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UniProtKB/Swiss-Prot entry P12036


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name NFH_HUMAN
Primary accession number P12036
Secondary accession numbers B4DYY4 Q96HF8 Q9UJS7 Q9UQ14
Integrated into Swiss-Prot on October 1, 1989
Sequence was last modified on March 24, 2009 (Sequence version 4)
Annotations were last modified on    June 16, 2009 (Entry version 98)
Name and origin of the protein
Protein name Neurofilament heavy polypeptide
Synonyms NF-H
Neurofilament triplet H protein
200 kDa neurofilament protein
Gene name
Name: NEFH
Synonyms: KIAA0845, NFH
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-811.
PubMed=3138108 [NCBI, ExPASy, EBI, Israel, Japan]
Lees J.F., Shneidman P.S., Skuntz S.F., Carden M.J., Lazzarini R.A.;
"The structure and organization of the human heavy neurofilament subunit (NF-H) and the gene encoding it.";
EMBO J. 7:1947-1955(1988).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Zhu Y., Han Y.;
"Molecular Cloning of human hSTE cDNA.";
Beijing Yi Ke Da Xue Xue Bao 31:531-531(1999).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Brain;
DOI=10.1093/dnares/5.6.355; PubMed=10048485 [NCBI, ExPASy, EBI, Israel, Japan]
Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.;
"Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.";
DNA Res. 5:355-364(1998).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Testis;
DOI=10.1038/ng1285; PubMed=14702039 [NCBI, ExPASy, EBI, Israel, Japan]
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human cDNAs.";
Nat. Genet. 36:40-45(2004).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/990031; PubMed=10591208 [NCBI, ExPASy, EBI, Israel, Japan]
Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H.;
"The DNA sequence of human chromosome 22.";
Nature 402:489-495(1999).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1) AND NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 606-1026 (ISOFORM 2).
TISSUE=Eye;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
Colinge J., Superti-Furga G., Bennett K.L.;
Submitted (OCT-2008) to UniProtKB.
[8]
VARIANT ALS LYS-796 DEL.
DOI=10.1093/hmg/3.10.1757; PubMed=7849698 [NCBI, ExPASy, EBI, Israel, Japan]
Figlewicz D.A., Krizus A., Martinoli M.G., Meininger V., Dib M., Rouleau G.A., Julien J.-P.;
"Variants of the heavy neurofilament subunit are associated with the development of amyotrophic lateral sclerosis.";
Hum. Mol. Genet. 3:1757-1761(1994).
Comments
  • FUNCTION: 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.
  • ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative splicing.
    Name1
    Isoform IDP12036-1
    This is the isoform sequence displayed in this entry.
    Name2
    Isoform IDP12036-2
    Note: No experimental confirmation available.
    Features which should be applied to build the isoform sequence: VSP_036706.
  • PTM: 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.
  • PTM: 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 coincident with a change in the neurofilament function.
  • POLYMORPHISM: The number of repeats is shown to vary between 29 and 30.
  • DISEASE: Defects in NEFH are a cause of susceptibility to amyotrophic lateral sclerosis (ALS) [MIM:105400]. ALS is a neurodegenerative disorder affecting upper and lower motor neurons, and resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology is likely to be multifactorial, involving both genetic and environmental factors.
  • SIMILARITY: Belongs to the intermediate filament family.
  • WEB RESOURCE: Name=Human Intermediate Filament Mutation Database; URL="http://www.interfil.org";.
  • WEB RESOURCE: Name=Alsod; Note=ALS genetic mutations db; URL="http://alsod.iop.kcl.ac.uk/Als/";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
X15306; CAA33366.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X15307; CAA33366.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X15308; CAA33366.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X15309; CAA33366.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF203032; AAF13722.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AB020652; BAA74868.2; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AK302660; BAG63896.1; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AC000035; -; NOT_ANNOTATED_CDS; Genomic_DNA.[EMBL / GenBank / DDBJ]
BC008648; AAH08648.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC073969; AAH73969.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00910602; -.
IPI00923396; -.
PIR S00979; QFHUH.
RefSeq NP_066554.2; -.
UniGene Hs.198760
3D structure databases
HSSP P08670; 1GK4. [HSSP ENTRY / PDB]
ModBase P12036.
PTM databases
PhosphoSite P12036; -.
Organism-specific databases
GeneCards GC22P028200; -.
H-InvDB HIX0016351; -.
HGNC HGNC:7737; NEFH.
GenAtlas NEFH.
HPA CAB007786; -.
MIM 105400; phenotype. [NCBI / EBI]
162230; gene. [NCBI / EBI]
Orphanet 803; Amyotrophic lateral sclerosis.
PharmGKB PA31540; -.
HUGE KIAA0845.
Gene expression databases
ArrayExpress P12036; -.
Bgee P12036; -.
CleanEx HS_NEFH; -.
GermOnline ENSG00000100285; Homo sapiens.
Ontologies
GO
GO:0030424; Cellular component: axon (traceable author statement from UniProtKB).
GO:0005883; Cellular component: neurofilament (non-traceable author statement from UniProtKB).
