NFL_RAT
ID NFL_RAT Reviewed; 542 AA.
AC P19527; Q63367;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Neurofilament light polypeptide;
DE Short=NF-L;
DE AltName: Full=68 kDa neurofilament protein;
DE AltName: Full=Neurofilament triplet L protein;
GN Name=Nefl; Synonyms=Nf68, Nfl;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2516804;
RA Chin S.S., Liem R.K.H.;
RT "Expression of rat neurofilament proteins NF-L and NF-M in transfected non-
RT neuronal cells.";
RL Eur. J. Cell Biol. 50:475-490(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 198-484.
RX PubMed=3925999; DOI=10.1016/0167-4781(85)90067-3;
RA Julien J.-P., Ramachandran K., Grosveld F.;
RT "Cloning of a cDNA encoding the smallest neurofilament protein from the
RT rat.";
RL Biochim. Biophys. Acta 825:398-404(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-11.
RX PubMed=7745611; DOI=10.1002/jnr.490400206;
RA Reeben M., Neuman T., Palgi J., Palm K., Paalme V., Saarma M.;
RT "Characterization of the rat light neurofilament (NF-L) gene promoter and
RT identification of NGF and cAMP responsive regions.";
RL J. Neurosci. Res. 40:177-188(1995).
RN [4]
RP PROTEIN SEQUENCE OF 2-14; 38-54; 56-84; 92-107; 117-126; 148-157; 165-172;
RP 212-224; 273-282; 285-294; 368-379; 381-391; 393-422 AND 439-463,
RP ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain, Hippocampus, and Spinal cord;
RA Lubec G., Pradeep J.J.P., Afjehi-Sadat L., Diao W., Kang S.U.;
RL Submitted (JUL-2007) to UniProtKB.
RN [5]
RP GLYCOSYLATION AT THR-21 AND SER-27.
RX PubMed=8344946; DOI=10.1016/s0021-9258(19)85471-6;
RA Dong D.L.-Y., Xu Z.-S., Chevrier M.R., Cotter R.J., Cleveland D.W.,
RA Hart G.W.;
RT "Glycosylation of mammalian neurofilaments. Localization of multiple O-
RT linked N-acetylglucosamine moieties on neurofilament polypeptides L and
RT M.";
RL J. Biol. Chem. 268:16679-16687(1993).
RN [6]
RP SUBUNIT, INTERACTION WITH NEFH; NEFM AND INA, AND TISSUE SPECIFICITY.
RX PubMed=9388258; DOI=10.1074/jbc.272.49.31073;
RA Athlan E.S., Mushynski W.E.;
RT "Heterodimeric associations between neuronal intermediate filament
RT proteins.";
RL J. Biol. Chem. 272:31073-31078(1997).
RN [7]
RP ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RA Lubec G., Chen W.-Q.;
RL Submitted (FEB-2007) to UniProtKB.
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-67; SER-103; SER-453;
RP SER-473; SER-503; THR-519; SER-522 AND SER-531, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Neurofilaments usually contain three intermediate filament
CC proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of
CC neuronal caliber. May additionally cooperate with the neuronal
CC intermediate filament proteins PRPH and INA to form neuronal
CC filamentous networks (By similarity). {ECO:0000250|UniProtKB:P08551}.
CC -!- SUBUNIT: Forms homodimers (in vitro) (PubMed:9388258). Forms
CC heterodimers with NEFH or NEFM; which can further hetero-oligomerize
CC (in vitro) (PubMed:9388258). Forms heterodimers with INA (in vitro)
CC (PubMed:9388258). Interacts with ARHGEF28. Interacts with TRIM2.
CC {ECO:0000250, ECO:0000269|PubMed:9388258}.
CC -!- SUBCELLULAR LOCATION: Cell projection, axon
CC {ECO:0000250|UniProtKB:P08551}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:P08551}.
CC -!- TISSUE SPECIFICITY: Expressed in the dorsal root ganglion neurons (at
CC protein level). {ECO:0000269|PubMed:9388258}.
CC -!- DOMAIN: The extra mass and high charge density that distinguish the
CC neurofilament proteins from all other intermediate filament proteins
CC are due to the tailpiece extensions. This region may form a charged
CC scaffolding structure suitable for interaction with other neuronal
CC components or ions.
CC -!- PTM: O-glycosylated; contains three N-acetylglucosamine side chains.
CC {ECO:0000269|PubMed:8344946}.
CC -!- PTM: Phosphorylated in the head and rod regions by the PKC kinase PKN1,
CC leading to the inhibition of polymerization. {ECO:0000250}.
CC -!- PTM: Ubiquitinated in the presence of TRIM2 and UBE2D1. {ECO:0000250}.
CC -!- MISCELLANEOUS: NF-L is the most abundant of the three neurofilament
CC proteins and, like the other nonepithelial intermediate filament
CC proteins, it can form homomeric 10-nm filaments.
