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Protein

NMDA receptor synaptonuclear signaling and neuronal migration factor

Gene

NSMF

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.1 Publication

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 (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Names & Taxonomyi

Protein namesi
Recommended name:
NMDA receptor synaptonuclear signaling and neuronal migration factor
Alternative name(s):
Nasal embryonic luteinizing hormone-releasing hormone factor
Short name:
Nasal embryonic LHRH factor
Gene namesi
Name:NSMF
Synonyms:NELF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000165802.19
HGNCiHGNC:29843 NSMF
MIMi608137 gene
neXtProtiNX_Q6X4W1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, Nucleus, Postsynaptic cell membrane, Synapse, Synaptosome

Pathology & Biotechi

Involvement in diseasei

Hypogonadotropic hypogonadism 9 with or without anosmia (HH9)3 Publications
The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. The genetics of hypogonadotropic hypogonadism involves various modes of transmission. Oligogenic inheritance has been reported in some patients carrying mutations in NSMF as well as in other HH-associated genes including FGFR1 (PubMed:23643382).1 Publication
Disease descriptionA disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
See also OMIM:614838
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069967196R → H in HH9; phenotype consistent with Kallmann syndrome; the patient also carries a mutation in FGFR1. 1 PublicationCorresponds to variant dbSNP:rs770597015Ensembl.1
Natural variantiVAR_023003480T → A in HH9; sporadic case. 2 PublicationsCorresponds to variant dbSNP:rs121918340EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi247 – 250RRKR → AAKA: Localizes predominantly in the cytoplasm. 1 Publication4
Mutagenesisi263 – 264RK → AA: Localizes both in the cytoplasm and the nucleus. 1 Publication2

Keywords - Diseasei

Disease mutation, Hypogonadotropic hypogonadism, Kallmann syndrome

Organism-specific databases

DisGeNETi26012
MalaCardsiNSMF
MIMi614838 phenotype
OpenTargetsiENSG00000165802
Orphaneti478 Kallmann syndrome
432 Normosmic congenital hypogonadotropic hypogonadism
PharmGKBiPA134917144

Polymorphism and mutation databases

BioMutaiNSMF
DMDMi71152011

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved
ChainiPRO_00000967782 – 530NMDA receptor synaptonuclear signaling and neuronal migration factorAdd BLAST529

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1
Modified residuei204PhosphoserineBy similarity1
Modified residuei290PhosphoserineBy similarity1
Modified residuei292PhosphoserineBy similarity1

Post-translational modificationi

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 (By similarity).By similarity

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

PaxDbiQ6X4W1
PeptideAtlasiQ6X4W1
PRIDEiQ6X4W1
ProteomicsDBi67783
67784 [Q6X4W1-2]
67785 [Q6X4W1-3]
67786 [Q6X4W1-4]
67787 [Q6X4W1-5]
67788 [Q6X4W1-6]

PTM databases

iPTMnetiQ6X4W1
PhosphoSitePlusiQ6X4W1

Expressioni

Tissue specificityi

Highly expressed in adult and fetal brain. Weakly expressed in heart, liver, spleen, testis, small intestine, skeletal muscle, peripheral white blood cells and kidney.2 Publications

Gene expression databases

BgeeiENSG00000165802
ExpressionAtlasiQ6X4W1 baseline and differential
GenevisibleiQ6X4W1 HS

Organism-specific databases

HPAiHPA044316

Interactioni

Subunit structurei

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 (By similarity).By similarity

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi117485, 8 interactors
IntActiQ6X4W1, 17 interactors
STRINGi9606.ENSP00000360530

Structurei

3D structure databases

ProteinModelPortaliQ6X4W1
SMRiQ6X4W1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 233Necessary and sufficient to elicit dendritic processes and synaptic contactsBy similarityAdd BLAST232

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi247 – 250Nuclear localization signal4

Sequence similaritiesi

Belongs to the NSMF family.Curated

Phylogenomic databases

eggNOGiENOG410IGJD Eukaryota
ENOG410YVK8 LUCA
GeneTreeiENSGT00390000000459
HOGENOMiHOG000231556
HOVERGENiHBG080324
InParanoidiQ6X4W1
OMAiSRPCQSW
OrthoDBiEOG091G05OV
PhylomeDBiQ6X4W1
TreeFamiTF331286

Family and domain databases

InterProiView protein in InterPro
IPR033374 NSMF
PANTHERiPTHR32061 PTHR32061, 1 hit

Sequences (6)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6X4W1-1) [UniParc]FASTAAdd to basket
Also known as: NELF-v1

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGAAASRRRA LRSEAMSSVA AKVRAARAFG EYLSQSHPEN RNGADHLLAD
60 70 80 90 100
AYSGHDGSPE MQPAPQNKRR LSLVSNGCYE GSLSEEPSIR KPAGEGPQPR
110 120 130 140 150
VYTISGEPAL LPSPEAEAIE LAVVKGRRQR HPHHHSQPLR ASPGGSREDV
160 170 180 190 200
SRPCQSWAGS RQGSKECPGC AQLAPGPTPR AFGLDQPPLP ETSGRRKKLE
210 220 230 240 250
RMYSVDRVSD DIPIRTWFPK ENLFSFQTAT TTMQAISVFR GYAERKRRKR
260 270 280 290 300
ENDSASVIQR NFRKHLRMVG SRRVKAQTFA ERRERSFSRS WSDPTPMKAD
310 320 330 340 350
TSHDSRDSSD LQSSHCTLDE AFEDLDWDTE KGLEAVACDT EGFVPPKVML
360 370 380 390 400
ISSKVPKAEY IPTIIRRDDP SIIPILYDHE HATFEDILEE IERKLNVYHK
410 420 430 440 450
GAKIWKMLIF CQGGPGHLYL LKNKVATFAK VEKEEDMIHF WKRLSRLMSK
460 470 480 490 500
VNPEPNVIHI MGCYILGNPN GEKLFQNLRT LMTPYRVTFE SPLELSAQGK
510 520 530
QMIETYFDFR LYRLWKSRQH SKLLDFDDVL
Length:530
Mass (Da):60,143
Last modified:July 5, 2004 - v1
Checksum:i7A18FDFD1F21A2D9
GO
Isoform 2 (identifier: Q6X4W1-2) [UniParc]FASTAAdd to basket
Also known as: NELF-v2

The sequence of this isoform differs from the canonical sequence as follows:
     236-237: Missing.

Show »
Length:528
Mass (Da):59,943
Checksum:i5F5BBEF6D681ABAB
GO
Isoform 3 (identifier: Q6X4W1-3) [UniParc]FASTAAdd to basket
Also known as: NELF-v3

The sequence of this isoform differs from the canonical sequence as follows:
     238-260: Missing.

Show »
Length:507
Mass (Da):57,339
Checksum:i66450F7F89841040
GO
Isoform 4 (identifier: Q6X4W1-4) [UniParc]FASTAAdd to basket
Also known as: NELF-v4

The sequence of this isoform differs from the canonical sequence as follows:
     278-307: Missing.

Show »
Length:500
Mass (Da):56,604
Checksum:i331136550FAD1DF0
GO
Isoform 5 (identifier: Q6X4W1-5) [UniParc]FASTAAdd to basket
Also known as: NELF-v5

The sequence of this isoform differs from the canonical sequence as follows:
     350-402: LISSKVPKAE...RKLNVYHKGA → VRPSPGSAPL...IPLGCLAARR
     403-530: Missing.

Show »
Length:402
Mass (Da):44,280
Checksum:i1D190ADD1D48A2EA
GO
Isoform 6 (identifier: Q6X4W1-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     236-237: Missing.
     238-260: Missing.

