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P07197

- NFM_HUMAN

UniProt

P07197 - NFM_HUMAN

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Protein

Neurofilament medium polypeptide

Gene

NEFM

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- 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.

GO - Molecular functioni

  1. microtubule binding Source: BHF-UCL
  2. structural constituent of cytoskeleton Source: ProtInc

GO - Biological processi

  1. axon cargo transport Source: Ensembl
  2. microtubule cytoskeleton organization Source: Ensembl
  3. neurofilament bundle assembly Source: BHF-UCL
  4. regulation of axon diameter Source: Ensembl
Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
Neurofilament medium polypeptide
Short name:
NF-M
Alternative name(s):
160 kDa neurofilament protein
Neurofilament 3
Neurofilament triplet M protein
Gene namesi
Name:NEFM
Synonyms:NEF3, NFM
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 8

Organism-specific databases

HGNCiHGNC:7734. NEFM.

Subcellular locationi

GO - Cellular componenti

  1. axon Source: UniProtKB
  2. neurofibrillary tangle Source: BHF-UCL
  3. neurofilament Source: ProtInc
  4. neuromuscular junction Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Intermediate filament

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA162397442.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 916915Neurofilament medium polypeptidePRO_0000063794Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineBy similarity
Glycosylationi47 – 471O-linked (GlcNAc)By similarity
Modified residuei320 – 3201PhosphotyrosineBy similarity
Glycosylationi431 – 4311O-linked (GlcNAc)By similarity
Modified residuei511 – 5111PhosphoserineBy similarity
Modified residuei545 – 5451PhosphoserineBy similarity
Modified residuei553 – 5531PhosphoserineBy similarity
Modified residuei559 – 5591PhosphoserineBy similarity
Modified residuei641 – 6411PhosphoserineBy similarity
Modified residuei646 – 6461PhosphoserineBy similarity
Modified residuei680 – 6801PhosphoserineBy similarity
Modified residuei685 – 6851PhosphoserineBy similarity
Modified residuei736 – 7361PhosphoserineBy similarity
Modified residuei783 – 7831PhosphoserineBy similarity
Modified residuei837 – 8371Phosphoserine1 Publication

Post-translational modificationi

There are a number of repeats of the tripeptide K-S-P, NFM is phosphorylated on a number of the serines in this motif. It is thought that phosphorylation of NFM 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 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.
Phosphorylated in the head and rod regions by the PKC kinase PKN1, leading to the inhibition of polymerization.

Keywords - PTMi

Acetylation, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP07197.
PaxDbiP07197.
PRIDEiP07197.

2D gel databases

UCD-2DPAGEP07197.

PTM databases

PhosphoSiteiP07197.

Expressioni

Gene expression databases

BgeeiP07197.
CleanExiHS_NEFM.
ExpressionAtlasiP07197. baseline and differential.
GenevestigatoriP07197.

Organism-specific databases

HPAiCAB010900.
CAB012976.
HPA022845.
HPA023138.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
RB1P064002EBI-1105035,EBI-491274
SMAD2Q157963EBI-1105035,EBI-1040141

Protein-protein interaction databases

BioGridi110818. 19 interactions.
IntActiP07197. 14 interactions.
STRINGi9606.ENSP00000221166.

Structurei

3D structure databases

ProteinModelPortaliP07197.
SMRiP07197. Positions 100-249, 265-334, 339-407.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati614 – 626131Add
BLAST
Repeati627 – 639132Add
BLAST
Repeati640 – 652133Add
BLAST
Repeati653 – 665134Add
BLAST
Repeati666 – 678135Add
BLAST
Repeati679 – 691136Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 104103HeadAdd
BLAST
Regioni105 – 412308RodAdd
BLAST
Regioni105 – 13632Coil 1AAdd
BLAST
Regioni137 – 14913Linker 1Add
BLAST
Regioni150 – 24899Coil 1BAdd
BLAST
Regioni249 – 26517Linker 12Add
BLAST
Regioni266 – 28722Coil 2AAdd
BLAST
Regioni288 – 2914Linker 2
Regioni292 – 412121Coil 2BAdd
BLAST
Regioni413 – 916504TailAdd
BLAST
Regioni614 – 691786 X 13 AA approximate tandem repeats of K-S-P-V-[PS]-K-S-P-V-E-E-[KA]-[GAK]Add
BLAST

Sequence similaritiesi

Belongs to the intermediate filament family.Curated

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiNOG151229.
GeneTreeiENSGT00760000118905.
HOGENOMiHOG000230977.
HOVERGENiHBG013015.
InParanoidiP07197.
KOiK04573.
OMAiKEDIAVN.
OrthoDBiEOG7FV3Q8.
PhylomeDBiP07197.
TreeFamiTF330122.

