UniProt functional annotation for O15259



	UniProt functional annotation for O15259

UniProt code: O15259.

Organism: Homo sapiens (Human).

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

Function: Together with BCAR1 it may play a role in the control of epithelial cell polarity (By similarity). Involved in the organization of apical junctions in kidney cells together with NPHP4 and RPGRIP1L/NPHP8 (By similarity). Does not seem to be strictly required for ciliogenesis (By similarity). Seems to help to recruit PTK2B/PYK2 to cell matrix adhesions, thereby initiating phosphorylation of PTK2B/PYK2 and PTK2B/PYK2-dependent signaling (By similarity). May play a role in the regulation of intraflagellar transport (IFT) during cilia assembly. Required for normal retina development (By similarity). In connecting photoreceptor cilia influences the movement of some IFT proteins such as IFT88 and WDR19. Involved in spermatogenesis (By similarity). {ECO:0000250|UniProtKB:Q9QY53}.

Subunit: Interacts with BCAR1, PTK2B/PYK2 and tensin. Interacts with INVS and NPHP3. Interacts with PACS1; the interaction is dependent on NPHP1 phosphorylation by CK2. Interacts with KIF7. Interacts with AHI1 and TNK2. Interacts with NPHP4 in a complex containing NPHP1, NPHP4 and RPGRIP1L. Interacts with IQCB1; the interaction likely requires additional interactors. Interacts with ANKS3 (By similarity).Interacts with SPATA7 (By similarity). Interacts with FLNA (By similarity). {ECO:0000250|UniProtKB:Q9QY53, ECO:0000269|PubMed:12244321, ECO:0000269|PubMed:12872122, ECO:0000269|PubMed:12872123, ECO:0000269|PubMed:16308564, ECO:0000269|PubMed:18477472, ECO:0000269|PubMed:18633336, ECO:0000269|PubMed:20856870, ECO:0000269|PubMed:21357692, ECO:0000269|PubMed:21565611, ECO:0000269|PubMed:21633164}.

Subcellular location: Cell junction {ECO:0000250|UniProtKB:Q9QY53}. Cell junction, adherens junction {ECO:0000250|UniProtKB:Q9QY53}. Cell projection, cilium {ECO:0000269|PubMed:16885411}. Cytoplasm, cytoskeleton, cilium axoneme {ECO:0000269|PubMed:16308564, ECO:0000269|PubMed:16885411}. Cell junction, tight junction. Note=In the retinal photoreceptor cell layer, localizes at the connecting cilium (By similarity). Colocalizes with E-cadherin and BCAR1 at or near the cell-cell adherens junctions (By similarity). Localized to respiratory cilia axoneme (PubMed:16308564, PubMed:16885411). Localized to the transition zone of respiratory cilia (PubMed:16885411). Localized to the transition zone of photoreceptor-connecting cilia and renal monocilia (By similarity). In cultured renal cells, it localizes diffusely in the cytoplasm but, as cells approach confluence, it accumulates at basolateral tight junctions (By similarity). {ECO:0000250|UniProtKB:Q9QY53, ECO:0000269|PubMed:16308564, ECO:0000269|PubMed:16885411}.

Tissue specificity: Widespread expression, with highest levels in pituitary gland, spinal cord, thyroid gland, testis, skeletal muscle, lymph node and trachea. Weakly expressed in heart, kidney and pancreas. Expressed in nasal epithelial cells (at protein level) (PubMed:16308564). Expressed in the renal collecting duct (at protein level) (PubMed:18477472). {ECO:0000269|PubMed:16308564, ECO:0000269|PubMed:18477472}.

Developmental stage: During in vitro ciliogenesis translocalizes from the cytoplasm to the ciliary transition zone during epithelial cell polarization. {ECO:0000269|PubMed:16885411}.

Domain: The SH3 domain mediates the stable interaction with Cas. {ECO:0000250}.

Ptm: Phosphorylation by CK2 is required for the interaction with PACS1 and the targeting to the base region of cilia. {ECO:0000269|PubMed:16308564, ECO:0000269|PubMed:21357692}.

Disease: Nephronophthisis 1 (NPHP1) [MIM:256100]: An autosomal recessive inherited disease characterized by anemia, polyuria, polydipsia, isosthenuria and death in uremia. Symmetrical destruction of the kidneys involving both tubules and glomeruli occurs. The underlying pathology is a chronic tubulo-interstitial nephropathy with characteristic tubular basement membrane thickening and medullary cyst formation. Associations with extrarenal symptoms, especially ocular lesions, are frequent. The age at death ranges from about 4 to 15 years. {ECO:0000269|PubMed:10839884}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Senior-Loken syndrome 1 (SLSN1) [MIM:266900]: A renal-retinal disorder characterized by progressive wasting of the filtering unit of the kidney (nephronophthisis), with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life. {ECO:0000269|PubMed:9856524}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Joubert syndrome 4 (JBTS4) [MIM:609583]: A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. Joubert syndrome type 4 is a phenotypically mild form. {ECO:0000269|PubMed:15138899, ECO:0000269|PubMed:26477546}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: Nephronophthisis type 1 patients deficient for NPHP1 show normal overall integrity of respiratory cilia.

