NSMF_RAT
ID NSMF_RAT Reviewed; 532 AA.
AC Q9EPI6; Q5PPF6; Q7TSC6; Q7TSC8; Q9EPI4; Q9EPI5;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=NMDA receptor synaptonuclear signaling and neuronal migration factor;
DE AltName: Full=Juxtasynaptic attractor of caldendrin on dendritic boutons protein;
DE Short=Jacob protein;
DE AltName: Full=Nasal embryonic luteinizing hormone-releasing hormone factor;
DE Short=Nasal embryonic LHRH factor;
GN Name=Nsmf; Synonyms=Jac, Nelf;
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] (ISOFORMS 1; 2 AND 4).
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Hoffmann B., Seidenbecher C.I., Kreutz M.R.;
RT "Characterization of the novel brain-specific protein Jacob.";
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 5).
RC STRAIN=Wistar; TISSUE=Hippocampus;
RA Dieterich D.C., Landwehr M., Hoffmann B., Seidenbecher C.I., Kreutz M.,
RA Richter K., Smalla K.H., Dresbach T., Zuschratter W., Boeckers T.M.,
RA Gundelfinger E.D., Kreutz M.R.;
RT "Cloning and functional characterization of jacob: - Juxtasynaptic
RT attractor of caldendrin on dendritic boutons.";
RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=15018815; DOI=10.1016/s1567-133x(01)00004-7;
RA Kramer P.R., Wray S.;
RT "Nasal embryonic LHRH factor (NELF) expression within the CNS and PNS of
RT the rodent.";
RL Gene Expr. Patterns 1:23-26(2001).
RN [5]
RP FUNCTION, INTERACTION WITH CABP1 AND KPNA1, MYRISTOYLATION AT GLY-2,
RP SUBCELLULAR LOCATION, MUTAGENESIS OF GLY-2; PHE-241; 247-ARG--ARG-252 AND
RP 260-ILE-GLN-261, AND TISSUE SPECIFICITY.
RX PubMed=18303947; DOI=10.1371/journal.pbio.0060034;
RA Dieterich D.C., Karpova A., Mikhaylova M., Zdobnova I., Konig I.,
RA Landwehr M., Kreutz M., Smalla K.H., Richter K., Landgraf P., Reissner C.,
RA Boeckers T.M., Zuschratter W., Spilker C., Seidenbecher C.I., Garner C.C.,
RA Gundelfinger E.D., Kreutz M.R.;
RT "Caldendrin-Jacob: a protein liaison that couples NMDA receptor signalling
RT to the nucleus.";
RL PLoS Biol. 6:E34-E34(2008).
RN [6]
RP PROTEOLYTIC PROCESSING, ALTERNATIVE SPLICING, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=19608740; DOI=10.1074/jbc.m109.022137;
RA Kindler S., Dieterich D.C., Schutt J., Sahin J., Karpova A., Mikhaylova M.,
RA Schob C., Gundelfinger E.D., Kreienkamp H.J., Kreutz M.R.;
RT "Dendritic mRNA targeting of Jacob and N-methyl-d-aspartate-induced nuclear
RT translocation after calpain-mediated proteolysis.";
RL J. Biol. Chem. 284:25431-25440(2009).
RN [7]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=21364755; DOI=10.1371/journal.pone.0017276;
RA Behnisch T., Yuanxiang P., Bethge P., Parvez S., Chen Y., Yu J.,
RA Karpova A., Frey J.U., Mikhaylova M., Kreutz M.R.;
RT "Nuclear translocation of jacob in hippocampal neurons after stimuli
RT inducing long-term potentiation but not long-term depression.";
RL PLoS ONE 6:E17276-E17276(2011).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-292 AND SER-294, 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: Couples NMDA-sensitive glutamate receptor signaling to the
CC nucleus and triggers long-lasting changes in the cytoarchitecture of
CC dendrites and spine synapse processes. Part of the cAMP response
CC element-binding protein (CREB) shut-off signaling pathway. Stimulates
CC outgrowth of olfactory axons and migration of gonadotropin-releasing
CC hormone (GnRH) and luteinizing-hormone-releasing hormone (LHRH)
CC neuronal cells. {ECO:0000269|PubMed:18303947}.
CC -!- SUBUNIT: Interacts with KPNA1; the interaction occurs in a calcium-
CC independent manner after synaptic NMDA receptor stimulation and is
CC required for nuclear import of NSMF but is competed by CABP1. Interacts
CC (via the central NLS-containing motif region) with CABP1 (via EF-hands
CC 1 and 2); the interaction occurs in a calcium-dependent manner after
CC synaptic NMDA receptor stimulation and prevents the nuclear import of
CC NSMF. Cannot be competed by calmodulin. {ECO:0000269|PubMed:18303947}.
