UniProt functional annotation for O00560



	UniProt functional annotation for O00560

UniProt code: O00560.

Organism: Homo sapiens (Human).

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

Function: Multifunctional adapter protein involved in diverse array of functions including trafficking of transmembrane proteins, neuro and immunomodulation, exosome biogenesis, and tumorigenesis (PubMed:26291527). Positively regulates TGFB1-mediated SMAD2/3 activation and TGFB1-induced epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types. May increase TGFB1 signaling by enhancing cell-surface expression of TGFR1 by preventing the interaction between TGFR1 and CAV1 and subsequent CAV1-dependent internalization and degradation of TGFR1 (PubMed:25893292). In concert with SDC1/4 and PDCD6IP, regulates exosome biogenesis (PubMed:22660413). Regulates migration, growth, proliferation, and cell cycle progression in a variety of cancer types (PubMed:26539120). In adherens junctions may function to couple syndecans to cytoskeletal proteins or signaling components. Seems to couple transcription factor SOX4 to the IL-5 receptor (IL5RA) (PubMed:11498591). May also play a role in vesicular trafficking (PubMed:11179419). Seems to be required for the targeting of TGFA to the cell surface in the early secretory pathway (PubMed:10230395). {ECO:0000269|PubMed:10230395, ECO:0000269|PubMed:11179419, ECO:0000269|PubMed:11498591, ECO:0000269|PubMed:22660413, ECO:0000269|PubMed:25893292, ECO:0000269|PubMed:26539120, ECO:0000303|PubMed:26291527}.

Subunit: Monomer and homodimer (By similarity). Interacts with SDC1, SDC2, SDC3, SDC4, NRXN2, EPHA7, EPHB1, NF2 isoform 1, TGFA and IL5RA. Interacts with NFASC and PTPRJ (By similarity). Interacts with SDCBP2 (PubMed:11152476). Interacts with PDCD6IP (PubMed:22660413). Forms a complex with PDCD6IP and SDC2 (PubMed:22660413). Interacts (via C- terminus) with TGFBR1 (PubMed:25893292). Binds to FZD7; this interaction is increased by inositol trisphosphate (IP3) (PubMed:27386966). Interacts with SMO (By similarity). {ECO:0000250|UniProtKB:O08992, ECO:0000250|UniProtKB:Q9JI92, ECO:0000269|PubMed:11152476, ECO:0000269|PubMed:22660413, ECO:0000269|PubMed:25893292, ECO:0000269|PubMed:27386966}.

Subcellular location: Cell junction, focal adhesion {ECO:0000269|PubMed:11179419}. Cell junction, adherens junction {ECO:0000269|PubMed:11179419}. Cell membrane {ECO:0000269|PubMed:11179419, ECO:0000269|PubMed:25893292, ECO:0000269|PubMed:27386966}; Peripheral membrane protein {ECO:0000269|PubMed:11179419, ECO:0000269|PubMed:27386966}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:17081065}; Peripheral membrane protein {ECO:0000269|PubMed:17081065}. Nucleus {ECO:0000269|PubMed:11179419}. Melanosome {ECO:0000269|PubMed:12643545, ECO:0000269|PubMed:17081065}. Cytoplasm, cytosol {ECO:0000269|PubMed:11179419}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:11179419}. Secreted, extracellular exosome {ECO:0000269|PubMed:22660413}. Membrane raft {ECO:0000269|PubMed:25893292}. Note=Mainly membrane-associated. Localized to adherens junctions, focal adhesions and endoplasmic reticulum. Colocalized with actin stress fibers. Also found in the nucleus. Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Associated to the plasma membrane in the presence of FZD7 and phosphatidylinositol 4,5-bisphosphate (PIP2) (PubMed:27386966). {ECO:0000269|PubMed:11179419, ECO:0000269|PubMed:12643545, ECO:0000269|PubMed:17081065, ECO:0000269|PubMed:27386966}.

Tissue specificity: Expressed in lung cancers, including adenocarcinoma, squamous cell carcinoma and small-cell carcinoma (at protein level) (PubMed:25893292). Widely expressed. Expressed in fetal kidney, liver, lung and brain. In adult highest expression in heart and placenta. {ECO:0000269|PubMed:25893292}.

Induction: By IFNG/IFN-gamma in melanoma cells.

Ptm: Phosphorylated on tyrosine residues.

