Reviewed, UniProtKB/Swiss-Prot Q9NZ94 (NLGN3_HUMAN)

Names and origin

Protein names

Recommended name:
    Neuroligin-3
Alternative name(s):
    Gliotactin homolog

Gene names

Name:	NLGN3
Synonyms:	KIAA1480, NL3

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	848 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	Neuronal cell surface protein thought to be involved in cell-cell-interactions by forming intercellular junctions through binding to beta-neurexins. May play a role in formation or maintenance of synaptic junctions. May also play a role in glia-glia or glia-neuron interactions in the developing peripheral nervous system.
Subunit structure	Interacts with neurexin 1-beta, neurexin 2-beta and neurexin 3-beta By similarity. Probably interacts through its C-terminus with DLG4/PSD-95 third PDZ domain.
Subcellular location	Membrane; Single-pass type I membrane proteinPotential.
Involvement in disease	Defects in NLGN3 may be the cause of susceptibility to X-linked autism 1 (AUTSX1) [MIM:300425]. AUTSX1 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. Defects in NLGN3 may be the cause of susceptibility to X-linked Asperger syndrome 1 (ASPGX1) [MIM:300494]. ASPGX1 is considered to be a form of childhood autism.
Sequence similarities	Belongs to the type-B carboxylesterase/lipase family.
Sequence caution	The sequence AAF71231.1 differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Potential poly-A sequence.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Domain	Signal Transmembrane
PTM	Glycoprotein Phosphoprotein
Gene Ontology (GO)
Biological process	social behavior Ref.5 Inferred from mutant phenotype. Source: UniProtKB synapse organization and biogenesis Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cell surface Inferred from direct assay. Source: UniProtKB synapse Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NZ94-1)

Also known as: HNL3s;

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: Q9NZ94-2)

Also known as: HNL3;

