UniProt functional annotation for P50479



	UniProt functional annotation for P50479

UniProt code: P50479.

Organism: Homo sapiens (Human).

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

Function: [Isoform 1]: Suppresses SRC activation by recognizing and binding to active SRC and facilitating PTPN13-mediated dephosphorylation of SRC 'Tyr-419' leading to its inactivation. Inactivated SRC dissociates from this protein allowing the initiation of a new SRC inactivation cycle (PubMed:19307596). Involved in reorganization of the actin cytoskeleton (PubMed:21636573). In nonmuscle cells, binds to ACTN1 (alpha-actinin-1), increases the affinity of ACTN1 to F-actin (filamentous actin), and promotes formation of actin stress fibers. Involved in regulation of the synaptic AMPA receptor transport in dendritic spines of hippocampal pyramidal neurons directing the receptors toward an insertion at the postsynaptic membrane. Links endosomal surface-internalized GRIA1- containing AMPA receptors to the alpha-actinin/actin cytoskeleton. Increases AMPA receptor-mediated excitatory postsynaptic currents in neurons (By similarity). {ECO:0000250|UniProtKB:P36202, ECO:0000269|PubMed:19307596, ECO:0000269|PubMed:21636573}.

Function: [Isoform 2]: Involved in reorganization of the actin cytoskeleton and in regulation of cell migration. In response to oxidative stress, binds to NQO1, which stabilizes it and protects it from ubiquitin-independent degradation by the core 20S proteasome. Stabilized protein is able to heterodimerize with isoform 1 changing the subcellular location of it from cytoskeleton and nuclei to cytosol, leading to loss of isoforms 1 ability to induce formation of actin stress fibers. Counteracts the effects produced by isoform 1 on organization of actin cytoskeleton and cell motility to fine-tune actin cytoskeleton rearrangement and to attenuate cell migration. {ECO:0000269|PubMed:21636573}.

Subunit: Homodimer (PubMed:25158098). Interacts with PTPN13 (PubMed:19307596). Interacts (via C-terminus only or via combined C- terminus and LIM domain, but not LIM domain only) with PTPN13 (via the second or fourth PDZ domains). Found in a complex with PTPN13 and TRIP6 (By similarity). Interacts (via PDZ domain) with ACTN1 and ACTN2 (via C-terminal SDL residues) (By similarity). Interacts (via PDZ domain) with TRIP6 (via the second LIM domain or via the third LIM domain plus C-terminus) (PubMed:10826496). Interacts (via LIM domain) with GRIA1 (via C-terminus); this interaction as well as the interaction with alpha-actinin is required for their colocalization in early endosomes. Interacts with PDLIM1 (By similarity). Forms (via LIM domain) a heterodimer with PDLIM3 (By similarity). Interacts directly with SRC (via kinase domain and to a lesser extent the SH2 domain) (PubMed:19307596). Isoform 2 interacts with NQO1. NQO1-stabilized isoform 2 heterodimerizes with isoform 1 (PubMed:21636573). {ECO:0000250|UniProtKB:P36202, ECO:0000250|UniProtKB:P70271, ECO:0000269|PubMed:10826496, ECO:0000269|PubMed:19307596, ECO:0000269|PubMed:21636573, ECO:0000269|PubMed:25158098}.

