Reviewed, UniProtKB/Swiss-Prot Q8N0W4 (NLGNX_HUMAN)

Names and origin

Protein names

Recommended name:
    Neuroligin-4, X-linked
      Short name=Neuroligin X
Alternative name(s):
    HNLX

Gene names

Name:	NLGN4X
Synonyms:	KIAA1260, NLGN4
ORF Names:	UNQ365/PRO701

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	816 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	Putative neuronal cell surface protein involved in cell-cell-interactions.
Subunit structure	Interacts through its C-terminus with DLG4/PSD-95 third PDZ domain. Ref.6 Ref.7
Subcellular location	Membrane; Single-pass type I membrane protein Potential.
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	Defects in NLGN4X may be the cause of susceptibility to X-linked autism 2 (AUTSX2) [MIM:300495]. AUTSX2 is a pervasive developmental disorder (PDD), prototypically 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. Ref.1 Defects in NLGN4X may be the cause of susceptibility to X-linked Asperger syndrome 2 (ASPGX2) [MIM:300497]. ASPGX2 is considered to be a form of childhood autism.
Sequence similarities	Belongs to the type-B carboxylesterase/lipase family.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW cell-cell junction organization Ref.7 Non-traceable author statement. Source: UniProtKB social behavior Ref.1 Inferred from mutant phenotype. Source: UniProtKB synapse organization Ref.7 Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cell surface Inferred from direct assay. Source: UniProtKB integral to plasma membrane Ref.7 Inferred from direct assay. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA
Molecular function	chloride ion binding Inferred from direct assay. Source: UniProtKB neurexin binding Inferred from physical interaction. Source: UniProtKB protein homodimerization activity Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 41

41

Ref.5

Chain

42 – 816

775

Neuroligin-4, X-linked

PRO_0000008648

Regions

Topological domain

42 – 676

635

Extracellular Potential

Transmembrane

677 – 697

21

Potential

Topological domain

698 – 816

119

Cytoplasmic Potential

Amino acid modifications

Glycosylation

102

1

N-linked (GlcNAc...) Potential

Glycosylation

511

1

N-linked (GlcNAc...) Potential

Disulfide bond

110 ↔ 146

By similarity

Disulfide bond

306 ↔ 317

By similarity

Disulfide bond

476 ↔ 510

By similarity

Natural variations

Alternative sequence

157

1

D → DGANTKKNADDITSNDRGED E in isoform 2.

VSP_013270

Natural variant

214

1

G → S in a colorectal cancer sample; somatic mutation. Ref.9

VAR_036576

Experimental info

Sequence conflict

456

1

Missing Ref.4

Secondary structure

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816

Helix Strand Turn

Details...

