ID DLG1_RAT Reviewed; 911 AA.
AC Q62696;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-APR-2013, entry version 131.
DE RecName: Full=Disks large homolog 1;
DE AltName: Full=Synapse-associated protein 97;
DE Short=SAP-97;
DE Short=SAP97;
GN Name=Dlg1; Synonyms=Dlgh1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC Muroidea; Muridae; Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Brain;
RX PubMed=7891172;
RA Mueller B.M., Kistner U., Veh R.W., Cases-Langhoff C., Becker B.,
RA Gundelfinger E.D., Garner C.C.;
RT "Molecular characterization and spatial distribution of SAP97, a novel
RT presynaptic protein homologous to SAP90 and the Drosophila discs-large
RT tumor suppressor protein.";
RL J. Neurosci. 15:2354-2366(1995).
RN [2]
RP INTERACTION WITH DLGAP1; DLGAP2; DLGAP3 AND DLGAP4.
RX PubMed=9115257; DOI=10.1074/jbc.272.18.11943;
RA Takeuchi M., Hata Y., Hirao K., Toyoda A., Irie M., Takai Y.;
RT "SAPAPs. A family of PSD-95/SAP90-associated proteins localized at
RT postsynaptic density.";
RL J. Biol. Chem. 272:11943-11951(1997).
RN [3]
RP INTERACTION WITH GRIA1.
RX PubMed=9677374; DOI=10.1074/jbc.273.31.19518;
RA Leonard A.S., Davare M.A., Horne M.C., Garner C.C., Hell J.W.;
RT "SAP97 is associated with the alpha-amino-3-hydroxy-5-methylisoxazole-
RT 4-propionic acid receptor GluR1 subunit.";
RL J. Biol. Chem. 273:19518-19524(1998).
RN [4]
RP INTERACTION WITH MAP1A.
RX PubMed=9786987;
RA Brenman J.E., Topinka J.R., Cooper E.C., McGee A.W., Rosen J.,
RA Milroy T., Ralston H.J., Bredt D.S.;
RT "Localization of postsynaptic density-93 to dendritic microtubules and
RT interaction with microtubule-associated protein 1A.";
RL J. Neurosci. 18:8805-8813(1998).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=10629225; DOI=10.1083/jcb.148.1.147;
RA Tiffany A.M., Manganas L.N., Kim E., Hsueh Y.P., Sheng M.,
RA Trimmer J.S.;
RT "PSD-95 and SAP97 exhibit distinct mechanisms for regulating K(+)
RT channel surface expression and clustering.";
RL J. Cell Biol. 148:147-158(2000).
RN [6]
RP INTERACTION WITH CASK, AND SUBCELLULAR LOCATION.
RX PubMed=11865057; DOI=10.1128/MCB.22.6.1778-1791.2002;
RA Lee S., Fan S., Makarova O., Straight S., Margolis B.;
RT "A novel and conserved protein-protein interaction domain of mammalian
RT Lin-2/CASK binds and recruits SAP97 to the lateral surface of
RT epithelia.";
RL Mol. Cell. Biol. 22:1778-1791(2002).
RN [7]
RP INDUCTION BY BDNF.
RX PubMed=14597197; DOI=10.1016/j.ydbio.2003.07.008;
RA Jourdi H., Iwakura Y., Narisawa-Saito M., Ibaraki K., Xiong H.,
RA Watanabe M., Hayashi Y., Takei N., Nawa H.;
RT "Brain-derived neurotrophic factor signal enhances and maintains the
RT expression of AMPA receptor-associated PDZ proteins in developing
RT cortical neurons.";
RL Dev. Biol. 263:216-230(2003).
RN [8]
RP MUTAGENESIS OF SER-232, PHOSPHORYLATION AT SER-232, AND INTERACTION
RP WITH GRIN2A.
RX PubMed=12933808; DOI=10.1074/jbc.M303576200;
RA Gardoni F., Mauceri D., Fiorentini C., Bellone C., Missale C.,
RA Cattabeni F., Di Luca M.;
RT "CaMKII-dependent phosphorylation regulates SAP97/NR2A interaction.";
RL J. Biol. Chem. 278:44745-44752(2003).
RN [9]
RP INTERACTION WITH CASK; LIN7A; LIN7B; LIN7C; APBA1 AND KCNJ12, AND
RP FUNCTION.
RX PubMed=14960569; DOI=10.1074/jbc.M400284200;
RA Leonoudakis D., Conti L.R., Radeke C.M., McGuire L.M.,
RA Vandenberg C.A.;
RT "A multiprotein trafficking complex composed of SAP97, CASK, Veli, and
RT Mint1 is associated with inward rectifier Kir2 potassium channels.";
RL J. Biol. Chem. 279:19051-19063(2004).
