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UniProtKB - P12036 (NFH_HUMAN)

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Protein

Neurofilament heavy polypeptide

Gene

NEFH

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. NF-H has an important function in mature axons that is not subserved by the two smaller NF proteins.

GO - Molecular functioni

  • dynein complex binding Source: BHF-UCL
  • kinesin binding Source: BHF-UCL
  • microtubule binding Source: BHF-UCL
  • protein binding, bridging Source: BHF-UCL
  • protein kinase binding Source: ARUK-UCL
  • structural constituent of cytoskeleton Source: BHF-UCL
  • structural molecule activity Source: BHF-UCL
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • axon development Source: BHF-UCL
  • axonogenesis Source: BHF-UCL
  • cell projection assembly Source: BHF-UCL
  • cellular response to leukemia inhibitory factor Source: Ensembl
  • microtubule cytoskeleton organization Source: Ensembl
  • neurofilament bundle assembly Source: BHF-UCL
  • neurofilament cytoskeleton organization Source: Ensembl
  • peripheral nervous system neuron axonogenesis Source: Ensembl
  • regulation of organelle transport along microtubule Source: BHF-UCL
View the complete GO annotation on QuickGO ...

Enzyme and pathway databases

SIGNORiP12036

Names & Taxonomyi

Protein namesi
Recommended name:
Neurofilament heavy polypeptide
Short name:
NF-H
Alternative name(s):
200 kDa neurofilament protein
Neurofilament triplet H protein
Gene namesi
Name:NEFH
Synonyms:KIAA0845, NFH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000100285.9
HGNCiHGNC:7737 NEFH
MIMi162230 gene
neXtProtiNX_P12036

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

Cytoplasm, Intermediate filament

Pathology & Biotechi

Involvement in diseasei

Amyotrophic lateral sclerosis (ALS)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.
See also OMIM:105400
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_023063796Missing in ALS. 1 Publication1
Charcot-Marie-Tooth disease 2CC (CMT2CC)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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:616924

Keywords - Diseasei

Amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease, Disease mutation, Neurodegeneration, Neuropathy

Organism-specific databases

DisGeNETi4744
MalaCardsiNEFH
MIMi105400 phenotype
616924 phenotype
Orphaneti803 Amyotrophic lateral sclerosis
PharmGKBiPA31540

Polymorphism and mutation databases

BioMutaiNEFH
DMDMi226726294

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000638001 – 1026Neurofilament heavy polypeptideAdd BLAST1026

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei76PhosphoserineBy similarity1
Modified residuei124PhosphoserineBy similarity1
Modified residuei347PhosphoserineBy similarity1
Modified residuei421PhosphoserineBy similarity1
Modified residuei511PhosphoserineBy similarity1
Modified residuei526PhosphoserineBy similarity1
Modified residuei532PhosphoserineBy similarity1
Modified residuei540PhosphoserineCombined sources1
Modified residuei546PhosphoserineBy similarity1
Modified residuei552PhosphoserineBy similarity1
Modified residuei560PhosphoserineBy similarity1
Modified residuei566PhosphoserineBy similarity1
Modified residuei574PhosphoserineCombined sources1
Modified residuei580PhosphoserineBy similarity1
Modified residuei586PhosphoserineBy similarity1
Modified residuei594PhosphoserineBy similarity1
Modified residuei600PhosphoserineBy similarity1
Modified residuei606PhosphoserineBy similarity1
Modified residuei614PhosphoserineBy similarity1
Modified residuei620PhosphoserineBy similarity1
Modified residuei628PhosphoserineCombined sources1
Modified residuei634PhosphoserineBy similarity1
Modified residuei640PhosphoserineBy similarity1
Modified residuei648PhosphoserineBy similarity1
Modified residuei654PhosphoserineBy similarity1
Modified residuei660PhosphoserineBy similarity1
Modified residuei668PhosphoserineBy similarity1
Modified residuei674PhosphoserineCombined sources1
Modified residuei682PhosphoserineBy similarity1
Modified residuei688PhosphoserineCombined sources1
Modified residuei696PhosphoserineBy similarity1
Modified residuei702PhosphoserineBy similarity1
Modified residuei710PhosphoserineBy similarity1
Modified residuei724PhosphoserineBy similarity1
Modified residuei730PhosphoserineBy similarity1
Modified residuei744PhosphoserineBy similarity1
Modified residuei758PhosphoserineBy similarity1
Modified residuei769PhosphoserineBy similarity1
Modified residuei774PhosphothreonineBy similarity1
Modified residuei793PhosphoserineBy similarity1
Modified residuei801PhosphoserineBy similarity1
Modified residuei828PhosphoserineBy similarity1
Modified residuei894PhosphoserineBy similarity1

