UniProt functional annotation for Q9Y5K6



	UniProt functional annotation for Q9Y5K6

UniProt code: Q9Y5K6.

Organism: Homo sapiens (Human).

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

Function: Seems to act as an adapter protein between membrane proteins and the actin cytoskeleton (PubMed:10339567). In collaboration with CBLC, modulates the rate of RET turnover and may act as regulatory checkpoint that limits the potency of GDNF on neuronal survival. Controls CBLC function, converting it from an inhibitor to a promoter of RET degradation (By similarity). May play a role in receptor clustering and cytoskeletal polarity in the junction between T-cell and antigen-presenting cell (By similarity). May anchor the podocyte slit diaphragm to the actin cytoskeleton in renal glomerolus. Also required for cytokinesis (PubMed:15800069). Plays a role in epithelial cell junctions formation (PubMed:22891260). {ECO:0000250|UniProtKB:F1LRS8, ECO:0000250|UniProtKB:Q9JLQ0, ECO:0000269|PubMed:10339567, ECO:0000269|PubMed:15800069, ECO:0000269|PubMed:22891260}.

Subunit: Homodimer. Interacts with F-actin, PKD2, NPHS1 and NPHS2. Interacts with WTIP. Interacts with DDN; interaction is direct. Interacts (via SH3 2 domain) with CBL (via phosphorylated C-terminus). Interacts with BCAR1/p130Cas (via SH3 domain). Interacts with MVB12A and ARHGAP17. Interacts with ANLN, CD2 and CBLB. Interacts with PDCD6IP and TSG101. Interacts with RIN3. Interacts directly with RET (inactive) and CBLC; upon RET activation by GDNF suggested to dissociate from RET as CBLC:CD2AP complex (Probable) (PubMed:10339567, PubMed:11067845, PubMed:15800069, PubMed:16678097, PubMed:16895919, PubMed:17020880, PubMed:17853893, PubMed:18753381, Ref.29). Interacts with CGNL1 and SH3BP1; probably part of a complex at cell junctions (PubMed:22891260). Interacts with CAPZA1 (PubMed:22891260). {ECO:0000269|PubMed:10339567, ECO:0000269|PubMed:11067845, ECO:0000269|PubMed:15800069, ECO:0000269|PubMed:16678097, ECO:0000269|PubMed:16895919, ECO:0000269|PubMed:17020880, ECO:0000269|PubMed:17853893, ECO:0000269|PubMed:18753381, ECO:0000269|PubMed:22891260, ECO:0000269|Ref.29, ECO:0000305}.

Subcellular location: Cytoplasm, cytoskeleton {ECO:0000269|PubMed:15800069}. Cell projection, ruffle {ECO:0000269|PubMed:10339567}. Cell junction {ECO:0000269|PubMed:22891260}. Note=Colocalizes with F-actin and BCAR1/p130Cas in membrane ruffles (PubMed:10339567). Located at podocyte slit diaphragm between podocyte foot processes (By similarity). During late anaphase and telophase, concentrates in the vicinity of the midzone microtubules and in the midbody in late telophase (PubMed:15800069). {ECO:0000250|UniProtKB:Q9JLQ0, ECO:0000269|PubMed:10339567, ECO:0000269|PubMed:15800069}.

Tissue specificity: Widely expressed in fetal and adult tissues.

Domain: The Pro-rich domain may mediate binding to SH3 domains.

Domain: Potential homodimerization is mediated by the coiled coil domain. {ECO:0000269|PubMed:10339567}.

Ptm: Phosphorylated on tyrosine residues; probably by c-Abl, Fyn and c- Src. {ECO:0000269|PubMed:10339567, ECO:0000269|PubMed:11067845, ECO:0000269|PubMed:15800069}.

Disease: Focal segmental glomerulosclerosis 3 (FSGS3) [MIM:607832]: A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation. {ECO:0000269|PubMed:12764198}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

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:		Seems to act as an adapter protein between membrane proteins and the actin cytoskeleton (PubMed:10339567). In collaboration with CBLC, modulates the rate of RET turnover and may act as regulatory checkpoint that limits the potency of GDNF on neuronal survival. Controls CBLC function, converting it from an inhibitor to a promoter of RET degradation (By similarity). May play a role in receptor clustering and cytoskeletal polarity in the junction between T-cell and antigen-presenting cell (By similarity). May anchor the podocyte slit diaphragm to the actin cytoskeleton in renal glomerolus. Also required for cytokinesis (PubMed:15800069). Plays a role in epithelial cell junctions formation (PubMed:22891260). {ECO:0000250\|UniProtKB:F1LRS8, ECO:0000250\|UniProtKB:Q9JLQ0, ECO:0000269\|PubMed:10339567, ECO:0000269\|PubMed:15800069, ECO:0000269\|PubMed:22891260}.


Subunit:		Homodimer. Interacts with F-actin, PKD2, NPHS1 and NPHS2. Interacts with WTIP. Interacts with DDN; interaction is direct. Interacts (via SH3 2 domain) with CBL (via phosphorylated C-terminus). Interacts with BCAR1/p130Cas (via SH3 domain). Interacts with MVB12A and ARHGAP17. Interacts with ANLN, CD2 and CBLB. Interacts with PDCD6IP and TSG101. Interacts with RIN3. Interacts directly with RET (inactive) and CBLC; upon RET activation by GDNF suggested to dissociate from RET as CBLC:CD2AP complex (Probable) (PubMed:10339567, PubMed:11067845, PubMed:15800069, PubMed:16678097, PubMed:16895919, PubMed:17020880, PubMed:17853893, PubMed:18753381, Ref.29). Interacts with CGNL1 and SH3BP1; probably part of a complex at cell junctions (PubMed:22891260). Interacts with CAPZA1 (PubMed:22891260). {ECO:0000269\|PubMed:10339567, ECO:0000269\|PubMed:11067845, ECO:0000269\|PubMed:15800069, ECO:0000269\|PubMed:16678097, ECO:0000269\|PubMed:16895919, ECO:0000269\|PubMed:17020880, ECO:0000269\|PubMed:17853893, ECO:0000269\|PubMed:18753381, ECO:0000269\|PubMed:22891260, ECO:0000269\|Ref.29, ECO:0000305}.
Subcellular location:		Cytoplasm, cytoskeleton {ECO:0000269\|PubMed:15800069}. Cell projection, ruffle {ECO:0000269\|PubMed:10339567}. Cell junction {ECO:0000269\|PubMed:22891260}. Note=Colocalizes with F-actin and BCAR1/p130Cas in membrane ruffles (PubMed:10339567). Located at podocyte slit diaphragm between podocyte foot processes (By similarity). During late anaphase and telophase, concentrates in the vicinity of the midzone microtubules and in the midbody in late telophase (PubMed:15800069). {ECO:0000250\|UniProtKB:Q9JLQ0, ECO:0000269\|PubMed:10339567, ECO:0000269\|PubMed:15800069}.
Tissue specificity:		Widely expressed in fetal and adult tissues.
Domain:		The Pro-rich domain may mediate binding to SH3 domains.
Domain:		Potential homodimerization is mediated by the coiled coil domain. {ECO:0000269\|PubMed:10339567}.
Ptm:		Phosphorylated on tyrosine residues; probably by c-Abl, Fyn and c- Src. {ECO:0000269\|PubMed:10339567, ECO:0000269\|PubMed:11067845, ECO:0000269\|PubMed:15800069}.
Disease:		Focal segmental glomerulosclerosis 3 (FSGS3) [MIM:607832]: A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation. {ECO:0000269\|PubMed:12764198}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.