The sequence of this isoform differs from the canonical sequence as follows:
     153-172: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Signal peptide	1 – 37	37	Potential
	Chain	38 – 848	811	Neuroligin-3
Regions
	Topological domain	38 – 709	672	Extracellular Potential
	Transmembrane	710 – 730	21	Potential
	Topological domain	731 – 848	118	Cytoplasmic Potential
Amino acid modifications
	Modified residue	792	1	Phosphotyrosine By similarity
	Glycosylation	98	1	N-linked (GlcNAc...) Potential
	Glycosylation	545	1	N-linked (GlcNAc...) Potential
	Disulfide bond	106 ↔ 141		By similarity
	Disulfide bond	340 ↔ 351		By similarity
	Disulfide bond	510 ↔ 544		By similarity
Natural variations
	Alternative sequence	153 – 172	20	Missing in isoform 2.
	Natural variant	451	1	R → C in AUTSX1 and ASPGX1.
Experimental info
	Sequence conflict	224	1	L → P in AAF71230. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (HNL3s) [UniParc]. Last modified May 23, 2003. Version 2. Checksum: B3EE2FAB7E427C82	FASTA	848	93,895
	10 20 30 40 50 60 MWLRLGPPSL SLSPKPTVGR SLCLTLWFLS LALRASTQAP APTVNTHFGK LRGARVPLPS 70 80 90 100 110 120 EILGPVDQYL GVPYAAPPIG EKRFLPPEPP PSWSGIRNAT HFPPVCPQNI HTAVPEVMLP 130 140 150 160 170 180 VWFTANLDIV ATYIQEPNED CLYLNVYVPT EDVKRISKEC ARKPNKKICR KGGSGAKKQG 190 200 210 220 230 240 EDLADNDGDE DEDIRDSGAK PVMVYIHGGS YMEGTGNMID GSILASYGNV IVITLNYRVG 250 260 270 280 290 300 VLGFLSTGDQ AAKGNYGLLD QIQALRWVSE NIAFFGGDPR RITVFGSGIG ASCVSLLTLS 310 320 330 340 350 360 HHSEGLFQRA IIQSGSALSS WAVNYQPVKY TSLLADKVGC NVLDTVDMVD CLRQKSAKEL 370 380 390 400 410 420 VEQDIQPARY HVAFGPVIDG DVIPDDPEIL MEQGEFLNYD IMLGVNQGEG LKFVEGVVDP 430 440 450 460 470 480 EDGVSGTDFD YSVSNFVDNL YGYPEGKDTL RETIKFMYTD WADRDNPETR RKTLVALFTD 490 500 510 520 530 540 HQWVEPSVVT ADLHARYGSP TYFYAFYHHC QSLMKPAWSD AAHGDEVPYV FGVPMVGPTD 550 560 570 580 590 600 LFPCNFSKND VMLSAVVMTY WTNFAKTGDP NKPVPQDTKF IHTKANRFEE VAWSKYNPRD 610 620 630 640 650 660 QLYLHIGLKP RVRDHYRATK VAFWKHLVPH LYNLHDMFHY TSTTTKVPPP DTTHSSHITR 670 680 690 700 710 720 RPNGKTWSTK RPAISPAYSN ENAQGSWNGD QDAGPLLVEN PRDYSTELSV TIAVGASLLF 730 740 750 760 770 780 LNVLAFAALY YRKDKRRQEP LRQPSPQRGA GAPELGAAPE EELAALQLGP THHECEAGPP 790 800 810 820 830 840 HDTLRLTALP DYTLTLRRSP DDIPLMTPNT ITMIPNSLVG LQTLHPYNTF AAGFNSTGLP HSHSTTRV
	Isoform 2 (HNL3) [UniParc]. Checksum: B72E4F3472678692		828	91,570
	10 20 30 40 50 60 MWLRLGPPSL SLSPKPTVGR SLCLTLWFLS LALRASTQAP APTVNTHFGK LRGARVPLPS 70 80 90 100 110 120 EILGPVDQYL GVPYAAPPIG EKRFLPPEPP PSWSGIRNAT HFPPVCPQNI HTAVPEVMLP 130 140 150 160 170 180 VWFTANLDIV ATYIQEPNED CLYLNVYVPT EDGSGAKKQG EDLADNDGDE DEDIRDSGAK 190 200 210 220 230 240 PVMVYIHGGS YMEGTGNMID GSILASYGNV IVITLNYRVG VLGFLSTGDQ AAKGNYGLLD 250 260 270 280 290 300 QIQALRWVSE NIAFFGGDPR RITVFGSGIG ASCVSLLTLS HHSEGLFQRA IIQSGSALSS 310 320 330 340 350 360 WAVNYQPVKY TSLLADKVGC NVLDTVDMVD CLRQKSAKEL VEQDIQPARY HVAFGPVIDG 370 380 390 400 410 420 DVIPDDPEIL MEQGEFLNYD IMLGVNQGEG LKFVEGVVDP EDGVSGTDFD YSVSNFVDNL 430 440 450 460 470 480 YGYPEGKDTL RETIKFMYTD WADRDNPETR RKTLVALFTD HQWVEPSVVT ADLHARYGSP 490 500 510 520 530 540 TYFYAFYHHC QSLMKPAWSD AAHGDEVPYV FGVPMVGPTD LFPCNFSKND VMLSAVVMTY 550 560 570 580 590 600 WTNFAKTGDP NKPVPQDTKF IHTKANRFEE VAWSKYNPRD QLYLHIGLKP RVRDHYRATK 610 620 630 640 650 660 VAFWKHLVPH LYNLHDMFHY TSTTTKVPPP DTTHSSHITR RPNGKTWSTK RPAISPAYSN 670 680 690 700 710 720 ENAQGSWNGD QDAGPLLVEN PRDYSTELSV TIAVGASLLF LNVLAFAALY YRKDKRRQEP 730 740 750 760 770 780 LRQPSPQRGA GAPELGAAPE EELAALQLGP THHECEAGPP HDTLRLTALP DYTLTLRRSP 790 800 810 820 DDIPLMTPNT ITMIPNSLVG LQTLHPYNTF AAGFNSTGLP HSHSTTRV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The structure and expression of the human neuroligin-3 gene." Philibert R.A., Winfield S.L., Sandhu H.K., Martin B.M., Ginns E.I. Gene 246:303-310(2000) [PubMed: 10767552] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2).
[2]	"Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:143-150(2000) [PubMed: 10819331] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 12-848. Tissue: Brain.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 410-848.
[4]	"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.
[5]	"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: VARIANT AUTSX1/ASPGX1 CYS-451.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF217411 mRNA. Translation: AAF71230.1. AF217412 mRNA. Translation: AAF71231.1. Sequence problems. AF217413 Genomic DNA. Translation: AAF71232.1. AF217413 Genomic DNA. Translation: AAF71233.1. AB040913 mRNA. Translation: BAA96004.1. Different initiation. AK074814 mRNA. Translation: BAC11226.1. Different initiation.
UniGene	Hs.438877
3D structure databases
HSSP	HSSP built from PDB template 1JMY based on UniProtKB P19835.
ModBase	Search...
Protein family/group databases
MEROPS	S09.987.
Genome annotation databases
Ensembl	ENSG00000196338. Homo sapiens. [Contig view]
Organism-specific databases
H-InvDB	HIX0016859.
HGNC	HGNC:14289. NLGN3.
HPA	HPA003183.
MIM	300336. gene. 300425. phenotype. 300494. phenotype.
Orphanet	1162. Asperger syndrome. 106. Autism.
PharmGKB	PA31649.
HUGE	Search...
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	Q9NZ94.
HOVERGEN	Q9NZ94.
Gene expression databases
ArrayExpress	Q9NZ94.
CleanEx	HS_NLGN3.
GermOnline	ENSG00000196338. Homo sapiens.
Family and domain databases
InterPro	IPR002018. CarbesteraseB. 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]
ProDom	Q9NZ94. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
Other Resources
LinkHub	Q9NZ94.
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

NLGN3_HUMAN

Accession

Primary (citable) accession number: Q9NZ94
Secondary accession number(s): Q8NCD0 , Q9NZ95, Q9NZ96, Q9NZ97, Q9P248

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 23, 2003
Last sequence update:	May 23, 2003
Last modified:	September 23, 2008
This is version 63 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)