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NMDA receptor synaptonuclear signaling and neuronal migration factor (Juxtasynaptic attractor of caldendrin on dendritic boutons protein) (Jacob protein) (Nasal embryonic luteinizing hormone-releasing hormone factor) (Nasal embryonic LHRH factor)

 NSMF_RAT                Reviewed;         532 AA.
Q9EPI6; Q5PPF6; Q7TSC6; Q7TSC8; Q9EPI4; Q9EPI5;
19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
01-MAR-2001, sequence version 1.
30-AUG-2017, entry version 92.
RecName: Full=NMDA receptor synaptonuclear signaling and neuronal migration factor;
AltName: Full=Juxtasynaptic attractor of caldendrin on dendritic boutons protein;
Short=Jacob protein;
AltName: Full=Nasal embryonic luteinizing hormone-releasing hormone factor;
Short=Nasal embryonic LHRH factor;
Name=Nsmf; Synonyms=Jac, Nelf;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
NCBI_TaxID=10116;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 4).
STRAIN=Sprague-Dawley; TISSUE=Brain;
Hoffmann B., Seidenbecher C.I., Kreutz M.R.;
"Characterization of the novel brain-specific protein Jacob.";
Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 5).
STRAIN=Wistar; TISSUE=Hippocampus;
Dieterich D.C., Landwehr M., Hoffmann B., Seidenbecher C.I.,
Kreutz M., Richter K., Smalla K.H., Dresbach T., Zuschratter W.,
Boeckers T.M., Gundelfinger E.D., Kreutz M.R.;
"Cloning and functional characterization of jacob: - Juxtasynaptic
attractor of caldendrin on dendritic boutons.";
Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Brain;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[4]
TISSUE SPECIFICITY.
PubMed=15018815; DOI=10.1016/S1567-133X(01)00004-7;
Kramer P.R., Wray S.;
"Nasal embryonic LHRH factor (NELF) expression within the CNS and PNS
of the rodent.";
Gene Expr. Patterns 1:23-26(2001).
[5]
FUNCTION, INTERACTION WITH CABP1 AND KPNA1, MYRISTOYLATION AT GLY-2,
SUBCELLULAR LOCATION, MUTAGENESIS OF GLY-2; PHE-241; 247-ARG--ARG-252
AND 260-ILE-GLN-261, AND TISSUE SPECIFICITY.
PubMed=18303947; DOI=10.1371/journal.pbio.0060034;
Dieterich D.C., Karpova A., Mikhaylova M., Zdobnova I., Konig I.,
Landwehr M., Kreutz M., Smalla K.H., Richter K., Landgraf P.,
Reissner C., Boeckers T.M., Zuschratter W., Spilker C.,
Seidenbecher C.I., Garner C.C., Gundelfinger E.D., Kreutz M.R.;
"Caldendrin-Jacob: a protein liaison that couples NMDA receptor
signalling to the nucleus.";
PLoS Biol. 6:E34-E34(2008).
[6]
PROTEOLYTIC PROCESSING, ALTERNATIVE SPLICING, SUBCELLULAR LOCATION,
AND TISSUE SPECIFICITY.
PubMed=19608740; DOI=10.1074/jbc.M109.022137;
Kindler S., Dieterich D.C., Schutt J., Sahin J., Karpova A.,
Mikhaylova M., Schob C., Gundelfinger E.D., Kreienkamp H.J.,
Kreutz M.R.;
"Dendritic mRNA targeting of Jacob and N-methyl-d-aspartate-induced
nuclear translocation after calpain-mediated proteolysis.";
J. Biol. Chem. 284:25431-25440(2009).
[7]
SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
PubMed=21364755; DOI=10.1371/journal.pone.0017276;
Behnisch T., Yuanxiang P., Bethge P., Parvez S., Chen Y., Yu J.,
Karpova A., Frey J.U., Mikhaylova M., Kreutz M.R.;
"Nuclear translocation of jacob in hippocampal neurons after stimuli
inducing long-term potentiation but not long-term depression.";
PLoS ONE 6:E17276-E17276(2011).
[8]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-292 AND SER-294, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=22673903; DOI=10.1038/ncomms1871;
Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A.,
Lundby C., Olsen J.V.;
"Quantitative maps of protein phosphorylation sites across 14
different rat organs and tissues.";
Nat. Commun. 3:876-876(2012).
-!- FUNCTION: Couples NMDA-sensitive glutamate receptor signaling to
the nucleus and triggers long-lasting changes in the
cytoarchitecture of dendrites and spine synapse processes. Part of
the cAMP response element-binding protein (CREB) shut-off
signaling pathway. Stimulates outgrowth of olfactory axons and
migration of gonadotropin-releasing hormone (GnRH) and
luteinizing-hormone-releasing hormone (LHRH) neuronal cells.
{ECO:0000269|PubMed:18303947}.
-!- SUBUNIT: Interacts with KPNA1; the interaction occurs in a
calcium-independent manner after synaptic NMDA receptor
stimulation and is required for nuclear import of NSMF but is
competed by CABP1. Interacts (via the central NLS-containing motif
region) with CABP1 (via EF-hands 1 and 2); the interaction occurs
in a calcium-dependent manner after synaptic NMDA receptor
stimulation and prevents the nuclear import of NSMF. Cannot be
competed by calmodulin. {ECO:0000269|PubMed:18303947}.
-!- INTERACTION:
P23565:Ina; NbExp=5; IntAct=EBI-6899705, EBI-6899875;
P27361:MAPK3 (xeno); NbExp=2; IntAct=EBI-6899705, EBI-73995;
-!- SUBCELLULAR LOCATION: Nucleus. Nucleus envelope. Nucleus membrane.
Nucleus matrix. Cytoplasm, cell cortex. Cytoplasm, cytoskeleton.
Cell membrane; Peripheral membrane protein. Cell projection,
dendrite. Cell junction, synapse. Cell junction, synapse,
synaptosome. Cell junction, synapse, postsynaptic cell membrane,
postsynaptic density. Membrane. Note=Found on the outside of the
luteinizing-hormone-releasing hormone (LHRH) cell membrane and
axons projecting from the olfactory pit and epithelium (By
similarity). Associates with transcriptionally active chromatin
regions. Detected at the nuclear membranes of CA1 neurons.
Cortical cytoskeleton. Localized in proximal apical dendrites.
Colocalizes with CABP1 in dendrites and dendritic spines.
Myristoylation is a prerequisite for extranuclear localization.
Translocates from dendrites to the nucleus during NMDA receptor-
dependent long-term potentiation (LTP) induction of synaptic
transmission at Schaffer collateral/CA1 synapses of hippocampal
primary neurons and in a importin-dependent manner. {ECO:0000250}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=5;
Comment=Additional isoforms seem to exist.;
Name=1;
IsoId=Q9EPI6-1; Sequence=Displayed;
Name=2;
IsoId=Q9EPI6-2; Sequence=VSP_014771;
Name=3;
IsoId=Q9EPI6-3; Sequence=VSP_014770;
Note=No experimental confirmation available.;
Name=4;
IsoId=Q9EPI6-4; Sequence=VSP_014771, VSP_014772;
Note=No experimental confirmation available.;
Name=5;
IsoId=Q9EPI6-5; Sequence=VSP_014773, VSP_014774;
Note=No experimental confirmation available.;
-!- TISSUE SPECIFICITY: Expressed in the radiatum and pyramidale
strata of the hippocampus (at protein level). Strongly expressed
in the brain. Expressed in the sensory and motor cortex,
hippocampus, olfactory bulb, thalamus and amygdala. In the
olfactory bulb expressed in the granular cell layer, mitral cell
layer and the glomerular layer. In the hippocampus highly
expressed in the regions associated with neuronal cell types as
CA1, CA2, CA3 and granule cells of the dentate gyrus. All isoforms
have been detected in the molecular layers of the hippocampus
(PubMed:19608740). {ECO:0000269|PubMed:15018815,
ECO:0000269|PubMed:18303947, ECO:0000269|PubMed:19608740,
ECO:0000269|PubMed:21364755}.
-!- PTM: Proteolytically processed after NMDA receptor activation.
Cleaved in a calcium-dependent and calpain-sensitive manner.
Calpain cleavage is essential for the translocation process from
dendrites to the nucleus. {ECO:0000269|PubMed:19608740}.
-!- MISCELLANEOUS: NSMF mRNAs expressed in the hippocampus exhibit a
prominent dendritic localization which is mediated by a dendritic
targeting element (DTE) residing in the 3'-untranslated region
(3'UTR). Transport from dendrites to the nucleus is induced by
NMDA receptor activation and results in a rapid stripping of
synaptic contacts and a reduction of dendritic complexity.
-!- SIMILARITY: Belongs to the NSMF family. {ECO:0000305}.
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution-NoDerivs License
-----------------------------------------------------------------------
EMBL; AJ293697; CAC20866.1; -; mRNA.
EMBL; AJ293698; CAC20867.1; -; mRNA.
EMBL; AJ293699; CAC20868.1; -; mRNA.
EMBL; AJ534640; CAD58977.1; -; mRNA.
EMBL; AJ534642; CAD58979.1; -; mRNA.
EMBL; BC087719; AAH87719.1; -; mRNA.
RefSeq; NP_001257555.1; NM_001270626.1.
RefSeq; NP_001257556.1; NM_001270627.1.
RefSeq; NP_001257557.1; NM_001270628.1.
RefSeq; NP_476538.2; NM_057190.2.
UniGene; Rn.7504; -.
IntAct; Q9EPI6; 4.
STRING; 10116.ENSRNOP00000058016; -.
iPTMnet; Q9EPI6; -.
PhosphoSitePlus; Q9EPI6; -.
PaxDb; Q9EPI6; -.
PRIDE; Q9EPI6; -.
GeneID; 117536; -.
KEGG; rno:117536; -.
UCSC; RGD:619819; rat. [Q9EPI6-1]
CTD; 26012; -.
RGD; 619819; Nsmf.
eggNOG; ENOG410IGJD; Eukaryota.
eggNOG; ENOG410YVK8; LUCA.