RN [10]
RP MUTAGENESIS OF SER-39, PHOSPHORYLATION AT SER-39, SUBCELLULAR
RP LOCATION, AND FUNCTION.
RX PubMed=15044483; DOI=10.1074/jbc.M402796200;
RA Mauceri D., Cattabeni F., Di Luca M., Gardoni F.;
RT "Calcium/calmodulin-dependent protein kinase II phosphorylation drives
RT synapse-associated protein 97 into spines.";
RL J. Biol. Chem. 279:23813-23821(2004).
RN [11]
RP FUNCTION.
RX PubMed=15504326; DOI=10.1016/j.neuron.2004.10.012;
RA Nakagawa T., Futai K., Lashuel H.A., Lo I., Okamoto K., Walz T.,
RA Hayashi Y., Sheng M.;
RT "Quaternary structure, protein dynamics, and synaptic function of
RT SAP97 controlled by L27 domain interactions.";
RL Neuron 44:453-467(2004).
RN [12]
RP INTERACTION WITH PTEN.
RX PubMed=15951562; DOI=10.1074/jbc.M504761200;
RA Valiente M., Andres-Pons A., Gomar B., Torres J., Gil A., Tapparel C.,
RA Antonarakis S.E., Pulido R.;
RT "Binding of PTEN to specific PDZ domains contributes to PTEN protein
RT stability and phosphorylation by microtubule-associated
RT serine/threonine kinases.";
RL J. Biol. Chem. 280:28936-28943(2005).
RN [13]
RP INTERACTION WITH LRFN2.
RX PubMed=16495444; DOI=10.1523/JNEUROSCI.3799-05.2006;
RA Wang C.Y., Chang K., Petralia R.S., Wang Y.X., Seabold G.K.,
RA Wenthold R.J.;
RT "A novel family of adhesion-like molecules that interacts with the
RT NMDA receptor.";
RL J. Neurosci. 26:2174-2183(2006).
RN [14]
RP INTERACTION WITH LRFN1.
RX PubMed=16630835; DOI=10.1016/j.neuron.2006.04.005;
RA Ko J., Kim S., Chung H.S., Kim K., Han K., Kim H., Jun H.,
RA Kaang B.-K., Kim E.;
RT "SALM synaptic cell adhesion-like molecules regulate the
RT differentiation of excitatory synapses.";
RL Neuron 50:233-245(2006).
RN [15]
RP INTERACTION WITH FRMPD4.
RX PubMed=19118189; DOI=10.1523/JNEUROSCI.3112-08.2008;
RA Lee H.W., Choi J., Shin H., Kim K., Yang J., Na M., Choi S.Y.,
RA Kang G.B., Eom S.H., Kim H., Kim E.;
RT "Preso, a novel PSD-95-interacting FERM and PDZ domain protein that
RT regulates dendritic spine morphogenesis.";
RL J. Neurosci. 28:14546-14556(2008).
RN [16]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INTERACTION
RP WITH KCND2; KCND3 AND CAMK2.
RX PubMed=19213956; DOI=10.1161/CIRCRESAHA.108.191007;
RA El-Haou S., Balse E., Neyroud N., Dilanian G., Gavillet B., Abriel H.,
RA Coulombe A., Jeromin A., Hatem S.N.;
RT "Kv4 potassium channels form a tripartite complex with the anchoring
RT protein SAP97 and CaMKII in cardiac myocytes.";
RL Circ. Res. 104:758-769(2009).
CC -!- FUNCTION: Essential multidomain scaffolding protein required for
CC normal development (By similarity). Recruits channels, receptors
CC and signaling molecules to discrete plasma membrane domains in
CC polarized cells. Regulates the excitability of cardiac myocytes by
CC modulating the functional expression of Kv4 channels. Functional
CC regulator of Kv1.5 channel (By similarity). May play a role in
CC adherens junction assembly, signal transduction, cell
CC proliferation, synaptogenesis and lymphocyte activation.
CC -!- SUBUNIT: Homotetramer (Probable). Interacts with KCNF1 (By
CC similarity). Interacts with CAMK2. Interacts through its PDZ
CC domains with GRIN2A, KCNA1, KCNA2, KCNA3, KCNA4, KCNA5, KCND2,
CC KCND3, GRIA1, GPR124 and GPR125. Interacts with cytoskeleton-
CC associated proteins EPB41 and EZR. Found in a complex with KCNA5
CC and CAV3. Found in a complex with APC and CTNNB1. Interacts with
CC CDH1 through binding to PIK3R1. Forms multiprotein complexes with
CC CASK, LIN7A, LIN7B, LIN7C, APBA1, and KCNJ12. Interacts through
CC its guanylate kinase-like domain with KIF13B. Interacts with TOPK.
