Q8NFZ4 (NLGN2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Neuroligin-2

Gene names

Name:	NLGN2
Synonyms:	KIAA1366

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	835 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 By similarity.
Subunit structure	Interacts with NRXN1, NRXN2 and NRXN3. Interacts (via its C-terminus) with DLG4/PSD-95 (via PDZ domain 3). Interacts with INADL. Interacts with GPHN By similarity. Ref.3
Subcellular location	Cell membrane; Single-pass type I membrane protein By similarity. Cell junction › synapse › postsynaptic cell membrane By similarity. Cell junction › synapse › presynaptic cell membrane By similarity. Note: Detected at postsynaptic membranes in brain. Detected at dendritic spines in cultured neurons. Colocalizes with GPHN and ARHGEF9 at neuronal cell membranes By similarity. Localized at presynaptic membranes in retina. Colocalizes with GABRG2 at inhibitory synapses in the retina By similarity.
Tissue specificity	Expressed in the blood vessel walls. Detected in colon, brian and pancreas islets of Langerhans (at protein level). Detected in brain, and at lower levels in pancreas islet beta cells. Ref.4 Ref.5
Sequence similarities	Belongs to the type-B carboxylesterase/lipase family.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell junction Cell membrane Membrane Postsynaptic cell membrane Synapse
Domain	Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell-cell junction maintenance Non-traceable author statement PubMed 10892652. Source: UniProtKB gephyrin clustering Inferred from sequence or structural similarity. Source: BHF-UCL locomotory exploration behavior Inferred from electronic annotation. Source: Compara neuromuscular process controlling balance Inferred from electronic annotation. Source: Compara neuron cell-cell adhesion Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of excitatory postsynaptic membrane potential Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of inhibitory postsynaptic membrane potential Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of synapse assembly Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of synaptic transmission, GABAergic Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of synaptic transmission, glutamatergic Inferred from sequence or structural similarity. Source: BHF-UCL postsynaptic density protein 95 clustering Inferred from sequence or structural similarity. Source: BHF-UCL postsynaptic membrane assembly Inferred from sequence or structural similarity. Source: BHF-UCL presynaptic membrane assembly Inferred from sequence or structural similarity. Source: BHF-UCL protein localization to synapse Inferred from sequence or structural similarity. Source: BHF-UCL regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity Inferred from sequence or structural similarity. Source: BHF-UCL regulation of respiratory gaseous exchange by neurological system process Inferred from electronic annotation. Source: Compara sensory perception of pain Inferred from electronic annotation. Source: Compara terminal button organization Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW cell surface Inferred from sequence or structural similarity. Source: BHF-UCL inhibitory synapse Inferred from sequence or structural similarity. Source: BHF-UCL integral to plasma membrane Inferred from sequence or structural similarity. Source: BHF-UCL postsynaptic membrane Non-traceable author statement PubMed 10892652. Source: UniProtKB presynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	cell adhesion molecule binding Inferred from sequence or structural similarity. Source: BHF-UCL neurexin family protein binding Non-traceable author statement PubMed 10892652. Source: UniProtKB receptor activity Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 14	14	Potential
	Chain	15 – 835	821	Neuroligin-2		PRO_0000008643
Regions
	Topological domain	15 – 677	663	Extracellular Potential
	Transmembrane	678 – 698	21	Helical; Potential
	Topological domain	699 – 835	137	Cytoplasmic Potential
Amino acid modifications
	Modified residue	713	1	Phosphoserine By similarity
	Glycosylation	98	1	N-linked (GlcNAc...) Potential
	Glycosylation	136	1	N-linked (GlcNAc...) Potential
	Glycosylation	522	1	N-linked (GlcNAc...) Potential
	Disulfide bond	106 ↔ 141		By similarity
	Disulfide bond	317 ↔ 328		By similarity
