UniProt functional annotation for Q8N3R9



	UniProt functional annotation for Q8N3R9

UniProt code: Q8N3R9.

Organism: Homo sapiens (Human).

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

Function: Plays a role in tight junction biogenesis and in the establishment of cell polarity in epithelial cells (PubMed:16678097, PubMed:25385611). Also involved in adherens junction biogenesis by ensuring correct localization of the exocyst complex protein EXOC4/SEC8 which allows trafficking of adherens junction structural component CDH1 to the cell surface (By similarity). Plays a role through its interaction with CDH5 in vascular lumen formation and endothelial membrane polarity (PubMed:27466317). Required during embryonic and postnatal retinal development (By similarity). Required for the maintenance of cerebellar progenitor cells in an undifferentiated proliferative state, preventing premature differentiation, and is required for cerebellar histogenesis, fissure formation, cerebellar layer organization and cortical development (By similarity). Plays a role in neuronal progenitor cell survival, potentially via promotion of mTOR signaling (By similarity). Plays a role in the radial and longitudinal extension of the myelin sheath in Schwann cells (By similarity). May modulate SC6A1/GAT1-mediated GABA uptake by stabilizing the transporter (By similarity). Plays a role in the T-cell receptor-mediated activation of NF-kappa-B (PubMed:21479189). Required for localization of EZR to the apical membrane of parietal cells and may play a role in the dynamic remodeling of the apical cytoskeleton (By similarity). Required for the normal polarized localization of the vesicular marker STX4 (By similarity). Required for the correct trafficking of the myelin proteins PMP22 and MAG (By similarity). Involved in promoting phosphorylation and cytoplasmic retention of transcriptional coactivators YAP1 and WWTR1/TAZ which leads to suppression of TGFB1-dependent transcription of target genes such as CCN2/CTGF, SERPINE1/PAI1, SNAI1/SNAIL1 and SMAD7 (By similarity). {ECO:0000250|UniProtKB:B4F7E7, ECO:0000250|UniProtKB:Q9JLB2, ECO:0000269|PubMed:16678097, ECO:0000269|PubMed:21479189, ECO:0000269|PubMed:25385611, ECO:0000269|PubMed:27466317}.

Function: (Microbial infection) Acts as an interaction partner for human coronaviruses SARS-CoV and, probably, SARS-CoV-2 envelope protein E which results in delayed formation of tight junctions and disregulation of cell polarity. {ECO:0000269|PubMed:20861307, ECO:0000303|PubMed:32891874}.

Subunit: Heterodimer with MPP1 (PubMed:17584769). Forms a heterotrimeric complex composed of PALS1, LIN7B and PATJ; the N- terminal L27 domain of PALS1 interacts with the L27 domain of PATJ and the C-terminal L27 domain of PALS1 interacts with the L27 domain of LIN7B (PubMed:22337881). Component of a complex composed of PALS1, CRB1 and MPP4 (PubMed:15914641). Component of a complex whose core is composed of ARHGAP17, AMOT, PALS1, PATJ and PARD3/PAR3 (PubMed:16678097). Component of a complex composed of PALS1, CRB1 and EPB41L5 (PubMed:17920587). Within the complex, interacts (via HOOK domain) with EPB41L5 (via FERM domain), and interacts with CRB1 (via intracellular domain) (PubMed:17920587). Component of a complex composed of PALS1, MPP3 and CRB1; PALS1 acts as a bridging protein between MPP3 (via guanylate kinase-like domain) and CRB1 (PubMed:16519681). Component of a complex composed of CRB3, PALS1 and PATJ (By similarity). Interacts (via PDZ domain) with PATJ (via N- terminus) (PubMed:12527193). Interacts with EZR (By similarity). Interacts (via PDZ domain) with CRB1 (via C-terminal ERLI motif) (PubMed:25385611, PubMed:25760605). While the PDZ domain is sufficient for interaction with CRB1, the adjacent SH3 and guanylate kinase-like domains are likely to contribute to a high affinity interaction (PubMed:25385611). Interacts with WWTR1/TAZ (via WW domain) (PubMed:21145499). Interacts with MPP7 (PubMed:16678097, PubMed:17332497). Interacts (via PDZ domain) with CRB3 (via C-terminus) (By similarity). Interacts with LIN7C (By similarity). Interacts with MPDZ (By similarity). Interacts with PARD6B (By similarity). Interacts with SC6A1 (By similarity). Interacts with CDH5; the interaction promotes PALS1 localization to cell junctions and is required for CDH5- mediated vascular lumen formation and endothelial cell (PubMed:27466317). Interacts with NPHP1 (via coiled coil and SH3 domains) (PubMed:19755384). Interacts with NPHP4 (PubMed:19755384). Interacts with CRB2 (By similarity). {ECO:0000250|UniProtKB:E2QY99, ECO:0000250|UniProtKB:Q9JLB2, ECO:0000269|PubMed:12527193, ECO:0000269|PubMed:15914641, ECO:0000269|PubMed:16519681, ECO:0000269|PubMed:16678097, ECO:0000269|PubMed:17332497, ECO:0000269|PubMed:17584769, ECO:0000269|PubMed:17920587, ECO:0000269|PubMed:19755384, ECO:0000269|PubMed:21145499, ECO:0000269|PubMed:22337881, ECO:0000269|PubMed:25385611, ECO:0000269|PubMed:25760605, ECO:0000269|PubMed:27466317}.

