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Protein

Neuroligin-4, X-linked

Gene

NLGN4X

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

Functioni

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

GO - Molecular functioni

  • carboxylic ester hydrolase activity Source: GO_Central
  • cell adhesion molecule binding Source: BHF-UCL
  • chloride ion binding Source: UniProtKB
  • neurexin family protein binding Source: BHF-UCL
  • protein homodimerization activity Source: UniProtKB
  • scaffold protein binding Source: BHF-UCL

GO - Biological processi

  • adult behavior Source: BHF-UCL
  • brainstem development Source: BHF-UCL
  • cell-cell junction organization Source: UniProtKB
  • cerebellum development Source: BHF-UCL
  • learning Source: BHF-UCL
  • negative regulation of excitatory postsynaptic potential Source: BHF-UCL
  • neuron cell-cell adhesion Source: BHF-UCL
  • neuron differentiation Source: BHF-UCL
  • organ growth Source: BHF-UCL
  • postsynaptic membrane assembly Source: GO_Central
  • presynapse assembly Source: ARUK-UCL
  • presynaptic membrane assembly Source: BHF-UCL
  • social behavior Source: UniProtKB
  • synapse organization Source: UniProtKB
  • synaptic vesicle endocytosis Source: GO_Central
  • vocalization behavior Source: BHF-UCL

Keywordsi

Biological processCell adhesion

Enzyme and pathway databases

ReactomeiR-HSA-6794361 Neurexins and neuroligins

Protein family/group databases

ESTHERihuman-NLGN4X Neuroligin
MEROPSiS09.988

Names & Taxonomyi

Protein namesi
Recommended name:
Neuroligin-4, X-linked
Short name:
Neuroligin X
Alternative name(s):
HNLX
Gene namesi
Name:NLGN4X
Synonyms:KIAA1260, NLGN4
ORF Names:UNQ365/PRO701
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000146938.14
HGNCiHGNC:14287 NLGN4X
MIMi300427 gene
neXtProtiNX_Q8N0W4

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini42 – 676ExtracellularSequence analysisAdd BLAST635
Transmembranei677 – 697HelicalSequence analysisAdd BLAST21
Topological domaini698 – 816CytoplasmicSequence analysisAdd BLAST119

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

Autism, X-linked 2 (AUTSX2)
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:300495
Asperger syndrome, X-linked, 2 (ASPGX2)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:300497

Keywords - Diseasei

Asperger syndrome, Autism, Autism spectrum disorder

Organism-specific databases

DisGeNETi57502
GeneReviewsiNLGN4X
MalaCardsiNLGN4X
MIMi300495 phenotype
300497 phenotype
OpenTargetsiENSG00000146938
Orphaneti1162 Asperger syndrome
106 Autism
PharmGKBiPA31650

Polymorphism and mutation databases

BioMutaiNLGN4X
DMDMi31076821

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 411 PublicationAdd BLAST41
ChainiPRO_000000864842 – 816Neuroligin-4, X-linkedAdd BLAST775

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi102N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi110 ↔ 1461 Publication
Disulfide bondi306 ↔ 3171 Publication
Disulfide bondi476 ↔ 5101 Publication
Glycosylationi511N-linked (GlcNAc...) asparagine1 Publication1
Modified residuei712PhosphoserineBy similarity1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ8N0W4
PaxDbiQ8N0W4
PeptideAtlasiQ8N0W4
PRIDEiQ8N0W4
ProteomicsDBi71472
71473 [Q8N0W4-2]

PTM databases

iPTMnetiQ8N0W4
PhosphoSitePlusiQ8N0W4

Expressioni

Tissue specificityi

Expressed at highest levels in heart. Expressed at lower levels in liver, skeletal muscle and pancreas and at very low levels in brain.1 Publication

Gene expression databases

BgeeiENSG00000146938
CleanExiHS_NLGN4X
ExpressionAtlasiQ8N0W4 baseline and differential
GenevisibleiQ8N0W4 HS

Organism-specific databases

HPAiHPA001651

Interactioni

Subunit structurei

Homodimer. Interacts with NRXN1 in a calcium-dependent manner. Interacts through its C-terminus with DLG4/PSD-95 third PDZ domain.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Nrxn1Q633735EBI-2862707,EBI-1780696From Rattus norvegicus.

