P07197 (NFM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Neurofilament medium polypeptide
Short name=NF-M

Alternative name(s):
160 kDa neurofilament protein
Neurofilament 3
Neurofilament triplet M protein

Gene names

Name:	NEFM
Synonyms:	NEF3, NFM

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	916 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.
Post-translational modification	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. Ref.8 Ref.9 Ref.10 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. Phosphorylated in the Head and Rod regions by the PKC kinase PKN1, leading to inhibit polymerization. Ref.8 Ref.9 Ref.10
Sequence similarities	Belongs to the intermediate filament family.

Ontologies

Keywords
Cellular component	Intermediate filament
Coding sequence diversity	Polymorphism
Domain	Coiled coil Repeat
PTM	Acetylation Glycoprotein Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Cellular component	neurofilament Traceable author statement. Source: ProtInc
Molecular function	protein binding Inferred from physical interaction. Source: IntAct structural constituent of cytoskeleton Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RB1	P06400	2	EBI-1105035,EBI-491274
SMAD2	Q15796	3	EBI-1105035,EBI-1040141

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed
	Chain	2 – 916	915	Neurofilament medium polypeptide		PRO_0000063794
Regions
	Repeat	614 – 626	13	1
	Repeat	627 – 639	13	2
	Repeat	640 – 652	13	3
	Repeat	653 – 665	13	4
	Repeat	666 – 678	13	5
	Repeat	679 – 691	13	6
	Region	2 – 104	103	Head
	Region	105 – 412	308	Rod
	Region	105 – 136	32	Coil 1A
	Region	137 – 149	13	Linker 1
	Region	150 – 248	99	Coil 1B
	Region	249 – 265	17	Linker 12
	Region	266 – 287	22	Coil 2A
	Region	288 – 291	4	Linker 2
	Region	292 – 412	121	Coil 2B
	Region	413 – 916	504	Tail
	Region	614 – 691	78	6 X 13 AA approximate tandem repeats of K-S-P-V-[PS]-K-S-P-V-E-E-[KA]-[GAK]
Amino acid modifications
	Modified residue	2	1	N-acetylserine By similarity
	Modified residue	320	1	Phosphotyrosine By similarity
	Modified residue	511	1	Phosphoserine Ref.10
	Modified residue	545	1	Phosphoserine By similarity
	Modified residue	553	1	Phosphoserine By similarity
	Modified residue	559	1	Phosphoserine By similarity
	Modified residue	615	1	Phosphoserine Ref.9 Ref.10
	Modified residue	620	1	Phosphoserine Ref.9 Ref.10
	Modified residue	628	1	Phosphoserine Ref.9
	Modified residue	633	1	Phosphoserine Ref.9
	Modified residue	654	1	Phosphoserine Ref.10
	Modified residue	659	1	Phosphoserine Ref.10
	Modified residue	667	1	Phosphoserine Ref.9
	Modified residue	672	1	Phosphoserine Ref.9
	Modified residue	680	1	Phosphoserine Ref.9 Ref.10
	Modified residue	685	1	Phosphoserine Ref.9 Ref.10
	Modified residue	736	1	Phosphoserine Ref.9 Ref.10
	Modified residue	783	1	Phosphoserine Ref.10
	Modified residue	788	1	Phosphoserine Ref.10
	Modified residue	837	1	Phosphoserine By similarity
	Glycosylation	47	1	O-linked (GlcNAc) By similarity
	Glycosylation	431	1	O-linked (GlcNAc) By similarity
Natural variations
	Natural variant	439	1	P → T. Ref.1 Ref.2 Ref.4 Ref.5 Corresponds to variant rs196864 [ dbSNP | Ensembl ].		VAR_060732
	Natural variant	725	1	P → Q. Corresponds to variant rs196863 [ dbSNP | Ensembl ].		VAR_056024
Experimental info
	Sequence conflict	482	1	V → A in CAA68276. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P07197 [UniParc]. Last modified December 15, 2009. Version 3. Checksum: 187B16CA6C6BF092	FASTA	916	102,472
	10 20 30 40 50 60 MSYTLDSLGN PSAYRRVTET RSSFSRVSGS PSSGFRSQSW SRGSPSTVSS SYKRSMLAPR 70 80 90 100 110 120 LAYSSAMLSS AESSLDFSQS SSLLNGGSGP GGDYKLSRSN EKEQLQGLND RFAGYIEKVH 130 140 150 160 170 180 YLEQQNKEIE AEIQALRQKQ ASHAQLGDAY DQEIRELRAT LEMVNHEKAQ VQLDSDHLEE 190 200 210 220 230 240 DIHRLKERFE EEARLRDDTE AAIRALRKDI EEASLVKVEL DKKVQSLQDE VAFLRSNHEE 250 260 270 280 290 300 EVADLLAQIQ ASHITVERKD YLKTDISTAL KEIRSQLESH SDQNMHQAEE WFKCRYAKLT 310 320 330 340 350 360 EAAEQNKEAI RSAKEEIAEY RRQLQSKSIE LESVRGTKES LERQLSDIEE RHNHDLSSYQ 370 380 390 400 410 420 DTIQQLENEL RGTKWEMARH LREYQDLLNV KMALDIEIAA YRKLLEGEET RFSTFAGSIT 430 440 450 460 470 480 GPLYTHRPPI TISSKIQKPK VEAPKLKVQH KFVEEIIEET KVEDEKSEME EALTAITEEL 490 500 510 520 530 540 AVSMKEEKKE AAEEKEEEPE AEEEEVAAKK SPVKATAPEV KEEEGEKEEE EGQEEEEEED 550 560 570 580 590 600 EGAKSDQAEE GGSEKEGSSE KEEGEQEEGE TEAEAEGEEA EAKEEKKVEE KSEEVATKEE 610 620 630 640 650 660 LVADAKVEKP EKAKSPVPKS PVEEKGKSPV PKSPVEEKGK SPVPKSPVEE KGKSPVPKSP 670 680 690 700 710 720 VEEKGKSPVS KSPVEEKAKS PVPKSPVEEA KSKAEVGKGE QKEEEEKEVK EAPKEEKVEK 730 740 750 760 770 780 KEEKPKDVPE KKKAESPVKE EAVAEVVTIT KSVKVHLEKE TKEEGKPLQQ EKEKEKAGGE 790 800 810 820 830 840 GGSEEEGSDK GAKGSRKEDI AVNGEVEGKE EVEQETKEKG SGREEEKGVV TNGLDLSPAD 850 860 870 880 890 900 EKKGGDKSEE KVVVTKTVEK ITSEGGDGAT KYITKSVTVT QKVEEHEETF EEKLVSTKKV 910 EKVTSHAIVK EVTQSD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 3608989] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-439.
[2]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed: 11230166] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT THR-439. Tissue: Retina.
[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: 16421571] [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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT THR-439.
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT THR-439. Tissue: Brain.
[6]	"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: 2450354] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE.
[7]	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, MASS SPECTROMETRY. Tissue: Fetal brain cortex.
[8]	"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: 8621664] [Abstract] Cited for: PHOSPHORYLATION BY PKN1.
[9]	"Phosphoproteomic analysis of synaptosomes from human cerebral cortex." DeGiorgis J.A., Jaffe H., Moreira J.E., Carlotti C.G. Jr., Leite J.P., Pant H.C., Dosemeci A. J. Proteome Res. 4:306-315(2005) [PubMed: 15822905] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-615; SER-620; SER-628; SER-633; SER-667; SER-672; SER-680; SER-685 AND SER-736, MASS SPECTROMETRY. Tissue: Brain cortex.
[10]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-511; SER-615; SER-620; SER-654; SER-659; SER-680; SER-685; SER-736; SER-783 AND SER-788, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[11]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Web resources

