055572
MTMR2Q136142EBI-475646,EBI-475631
PPP1R18Q6NYC83EBI-475646,EBI-2557469
taxP140794EBI-475646,EBI-9675698From a different organism.
TERF1P542742EBI-475646,EBI-710997

GO - Molecular functioni

  • identical protein binding Source: UniProtKB
  • protein binding, bridging Source: BHF-UCL
  • protein C-terminus binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110822. 48 interactors.
IntActiP07196. 30 interactors.
MINTiMINT-1370620.

Structurei

3D structure databases

ProteinModelPortaliP07196.
SMRiP07196.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 92HeadAdd BLAST91
Regioni93 – 396RodAdd BLAST304
Regioni93 – 124Coil 1AAdd BLAST32
Regioni125 – 137Linker 1Add BLAST13
Regioni138 – 234Coil 1BAdd BLAST97
Regioni235 – 252Linker 12Add BLAST18
Regioni253 – 271Coil 2AAdd BLAST19
Regioni272 – 280Linker 29
Regioni281 – 396Coil 2BAdd BLAST116
Regioni381 – 391Epitope; recognized by IF-specific monoclonal antibodyAdd BLAST11
Regioni397 – 543TailAdd BLAST147
Regioni397 – 443Tail, subdomain AAdd BLAST47
Regioni444 – 543Tail, subdomain B (acidic)Add BLAST100

Domaini

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.

Sequence similaritiesi

Belongs to the intermediate filament family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

GeneTreeiENSGT00830000128228.
HOVERGENiHBG013015.
InParanoidiP07196.
KOiK04572.
OMAiRSFPTYY.
OrthoDBiEOG091G12MK.
PhylomeDBiP07196.

Family and domain databases

InterProiIPR001664. IF.
IPR006821. Intermed_filament_DNA-bd.
IPR018039. Intermediate_filament_CS.
IPR027692. NF-L.
[Graphical view]
PANTHERiPTHR23239. PTHR23239. 1 hit.
PTHR23239:SF22. PTHR23239:SF22. 1 hit.
PfamiPF00038. Filament. 1 hit.
PF04732. Filament_head. 1 hit.
[Graphical view]
SMARTiSM01391. Filament. 1 hit.
[Graphical view]
PROSITEiPS00226. IF. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P07196-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSSFSYEPYY STSYKRRYVE TPRVHISSVR SGYSTARSAY SSYSAPVSSS
60 70 80 90 100
LSVRRSYSSS SGSLMPSLEN LDLSQVAAIS NDLKSIRTQE KAQLQDLNDR
110 120 130 140 150
FASFIERVHE LEQQNKVLEA ELLVLRQKHS EPSRFRALYE QEIRDLRLAA
160 170 180 190 200
EDATNEKQAL QGEREGLEET LRNLQARYEE EVLSREDAEG RLMEARKGAD
210 220 230 240 250
EAALARAELE KRIDSLMDEI SFLKKVHEEE IAELQAQIQY AQISVEMDVT
260 270 280 290 300
KPDLSAALKD IRAQYEKLAA KNMQNAEEWF KSRFTVLTES AAKNTDAVRA
310 320 330 340 350
AKDEVSESRR LLKAKTLEIE ACRGMNEALE KQLQELEDKQ NADISAMQDT
360 370 380 390 400
INKLENELRT TKSEMARYLK EYQDLLNVKM ALDIEIAAYR KLLEGEETRL
410 420 430 440 450
SFTSVGSITS GYSQSSQVFG RSAYGGLQTS SYLMSTRSFP SYYTSHVQEE
460 470 480 490 500
QIEVEETIEA AKAEEAKDEP PSEGEAEEEE KDKEEAEEEE AAEEEEAAKE
510 520 530 540
ESEEAKEEEE GGEGEEGEET KEAEEEEKKV EGAGEEQAAK KKD
Length:543
Mass (Da):61,517
Last modified:January 23, 2007 - v3
Checksum:i98C1712D8ACFF33A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti28Missing in CAA29097 (PubMed:3034332).Curated1
Sequence conflicti155N → TN (PubMed:3034332).Curated1
Sequence conflicti161Q → R in CAA29097 (PubMed:3034332).Curated1
Sequence conflicti165E → EE in CAA29097 (PubMed:3034332).Curated1
Sequence conflicti195A → R in CAA29097 (PubMed:3034332).Curated1
Sequence conflicti452I → T in CAA29097 (PubMed:3034332).Curated1
Sequence conflicti461A → S in CAA29097 (PubMed:3034332).Curated1
Sequence conflicti472S → D AA sequence (PubMed:6135695).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0160177E → K in a Charcot-Marie-Tooth disease patient. 1 PublicationCorresponds to variant rs57848467dbSNPEnsembl.1
Natural variantiVAR_0160188P → L in CMT1F. 1 PublicationCorresponds to variant rs61491953dbSNPEnsembl.1
Natural variantiVAR_0160198P → Q in CMT1F. 1 PublicationCorresponds to variant rs61491953dbSNPEnsembl.1
Natural variantiVAR_0160208P → R in CMT2E and CMT1F. 3 PublicationsCorresponds to variant rs60261494dbSNPEnsembl.1
Natural variantiVAR_01602122P → S in CMT2E. 2 PublicationsCorresponds to variant rs28928910dbSNPEnsembl.1
Natural variantiVAR_01602290E → K in CMT1F. 1 PublicationCorresponds to variant rs58332872dbSNPEnsembl.1
Natural variantiVAR_01602398N → S in CMT1F. 1 PublicationCorresponds to variant rs58982919dbSNPEnsembl.1
Natural variantiVAR_009703332Q → P in CMT2E. 1 PublicationCorresponds to variant rs59443585dbSNPEnsembl.1
Natural variantiVAR_021613336L → P in CMT2E. 1 PublicationCorresponds to variant rs587777881dbSNPEnsembl.1
Natural variantiVAR_021614396E → K in CMT1F and CMT2E. 3 PublicationsCorresponds to variant rs62636503dbSNPEnsembl.1
Natural variantiVAR_016024468D → N.1 PublicationCorresponds to variant rs57153321dbSNPEnsembl.1
Natural variantiVAR_016025527Missing in CMT1F. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS75712.1.
PIRiS07144.
RefSeqiNP_006149.2. NM_006158.4.
UniGeneiHs.521461.

