UniProt functional annotation for Q86UL8



	UniProt functional annotation for Q86UL8

UniProt code: Q86UL8.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Seems to act as scaffold molecule at synaptic junctions by assembling neurotransmitter receptors and cell adhesion proteins. May play a role in regulating activin-mediated signaling in neuronal cells. Enhances the ability of PTEN to suppress AKT1 activation. Plays a role in nerve growth factor (NGF)-induced recruitment of RAPGEF2 to late endosomes and neurite outgrowth. {ECO:0000269|PubMed:10760291}.

Subunit: Interacts (via its WW domains) with DRPLA (PubMed:9647693). Interacts (via its second PDZ domain) with PTEN (via unphosphorylated C-terminus); this interaction diminishes the degradation rate of PTEN (PubMed:10760291, PubMed:11707428). Interacts (via guanylate kinase domain) with DLGAP1 (By similarity). Interacts (via the PDZ domains) with GRIN2A, GRID2 and NLGN1 (By similarity). Interacts with CTNND2, CTNNB1, MAGUIN-1, ACVR2A, SMAD2 and SMAD3 (By similarity). Part of a complex consisting of AIP1, ACVR2A, ACVR1B and SMAD3 (By similarity). May interact with HTR2A (By similarity). Interacts with IGSF9, RAPGEF2 and HTR4 (By similarity). Identified in a complex with ACTN4, CASK, IQGAP1, NPHS1, SPTAN1 and SPTBN1 (By similarity). Found in a complex, at least composed of KIDINS220, MAGI2, NTRK1 and RAPGEF2; the complex is mainly formed at late endosomes in a NGF-dependent manner (By similarity). Interacts with RAPGEF2; the interaction occurs before or after nerve growth factor (NGF) stimulation (By similarity). Interacts (via PDZ domain) with KIDINS220 (via C-terminal domain) (By similarity). Interacts with DDN (PubMed:16464232). Interacts with DLL1 (By similarity). Found in a complex with IGSF9B and NLGN2; the interaction with IGSF9B is mediated via the PDZ 5 and PDZ 6 domains, while the interaction with NLGN2 is mediated via the WW1, WW2 and PDZ2 domains (PubMed:23751499). {ECO:0000250|UniProtKB:O88382, ECO:0000250|UniProtKB:Q9WVQ1, ECO:0000269|PubMed:10760291, ECO:0000269|PubMed:11707428, ECO:0000269|PubMed:16464232, ECO:0000269|PubMed:23751499, ECO:0000269|PubMed:9647693}.

Subcellular location: Cytoplasm {ECO:0000250}. Late endosome {ECO:0000250}. Cell junction, synapse, synaptosome {ECO:0000250}. Cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Note=Localized diffusely in the cytoplasm before nerve growth factor (NGF) stimulation. Recruited to late endosomes after NGF stimulation. Membrane-associated in synaptosomes (By similarity). {ECO:0000250}.

Tissue specificity: Specifically expressed in brain. {ECO:0000269|PubMed:9647693}.

Disease: Nephrotic syndrome 15 (NPHS15) [MIM:617609]: A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. NPHS15 is an autosomal recessive form with onset in the first months of life. Disease severity is variable. Some patients show rapid progression to end-stage renal failure. {ECO:0000269|PubMed:27932480}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the MAGUK family. {ECO:0000305}.

Sequence caution: Sequence=BAA31680.2; Type=Erroneous initiation; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Seems to act as scaffold molecule at synaptic junctions by assembling neurotransmitter receptors and cell adhesion proteins. May play a role in regulating activin-mediated signaling in neuronal cells. Enhances the ability of PTEN to suppress AKT1 activation. Plays a role in nerve growth factor (NGF)-induced recruitment of RAPGEF2 to late endosomes and neurite outgrowth. {ECO:0000269\|PubMed:10760291}.


Subunit:		Interacts (via its WW domains) with DRPLA (PubMed:9647693). Interacts (via its second PDZ domain) with PTEN (via unphosphorylated C-terminus); this interaction diminishes the degradation rate of PTEN (PubMed:10760291, PubMed:11707428). Interacts (via guanylate kinase domain) with DLGAP1 (By similarity). Interacts (via the PDZ domains) with GRIN2A, GRID2 and NLGN1 (By similarity). Interacts with CTNND2, CTNNB1, MAGUIN-1, ACVR2A, SMAD2 and SMAD3 (By similarity). Part of a complex consisting of AIP1, ACVR2A, ACVR1B and SMAD3 (By similarity). May interact with HTR2A (By similarity). Interacts with IGSF9, RAPGEF2 and HTR4 (By similarity). Identified in a complex with ACTN4, CASK, IQGAP1, NPHS1, SPTAN1 and SPTBN1 (By similarity). Found in a complex, at least composed of KIDINS220, MAGI2, NTRK1 and RAPGEF2; the complex is mainly formed at late endosomes in a NGF-dependent manner (By similarity). Interacts with RAPGEF2; the interaction occurs before or after nerve growth factor (NGF) stimulation (By similarity). Interacts (via PDZ domain) with KIDINS220 (via C-terminal domain) (By similarity). Interacts with DDN (PubMed:16464232). Interacts with DLL1 (By similarity). Found in a complex with IGSF9B and NLGN2; the interaction with IGSF9B is mediated via the PDZ 5 and PDZ 6 domains, while the interaction with NLGN2 is mediated via the WW1, WW2 and PDZ2 domains (PubMed:23751499). {ECO:0000250\|UniProtKB:O88382, ECO:0000250\|UniProtKB:Q9WVQ1, ECO:0000269\|PubMed:10760291, ECO:0000269\|PubMed:11707428, ECO:0000269\|PubMed:16464232, ECO:0000269\|PubMed:23751499, ECO:0000269\|PubMed:9647693}.
Subcellular location:		Cytoplasm {ECO:0000250}. Late endosome {ECO:0000250}. Cell junction, synapse, synaptosome {ECO:0000250}. Cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Note=Localized diffusely in the cytoplasm before nerve growth factor (NGF) stimulation. Recruited to late endosomes after NGF stimulation. Membrane-associated in synaptosomes (By similarity). {ECO:0000250}.
Tissue specificity:		Specifically expressed in brain. {ECO:0000269\|PubMed:9647693}.
Disease:		Nephrotic syndrome 15 (NPHS15) [MIM:617609]: A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. NPHS15 is an autosomal recessive form with onset in the first months of life. Disease severity is variable. Some patients show rapid progression to end-stage renal failure. {ECO:0000269\|PubMed:27932480}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the MAGUK family. {ECO:0000305}.
Sequence caution:		Sequence=BAA31680.2; Type=Erroneous initiation; Evidence={ECO:0000305};