Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q8N0W4 (NLGNX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Neuroligin-4, X-linked

Short name=Neuroligin X
Alternative name(s):
HNLX
Gene names
Name:NLGN4X
Synonyms:KIAA1260, NLGN4
ORF Names:UNQ365/PRO701
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length816 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Putative neuronal cell surface protein involved in cell-cell-interactions.

Subunit structure

Homodimer. Interacts with NRXN1 in a calcium-dependent manner. Interacts through its C-terminus with DLG4/PSD-95 third PDZ domain. Ref.6 Ref.7 Ref.9

Subcellular location

Cell membrane; Single-pass type I membrane protein. Cell junctionsynapsepostsynaptic cell membranepostsynaptic density.

Tissue specificity

Expressed at highest levels in heart. Expressed at lower levels in liver, skeletal muscle and pancreas and at very low levels in brain. Ref.7

Involvement in disease

Autism, X-linked 2 (AUTSX2) [MIM:300495]: A complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate mental retardation.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.1

Asperger syndrome, X-linked, 2 (ASPGX2) [MIM:300497]: A syndrome with features similar to autism. Affected individuals exhibit qualitative impairment in social interaction, as manifest by impairment in the use of non-verbal behaviors such as eye-to-eye gaze, facial expression, body postures, and gestures, failure to develop appropriate peer relationships, and lack of social sharing or reciprocity. Patients also exhibit restricted, repetitive and stereotyped patterns of behavior, interests, and activities, including abnormal preoccupation with certain activities and inflexible adherence to routines or rituals. Asperger syndrome is primarily distinguished from autism by the higher cognitive abilities and a more normal and timely development of language and communicative phrases.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.1 Ref.8

Sequence similarities

Belongs to the type-B carboxylesterase/lipase family.

Sequence caution

The sequence BAA86574.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processCell adhesion
   Cellular componentCell junction
Cell membrane
Membrane
Postsynaptic cell membrane
Synapse
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processadult behavior

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

brainstem development

Inferred from sequence or structural similarity PubMed 18227507. Source: BHF-UCL

cell-cell junction organization

Non-traceable author statement Ref.7. Source: UniProtKB

cerebellum development

Inferred from sequence or structural similarity PubMed 18227507. Source: BHF-UCL

learning

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

negative regulation of excitatory postsynaptic membrane potential

Inferred from direct assay PubMed 19726642. Source: BHF-UCL

neuron cell-cell adhesion

Traceable author statement PubMed 18923512. Source: BHF-UCL

neuron differentiation

Non-traceable author statement PubMed 21278334. Source: BHF-UCL

organ growth

Inferred from sequence or structural similarity PubMed 18227507. Source: BHF-UCL

presynaptic membrane assembly

Inferred from direct assay PubMed 19726642. Source: BHF-UCL

social behavior

Inferred from mutant phenotype Ref.1. Source: UniProtKB

synapse organization

Inferred from mutant phenotype PubMed 15150161. Source: UniProtKB

vocalization behavior

Inferred from mutant phenotype Ref.1PubMed 19726642. Source: BHF-UCL

   Cellular_componentcell junction

Inferred from electronic annotation. Source: UniProtKB-KW

cell surface

Inferred from direct assay PubMed 15150161PubMed 17292328. Source: UniProtKB

dendrite

Inferred from direct assay PubMed 19726642. Source: BHF-UCL

excitatory synapse

Inferred from direct assay PubMed 15620359. Source: BHF-UCL

integral component of membrane

Non-traceable author statement PubMed 16377159. Source: UniProtKB

integral component of plasma membrane

Inferred from direct assay Ref.7. Source: UniProtKB

plasma membrane

Inferred from direct assay PubMed 19726642. Source: BHF-UCL

postsynaptic density

Inferred from electronic annotation. Source: UniProtKB-SubCell

postsynaptic membrane

Inferred from electronic annotation. Source: UniProtKB-KW

synapse

Inferred from sequence or structural similarity PubMed 18227507. Source: BHF-UCL

   Molecular_functioncell adhesion molecule binding

Traceable author statement PubMed 18923512. Source: BHF-UCL

chloride ion binding

Inferred from direct assay Ref.9. Source: UniProtKB

neurexin family protein binding

Inferred from physical interaction Ref.9. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.7PubMed 17292328. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay Ref.9. Source: UniProtKB

receptor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Nrxn1Q633735EBI-2862707,EBI-1780696From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8N0W4-1)

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.
Isoform 2 (identifier: Q8N0W4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     157-157: D → DGANTKKNADDITSNDRGEDE
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 4141 Ref.5
Chain42 – 816775Neuroligin-4, X-linked
PRO_0000008648