CC -!- INTERACTION:
CC Q9EPI6; P23565: Ina; NbExp=5; IntAct=EBI-6899705, EBI-6899875;
CC Q9EPI6; P27361: MAPK3; Xeno; NbExp=2; IntAct=EBI-6899705, EBI-73995;
CC Q9EPI6-1; O88751-1: Cabp1; NbExp=4; IntAct=EBI-15688762, EBI-15688755;
CC -!- SUBCELLULAR LOCATION: Nucleus. Nucleus envelope. Nucleus membrane.
CC Nucleus matrix. Cytoplasm, cell cortex. Cytoplasm, cytoskeleton. Cell
CC membrane; Peripheral membrane protein. Cell projection, dendrite.
CC Synapse. Synapse, synaptosome. Postsynaptic density. Membrane.
CC Note=Found on the outside of the luteinizing-hormone-releasing hormone
CC (LHRH) cell membrane and axons projecting from the olfactory pit and
CC epithelium (By similarity). Associates with transcriptionally active
CC chromatin regions. Detected at the nuclear membranes of CA1 neurons.
CC Cortical cytoskeleton. Localized in proximal apical dendrites.
CC Colocalizes with CABP1 in dendrites and dendritic spines.
CC Myristoylation is a prerequisite for extranuclear localization.
CC Translocates from dendrites to the nucleus during NMDA receptor-
CC dependent long-term potentiation (LTP) induction of synaptic
CC transmission at Schaffer collateral/CA1 synapses of hippocampal primary
CC neurons and in an importin-dependent manner. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=Q9EPI6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9EPI6-2; Sequence=VSP_014771;
CC Name=3;
CC IsoId=Q9EPI6-3; Sequence=VSP_014770;
CC Name=4;
CC IsoId=Q9EPI6-4; Sequence=VSP_014771, VSP_014772;
CC Name=5;
CC IsoId=Q9EPI6-5; Sequence=VSP_014773, VSP_014774;
CC -!- TISSUE SPECIFICITY: Expressed in the radiatum and pyramidale strata of
CC the hippocampus (at protein level). Strongly expressed in the brain.
CC Expressed in the sensory and motor cortex, hippocampus, olfactory bulb,
CC thalamus and amygdala. In the olfactory bulb expressed in the granular
CC cell layer, mitral cell layer and the glomerular layer. In the
CC hippocampus highly expressed in the regions associated with neuronal
CC cell types as CA1, CA2, CA3 and granule cells of the dentate gyrus. All
CC isoforms have been detected in the molecular layers of the hippocampus
CC (PubMed:19608740). {ECO:0000269|PubMed:15018815,
CC ECO:0000269|PubMed:18303947, ECO:0000269|PubMed:19608740,
CC ECO:0000269|PubMed:21364755}.
CC -!- PTM: Proteolytically processed after NMDA receptor activation. Cleaved
CC in a calcium-dependent and calpain-sensitive manner. Calpain cleavage
CC is essential for the translocation process from dendrites to the
CC nucleus. {ECO:0000269|PubMed:19608740}.
CC -!- MISCELLANEOUS: NSMF mRNAs expressed in the hippocampus exhibit a
CC prominent dendritic localization which is mediated by a dendritic
CC targeting element (DTE) residing in the 3'-untranslated region (3'UTR).
CC Transport from dendrites to the nucleus is induced by NMDA receptor
CC activation and results in a rapid stripping of synaptic contacts and a
CC reduction of dendritic complexity.
CC -!- SIMILARITY: Belongs to the NSMF family. {ECO:0000305}.
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DR EMBL; AJ293697; CAC20866.1; -; mRNA.
DR EMBL; AJ293698; CAC20867.1; -; mRNA.
DR EMBL; AJ293699; CAC20868.1; -; mRNA.
DR EMBL; AJ534640; CAD58977.1; -; mRNA.
DR EMBL; AJ534642; CAD58979.1; -; mRNA.
DR EMBL; BC087719; AAH87719.1; -; mRNA.
DR RefSeq; NP_001257555.1; NM_001270626.1.
DR RefSeq; NP_001257556.1; NM_001270627.1.
DR RefSeq; NP_001257557.1; NM_001270628.1.
DR RefSeq; NP_476538.2; NM_057190.2.
DR AlphaFoldDB; Q9EPI6; -.
DR SMR; Q9EPI6; -.
DR BioGRID; 250751; 3.
DR IntAct; Q9EPI6; 7.
DR MINT; Q9EPI6; -.
DR STRING; 10116.ENSRNOP00000058016; -.
DR iPTMnet; Q9EPI6; -.
DR PhosphoSitePlus; Q9EPI6; -.
DR PaxDb; Q9EPI6; -.
DR PRIDE; Q9EPI6; -.
DR GeneID; 117536; -.
DR KEGG; rno:117536; -.
DR UCSC; RGD:619819; rat. [Q9EPI6-1]
DR CTD; 26012; -.
DR RGD; 619819; Nsmf.
DR eggNOG; ENOG502QRME; Eukaryota.
