ID   NFM_RAT                 Reviewed;         846 AA.
AC   P12839; Q63370;
DT   01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 4.
DT   27-MAR-2024, entry version 176.
DE   RecName: Full=Neurofilament medium polypeptide;
DE            Short=NF-M;
DE   AltName: Full=160 kDa neurofilament protein;
DE   AltName: Full=Neurofilament 3;
DE   AltName: Full=Neurofilament triplet M protein;
GN   Name=Nefm; Synonyms=Nef3, Nfm;
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=2441012;
RA   Napolitano E.W., Chin S.S.M., Colman D.R., Liem R.K.H.;
RT   "Complete amino acid sequence and in vitro expression of rat NF-M, the
RT   middle molecular weight neurofilament protein.";
RL   J. Neurosci. 7:2590-2599(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Wistar;
RX   PubMed=1321159; DOI=10.1083/jcb.118.2.397;
RA   Kelly B.M., Gillespie C.S., Sherman D.L., Brophy P.J.;
RT   "Schwann cells of the myelin-forming phenotype express neurofilament
RT   protein NF-M.";
RL   J. Cell Biol. 118:397-410(1992).
RN   [3]
RP   PROTEIN SEQUENCE OF 102-117; 139-154; 168-183; 207-216; 223-258; 352-371;
RP   391-410; 412-427; 452-461 AND 686-693, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RC   STRAIN=Sprague-Dawley; TISSUE=Brain, Hippocampus, and Spinal cord;
RA   Lubec G., Afjehi-Sadat L., Diao W., Kang S.U., Lubec S.;
RL   Submitted (SEP-2007) to UniProtKB.
RN   [4]
RP   PHOSPHORYLATION AT SER-503; SER-507; SER-537; SER-604; SER-609 AND SER-667,
RP   AND SEQUENCE REVISION TO 500.
RX   PubMed=1537832; DOI=10.1016/s0021-9258(18)42856-6;
RA   Xu Z.-S., Liu W.-S., Willard M.B.;
RT   "Identification of six phosphorylation sites in the COOH-terminal tail
RT   region of the rat neurofilament protein M.";
RL   J. Biol. Chem. 267:4467-4471(1992).
RN   [5]
RP   GLYCOSYLATION AT THR-48 AND THR-431.
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   INTERACTION WITH NEFL 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-31; SER-345; SER-417;
RP   SER-429; SER-467; SER-483; SER-503; SER-507; SER-537; SER-545; SER-550;
RP   SER-551; THR-564; SER-604; SER-609; SER-643; SER-667; SER-713; SER-721;
RP   SER-751 AND SER-767, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   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:P08553}.
CC   -!- SUBUNIT: Forms heterodimers with NEFL; which can further hetero-
CC       oligomerize (in vitro) (PubMed:9388258). Forms heterodimers with INA
CC       (in vitro) (PubMed:9388258). {ECO:0000269|PubMed:9388258}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC       {ECO:0000250|UniProtKB:P08553}. Cell projection, axon
CC       {ECO:0000250|UniProtKB:P08553}.
CC   -!- TISSUE SPECIFICITY: Expressed in the dorsal root ganglion neurons (at
CC       protein level). {ECO:0000269|PubMed:9388258}.
CC   -!- PTM: There are a number of repeats of the tripeptide K-S-P, NFM is
CC       phosphorylated on a number of the serines in this motif. It is thought
CC       that phosphorylation of NFM results in the formation of interfilament
CC       cross bridges that are important in the maintenance of axonal caliber.
CC       {ECO:0000269|PubMed:1537832}.
CC   -!- PTM: Phosphorylation seems to play a major role in the functioning of
CC       the larger neurofilament polypeptides (NF-M and NF-H), the levels of
CC       phosphorylation being altered developmentally and coincidentally with a
CC       change in the neurofilament function. {ECO:0000269|PubMed:1537832}.
CC   -!- PTM: Phosphorylated in the head and rod regions by the PKC kinase PKN1,
CC       leading to the inhibition of polymerization. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the intermediate filament family.
CC       {ECO:0000255|PROSITE-ProRule:PRU01188}.
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DR   EMBL; M18628; AAA41696.1; -; mRNA.
DR   EMBL; Z12152; CAA78136.1; -; mRNA.
DR   PIR; A45669; A45669.
DR   RefSeq; NP_058725.1; NM_017029.2.
DR   AlphaFoldDB; P12839; -.
DR   SMR; P12839; -.
DR   BioGRID; 246731; 6.