Regions

Topological domain42 – 676635Extracellular Potential
Transmembrane677 – 69721Helical; Potential
Topological domain698 – 816119Cytoplasmic Potential
Region359 – 3646Interaction with NRXN1

Amino acid modifications

Glycosylation1021N-linked (GlcNAc...) Ref.9
Glycosylation5111N-linked (GlcNAc...) Ref.9
Disulfide bond110 ↔ 146 Ref.9
Disulfide bond306 ↔ 317 Ref.9
Disulfide bond476 ↔ 510 Ref.9

Natural variations

Alternative sequence1571D → DGANTKKNADDITSNDRGED E in isoform 2.
VSP_013270
Natural variant2141G → S in a colorectal cancer sample; somatic mutation. Ref.10
VAR_036576

Experimental info

Sequence conflict4561Missing in AAQ88925. Ref.4

Secondary structure

................................................................................................... 816
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2002. Version 1.
Checksum: EA1320D690F76BBD

FASTA81691,915
        10         20         30         40         50         60 
MSRPQGLLWL PLLFTPVCVM LNSNVLLWLT ALAIKFTLID SQAQYPVVNT NYGKIRGLRT 

        70         80         90        100        110        120 
PLPNEILGPV EQYLGVPYAS PPTGERRFQP PEPPSSWTGI RNTTQFAAVC PQHLDERSLL 

       130        140        150        160        170        180 
HDMLPIWFTA NLDTLMTYVQ DQNEDCLYLN IYVPTEDDIH DQNSKKPVMV YIHGGSYMEG 

       190        200        210        220        230        240 
TGNMIDGSIL ASYGNVIVIT INYRLGILGF LSTGDQAAKG NYGLLDQIQA LRWIEENVGA 

       250        260        270        280        290        300 
FGGDPKRVTI FGSGAGASCV SLLTLSHYSE GLFQKAIIQS GTALSSWAVN YQPAKYTRIL 

       310        320        330        340        350        360 
ADKVGCNMLD TTDMVECLRN KNYKELIQQT ITPATYHIAF GPVIDGDVIP DDPQILMEQG 

       370        380        390        400        410        420 
EFLNYDIMLG VNQGEGLKFV DGIVDNEDGV TPNDFDFSVS NFVDNLYGYP EGKDTLRETI 

       430        440        450        460        470        480 
KFMYTDWADK ENPETRRKTL VALFTDHQWV APAVATADLH AQYGSPTYFY AFYHHCQSEM 

       490        500        510        520        530        540 
KPSWADSAHG DEVPYVFGIP MIGPTELFSC NFSKNDVMLS AVVMTYWTNF AKTGDPNQPV 

       550        560        570        580        590        600 
PQDTKFIHTK PNRFEEVAWS KYNPKDQLYL HIGLKPRVRD HYRATKVAFW LELVPHLHNL 

       610        620        630        640        650        660 
NEIFQYVSTT TKVPPPDMTS FPYGTRRSPA KIWPTTKRPA ITPANNPKHS KDPHKTGPED 

       670        680        690        700        710        720 
TTVLIETKRD YSTELSVTIA VGASLLFLNI LAFAALYYKK DKRRHETHRR PSPQRNTTND 

       730        740        750        760        770        780 
IAHIQNEEIM SLQMKQLEHD HECESLQAHD TLRLTCPPDY TLTLRRSPDD IPLMTPNTIT 

       790        800        810 
MIPNTLTGMQ PLHTFNTFSG GQNSTNLPHG HSTTRV 

« Hide

Isoform 2 [UniParc].

Checksum: F82E9A2505E6CA96
Show »