Similarity: Belongs to the nephrocystin-1 family. {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:		Together with BCAR1 it may play a role in the control of epithelial cell polarity (By similarity). Involved in the organization of apical junctions in kidney cells together with NPHP4 and RPGRIP1L/NPHP8 (By similarity). Does not seem to be strictly required for ciliogenesis (By similarity). Seems to help to recruit PTK2B/PYK2 to cell matrix adhesions, thereby initiating phosphorylation of PTK2B/PYK2 and PTK2B/PYK2-dependent signaling (By similarity). May play a role in the regulation of intraflagellar transport (IFT) during cilia assembly. Required for normal retina development (By similarity). In connecting photoreceptor cilia influences the movement of some IFT proteins such as IFT88 and WDR19. Involved in spermatogenesis (By similarity). {ECO:0000250\|UniProtKB:Q9QY53}.


Subunit:		Interacts with BCAR1, PTK2B/PYK2 and tensin. Interacts with INVS and NPHP3. Interacts with PACS1; the interaction is dependent on NPHP1 phosphorylation by CK2. Interacts with KIF7. Interacts with AHI1 and TNK2. Interacts with NPHP4 in a complex containing NPHP1, NPHP4 and RPGRIP1L. Interacts with IQCB1; the interaction likely requires additional interactors. Interacts with ANKS3 (By similarity).Interacts with SPATA7 (By similarity). Interacts with FLNA (By similarity). {ECO:0000250\|UniProtKB:Q9QY53, ECO:0000269\|PubMed:12244321, ECO:0000269\|PubMed:12872122, ECO:0000269\|PubMed:12872123, ECO:0000269\|PubMed:16308564, ECO:0000269\|PubMed:18477472, ECO:0000269\|PubMed:18633336, ECO:0000269\|PubMed:20856870, ECO:0000269\|PubMed:21357692, ECO:0000269\|PubMed:21565611, ECO:0000269\|PubMed:21633164}.
Subcellular location:		Cell junction {ECO:0000250\|UniProtKB:Q9QY53}. Cell junction, adherens junction {ECO:0000250\|UniProtKB:Q9QY53}. Cell projection, cilium {ECO:0000269\|PubMed:16885411}. Cytoplasm, cytoskeleton, cilium axoneme {ECO:0000269\|PubMed:16308564, ECO:0000269\|PubMed:16885411}. Cell junction, tight junction. Note=In the retinal photoreceptor cell layer, localizes at the connecting cilium (By similarity). Colocalizes with E-cadherin and BCAR1 at or near the cell-cell adherens junctions (By similarity). Localized to respiratory cilia axoneme (PubMed:16308564, PubMed:16885411). Localized to the transition zone of respiratory cilia (PubMed:16885411). Localized to the transition zone of photoreceptor-connecting cilia and renal monocilia (By similarity). In cultured renal cells, it localizes diffusely in the cytoplasm but, as cells approach confluence, it accumulates at basolateral tight junctions (By similarity). {ECO:0000250\|UniProtKB:Q9QY53, ECO:0000269\|PubMed:16308564, ECO:0000269\|PubMed:16885411}.
Tissue specificity:		Widespread expression, with highest levels in pituitary gland, spinal cord, thyroid gland, testis, skeletal muscle, lymph node and trachea. Weakly expressed in heart, kidney and pancreas. Expressed in nasal epithelial cells (at protein level) (PubMed:16308564). Expressed in the renal collecting duct (at protein level) (PubMed:18477472). {ECO:0000269\|PubMed:16308564, ECO:0000269\|PubMed:18477472}.
Developmental stage:		During in vitro ciliogenesis translocalizes from the cytoplasm to the ciliary transition zone during epithelial cell polarization. {ECO:0000269\|PubMed:16885411}.
Domain:		The SH3 domain mediates the stable interaction with Cas. {ECO:0000250}.
Ptm:		Phosphorylation by CK2 is required for the interaction with PACS1 and the targeting to the base region of cilia. {ECO:0000269\|PubMed:16308564, ECO:0000269\|PubMed:21357692}.
Disease:		Nephronophthisis 1 (NPHP1) [MIM:256100]: An autosomal recessive inherited disease characterized by anemia, polyuria, polydipsia, isosthenuria and death in uremia. Symmetrical destruction of the kidneys involving both tubules and glomeruli occurs. The underlying pathology is a chronic tubulo-interstitial nephropathy with characteristic tubular basement membrane thickening and medullary cyst formation. Associations with extrarenal symptoms, especially ocular lesions, are frequent. The age at death ranges from about 4 to 15 years. {ECO:0000269\|PubMed:10839884}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Senior-Loken syndrome 1 (SLSN1) [MIM:266900]: A renal-retinal disorder characterized by progressive wasting of the filtering unit of the kidney (nephronophthisis), with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life. {ECO:0000269\|PubMed:9856524}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Joubert syndrome 4 (JBTS4) [MIM:609583]: A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. Joubert syndrome type 4 is a phenotypically mild form. {ECO:0000269\|PubMed:15138899, ECO:0000269\|PubMed:26477546}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		Nephronophthisis type 1 patients deficient for NPHP1 show normal overall integrity of respiratory cilia.
Similarity:		Belongs to the nephrocystin-1 family. {ECO:0000305}.