NEST_RAT
ID NEST_RAT Reviewed; 1893 AA.
AC P21263; Q8CJ14;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 2.
DT 25-MAY-2022, entry version 131.
DE RecName: Full=Nestin;
GN Name=Nes;
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] (ISOFORM 2).
RX PubMed=1689217; DOI=10.1016/0092-8674(90)90662-x;
RA Lendahl U., Zimmerman L.B., McKay R.D.G.;
RT "CNS stem cells express a new class of intermediate filament protein.";
RL Cell 60:585-595(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RC TISSUE=Glial tumor;
RX PubMed=12686602; DOI=10.1091/mbc.e02-08-0545;
RA Chou Y.-H., Khuon S., Herrmann H., Goldman R.D.;
RT "Nestin promotes the phosphorylation-dependent disassembly of vimentin
RT intermediate filaments during mitosis.";
RL Mol. Biol. Cell 14:1468-1478(2003).
RN [3]
RP PROTEIN SEQUENCE OF 314-319, AND PHOSPHORYLATION AT THR-316.
RX PubMed=11278541; DOI=10.1074/jbc.m009669200;
RA Sahlgren C.M., Mikhailov A., Hellman J., Chou Y.H., Lendahl U.,
RA Goldman R.D., Eriksson J.E.;
RT "Mitotic reorganization of the intermediate filament protein nestin
RT involves phosphorylation by cdc2 kinase.";
RL J. Biol. Chem. 276:16456-16463(2001).
RN [4]
RP INTERACTION WITH FHOD3.
RX PubMed=15966898; DOI=10.1111/j.1365-2443.2005.00867.x;
RA Kanaya H., Takeya R., Takeuchi K., Watanabe N., Jing N., Sumimoto H.;
RT "Fhos2, a novel formin-related actin-organizing protein, probably
RT associates with the nestin intermediate filament.";
RL Genes Cells 10:665-678(2005).
RN [5]
RP FUNCTION.
RC STRAIN=Sprague-Dawley;
RX PubMed=20510364; DOI=10.1016/j.mcn.2010.05.006;
RA Xue X.J., Yuan X.B.;
RT "Nestin is essential for mitogen-stimulated proliferation of neural
RT progenitor cells.";
RL Mol. Cell. Neurosci. 45:26-36(2010).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-620; SER-729; SER-817;
RP SER-1049; SER-1166; SER-1594; SER-1866; SER-1889 AND SER-1890, AND
RP IDENTIFICATION BY MASS 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: Required for brain and eye development (By similarity).
CC Promotes the disassembly of phosphorylated vimentin intermediate
CC filaments (IF) during mitosis and may play a role in the trafficking
CC and distribution of IF proteins and other cellular factors to daughter
CC cells during progenitor cell division. Required for survival, renewal
CC and mitogen-stimulated proliferation of neural progenitor cells.
CC {ECO:0000250, ECO:0000269|PubMed:12686602,
CC ECO:0000269|PubMed:20510364}.
CC -!- SUBUNIT: Forms homodimers and homotetramers in vitro. In mixtures with
CC other intermediate filament proteins such as vimentin and alpha-
CC internexin, this protein preferentially forms heterodimers which can
CC assemble to form intermediate filaments if nestin does not exceed 25%
CC (By similarity). Interacts with FHOD3. {ECO:0000250,
CC ECO:0000269|PubMed:15966898}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P21263-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P21263-2; Sequence=VSP_024924;
CC -!- TISSUE SPECIFICITY: CNS stem cells.
CC -!- DEVELOPMENTAL STAGE: Upon terminal neural differentiation, nestin is
CC down-regulated and replaced by neurofilaments.
CC -!- PTM: Constitutively phosphorylated. This increases during mitosis when
CC the cytoplasmic intermediate filament network is reorganized.
CC {ECO:0000269|PubMed:11278541}.
CC -!- SIMILARITY: Belongs to the intermediate filament family.
CC {ECO:0000255|PROSITE-ProRule:PRU01188}.
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DR EMBL; M34384; AAA41685.1; -; mRNA.
DR EMBL; AF538924; AAN33053.1; -; mRNA.
DR PIR; A34736; A34736.
DR AlphaFoldDB; P21263; -.
DR SMR; P21263; -.
DR IntAct; P21263; 5.
DR MINT; P21263; -.
DR STRING; 10116.ENSRNOP00000025314; -.
DR iPTMnet; P21263; -.
DR PhosphoSitePlus; P21263; -.
DR jPOST; P21263; -.
DR PaxDb; P21263; -.
DR PRIDE; P21263; -.
DR UCSC; RGD:3162; rat. [P21263-1]
DR RGD; 3162; Nes.
