UniProt functional annotation for Q12959



	UniProt functional annotation for Q12959

UniProt code: Q12959.

Organism: Homo sapiens (Human).

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

Function: Essential multidomain scaffolding protein required for normal development (By similarity). Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. May play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels. Functional regulator of Kv1.5 channel. During long-term depression in hippocampal neurons, it recruits ADAM10 to the plasma membrane (PubMed:23676497). {ECO:0000250, ECO:0000269|PubMed:10656683, ECO:0000269|PubMed:12445884, ECO:0000269|PubMed:14699157, ECO:0000269|PubMed:15263016, ECO:0000269|PubMed:19213956, ECO:0000269|PubMed:20605917, ECO:0000269|PubMed:23676497}.

Subunit: Homotetramer (Probable). Interacts (via guanylate kinase-like domain) with DLGAP1, DLGAP2, DLGAP3, DLGAP4 and MAP1A (By similarity). Interacts (via guanylate kinase-like domain) with KIF13B (PubMed:10859302). May interact with HTR2A (By similarity). Interacts (via PDZ domains) with GRIA1 (By similarity). Interacts (via PDZ domains) with GRIN2A (By similarity). Interacts (via PDZ domains) with KCND2 and KCND3 (PubMed:19213956). Interacts (via PDZ domains) with KCNA1, KCNA2, KCNA3 and KCNA4 (PubMed:7477295). Interacts (via PDZ domains) with ADGRA3 (PubMed:15021905). Interacts with KCNF1 (PubMed:12445884). Interacts with CAMK2 (By similarity). Interacts with cytoskeleton-associated protein EPB41 (PubMed:7937897, PubMed:8922391). Interacts with cytoskeleton-associated protein EZR (By similarity). Found in a complex with KCNA5 and CAV3 (By similarity). Found in a complex with APC and CTNNB1 (PubMed:8638125, PubMed:10656683). Interacts with CDH1 through binding to PIK3R1 (PubMed:14699157). Forms multiprotein complexes with CASK, LIN7A, LIN7B, LIN7C, APBA1, and KCNJ12 (By similarity). Interacts with TOPK (PubMed:10779557). Forms a tripartite complex composed of DLG1, MPP7 and LIN7 (LIN7A or LIN7C) (PubMed:17237226, PubMed:17332497, PubMed:20702775). May interact with TJAP1 (PubMed:11602598). Interacts with PTEN (By similarity). Interacts with FRMPD4 (via C-terminus) (PubMed:19118189). Interacts with LRFN1, LRFN2 and LRFN4 (PubMed:16630835). Interacts with SFPQ (PubMed:20605917). Interacts (via PDZ domains) with ADGRA2 (via PDZ- binding motif) (PubMed:15021905, PubMed:25558062). Interacts with ADAM10; this interaction recruits ADAM10 to the cell membrane during long-term depression in hippocampal neurons (PubMed:23676497). Interacts with DGKI (via PDZ-binding motif) (By similarity). {ECO:0000250|UniProtKB:Q62696, ECO:0000250|UniProtKB:Q811D0, ECO:0000269|PubMed:10656683, ECO:0000269|PubMed:10779557, ECO:0000269|PubMed:10859302, ECO:0000269|PubMed:11602598, ECO:0000269|PubMed:12445884, ECO:0000269|PubMed:14699157, ECO:0000269|PubMed:15021905, ECO:0000269|PubMed:16630835, ECO:0000269|PubMed:17237226, ECO:0000269|PubMed:17332497, ECO:0000269|PubMed:19118189, ECO:0000269|PubMed:19213956, ECO:0000269|PubMed:20605917, ECO:0000269|PubMed:20702775, ECO:0000269|PubMed:23676497, ECO:0000269|PubMed:25558062, ECO:0000269|PubMed:7477295, ECO:0000269|PubMed:7937897, ECO:0000269|PubMed:8638125, ECO:0000269|PubMed:8922391, ECO:0000305}.

Subunit: (Microbial infection) Interacts with HTLV-1 protein Tax. {ECO:0000269|PubMed:10557085}.

Subunit: (Microbial infection) Interacts with human papillomavirus 18/HPV-18 protein E6. {ECO:0000269|PubMed:9192623}.