CC Forms a tripartite complex composed of DLG1, MPP7 and LIN7 (LIN7A
CC or LIN7C). May interact with HTR2A and TJAP1 (By similarity).
CC Interacts through its guanylate kinase-like domain with DLGAP1,
CC DLGAP2, DLGAP3, DLGAP4 and MAP1A. Interacts with LRFN1 and LRFN2.
CC Interacts with LRFN4 and SFPQ (By similarity). Interacts with
CC PTEN. Interacts with FRMPD4 (via C-terminus).
CC -!- INTERACTION:
CC Q460M5:Lrfn2; NbExp=2; IntAct=EBI-389325, EBI-877185;
CC P34926:Map1a; NbExp=2; IntAct=EBI-389325, EBI-631571;
CC P60484:PTEN (xeno); NbExp=2; IntAct=EBI-389325, EBI-696162;
CC -!- SUBCELLULAR LOCATION: Membrane; Peripheral membrane protein (By
CC similarity). Basolateral cell membrane (By similarity).
CC Endoplasmic reticulum membrane (By similarity). Cell junction,
CC synapse, postsynaptic cell membrane, postsynaptic density (By
CC similarity). Cell junction, synapse. Cell membrane, sarcolemma.
CC Note=Colocalizes with EPB41 at regions of intercellular contacts.
CC Basolateral in epithelial cells. May also associate with
CC endoplasmic reticulum membranes. Mainly found in neurons soma,
CC moderately found at postsynaptic densities (By similarity).
CC -!- TISSUE SPECIFICITY: Widely expressed. Strongly expressed in
CC epithelial cells, in the small intestine it is only detected in
CC the vili. Expressed in brain, heart (at protein level), muscle,
CC lung and liver. In the brain it was detected in olfactory bulbs,
CC cerebral cortex, hippocampus, and spinal cord (at protein level).
CC -!- INDUCTION: By BDNF.
CC -!- DOMAIN: The PDZ domains may also mediate association to membranes
CC by binding to EPB41 and GPR124 together with the L27 domain that
CC binds CASK and DLG2 (By similarity).
CC -!- DOMAIN: The L27 domain may regulate DLG1 self-association. The N-
CC terminal alternatively spliced region is capable of binding
CC several SH3 domains and also moderates the level of protein
CC oligomerization (By similarity).
CC -!- PTM: Phosphorylated by MAPK12 (By similarity). Phosphorylation of
CC Ser-39 modulates transport to the plasma membrane and
CC phosphorylation of Ser-232 regulates association with GRIN2A.
CC -!- SIMILARITY: Belongs to the MAGUK family.
CC -!- SIMILARITY: Contains 1 guanylate kinase-like domain.
CC -!- SIMILARITY: Contains 1 L27 domain.
CC -!- SIMILARITY: Contains 3 PDZ (DHR) domains.
CC -!- SIMILARITY: Contains 1 SH3 domain.
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DR EMBL; U14950; AAA79976.1; -; mRNA.
DR IPI; IPI00207201; -.
DR PIR; I56552; I56552.
DR RefSeq; NP_036920.1; NM_012788.1.
DR UniGene; Rn.89331; -.
DR PDB; 1RSO; NMR; -; A/C=4-63.
DR PDB; 1ZOK; NMR; -; A=221-313.
DR PDB; 2AWU; X-ray; 2.44 A; A/B=318-409.
DR PDB; 2AWW; X-ray; 2.21 A; A/B=318-409.
DR PDB; 2AWX; X-ray; 1.80 A; A/B=318-409.
DR PDB; 2G2L; X-ray; 2.35 A; A/B=318-409.
DR PDB; 2I0I; X-ray; 2.80 A; A/B/C=459-543.
DR PDB; 2I0L; X-ray; 2.31 A; A/B=318-401.
DR PDB; 3UAT; X-ray; 2.70 A; A=578-911.
DR PDBsum; 1RSO; -.
DR PDBsum; 1ZOK; -.
DR PDBsum; 2AWU; -.
DR PDBsum; 2AWW; -.
DR PDBsum; 2AWX; -.
DR PDBsum; 2G2L; -.
DR PDBsum; 2I0I; -.
DR PDBsum; 2I0L; -.
