Disks large homolog 4

Details

Name
Disks large homolog 4
Kind
protein
Synonyms
  • Postsynaptic density protein 95
  • PSD-95
  • PSD95
  • SAP-90
  • SAP90
  • Synapse-associated protein 90
Gene Name
DLG4
UniProtKB Entry
P78352Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0009445|Disks large homolog 4
MDCLCIVTTKKYRYQDEDTPPLEHSPAHLPNQANSPPVIVNTDTLEAPGYELQVNGTEGE
MEYEEITLERGNSGLGFSIAGGTDNPHIGDDPSIFITKIIPGGAAAQDGRLRVNDSILFV
NEVDVREVTHSAAVEALKEAGSIVRLYVMRRKPPAEKVMEIKLIKGPKGLGFSIAGGVGN
QHIPGDNSIYVTKIIEGGAAHKDGRLQIGDKILAVNSVGLEDVMHEDAVAALKNTYDVVY
LKVAKPSNAYLSDSYAPPDITTSYSQHLDNEISHSSYLGTDYPTAMTPTSPRRYSPVAKD
LLGEEDIPREPRRIVIHRGSTGLGFNIVGGEDGEGIFISFILAGGPADLSGELRKGDQIL
SVNGVDLRNASHEQAAIALKNAGQTVTIIAQYKPEEYSRFEAKIHDLREQLMNSSLGSGT
ASLRSNPKRGFYIRALFDYDKTKDCGFLSQALSFRFGDVLHVIDASDEEWWQARRVHSDS
ETDDIGFIPSKRRVERREWSRLKAKDWGSSSGSQGREDSVLSYETVTQMEVHYARPIIIL
GPTKDRANDDLLSEFPDKFGSCVPHTTRPKREYEIDGRDYHFVSSREKMEKDIQAHKFIE
AGQYNSHLYGTSVQSVREVAEQGKHCILDVSANAVRRLQAAHLHPIAIFIRPRSLENVLE
INKRITEEQARKAFDRATKLEQEFTECFSAIVEGDSFEEIYHKVKRVIEDLSGPYIWVPA
RERL
Number of residues
724
Molecular Weight
80494.615
Theoretical pI
Not Available
GO Classification
Functions
protein kinase binding / protein-containing complex binding
Processes
cell-cell adhesion / cellular response to potassium ion / chemical synaptic transmission / establishment or maintenance of epithelial cell apical/basal polarity / neurotransmitter receptor localization to postsynaptic specialization membrane / positive regulation of neuron projection arborization / positive regulation of protein tyrosine kinase activity / postsynaptic neurotransmitter receptor diffusion trapping / protein-containing complex assembly / regulation of NMDA receptor activity
Components
adherens junction / basolateral plasma membrane / glutamatergic synapse / neuromuscular junction / neuron projection / postsynaptic density membrane / synaptic membrane
General Function
Postsynaptic scaffolding protein that plays a critical role in synaptogenesis and synaptic plasticity by providing a platform for the postsynaptic clustering of crucial synaptic proteins. Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B. Also regulates AMPA-type glutamate receptor (AMPAR) immobilization at postsynaptic density keeping the channels in an activated state in the presence of glutamate and preventing synaptic depression (By similarity). Under basal conditions, cooperates with FYN to stabilize palmitoyltransferase ZDHHC5 at the synaptic membrane through FYN-mediated phosphorylation of ZDHHC5 and its subsequent inhibition of association with endocytic proteins (PubMed:26334723)
Specific Function
acetylcholine receptor binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0013164|Disks large homolog 4 (DLG4)
ATGGACTGTCTCTGTATAGTGACAACCAAGAAATACCGCTACCAAGATGAAGACACGCCC
CCTCTGGAGCACAGCCCGGCCCACCTCCCCAACCAGGCCAATTCTCCCCCAGTGATTGTC
AACACAGATACCCTAGAAGCCCCAGGATATGTGAACGGGACCGAGGGGGAGATGGAATAC