	Disulfide bond	487 ↔ 521		By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q8NFZ4 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 359938630193EF87	FASTA	835	90,820
	10 20 30 40 50 60 MWLLALCLVG LAGAQRGGGG PGGGAPGGPG LGLGSLGEER FPVVNTAYGR VRGVRRELNN 70 80 90 100 110 120 EILGPVVQFL GVPYATPPLG ARRFQPPEAP ASWPGVRNAT TLPPACPQNL HGALPAIMLP 130 140 150 160 170 180 VWFTDNLEAA ATYVQNQSED CLYLNLYVPT EDGPLTKKRD EATLNPPDTD IRDPGKKPVM 190 200 210 220 230 240 LFLHGGSYME GTGNMFDGSV LAAYGNVIVA TLNYRLGVLG FLSTGDQAAK GNYGLLDQIQ 250 260 270 280 290 300 ALRWLSENIA HFGGDPERIT IFGSGAGASC VNLLILSHHS EGLFQKAIAQ SGTAISSWSV 310 320 330 340 350 360 NYQPLKYTRL LAAKVGCDRE DSAEAVECLR RKPSRELVDQ DVQPARYHIA FGPVVDGDVV 370 380 390 400 410 420 PDDPEILMQQ GEFLNYDMLI GVNQGEGLKF VEDSAESEDG VSASAFDFTV SNFVDNLYGY 430 440 450 460 470 480 PEGKDVLRET IKFMYTDWAD RDNGEMRRKT LLALFTDHQW VAPAVATAKL HADYQSPVYF 490 500 510 520 530 540 YTFYHHCQAE GRPEWADAAH GDELPYVFGV PMVGATDLFP CNFSKNDVML SAVVMTYWTN 550 560 570 580 590 600 FAKTGDPNQP VPQDTKFIHT KPNRFEEVVW SKFNSKEKQY LHIGLKPRVR DNYRANKVAF 610 620 630 640 650 660 WLELVPHLHN LHTELFTTTT RLPPYATRWP PRPPAGAPGT RRPPPPATLP PEPEPEPGPR 670 680 690 700 710 720 AYDRFPGDSR DYSTELSVTV AVGASLLFLN ILAFAALYYK RDRRQELRCR RLSPPGGSGS 730 740 750 760 770 780 GVPGGGPLLP AAGRELPPEE ELVSLQLKRG GGVGADPAEA LRPACPPDYT LALRRAPDDV 790 800 810 820 830 PLLAPGALTL LPSGLGPPPP PPPPSLHPFG PFPPPPPTAT SHNNTLPHPH STTRV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism." Jamain S., Quach H., Betancur C., Rastam M., Colineaux C., Gillberg I.C., Soderstrom H., Giros B., Leboyer M., Gillberg C., Bourgeron T., Nyden A., Philippe A., Cohen D., Chabane N., Mouren-Simeoni M.C., Brice A., Sponheim E. , Spurkland I., Skjeldal O.H., Coleman M., Pearl P.L., Cohen I.L., Tsiouris J., Zappella M., Menchetti G., Pompella A., Aschauer H., Van Maldergem L. Nat. Genet. 34:27-29(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:65-73(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 286-835. Tissue: Brain.
[3]	"Binding of neuroligins to PSD-95." Irie M., Hata Y., Takeuchi M., Ichtchenko K., Toyoda A., Hirao K., Takai Y., Rosahl T.W., Suedhof T.C. Science 277:1511-1515(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DLG4.
[4]	"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.
[5]	"The synaptic proteins neurexins and neuroligins are widely expressed in the vascular system and contribute to its functions." Bottos A., Destro E., Rissone A., Graziano S., Cordara G., Assenzio B., Cera M.R., Mascia L., Bussolino F., Arese M. Proc. Natl. Acad. Sci. U.S.A. 106:20782-20787(2009) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF376802 mRNA. Translation: AAM46111.1. AB037787 mRNA. Translation: BAA92604.1.
IPI	IPI00176424.
RefSeq	NP_065846.1. NM_020795.2.
UniGene	Hs.26229.
3D structure databases
ProteinModelPortal	Q8NFZ4.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000305288.
Protein family/group databases
MEROPS	S09.995.
PTM databases
PhosphoSite	Q8NFZ4.
Polymorphism databases
DMDM	31076824.
Proteomic databases
PaxDb	Q8NFZ4.
PRIDE	Q8NFZ4.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000302926; ENSP00000305288; ENSG00000169992. ENST00000575301; ENSP00000461168; ENSG00000169992.
GeneID	57555.
KEGG	hsa:57555.
UCSC	uc002ggt.1. human.
Organism-specific databases
CTD	57555.
GeneCards	GC17P007311.
HGNC	HGNC:14290. NLGN2.
MIM	606479. gene.
neXtProt	NX_Q8NFZ4.
PharmGKB	PA31648.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2272.
HOGENOM	HOG000231424.
HOVERGEN	HBG008839.
InParanoid	Q8NFZ4.
KO	K07378.
OMA	DIRDPGK.
OrthoDB	EOG4ZPDTP.
PhylomeDB	Q8NFZ4.
Gene expression databases
Bgee	Q8NFZ4.
CleanEx	HS_NLGN2.
Genevestigator	Q8NFZ4.
GermOnline	ENSG00000169992. Homo sapiens.
Family and domain databases
InterPro	IPR002018. CarbesteraseB. IPR019819. Carboxylesterase_B_CS. IPR000460. Neuroligin. [Graphical view]
Pfam	PF00135. COesterase. 1 hit. [Graphical view]
PRINTS	PR01090. NEUROLIGIN.
PROSITE	PS00941. CARBOXYLESTERASE_B_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	57555.
NextBio	64034.
SOURCE	Search...

Entry information

Entry name

NLGN2_HUMAN

Accession

Primary (citable) accession number: Q8NFZ4
Secondary accession number(s): Q9P2I1

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 23, 2003
Last sequence update:	October 1, 2002
Last modified:	May 1, 2013
This is version 90 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.