Human Gene NEFL (ENST00000610854.1) Description and Page Index
  Description: Homo sapiens neurofilament light (NEFL), mRNA. (from RefSeq NM_006158)
RefSeq Summary (NM_006158): Neurofilaments are type IV intermediate filament heteropolymers composed of light, medium, and heavy chains. Neurofilaments comprise the axoskeleton and they functionally maintain the neuronal caliber. They may also play a role in intracellular transport to axons and dendrites. This gene encodes the light chain neurofilament protein. Mutations in this gene cause Charcot-Marie-Tooth disease types 1F (CMT1F) and 2E (CMT2E), disorders of the peripheral nervous system that are characterized by distinct neuropathies. A pseudogene has been identified on chromosome Y. [provided by RefSeq, Oct 2008]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: SRR1803616.75985.1, SRR1803617.69252.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA2145743, SAMEA2145774 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## RefSeq Select criteria :: based on single protein-coding transcript ##RefSeq-Attributes-END##
Gencode Transcript: ENST00000610854.1
Gencode Gene: ENSG00000277586.2
Transcript (Including UTRs)
   Position: hg38 chr8:24,950,955-24,957,110 Size: 6,156 Total Exon Count: 4 Strand: -
Coding Region
   Position: hg38 chr8:24,952,810-24,956,515 Size: 3,706 Coding Exon Count: 4 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDMicroarray Expression
RNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA DescriptionsPathways
Other NamesGeneReviewsMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr8:24,950,955-24,957,110)mRNA (may differ from genome)Protein (543 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
HPRDLynxMGImyGene2neXtProtOMIM
PubMedReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: NFL_HUMAN
DESCRIPTION: RecName: Full=Neurofilament light polypeptide; Short=NF-L; AltName: Full=68 kDa neurofilament protein; AltName: Full=Neurofilament triplet L protein;
FUNCTION: Neurofilaments usually contain three intermediate filament proteins: L, M, and H which are involved in the maintenance of neuronal caliber.
SUBUNIT: Interacts with ARHGEF28 (By similarity). Interacts with TRIM2 (By similarity).
INTERACTION: Q13614:MTMR2; NbExp=2; IntAct=EBI-475646, EBI-475631;
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.
PTM: O-glycosylated (By similarity).
PTM: Phosphorylated in the head and rod regions by the PKC kinase PKN1, leading to the inhibition of polymerization.
PTM: Ubiquitinated in the presence of TRIM2 and UBE2D1 (By similarity).
DISEASE: Defects in NEFL are the cause of Charcot-Marie-Tooth disease type 1F (CMT1F) [MIM:607734]. CMT1F is a form of Charcot- Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathy or CMT1, and primary peripheral axonal neuropathy or CMT2. Neuropathies of the CMT1 group 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).
DISEASE: Defects in NEFL are the cause of Charcot-Marie-Tooth disease type 2E (CMT2E) [MIM:607684]. CMT2E is an autosomal dominant form of Charcot-Marie-Tooth disease type 2. Neuropathies of the CMT2 group are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy.
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.
SIMILARITY: Belongs to the intermediate filament family.
WEB RESOURCE: Name=Inherited peripheral neuropathies mutation db; URL="http://www.molgen.ua.ac.be/CMTMutations/";
WEB RESOURCE: Name=Human Intermediate Filament Mutation Database; URL="http://www.interfil.org";
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/NEFL";

-  MalaCards Disease Associations
  MalaCards Gene Search: NEFL
Diseases sorted by gene-association score: charcot-marie-tooth disease, type 2e* (1569), charcot-marie-tooth disease, type 1f* (1550), charcot-marie-tooth disease type 2b5* (350), charcot-marie-tooth disease, axonal, type 2s* (200), charcot-marie-tooth neuropathy type 2e/1f* (200), tooth disease (19), charcot-marie-tooth disease (14), lateral sclerosis (3), amyotrophic lateral sclerosis 1 (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • C017947 sodium arsenite
  • D000535 Aluminum
  • D001564 Benzo(a)pyrene
  • D003042 Cocaine
  • D014635 Valproic Acid
  • C010845 aluminum chloride
  • C018021 cobaltous chloride
  • C004925 methylmercuric chloride
  • C070379 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
  • C060229 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
          more ... click here to view the complete list

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -221.80595-0.373 Picture PostScript Text
3' UTR -424.201855-0.229 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR016044 - F
IPR001664 - IF
IPR006821 - Intermed_filament_DNA-bd
IPR018039 - Intermediate_filament_CS

Pfam Domains:
PF00038 - Intermediate filament protein
PF04732 - Intermediate filament head (DNA binding) region

ModBase Predicted Comparative 3D Structure on P07196
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005088 Ras guanyl-nucleotide exchange factor activity
GO:0005198 structural molecule activity
GO:0005200 structural constituent of cytoskeleton
GO:0005515 protein binding
GO:0008022 protein C-terminus binding
GO:0019904 protein domain specific binding
GO:0030674 protein binding, bridging
GO:0042802 identical protein binding
GO:0043274 phospholipase binding
GO:0046982 protein heterodimerization activity