Subcellular location: Membrane {ECO:0000269|PubMed:10859302, ECO:0000269|PubMed:11723125, ECO:0000269|PubMed:8922391}; Peripheral membrane protein {ECO:0000269|PubMed:8922391}. Basolateral cell membrane {ECO:0000269|PubMed:12807908}. Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q62696}. Cell junction, synapse, postsynaptic density {ECO:0000250|UniProtKB:Q62696}. Cell junction, synapse {ECO:0000250|UniProtKB:Q62696}. Cell membrane, sarcolemma {ECO:0000269|PubMed:12445884}. Apical cell membrane {ECO:0000269|PubMed:12445884}. Cell junction {ECO:0000269|PubMed:10859302, ECO:0000269|PubMed:11723125, ECO:0000269|PubMed:7937897}. Cytoplasm {ECO:0000269|PubMed:10859302}. Note=Colocalizes with EPB41 at regions of intercellular contacts. Basolateral in epithelial cells (PubMed:12807908). May also associate with endoplasmic reticulum membranes. Mainly found in neurons soma, moderately found at postsynaptic densities (By similarity). {ECO:0000250|UniProtKB:Q62696, ECO:0000269|PubMed:10859302, ECO:0000269|PubMed:12807908, ECO:0000269|PubMed:8922391, ECO:0000269|PubMed:9192623}.

Tissue specificity: Abundantly expressed in atrial myocardium (at protein level). Expressed in lung fibroblasts, cervical epithelial and B-cells (at protein level). Expressed in the brain (at protein level) (PubMed:23676497). Widely expressed, with isoforms displaying different expression profiles. {ECO:0000269|PubMed:12445884, ECO:0000269|PubMed:19213956, ECO:0000269|PubMed:23676497, ECO:0000269|PubMed:7937897}.

Domain: The alternatively spliced domain I3 corresponding to amino acids (636-669) of isoform 4 is an EPB41 binding site mediating association to membranes in polarized and non-polarized cells.

Domain: The PDZ domains may also mediate association to membranes by binding to EPB41 and ADGRA2 together with the L27 domain that binds CASK and DLG2.

Domain: The L27 domain may regulate DLG1 self-association. The N- terminal alternatively spliced region is capable of binding several SH3 domains and also moderates the level of protein oligomerization.

Ptm: Phosphorylated by MAPK12. Phosphorylation of Ser-232 regulates association with GRIN2A (By similarity). {ECO:0000250}.

Similarity: Belongs to the MAGUK 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:		Essential multidomain scaffolding protein required for normal development (By similarity). Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. May play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels. Functional regulator of Kv1.5 channel. During long-term depression in hippocampal neurons, it recruits ADAM10 to the plasma membrane (PubMed:23676497). {ECO:0000250, ECO:0000269\|PubMed:10656683, ECO:0000269\|PubMed:12445884, ECO:0000269\|PubMed:14699157, ECO:0000269\|PubMed:15263016, ECO:0000269\|PubMed:19213956, ECO:0000269\|PubMed:20605917, ECO:0000269\|PubMed:23676497}.


