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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
Interactions
molecular events
Related
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
General
phosphoprotein
scaffold protein
Properties
SIZE: entity length = 904 aa
MW = 100 kD
COMPARTMENT: endoplasmic reticulum
MOTIF: L27 domain {4-64}
Thr phosphorylation site {T115}
Ser phosphorylation site {S122}
SH3 domains interaction {162-212}
PDZ domain
NAME: PDZ domain
SITE: 224-310
MOTIF: Ser phosphorylation site {S232}
Ser phosphorylation site {S301}
PDZ domain
NAME: PDZ domain
SITE: 319-405
MOTIF: Tyr phosphorylation site {Y399}
PDZ domain
NAME: PDZ domain
SITE: 466-546
Ser phosphorylation site {S575}
src homology 3 [SH3] domain
SITE: 581-651
MOTIF: Ser phosphorylation site {S619}
Thr phosphorylation site {T683}
Ser phosphorylation site {S684}
Ser phosphorylation site {S687}
domain {714-889}
MOTIF: Tyr phosphorylation site {Y760}
HOMOLOGY: guanylate kinase
Database Correlations
OMIM 601014
UniProt Q12959
PFAM correlations
Entrez Gene 1739
Kegg hsa:1739
References
- UniProt :accession Q12959
- Sheng M.
Molecular organization of the postsynaptic specialization.
Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7058-61. Review.
PMID: 11416187
Component-of
molecular complex