Biological Process:
GO:0000165 MAPK cascade
GO:0000226 microtubule cytoskeleton organization
GO:0008089 anterograde axonal transport
GO:0008090 retrograde axonal transport
GO:0009636 response to toxic substance
GO:0010033 response to organic substance
GO:0014012 peripheral nervous system axon regeneration
GO:0019896 axonal transport of mitochondrion
GO:0021510 spinal cord development
GO:0021766 hippocampus development
GO:0021987 cerebral cortex development
GO:0031133 regulation of axon diameter
GO:0033693 neurofilament bundle assembly
GO:0040011 locomotion
GO:0043434 response to peptide hormone
GO:0043524 negative regulation of neuron apoptotic process
GO:0045105 intermediate filament polymerization or depolymerization
GO:0045109 intermediate filament organization
GO:0045110 intermediate filament bundle assembly
GO:0048812 neuron projection morphogenesis
GO:0050772 positive regulation of axonogenesis
GO:0050885 neuromuscular process controlling balance
GO:0051258 protein polymerization
GO:0051412 response to corticosterone
GO:0060052 neurofilament cytoskeleton organization
GO:0061564 axon development
GO:1903935 response to sodium arsenite
GO:1903937 response to acrylamide

Cellular Component:
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005882 intermediate filament
GO:0005883 neurofilament
GO:0030424 axon
GO:0030426 growth cone
GO:0043005 neuron projection
GO:0043209 myelin sheath
GO:1904115 axon cytoplasm
GO:0033596 TSC1-TSC2 complex


-  Descriptions from all associated GenBank mRNAs
  BC037803 - Homo sapiens cDNA clone IMAGE:4796752.
AK075003 - Homo sapiens cDNA FLJ90522 fis, clone NT2RP4000108, highly similar to Neurofilament triplet L protein.
AK127430 - Homo sapiens cDNA FLJ45522 fis, clone BRTHA2025869, highly similar to Neurofilament triplet L protein.
BC039237 - Homo sapiens neurofilament, light polypeptide, mRNA (cDNA clone MGC:32648 IMAGE:4280159), complete cds.
AL713644 - Homo sapiens mRNA; cDNA DKFZp761K0922 (from clone DKFZp761K0922).
AK225975 - Homo sapiens mRNA for Neurofilament triplet L protein variant, clone: FCC112D04.
BC066952 - Homo sapiens neurofilament, light polypeptide, mRNA (cDNA clone MGC:87388 IMAGE:5264373), complete cds.
AK057731 - Homo sapiens cDNA FLJ25002 fis, clone CBL00553, highly similar to NEUROFILAMENT TRIPLET L PROTEIN.
AK299095 - Homo sapiens cDNA FLJ53642 complete cds, highly similar to Neurofilament triplet L protein.
DQ593936 - Homo sapiens piRNA piR-60048, complete sequence.
AY156690 - Homo sapiens light molecular weight neurofilament protein (NEFL) mRNA, complete cds.
AK314591 - Homo sapiens cDNA, FLJ95425.
DQ892646 - Synthetic construct clone IMAGE:100005276; FLH188598.01X; RZPDo839E0173D neurofilament, light polypeptide 68kDa (NEFL) gene, encodes complete protein.
DQ895884 - Synthetic construct Homo sapiens clone IMAGE:100010344; FLH188594.01L; RZPDo839E0163D neurofilament, light polypeptide 68kDa (NEFL) gene, encodes complete protein.
AB463926 - Synthetic construct DNA, clone: pF1KB8148, Homo sapiens NEFL gene for neurofilament, light polypeptide 68kDa, without stop codon, in Flexi system.
DQ587097 - Homo sapiens piRNA piR-54209, complete sequence.
KU178228 - Homo sapiens neurofilament light polypeptide isoform 1 (NEFL) mRNA, partial cds, alternatively spliced.
KU178229 - Homo sapiens neurofilament light polypeptide isoform 2 (NEFL) mRNA, partial cds.
KJ901599 - Synthetic construct Homo sapiens clone ccsbBroadEn_10993 NEFL gene, encodes complete protein.
CU688222 - Synthetic construct Homo sapiens gateway clone IMAGE:100021094 5' read NEFL mRNA.
U57341 - Human neurofilament triplet L protein mRNA, partial cds.
CU691684 - Synthetic construct Homo sapiens gateway clone IMAGE:100022310 5' read NEFL mRNA.
DQ576794 - Homo sapiens piRNA piR-44906, complete sequence.
JD031368 - Sequence 12392 from Patent EP1572962.
JD025322 - Sequence 6346 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa05014 - Amyotrophic lateral sclerosis (ALS)

Reactome (by CSHL, EBI, and GO)

Protein P07196 (Reactome details) participates in the following event(s):

R-HSA-432172 Activation of NMDA receptor
R-HSA-432162 Unblocking of NMDA receptor
R-HSA-442760 Activation of RasGRF
R-HSA-432164 Ca2+ influx into the post-synaptic cell
R-HSA-445367 CaMKII enters cytoplasm
R-HSA-442732 Ras activation
R-HSA-5672965 RAS GEFs promote RAS nucleotide exchange
R-HSA-438066 Unblocking of NMDA receptor, glutamate binding and activation
R-HSA-442982 Ras activation upon Ca2+ influx through NMDA receptor
R-HSA-442755 Activation of NMDA receptor and postsynaptic events
R-HSA-442742 CREB phosphorylation through the activation of Ras
R-HSA-442729 CREB phosphorylation through the activation of CaMKII
R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-438064 Post NMDA receptor activation events
R-HSA-112315 Transmission across Chemical Synapses
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-112316 Neuronal System
R-HSA-5684996 MAPK1/MAPK3 signaling
R-HSA-5683057 MAPK family signaling cascades
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: B9ZVN2, NF68, NFL, NFL_HUMAN, NM_006158, P07196, Q16154, Q8IU72, uc033bfe.1, uc033bfe.2
UCSC ID: uc033bfe.2
RefSeq Accession: NM_006158
Protein: P07196 (aka NFL_HUMAN)
CCDS: CCDS75712.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene NEFL:
cmt (Charcot-Marie-Tooth Hereditary Neuropathy Overview)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.