UniProt functional annotation for Q99NH2



	UniProt functional annotation for Q99NH2

UniProt code: Q99NH2.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Adapter protein involved in asymmetrical cell division and cell polarization processes (By similarity). Seems to play a central role in the formation of epithelial tight junctions (By similarity). Targets the phosphatase PTEN to cell junctions (By similarity). Association with PARD6B may prevent the interaction of PARD3 with F11R/JAM1, thereby preventing tight junction assembly (PubMed:11839275). The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins (By similarity). Required for establishment of neuronal polarity and normal axon formation in cultured hippocampal neurons (By similarity). Involved in Schwann cell peripheral myelination (PubMed:21949390). {ECO:0000250|UniProtKB:Q8TEW0, ECO:0000250|UniProtKB:Q9Z340, ECO:0000269|PubMed:11839275, ECO:0000269|PubMed:21949390}.

Subunit: Interacts with PRCKI and CDH5. Interacts (via PDZ 3 domain) with PTEN (via C-terminus). Component of a complex whose core is composed of ARHGAP17, AMOT, PALS1, PATJ and PARD3/PAR3. Interacts with LIMK2, AURKA and AURKB. Component of the Par polarity complex, composed of at least phosphorylated PRKCZ, PARD3 and TIAM1. Interacts with ECT2 and FBF1 (By similarity). Interacts (via PDZ 1 domain) with F11R/JAM1, PARD6A and PARD6B. Part of a complex with PARD6A or PARD6B, PRKCI or PRKCZ and CDC42 or RAC1. Directly interacts with TIAM1 and TIAM2. Interacts with SIRT2. Interacts (via coiled-coil domain) with FRMD4A (PubMed:20080746). Found in a complex with PARD3, CYTH1 and FRMD4A (PubMed:20080746). Interacts with SAPCD2 (By similarity). Interacts with PRKCA (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q8TEW0, ECO:0000269|PubMed:10934474, ECO:0000269|PubMed:10934475, ECO:0000269|PubMed:11447115, ECO:0000269|PubMed:11839275, ECO:0000269|PubMed:19893486, ECO:0000269|PubMed:20047332, ECO:0000269|PubMed:20080746}.

Subunit: [Isoform 2]: Interacts with PRKCZ. {ECO:0000269|PubMed:10934475}.

Subcellular location: Cytoplasm. Endomembrane system. Cell junction. Cell junction, tight junction {ECO:0000269|PubMed:10934475, ECO:0000269|PubMed:20080746}. Cell junction, adherens junction {ECO:0000269|PubMed:20080746}. Cytoplasm, cell cortex. Cytoplasm, cytoskeleton. Cell membrane {ECO:0000250}. Note=Localized along the cell-cell contact region. Colocalizes with PARD6A and PRKCI at epithelial tight junctions. Colocalizes with the cortical actin that overlays the meiotic spindle during metaphase I and metaphase II. Presence of KRIT1, CDH5 and RAP1B is required for its localization to the cell junction (By similarity). Colocalized with SIRT2 in internode region of myelin sheath. {ECO:0000250}.

Tissue specificity: All isoforms are expressed in heart, while expression in brain is mainly limited to isoform 1, and to isoform 3 to a weaker level.

Developmental stage: Expressed at the outer limiting membrane of the retina at 3 months of age. {ECO:0000269|PubMed:23001562}.

Developmental stage: [Isoform 2]: Not expressed in the oocyte. {ECO:0000269|PubMed:15766746}.

Developmental stage: [Isoform 1]: Expressed in the oocyte from 9.5 dpc to 14.5 dpc. {ECO:0000269|PubMed:15766746}.

Developmental stage: [Isoform 3]: Expressed in the oocyte from 9.5 dpc to 14.5 dpc. {ECO:0000269|PubMed:15766746}.

Developmental stage: [Isoform 4]: Expression increases steadily throughout oocyte maturation. {ECO:0000269|PubMed:15766746}.

Developmental stage: [Isoform 5]: Expression decreases in the egg as compared to the oocyte. {ECO:0000269|PubMed:15766746}.

Domain: Contains a conserved N-terminal oligomerization domain (NTD) that is involved in oligomerization and is essential for proper subapical membrane localization. {ECO:0000250}.

Domain: The second PDZ domain mediates interaction with membranes containing phosphoinositol lipids. {ECO:0000250}.

Ptm: Acetylated. Deacetylated by SIRT2, thereby inhibiting Schwann cell peripheral myelination. {ECO:0000269|PubMed:21949390}.

Ptm: Phosphorylation at Ser-824 by PRKCZ and PRKCI occurs at the most apical tip of epithelial cell-cell contacts during the initial phase of tight junction formation and may promote dissociation of the complex with PARD6. EGF-induced Tyr-1123 phosphorylation mediates dissociation from LIMK2 (By similarity). Phosphorylation by AURKA at Ser-958 is required for the normal establishment of neuronal polarity (By similarity). Isoform 4 and isoform 5 are phosphorylated during oocyte maturation (Probable). {ECO:0000250, ECO:0000305}.