DR PDBsum; 3UAT; -.
DR ProteinModelPortal; Q62696; -.
DR SMR; Q62696; 4-63, 221-313, 318-400, 462-542, 583-911.
DR IntAct; Q62696; 15.
DR MINT; MINT-93379; -.
DR STRING; 10116.ENSRNOP00000055673; -.
DR PhosphoSite; Q62696; -.
DR PaxDb; Q62696; -.
DR PRIDE; Q62696; -.
DR GeneID; 25252; -.
DR KEGG; rno:25252; -.
DR UCSC; RGD:2505; rat.
DR CTD; 1739; -.
DR RGD; 2505; Dlg1.
DR eggNOG; COG0194; -.
DR HOGENOM; HOG000232102; -.
DR HOVERGEN; HBG107814; -.
DR KO; K12076; -.
DR OrthoDB; EOG447FSN; -.
DR EvolutionaryTrace; Q62696; -.
DR NextBio; 605875; -.
DR ArrayExpress; Q62696; -.
DR Genevestigator; Q62696; -.
DR GermOnline; ENSRNOG00000038597; Rattus norvegicus.
DR GO; GO:0009925; C:basal plasma membrane; IDA:RGD.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0014069; C:postsynaptic density; TAS:UniProtKB.
DR GO; GO:0045211; C:postsynaptic membrane; TAS:RGD.
DR GO; GO:0042734; C:presynaptic membrane; IDA:RGD.
DR GO; GO:0030315; C:T-tubule; IDA:RGD.
DR GO; GO:0019902; F:phosphatase binding; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISS:UniProtKB.
DR GO; GO:0007015; P:actin filament organization; ISS:UniProtKB.
DR GO; GO:0016337; P:cell-cell adhesion; ISS:UniProtKB.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0001935; P:endothelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0043268; P:positive regulation of potassium ion transport; IMP:RGD.
DR GO; GO:0032880; P:regulation of protein localization; IMP:RGD.
DR InterPro; IPR008144; Guanylate_kin.
DR InterPro; IPR008145; Guanylate_kin/L-typ_Ca_channel.
DR InterPro; IPR020590; Guanylate_kinase_CS.
DR InterPro; IPR004172; L27.
DR InterPro; IPR015143; L27_1.
DR InterPro; IPR016313; M-assoc_guanylate_kinase.
DR InterPro; IPR019590; MAGUK_PEST_N.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR019583; PDZ_assoc.
DR InterPro; IPR011511; SH3_2.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF00625; Guanylate_kin; 1.
DR Pfam; PF09058; L27_1; 1.
DR Pfam; PF10608; MAGUK_N_PEST; 1.
DR Pfam; PF00595; PDZ; 3.
DR Pfam; PF10600; PDZ_assoc; 1.
DR Pfam; PF07653; SH3_2; 1.
DR PIRSF; PIRSF001741; MAGUK_DLGH; 1.
DR SMART; SM00072; GuKc; 1.
DR SMART; SM00569; L27; 1.
DR SMART; SM00228; PDZ; 3.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50156; PDZ; 3.
DR SUPFAM; SSF50044; SH3; 1.
DR PROSITE; PS00856; GUANYLATE_KINASE_1; 1.
DR PROSITE; PS50052; GUANYLATE_KINASE_2; 1.
DR PROSITE; PS51022; L27; 1.
DR PROSITE; PS50106; PDZ; 3.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell junction; Cell membrane; Complete proteome;
KW Endoplasmic reticulum; Membrane; Phosphoprotein;
KW Postsynaptic cell membrane; Reference proteome; Repeat; SH3 domain;
KW Synapse.
FT CHAIN 1 911 Disks large homolog 1.
FT /FTId=PRO_0000094550.
FT DOMAIN 4 64 L27.
FT DOMAIN 224 310 PDZ 1.
FT DOMAIN 318 404 PDZ 2.
FT DOMAIN 465 545 PDZ 3.
FT DOMAIN 580 650 SH3.
FT DOMAIN 721 896 Guanylate kinase-like.
FT REGION 162 212 Interaction with SH3 domains (By
FT similarity).
FT MOD_RES 39 39 Phosphoserine; by CaMK2.
FT MOD_RES 122 122 Phosphoserine (By similarity).
FT MOD_RES 158 158 Phosphoserine (By similarity).
FT MOD_RES 232 232 Phosphoserine; by CaMK2.
FT MOD_RES 301 301 Phosphoserine (By similarity).
FT MOD_RES 398 398 Phosphotyrosine (By similarity).
FT MOD_RES 567 567 Phosphoserine (By similarity).
