P07196 (NFL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	543 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.14 Ref.15 Ref.16 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 regeneration 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.11 Ref.12 Ref.13 Ref.15 Ref.17
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.

Ontologies

Keywords
Cellular component	Intermediate filament
Coding sequence diversity	Polymorphism
Disease	Charcot-Marie-Tooth disease Disease mutation Neuropathy
Domain	Coiled coil
PTM	Acetylation Glycoprotein Phosphoprotein Ubl conjugation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	anterograde axon cargo transport Inferred from mutant phenotype PubMed 15857389. Source: UniProtKB axon transport of mitochondrion Inferred from mutant phenotype PubMed 15857389. Source: UniProtKB neurofilament bundle assembly Inferred from direct assay Ref.2. Source: UniProtKB retrograde axon cargo transport Inferred from mutant phenotype PubMed 15857389. Source: UniProtKB synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome neurofilament Inferred from direct assay PubMed 15857389. Source: UniProtKB
Molecular_function	structural constituent of cytoskeleton Inferred from direct assay Ref.2. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MTMR2	Q13614	2	EBI-475646,EBI-475631

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 543	542	Neurofilament light polypeptide		PRO_0000063787
Regions
	Region	2 – 92	91	Head
	Region	93 – 396	304	Rod
	Region	93 – 124	32	Coil 1A
	Region	125 – 137	13	Linker 1
	Region	138 – 234	97	Coil 1B
	Region	235 – 252	18	Linker 12
	Region	253 – 271	19	Coil 2A
	Region	272 – 280	9	Linker 2
	Region	281 – 396	116	Coil 2B
	Region	381 – 391	11	Epitope; recognized by IF-specific monoclonal antibody
	Region	397 – 543	147	Tail
	Region	397 – 443	47	Tail, subdomain A
	Region	444 – 543	100	Tail, subdomain B (acidic)
Amino acid modifications
	Modified residue	2	1	N-acetylserine By similarity
	Modified residue	43	1	Phosphotyrosine By similarity
	Modified residue	56	1	Phosphoserine By similarity
	Modified residue	67	1	Phosphoserine By similarity
	Modified residue	424	1	Phosphotyrosine By similarity
	Modified residue	432	1	Phosphotyrosine By similarity
	Modified residue	472	1	Phosphoserine By similarity
	Glycosylation	21	1	O-linked (GlcNAc) By similarity
	Glycosylation	27	1	O-linked (GlcNAc) By similarity
Natural variations
	Natural variant	7	1	E → K in a Charcot-Marie-Tooth disease patient. Ref.14 Corresponds to variant rs57848467 [ dbSNP | Ensembl ].		VAR_016017
	Natural variant	8	1	P → L in CMT1F. Ref.14		VAR_016018
	Natural variant	8	1	P → Q in CMT1F. Ref.14		VAR_016019
	Natural variant	8	1	P → R in CMT2E and CMT1F; severely reduced nerve conduction velocities in some patients. Ref.12 Ref.14 Ref.17 Corresponds to variant rs60261494 [ dbSNP | Ensembl ].		VAR_016020
	Natural variant	22	1	P → S in CMT2E. Ref.13 Ref.17 Corresponds to variant rs28928910 [ dbSNP | Ensembl ].		VAR_016021
	Natural variant	90	1	E → K in CMT1F. Ref.14 Corresponds to variant rs58332872 [ dbSNP | Ensembl ].		VAR_016022
	Natural variant	98	1	N → S in CMT1F. Ref.14 Corresponds to variant rs58982919 [ dbSNP | Ensembl ].		VAR_016023
	Natural variant	332	1	Q → P in CMT2E. Ref.11 Corresponds to variant rs59443585 [ dbSNP | Ensembl ].		VAR_009703
	Natural variant	336	1	L → P in CMT2E. Ref.15		VAR_021613
	Natural variant	396	1	E → K in CMT1F and CMT2E. Ref.15 Ref.16 Ref.17		VAR_021614
	Natural variant	468	1	D → N. Ref.14 Corresponds to variant rs57153321 [ dbSNP | Ensembl ].		VAR_016024
	Natural variant	527	1	Missing in CMT1F. Ref.14		VAR_016025
Experimental info
	Sequence conflict	28	1	Missing in CAA29097. Ref.1
	Sequence conflict	155	1	N → TN Ref.1
	Sequence conflict	161	1	Q → R in CAA29097. Ref.1
	Sequence conflict	165	1	E → EE in CAA29097. Ref.1
	Sequence conflict	195	1	A → R in CAA29097. Ref.1
	Sequence conflict	452	1	I → T in CAA29097. Ref.1
	Sequence conflict	461	1	A → S in CAA29097. Ref.1
	Sequence conflict	472	1	S → D AA sequence Ref.8

Sequences

	Sequence		Length	Mass (Da)
	P07196 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 98C1712D8ACFF33A	FASTA	543	61,517
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, 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]	"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.
[12]	"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.
[13]	"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.
[14]	"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.
[15]	"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.
[16]	"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.
[17]	"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.

Web resources

Inherited peripheral neuropathies mutation db

Human Intermediate Filament Mutation Database

GeneReviews

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.
IPI	IPI00237671.
PIR	S07144.
RefSeq	NP_006149.2. NM_006158.4.
UniGene	Hs.521461.
3D structure databases
ProteinModelPortal	P07196.
ModBase	Search...
Protein-protein interaction databases
IntAct	P07196. 11 interactions.
MINT	MINT-1370620.
STRING	9606.ENSP00000221169.
PTM databases
PhosphoSite	P07196.
Polymorphism databases
DMDM	62511894.
2D gel databases
UCD-2DPAGE	P07196.
Proteomic databases
PaxDb	P07196.
PRIDE	P07196.
Protocols and materials databases
DNASU	4747.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	4747.
KEGG	hsa:4747.
UCSC	uc003xee.3. human.
Organism-specific databases
CTD	4747.
GeneCards	GC08M024808.
HGNC	HGNC:7739. NEFL.
MIM	162280. gene. 607684. phenotype. 607734. phenotype.
neXtProt	NX_P07196.
Orphanet	99939. 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.
PharmGKB	PA31542.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG145720.
HOVERGEN	HBG013015.
InParanoid	P07196.
KO	K04572.
OrthoDB	EOG42Z4QC.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System.
Gene expression databases
CleanEx	HS_NEFL.
Genevestigator	P07196.
GermOnline	ENSG00000104725. Homo sapiens.
Family and domain databases
InterPro	IPR016044. F. IPR001664. IF. IPR006821. Intermed_filament_DNA-bd. IPR018039. Intermediate_filament_CS. [Graphical view]
PANTHER	PTHR23239. PTHR23239. 1 hit.
Pfam	PF00038. Filament. 1 hit. PF04732. Filament_head. 1 hit. [Graphical view]
PROSITE	PS00226. IF. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	NEFL. human.
GenomeRNAi	4747.
NextBio	18298.
SOURCE	Search...

Entry information

Entry name

NFL_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 150 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.