DR InParanoid; Q9EPI6; -.
DR OrthoDB; 611342at2759; -.
DR PhylomeDB; Q9EPI6; -.
DR TreeFam; TF331286; -.
DR PRO; PR:Q9EPI6; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0097440; C:apical dendrite; IDA:UniProtKB.
DR GO; GO:0030863; C:cortical cytoskeleton; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; IDA:SynGO.
DR GO; GO:0000791; C:euchromatin; IDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IDA:UniProtKB.
DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
DR GO; GO:0016363; C:nuclear matrix; IDA:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0098794; C:postsynapse; IDA:SynGO.
DR GO; GO:0014069; C:postsynaptic density; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IDA:UniProtKB.
DR GO; GO:0048306; F:calcium-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IDA:UniProtKB.
DR GO; GO:0071257; P:cellular response to electrical stimulus; IDA:UniProtKB.
DR GO; GO:0071371; P:cellular response to gonadotropin stimulus; ISS:UniProtKB.
DR GO; GO:2001224; P:positive regulation of neuron migration; ISS:UniProtKB.
DR GO; GO:0035307; P:positive regulation of protein dephosphorylation; IMP:UniProtKB.
DR GO; GO:0099527; P:postsynapse to nucleus signaling pathway; IDA:SynGO.
DR GO; GO:0048814; P:regulation of dendrite morphogenesis; IMP:UniProtKB.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; IMP:UniProtKB.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; IMP:UniProtKB.
DR InterPro; IPR033374; NSMF.
DR PANTHER; PTHR32061; PTHR32061; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell projection; Cytoplasm;
KW Cytoskeleton; Lipoprotein; Membrane; Myristate; Nucleus; Phosphoprotein;
KW Reference proteome; Synapse; Synaptosome.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..532
FT /note="NMDA receptor synaptonuclear signaling and neuronal
FT migration factor"
FT /id="PRO_0000096780"
FT REGION 2..235
FT /note="Necessary and sufficient to elicit dendritic
FT processes and synaptic contacts"
FT REGION 34..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 127..174
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 275..315
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 247..252
FT /note="Nuclear localization signal"
FT COMPBIAS 141..164
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 206
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99NF2"
FT MOD_RES 292
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 294
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:18303947"
FT VAR_SEQ 238..262
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_014770"
FT VAR_SEQ 240..262
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_014771"
FT VAR_SEQ 280..309
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_014772"
FT VAR_SEQ 310..336
FT /note="SSDLQSSHCTLDEACEDLDWDTEKGLE -> TNLLQGAQGRVHPNHHPQRRP
FT IHHPHP (in isoform 5)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_014773"
FT VAR_SEQ 337..532
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_014774"
FT MUTAGEN 2
FT /note="G->A: Exclusive nuclear localization. Shows a
FT reduction in synaptic contacts and dendritic processes."
FT /evidence="ECO:0000269|PubMed:18303947"
FT MUTAGEN 241
FT /note="F->E: Loss of CABP1 binding."
FT /evidence="ECO:0000269|PubMed:18303947"
FT MUTAGEN 247..252
FT /note="Missing: Extranuclear localization and reduced CABP1
FT and KPNA1 binding. Shows a reduction in synaptic contacts
FT and dendritic processes."
FT /evidence="ECO:0000269|PubMed:18303947"
FT MUTAGEN 260..261
FT /note="IQ->GG: No effect on CABP1 binding."
FT /evidence="ECO:0000269|PubMed:18303947"
FT CONFLICT 174
FT /note="K -> Q (in Ref. 3; AAH87719)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 532 AA; 60282 MW; 01AEF4B6A09EB753 CRC64;
MGAAASRRRA LRSEAMSSVA AKVRAARAFG EYLSQSHPEN RNGADHLLAD AYSGHEGSPE
MQPAPHNKRR LSLVSNGRYE GSISDEAVSG KTATEGPQPR VYTISREPAL LPGSEAEAIE
LAVVKGRRQR ERHPHHHSQP LRASPGSSRE DISRPCQSWA GSRQGSKECP GCAKLVPGPS
PRAFGLEQPP LPEASGRHKK LERMYSVDGV SDDVPIRTWF PKENPFSFQT ATTTMQAISV
FRGYAERKRR KRENDSASVI QRNFRKHLRM VGSRRVKAQT FAERRERSFS RSWSDPTPMK
ADTSHDSRDS SDLQSSHCTL DEACEDLDWD TEKGLEATAC DTEGFLPPKV MLISSKVPKA
EYIPTIIRRD DPSIIPILYD HEHATFEDIL EEIEKKLNIY HKGAKIWKML IFCQGGPGHL
YLLKNKVATF AKVEKEEDMI HFWKRLSRLM SKVNPEPNVI HIMGCYILGN PNGEKLFQNL
RTLMTPYKVT FESPLELSAQ GKQMIETYFD FRLYRLWKSR QHSKLLDFDD VL