GO:0008219; Biological process: cell death (inferred from electronic annotation from UniProtKB-KW).
GO:0007399; Biological process: nervous system development (non-traceable author statement from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR010790; DUF1388.
IPR016044; F.
IPR018039; Intermediate_filament_CS.
Graphical view of domain structure.
Pfam PF07142; DUF1388; 3.
PF00038; Filament; 1.
Pfam graphical view of domain structure.
PROSITE PS00226; IF; 1.
Proteomic databases
PRIDE P12036; -.
Genome annotation databases
Ensembl ENSG00000100285; Homo sapiens. [Contig view]
GeneID 4744; -.
KEGG hsa:4744; -.
Phylogenomic databases
HOGENOM P12036; -.
HOVERGEN P12036; -.
Other
NextBio 18288; -.
SOURCE NEFH; Homo sapiens.
ProtoNet P12036.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Alternative splicing; Amyotrophic lateral sclerosis; Coiled coil; Disease mutation; Intermediate filament; Neurodegeneration; Phosphoprotein; Polymorphism; Repeat.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   1026  1026     Neurofilament heavy polypeptide. PRO_0000063800
REPEAT   525    530  6     1. 
REPEAT   531    536  6     2. 
REPEAT   539    544  6     3. 
REPEAT   545    550  6     4. 
REPEAT   559    564  6     5. 
REPEAT   573    578  6     6. 
REPEAT   579    584  6     7. 
REPEAT   593    598  6     8. 
REPEAT   599    604  6     9. 
REPEAT   613    618  6     10. 
REPEAT   627    632  6     11. 
REPEAT   633    638  6     12. 
REPEAT   647    652  6     13. 
REPEAT   653    658  6     14. 
REPEAT   667    672  6     15. 
REPEAT   673    678  6     16. 
REPEAT   681    686  6     17. 
REPEAT   687    692  6     18. 
REPEAT   695    700  6     19. 
REPEAT   701    706  6     20. 
REPEAT   709    714  6     21. 
REPEAT   715    720  6     22. 
REPEAT   723    728  6     23. 
REPEAT   729    734  6     24. 
REPEAT   743    748  6     25. 
REPEAT   751    756  6     26. 
REPEAT   768    773  6     27. 
REPEAT   792    797  6     28. 
REPEAT   800    805  6     29. 
REPEAT   827    832  6     30. 
REGION   1    100  100     Head. 
REGION   101    413  313     Rod. 
REGION   101    132  32     Coil 1A. 
REGION   133    145  13     Linker 1. 
REGION   146    244  99     Coil 1B. 
REGION   245    266  22     Linker 12. 
REGION   267    288  22     Coil 2A. 
REGION   289    292  4     Linker 2. 
REGION   293    413  121     Coil 2B. 
REGION   414   1026  613     Tail. 
REGION   525    832  308     30 X 6 AA repeats of K-S-P-[AEPV]-[EAK]-[AEVK]. 
MOD_RES   61     61        Phosphoserine (By similarity). 
MOD_RES   501    501        Phosphothreonine (By similarity). 
MOD_RES   503    503        Phosphoserine (By similarity). 
MOD_RES   526    526        Phosphoserine (By similarity). 
MOD_RES   532    532        Phosphoserine (By similarity). 
MOD_RES   540    540        Phosphoserine (By similarity). 
MOD_RES   546    546        Phosphoserine (By similarity). 
MOD_RES   552    552        Phosphoserine (By similarity). 
MOD_RES   560    560        Phosphoserine (By similarity). 
MOD_RES   566    566        Phosphoserine (By similarity). 
MOD_RES   574    574        Phosphoserine (By similarity). 
MOD_RES   600    600        Phosphoserine (By similarity). 
MOD_RES   606    606        Phosphoserine (By similarity). 
MOD_RES   614    614        Phosphoserine (By similarity). 
MOD_RES   620    620        Phosphoserine (By similarity). 
MOD_RES   628    628        Phosphoserine (By similarity). 
MOD_RES   634    634        Phosphoserine (By similarity). 
MOD_RES   640    640        Phosphoserine (By similarity). 
MOD_RES   648    648        Phosphoserine (By similarity). 
MOD_RES   654    654        Phosphoserine (By similarity). 
MOD_RES   660    660        Phosphoserine (By similarity). 
MOD_RES   668    668        Phosphoserine (By similarity). 
MOD_RES   674    674        Phosphoserine (By similarity). 
MOD_RES   682    682        Phosphoserine (By similarity). 
MOD_RES   688    688        Phosphoserine (By similarity). 
MOD_RES   696    696        Phosphoserine (By similarity). 
MOD_RES   702    702        Phosphoserine (By similarity). 
MOD_RES   710    710        Phosphoserine (By similarity). 
MOD_RES   724    724        Phosphoserine (By similarity). 
MOD_RES   769    769        Phosphoserine (By similarity). 
MOD_RES   774    774        Phosphothreonine (By similarity). 
MOD_RES   801    801        Phosphoserine (By similarity). 
MOD_RES   828    828        Phosphoserine (By similarity). 
VAR_SEQ   750    812        Missing (in isoform 2). VSP_036706
VARIANT   575    575  1     P -> S (in dbSNP:rs6006164 [NCBI]). VAR_054787 
VARIANT   615    615  1     P -> L (in dbSNP:rs5763269 [NCBI]). VAR_056025 
VARIANT   796    796  1     Missing (in ALS). VAR_023063
VARIANT   811    811  1     E -> A (in dbSNP:rs165602 [NCBI]). VAR_026163 
CONFLICT   647    652        Missing (in Ref. 1; CAA33366 and 5; AC000035). 
Sequence information
Length: 1026 AA [This is the length of the unprocessed precursor] Molecular weight: 112479 Da [This is the MW of the unprocessed precursor] CRC64: 0879B6A08D208C17 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MMSFGGADAL LGAPFAPLHG GGSLHYALAR KGGAGGTRSA AGSSSGFHSW TRTSVSSVSA 