DR eggNOG; ENOG502RYFK; Eukaryota.
DR InParanoid; P21263; -.
DR PhylomeDB; P21263; -.
DR PRO; PR:P21263; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005882; C:intermediate filament; IDA:RGD.
DR GO; GO:0031730; F:CCR5 chemokine receptor binding; IPI:RGD.
DR GO; GO:0019215; F:intermediate filament binding; ISS:UniProtKB.
DR GO; GO:0007420; P:brain development; ISS:UniProtKB.
DR GO; GO:0048858; P:cell projection morphogenesis; ISO:RGD.
DR GO; GO:0031076; P:embryonic camera-type eye development; ISS:UniProtKB.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; ISO:RGD.
DR GO; GO:0043086; P:negative regulation of catalytic activity; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:RGD.
DR GO; GO:0032091; P:negative regulation of protein binding; ISO:RGD.
DR GO; GO:0007399; P:nervous system development; ISO:RGD.
DR GO; GO:0030182; P:neuron differentiation; NAS:RGD.
DR GO; GO:0030844; P:positive regulation of intermediate filament depolymerization; IDA:UniProtKB.
DR GO; GO:2000179; P:positive regulation of neural precursor cell proliferation; IMP:UniProtKB.
DR GO; GO:0010212; P:response to ionizing radiation; IEP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0072089; P:stem cell proliferation; ISO:RGD.
DR InterPro; IPR018039; IF_conserved.
DR InterPro; IPR039008; IF_rod_dom.
DR InterPro; IPR031211; Nestin.
DR PANTHER; PTHR47051; PTHR47051; 3.
DR Pfam; PF00038; Filament; 2.
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; Alternative splicing; Coiled coil; Developmental protein;
KW Direct protein sequencing; Intermediate filament; Isopeptide bond;
KW Neurogenesis; Phosphoprotein; Reference proteome; Ubl conjugation.
FT CHAIN 1..1893
FT /note="Nestin"
FT /id="PRO_0000063854"
FT DOMAIN 8..314
FT /note="IF rod"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01188"
FT REGION 1..7
FT /note="Head"
FT REGION 8..43
FT /note="Coil 1A"
FT REGION 44..55
FT /note="Linker 1"
FT REGION 56..151
FT /note="Coil 1B"
FT REGION 150..172
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 152..174
FT /note="Linker 12"
FT REGION 175..193
FT /note="Coil 2A"
FT REGION 194..196
FT /note="Linker 2"
FT REGION 197..314
FT /note="Coil 2B"
FT REGION 315..1893
FT /note="Tail"
FT REGION 437..479
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 507..529
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 556..879
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 949..1130
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1155..1222
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1237..1263
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1336..1369
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1388..1824
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1870..1893
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 569..593
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 607..621
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 670..706
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 713..740
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 757..879
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 980..1060
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1388..1404
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1473..1491
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1562..1576
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1631..1645
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1686..1709
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P48681"
FT MOD_RES 312
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48681"
FT MOD_RES 316
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:11278541"
FT MOD_RES 356
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48681"
FT MOD_RES 359
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48681"
FT MOD_RES 389
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P48681"
FT MOD_RES 562
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48681"
FT MOD_RES 620
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 685
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48681"
FT MOD_RES 729
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 817