FT MOD_RES 574 574 Phosphoserine (By similarity).
FT MOD_RES 618 618 Phosphoserine (By similarity).
FT MOD_RES 683 683 Phosphothreonine (By similarity).
FT MOD_RES 684 684 Phosphoserine (By similarity).
FT MOD_RES 687 687 Phosphoserine (By similarity).
FT MUTAGEN 39 39 S->A: No enrichment in postsynaptic
FT density upon CaMK2 activation.
FT MUTAGEN 39 39 S->D: Localizes at the postsynaptic
FT density.
FT MUTAGEN 232 232 S->A: No effect on association with
FT GRIN2B.
FT MUTAGEN 232 232 S->D: Partial loss of association with
FT GRIN2B.
FT HELIX 5 20
FT STRAND 23 26
FT HELIX 28 42
FT HELIX 44 52
FT STRAND 55 61
FT STRAND 225 227
FT STRAND 235 239
FT STRAND 242 246
FT STRAND 254 258
FT STRAND 260 262
FT HELIX 263 267
FT STRAND 277 279
FT HELIX 289 297
FT STRAND 301 306
FT STRAND 318 322
FT STRAND 327 334
FT STRAND 347 352
FT HELIX 357 361
FT STRAND 369 373
FT HELIX 383 391
FT STRAND 395 402
FT STRAND 405 407
FT STRAND 464 469
FT STRAND 476 481
FT STRAND 483 486
FT STRAND 488 493
FT HELIX 498 502
FT HELIX 524 532
FT STRAND 536 542
FT STRAND 583 587
FT TURN 593 595
FT STRAND 611 616
FT STRAND 619 628
FT STRAND 638 641
FT HELIX 643 651
FT STRAND 709 717
FT STRAND 724 728
FT HELIX 731 741
FT TURN 743 745
FT TURN 763 765
FT HELIX 773 781
FT STRAND 785 791
FT STRAND 794 799
FT HELIX 800 807
FT TURN 808 810
FT STRAND 812 815
FT HELIX 820 827
FT STRAND 833 837
FT HELIX 842 848
FT HELIX 854 871
FT HELIX 872 874
FT STRAND 876 879
FT HELIX 884 898
FT STRAND 900 906
SQ SEQUENCE 911 AA; 100571 MW; 18CEBD31DD0CAF8B CRC64;
MPVRKQDTQR ALHLLEEYRS KLSQTEDRQL RSSIERVISI FQSNLFQALI DIQEFYEVTL
LDNPKCVDHS KQCEPVQPGN PWESGSLSSA AVTSESLPGG LSPPVEKYRY QDEEVLPSER
ISPQVPNEVL GPELVHVSEK SLSEIENVHG FVSHSHISPI KPTEAVPPSS PIVPVTPALP
VPAESPVVLP STPQANPPPV LVNTDSLETP TYVNGTDADY EYEEITLERG NSGLGFSIAG
GTDNPHIGDD SSIFITKIIT GGAAAQDGRL RVNDCILRVN EADVRDVTHS KAVEALKEAG
SIVRLYVKRR KAFRKNHEIK LIKGPKGLGF SIAGGVGNQH IPGDNSIYVT KIIEGGAAHK
DGKLQIGDKL LAVNSVCLEE VTHEEAVTAL KNTSDFVYLK AAKPTSMYIN DGYAPPDITN
SSSQSVDNHV SPSSYLGQTP ASPARYSPIS KAVLGDDEIT REPRKVVLHR GSTGLGFNIV
GGEDGEGIFI SFILAGGPAD LSGELRKGDR IISVNSVDLR AASHEQAAAA LKNAGQAVTI
VAQYRPEEYS RFEAKIHDLR ETMMNSSVSS GSGSLRTSQK RSLYVRALFD YDKTKDSGLP
SQGLNFKFGD ILHVINASDD EWWQARQVTP DGESDEVGVI PSKRRVEKKE RARLKTVKFN
SKTRGDKGEI PDDMGSKGLK HVTSNASDSE SSYHEYGCSK GGQEEYVLSY EPVNQQEVNY
TRPVIILGPM KDRVNDDLIS EFPDKFGSCV PHTTRPKRDY EVDGRDYHFV TSREQMEKDI
QEHKFIEAGQ YNNHLYGTSV QSVRAVAEKG KHCILDVSGN AIKRLQIAQL YPISIFIKPK
SMENIMEMNK RLTDEQARKT FERAVRLEQE FTEHFTAIVQ GDTLEDIYNQ VKQIIEEQSG
PYIWVPAKEK L
//
