UniProt functional annotation for O75970



	UniProt functional annotation for O75970

UniProt code: O75970.

Organism: Homo sapiens (Human).

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

Function: Member of the NMDAR signaling complex that may play a role in control of AMPAR potentiation and synaptic plasticity in excitatory synapses (PubMed:11150294, PubMed:15312654). Promotes clustering of HT2RC at the cell surface (By similarity). {ECO:0000250|UniProtKB:O55164, ECO:0000269|PubMed:11150294, ECO:0000269|PubMed:15312654}.

Subunit: Interacts with CLDN5, DLG4, GRIN1, F11R/JAM, CLDN1, NG2, CRB1, MPP4 and PALS1 (By similarity). Interacts with HTR2A, HTR2B, HTR2C, PLEKHA1/TAPP1, PLEKHA2/TAPP2, CXADR, SYNGAP1, CAMK2A and CAMK2B. Interacts with FAT4 (via cytoplasmic domain) (By similarity). Interacts with DLL1 (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q8VBX6, ECO:0000269|PubMed:11150294, ECO:0000269|PubMed:11802782, ECO:0000269|PubMed:15312654, ECO:0000269|PubMed:15316081, ECO:0000269|PubMed:15364909, ECO:0000269|PubMed:9537516}.

Subunit: (Microbial infection) Interacts with human adenovirus type 9 E4-ORF1 protein. {ECO:0000269|PubMed:11000240}.

Subunit: (Microbial infection) Interacts with human papillomavirus 18/HPV18 protein E6. {ECO:0000269|PubMed:11000240}.

Subcellular location: Cell membrane; Peripheral membrane protein; Cytoplasmic side. Apical cell membrane; Peripheral membrane protein; Cytoplasmic side. Cell junction, synapse, postsynaptic density. Cell projection, dendrite. Cell junction, tight junction. Cell junction, synapse. Cell junction, synapse, synaptosome. Note=Colocalizes with HTR2C on the apical membrane of epithelial choroid plexus cells (By similarity). Highly enriched in postsynaptic densities (PSD). Localized to punctae on dendrites of hippocampal neurons and colocalizes with the synaptic marker DLG4. Localized mainly in the Schmidt-Lanterman incisures of myelinating Schwann cells (By similarity). In the retina, localizes to the sub-apical region adjacent to the adherens junction complex at the outer limiting membrane. Enriched at the tight junctions of epithelial cells. Association to the tight junctions depends on CXADR. {ECO:0000250, ECO:0000250|UniProtKB:O55164}.

Tissue specificity: Expressed in heart, brain, placenta, liver, skeletal muscle, kidney and pancreas. {ECO:0000269|PubMed:9537516}.

Domain: The PDZ domain 1 binds NG2. The PDZ domains 7 and 10 bind the Ad9 E4-ORF1 oncoprotein. The PDZ domain 9 binds F11R. The PDZ domain 10 binds the C-terminus of CLDN1 and KIT and the C-terminal PDZ-binding motif of HTR2C. The PDZ domain 13 binds CXADR (By similarity). The PDZ domain 2 binds CAMK2A and CAMK2B. The PDZ domains 10 and 13 bind PLEKHA1 and PLEKHA2. The PDZ domain 13 binds SYNGAP1. {ECO:0000250, ECO:0000269|PubMed:11150294, ECO:0000269|PubMed:11802782, ECO:0000269|PubMed:15312654}.

Disease: Hydrocephalus, congenital, 2, with or without brain or eye anomalies (HYC2) [MIM:615219]: A form of congenital hydrocephalus, a disease characterized by onset in utero of enlarged ventricles due to accumulation of ventricular cerebrospinal fluid. HYC2 affected individuals have variable neurologic impairment. Some individuals have other brain abnormalities, including lissencephaly, thinning of the corpus callosum, and neuronal heterotopia. Most patients have delayed motor development and some have delayed intellectual development and/or seizures. Additional congenital features, including cardiac septal defects, iris coloboma, and non-specific dysmorphic features, may be observed. HYC2 inheritance is autosomal recessive. {ECO:0000269|PubMed:23240096, ECO:0000269|PubMed:28556411}. Note=The disease is caused by variants affecting the gene represented in this entry.