Subunit:		Homotetramer (Probable). Interacts (via guanylate kinase-like domain) with DLGAP1, DLGAP2, DLGAP3, DLGAP4 and MAP1A (By similarity). Interacts (via guanylate kinase-like domain) with KIF13B (PubMed:10859302). May interact with HTR2A (By similarity). Interacts (via PDZ domains) with GRIA1 (By similarity). Interacts (via PDZ domains) with GRIN2A (By similarity). Interacts (via PDZ domains) with KCND2 and KCND3 (PubMed:19213956). Interacts (via PDZ domains) with KCNA1, KCNA2, KCNA3 and KCNA4 (PubMed:7477295). Interacts (via PDZ domains) with ADGRA3 (PubMed:15021905). Interacts with KCNF1 (PubMed:12445884). Interacts with CAMK2 (By similarity). Interacts with cytoskeleton-associated protein EPB41 (PubMed:7937897, PubMed:8922391). Interacts with cytoskeleton-associated protein EZR (By similarity). Found in a complex with KCNA5 and CAV3 (By similarity). Found in a complex with APC and CTNNB1 (PubMed:8638125, PubMed:10656683). Interacts with CDH1 through binding to PIK3R1 (PubMed:14699157). Forms multiprotein complexes with CASK, LIN7A, LIN7B, LIN7C, APBA1, and KCNJ12 (By similarity). Interacts with TOPK (PubMed:10779557). Forms a tripartite complex composed of DLG1, MPP7 and LIN7 (LIN7A or LIN7C) (PubMed:17237226, PubMed:17332497, PubMed:20702775). May interact with TJAP1 (PubMed:11602598). Interacts with PTEN (By similarity). Interacts with FRMPD4 (via C-terminus) (PubMed:19118189). Interacts with LRFN1, LRFN2 and LRFN4 (PubMed:16630835). Interacts with SFPQ (PubMed:20605917). Interacts (via PDZ domains) with ADGRA2 (via PDZ- binding motif) (PubMed:15021905, PubMed:25558062). Interacts with ADAM10; this interaction recruits ADAM10 to the cell membrane during long-term depression in hippocampal neurons (PubMed:23676497). Interacts with DGKI (via PDZ-binding motif) (By similarity). {ECO:0000250\|UniProtKB:Q62696, ECO:0000250\|UniProtKB:Q811D0, ECO:0000269\|PubMed:10656683, ECO:0000269\|PubMed:10779557, ECO:0000269\|PubMed:10859302, ECO:0000269\|PubMed:11602598, ECO:0000269\|PubMed:12445884, ECO:0000269\|PubMed:14699157, ECO:0000269\|PubMed:15021905, ECO:0000269\|PubMed:16630835, ECO:0000269\|PubMed:17237226, ECO:0000269\|PubMed:17332497, ECO:0000269\|PubMed:19118189, ECO:0000269\|PubMed:19213956, ECO:0000269\|PubMed:20605917, ECO:0000269\|PubMed:20702775, ECO:0000269\|PubMed:23676497, ECO:0000269\|PubMed:25558062, ECO:0000269\|PubMed:7477295, ECO:0000269\|PubMed:7937897, ECO:0000269\|PubMed:8638125, ECO:0000269\|PubMed:8922391, ECO:0000305}.
Subunit:		(Microbial infection) Interacts with HTLV-1 protein Tax. {ECO:0000269\|PubMed:10557085}.
Subunit:		(Microbial infection) Interacts with human papillomavirus 18/HPV-18 protein E6. {ECO:0000269\|PubMed:9192623}.
Subcellular location:		Membrane {ECO:0000269\|PubMed:10859302, ECO:0000269\|PubMed:11723125, ECO:0000269\|PubMed:8922391}; Peripheral membrane protein {ECO:0000269\|PubMed:8922391}. Basolateral cell membrane {ECO:0000269\|PubMed:12807908}. Endoplasmic reticulum membrane {ECO:0000250\|UniProtKB:Q62696}. Cell junction, synapse, postsynaptic density {ECO:0000250\|UniProtKB:Q62696}. Cell junction, synapse {ECO:0000250\|UniProtKB:Q62696}. Cell membrane, sarcolemma {ECO:0000269\|PubMed:12445884}. Apical cell membrane {ECO:0000269\|PubMed:12445884}. Cell junction {ECO:0000269\|PubMed:10859302, ECO:0000269\|PubMed:11723125, ECO:0000269\|PubMed:7937897}. Cytoplasm {ECO:0000269\|PubMed:10859302}. Note=Colocalizes with EPB41 at regions of intercellular contacts. Basolateral in epithelial cells (PubMed:12807908). May also associate with endoplasmic reticulum membranes. Mainly found in neurons soma, moderately found at postsynaptic densities (By similarity). {ECO:0000250\|UniProtKB:Q62696, ECO:0000269\|PubMed:10859302, ECO:0000269\|PubMed:12807908, ECO:0000269\|PubMed:8922391, ECO:0000269\|PubMed:9192623}.
Tissue specificity:		Abundantly expressed in atrial myocardium (at protein level). Expressed in lung fibroblasts, cervical epithelial and B-cells (at protein level). Expressed in the brain (at protein level) (PubMed:23676497). Widely expressed, with isoforms displaying different expression profiles. {ECO:0000269\|PubMed:12445884, ECO:0000269\|PubMed:19213956, ECO:0000269\|PubMed:23676497, ECO:0000269\|PubMed:7937897}.
Domain:		The alternatively spliced domain I3 corresponding to amino acids (636-669) of isoform 4 is an EPB41 binding site mediating association to membranes in polarized and non-polarized cells.
Domain:		The PDZ domains may also mediate association to membranes by binding to EPB41 and ADGRA2 together with the L27 domain that binds CASK and DLG2.
Domain:		The L27 domain may regulate DLG1 self-association. The N- terminal alternatively spliced region is capable of binding several SH3 domains and also moderates the level of protein oligomerization.
Ptm:		Phosphorylated by MAPK12. Phosphorylation of Ser-232 regulates association with GRIN2A (By similarity). {ECO:0000250}.
Similarity:		Belongs to the MAGUK family. {ECO:0000305}.