GO - Molecular functioni

  • cell adhesion molecule binding Source: BHF-UCL
  • neurexin family protein binding Source: BHF-UCL
  • protein homodimerization activity Source: UniProtKB
  • scaffold protein binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi121567, 2 interactors
IntActiQ8N0W4, 3 interactors
MINTiQ8N0W4
STRINGi9606.ENSP00000275857

Structurei

Secondary structure

1816
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi47 – 50Combined sources4
Beta strandi53 – 56Combined sources4
Beta strandi58 – 60Combined sources3
Beta strandi70 – 77Combined sources8
Helixi84 – 86Combined sources3
Beta strandi98 – 102Combined sources5
Turni116 – 118Combined sources3
Helixi119 – 122Combined sources4
Helixi128 – 134Combined sources7
Helixi136 – 140Combined sources5
Beta strandi148 – 154Combined sources7
Beta strandi166 – 172Combined sources7
Turni176 – 178Combined sources3
Helixi182 – 184Combined sources3
Helixi188 – 194Combined sources7
Beta strandi197 – 201Combined sources5
Helixi206 – 210Combined sources5
Helixi222 – 237Combined sources16
Helixi238 – 241Combined sources4
Beta strandi243 – 253Combined sources11
Helixi255 – 263Combined sources9
Helixi267 – 269Combined sources3
Turni270 – 272Combined sources3
Beta strandi274 – 280Combined sources7
Beta strandi283 – 285Combined sources3
Turni286 – 288Combined sources3
Helixi293 – 303Combined sources11
Helixi311 – 319Combined sources9
Helixi323 – 327Combined sources5
Beta strandi339 – 341Combined sources3
Beta strandi346 – 349Combined sources4
Helixi353 – 358Combined sources6
Helixi361 – 364Combined sources4
Beta strandi365 – 372Combined sources8
Turni373 – 376Combined sources4
Helixi377 – 380Combined sources4
Turni381 – 383Combined sources3
Helixi392 – 406Combined sources15
Beta strandi410 – 412Combined sources3
Helixi413 – 423Combined sources11
Helixi433 – 448Combined sources16
Helixi450 – 461Combined sources12
Beta strandi467 – 472Combined sources6
Beta strandi478 – 481Combined sources4
Turni489 – 492Combined sources4
Helixi493 – 496Combined sources4
Helixi499 – 501Combined sources3
Beta strandi505 – 507Combined sources3
Helixi514 – 533Combined sources20
Turni564 – 566Combined sources3
Beta strandi568 – 575Combined sources8
Beta strandi577 – 581Combined sources5
Helixi584 – 591Combined sources8
Helixi594 – 596Combined sources3

3D structure databases

ProteinModelPortaliQ8N0W4
SMRiQ8N0W4
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8N0W4

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni359 – 364Interaction with NRXN16

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1516 Eukaryota
COG2272 LUCA
GeneTreeiENSGT00760000118946
HOGENOMiHOG000231424
HOVERGENiHBG008839
InParanoidiQ8N0W4
KOiK07378
PhylomeDBiQ8N0W4
TreeFamiTF326187

Family and domain databases

Gene3Di3.40.50.1820, 1 hit
InterProiView protein in InterPro
IPR029058 AB_hydrolase
IPR002018 CarbesteraseB
IPR019819 Carboxylesterase_B_CS
IPR000460 Nlgn
IPR030025 NLGN4
PANTHERiPTHR43903:SF5 PTHR43903:SF5, 1 hit
PfamiView protein in Pfam
PF00135 COesterase, 1 hit
PRINTSiPR01090 NEUROLIGIN
SUPFAMiSSF53474 SSF53474, 1 hit
PROSITEiView protein in PROSITE
PS00941 CARBOXYLESTERASE_B_2, 1 hit