HOGENOM; HOG000231556; -.
HOVERGEN; HBG080324; -.
InParanoid; Q9EPI6; -.
PhylomeDB; Q9EPI6; -.
TreeFam; TF331286; -.
PRO; PR:Q9EPI6; -.
Proteomes; UP000002494; Unplaced.
GO; GO:0097440; C:apical dendrite; IDA:UniProtKB.
GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
GO; GO:0030863; C:cortical cytoskeleton; IDA:UniProtKB.
GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
GO; GO:0030425; C:dendrite; IDA:UniProtKB.
GO; GO:0043197; C:dendritic spine; IDA:SynGO.
GO; GO:0016020; C:membrane; IDA:UniProtKB.
GO; GO:0043005; C:neuron projection; IDA:UniProtKB.
GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
GO; GO:0005719; C:nuclear euchromatin; IDA:UniProtKB.
GO; GO:0016363; C:nuclear matrix; IDA:UniProtKB.
GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB.
GO; GO:0005634; C:nucleus; IDA:UniProtKB.
GO; GO:0043204; C:perikaryon; IDA:UniProtKB.
GO; GO:0014069; C:postsynaptic density; IDA:UniProtKB.
GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-KW.
GO; GO:0045202; C:synapse; IDA:UniProtKB.
GO; GO:0048306; F:calcium-dependent protein binding; IDA:UniProtKB.
GO; GO:0071230; P:cellular response to amino acid stimulus; IDA:UniProtKB.
GO; GO:0071257; P:cellular response to electrical stimulus; IDA:UniProtKB.
GO; GO:0071371; P:cellular response to gonadotropin stimulus; ISS:UniProtKB.
GO; GO:2001224; P:positive regulation of neuron migration; ISS:UniProtKB.
GO; GO:0035307; P:positive regulation of protein dephosphorylation; IMP:UniProtKB.
GO; GO:0099527; P:postsynapse to nucleus signaling pathway; IMP:SynGO.
GO; GO:0048814; P:regulation of dendrite morphogenesis; IMP:UniProtKB.
GO; GO:0043523; P:regulation of neuron apoptotic process; IMP:UniProtKB.
GO; GO:0048168; P:regulation of neuronal synaptic plasticity; IMP:UniProtKB.
InterPro; IPR033374; NSMF.
PANTHER; PTHR32061; PTHR32061; 1.
1: Evidence at protein level;
Alternative splicing; Cell junction; Cell membrane; Cell projection;
Complete proteome; Cytoplasm; Cytoskeleton; Lipoprotein; Membrane;
Myristate; Nucleus; Phosphoprotein; Postsynaptic cell membrane;
Reference proteome; Synapse; Synaptosome.
INIT_MET 1 1 Removed.
CHAIN 2 532 NMDA receptor synaptonuclear signaling
and neuronal migration factor.
/FTId=PRO_0000096780.
REGION 2 235 Necessary and sufficient to elicit
dendritic processes and synaptic
contacts.
MOTIF 247 252 Nuclear localization signal.
MOD_RES 206 206 Phosphoserine.
{ECO:0000250|UniProtKB:Q99NF2}.
MOD_RES 292 292 Phosphoserine.
{ECO:0000244|PubMed:22673903}.
MOD_RES 294 294 Phosphoserine.
{ECO:0000244|PubMed:22673903}.
LIPID 2 2 N-myristoyl glycine.
{ECO:0000269|PubMed:18303947}.
VAR_SEQ 238 262 Missing (in isoform 3).
{ECO:0000303|Ref.2}.
/FTId=VSP_014770.
VAR_SEQ 240 262 Missing (in isoform 2 and isoform 4).
{ECO:0000303|Ref.1}.
/FTId=VSP_014771.
VAR_SEQ 280 309 Missing (in isoform 4).
{ECO:0000303|Ref.1}.
/FTId=VSP_014772.
VAR_SEQ 310 336 SSDLQSSHCTLDEACEDLDWDTEKGLE -> TNLLQGAQGR
VHPNHHPQRRPIHHPHP (in isoform 5).
{ECO:0000303|Ref.2}.
/FTId=VSP_014773.
VAR_SEQ 337 532 Missing (in isoform 5).
{ECO:0000303|Ref.2}.
/FTId=VSP_014774.
MUTAGEN 2 2 G->A: Exclusive nuclear localization.
Shows a reduction in synaptic contacts
and dendritic processes.
{ECO:0000269|PubMed:18303947}.
MUTAGEN 241 241 F->E: Loss of CABP1 binding.
{ECO:0000269|PubMed:18303947}.
MUTAGEN 247 252 Missing: Extranuclear localization and
reduced CABP1 and KPNA1 binding. Shows a
reduction in synaptic contacts and
dendritic processes.
{ECO:0000269|PubMed:18303947}.
MUTAGEN 260 261 IQ->GG: No effect on CABP1 binding.
{ECO:0000269|PubMed:18303947}.
CONFLICT 174 174 K -> Q (in Ref. 3; AAH87719).
{ECO:0000305}.
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


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