GAGGAAATCACATTGGAAAGGGGTAACTCAGGTCTGGGCTTCAGCATCGCAGGTGGCACT
GACAACCCACACATCGGTGACGACCCATCCATTTTCATCACCAAGATCATTCCTGGTGGG
GCTGCGGCCCAGGATGGCCGCCTCAGGGTCAACGACAGCATCCTGTTTGTAAATGAAGTG
GACGTGCGCGAGGTGACCCACTCAGCGGCGGTGGAAGCCCTCAAAGAGGCAGGCTCCATC
GTTCGCCTCTATGTCATGCGCCGGAAGCCCCCGGCTGAGAAGGTCATGGAGATCAAGCTC
ATCAAGGGGCCTAAAGGTCTTGGCTTCAGCATCGCAGGGGGCGTAGGGAACCAGCACATC
CCAGGAGATAATAGCATCTATGTAACAAAGATCATCGAAGGGGGTGCTGCCCACAAGGAT
GGGAGGTTGCAGATTGGAGACAAGATCCTGGCGGTCAACAGTGTGGGGCTAGAGGACGTC
ATGCATGAAGATGCTGTGGCAGCCCTGAAGAACACGTATGATGTTGTCTACCTAAAGGTG
GCCAAGCCCAGCAATGCCTACCTGAGTGACAGCTATGCTCCCCCAGACATCACAACCTCT
TATTCCCAGCACCTGGACAATGAGATCAGTCACAGCAGCTACCTGGGCACCGACTACCCC
ACAGCCATGACCCCCACTTCCCCTCGGCGCTACTCTCCAGTGGCCAAGGACCTGCTCGGG
GAGGAAGACATTCCCCGAGAACCGAGGCGAATTGTGATCCACCGGGGCTCCACGGGCCTG
GGCTTCAACATCGTGGGTGGCGAGGACGGTGAAGGCATCTTCATCTCCTTTATCCTGGCC
GGGGGCCCTGCAGACCTCAGTGGGGAGCTGCGGAAGGGGGACCAGATCCTGTCGGTCAAC
GGTGTGGACCTCCGAAATGCCAGCCATGAGCAGGCTGCCATTGCCCTGAAGAATGCGGGT
CAGACGGTCACGATCATCGCTCAGTATAAACCAGAAGAGTACAGCCGATTCGAGGCCAAG
ATCCACGACCTTCGGGAACAGCTCATGAACAGCAGCCTGGGCTCAGGGACTGCGTCCCTG
CGGAGCAACCCCAAAAGGGGTTTCTACATCAGGGCCCTGTTTGATTACGACAAGACCAAG
GACTGCGGCTTCCTGAGCCAGGCCCTGAGCTTCCGCTTTGGGGATGTGCTGCATGTCATC
GATGCTAGTGATGAGGAGTGGTGGCAGGCACGGCGGGTCCACTCTGACAGTGAGACCGAC
GACATTGGGTTCATCCCCAGCAAACGGCGGGTTGAGCGACGAGAGTGGTCAAGGTTAAAG
GCCAAGGACTGGGGCTCCAGCTCTGGATCGCAGGGTCGAGAAGACTCGGTTCTGAGCTAC
GAGACAGTGACGCAGATGGAAGTGCACTATGCTCGCCCCATCATCATCCTTGGGCCCACC
AAGGACCGCGCCAACGATGATCTTCTCTCCGAGTTCCCCGACAAGTTTGGATCCTGTGTT
CCCCATACGACACGGCCCAAGCGGGAGTATGAGATAGATGGCCGGGATTACCACTTTGTG
TCGTCCCGGGAGAAAATGGAGAAGGACATTCAGGCGCACAAGTTCATTGAGGCCGGCCAG
TACAACAGCCACCTCTATGGGACCAGCGTCCAGTCCGTGCGAGAGGTGGCAGAGCAGGGG
AAGCACTGCATCCTCGATGTCTCGGCCAATGCCGTGCGGCGGCTGCAGGCGGCCCACCTG
CACCCCATCGCCATCTTCATCCGCCCCCGCTCCCTGGAGAATGTGCTAGAGATTAACAAG
CGGATCACAGAGGAGCAAGCCCGCAAAGCCTTCGACAGAGCCACCAAGCTGGAGCAGGAG
TTCACAGAGTGCTTCTCAGCCATCGTGGAGGGTGACAGCTTTGAGGAGATCTACCACAAG
GTGAAGCGTGTCATCGAGGACCTCTCAGGCCCCTACATCTGGGTTCCAGCCCGAGAGAGA
CTCTGA
Chromosome Location
17
Locus
17p13.1
External Identifiers
ResourceLink
UniProtKB IDP78352
UniProtKB Entry NameDLG4_HUMAN
GeneCard IDDLG4
HGNC IDHGNC:2903
PDB ID(s)1KEF, 2MES, 3I4W, 3K82, 3ZRT, 5J7J, 5JXB, 6QJD, 6QJF, 6QJG, 6QJI, 6QJJ, 6QJK, 6QJL, 6QJN, 6SPV, 6SPZ, 8AH4, 8AH5, 8AH6, 8AH7, 8AH8
KEGG IDhsa:1742
NCBI Gene ID1742
General References
  1. Stathakis DG, Hoover KB, You Z, Bryant PJ: Human postsynaptic density-95 (PSD95): location of the gene (DLG4) and possible function in nonneural as well as in neural tissues. Genomics. 1997 Aug 15;44(1):71-82. [Article]
  2. Stathakis DG, Udar N, Sandgren O, Andreasson S, Bryant PJ, Small K, Forsman-Semb K: Genomic organization of human DLG4, the gene encoding postsynaptic density 95. J Neurochem. 1999 Dec;73(6):2250-65. [Article]
