Disks large homolog 1 (DLG1)

The protein contains 904 amino acids for an estimated molecular weight of 100455 Da.

 

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). (updated: July 31, 2019)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  4. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 79%
Model score: 0

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VariantDescription
dbSNP:rs1802668
dbSNP:rs1134986
dbSNP:rs34492126

Biological Process

Actin filament organization GO Logo
Activation of protein kinase activity GO Logo
Amyloid precursor protein metabolic process GO Logo
Astral microtubule organization GO Logo
Axon guidance GO Logo
Bicellular tight junction assembly GO Logo
Branching involved in ureteric bud morphogenesis GO Logo
Cell-cell adhesion GO Logo
Cellular protein-containing complex localization GO Logo
Chemical synaptic transmission GO Logo
Cortical actin cytoskeleton organization GO Logo
Cortical microtubule organization GO Logo
Dephosphorylation GO Logo
Embryonic skeletal system morphogenesis GO Logo
Endothelial cell proliferation GO Logo
Establishment of centrosome localization GO Logo
Establishment or maintenance of cell polarity GO Logo
Establishment or maintenance of epithelial cell apical/basal polarity GO Logo
Hard palate development GO Logo
Immunological synapse formation GO Logo
Lens development in camera-type eye GO Logo
MAPK cascade GO Logo
Membrane raft organization GO Logo
Mitotic cell cycle checkpoint signaling GO Logo
Negative regulation of epithelial cell proliferation GO Logo
Negative regulation of ERK1 and ERK2 cascade GO Logo
Negative regulation of G1/S transition of mitotic cell cycle GO Logo
Negative regulation of mitotic cell cycle GO Logo
Negative regulation of p38MAPK cascade GO Logo
Negative regulation of protein kinase B signaling GO Logo
Negative regulation of T cell proliferation GO Logo
Negative regulation of transcription by RNA polymerase II GO Logo
Nervous system development GO Logo
Neurotransmitter receptor localization to postsynaptic specialization membrane GO Logo
Nucleotide phosphorylation GO Logo
Peristalsis GO Logo
Positive regulation of actin filament polymerization GO Logo
Positive regulation of cell population proliferation GO Logo
Positive regulation of establishment of protein localization to plasma membrane GO Logo
Positive regulation of potassium ion transport GO Logo
Positive regulation of protein localization to plasma membrane GO Logo
Protein localization to plasma membrane GO Logo
Receptor clustering GO Logo
Receptor localization to synapse GO Logo
Regulation of cell shape GO Logo
Regulation of membrane potential GO Logo
Regulation of myelination GO Logo
Regulation of NMDA receptor activity GO Logo
Regulation of potassium ion export across plasma membrane GO Logo
Regulation of potassium ion import GO Logo
Regulation of protein localization to synapse GO Logo
Regulation of sodium ion transmembrane transport GO Logo
Regulation of ventricular cardiac muscle cell action potential GO Logo
Regulation of voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization GO Logo
Reproductive structure development GO Logo
Single organismal cell-cell adhesion GO Logo
Smooth muscle tissue development GO Logo
T cell activation GO Logo
T cell cytokine production GO Logo
Viral process GO Logo

The reference OMIM entry for this protein is 601014

Discs large, drosophila, homolog of, 1; dlg1
Synapse-associated protein 97; sap97

CLONING

Azim et al. (1995) noted that in Drosophila more than 50 genes have been identified that lead to loss of cell proliferation control, indicating that they are tumor suppressor genes. Many of these genes have been cloned and sequenced, and most have clear mammalian homologs. The Drosophila 'discs large' tumor suppressor protein, Dlg, is the prototype of a family of proteins termed MAGUKs (membrane-associated guanylate kinase homologs). MAGUKs are localized at the membrane-cytoskeleton interface, usually at cell-cell junctions, where they appear to have both structural and signaling roles. They contain several distinct domains, including a modified guanylate kinase domain, an SH3 motif, and 1 or 3 copies of the DHR (GLGF/PDZ) domain. Recessive lethal mutations in the 'discs large' tumor suppressor gene interfere with the formation of septate junctions (thought to be the arthropod equivalent of tight junctions) between epithelial cells, and they also cause neoplastic overgrowth of imaginal discs, suggesting a role for cell junctions in proliferation control. A homolog of the Drosophila Dlg protein was isolated from human B lymphocytes (Lue et al., 1994) and shown to bind directly to the membrane cytoskeletal protein 4.1 (130500). The presence of human DLG isoforms with or without the protein 4.1-binding domain suggested that the tissue-specific cytoskeletal interactions of the protein may be regulated by alternative splicing of its transcripts. Mori et al. (1998) identified a number of novel splicing variants, some of which were transcribed in a tissue-specific manner, as well as alteration of splicing patterns in cell lines from neuroblastomas.

GENE FUNCTION

Hanada et al. (1997) showed by immunoblot analysis that immunoprecipitates of DLG1 in T lymphocytes contain the Src family tyrosine kinase p56(lck) (LCK; 153390) but not p59(fyn) (FYN; 137025) or PIK3 (see PIK3CA, 171834). Binding analysis demonstrated that LCK interacts with the proline-rich N-terminal domain of DLG1. Additionally, DLG1 interacts with the Kv1.3 channel (see KCNAB1, 601141). Hanada et al. (1997) suggested that DLG1 may function as a coupler of tyrosine kinase and a voltage-gated potassium channel in T lymphocytes. Ohshiro et al. (2000) demonstrated in Drosophila that lethal giant larvae (Lgl) (LLGL1; 600966) is essential for asymmetric cortical localization of all basal determinants in mitotic neuroblasts, and is therefore indispensable for neural fate decisions. Lgl, which itself is uniformly cortical, interacts with several types of myosin to localize the determinants. Dlg, another tumor suppressor gene, participates in this process by regulating the localization of Lgl. The localization of the apical components is unaffected in Lgl or Dlg mutants. Thus, Lgl and Dlg act in a common process that differentially mediates cortical protein targeting in mitotic neuroblasts, and creates intrinsic differences between daughter cells. Peng et al. (2000) showed that Drosophila Lgl and Dlg regulate basal protein targeting, but not apical complex formation or spindle orientation, in both embryonic and larval neuroblasts. Dlg protein is apically enriched and is required for maintaining cortical localization of Lgl protein. Basal protein targeting requires microfilament and myosin function, yet the Lgl phenotype is strongly suppressed by reducing levels of myosin II. Peng et al. (2000) concluded that Dlg and Lgl promote, and myosin II inhibits, actomyo ... More on the omim web site

Subscribe to this protein entry history

Aug. 20, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

May 12, 2019: Protein entry updated
Automatic update: model status changed

Nov. 17, 2018: Protein entry updated
Automatic update: model status changed

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

Oct. 27, 2017: Protein entry updated
Automatic update: model status changed

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601014 was added.

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed