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Protein

Neurofilament light polypeptide

Gene

NEFL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.

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.

GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

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 upon Ca2+ influx through NMDA receptor
R-HSA-5673001 RAF/MAP kinase cascade
SIGNORiP07196

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

EuPathDBiHostDB:ENSG00000277586.1
HGNCiHGNC:7739 NEFL
MIMi162280 gene
neXtProtiNX_P07196

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 dbSNP:rs61491953EnsemblClinVar.1
Natural variantiVAR_0160198P → Q in CMT1F. 1 PublicationCorresponds to variant dbSNP:rs61491953EnsemblClinVar.1
Natural variantiVAR_01602290E → K in CMT1F. 1 PublicationCorresponds to variant dbSNP:rs58332872EnsemblClinVar.1
Natural variantiVAR_01602398N → S in CMT1F. 1 PublicationCorresponds to variant dbSNP:rs58982919EnsemblClinVar.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.
See also OMIM:607684
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01602122P → S in CMT2E. 2 PublicationsCorresponds to variant dbSNP:rs28928910EnsemblClinVar.1
Natural variantiVAR_009703332Q → P in CMT2E. 1 PublicationCorresponds to variant dbSNP:rs59443585EnsemblClinVar.1
Natural variantiVAR_021613336L → P in CMT2E. 1 PublicationCorresponds to variant dbSNP:rs587777881EnsemblClinVar.1

Keywords - Diseasei

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

Organism-specific databases

DisGeNETi4747
GeneReviewsiNEFL
MalaCardsiNEFL
MIMi607684 phenotype
607734 phenotype
OpenTargetsiENSG00000277586
Orphaneti99939 Autosomal dominant Charcot-Marie-Tooth disease type 2E
101085 Charcot-Marie-Tooth disease type 1F
228374 Charcot-Marie-Tooth disease type 2B5
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) threonineBy similarity1
Modified residuei23Asymmetric dimethylarginine; alternateBy similarity1
Modified residuei23Omega-N-methylarginine; alternateBy similarity1
Glycosylationi27O-linked (GlcNAc) serineBy 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
ProteomicsDBi51961

2D gel databases

UCD-2DPAGEiP07196

PTM databases

iPTMnetiP07196
PhosphoSitePlusiP07196
SwissPalmiP07196

Expressioni

Gene expression databases

BgeeiENSG00000277586 Expressed in 198 organ(s), highest expression level in dorsal root ganglion
CleanExiHS_NEFL
ExpressionAtlasiP07196 baseline and differential
GenevisibleiP07196 HS

Organism-specific databases

HPAiHPA014850
HPA015021

Interactioni

Subunit structurei

Interacts with ARHGEF28. Interacts with TRIM2.By similarity

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110822, 52 interactors
IntActiP07196, 43 interactors
MINTiP07196

Structurei

3D structure databases

ProteinModelPortaliP07196
SMRiP07196
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini90 – 400IF rodPROSITE-ProRule annotationAdd BLAST311

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 92HeadAdd BLAST91
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.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

GeneTreeiENSGT00910000143989
HOVERGENiHBG013015
InParanoidiP07196
KOiK04572
OMAiPTYYTSH
OrthoDBiEOG091G12MK
PhylomeDBiP07196

Family and domain databases

InterProiView protein in InterPro
IPR001664 IF
IPR018039 IF_conserved
IPR039008 IF_rod_dom
IPR006821 Intermed_filament_DNA-bd
IPR027692 NF-L
PANTHERiPTHR23239 PTHR23239, 1 hit
PTHR23239:SF22 PTHR23239:SF22, 1 hit
PfamiView protein in Pfam
PF00038 Filament, 1 hit
PF04732 Filament_head, 1 hit
SMARTiView protein in SMART
SM01391 Filament, 1 hit
PROSITEiView protein in PROSITE
PS00226 IF_ROD_1, 1 hit
PS51842 IF_ROD_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087X0W2A0A087X0W2_HUMAN
Neurofilament light polypeptide
NEFL
284Annotation score:
A0A0S2Z436A0A0S2Z436_HUMAN
Neurofilament light polypeptide iso...
NEFL
284Annotation score:

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 dbSNP:rs57848467EnsemblClinVar.1
Natural variantiVAR_0160188P → L in CMT1F. 1 PublicationCorresponds to variant dbSNP:rs61491953EnsemblClinVar.1
Natural variantiVAR_0160198P → Q in CMT1F. 1 PublicationCorresponds to variant dbSNP:rs61491953EnsemblClinVar.1
Natural variantiVAR_0160208P → R in CMT2E and CMT1F. 3 PublicationsCorresponds to variant dbSNP:rs60261494EnsemblClinVar.1
Natural variantiVAR_01602122P → S in CMT2E. 2 PublicationsCorresponds to variant dbSNP:rs28928910EnsemblClinVar.1
Natural variantiVAR_01602290E → K in CMT1F. 1 PublicationCorresponds to variant dbSNP:rs58332872EnsemblClinVar.1
Natural variantiVAR_01602398N → S in CMT1F. 1 PublicationCorresponds to variant dbSNP:rs58982919EnsemblClinVar.1
Natural variantiVAR_009703332Q → P in CMT2E. 1 PublicationCorresponds to variant dbSNP:rs59443585EnsemblClinVar.1
Natural variantiVAR_021613336L → P in CMT2E. 1 PublicationCorresponds to variant dbSNP:rs587777881EnsemblClinVar.1
Natural variantiVAR_021614396E → K in CMT1F and CMT2E. 3 PublicationsCorresponds to variant dbSNP:rs62636503EnsemblClinVar.1
Natural variantiVAR_016024468D → N1 PublicationCorresponds to variant dbSNP:rs57153321EnsemblClinVar.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

Similar proteinsi

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, 52 interactors
IntActiP07196, 43 interactors
MINTiP07196

PTM databases

iPTMnetiP07196
PhosphoSitePlusiP07196
SwissPalmiP07196

Polymorphism and mutation databases

DMDMi62511894

2D gel databases

UCD-2DPAGEiP07196

Proteomic databases

EPDiP07196
MaxQBiP07196
PeptideAtlasiP07196
PRIDEiP07196
ProteomicsDBi51961

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
EuPathDBiHostDB:ENSG00000277586.1
GeneCardsiNEFL
GeneReviewsiNEFL
HGNCiHGNC:7739 NEFL
HPAiHPA014850
HPA015021
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 Charcot-Marie-Tooth disease type 2B5
PharmGKBiPA31542
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00910000143989
HOVERGENiHBG013015
InParanoidiP07196
KOiK04572
OMAiPTYYTSH
OrthoDBiEOG091G12MK
PhylomeDBiP07196

Enzyme and pathway databases

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 upon Ca2+ influx through NMDA receptor
R-HSA-5673001 RAF/MAP kinase cascade
SIGNORiP07196

Miscellaneous databases

ChiTaRSiNEFL human
GeneWikiiNEFL
GenomeRNAii4747
PROiPR:P07196
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000277586 Expressed in 198 organ(s), highest expression level in dorsal root ganglion
CleanExiHS_NEFL
ExpressionAtlasiP07196 baseline and differential
GenevisibleiP07196 HS

Family and domain databases

InterProiView protein in InterPro
IPR001664 IF
IPR018039 IF_conserved
IPR039008 IF_rod_dom
IPR006821 Intermed_filament_DNA-bd
IPR027692 NF-L
PANTHERiPTHR23239 PTHR23239, 1 hit
PTHR23239:SF22 PTHR23239:SF22, 1 hit
PfamiView protein in Pfam
PF00038 Filament, 1 hit
PF04732 Filament_head, 1 hit
SMARTiView protein in SMART
SM01391 Filament, 1 hit
PROSITEiView protein in PROSITE
PS00226 IF_ROD_1, 1 hit
PS51842 IF_ROD_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNFL_HUMAN
AccessioniPrimary (citable) accession number: P07196
Secondary accession number(s): B9ZVN2, Q16154, Q8IU72
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: January 23, 2007
Last modified: November 7, 2018
This is version 206 of the entry and version 3 of the sequence. See 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

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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