Beta strand

47 – 50

4

Beta strand

53 – 56

4

Beta strand

58 – 60

3

Beta strand

70 – 77

8

Helix

84 – 86

3

Beta strand

98 – 102

5

Helix

119 – 122

4

Helix

128 – 134

7

Helix

136 – 140

5

Beta strand

148 – 154

7

Beta strand

166 – 172

7

Turn

176 – 178

3

Helix

182 – 184

3

Helix

188 – 194

7

Beta strand

197 – 201

5

Helix

206 – 210

5

Helix

222 – 237

16

Helix

238 – 241

4

Beta strand

243 – 253

11

Helix

255 – 263

9

Helix

267 – 269

3

Beta strand

274 – 280

7

Beta strand

283 – 285

3

Turn

286 – 288

3

Helix

293 – 303

11

Helix

311 – 319

9

Helix

323 – 327

5

Beta strand

339 – 341

3

Beta strand

346 – 349

4

Helix

353 – 358

6

Helix

361 – 364

4

Beta strand

365 – 372

8

Turn

373 – 376

4

Helix

377 – 380

4

Turn

381 – 383

3

Helix

392 – 406

15

Helix

413 – 423

11

Helix

433 – 448

16

Helix

450 – 461

12

Beta strand

467 – 472

6

Turn

489 – 492

4

Helix

493 – 496

4

Helix

499 – 501

3

Beta strand

505 – 507

3

Helix

514 – 533

20

Turn

564 – 566

3

Beta strand

568 – 575

8

Beta strand

577 – 581

5

Helix

584 – 591

8

Helix

594 – 596

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: EA1320D690F76BBD	FASTA	816	91,915
	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
	Isoform 2. Checksum: F82E9A2505E6CA96	FASTA	836	94,047
	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 IYVPTEDGAN TKKNADDITS NDRGEDEDIH 190 200 210 220 230 240 DQNSKKPVMV YIHGGSYMEG TGNMIDGSIL ASYGNVIVIT INYRLGILGF LSTGDQAAKG 250 260 270 280 290 300 NYGLLDQIQA LRWIEENVGA FGGDPKRVTI FGSGAGASCV SLLTLSHYSE GLFQKAIIQS 310 320 330 340 350 360 GTALSSWAVN YQPAKYTRIL ADKVGCNMLD TTDMVECLRN KNYKELIQQT ITPATYHIAF 370 380 390 400 410 420 GPVIDGDVIP DDPQILMEQG EFLNYDIMLG VNQGEGLKFV DGIVDNEDGV TPNDFDFSVS 430 440 450 460 470 480 NFVDNLYGYP EGKDTLRETI KFMYTDWADK ENPETRRKTL VALFTDHQWV APAVATADLH 490 500 510 520 530 540 AQYGSPTYFY AFYHHCQSEM KPSWADSAHG DEVPYVFGIP MIGPTELFSC NFSKNDVMLS 550 560 570 580 590 600 AVVMTYWTNF AKTGDPNQPV PQDTKFIHTK PNRFEEVAWS KYNPKDQLYL HIGLKPRVRD 610 620 630 640 650 660 HYRATKVAFW LELVPHLHNL NEIFQYVSTT TKVPPPDMTS FPYGTRRSPA KIWPTTKRPA 670 680 690 700 710 720 ITPANNPKHS KDPHKTGPED TTVLIETKRD YSTELSVTIA VGASLLFLNI LAFAALYYKK 730 740 750 760 770 780 DKRRHETHRR PSPQRNTTND IAHIQNEEIM SLQMKQLEHD HECESLQAHD TLRLTCPPDY 790 800 810 820 830 TLTLRRSPDD IPLMTPNTIT MIPNTLTGMQ PLHTFNTFSG GQNSTNLPHG HSTTRV

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: 12669065] [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: 10574462] [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: 15489334] [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. , 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: 12975309] [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: 15340161] [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: 9278515] [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: 11368788] [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: 14963808] [Abstract] Cited for: INVOLVEMENT IN ATSX2 AND ASPGX2.
[9]	"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. , 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: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] SER-214.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF376803 mRNA. Translation: AAM46112.1.
AB033086 mRNA. Translation: BAA86574.1. Different initiation.
BC034018 mRNA. Translation: AAH34018.1.
AY358562 mRNA. Translation: AAQ88925.1.

IPI

IPI00181174.
IPI00472566.

RefSeq

NP_065793.1.
NP_851849.1.

UniGene

Hs.21107

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2VH8	X-ray	3.90	A/B	43-597	[»]
3BE8	X-ray	2.20	A/B	44-619	[»]

ModBase

Search...

Protein family/group databases

MEROPS

S09.988.

Proteomic databases

PRIDE

Q8N0W4.

Genome annotation databases

Ensembl

ENSG00000146938. Homo sapiens. [Contig view]

GeneID

57502.

KEGG

hsa:57502.

Organism-specific databases

GeneCards

GC0XM005818.

H-InvDB

HIX0016638.

HGNC

HGNC:14287. NLGN4X.

HPA

HPA001651.

MIM

300427. gene.
300495. phenotype.
300497. phenotype.

Orphanet

1162. Asperger syndrome.
106. Autism.

PharmGKB

PA31650.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q8N0W4.

OMA

Q8N0W4. CLRNKNY.

Gene expression databases

ArrayExpress

Q8N0W4.

Bgee

Q8N0W4.

CleanEx

HS_NLGN4X.

GermOnline

ENSG00000146938. Homo sapiens.

Family and domain databases

InterPro

IPR002018. CarbesteraseB.
IPR019819. Carboxylesterase_B_CS.
IPR000460. Neuroligin.
[Graphical view]

PANTHER

PTHR11559. CarbesteraseB. 1 hit.

Pfam

PF00135. COesterase. 1 hit.
[Graphical view]

PRINTS

PR01090. NEUROLIGIN.

PROSITE

PS00941. CARBOXYLESTERASE_B_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

63827.

SOURCE

Search...

Entry information

Entry name

NLGNX_HUMAN

Accession

Primary (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:	June 16, 2009
This is version 64 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)