Family and domain databases

InterProiIPR001664. IF.
IPR006821. Intermed_filament_DNA-bd.
IPR018039. Intermediate_filament_CS.
IPR002957. Keratin_I.
IPR027697. NF-M.
[Graphical view]
PANTHERiPTHR23239. PTHR23239. 1 hit.
PTHR23239:SF19. PTHR23239:SF19. 1 hit.
PfamiPF00038. Filament. 1 hit.
PF04732. Filament_head. 1 hit.
[Graphical view]
PRINTSiPR01248. TYPE1KERATIN.
PROSITEiPS00226. IF. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P07197-1) [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
MSYTLDSLGN PSAYRRVTET RSSFSRVSGS PSSGFRSQSW SRGSPSTVSS
60 70 80 90 100
SYKRSMLAPR LAYSSAMLSS AESSLDFSQS SSLLNGGSGP GGDYKLSRSN
110 120 130 140 150
EKEQLQGLND RFAGYIEKVH YLEQQNKEIE AEIQALRQKQ ASHAQLGDAY
160 170 180 190 200
DQEIRELRAT LEMVNHEKAQ VQLDSDHLEE DIHRLKERFE EEARLRDDTE
210 220 230 240 250
AAIRALRKDI EEASLVKVEL DKKVQSLQDE VAFLRSNHEE EVADLLAQIQ
260 270 280 290 300
ASHITVERKD YLKTDISTAL KEIRSQLESH SDQNMHQAEE WFKCRYAKLT
310 320 330 340 350
EAAEQNKEAI RSAKEEIAEY RRQLQSKSIE LESVRGTKES LERQLSDIEE
360 370 380 390 400
RHNHDLSSYQ DTIQQLENEL RGTKWEMARH LREYQDLLNV KMALDIEIAA
410 420 430 440 450
YRKLLEGEET RFSTFAGSIT GPLYTHRPPI TISSKIQKPK VEAPKLKVQH
460 470 480 490 500
KFVEEIIEET KVEDEKSEME EALTAITEEL AVSMKEEKKE AAEEKEEEPE
510 520 530 540 550
AEEEEVAAKK SPVKATAPEV KEEEGEKEEE EGQEEEEEED EGAKSDQAEE
560 570 580 590 600
GGSEKEGSSE KEEGEQEEGE TEAEAEGEEA EAKEEKKVEE KSEEVATKEE
610 620 630 640 650
LVADAKVEKP EKAKSPVPKS PVEEKGKSPV PKSPVEEKGK SPVPKSPVEE
660 670 680 690 700
KGKSPVPKSP VEEKGKSPVS KSPVEEKAKS PVPKSPVEEA KSKAEVGKGE
710 720 730 740 750
QKEEEEKEVK EAPKEEKVEK KEEKPKDVPE KKKAESPVKE EAVAEVVTIT
760 770 780 790 800
KSVKVHLEKE TKEEGKPLQQ EKEKEKAGGE GGSEEEGSDK GAKGSRKEDI
810 820 830 840 850
AVNGEVEGKE EVEQETKEKG SGREEEKGVV TNGLDLSPAD EKKGGDKSEE
860 870 880 890 900
KVVVTKTVEK ITSEGGDGAT KYITKSVTVT QKVEEHEETF EEKLVSTKKV
910
EKVTSHAIVK EVTQSD
Length:916
Mass (Da):102,472
Last modified:December 15, 2009 - v3
Checksum:i187B16CA6C6BF092
GO
Isoform 2 (identifier: P07197-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     2-376: Missing.

Note: No experimental confirmation available.

Show »
Length:541
Mass (Da):59,599
Checksum:iC74BDA0C506CDB10
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti482 – 4821V → A in CAA68276. (PubMed:3608989)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti439 – 4391P → T.6 Publications
Corresponds to variant rs196864 [ dbSNP | Ensembl ].
VAR_060732
Natural varianti725 – 7251P → Q.
Corresponds to variant rs196863 [ dbSNP | Ensembl ].
VAR_056024

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei2 – 376375Missing in isoform 2. 1 PublicationVSP_046306Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Y00067 Genomic DNA. Translation: CAA68276.1.
EF560736 mRNA. Translation: ABQ59046.1.
AK294681 mRNA. Translation: BAG57843.1.
AF106564 Genomic DNA. No translation available.
CH471080 Genomic DNA. Translation: EAW63602.1.
BC096757 mRNA. Translation: AAH96757.1.
CCDSiCCDS6046.1. [P07197-1]
PIRiA27864.
RefSeqiNP_005373.2. NM_005382.2. [P07197-1]
UniGeneiHs.458657.
Hs.730072.