CC -!- SIMILARITY: Belongs to the intermediate filament family.
CC {ECO:0000255|PROSITE-ProRule:PRU01188}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF031880; AAB87069.1; -; mRNA.
DR EMBL; M25638; AAA41694.1; -; mRNA.
DR EMBL; X53981; CAA37931.1; -; Genomic_DNA.
DR PIR; A21762; A21762.
DR PIR; I60434; I60434.
DR RefSeq; NP_113971.1; NM_031783.1.
DR AlphaFoldDB; P19527; -.
DR SMR; P19527; -.
DR BioGRID; 249778; 8.
DR DIP; DIP-1N; -.
DR IntAct; P19527; 3.
DR MINT; P19527; -.
DR STRING; 10116.ENSRNOP00000018599; -.
DR GlyConnect; 431; 1 O-Linked glycan (2 sites).
DR GlyGen; P19527; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; P19527; -.
DR PhosphoSitePlus; P19527; -.
DR SwissPalm; P19527; -.
DR World-2DPAGE; 0004:P19527; -.
DR jPOST; P19527; -.
DR PaxDb; P19527; -.
DR PRIDE; P19527; -.
DR Ensembl; ENSRNOT00000018599; ENSRNOP00000018599; ENSRNOG00000013658.
DR GeneID; 83613; -.
DR KEGG; rno:83613; -.
DR UCSC; RGD:621458; rat.
DR CTD; 4747; -.
DR RGD; 621458; Nefl.
DR eggNOG; ENOG502QSXY; Eukaryota.
DR GeneTree; ENSGT00940000156208; -.
DR HOGENOM; CLU_012560_7_3_1; -.
DR InParanoid; P19527; -.
DR OMA; YEPYYAT; -.
DR OrthoDB; 655109at2759; -.
DR PhylomeDB; P19527; -.
DR TreeFam; TF330122; -.
DR Reactome; R-RNO-438066; Unblocking of NMDA receptors, glutamate binding and activation.
DR Reactome; R-RNO-5673001; RAF/MAP kinase cascade.
DR PRO; PR:P19527; -.
DR Proteomes; UP000002494; Chromosome 15.
DR Bgee; ENSRNOG00000013658; Expressed in Ammon's horn and 8 other tissues.
DR Genevisible; P19527; RN.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0098981; C:cholinergic synapse; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030426; C:growth cone; IDA:RGD.
DR GO; GO:0005882; C:intermediate filament; ISO:RGD.
DR GO; GO:0005883; C:neurofilament; IDA:RGD.
DR GO; GO:0031594; C:neuromuscular junction; ISO:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0099160; C:postsynaptic intermediate filament cytoskeleton; ISO:RGD.
DR GO; GO:0099182; C:presynaptic intermediate filament cytoskeleton; ISO:RGD.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0043274; F:phospholipase binding; IPI:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:RGD.
DR GO; GO:0019904; F:protein domain specific binding; IPI:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISO:RGD.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; ISO:RGD.
DR GO; GO:0099184; F:structural constituent of postsynaptic intermediate filament cytoskeleton; ISO:RGD.
DR GO; GO:0008089; P:anterograde axonal transport; ISO:RGD.
DR GO; GO:0019896; P:axonal transport of mitochondrion; ISO:RGD.
DR GO; GO:0007409; P:axonogenesis; IEA:Ensembl.
DR GO; GO:0021987; P:cerebral cortex development; IEP:RGD.
DR GO; GO:0021766; P:hippocampus development; IEP:RGD.
DR GO; GO:0045110; P:intermediate filament bundle assembly; ISO:RGD.
DR GO; GO:0045109; P:intermediate filament organization; ISO:RGD.
DR GO; GO:0045105; P:intermediate filament polymerization or depolymerization; IDA:RGD.
DR GO; GO:0040011; P:locomotion; ISO:RGD.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; ISO:RGD.
DR GO; GO:0097049; P:motor neuron apoptotic process; IEA:Ensembl.
DR GO; GO:2000672; P:negative regulation of motor neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:RGD.
DR GO; GO:0033693; P:neurofilament bundle assembly; IDA:RGD.
DR GO; GO:0060052; P:neurofilament cytoskeleton organization; ISO:RGD.
DR GO; GO:0050885; P:neuromuscular process controlling balance; ISO:RGD.
DR GO; GO:0048812; P:neuron projection morphogenesis; ISO:RGD.
DR GO; GO:0014012; P:peripheral nervous system axon regeneration; ISO:RGD.
DR GO; GO:0050772; P:positive regulation of axonogenesis; ISO:RGD.
DR GO; GO:0051258; P:protein polymerization; IDA:RGD.
DR GO; GO:0031133; P:regulation of axon diameter; ISO:RGD.
DR GO; GO:1903937; P:response to acrylamide; IEP:RGD.