Subunit: (Microbial infection) Interacts (via PDZ domain) with human coronaviruses SARS-CoV and, probably, SARS-CoV-2 envelope small membrane protein E (via C-terminus); this inhibits the interaction between PALS1 and CRB3. {ECO:0000269|PubMed:20861307, ECO:0000303|PubMed:32891874}.

Subcellular location: Golgi apparatus {ECO:0000269|PubMed:21479189}. Cell membrane; Peripheral membrane protein. Endomembrane system; Peripheral membrane protein. Cell junction, tight junction {ECO:0000269|PubMed:20861307}. Cell junction, adherens junction {ECO:0000269|PubMed:16519681}. Cell projection, axon {ECO:0000250|UniProtKB:Q9JLB2}. Perikaryon {ECO:0000250|UniProtKB:Q9JLB2}. Apical cell membrane {ECO:0000269|PubMed:15914641, ECO:0000269|PubMed:16519681, ECO:0000269|PubMed:25385611}. Note=Localized to the tight junctions of epithelial cells (By similarity). Localized to the Golgi apparatus in T lymphocytes (PubMed:21479189). Localized to a subset of intracellular vesicles (By similarity). Localized to the Purkinje cell body and axon (By similarity). Localized to intercellular junctions in vascular endothelial cells (PubMed:27466317). Localized to Schmidt-Lanterman incisures, the adaxonal domain, and the inner part of paranodal loops in myelinating Schwann cells of the sciatic nerve (By similarity). Localized to apical membrane domains of the outer limiting membrane (OLM) junctions in the retina (By similarity). Colocalizes with CRB1 at the OLM, apical to the adherens junction (PubMed:15914641). Colocalizes with MPP1 in the retina at the OLM (PubMed:17584769). Colocalizes with MPP3 to the subapical region of adherens junctions in the retina OLM (PubMed:16519681). {ECO:0000250|UniProtKB:Q9JLB2, ECO:0000269|PubMed:15914641, ECO:0000269|PubMed:16519681, ECO:0000269|PubMed:17584769, ECO:0000269|PubMed:21479189, ECO:0000269|PubMed:27466317}.

Subcellular location: Endoplasmic reticulum-Golgi intermediate compartment {ECO:0000269|PubMed:20861307}. Golgi apparatus {ECO:0000269|PubMed:20861307}. Note=(Microbial infection) Following infection by human SARS coronavirus, partially localized at the site of viral replication; the endoplasmic reticulum-Golgi intermediate compartment, reducing its levels at cell-cell contacts which results in delayed formation of tight junctions and affects establishment of cell polarity. {ECO:0000269|PubMed:20861307}.

Tissue specificity: Expressed at the outer limiting membrane in the retina (at protein level) (PubMed:15914641, PubMed:15558731, PubMed:16519681, PubMed:17584769). Expressed in T lymphocytes (at protein level) (PubMed:21479189). Expressed in the kidney (at protein level) (PubMed:17584769). {ECO:0000269|PubMed:15558731, ECO:0000269|PubMed:15914641, ECO:0000269|PubMed:16519681, ECO:0000269|PubMed:17584769, ECO:0000269|PubMed:21479189}.

Domain: The L27 domain 1 functions in targeting to the tight junctions by binding to and stabilizing PATJ. {ECO:0000250|UniProtKB:Q9JLB2}.

Domain: The PDZ domain binds to the C-terminus of SC6A1. {ECO:0000250|UniProtKB:Q9JLB2}.

