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Protein

Neuroligin-2

Gene

Nlgn2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transmembrane scaffolding protein involved in cell-cell interactions via its interactions with neurexin family members. Mediates cell-cell interactions both in neurons and in other types of cells, such as Langerhans beta cells. Plays a role in synapse function and synaptic signal transmission, especially via gamma-aminobutyric acid receptors (GABA(A) receptors). Functions by recruiting and clustering synaptic proteins. Promotes clustering of postsynaptic GABRG2 and GPHN. Modulates signaling by inhibitory synapses, and thereby plays a role in controlling the ratio of signaling by excitatory and inhibitory synapses and information processing. Required for normal signal amplitude from inhibitory synapses, but is not essential for normal signal frequency. May promote the initial formation of synapses, but is not essential for this. In vitro, triggers the de novo formation of presynaptic structures. Mediates cell-cell interactions between Langerhans beta cells and modulates insulin secretion.2 Publications

GO - Molecular functioni

GO - Biological processi

  • brain development Source: RGD
  • gephyrin clustering involved in postsynaptic density assembly Source: BHF-UCL
  • insulin metabolic process Source: RGD
  • jump response Source: BHF-UCL
  • locomotory exploration behavior Source: BHF-UCL
  • modulation of synaptic transmission Source: BHF-UCL
  • neuromuscular process controlling balance Source: BHF-UCL
  • neuron cell-cell adhesion Source: BHF-UCL
  • positive regulation of cell proliferation Source: RGD
  • positive regulation of dendritic spine development Source: RGD
  • positive regulation of excitatory postsynaptic potential Source: BHF-UCL
  • positive regulation of inhibitory postsynaptic potential Source: BHF-UCL
  • positive regulation of insulin secretion Source: RGD
  • positive regulation of protein localization to synapse Source: RGD
  • positive regulation of synapse assembly Source: BHF-UCL
  • positive regulation of synaptic transmission, GABAergic Source: BHF-UCL
  • positive regulation of synaptic transmission, glutamatergic Source: BHF-UCL
  • positive regulation of t-SNARE clustering Source: RGD
  • postsynaptic density protein 95 clustering Source: BHF-UCL
  • postsynaptic membrane assembly Source: BHF-UCL
  • presynaptic membrane assembly Source: BHF-UCL
  • protein localization to synapse Source: BHF-UCL
  • regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity Source: BHF-UCL
  • regulation of respiratory gaseous exchange by neurological system process Source: BHF-UCL
  • sensory perception of pain Source: BHF-UCL
  • social behavior Source: BHF-UCL
  • synapse assembly Source: BHF-UCL
  • synapse organization Source: MGI
  • terminal button organization Source: BHF-UCL
  • thigmotaxis Source: BHF-UCL
Complete GO annotation...

Keywords - Biological processi

Cell adhesion

Protein family/group databases

ESTHERiratno-2neur. Neuroligin.
MEROPSiS09.995.

Names & Taxonomyi

Protein namesi
Recommended name:
Neuroligin-2
Gene namesi
Name:Nlgn2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi621118. Nlgn2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini15 – 678664ExtracellularSequence analysisAdd
BLAST
Transmembranei679 – 69921HelicalSequence analysisAdd
BLAST
Topological domaini700 – 836137CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • cell junction Source: UniProtKB-KW
  • cell surface Source: BHF-UCL
  • cytoplasm Source: RGD
  • dendritic shaft Source: RGD
  • excitatory synapse Source: RGD
  • inhibitory synapse Source: BHF-UCL
  • integral component of plasma membrane Source: BHF-UCL
  • plasma membrane Source: BHF-UCL
  • postsynaptic membrane Source: RGD
  • presynaptic membrane Source: UniProtKB-SubCell
  • ribbon synapse Source: RGD
  • synapse Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi770 – 7701Y → A: Abolishes interaction with GPHN. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 14141 PublicationAdd
BLAST
Chaini15 – 836822Neuroligin-2PRO_0000008644Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi98 – 981N-linked (GlcNAc...)Sequence analysis
Disulfide bondi106 ↔ 141By similarity
Glycosylationi136 – 1361N-linked (GlcNAc...)Sequence analysis
Disulfide bondi317 ↔ 328By similarity
Disulfide bondi487 ↔ 521By similarity
Glycosylationi522 – 5221N-linked (GlcNAc...)Sequence analysis
Modified residuei714 – 7141PhosphoserineCombined sources
Modified residuei719 – 7191PhosphoserineBy similarity
Modified residuei770 – 7701PhosphotyrosineBy similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ62888.
PRIDEiQ62888.

