disks large homolog 1; synapse-associated protein 97; SAP-97; SAP97; hDlg (DLG1)

Function

• essential multidomain scaffolding protein required for normal development (putative)
• recruits channels, receptors & signaling molecules to discrete plasma membrane domains in polarized cells
• may play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis & lymphocyte activation
• regulates excitability of cardiac myocytes by modulating the functional expression of Kv4 channels
• functional regulator of Kv1.5 channel
• phosphorylation of Ser-232 regulates association with GRIN2A
• isoform 2 is phosphorylated on Ser-698
• isoform 3 is phosphorylated on Ser-665 (putative)
• homotetramer (probable)
• interacts through its guanylate kinase-like domain with DLGAP1, DLGAP2, DLGAP3, DLGAP4 & MAP1A
• may interact with HTR2A (putative)
• interacts with LRFN1
• interacts through its PDZ domains with GRIN2A, KCNA1, KCNA2, KCNA3, KCNA4, KCNA5, KCND2, KCND3, GRIA1, GPR124 & GPR125, & GlUR1 subunit of the AMPA receptor
• interacts with KCNF1
• interacts with CAMK2
• interacts with cytoskeleton-associated proteins EPB41 & EZR
• found in a complex with KCNA5 & CAV3
• found in a complex with APC & CTNNB1
• interacts with CDH1 through binding to PIK3R1
• forms multiprotein complexes with CASK, LIN7A, LIN7B, LIN7C, APBA1, & KCNJ12
• interacts through its guanylate kinase-like domain with KIF13B
• forms a tripartite complex composed of DLG1, MPP7 & LIN7 (LIN7A or LIN7C)
• may interact with TJAP1
• interacts with TOPK & the HTLV-1 viral Tax & HPV-18 E6 papillomavirus (HPV) oncoproteins
• interacts with PTEN
• interacts with FRMPD4 (via C-terminus)

Structure

• homolog of drosophila dlg protein
• alternatively spliced domain I3 corresponding to amino acids (636-669) of isoform 4 is an EPB41 binding site mediating association to membranes in polarized & non-polarized cells
• the PDZ domains may also mediate association to membranes by binding to EPB41 & GPR124 together with the L27 domain that binds CASK & DLG2
• the L27 domain may regulate DLG1 self-association
• the N-terminal alternatively spliced region is capable of binding several SH3 domains & also moderates the level of protein oligomerization
• belongs to the MAGUK family
• contains 1 guanylate kinase-like domain
• contains 1 L27 domain
• contains 3 PDZ domain (DHR domain)s
• contains 1 SH3 domain

Compartment

• membrane; peripheral membrane
• basolateral cell membrane (putative)
• endoplasmic reticulum membrane (putative)
• cell junction
• synapse, postsynaptic cell membrane, postsynaptic density
• sarcolemma
• colocalizes with EPB41 at regions of intercellular contacts basolateral in epithelial cells
• may also associate with endoplasmic reticulum membranes
• mainly found in neurons soma,
• moderately found at postsynaptic densities (putative)

Alternative splicing

named isoforms=7

Expression

a

• abundantly expressed in atrial myocardium (at protein level)
• expressed in lung fibroblasts, cervical epithelial & B-cells (at protein level)
• widely expressed, with isoforms displaying different expression profiles

More general terms

• scaffold protein
• phosphoprotein

Additional terms

• discs large homolog
• disks large-associated protein 1; DAP-1; guanylate kinase-associated protein; hGKAP; SAP90/PSD-95-associated protein 1; SAPAP1; PSD-95/SAP90-binding protein 1 (DLGAP1 DAP1 GKAP)
• drosophila discs large [dlg] protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1739
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1739
• OMIM: https://mirror.omim.org/entry/601014
• UniProt: http://www.uniprot.org/uniprot/Q12959.html