Post-translational modificationi

There are a number of repeats of the tripeptide K-S-P, NFH is phosphorylated on a number of the serines in this motif. It is thought that phosphorylation of NFH results in the formation of interfilament cross bridges that are important in the maintenance of axonal caliber.1 Publication
Phosphorylation seems to play a major role in the functioning of the larger neurofilament polypeptides (NF-M and NF-H), the levels of phosphorylation being altered developmentally and coincidentally with a change in the neurofilament function.1 Publication
Phosphorylated in the head and rod regions by the PKC kinase PKN1, leading to the inhibition of polymerization.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP12036
MaxQBiP12036
PaxDbiP12036
PeptideAtlasiP12036
PRIDEiP12036
ProteomicsDBi52821
52822 [P12036-2]

2D gel databases

UCD-2DPAGEiP12036

PTM databases

CarbonylDBiP12036
iPTMnetiP12036
PhosphoSitePlusiP12036
SwissPalmiP12036

Expressioni

Gene expression databases

BgeeiENSG00000100285
CleanExiHS_NEFH
GenevisibleiP12036 HS

Organism-specific databases

HPAiCAB007786
HPA061615

Interactioni

GO - Molecular functioni

  • kinesin binding Source: BHF-UCL
  • microtubule binding Source: BHF-UCL
  • protein binding, bridging Source: BHF-UCL
  • protein kinase binding Source: ARUK-UCL
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi110819, 25 interactors
IntActiP12036, 14 interactors
STRINGi9606.ENSP00000311997

Structurei

3D structure databases

ProteinModelPortaliP12036
SMRiP12036
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini97 – 413IF rodPROSITE-ProRule annotationAdd BLAST317
Repeati525 – 53016
Repeati531 – 53626
Repeati539 – 54436
Repeati545 – 55046
Repeati559 – 56456
Repeati573 – 57866
Repeati579 – 58476
Repeati593 – 59886
Repeati599 – 60496
Repeati613 – 618106
Repeati627 – 632116
Repeati633 – 638126
Repeati647 – 652136
Repeati653 – 658146
Repeati667 – 672156
Repeati673 – 678166
Repeati681 – 686176
Repeati687 – 692186
Repeati695 – 700196
Repeati701 – 706206
Repeati709 – 714216
Repeati715 – 720226
Repeati723 – 728236
Repeati729 – 734246
Repeati743 – 748256
Repeati751 – 756266
Repeati768 – 773276
Repeati792 – 797286
Repeati800 – 805296
Repeati827 – 832306

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 100HeadAdd BLAST100
Regioni101 – 132Coil 1AAdd BLAST32
Regioni133 – 145Linker 1Add BLAST13
Regioni146 – 244Coil 1BAdd BLAST99
Regioni245 – 266Linker 12Add BLAST22
Regioni267 – 288Coil 2AAdd BLAST22
Regioni289 – 292Linker 24
Regioni293 – 413Coil 2BAdd BLAST121
Regioni414 – 1026TailAdd BLAST613
Regioni525 – 83230 X 6 AA repeats of K-S-P-[AEPV]-[EAK]-[AEVK]Add BLAST308

Sequence similaritiesi

Belongs to the intermediate filament family.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiENOG410IGME Eukaryota
ENOG410XPTM LUCA
HOGENOMiHOG000230977
HOVERGENiHBG013015
InParanoidiP12036
KOiK04574
OrthoDBiEOG091G12MK
PhylomeDBiP12036
TreeFamiTF330122

Family and domain databases

InterProiView protein in InterPro
IPR010790 DUF1388
IPR018039 IF_conserved
IPR039008 IF_rod_dom
IPR033183 NF-H
PANTHERiPTHR23214 PTHR23214, 2 hits
PfamiView protein in Pfam
PF07142 DUF1388, 9 hits
PF00038 Filament, 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