Similarity: Belongs to the PAR3 family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Adapter protein involved in asymmetrical cell division and cell polarization processes (By similarity). Seems to play a central role in the formation of epithelial tight junctions (By similarity). Targets the phosphatase PTEN to cell junctions (By similarity). Association with PARD6B may prevent the interaction of PARD3 with F11R/JAM1, thereby preventing tight junction assembly (PubMed:11839275). The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins (By similarity). Required for establishment of neuronal polarity and normal axon formation in cultured hippocampal neurons (By similarity). Involved in Schwann cell peripheral myelination (PubMed:21949390). {ECO:0000250\|UniProtKB:Q8TEW0, ECO:0000250\|UniProtKB:Q9Z340, ECO:0000269\|PubMed:11839275, ECO:0000269\|PubMed:21949390}.


Subunit:		Interacts with PRCKI and CDH5. Interacts (via PDZ 3 domain) with PTEN (via C-terminus). Component of a complex whose core is composed of ARHGAP17, AMOT, PALS1, PATJ and PARD3/PAR3. Interacts with LIMK2, AURKA and AURKB. Component of the Par polarity complex, composed of at least phosphorylated PRKCZ, PARD3 and TIAM1. Interacts with ECT2 and FBF1 (By similarity). Interacts (via PDZ 1 domain) with F11R/JAM1, PARD6A and PARD6B. Part of a complex with PARD6A or PARD6B, PRKCI or PRKCZ and CDC42 or RAC1. Directly interacts with TIAM1 and TIAM2. Interacts with SIRT2. Interacts (via coiled-coil domain) with FRMD4A (PubMed:20080746). Found in a complex with PARD3, CYTH1 and FRMD4A (PubMed:20080746). Interacts with SAPCD2 (By similarity). Interacts with PRKCA (By similarity). {ECO:0000250, ECO:0000250\|UniProtKB:Q8TEW0, ECO:0000269\|PubMed:10934474, ECO:0000269\|PubMed:10934475, ECO:0000269\|PubMed:11447115, ECO:0000269\|PubMed:11839275, ECO:0000269\|PubMed:19893486, ECO:0000269\|PubMed:20047332, ECO:0000269\|PubMed:20080746}.
Subunit:		[Isoform 2]: Interacts with PRKCZ. {ECO:0000269\|PubMed:10934475}.
Subcellular location:		Cytoplasm. Endomembrane system. Cell junction. Cell junction, tight junction {ECO:0000269\|PubMed:10934475, ECO:0000269\|PubMed:20080746}. Cell junction, adherens junction {ECO:0000269\|PubMed:20080746}. Cytoplasm, cell cortex. Cytoplasm, cytoskeleton. Cell membrane {ECO:0000250}. Note=Localized along the cell-cell contact region. Colocalizes with PARD6A and PRKCI at epithelial tight junctions. Colocalizes with the cortical actin that overlays the meiotic spindle during metaphase I and metaphase II. Presence of KRIT1, CDH5 and RAP1B is required for its localization to the cell junction (By similarity). Colocalized with SIRT2 in internode region of myelin sheath. {ECO:0000250}.
Tissue specificity:		All isoforms are expressed in heart, while expression in brain is mainly limited to isoform 1, and to isoform 3 to a weaker level.
Developmental stage:		Expressed at the outer limiting membrane of the retina at 3 months of age. {ECO:0000269\|PubMed:23001562}.
Developmental stage:		[Isoform 2]: Not expressed in the oocyte. {ECO:0000269\|PubMed:15766746}.
Developmental stage:		[Isoform 1]: Expressed in the oocyte from 9.5 dpc to 14.5 dpc. {ECO:0000269\|PubMed:15766746}.
Developmental stage:		[Isoform 3]: Expressed in the oocyte from 9.5 dpc to 14.5 dpc. {ECO:0000269\|PubMed:15766746}.
Developmental stage:		[Isoform 4]: Expression increases steadily throughout oocyte maturation. {ECO:0000269\|PubMed:15766746}.
Developmental stage:		[Isoform 5]: Expression decreases in the egg as compared to the oocyte. {ECO:0000269\|PubMed:15766746}.
Domain:		Contains a conserved N-terminal oligomerization domain (NTD) that is involved in oligomerization and is essential for proper subapical membrane localization. {ECO:0000250}.
Domain:		The second PDZ domain mediates interaction with membranes containing phosphoinositol lipids. {ECO:0000250}.
Ptm:		Acetylated. Deacetylated by SIRT2, thereby inhibiting Schwann cell peripheral myelination. {ECO:0000269\|PubMed:21949390}.
Ptm:		Phosphorylation at Ser-824 by PRKCZ and PRKCI occurs at the most apical tip of epithelial cell-cell contacts during the initial phase of tight junction formation and may promote dissociation of the complex with PARD6. EGF-induced Tyr-1123 phosphorylation mediates dissociation from LIMK2 (By similarity). Phosphorylation by AURKA at Ser-958 is required for the normal establishment of neuronal polarity (By similarity). Isoform 4 and isoform 5 are phosphorylated during oocyte maturation (Probable). {ECO:0000250, ECO:0000305}.
Similarity:		Belongs to the PAR3 family. {ECO:0000305}.