Genome annotation databases

EnsembliENST00000221166; ENSP00000221166; ENSG00000104722. [P07197-1]
GeneIDi4741.
KEGGihsa:4741.
UCSCiuc003xed.4. human. [P07197-1]

Polymorphism databases

DMDMi281185500.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Human Intermediate Filament Mutation Database

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Y00067 Genomic DNA. Translation: CAA68276.1 .
EF560736 mRNA. Translation: ABQ59046.1 .
AK294681 mRNA. Translation: BAG57843.1 .
AF106564 Genomic DNA. No translation available.
CH471080 Genomic DNA. Translation: EAW63602.1 .
BC096757 mRNA. Translation: AAH96757.1 .
CCDSi CCDS6046.1. [P07197-1 ]
PIRi A27864.
RefSeqi NP_005373.2. NM_005382.2. [P07197-1 ]
UniGenei Hs.458657.
Hs.730072.

3D structure databases

ProteinModelPortali P07197.
SMRi P07197. Positions 100-249, 265-334, 339-407.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 110818. 19 interactions.
IntActi P07197. 14 interactions.
STRINGi 9606.ENSP00000221166.

PTM databases

PhosphoSitei P07197.

Polymorphism databases

DMDMi 281185500.

2D gel databases

UCD-2DPAGE P07197.

Proteomic databases

MaxQBi P07197.
PaxDbi P07197.
PRIDEi P07197.

Protocols and materials databases

DNASUi 4741.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000221166 ; ENSP00000221166 ; ENSG00000104722 . [P07197-1 ]
GeneIDi 4741.
KEGGi hsa:4741.
UCSCi uc003xed.4. human. [P07197-1 ]

Organism-specific databases

CTDi 4741.
GeneCardsi GC08P024770.
H-InvDB HIX0034266.
HIX0034491.
HGNCi HGNC:7734. NEFM.
HPAi CAB010900.
CAB012976.
HPA022845.
HPA023138.
MIMi 162250. gene.
neXtProti NX_P07197.
PharmGKBi PA162397442.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG151229.
GeneTreei ENSGT00760000118905.
HOGENOMi HOG000230977.
HOVERGENi HBG013015.
InParanoidi P07197.
KOi K04573.
OMAi KEDIAVN.
OrthoDBi EOG7FV3Q8.
PhylomeDBi P07197.
TreeFami TF330122.

Miscellaneous databases

ChiTaRSi NEFM. human.
GeneWikii NEFM.
GenomeRNAii 4741.
NextBioi 18284.
PROi P07197.
SOURCEi Search...

Gene expression databases

Bgeei P07197.
CleanExi HS_NEFM.
ExpressionAtlasi P07197. baseline and differential.
Genevestigatori P07197.

Family and domain databases

InterProi IPR001664. IF.
IPR006821. Intermed_filament_DNA-bd.
IPR018039. Intermediate_filament_CS.
IPR002957. Keratin_I.
IPR027697. NF-M.
[Graphical view ]
PANTHERi PTHR23239. PTHR23239. 1 hit.
PTHR23239:SF19. PTHR23239:SF19. 1 hit.
Pfami PF00038. Filament. 1 hit.
PF04732. Filament_head. 1 hit.
[Graphical view ]
PRINTSi PR01248. TYPE1KERATIN.
PROSITEi PS00226. IF. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "The human mid-size neurofilament subunit: a repeated protein sequence and the relationship of its gene to the intermediate filament gene family."
    Myers M.W., Lazzarini R.A., Lee V.M.-Y., Schlaepfer W.W., Nelson D.L.
    EMBO J. 6:1617-1626(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-439.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT THR-439.
    Tissue: Retina.
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    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.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT THR-439.
    Tissue: Brain.
  4. "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].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT THR-439.
  6. "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] (ISOFORM 1), VARIANT THR-439.
    Tissue: Brain.
  7. "Identification of the major multiphosphorylation site in mammalian neurofilaments."
    Lee V.M.-Y., Otvos L. Jr., Carden M.J., Hollosi M., Dietzschold B., Lazzarini R.A.
    Proc. Natl. Acad. Sci. U.S.A. 85:1998-2002(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: PARTIAL PROTEIN SEQUENCE.
  8. Lubec G., Chen W.-Q., Sun Y.
    Submitted (DEC-2008) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 128-137; 140-155; 169-184 AND 592-606, IDENTIFICATION BY MASS SPECTROMETRY.
    Tissue: Fetal brain cortex.
  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. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
    Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
    Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-837, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  11. Cited for: VARIANT [LARGE SCALE ANALYSIS] THR-439, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiNFM_HUMAN
AccessioniPrimary (citable) accession number: P07197
Secondary accession number(s): B4DGN2, E9PBF7, Q4QRK6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: December 15, 2009
Last modified: October 29, 2014
This is version 153 of the entry and version 3 of the sequence. [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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: 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

External Data

Dasty 3