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

Sequence caution: Sequence=AAH53366.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=BAB14172.1; Type=Erroneous initiation; Note=Truncated N-terminus.; 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:		Plays a role in tight junction biogenesis and in the establishment of cell polarity in epithelial cells (PubMed:16678097, PubMed:25385611). Also involved in adherens junction biogenesis by ensuring correct localization of the exocyst complex protein EXOC4/SEC8 which allows trafficking of adherens junction structural component CDH1 to the cell surface (By similarity). Plays a role through its interaction with CDH5 in vascular lumen formation and endothelial membrane polarity (PubMed:27466317). Required during embryonic and postnatal retinal development (By similarity). Required for the maintenance of cerebellar progenitor cells in an undifferentiated proliferative state, preventing premature differentiation, and is required for cerebellar histogenesis, fissure formation, cerebellar layer organization and cortical development (By similarity). Plays a role in neuronal progenitor cell survival, potentially via promotion of mTOR signaling (By similarity). Plays a role in the radial and longitudinal extension of the myelin sheath in Schwann cells (By similarity). May modulate SC6A1/GAT1-mediated GABA uptake by stabilizing the transporter (By similarity). Plays a role in the T-cell receptor-mediated activation of NF-kappa-B (PubMed:21479189). Required for localization of EZR to the apical membrane of parietal cells and may play a role in the dynamic remodeling of the apical cytoskeleton (By similarity). Required for the normal polarized localization of the vesicular marker STX4 (By similarity). Required for the correct trafficking of the myelin proteins PMP22 and MAG (By similarity). Involved in promoting phosphorylation and cytoplasmic retention of transcriptional coactivators YAP1 and WWTR1/TAZ which leads to suppression of TGFB1-dependent transcription of target genes such as CCN2/CTGF, SERPINE1/PAI1, SNAI1/SNAIL1 and SMAD7 (By similarity). {ECO:0000250\|UniProtKB:B4F7E7, ECO:0000250\|UniProtKB:Q9JLB2, ECO:0000269\|PubMed:16678097, ECO:0000269\|PubMed:21479189, ECO:0000269\|PubMed:25385611, ECO:0000269\|PubMed:27466317}.



Function:		(Microbial infection) Acts as an interaction partner for human coronaviruses SARS-CoV and, probably, SARS-CoV-2 envelope protein E which results in delayed formation of tight junctions and disregulation of cell polarity. {ECO:0000269\|PubMed:20861307, ECO:0000303\|PubMed:32891874}.