        70         80         90        100        110        120 
SPSRFRGAGA ASSTDSLDTL SNGPEGCMVA VATSRSEKEQ LQALNDRFAG YIDKVRQLEA 

       130        140        150        160        170        180 
HNRSLEGEAA ALRQQQAGRS AMGELYEREV REMRGAVLRL GAARGQLRLE QEHLLEDIAH 

       190        200        210        220        230        240 
VRQRLDDEAR QREEAEAAAR ALARFAQEAE AARVDLQKKA QALQEECGYL RRHHQEEVGE 

       250        260        270        280        290        300 
LLGQIQGSGA AQAQMQAETR DALKCDVTSA LREIRAQLEG HAVQSTLQSE EWFRVRLDRL 

       310        320        330        340        350        360 
SEAAKVNTDA MRSAQEEITE YRRQLQARTT ELEALKSTKD SLERQRSELE DRHQADIASY 

       370        380        390        400        410        420 
QEAIQQLDAE LRNTKWEMAA QLREYQDLLN VKMALDIEIA AYRKLLEGEE CRIGFGPIPF 

       430        440        450        460        470        480 
SLPEGLPKIP SVSTHIKVKS EEKIKVVEKS EKETVIVEEQ TEETQVTEEV TEEEEKEAKE 

       490        500        510        520        530        540 
EEGKEEEGGE EEEAEGGEEE TKSPPAEEAA SPEKEAKSPV KEEAKSPAEA KSPEKEEAKS 

       550        560        570        580        590        600 
PAEVKSPEKA KSPAKEEAKS PPEAKSPEKE EAKSPAEVKS PEKAKSPAKE EAKSPAEAKS 

       610        620        630        640        650        660 
PEKAKSPVKE EAKSPAEAKS PVKEEAKSPA EVKSPEKAKS PTKEEAKSPE KAKSPEKAKS 

       670        680        690        700        710        720 
PEKEEAKSPE KAKSPVKAEA KSPEKAKSPV KAEAKSPEKA KSPVKEEAKS PEKAKSPVKE 

       730        740        750        760        770        780 
EAKSPEKAKS PVKEEAKTPE KAKSPVKEEA KSPEKAKSPE KAKTLDVKSP EAKTPAKEEA 

       790        800        810        820        830        840 
RSPADKFPEK AKSPVKEEVK SPEKAKSPLK EDAKAPEKEI PKKEEVKSPV KEEEKPQEVK 

       850        860        870        880        890        900 
VKEPPKKAEE EKAPATPKTE EKKDSKKEEA PKKEAPKPKV EEKKEPAVEK PKESKVEAKK 

       910        920        930        940        950        960 
EEAEDKKKVP TPEKEAPAKV EVKEDAKPKE KTEVAKKEPD DAKAKEPSKP AEKKEAAPEK 

       970        980        990       1000       1010       1020 
KDTKEEKAKK PEEKPKTEAK AKEDDKTLSK EPSKPKAEKA EKSSSTDQKD SKPPEKATED 


KAAKGK 

P12036 in FASTA format

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