FASTA83694,047

References

« Hide '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. expand/collapse author list , 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] (ISOFORM 1), DISEASE.
[2]"Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.
DNA Res. 6:337-345(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Lung.
[4]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4-816 (ISOFORM 2).
[5]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 42-56.
[6]"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.
[7]"Identification of a novel neuroligin in humans which binds to PSD-95 and has a widespread expression."
Bolliger M.F., Frei K., Winterhalter K.H., Gloor S.M.
Biochem. J. 356:581-588(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DLG4, TISSUE SPECIFICITY.
[8]"X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family."
Laumonnier F., Bonnet-Brilhault F., Gomot M., Blanc R., David A., Moizard M.-P., Raynaud M., Ronce N., Lemonnier E., Calvas P., Laudier B., Chelly J., Fryns J.-P., Ropers H.-H., Hamel B.C.J., Andres C., Barthelemy C., Moraine C., Briault S.
Am. J. Hum. Genet. 74:552-557(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN ATSX2 AND ASPGX2.
[9]"Structural analysis of the synaptic protein neuroligin and its beta-neurexin complex: determinants for folding and cell adhesion."
Fabrichny I.P., Leone P., Sulzenbacher G., Comoletti D., Miller M.T., Taylor P., Bourne Y., Marchot P.
Neuron 56:979-991(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 44-619 ALONE AND IN COMPLEX WITH RAT NRXN1, GLYCOSYLATION AT ASN-102 AND ASN-511, SUBUNIT, DISULFIDE BONDS.
[10]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] SER-214.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF376803 mRNA. Translation: AAM46112.1.
AB033086 mRNA. Translation: BAA86574.1. Different initiation.
BC034018 mRNA. Translation: AAH34018.1.
AY358562 mRNA. Translation: AAQ88925.1.
CCDSCCDS14126.1. [Q8N0W4-1]
RefSeqNP_001269074.1. NM_001282145.1. [Q8N0W4-1]
NP_001269075.1. NM_001282146.1. [Q8N0W4-1]
NP_065793.1. NM_020742.3. [Q8N0W4-1]
NP_851849.1. NM_181332.2. [Q8N0W4-1]
XP_005274621.1. XM_005274564.1. [Q8N0W4-2]
XP_005274622.1. XM_005274565.1. [Q8N0W4-2]
XP_005274623.1. XM_005274566.2. [Q8N0W4-2]
XP_005274625.1. XM_005274568.1. [Q8N0W4-2]
XP_006724567.1. XM_006724504.1. [Q8N0W4-2]
UniGeneHs.21107.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2WQZX-ray3.90A/B43-619[»]
2XB6X-ray2.60A/B44-619[»]
3BE8X-ray2.20A/B44-619[»]
ProteinModelPortalQ8N0W4.
SMRQ8N0W4. Positions 41-599.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121567. 1 interaction.
IntActQ8N0W4. 3 interactions.
STRING9606.ENSP00000275857.

Protein family/group databases

MEROPSS09.988.

PTM databases

PhosphoSiteQ8N0W4.

Polymorphism databases

DMDM31076821.

Proteomic databases

PaxDbQ8N0W4.
PRIDEQ8N0W4.

Protocols and materials databases

DNASU57502.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000275857; ENSP00000275857; ENSG00000146938. [Q8N0W4-1]
ENST00000381092; ENSP00000370482; ENSG00000146938. [Q8N0W4-1]
ENST00000381093; ENSP00000370483; ENSG00000146938. [Q8N0W4-2]
ENST00000381095; ENSP00000370485; ENSG00000146938. [Q8N0W4-1]
ENST00000538097; ENSP00000439203; ENSG00000146938. [Q8N0W4-1]
GeneID57502.
KEGGhsa:57502.
UCSCuc004crp.3. human. [Q8N0W4-2]
uc004crq.3. human. [Q8N0W4-1]

Organism-specific databases

CTD57502.
GeneCardsGC0XM005758.
GeneReviewsNLGN4X.
HGNCHGNC:14287. NLGN4X.
HPAHPA001651.
MIM300427. gene.
300495. phenotype.
300497. phenotype.
neXtProtNX_Q8N0W4.
Orphanet1162. Asperger syndrome.
106. Autism.
PharmGKBPA31650.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2272.
HOGENOMHOG000231424.
HOVERGENHBG008839.
KOK07378.
OMAHISFGPV.
OrthoDBEOG7RBZ7R.
PhylomeDBQ8N0W4.
TreeFamTF326187.

Gene expression databases

ArrayExpressQ8N0W4.
BgeeQ8N0W4.
CleanExHS_NLGN4X.
GenevestigatorQ8N0W4.

Family and domain databases

Gene3D3.40.50.1820. 1 hit.
InterProIPR029058. AB_hydrolase.
IPR002018. CarbesteraseB.
IPR019819. Carboxylesterase_B_CS.
IPR000460. Neuroligin.
[Graphical view]
PfamPF00135. COesterase. 1 hit.
[Graphical view]
PRINTSPR01090. NEUROLIGIN.
SUPFAMSSF53474. SSF53474. 1 hit.
PROSITEPS00941. CARBOXYLESTERASE_B_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ8N0W4.
GeneWikiNLGN4X.
GenomeRNAi57502.
NextBio63827.
PROQ8N0W4.
SOURCESearch...

Entry information

Entry nameNLGNX_HUMAN
AccessionPrimary (citable) accession number: Q8N0W4
Secondary accession number(s): Q6UX10, Q9ULG0
Entry history
Integrated into UniProtKB/Swiss-Prot: May 23, 2003
Last sequence update: October 1, 2002
Last modified: July 9, 2014
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM