Search
neurofilament heavy polypeptide; NF-H; neurofilament triplet H protein; 200 kD neurofilament protein (NEFH, KIAA0845, NFH)
Function:
- heavy chain of neurofilaments
- function in mature axons that is not subserved by the two smaller neurofilament proteins
- phosphorylation results in the formation of interfilament cross bridges that are important in the maintenance of axonal caliber
- phosphorylation seems to play a major role in functioning of the larger neurofilament polypeptides (NF-M & NF-H), the levels of phosphorylation are altered developmentally & coincident with a change in the neurofilament function
- can form neurofilaments in association with neurofilament L. [3]
- phosphorylated in C-terminal domain [3]
Structure:
- belongs to the intermediate filament family
- there are a number of repeats of the tripeptide K-S-P; phosphorylated on a number of the Ser in this motif
Alternative splicing: named isoforms=2
Polymorphism:
- the number of repeats is shown to vary between 29-30
Pathology:
- defects in NEFH are a cause of susceptibility to amyotrophic lateral sclerosis (ALS)
Laboratory:
- neurofilament heavy chain Ab in CSF
Interactions
molecular events
General
neurofilament protein
Properties
SIZE: entity length = 1026 aa
MW = 112 kD
COMPARTMENT: cytoplasm
CELL: neuron
MOTIF: Head {1-100}
MOTIF: Ser phosphorylation site {S61}
Rod {101-413}
MOTIF: Coil 1A {101-132}
Linker 1 {133-145}
Coil 1B {146-244}
Linker 12 {245-266}
Coil 2A {267-288}
Linker 2 {289-292}
Coil 2B {293-413}
Tail {414-1026}
MOTIF: Thr phosphorylation site {T501}
Ser phosphorylation site {S503}
repeats {525-832} (30)
Database Correlations
OMIM correlations
UniProt P12036
PFAM correlations
Entrez Gene 4744
Kegg hsa:4744
References
- Alperts et al Molecular Biology of the Cell, Garland
Publishing, New York, NY 1989 pg 662
- Wang KK et al
Calmodulin-binding proteins as calpain substrates.
Biochem J 262:693 1989
PMID: 2556106
- Cairns NJ, Lee VM, Trojanowski JQ.
The cytoskeleton in neurodegenerative diseases.
J Pathol. 2004 Nov;204(4):438-49. Review.
PMID: 15495240
- UniProt :accession P12036
- Human intermediate Filament mutation Database
http://www.interfil.org
- ALS genetic mutations db
http://alsod.iop.kcl.ac.uk/als/