Note: No experimental confirmation available.
Show »
Length:505
Mass (Da):57,139
Checksum:i62E57810A53AC45E
GO

Sequence cautioni

The sequence BAB55139 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAI14577 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAI14578 differs from that shown. Reason: Erroneous gene model prediction.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069967196R → H in HH9; phenotype consistent with Kallmann syndrome; the patient also carries a mutation in FGFR1. 1 PublicationCorresponds to variant dbSNP:rs770597015Ensembl.1
Natural variantiVAR_023003480T → A in HH9; sporadic case. 2 PublicationsCorresponds to variant dbSNP:rs121918340EnsemblClinVar.1
Natural variantiVAR_059699511L → V. Corresponds to variant dbSNP:rs34177733Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_014759236 – 237Missing in isoform 2 and isoform 6. 3 Publications2
Alternative sequenceiVSP_014760238 – 260Missing in isoform 3 and isoform 6. 2 PublicationsAdd BLAST23
Alternative sequenceiVSP_014761278 – 307Missing in isoform 4. 1 PublicationAdd BLAST30
Alternative sequenceiVSP_014762350 – 402LISSK…YHKGA → VRPSPGSAPLHPEQDSAPTR VQPALPGTTQPSPAAWGRVS HRAIPLGCLAARR in isoform 5. 1 PublicationAdd BLAST53
Alternative sequenceiVSP_014763403 – 530Missing in isoform 5. 1 PublicationAdd BLAST128

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY255128 mRNA Translation: AAP83576.1
AY255129 mRNA Translation: AAP83577.1
AY255130 mRNA Translation: AAP83578.1
AY255131 mRNA Translation: AAP83579.1
AY255132 mRNA Translation: AAP83580.1
AK027474 mRNA Translation: BAB55139.1 Different initiation.
AK074602 mRNA Translation: BAC11086.1
AL365502 Genomic DNA Translation: CAI14577.1 Sequence problems.
AL365502 Genomic DNA Translation: CAI14578.1 Sequence problems.
BC072412 mRNA Translation: AAH72412.1
BC110498 mRNA Translation: AAI10499.1
AL389944 mRNA Translation: CAB97524.1
AL389946 mRNA Translation: CAB97525.1
AL389945 mRNA Translation: CAB97542.1
CCDSiCCDS48067.1 [Q6X4W1-6]
CCDS48068.1 [Q6X4W1-3]
CCDS48069.1 [Q6X4W1-1]
CCDS55357.1 [Q6X4W1-4]
CCDS7044.1 [Q6X4W1-2]
PIRiT17341
RefSeqiNP_001124441.1, NM_001130969.1 [Q6X4W1-1]
NP_001124442.1, NM_001130970.1 [Q6X4W1-3]
NP_001124443.1, NM_001130971.1 [Q6X4W1-6]
NP_001171535.1, NM_001178064.1 [Q6X4W1-4]
NP_056352.3, NM_015537.4 [Q6X4W1-2]
UniGeneiHs.455336

Genome annotation databases

EnsembliENST00000265663; ENSP00000265663; ENSG00000165802 [Q6X4W1-2]
ENST00000371472; ENSP00000360527; ENSG00000165802 [Q6X4W1-2]
ENST00000371473; ENSP00000360528; ENSG00000165802 [Q6X4W1-4]
ENST00000371474; ENSP00000360529; ENSG00000165802 [Q6X4W1-6]
ENST00000371475; ENSP00000360530; ENSG00000165802 [Q6X4W1-1]
ENST00000437259; ENSP00000412007; ENSG00000165802 [Q6X4W1-3]
GeneIDi26012
KEGGihsa:26012
UCSCiuc004cmz.4 human [Q6X4W1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNSMF_HUMAN
AccessioniPrimary (citable) accession number: Q6X4W1
Secondary accession number(s): Q2TB96
, Q6X4V7, Q6X4V8, Q6X4V9, Q8N2M2, Q96SY1, Q9NPM4, Q9NPP3, Q9NPS3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: July 5, 2004
Last modified: June 20, 2018
This is version 124 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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