Human Intermediate Filament Mutation Database

Cross-references

Sequence databases
EMBL GenBank DDBJ	Y00067 Genomic DNA. Translation: CAA68276.1. EF560736 mRNA. Translation: ABQ59046.1. AF106564 Genomic DNA. No translation available. CH471080 Genomic DNA. Translation: EAW63602.1. BC096757 mRNA. Translation: AAH96757.1.
IPI	IPI00217507.
PIR	A27864.
RefSeq	NP_005373.2. NM_005382.2.
UniGene	Hs.458657. Hs.730072.
3D structure databases
ProteinModelPortal	P07197.
SMR	P07197. Positions 99-136, 140-248, 264-334, 339-407.
ModBase	Search...
Protein-protein interaction databases
IntAct	P07197. 11 interactions.
STRING	P07197.
PTM databases
PhosphoSite	P07197.
Polymorphism databases
DMDM	281185500.
2D gel databases
UCD-2DPAGE	P07197.
Proteomic databases
PRIDE	P07197.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000221166; ENSP00000221166; ENSG00000104722.
GeneID	4741.
KEGG	hsa:4741.
Organism-specific databases
CTD	4741.
GeneCards	GC08P024828.
H-InvDB	HIX0034266. HIX0034491.
HGNC	HGNC:7734. NEFM.
HPA	CAB010900. CAB012976. HPA022845. HPA023138.
MIM	162250. gene.
neXtProt	NX_P07197.
PharmGKB	PA162397442.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG07994.
HOGENOM	HBG125365.
HOVERGEN	HBG013015.
InParanoid	P07197.
OMA	GPGGDYK.
OrthoDB	EOG4VMFFD.
PhylomeDB	P07197.
Gene expression databases
ArrayExpress	P07197.
Bgee	P07197.
CleanEx	HS_NEFM.
Genevestigator	P07197.
GermOnline	ENSG00000104722. Homo sapiens.
Family and domain databases
InterPro	IPR016044. F. IPR001664. IF. IPR006821. Intermed_filament_DNA-bd. IPR018039. Intermediate_filament_CS. IPR002957. Keratin_I. [Graphical view]
KO	K04573.
PANTHER	PTHR23239. IF. 1 hit.
Pfam	PF00038. Filament. 1 hit. PF04732. Filament_head. 1 hit. [Graphical view]
PRINTS	PR01248. TYPE1KERATIN.
PROSITE	PS00226. IF. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

NFM_HUMAN

Accession

Primary (citable) accession number: P07197
Secondary accession number(s): Q4QRK6

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	December 15, 2009
Last modified:	January 25, 2012
This is version 126 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.