Subunit:		Heterodimer with MPP1 (PubMed:17584769). Forms a heterotrimeric complex composed of PALS1, LIN7B and PATJ; the N- terminal L27 domain of PALS1 interacts with the L27 domain of PATJ and the C-terminal L27 domain of PALS1 interacts with the L27 domain of LIN7B (PubMed:22337881). Component of a complex composed of PALS1, CRB1 and MPP4 (PubMed:15914641). Component of a complex whose core is composed of ARHGAP17, AMOT, PALS1, PATJ and PARD3/PAR3 (PubMed:16678097). Component of a complex composed of PALS1, CRB1 and EPB41L5 (PubMed:17920587). Within the complex, interacts (via HOOK domain) with EPB41L5 (via FERM domain), and interacts with CRB1 (via intracellular domain) (PubMed:17920587). Component of a complex composed of PALS1, MPP3 and CRB1; PALS1 acts as a bridging protein between MPP3 (via guanylate kinase-like domain) and CRB1 (PubMed:16519681). Component of a complex composed of CRB3, PALS1 and PATJ (By similarity). Interacts (via PDZ domain) with PATJ (via N- terminus) (PubMed:12527193). Interacts with EZR (By similarity). Interacts (via PDZ domain) with CRB1 (via C-terminal ERLI motif) (PubMed:25385611, PubMed:25760605). While the PDZ domain is sufficient for interaction with CRB1, the adjacent SH3 and guanylate kinase-like domains are likely to contribute to a high affinity interaction (PubMed:25385611). Interacts with WWTR1/TAZ (via WW domain) (PubMed:21145499). Interacts with MPP7 (PubMed:16678097, PubMed:17332497). Interacts (via PDZ domain) with CRB3 (via C-terminus) (By similarity). Interacts with LIN7C (By similarity). Interacts with MPDZ (By similarity). Interacts with PARD6B (By similarity). Interacts with SC6A1 (By similarity). Interacts with CDH5; the interaction promotes PALS1 localization to cell junctions and is required for CDH5- mediated vascular lumen formation and endothelial cell (PubMed:27466317). Interacts with NPHP1 (via coiled coil and SH3 domains) (PubMed:19755384). Interacts with NPHP4 (PubMed:19755384). Interacts with CRB2 (By similarity). {ECO:0000250\|UniProtKB:E2QY99, ECO:0000250\|UniProtKB:Q9JLB2, ECO:0000269\|PubMed:12527193, ECO:0000269\|PubMed:15914641, ECO:0000269\|PubMed:16519681, ECO:0000269\|PubMed:16678097, ECO:0000269\|PubMed:17332497, ECO:0000269\|PubMed:17584769, ECO:0000269\|PubMed:17920587, ECO:0000269\|PubMed:19755384, ECO:0000269\|PubMed:21145499, ECO:0000269\|PubMed:22337881, ECO:0000269\|PubMed:25385611, ECO:0000269\|PubMed:25760605, ECO:0000269\|PubMed:27466317}.
Subunit:		(Microbial infection) Interacts (via PDZ domain) with human coronaviruses SARS-CoV and, probably, SARS-CoV-2 envelope small membrane protein E (via C-terminus); this inhibits the interaction between PALS1 and CRB3. {ECO:0000269\|PubMed:20861307, ECO:0000303\|PubMed:32891874}.
Subcellular location:		Golgi apparatus {ECO:0000269\|PubMed:21479189}. Cell membrane; Peripheral membrane protein. Endomembrane system; Peripheral membrane protein. Cell junction, tight junction {ECO:0000269\|PubMed:20861307}. Cell junction, adherens junction {ECO:0000269\|PubMed:16519681}. Cell projection, axon {ECO:0000250\|UniProtKB:Q9JLB2}. Perikaryon {ECO:0000250\|UniProtKB:Q9JLB2}. Apical cell membrane {ECO:0000269\|PubMed:15914641, ECO:0000269\|PubMed:16519681, ECO:0000269\|PubMed:25385611}. Note=Localized to the tight junctions of epithelial cells (By similarity). Localized to the Golgi apparatus in T lymphocytes (PubMed:21479189). Localized to a subset of intracellular vesicles (By similarity). Localized to the Purkinje cell body and axon (By similarity). Localized to intercellular junctions in vascular endothelial cells (PubMed:27466317). Localized to Schmidt-Lanterman incisures, the adaxonal domain, and the inner part of paranodal loops in myelinating Schwann cells of the sciatic nerve (By similarity). Localized to apical membrane domains of the outer limiting membrane (OLM) junctions in the retina (By similarity). Colocalizes with CRB1 at the OLM, apical to the adherens junction (PubMed:15914641). Colocalizes with MPP1 in the retina at the OLM (PubMed:17584769). Colocalizes with MPP3 to the subapical region of adherens junctions in the retina OLM (PubMed:16519681). {ECO:0000250\|UniProtKB:Q9JLB2, ECO:0000269\|PubMed:15914641, ECO:0000269\|PubMed:16519681, ECO:0000269\|PubMed:17584769, ECO:0000269\|PubMed:21479189, ECO:0000269\|PubMed:27466317}.
Subcellular location:		Endoplasmic reticulum-Golgi intermediate compartment {ECO:0000269\|PubMed:20861307}. Golgi apparatus {ECO:0000269\|PubMed:20861307}. Note=(Microbial infection) Following infection by human SARS coronavirus, partially localized at the site of viral replication; the endoplasmic reticulum-Golgi intermediate compartment, reducing its levels at cell-cell contacts which results in delayed formation of tight junctions and affects establishment of cell polarity. {ECO:0000269\|PubMed:20861307}.
Tissue specificity:		Expressed at the outer limiting membrane in the retina (at protein level) (PubMed:15914641, PubMed:15558731, PubMed:16519681, PubMed:17584769). Expressed in T lymphocytes (at protein level) (PubMed:21479189). Expressed in the kidney (at protein level) (PubMed:17584769). {ECO:0000269\|PubMed:15558731, ECO:0000269\|PubMed:15914641, ECO:0000269\|PubMed:16519681, ECO:0000269\|PubMed:17584769, ECO:0000269\|PubMed:21479189}.
Domain:		The L27 domain 1 functions in targeting to the tight junctions by binding to and stabilizing PATJ. {ECO:0000250\|UniProtKB:Q9JLB2}.
Domain:		The PDZ domain binds to the C-terminus of SC6A1. {ECO:0000250\|UniProtKB:Q9JLB2}.
Similarity:		Belongs to the MAGUK family. {ECO:0000305}.
Sequence caution:		Sequence=AAH53366.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=BAB14172.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};