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:		Multifunctional adapter protein involved in diverse array of functions including trafficking of transmembrane proteins, neuro and immunomodulation, exosome biogenesis, and tumorigenesis (PubMed:26291527). Positively regulates TGFB1-mediated SMAD2/3 activation and TGFB1-induced epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types. May increase TGFB1 signaling by enhancing cell-surface expression of TGFR1 by preventing the interaction between TGFR1 and CAV1 and subsequent CAV1-dependent internalization and degradation of TGFR1 (PubMed:25893292). In concert with SDC1/4 and PDCD6IP, regulates exosome biogenesis (PubMed:22660413). Regulates migration, growth, proliferation, and cell cycle progression in a variety of cancer types (PubMed:26539120). In adherens junctions may function to couple syndecans to cytoskeletal proteins or signaling components. Seems to couple transcription factor SOX4 to the IL-5 receptor (IL5RA) (PubMed:11498591). May also play a role in vesicular trafficking (PubMed:11179419). Seems to be required for the targeting of TGFA to the cell surface in the early secretory pathway (PubMed:10230395). {ECO:0000269\|PubMed:10230395, ECO:0000269\|PubMed:11179419, ECO:0000269\|PubMed:11498591, ECO:0000269\|PubMed:22660413, ECO:0000269\|PubMed:25893292, ECO:0000269\|PubMed:26539120, ECO:0000303\|PubMed:26291527}.


Subunit:		Monomer and homodimer (By similarity). Interacts with SDC1, SDC2, SDC3, SDC4, NRXN2, EPHA7, EPHB1, NF2 isoform 1, TGFA and IL5RA. Interacts with NFASC and PTPRJ (By similarity). Interacts with SDCBP2 (PubMed:11152476). Interacts with PDCD6IP (PubMed:22660413). Forms a complex with PDCD6IP and SDC2 (PubMed:22660413). Interacts (via C- terminus) with TGFBR1 (PubMed:25893292). Binds to FZD7; this interaction is increased by inositol trisphosphate (IP3) (PubMed:27386966). Interacts with SMO (By similarity). {ECO:0000250\|UniProtKB:O08992, ECO:0000250\|UniProtKB:Q9JI92, ECO:0000269\|PubMed:11152476, ECO:0000269\|PubMed:22660413, ECO:0000269\|PubMed:25893292, ECO:0000269\|PubMed:27386966}.
Subcellular location:		Cell junction, focal adhesion {ECO:0000269\|PubMed:11179419}. Cell junction, adherens junction {ECO:0000269\|PubMed:11179419}. Cell membrane {ECO:0000269\|PubMed:11179419, ECO:0000269\|PubMed:25893292, ECO:0000269\|PubMed:27386966}; Peripheral membrane protein {ECO:0000269\|PubMed:11179419, ECO:0000269\|PubMed:27386966}. Endoplasmic reticulum membrane {ECO:0000269\|PubMed:17081065}; Peripheral membrane protein {ECO:0000269\|PubMed:17081065}. Nucleus {ECO:0000269\|PubMed:11179419}. Melanosome {ECO:0000269\|PubMed:12643545, ECO:0000269\|PubMed:17081065}. Cytoplasm, cytosol {ECO:0000269\|PubMed:11179419}. Cytoplasm, cytoskeleton {ECO:0000269\|PubMed:11179419}. Secreted, extracellular exosome {ECO:0000269\|PubMed:22660413}. Membrane raft {ECO:0000269\|PubMed:25893292}. Note=Mainly membrane-associated. Localized to adherens junctions, focal adhesions and endoplasmic reticulum. Colocalized with actin stress fibers. Also found in the nucleus. Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Associated to the plasma membrane in the presence of FZD7 and phosphatidylinositol 4,5-bisphosphate (PIP2) (PubMed:27386966). {ECO:0000269\|PubMed:11179419, ECO:0000269\|PubMed:12643545, ECO:0000269\|PubMed:17081065, ECO:0000269\|PubMed:27386966}.
Tissue specificity:		Expressed in lung cancers, including adenocarcinoma, squamous cell carcinoma and small-cell carcinoma (at protein level) (PubMed:25893292). Widely expressed. Expressed in fetal kidney, liver, lung and brain. In adult highest expression in heart and placenta. {ECO:0000269\|PubMed:25893292}.
Induction:		By IFNG/IFN-gamma in melanoma cells.
Ptm:		Phosphorylated on tyrosine residues.