UniProt functional annotation for O14745



	UniProt functional annotation for O14745

UniProt code: O14745.

Organism: Homo sapiens (Human).

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

Function: Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. Necessary for recycling of internalized ADRB2. Was first known to play a role in the regulation of the activity and subcellular location of SLC9A3. Necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3. May enhance Wnt signaling. May participate in HTR4 targeting to microvilli (By similarity). Involved in the regulation of phosphate reabsorption in the renal proximal tubules. Involved in sperm capacitation. May participate in the regulation of the chloride and bicarbonate homeostasis in spermatozoa. {ECO:0000250, ECO:0000269|PubMed:10499588, ECO:0000269|PubMed:18784102, ECO:0000269|PubMed:9096337, ECO:0000269|PubMed:9430655}.

Subunit: Homodimer, and heterodimer with SLC9A3R2. Binds the N-termini of EZR, RDX and MSN. Binds the C-termini of PDGFRA, PDGFRB, ADRB2, NOS2 and CFTR. Binds ARHGAP17, EPI64, RACK1, OPRK1, GNAQ, CTNNB1 and PLCB3. Binds PDZK1 (By similarity). Interacts with CLCN3. Binds the C-terminus of PAG1. In resting T-cells, part of a PAG1-SLC9A3R1-MSN complex which is disrupted upon TCR activation. Forms a complex with CFTR and SLC4A7. Forms a complex with SLC4A7 and ATP6V1B1. Interacts with TRPC4 (via the PDZ-binding domain). Directly interacts with HTR4 (By similarity). Interacts (via the PDZ 1 domain) with PODXL (via the C-terminal PDZ- binding motif DTHL); interaction is not detected in glomerular epithelium cells. Interacts (via the PDZ 1 domain) with PODXL (via the C-terminal PDZ-binding motif DTHL); the interaction take place early in the secretory pathway and is necessary for its apical membrane sorting (By similarity). Interacts with SLC26A3 (By similarity). Interacts with MCC. Interacts with SLC34A1. Interacts (via the PDZ domains) with SLC26A6 isoform 4 and isoform 5. {ECO:0000250, ECO:0000269|PubMed:10499588, ECO:0000269|PubMed:11285285, ECO:0000269|PubMed:11304524, ECO:0000269|PubMed:11684085, ECO:0000269|PubMed:11882663, ECO:0000269|PubMed:11956211, ECO:0000269|PubMed:12004055, ECO:0000269|PubMed:12080081, ECO:0000269|PubMed:12154080, ECO:0000269|PubMed:12193606, ECO:0000269|PubMed:12403779, ECO:0000269|PubMed:12444018, ECO:0000269|PubMed:12444019, ECO:0000269|PubMed:12471024, ECO:0000269|PubMed:12830000, ECO:0000269|PubMed:15020681, ECO:0000269|PubMed:16615918, ECO:0000269|PubMed:19555689, ECO:0000269|PubMed:22506049, ECO:0000269|PubMed:9096337, ECO:0000269|PubMed:9314537, ECO:0000269|PubMed:9430655}.

Subcellular location: Cytoplasm {ECO:0000250}. Apical cell membrane {ECO:0000250}. Endomembrane system; Peripheral membrane protein. Cell projection, filopodium. Cell projection, ruffle. Cell projection, microvillus. Note=Translocates from the cytoplasm to the apical cell membrane in a PODXL-dependent manner. Colocalizes with CFTR at the midpiece of sperm tail (By similarity). Colocalizes with actin in microvilli-rich apical regions of the syncytiotrophoblast. Found in microvilli, ruffling membrane and filopodia of HeLa cells. Present in lipid rafts of T-cells. {ECO:0000250}.

Tissue specificity: Detected in liver, kidney, pancreas, prostate, spleen, small intestine and placenta, in particular in the syncytiotrophoblast. {ECO:0000269|PubMed:9096337, ECO:0000269|PubMed:9314537}.

Induction: By estrogen. {ECO:0000269|PubMed:12145337}.

Ptm: Phosphorylated on serine residues. {ECO:0000269|PubMed:9314537}.

Disease: Nephrolithiasis/osteoporosis, hypophosphatemic, 2 (NPHLOP2) [MIM:612287]: A disease characterized by decreased renal phosphate absorption, renal phosphate wasting, hypophosphatemia, hyperphosphaturia, hypercalciuria, nephrolithiasis and osteoporosis. {ECO:0000269|PubMed:18784102, ECO:0000269|PubMed:22506049}. Note=The disease is caused by variants affecting the gene represented in this entry.