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 903
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6P5H2"
FT MOD_RES 1005
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6P5H2"
FT MOD_RES 1049
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1145
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48681"
FT MOD_RES 1166
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1216
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48681"
FT MOD_RES 1229
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48681"
FT MOD_RES 1322
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48681"
FT MOD_RES 1570
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48681"
FT MOD_RES 1594
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1686
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48681"
FT MOD_RES 1695
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48681"
FT MOD_RES 1772
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48681"
FT MOD_RES 1774
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48681"
FT MOD_RES 1866
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1889
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1890
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CROSSLNK 1136
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0000250|UniProtKB:P48681"
FT CROSSLNK 1136
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P48681"
FT VAR_SEQ 736..823
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:1689217"
FT /id="VSP_024924"
FT CONFLICT 168..172
FT /note="GSPVR -> RIPGP (in Ref. 1; AAA41685)"
FT /evidence="ECO:0000305"
FT CONFLICT 425..426
FT /note="AE -> LK (in Ref. 1; AAA41685)"
FT /evidence="ECO:0000305"
FT CONFLICT 460
FT /note="T -> N (in Ref. 1; AAA41685)"
FT /evidence="ECO:0000305"
FT CONFLICT 477
FT /note="G -> E (in Ref. 1; AAA41685)"
FT /evidence="ECO:0000305"
FT CONFLICT 943
FT /note="N -> D (in Ref. 1; AAA41685)"
FT /evidence="ECO:0000305"
FT CONFLICT 1011
FT /note="R -> Q (in Ref. 1; AAA41685)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1893 AA; 208797 MW; 03AE6B616A1A7623 CRC64;
MEGCVGEESF QMWELNRRLE AYLTRVKTLE EQNQLLSAEL GGLRAQSGDT SWRARADDEL
ASLRILVDQR WREKLEAEVQ RDNLAEELES VAGRCQQVRL ARERTVQEAA CSRRALEAEK
NARGWLSTQA AELERELEAL RAAHEEERAH LNAQAACAPR RPPAPPHGSP VRAPEVEDLA
RRLGEVWRGA VRDYQERVAH MESSLGQARE RLSQAVRGAR ECRLEVQQLQ ADRDSLQERR
EALEQRLEGR WQDRLQATDK FQLAVEALEQ EKQGLQSQIA QILEGGQQLA HLKMSLSLEV
ATYRTLLEAE NSRLQTPGRG SQASLGFLDP KLKPNFLGIP EDQYLGSVLP ALSPTSFPSP
LPNTLETPVT AFLKTQEFLQ ARTPTLASTP IPPISEAPCP PNAEVRAQEV PLSLLQTQAP
EPLWAEATVP SSSAILPELE EPGGKQQGHF PDDLTSLATT LNPHHPTLEA KDGESSGSRV
SSIFQEDEGQ IWELVEKEAD IEVKVENSSA QKTQESGLDT EETQDSQGPL QKETLKALGE
EPLMSLKIQN YETAGKENCN SSTEGHLGTL EGPEKEKQIP LKSLEEKNVE SEKTLENGVP
VLSELLGKED TRTEDQELMS PKGTLKRFSS LGKESQEVVR PSKEGNLESW TAFKEESQHP
LGFPGAEDQM LERLVEKEDQ SFPRSPEEED QEACRPLQKE NQEPLGYEEA EGQILERLIE
KESQESLRSP EEEDQEAGRS LQKGNQEPLG YEEAEGQILE RLIEKESQES LRSAEEEDQE
ACRSLQKENQ EPLGYEEAED QILERLIEKE SQESLRSPEE EDQEAGRSLQ KENQEPLGYE
EAEDQMLERL IEKESQESLK SPEENQRIGK PLERENQKSL RYLEENQETF VPLESRNQRP
LRSLEVEEEE QRIVKPLEKV SQDSLGSLAE ENVQPLRYLE EDNCINKSLL EDKTHKSLGS
LEDRNGDSII IPQESETQVS LRPPEEEDQR IVNHLEKESQ EFSRSSEEEE RVMERSLEGE
NHESLSSVEK EDQMVESQLE KESQDSGKSL EDESQETFGP LEKENAESLR SLAGQDQEEQ
KLEQETQQTL RAVGNEQMAV SPPEKVDPEL PKPLGNDQEI ARSLGKENQE SLVSLKEKGI
ETVKSLETEI IEPLETAEED LERRKSIDTQ EPLWSTEVAR ETVEPPEDEP PGSLGSVDEN
RETLTSLEKE SQELSSLGKW NVETRVEDSQ QCLQVEEGLQ EEQHQESLRE VKQELPSSGN
QQRWEDVVEG KAVGQEAPLA TTGVGTEDKA ELHLRGQGGE EEAAAEGELL QDIVGEAWSL
GSSEPKEQRV PAEALDNLEG GALEVPVAQS MPEVTERDED RAQAGEQDSI EVTLGLEAAR
TGLELEQEVV GLEDPRHFAR EEAIPPSLGE ESVKAKIAQG LEGPGKEPKE AGALDSGILE
LPKTSSEALE CQGHEESESM EGWEEEEASL ETSDHEGSDA PQPRPPETEE DEGAQAALTA
PGPKLLEPCS PIPILTDAHE LQPQAEGIQE AGWQPEAGSE ALERVENEPE FGLGEIPEGL
QDWEEGREES EADDLGETLP DSTPLGLYLR SPASPKWDLA GEQRLSPQGD AGKEDWGPAV
PAAQGLSGPP EEEEEQGHGS DLSSEEFEDL GTEASLLPGV PKEVADHVGQ VPPVLQPACW
DQGGESDGFA DEEESGEEGE EEDADEEGAE SGAQWWGSGA SGGGCKVQDI AQRGDPVQES
VGVSGLWDDG LRGAAANVPA LEMVSQDSAE PSGSEESESA SLEGEEGQVT DHLDAPQEVT
SMVPGVGDAF DIGGQSPNLD SEQVNGKMEN GLEQAEGQVV LDGDEDQELL LQGQEVGALK
VPLVASPVHL GPSQPLKFTL SGVDGDSWSS GED