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  4. Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L, Young SK, Abouelleil A, Allen NR, Bi W, Bloom T, Borowsky ML, Bugalter BE, Butler J, Chang JL, Chen CK, Cook A, Corum B, Cuomo CA, de Jong PJ, DeCaprio D, Dewar K, FitzGerald M, Gilbert J, Gibson R, Gnerre S, Goldstein S, Grafham DV, Grocock R, Hafez N, Hagopian DS, Hart E, Norman CH, Humphray S, Jaffe DB, Jones M, Kamal M, Khodiyar VK, LaButti K, Laird G, Lehoczky J, Liu X, Lokyitsang T, Loveland J, Lui A, Macdonald P, Major JE, Matthews L, Mauceli E, McCarroll SA, Mihalev AH, Mudge J, Nguyen C, Nicol R, O'Leary SB, Osoegawa K, Schwartz DC, Shaw-Smith C, Stankiewicz P, Steward C, Swarbreck D, Venkataraman V, Whittaker CA, Yang X, Zimmer AR, Bradley A, Hubbard T, Birren BW, Rogers J, Lander ES, Nusbaum C: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature. 2006 Apr 20;440(7087):1045-9. [Article]
  5. Kim E, Niethammer M, Rothschild A, Jan YN, Sheng M: Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases. Nature. 1995 Nov 2;378(6552):85-8. [Article]
  6. Irie M, Hata Y, Takeuchi M, Ichtchenko K, Toyoda A, Hirao K, Takai Y, Rosahl TW, Sudhof TC: Binding of neuroligins to PSD-95. Science. 1997 Sep 5;277(5331):1511-5. [Article]
  7. Hanada T, Lin L, Tibaldi EV, Reinherz EL, Chishti AH: GAKIN, a novel kinesin-like protein associates with the human homologue of the Drosophila discs large tumor suppressor in T lymphocytes. J Biol Chem. 2000 Sep 15;275(37):28774-84. [Article]
  8. Garcia RA, Vasudevan K, Buonanno A: The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at neuronal synapses. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3596-601. [Article]
  9. Chetkovich DM, Bunn RC, Kuo SH, Kawasaki Y, Kohwi M, Bredt DS: Postsynaptic targeting of alternative postsynaptic density-95 isoforms by distinct mechanisms. J Neurosci. 2002 Aug 1;22(15):6415-25. [Article]
  10. Ko J, Kim S, Chung HS, Kim K, Han K, Kim H, Jun H, Kaang BK, Kim E: SALM synaptic cell adhesion-like molecules regulate the differentiation of excitatory synapses. Neuron. 2006 Apr 20;50(2):233-45. [Article]
  11. Lee HW, Choi J, Shin H, Kim K, Yang J, Na M, Choi SY, Kang GB, Eom SH, Kim H, Kim E: Preso, a novel PSD-95-interacting FERM and PDZ domain protein that regulates dendritic spine morphogenesis. J Neurosci. 2008 Dec 31;28(53):14546-56. doi: 10.1523/JNEUROSCI.3112-08.2008. [Article]
  12. Fujita-Jimbo E, Tanabe Y, Yu Z, Kojima K, Mori M, Li H, Iwamoto S, Yamagata T, Momoi MY, Momoi T: The association of GPR85 with PSD-95-neuroligin complex and autism spectrum disorder: a molecular analysis. Mol Autism. 2015 Mar 13;6:17. doi: 10.1186/s13229-015-0012-5. eCollection 2015. [Article]
  13. Piserchio A, Pellegrini M, Mehta S, Blackman SM, Garcia EP, Marshall J, Mierke DF: The PDZ1 domain of SAP90. Characterization of structure and binding. J Biol Chem. 2002 Mar 1;277(9):6967-73. Epub 2001 Dec 14. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Guanosine-5'-MonophosphateexperimentalyestargetinhibitorDetails
GuanidineapprovedunknowntargetDetails