Genome annotation databases

EnsembliENST00000610854; ENSP00000482169; ENSG00000277586.
GeneIDi4747.
KEGGihsa:4747.
UCSCiuc033bfe.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Inherited peripheral neuropathies mutation db
Human Intermediate Filament Mutation Database

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS75712.1.
PIRiS07144.
RefSeqiNP_006149.2. NM_006158.4.
UniGeneiHs.521461.

3D structure databases

ProteinModelPortaliP07196.
SMRiP07196.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110822. 48 interactors.
IntActiP07196. 30 interactors.
MINTiMINT-1370620.

PTM databases

iPTMnetiP07196.
PhosphoSitePlusiP07196.
SwissPalmiP07196.

Polymorphism and mutation databases

DMDMi62511894.

2D gel databases

UCD-2DPAGEP07196.

Proteomic databases

EPDiP07196.
MaxQBiP07196.
PeptideAtlasiP07196.
PRIDEiP07196.

Protocols and materials databases

DNASUi4747.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000610854; ENSP00000482169; ENSG00000277586.
GeneIDi4747.
KEGGihsa:4747.
UCSCiuc033bfe.2. human.

Organism-specific databases

CTDi4747.
DisGeNETi4747.
GeneCardsiNEFL.
GeneReviewsiNEFL.
HGNCiHGNC:7739. NEFL.
HPAiHPA014850.
MalaCardsiNEFL.
MIMi162280. gene.
607684. phenotype.
607734. phenotype.
neXtProtiNX_P07196.
OpenTargetsiENSG00000277586.
Orphaneti99939. 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.
PharmGKBiPA31542.
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00830000128228.
HOVERGENiHBG013015.
InParanoidiP07196.
KOiK04572.
OMAiRSFPTYY.
OrthoDBiEOG091G12MK.
PhylomeDBiP07196.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000104725-MONOMER.
ReactomeiR-HSA-438066. Unblocking of NMDA receptor, glutamate binding and activation.
R-HSA-442729. CREB phosphorylation through the activation of CaMKII.
R-HSA-442982. Ras activation uopn Ca2+ infux through NMDA receptor.
R-HSA-5673001. RAF/MAP kinase cascade.

Miscellaneous databases

ChiTaRSiNEFL. human.
GeneWikiiNEFL.
GenomeRNAii4747.
PROiP07196.
SOURCEiSearch...

Gene expression databases

CleanExiHS_NEFL.
ExpressionAtlasiP07196. baseline and differential.
GenevisibleiP07196. HS.

Family and domain databases

InterProiIPR001664. IF.
IPR006821. Intermed_filament_DNA-bd.
IPR018039. Intermediate_filament_CS.
IPR027692. NF-L.
[Graphical view]
PANTHERiPTHR23239. PTHR23239. 1 hit.
PTHR23239:SF22. PTHR23239:SF22. 1 hit.
PfamiPF00038. Filament. 1 hit.
PF04732. Filament_head. 1 hit.
[Graphical view]
SMARTiSM01391. Filament. 1 hit.
[Graphical view]
PROSITEiPS00226. IF. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNFL_HUMAN
AccessioniPrimary (citable) accession number: P07196
Secondary accession number(s): B9ZVN2, Q16154, Q8IU72
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 188 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

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.

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.