Subcellular location: [Isoform 1]: Cytoplasm, cytoskeleton {ECO:0000269|PubMed:21636573}. Nucleus {ECO:0000269|PubMed:10826496, ECO:0000269|PubMed:21636573}. Cytoplasm {ECO:0000269|PubMed:21636573}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:19307596}. Cell projection, lamellipodium {ECO:0000269|PubMed:10826496}. Cell projection, dendritic spine {ECO:0000250|UniProtKB:P36202}. Early endosome membrane {ECO:0000250|UniProtKB:P36202}; Peripheral membrane protein {ECO:0000250|UniProtKB:P36202}; Cytoplasmic side {ECO:0000250|UniProtKB:P36202}. Recycling endosome membrane {ECO:0000250|UniProtKB:P36202}; Peripheral membrane protein {ECO:0000250|UniProtKB:P36202}; Cytoplasmic side {ECO:0000250|UniProtKB:P36202}. Cell junction, synapse, synaptosome {ECO:0000250|UniProtKB:P36202}. Note=Localizes to actin stress fibers in nonmuscle cells. Colocalizes with GRIA1 in early endosomes. Enriched in numerous but not all spine-like structures along dendritic branches. Colocalizes with actin and enriched at sites containing larger amounts of actin and alpha-actinin. Targeted efficiently to spines via its PDZ domain-mediated interaction with the alpha-actinin/actin cytoskeletal complex. Localizes to synaptosomes in brain (By similarity). Colocalizes with F-actin (PubMed:10826496). Colocalizes with TRIP6 at cell-cell contacts and lamellipodia (PubMed:10826496). In the cytoplasm, displays a fibrillar pattern with characteristic thick fibers and occasional clusters. Colocalizes with the actin stress fibers. Oxidative stress induces redistribution from cytoskeleton to cytosol (PubMed:21636573). Colocalizes with SRC at the perinuclear region, but not at focal adhesions (PubMed:19307596). {ECO:0000250|UniProtKB:P36202, ECO:0000269|PubMed:10826496, ECO:0000269|PubMed:19307596, ECO:0000269|PubMed:21636573}.

Subcellular location: [Isoform 2]: Cytoplasm {ECO:0000269|PubMed:21636573}. Note=Stains more diffusely in the cytoplasm with thin fibers forming a dense mesh-like pattern. {ECO:0000269|PubMed:21636573}.

Tissue specificity: [Isoform 2]: Found in brain. {ECO:0000269|PubMed:9573374}.

Induction: [Isoform 2]: Expression is up-regulated by UV irradiation and to a lesser extent by oxidative stress. {ECO:0000269|PubMed:21636573}.

Ptm: Phosphorylated on tyrosine residue(s). Can be dephosphorylated by PTPN13. {ECO:0000250|UniProtKB:P70271}.

Polymorphism: Genetic variations in PDLIM4 may be correlated with bone mineral density (BMD). Low BMD is a risk factor for osteoporotic fracture. Osteoporosis is characterized by reduced bone mineral density, disruption of bone microarchitecture, and the alteration of the amount and variety of non-collagenous proteins in bone. Osteoporotic bones are more at risk of fracture.

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:		[Isoform 1]: Suppresses SRC activation by recognizing and binding to active SRC and facilitating PTPN13-mediated dephosphorylation of SRC 'Tyr-419' leading to its inactivation. Inactivated SRC dissociates from this protein allowing the initiation of a new SRC inactivation cycle (PubMed:19307596). Involved in reorganization of the actin cytoskeleton (PubMed:21636573). In nonmuscle cells, binds to ACTN1 (alpha-actinin-1), increases the affinity of ACTN1 to F-actin (filamentous actin), and promotes formation of actin stress fibers. Involved in regulation of the synaptic AMPA receptor transport in dendritic spines of hippocampal pyramidal neurons directing the receptors toward an insertion at the postsynaptic membrane. Links endosomal surface-internalized GRIA1- containing AMPA receptors to the alpha-actinin/actin cytoskeleton. Increases AMPA receptor-mediated excitatory postsynaptic currents in neurons (By similarity). {ECO:0000250\|UniProtKB:P36202, ECO:0000269\|PubMed:19307596, ECO:0000269\|PubMed:21636573}.



Function:		[Isoform 2]: Involved in reorganization of the actin cytoskeleton and in regulation of cell migration. In response to oxidative stress, binds to NQO1, which stabilizes it and protects it from ubiquitin-independent degradation by the core 20S proteasome. Stabilized protein is able to heterodimerize with isoform 1 changing the subcellular location of it from cytoskeleton and nuclei to cytosol, leading to loss of isoforms 1 ability to induce formation of actin stress fibers. Counteracts the effects produced by isoform 1 on organization of actin cytoskeleton and cell motility to fine-tune actin cytoskeleton rearrangement and to attenuate cell migration. {ECO:0000269\|PubMed:21636573}.