Sequence caution: Sequence=AAH49220.1; Type=Erroneous initiation; Note=Extended 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:		Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. Necessary for recycling of internalized ADRB2. Was first known to play a role in the regulation of the activity and subcellular location of SLC9A3. Necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3. May enhance Wnt signaling. May participate in HTR4 targeting to microvilli (By similarity). Involved in the regulation of phosphate reabsorption in the renal proximal tubules. Involved in sperm capacitation. May participate in the regulation of the chloride and bicarbonate homeostasis in spermatozoa. {ECO:0000250, ECO:0000269\|PubMed:10499588, ECO:0000269\|PubMed:18784102, ECO:0000269\|PubMed:9096337, ECO:0000269\|PubMed:9430655}.


Subunit:		Homodimer, and heterodimer with SLC9A3R2. Binds the N-termini of EZR, RDX and MSN. Binds the C-termini of PDGFRA, PDGFRB, ADRB2, NOS2 and CFTR. Binds ARHGAP17, EPI64, RACK1, OPRK1, GNAQ, CTNNB1 and PLCB3. Binds PDZK1 (By similarity). Interacts with CLCN3. Binds the C-terminus of PAG1. In resting T-cells, part of a PAG1-SLC9A3R1-MSN complex which is disrupted upon TCR activation. Forms a complex with CFTR and SLC4A7. Forms a complex with SLC4A7 and ATP6V1B1. Interacts with TRPC4 (via the PDZ-binding domain). Directly interacts with HTR4 (By similarity). Interacts (via the PDZ 1 domain) with PODXL (via the C-terminal PDZ- binding motif DTHL); interaction is not detected in glomerular epithelium cells. Interacts (via the PDZ 1 domain) with PODXL (via the C-terminal PDZ-binding motif DTHL); the interaction take place early in the secretory pathway and is necessary for its apical membrane sorting (By similarity). Interacts with SLC26A3 (By similarity). Interacts with MCC. Interacts with SLC34A1. Interacts (via the PDZ domains) with SLC26A6 isoform 4 and isoform 5. {ECO:0000250, ECO:0000269\|PubMed:10499588, ECO:0000269\|PubMed:11285285, ECO:0000269\|PubMed:11304524, ECO:0000269\|PubMed:11684085, ECO:0000269\|PubMed:11882663, ECO:0000269\|PubMed:11956211, ECO:0000269\|PubMed:12004055, ECO:0000269\|PubMed:12080081, ECO:0000269\|PubMed:12154080, ECO:0000269\|PubMed:12193606, ECO:0000269\|PubMed:12403779, ECO:0000269\|PubMed:12444018, ECO:0000269\|PubMed:12444019, ECO:0000269\|PubMed:12471024, ECO:0000269\|PubMed:12830000, ECO:0000269\|PubMed:15020681, ECO:0000269\|PubMed:16615918, ECO:0000269\|PubMed:19555689, ECO:0000269\|PubMed:22506049, ECO:0000269\|PubMed:9096337, ECO:0000269\|PubMed:9314537, ECO:0000269\|PubMed:9430655}.
Subcellular location:		Cytoplasm {ECO:0000250}. Apical cell membrane {ECO:0000250}. Endomembrane system; Peripheral membrane protein. Cell projection, filopodium. Cell projection, ruffle. Cell projection, microvillus. Note=Translocates from the cytoplasm to the apical cell membrane in a PODXL-dependent manner. Colocalizes with CFTR at the midpiece of sperm tail (By similarity). Colocalizes with actin in microvilli-rich apical regions of the syncytiotrophoblast. Found in microvilli, ruffling membrane and filopodia of HeLa cells. Present in lipid rafts of T-cells. {ECO:0000250}.
Tissue specificity:		Detected in liver, kidney, pancreas, prostate, spleen, small intestine and placenta, in particular in the syncytiotrophoblast. {ECO:0000269\|PubMed:9096337, ECO:0000269\|PubMed:9314537}.
Induction:		By estrogen. {ECO:0000269\|PubMed:12145337}.
Ptm:		Phosphorylated on serine residues. {ECO:0000269\|PubMed:9314537}.
Disease:		Nephrolithiasis/osteoporosis, hypophosphatemic, 2 (NPHLOP2) [MIM:612287]: A disease characterized by decreased renal phosphate absorption, renal phosphate wasting, hypophosphatemia, hyperphosphaturia, hypercalciuria, nephrolithiasis and osteoporosis. {ECO:0000269\|PubMed:18784102, ECO:0000269\|PubMed:22506049}. Note=The disease is caused by variants affecting the gene represented in this entry.
Sequence caution:		Sequence=AAH49220.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};