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: Q8N0W4-1) [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
MSRPQGLLWL PLLFTPVCVM LNSNVLLWLT ALAIKFTLID SQAQYPVVNT
60 70 80 90 100
NYGKIRGLRT PLPNEILGPV EQYLGVPYAS PPTGERRFQP PEPPSSWTGI
110 120 130 140 150
RNTTQFAAVC PQHLDERSLL HDMLPIWFTA NLDTLMTYVQ DQNEDCLYLN
160 170 180 190 200
IYVPTEDDIH DQNSKKPVMV YIHGGSYMEG TGNMIDGSIL ASYGNVIVIT
210 220 230 240 250
INYRLGILGF LSTGDQAAKG NYGLLDQIQA LRWIEENVGA FGGDPKRVTI
260 270 280 290 300
FGSGAGASCV SLLTLSHYSE GLFQKAIIQS GTALSSWAVN YQPAKYTRIL
310 320 330 340 350
ADKVGCNMLD TTDMVECLRN KNYKELIQQT ITPATYHIAF GPVIDGDVIP
360 370 380 390 400
DDPQILMEQG EFLNYDIMLG VNQGEGLKFV DGIVDNEDGV TPNDFDFSVS
410 420 430 440 450
NFVDNLYGYP EGKDTLRETI KFMYTDWADK ENPETRRKTL VALFTDHQWV
460 470 480 490 500
APAVATADLH AQYGSPTYFY AFYHHCQSEM KPSWADSAHG DEVPYVFGIP
510 520 530 540 550
MIGPTELFSC NFSKNDVMLS AVVMTYWTNF AKTGDPNQPV PQDTKFIHTK
560 570 580 590 600
PNRFEEVAWS KYNPKDQLYL HIGLKPRVRD HYRATKVAFW LELVPHLHNL
610 620 630 640 650
NEIFQYVSTT TKVPPPDMTS FPYGTRRSPA KIWPTTKRPA ITPANNPKHS
660 670 680 690 700
KDPHKTGPED TTVLIETKRD YSTELSVTIA VGASLLFLNI LAFAALYYKK
710 720 730 740 750
DKRRHETHRR PSPQRNTTND IAHIQNEEIM SLQMKQLEHD HECESLQAHD
760 770 780 790 800
TLRLTCPPDY TLTLRRSPDD IPLMTPNTIT MIPNTLTGMQ PLHTFNTFSG
810
GQNSTNLPHG HSTTRV
Length:816
Mass (Da):91,915
Last modified:October 1, 2002 - v1
Checksum:iEA1320D690F76BBD
GO
Isoform 2 (identifier: Q8N0W4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     157-157: D → DGANTKKNADDITSNDRGEDE

Note: No experimental confirmation available.
Show »
Length:836
Mass (Da):94,047
Checksum:iF82E9A2505E6CA96
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti456Missing in AAQ88925 (PubMed:12975309).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036576214G → S in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs749477993Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_013270157D → DGANTKKNADDITSNDRGED E in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF376803 mRNA Translation: AAM46112.1
AB033086 mRNA Translation: BAA86574.1 Different initiation.
BC034018 mRNA Translation: AAH34018.1
AY358562 mRNA Translation: AAQ88925.1
CCDSiCCDS14126.1 [Q8N0W4-1]
RefSeqiNP_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_005274564.2 [Q8N0W4-2]
XP_005274622.1, XM_005274565.2 [Q8N0W4-2]
XP_005274623.1, XM_005274566.4 [Q8N0W4-2]
XP_006724567.1, XM_006724504.3 [Q8N0W4-2]
XP_011543849.1, XM_011545547.2 [Q8N0W4-2]
XP_011543850.1, XM_011545548.2 [Q8N0W4-2]
XP_016885179.1, XM_017029690.1 [Q8N0W4-2]
XP_016885180.1, XM_017029691.1 [Q8N0W4-1]
XP_016885181.1, XM_017029692.1 [Q8N0W4-1]
XP_016885182.1, XM_017029693.1 [Q8N0W4-1]
UniGeneiHs.21107

Genome annotation databases

EnsembliENST00000275857; ENSP00000275857; ENSG00000146938 [Q8N0W4-1]
ENST00000381092; ENSP00000370482; ENSG00000146938 [Q8N0W4-1]
ENST00000381093; ENSP00000370483; ENSG00000146938 [Q8N0W4-1]
ENST00000381095; ENSP00000370485; ENSG00000146938 [Q8N0W4-1]
ENST00000538097; ENSP00000439203; ENSG00000146938 [Q8N0W4-2]
GeneIDi57502
KEGGihsa:57502
UCSCiuc004crq.5 human [Q8N0W4-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNLGNX_HUMAN
AccessioniPrimary (citable) accession number: Q8N0W4
Secondary accession number(s): Q6UX10, Q9ULG0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 23, 2003
Last sequence update: October 1, 2002
Last modified: July 18, 2018
This is version 148 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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