PTM databases

iPTMnetiQ62888.
PhosphoSiteiQ62888.

Expressioni

Tissue specificityi

Detected on hippocampus neurons, especially at inhibitory synapses. Detected in retina, in the outer and inner plexiform layer. Detected in pancreas, in islet of Langerhans beta cells (at protein level). Expressed in brain, spinal chord and dorsal root ganglion. Detected in brain, and at lower levels in pancreas islet beta cells.7 Publications

Interactioni

Subunit structurei

Interacts with NRXN1, NRXN2 and NRXN3 (PubMed:8576240, PubMed:18334216, PubMed:20624592). Interacts (via its C-terminus) with DLG4/PSD-95 (via PDZ domain 3) (By similarity). Interacts with INADL (PubMed:9647694). Interacts with GPHN (PubMed:19755106). Interacts with MDGA1 and MDGA2 (PubMed:23248271). Found in a complex with MAGI2 and IGSF9B, where it interacts with MAGI2 (via WW 1, WW 2 and PDZ 2 domains) (PubMed:23751499).By similarity7 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi250669. 13 interactions.
IntActiQ62888. 4 interactions.
MINTiMINT-1891708.
STRINGi10116.ENSRNOP00000053713.

Structurei

3D structure databases

ProteinModelPortaliQ62888.
SMRiQ62888. Positions 42-609.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1516. Eukaryota.
COG2272. LUCA.
HOGENOMiHOG000231424.
HOVERGENiHBG008839.
InParanoidiQ62888.
KOiK07378.
PhylomeDBiQ62888.

Family and domain databases

Gene3Di3.40.50.1820. 1 hit.
InterProiIPR029058. AB_hydrolase.
IPR002018. CarbesteraseB.
IPR019819. Carboxylesterase_B_CS.
IPR000460. Nlgn.
IPR030023. NLGN2.
[Graphical view]
PANTHERiPTHR11559:SF53. PTHR11559:SF53. 2 hits.
PfamiPF00135. COesterase. 1 hit.
[Graphical view]
PRINTSiPR01090. NEUROLIGIN.
SUPFAMiSSF53474. SSF53474. 1 hit.
PROSITEiPS00941. CARBOXYLESTERASE_B_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q62888-1) [UniParc]FASTAAdd to basket

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
MWLLALCLVG LAGAQRGGGG PGGGAPGGPG LGLGSLGEER FPVVNTAYGR
60 70 80 90 100
VRGVRRELNN EILGPVVQFL GVPYATPPLG ARRFQPPEAP ASWPGVRNAT
110 120 130 140 150
TLPPACPQNL HGALPAIMLP VWFTDNLEAA ATYVQNQSED CLYLNLYVPT
160 170 180 190 200
EDGPLTKKRD EATLNPPDTD IRDSGKKPVM LFLHGGSYME GTGNMFDGSV
210 220 230 240 250
LAAYGNVIVA TLNYRLGVLG FLSTGDQAAK GNYGLLDQIQ ALRWLSENIA
260 270 280 290 300
HFGGDPERIT IFGSGAGASC VNLLILSHHS EGLFQKAIAQ SGTAISSWSV
310 320 330 340 350
NYQPLKYTRL LAAKVGCDRE DSTEAVECLR RKSSRELVDQ DVQPARYHIA
360 370 380 390 400
FGPVVDGDVV PDDPEILMQQ GEFLNYDMLI GVNQGEGLKF VEDSAESEDG
410 420 430 440 450
VSASAFDFTV SNFVDNLYGY PEGKDVLRET IKFMYTDWAD RDNGEMRRKT
460 470 480 490 500
LLALFTDHQW VAPAVATAKL HADYQSPVYF YTFYHHCQAE GRPEWADAAH
510 520 530 540 550
GDELPYVFGV PMVGATDLFP CNFSKNDVML SAVVMTYWTN FAKTGDPNQP
560 570 580 590 600
VPQDTKFIHT KPNRFEEVVW SKFNSKEKQY LHIGLKPRVR DNYRANKVAF
610 620 630 640 650
WLELVPHLHN LHTELFTTTT RLPPYATRWP PRTPGPGTSG TRRPPPPATL
660 670 680 690 700
PPESDIDLGP RAYDRFPGDS RDYSTELSVT VAVGASLLFL NILAFAALYY
710 720 730 740 750
KRDRRQELRC RRLSPPGGSG SGVPGGGPLL PTAGRELPPE EELVSLQLKR
760 770 780 790 800
GGGVGADPAE ALRPACPPDY TLALRRAPDD VPLLAPGALT LLPSGLGPPP
810 820 830
PPPPPSLHPF GPFPPPPPTA TSHNNTLPHP HSTTRV
Length:836
Mass (Da):90,961
Last modified:November 1, 1996 - v1
Checksum:i1AD51CB1BE4BF9CF
GO
Isoform 2 (identifier: Q62888-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     153-169: Missing.

Show »
Length:819
Mass (Da):89,126
Checksum:iE60AFEF27FC6F6F2
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei153 – 16917Missing in isoform 2. 1 PublicationVSP_007533Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U41662 mRNA. Translation: AAA97870.1.
RefSeqiNP_446444.1. NM_053992.1. [Q62888-1]
UniGeneiRn.55111.

Genome annotation databases

GeneIDi117096.
KEGGirno:117096.
UCSCiRGD:621118. rat. [Q62888-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U41662 mRNA. Translation: AAA97870.1.
RefSeqiNP_446444.1. NM_053992.1. [Q62888-1]
UniGeneiRn.55111.

3D structure databases

ProteinModelPortaliQ62888.
SMRiQ62888. Positions 42-609.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi250669. 13 interactions.
IntActiQ62888. 4 interactions.
MINTiMINT-1891708.
STRINGi10116.ENSRNOP00000053713.

Protein family/group databases

ESTHERiratno-2neur. Neuroligin.
MEROPSiS09.995.

PTM databases

iPTMnetiQ62888.
PhosphoSiteiQ62888.

Proteomic databases

PaxDbiQ62888.
PRIDEiQ62888.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi117096.
KEGGirno:117096.
UCSCiRGD:621118. rat. [Q62888-1]

Organism-specific databases

CTDi57555.
RGDi621118. Nlgn2.

Phylogenomic databases

eggNOGiKOG1516. Eukaryota.
COG2272. LUCA.
HOGENOMiHOG000231424.
HOVERGENiHBG008839.
InParanoidiQ62888.
KOiK07378.
PhylomeDBiQ62888.

Miscellaneous databases

PROiQ62888.