DR   DIP; DIP-208N; -.
DR   IntAct; P12839; 2.
DR   MINT; P12839; -.
DR   STRING; 10116.ENSRNOP00000018637; -.
DR   GlyConnect; 432; 1 O-GlcNAc glycan (2 sites).
DR   GlyCosmos; P12839; 2 sites, 1 glycan.
DR   GlyGen; P12839; 4 sites, 1 O-linked glycan (4 sites).
DR   iPTMnet; P12839; -.
DR   PhosphoSitePlus; P12839; -.
DR   jPOST; P12839; -.
DR   PaxDb; 10116-ENSRNOP00000065853; -.
DR   GeneID; 24588; -.
DR   KEGG; rno:24588; -.
DR   UCSC; RGD:3160; rat.
DR   AGR; RGD:3160; -.
DR   RGD; 3160; Nefm.
DR   eggNOG; KOG1216; Eukaryota.
DR   InParanoid; P12839; -.
DR   OrthoDB; 4640531at2759; -.
DR   PhylomeDB; P12839; -.
DR   PRO; PR:P12839; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0030424; C:axon; IDA:BHF-UCL.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005856; C:cytoskeleton; IDA:UniProtKB.
DR   GO; GO:0005882; C:intermediate filament; IDA:RGD.
DR   GO; GO:0097418; C:neurofibrillary tangle; 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; ISO:RGD.
DR   GO; GO:0043204; C:perikaryon; IDA:RGD.
DR   GO; GO:0014069; C:postsynaptic density; ISO: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:0044877; F:protein-containing complex binding; IDA:RGD.
DR   GO; GO:0005102; F:signaling receptor binding; IPI:RGD.
DR   GO; GO:0005200; F:structural constituent of cytoskeleton; IBA:GO_Central.
DR   GO; GO:0015643; F:toxic substance binding; IDA:RGD.
DR   GO; GO:0008088; P:axo-dendritic transport; ISO:RGD.
DR   GO; GO:0031103; P:axon regeneration; IEP:RGD.
DR   GO; GO:0071392; P:cellular response to estradiol stimulus; IEP:RGD.
DR   GO; GO:0034599; P:cellular response to oxidative stress; IEP:RGD.
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:0045104; P:intermediate filament cytoskeleton organization; ISO:RGD.
DR   GO; GO:0045105; P:intermediate filament polymerization or depolymerization; IDA:RGD.
DR   GO; GO:0000226; P:microtubule cytoskeleton organization; 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:0031133; P:regulation of axon diameter; ISO:RGD.
DR   GO; GO:1903937; P:response to acrylamide; IEP:RGD.
DR   GO; GO:0021510; P:spinal cord development; IEP:RGD.
DR   Gene3D; 1.20.5.170; -; 1.
DR   Gene3D; 1.20.5.500; Single helix bin; 1.
DR   Gene3D; 1.20.5.1160; Vasodilator-stimulated phosphoprotein; 1.
DR   InterPro; IPR018039; IF_conserved.
DR   InterPro; IPR039008; IF_rod_dom.
DR   InterPro; IPR006821; Intermed_filament_DNA-bd.
DR   InterPro; IPR002957; Keratin_I.
DR   PANTHER; PTHR45652; GLIAL FIBRILLARY ACIDIC PROTEIN; 1.
DR   PANTHER; PTHR45652:SF3; NEUROFILAMENT MEDIUM POLYPEPTIDE; 1.
DR   Pfam; PF00038; Filament; 1.
DR   Pfam; PF04732; Filament_head; 1.
DR   PRINTS; PR01248; TYPE1KERATIN.
DR   SMART; SM01391; Filament; 1.
DR   SUPFAM; SSF64593; Intermediate filament protein, coiled coil region; 2.
DR   PROSITE; PS00226; IF_ROD_1; 1.
DR   PROSITE; PS51842; IF_ROD_2; 1.
DR   World-2DPAGE; 0004:P12839; -.