Subunit:		Homodimer (PubMed:25158098). Interacts with PTPN13 (PubMed:19307596). Interacts (via C-terminus only or via combined C- terminus and LIM domain, but not LIM domain only) with PTPN13 (via the second or fourth PDZ domains). Found in a complex with PTPN13 and TRIP6 (By similarity). Interacts (via PDZ domain) with ACTN1 and ACTN2 (via C-terminal SDL residues) (By similarity). Interacts (via PDZ domain) with TRIP6 (via the second LIM domain or via the third LIM domain plus C-terminus) (PubMed:10826496). Interacts (via LIM domain) with GRIA1 (via C-terminus); this interaction as well as the interaction with alpha-actinin is required for their colocalization in early endosomes. Interacts with PDLIM1 (By similarity). Forms (via LIM domain) a heterodimer with PDLIM3 (By similarity). Interacts directly with SRC (via kinase domain and to a lesser extent the SH2 domain) (PubMed:19307596). Isoform 2 interacts with NQO1. NQO1-stabilized isoform 2 heterodimerizes with isoform 1 (PubMed:21636573). {ECO:0000250\|UniProtKB:P36202, ECO:0000250\|UniProtKB:P70271, ECO:0000269\|PubMed:10826496, ECO:0000269\|PubMed:19307596, ECO:0000269\|PubMed:21636573, ECO:0000269\|PubMed:25158098}.
Subcellular location:		[Isoform 1]: Cytoplasm, cytoskeleton {ECO:0000269\|PubMed:21636573}. Nucleus {ECO:0000269\|PubMed:10826496, ECO:0000269\|PubMed:21636573}. Cytoplasm {ECO:0000269\|PubMed:21636573}. Cytoplasm, perinuclear region {ECO:0000269\|PubMed:19307596}. Cell projection, lamellipodium {ECO:0000269\|PubMed:10826496}. Cell projection, dendritic spine {ECO:0000250\|UniProtKB:P36202}. Early endosome membrane {ECO:0000250\|UniProtKB:P36202}; Peripheral membrane protein {ECO:0000250\|UniProtKB:P36202}; Cytoplasmic side {ECO:0000250\|UniProtKB:P36202}. Recycling endosome membrane {ECO:0000250\|UniProtKB:P36202}; Peripheral membrane protein {ECO:0000250\|UniProtKB:P36202}; Cytoplasmic side {ECO:0000250\|UniProtKB:P36202}. Cell junction, synapse, synaptosome {ECO:0000250\|UniProtKB:P36202}. Note=Localizes to actin stress fibers in nonmuscle cells. Colocalizes with GRIA1 in early endosomes. Enriched in numerous but not all spine-like structures along dendritic branches. Colocalizes with actin and enriched at sites containing larger amounts of actin and alpha-actinin. Targeted efficiently to spines via its PDZ domain-mediated interaction with the alpha-actinin/actin cytoskeletal complex. Localizes to synaptosomes in brain (By similarity). Colocalizes with F-actin (PubMed:10826496). Colocalizes with TRIP6 at cell-cell contacts and lamellipodia (PubMed:10826496). In the cytoplasm, displays a fibrillar pattern with characteristic thick fibers and occasional clusters. Colocalizes with the actin stress fibers. Oxidative stress induces redistribution from cytoskeleton to cytosol (PubMed:21636573). Colocalizes with SRC at the perinuclear region, but not at focal adhesions (PubMed:19307596). {ECO:0000250\|UniProtKB:P36202, ECO:0000269\|PubMed:10826496, ECO:0000269\|PubMed:19307596, ECO:0000269\|PubMed:21636573}.
Subcellular location:		[Isoform 2]: Cytoplasm {ECO:0000269\|PubMed:21636573}. Note=Stains more diffusely in the cytoplasm with thin fibers forming a dense mesh-like pattern. {ECO:0000269\|PubMed:21636573}.
Tissue specificity:		[Isoform 2]: Found in brain. {ECO:0000269\|PubMed:9573374}.
Induction:		[Isoform 2]: Expression is up-regulated by UV irradiation and to a lesser extent by oxidative stress. {ECO:0000269\|PubMed:21636573}.
Ptm:		Phosphorylated on tyrosine residue(s). Can be dephosphorylated by PTPN13. {ECO:0000250\|UniProtKB:P70271}.
Polymorphism:		Genetic variations in PDLIM4 may be correlated with bone mineral density (BMD). Low BMD is a risk factor for osteoporotic fracture. Osteoporosis is characterized by reduced bone mineral density, disruption of bone microarchitecture, and the alteration of the amount and variety of non-collagenous proteins in bone. Osteoporotic bones are more at risk of fracture.