Family and domain databases

Gene3Di3.40.50.1820. 1 hit.
InterProiIPR029058. AB_hydrolase.
IPR002018. CarbesteraseB.
IPR019819. Carboxylesterase_B_CS.
IPR000460. Nlgn.
IPR030023. NLGN2.
[Graphical view]
PANTHERiPTHR11559:SF53. PTHR11559:SF53. 2 hits.
PfamiPF00135. COesterase. 1 hit.
[Graphical view]
PRINTSiPR01090. NEUROLIGIN.
SUPFAMiSSF53474. SSF53474. 1 hit.
PROSITEiPS00941. CARBOXYLESTERASE_B_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Structures, alternative splicing, and neurexin binding of multiple neuroligins."
    Ichtchenko K., Nguyen T., Suedhof T.C.
    J. Biol. Chem. 271:2676-2682(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PROTEIN SEQUENCE OF N-TERMINUS, TISSUE SPECIFICITY, INTERACTION WITH NEUREXIN 1-BETA; NEUREXIN 2-BETA AND NEUREXIN 3-BETA.
    Tissue: Forebrain.
  2. "CIPP, a novel multivalent PDZ domain protein, selectively interacts with Kir4.0 family members, NMDA receptor subunits, neurexins, and neuroligins."
    Kurschner C., Mermelstein P.G., Holden W.T., Surmeier D.J.
    Mol. Cell. Neurosci. 11:161-172(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH INADL.
  3. "Neuroligin 3 is a vertebrate gliotactin expressed in the olfactory ensheathing glia, a growth-promoting class of macroglia."
    Gilbert M., Smith J., Roskams A.J., Auld V.J.
    Glia 34:151-164(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  4. "Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins."
    Graf E.R., Zhang X., Jin S.X., Linhoff M.W., Craig A.M.
    Cell 119:1013-1026(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  5. "Expression of neurexin, neuroligin, and their cytoplasmic binding partners in the pancreatic beta-cells and the involvement of neuroligin in insulin secretion."
    Suckow A.T., Comoletti D., Waldrop M.A., Mosedale M., Egodage S., Taylor P., Chessler S.D.
    Endocrinology 149:6006-6017(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, ALTERNATIVE SPLICING.
  6. Cited for: SUBCELLULAR LOCATION.
  7. "Crystal structures of beta-neurexin 1 and beta-neurexin 2 ectodomains and dynamics of splice insertion sequence 4."
    Koehnke J., Jin X., Trbovic N., Katsamba P.S., Brasch J., Ahlsen G., Scheiffele P., Honig B., Palmer A.G. III, Shapiro L.
    Structure 16:410-421(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NRXN1.
  8. "Neuroligin 2 drives postsynaptic assembly at perisomatic inhibitory synapses through gephyrin and collybistin."
    Poulopoulos A., Aramuni G., Meyer G., Soykan T., Hoon M., Papadopoulos T., Zhang M., Paarmann I., Fuchs C., Harvey K., Jedlicka P., Schwarzacher S.W., Betz H., Harvey R.J., Brose N., Zhang W., Varoqueaux F.
    Neuron 63:628-642(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH GPHN, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF TYR-770.
  9. "Synaptic localization of neuroligin 2 in the rodent retina: comparative study with the dystroglycan-containing complex."
    Lui L., Levinson J.N., Noel G., Handrigan G.R., Richman J.M., El-Husseini A., Moukhles H.
    J. Neurosci. Res. 88:837-849(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  10. "Splice form dependence of beta-neurexin/neuroligin binding interactions."
    Koehnke J., Katsamba P.S., Ahlsen G., Bahna F., Vendome J., Honig B., Shapiro L., Jin X.
    Neuron 67:61-74(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NRXN1.
  11. "Postsynaptic scaffolding molecules modulate the localization of neuroligins."
    Levinson J.N., Li R., Kang R., Moukhles H., El-Husseini A., Bamji S.X.
    Neuroscience 165:782-793(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  12. "Transcellular neuroligin-2 interactions enhance insulin secretion and are integral to pancreatic beta-cell function."
    Suckow A.T., Zhang C., Egodage S., Comoletti D., Taylor P., Miller M.T., Sweet I.R., Chessler S.D.
    J. Biol. Chem. 287:19816-19826(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  13. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-714, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  14. "The adhesion protein IgSF9b is coupled to neuroligin 2 via S-SCAM to promote inhibitory synapse development."
    Woo J., Kwon S.K., Nam J., Choi S., Takahashi H., Krueger D., Park J., Lee Y., Bae J.Y., Lee D., Ko J., Kim H., Kim M.H., Bae Y.C., Chang S., Craig A.M., Kim E.
    J. Cell Biol. 201:929-944(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION IN A COMPLEX WITH MAGI2 AND IGSF9B.
  15. "MDGAs interact selectively with neuroligin-2 but not other neuroligins to regulate inhibitory synapse development."
    Lee K., Kim Y., Lee S.-J., Qiang Y., Lee D., Lee H.W., Kim H., Je H.S., Suedhof T.C., Ko J.
    Proc. Natl. Acad. Sci. U.S.A. 110:336-341(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MDGA1 AND MDGA2.

Entry informationi

Entry nameiNLGN2_RAT
AccessioniPrimary (citable) accession number: Q62888
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 23, 2003
Last sequence update: November 1, 1996
Last modified: June 8, 2016
This is version 121 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.