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.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|Ref.7"
FT   CHAIN           2..846
FT                   /note="Neurofilament medium polypeptide"
FT                   /id="PRO_0000063798"
FT   DOMAIN          100..411
FT                   /note="IF rod"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01188"
FT   REGION          1..52
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2..104
FT                   /note="Head"
FT   REGION          104..135
FT                   /note="Coil 1A"
FT   REGION          136..148
FT                   /note="Linker 1"
FT   REGION          149..247
FT                   /note="Coil 1B"
FT   REGION          248..264
FT                   /note="Linker 12"
FT   REGION          265..286
FT                   /note="Coil 2A"
FT   REGION          287..290
FT                   /note="Linker 2"
FT   REGION          291..411
FT                   /note="Coil 2B"
FT   REGION          412..845
FT                   /note="Tail"
FT   REGION          483..783
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        498..513
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        514..537
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        538..552
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        553..572
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        573..678
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        686..734
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        768..783
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.7"
FT   MOD_RES         31
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         43
FT                   /note="Omega-N-methylarginine"
FT                   /evidence="ECO:0000250|UniProtKB:P08553"
FT   MOD_RES         98
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P08553"
FT   MOD_RES         225
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P08553"
FT   MOD_RES         319
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P08553"
FT   MOD_RES         345
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         417
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         429
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         467
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         483
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         503
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:1537832,
FT                   ECO:0007744|PubMed:22673903"
FT   MOD_RES         507
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:1537832,
FT                   ECO:0007744|PubMed:22673903"
FT   MOD_RES         537
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:1537832,
FT                   ECO:0007744|PubMed:22673903"
FT   MOD_RES         545
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         550
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         551
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         564
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         604
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:1537832,
FT                   ECO:0007744|PubMed:22673903"
FT   MOD_RES         609
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:1537832,
FT                   ECO:0007744|PubMed:22673903"
FT   MOD_RES         643
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         667
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:1537832,
FT                   ECO:0007744|PubMed:22673903"
FT   MOD_RES         687
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O77788"
FT   MOD_RES         713
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         721
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         751
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         767
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   CARBOHYD        48
FT                   /note="O-linked (GlcNAc) threonine"
FT                   /evidence="ECO:0000269|PubMed:8344946"
FT                   /id="CAR_000130"
FT   CARBOHYD        431
FT                   /note="O-linked (GlcNAc) threonine"
FT                   /evidence="ECO:0000269|PubMed:8344946"
FT                   /id="CAR_000131"
FT   CONFLICT        18
FT                   /note="Missing (in Ref. 2; CAA78136)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        22
FT                   /note="R -> P (in Ref. 2; CAA78136)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        205
FT                   /note="V -> L (in Ref. 2; CAA78136)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        501
FT                   /note="Missing (in Ref. 1; AAA41696)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   846 AA;  95791 MW;  14DE91A1D1F68EC8 CRC64;
     MSYTLDSLGN PSAYRRVPTE TRSSFSRVSG SPSSGFRSQS WSRGSPSTVS SSYKRSALAP
     RLAYSSAMLS SAESSLDFSQ SSSLLNGGSG GDYKLSRSNE KEQLQGLNDR FAGYIEKVHY
     LEQQNKEIEA EIHALRQKQA SHAQLGDAYD QEIRELRATL EMVNHEKAQV QLDSDHLEED
     IHRLKERFEE EARLRDDTEA AIRAVRKDIE ESSMVKVELD KKVQSLQDEV AFLRSNHEEE
     VADLLAQIQA SHITVERKDY LKTDISTALK EIRSQLECHS DQNMHQAEEW FKCRYAKLTE
     AAEQNKEAIR SAKEEIAEYR RQLQSKSIEL ESVRGTKESL ERQLSDIEER HNHDLSSYQD
     TIQQLENELR GTKWEMARHL REYQDLLNVK MALDIEIAAY RKLLEGEETR FSTFSGSITG
     PLYTHRQPSV TISSKIQKTK VEAPKLKVQH KFVEEIIEET KVEDEKSEME DALTVIAEEL
     AASAKEEKEE AEEKEEEPEV EKSPVKSPEA KEEEEGEKEE EEEGQEEEEE EDEGVKSDQA
     EEGGSEKEGS SEKDEGEQEE EGETEAEGEG EEAEAKEEKK TEGKVEEMAI KEEIKVEKPE
     KAKSPVPKSP VEEVKPKPEA KAGKDEQKEE EKVEEKKEVA KESPKEEKVE KKEEKPKDVP
     DKKKAESPVK EKAVEEMITI TKSVKVSLEK DTKEEKPQQQ EKVKEKAEEE GGSEEEVGDK
     SPQESKKEDI AINGEVEGKE EEEQETQEKG SGQEEEKGVV TNGLDVSPAE EKKGEDRSDD
     KVVVTKKVEK ITSEGGDGAT KYITKSVTVT QKVEEHEETF EEKLVSTKKV EKVTSHAIVK
     EVTQGD
//