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P12036-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MMSFGGADAL LGAPFAPLHG GGSLHYALAR KGGAGGTRSA AGSSSGFHSW 
        60         70         80         90        100
TRTSVSSVSA SPSRFRGAGA ASSTDSLDTL SNGPEGCMVA VATSRSEKEQ 
       110        120        130        140        150
LQALNDRFAG YIDKVRQLEA HNRSLEGEAA ALRQQQAGRS AMGELYEREV 
       160        170        180        190        200
REMRGAVLRL GAARGQLRLE QEHLLEDIAH VRQRLDDEAR QREEAEAAAR 
       210        220        230        240        250
ALARFAQEAE AARVDLQKKA QALQEECGYL RRHHQEEVGE LLGQIQGSGA 
       260        270        280        290        300
AQAQMQAETR DALKCDVTSA LREIRAQLEG HAVQSTLQSE EWFRVRLDRL 
       310        320        330        340        350
SEAAKVNTDA MRSAQEEITE YRRQLQARTT ELEALKSTKD SLERQRSELE 
       360        370        380        390        400
DRHQADIASY QEAIQQLDAE LRNTKWEMAA QLREYQDLLN VKMALDIEIA 
       410        420        430        440        450
AYRKLLEGEE CRIGFGPIPF SLPEGLPKIP SVSTHIKVKS EEKIKVVEKS 
       460        470        480        490        500
EKETVIVEEQ TEETQVTEEV TEEEEKEAKE EEGKEEEGGE EEEAEGGEEE 
       510        520        530        540        550
TKSPPAEEAA SPEKEAKSPV KEEAKSPAEA KSPEKEEAKS PAEVKSPEKA 
       560        570        580        590        600
KSPAKEEAKS PPEAKSPEKE EAKSPAEVKS PEKAKSPAKE EAKSPAEAKS 
       610        620        630        640        650
PEKAKSPVKE EAKSPAEAKS PVKEEAKSPA EVKSPEKAKS PTKEEAKSPE 
       660        670        680        690        700
KAKSPEKAKS PEKEEAKSPE KAKSPVKAEA KSPEKAKSPV KAEAKSPEKA 
       710        720        730        740        750
KSPVKEEAKS PEKAKSPVKE EAKSPEKAKS PVKEEAKTPE KAKSPVKEEA 
       760        770        780        790        800
KSPEKAKSPE KAKTLDVKSP EAKTPAKEEA RSPADKFPEK AKSPVKEEVK 
       810        820        830        840        850
SPEKAKSPLK EDAKAPEKEI PKKEEVKSPV KEEEKPQEVK VKEPPKKAEE 
       860        870        880        890        900
EKAPATPKTE EKKDSKKEEA PKKEAPKPKV EEKKEPAVEK PKESKVEAKK 
       910        920        930        940        950
EEAEDKKKVP TPEKEAPAKV EVKEDAKPKE KTEVAKKEPD DAKAKEPSKP 
       960        970        980        990       1000
AEKKEAAPEK KDTKEEKAKK PEEKPKTEAK AKEDDKTLSK EPSKPKAEKA 
      1010       1020 
EKSSSTDQKD SKPPEKATED KAAKGK
Length:1,026
Mass (Da):112,479
Last modified:March 24, 2009 - v4
Checksum:i0879B6A08D208C17
GO
Isoform 2 (identifier: P12036-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     750-812: Missing.

Note: No experimental confirmation available.
Show »
Length:963
Mass (Da):105,639
Checksum:i6E272AB8F3FBF5EA
GO

Sequence cautioni

The sequence BAA74868 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAG63896 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti647 – 652Missing in CAA33366 (PubMed:3138108).Curated6
Sequence conflicti647 – 652Missing in AC000035 (PubMed:10591208).Curated6

Polymorphismi

The number of repeats is shown to vary between 29 and 30.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_054787575P → S. Corresponds to variant dbSNP:rs6006164Ensembl.1
Natural variantiVAR_056025615P → L. Corresponds to variant dbSNP:rs5763269EnsemblClinVar.1
Natural variantiVAR_023063796Missing in ALS. 1 Publication1
Natural variantiVAR_026163811E → A1 PublicationCorresponds to variant dbSNP:rs165602Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_036706750 – 812Missing in isoform 2. 1 PublicationAdd BLAST63

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X15306
, X15307, X15308, X15309 Genomic DNA Translation: CAA33366.1
AF203032 mRNA Translation: AAF13722.1
AB020652 mRNA Translation: BAA74868.2 Different initiation.
AK302660 mRNA Translation: BAG63896.1 Different initiation.
AC000035 Genomic DNA No translation available.
BC008648 mRNA Translation: AAH08648.1
BC073969 mRNA Translation: AAH73969.1
PIRiS00979 QFHUH
RefSeqiNP_066554.2, NM_021076.3
UniGeneiHs.198760

Genome annotation databases

EnsembliENST00000310624; ENSP00000311997; ENSG00000100285
GeneIDi4744
KEGGihsa:4744
UCSCiuc003afo.4 human [P12036-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNFH_HUMAN
AccessioniPrimary (citable) accession number: P12036
Secondary accession number(s): B4DYY4
, Q96HF8, Q9UJS7, Q9UQ14
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: March 24, 2009
Last modified: July 18, 2018
This is version 180 of the entry and version 4 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, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: 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

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