Sequence caution: Sequence=AAC61870.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305}; Sequence=BAC05409.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAE06123.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAI56786.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; 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:		Member of the NMDAR signaling complex that may play a role in control of AMPAR potentiation and synaptic plasticity in excitatory synapses (PubMed:11150294, PubMed:15312654). Promotes clustering of HT2RC at the cell surface (By similarity). {ECO:0000250\|UniProtKB:O55164, ECO:0000269\|PubMed:11150294, ECO:0000269\|PubMed:15312654}.


Subunit:		Interacts with CLDN5, DLG4, GRIN1, F11R/JAM, CLDN1, NG2, CRB1, MPP4 and PALS1 (By similarity). Interacts with HTR2A, HTR2B, HTR2C, PLEKHA1/TAPP1, PLEKHA2/TAPP2, CXADR, SYNGAP1, CAMK2A and CAMK2B. Interacts with FAT4 (via cytoplasmic domain) (By similarity). Interacts with DLL1 (By similarity). {ECO:0000250, ECO:0000250\|UniProtKB:Q8VBX6, ECO:0000269\|PubMed:11150294, ECO:0000269\|PubMed:11802782, ECO:0000269\|PubMed:15312654, ECO:0000269\|PubMed:15316081, ECO:0000269\|PubMed:15364909, ECO:0000269\|PubMed:9537516}.
Subunit:		(Microbial infection) Interacts with human adenovirus type 9 E4-ORF1 protein. {ECO:0000269\|PubMed:11000240}.
Subunit:		(Microbial infection) Interacts with human papillomavirus 18/HPV18 protein E6. {ECO:0000269\|PubMed:11000240}.
Subcellular location:		Cell membrane; Peripheral membrane protein; Cytoplasmic side. Apical cell membrane; Peripheral membrane protein; Cytoplasmic side. Cell junction, synapse, postsynaptic density. Cell projection, dendrite. Cell junction, tight junction. Cell junction, synapse. Cell junction, synapse, synaptosome. Note=Colocalizes with HTR2C on the apical membrane of epithelial choroid plexus cells (By similarity). Highly enriched in postsynaptic densities (PSD). Localized to punctae on dendrites of hippocampal neurons and colocalizes with the synaptic marker DLG4. Localized mainly in the Schmidt-Lanterman incisures of myelinating Schwann cells (By similarity). In the retina, localizes to the sub-apical region adjacent to the adherens junction complex at the outer limiting membrane. Enriched at the tight junctions of epithelial cells. Association to the tight junctions depends on CXADR. {ECO:0000250, ECO:0000250\|UniProtKB:O55164}.
Tissue specificity:		Expressed in heart, brain, placenta, liver, skeletal muscle, kidney and pancreas. {ECO:0000269\|PubMed:9537516}.
Domain:		The PDZ domain 1 binds NG2. The PDZ domains 7 and 10 bind the Ad9 E4-ORF1 oncoprotein. The PDZ domain 9 binds F11R. The PDZ domain 10 binds the C-terminus of CLDN1 and KIT and the C-terminal PDZ-binding motif of HTR2C. The PDZ domain 13 binds CXADR (By similarity). The PDZ domain 2 binds CAMK2A and CAMK2B. The PDZ domains 10 and 13 bind PLEKHA1 and PLEKHA2. The PDZ domain 13 binds SYNGAP1. {ECO:0000250, ECO:0000269\|PubMed:11150294, ECO:0000269\|PubMed:11802782, ECO:0000269\|PubMed:15312654}.
Disease:		Hydrocephalus, congenital, 2, with or without brain or eye anomalies (HYC2) [MIM:615219]: A form of congenital hydrocephalus, a disease characterized by onset in utero of enlarged ventricles due to accumulation of ventricular cerebrospinal fluid. HYC2 affected individuals have variable neurologic impairment. Some individuals have other brain abnormalities, including lissencephaly, thinning of the corpus callosum, and neuronal heterotopia. Most patients have delayed motor development and some have delayed intellectual development and/or seizures. Additional congenital features, including cardiac septal defects, iris coloboma, and non-specific dysmorphic features, may be observed. HYC2 inheritance is autosomal recessive. {ECO:0000269\|PubMed:23240096, ECO:0000269\|PubMed:28556411}. Note=The disease is caused by variants affecting the gene represented in this entry.
Sequence caution:		Sequence=AAC61870.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305}; Sequence=BAC05409.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAE06123.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAI56786.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};