DR GO; GO:0051412; P:response to corticosterone; IEP:RGD.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR GO; GO:1903935; P:response to sodium arsenite; IDA:RGD.
DR GO; GO:0009636; P:response to toxic substance; IEP:RGD.
DR GO; GO:0008090; P:retrograde axonal transport; ISO:RGD.
DR GO; GO:0021510; P:spinal cord development; IEP:RGD.
DR GO; GO:0060074; P:synapse maturation; ISO:RGD.
DR InterPro; IPR018039; IF_conserved.
DR InterPro; IPR039008; IF_rod_dom.
DR InterPro; IPR006821; Intermed_filament_DNA-bd.
DR InterPro; IPR027692; NF-L.
DR PANTHER; PTHR45652:SF8; PTHR45652:SF8; 1.
DR Pfam; PF00038; Filament; 1.
DR Pfam; PF04732; Filament_head; 1.
DR SMART; SM01391; Filament; 1.
DR PROSITE; PS00226; IF_ROD_1; 1.
DR PROSITE; PS51842; IF_ROD_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cell projection; Coiled coil; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Glycoprotein; Intermediate filament;
KW Methylation; Phosphoprotein; Reference proteome; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.4, ECO:0000269|Ref.7"
FT CHAIN 2..542
FT /note="Neurofilament light polypeptide"
FT /id="PRO_0000063790"
FT DOMAIN 90..401
FT /note="IF rod"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01188"
FT REGION 2..93
FT /note="Head"
FT REGION 94..125
FT /note="Coil 1A"
FT REGION 126..138
FT /note="Linker 1"
FT REGION 139..234
FT /note="Coil 1B"
FT REGION 235..253
FT /note="Linker 12"
FT REGION 254..272
FT /note="Coil 2A"
FT REGION 273..281
FT /note="Linker 2"
FT REGION 282..397
FT /note="Coil 2B"
FT REGION 382..392
FT /note="Epitope; recognized by IF-specific monoclonal
FT antibody"
FT REGION 398..542
FT /note="Tail"
FT REGION 398..444
FT /note="Tail, subdomain A"
FT REGION 445..542
FT /note="Tail, subdomain B (acidic)"
FT REGION 451..542
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 451..470
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 471..524
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 525..542
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000269|Ref.4, ECO:0000269|Ref.7"
FT MOD_RES 23
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P08551"
FT MOD_RES 23
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P08551"
FT MOD_RES 30
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P08551"
FT MOD_RES 43
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P08551"
FT MOD_RES 56
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02548"
FT MOD_RES 67
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 103
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 453
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 473
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 503
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 519
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 522
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 531
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CARBOHYD 21
FT /note="O-linked (GlcNAc) threonine"
FT /evidence="ECO:0000269|PubMed:8344946"
FT /id="CAR_000128"
FT CARBOHYD 27
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000269|PubMed:8344946"
FT /id="CAR_000129"
FT CONFLICT 198..203
FT /note="GADEAA -> KARMSS (in Ref. 2; AAA41694)"
FT /evidence="ECO:0000305"
FT CONFLICT 400
FT /note="R -> K (in Ref. 2; AAA41694)"
FT /evidence="ECO:0000305"
FT CONFLICT 477
FT /note="A -> E (in Ref. 2; AAA41694)"
FT /evidence="ECO:0000305"
FT CONFLICT 481..484
FT /note="EKEK -> KKDE (in Ref. 2; AAA41694)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 542 AA; 61335 MW; 1FCC739AF23BCCA8 CRC64;
MSSFSYEPYF STSYKRRYVE TPRVHISSVR SGYSTARSAY SSYSAPVSSS LSVRRSYSSS
SGSLMPSLEN LDLSQVAAIS NDLKSIRTQE KAQLQDLNDR FASFIERVHE LEQQNKVLEA
ELLVLRQKHS EPSRFRALYE QEIRDLRLAA EDATNEKQAL QGEREGLEET LRNLQARYEE
EVLSREDAEG RLMEARKGAD EAALARAELE KRIDSLMDEI AFLKKVHEEE IAELQAQIQY
AQISVEMDVS SKPDLSAALK DIRAQYEKLA AKNMQNAEEW FKSRFTVLTE SAAKNTDAVR
AAKDEVSESR RLLKAKTLEI EACRGMNEAL EKQLQELEDK QNADISAMQD TINKLENELR
STKSEMARYL KEYQDLLNVK MALDIEIAAY RKLLEGEETR LSFTSVGSIT SGYSQSSQVF
GRSAYSGLQS SSYLMSARAF PAYYTSHVQE EQSEVEETIE ATKAEEAKDE PPSEGEAEEE
EKEKEEGEEE EGAEEEEAAK DESEDAKEEE GGEGEEEDTK ESEEEEKKEE SAGEEQAAKK
KD
