Reviewed, UniProtKB/Swiss-Prot Q62696 (DLG1_RAT)

Names and origin

Protein names

Recommended name:
    Disks large homolog 1
Alternative name(s):
    Synapse-associated protein 97
      Short name=SAP-97

Gene names

Name:	Dlg1
Synonyms:	Dlgh1

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	911 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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.
Subunit structure	Homotetramer Probable. Interacts through its PDZ domains with GRIN2A, KCNA1, KCNA2, KCNA3, KCNA4, KCNA5, GRIA1, GPR124 and GPR125. Interacts with cytoskeleton-associated proteins EPB41 and EZR. Found in a complex with KCNA5 and CAV3. Found in a complex with APC and CTNNB1. Interacts with CDH1 through binding to PIK3R1. Forms multiprotein complexes with CASK, LIN7A, LIN7B, LIN7C, APBA1, and KCNJ12. Interacts through its guanylate kinase-like domain with KIF13B. Interacts with TOPK. Forms a tripartite complex composed of DLG1, MPP7 and LIN7 (LIN7A or LIN7C). May interact with HTR2A and TJAP1 By similarity. Interacts through its guanylate kinase-like domain with DLGAP1, DLGAP2, DLGAP3, DLGAP4 and MAP1A. Interacts with LRFN1.
Subcellular location	Membrane; Peripheral membrane proteinBy similarity. Basolateral cell membraneBy similarity. Endoplasmic reticulum membraneBy similarity. Cell junction › synapse › postsynaptic cell membrane › postsynaptic densityBy similarity. Cell junction › synapse. Note= 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 By similarity.
Tissue specificity	Widely expressed. Strongly expressed in epithelial cells, in the small intestine it is only detected in the vili. In the brain it was detected in olfactory bulbs, cerebral cortex, hippocampus, and spinal cord (at protein level). Expressed in brain, heart, muscle, lung and liver.
Induction	By BDNF.
Domain	The PDZ domains may also mediate association to membranes by binding to EPB41 and GPR124 together with the L27 domain that binds CASK and DLG2 By similarity. The L27 domain may regulate DLG1 self-association. The N-terminal alternatively spliced region is capable of binding several SH3 domains and also moderates the level of protein oligomerization By similarity.
Post-translational modification	Phosphorylation of Ser-39 modulates transport to the plasma membrane and phosphorylation of Ser-232 regulates association with GRIN2A.
Sequence similarities	Belongs to the MAGUK family. Contains 1 guanylate kinase-like domain. Contains 1 L27 domain. Contains 3 PDZ (DHR) domains. Contains 1 SH3 domain.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Endoplasmic reticulum Membrane Postsynaptic cell membrane Synapse
Domain	Repeat SH3 domain
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	actin filament organization Inferred from sequence or structural similarity. Source: UniProtKB cell-cell adhesion Inferred from sequence or structural similarity. Source: UniProtKB cortical actin cytoskeleton organization Inferred from sequence or structural similarity. Source: UniProtKB endothelial cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of mitotic cell cycle Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	basolateral plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB cell junction Inferred from electronic annotation. Source: UniProtKB-KW endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell postsynaptic density Traceable author statement. Source: UniProtKB postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	phosphatase binding Inferred from sequence or structural similarity. Source: UniProtKB protein C-terminus binding Inferred from physical interaction. Source: UniProtKB protein kinase binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ADRB1	P08588	1	EBI-389325,EBI-991009	From a different organism.
ATP2B2	Q01814-1	1	EBI-389325,EBI-1174262	From a different organism.
ATP2B4	P23634-6	1	EBI-389325,EBI-1174437	From a different organism.
Lrfn2	Q460M5	1	EBI-389325,EBI-877185
Map1a	P34926	2	EBI-389325,EBI-631571
PTEN	P60484	1	EBI-389325,EBI-696162	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 911

911

Disks large homolog 1

PRO_0000094550

Regions

Domain

4 – 64

61

L27

Domain

224 – 310

87

PDZ 1

Domain

318 – 404

87

PDZ 2

Domain

465 – 545

81

PDZ 3

Domain

580 – 650

71

SH3

Domain

721 – 896

176

Guanylate kinase-like

Region

162 – 212

51

Interaction with SH3 domains By similarity

Amino acid modifications

Modified residue

39

1

Phosphoserine; by CaMK2

Modified residue

122

1

Phosphoserine By similarity

Modified residue

232

1

Phosphoserine; by CaMK2

Modified residue

301

1

Phosphoserine By similarity

Modified residue

398

1

Phosphotyrosine By similarity

Modified residue

574

1

Phosphoserine By similarity

Modified residue

618

1

Phosphoserine By similarity

Modified residue

683

1

Phosphothreonine By similarity

Modified residue

684

1

Phosphoserine By similarity

Modified residue

687

1

Phosphoserine By similarity

Modified residue

767

1

Phosphotyrosine By similarity

Experimental info

Mutagenesis

39

1

S → A: No enrichment in postsynaptic density upon CaMK2 activation

Mutagenesis

39

1

S → D: Localizes at the postsynaptic density

Mutagenesis

232

1

S → A: No effect on association with GRIN2B

Mutagenesis

232

1

S → D: Partial loss of association with GRIN2B

Secondary structure

1

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911

Helix Strand Turn

Details...

Helix

5 – 20

16

Beta strand

23 – 26

4

Helix

28 – 42

15

Helix

44 – 52

9

Beta strand

55 – 61

7

Beta strand

225 – 227

3

Beta strand

235 – 239

5

Beta strand

242 – 246

5

Beta strand

254 – 258

5

Beta strand

260 – 262

3

Helix

263 – 267

5

Beta strand

277 – 279

3

Helix

289 – 297

9

Beta strand

301 – 306

6

Beta strand

318 – 322

5

Beta strand

327 – 334

8

Beta strand

347 – 352

6

Helix

357 – 361

5

Beta strand

369 – 373

5

Helix

383 – 391

9

Beta strand

395 – 402

8

Beta strand

405 – 407

3

Beta strand

464 – 469

6

Beta strand

476 – 481

6

Beta strand

483 – 486

4

Beta strand

488 – 493

6

Helix

498 – 502

5

Helix

524 – 532

9

Beta strand

536 – 542

7

Sequences

	Sequence		Length	Mass (Da)
	Q62696-1 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: 18CEBD31DD0CAF8B	FASTA	911	100,571
	10 20 30 40 50 60 MPVRKQDTQR ALHLLEEYRS KLSQTEDRQL RSSIERVISI FQSNLFQALI DIQEFYEVTL 70 80 90 100 110 120 LDNPKCVDHS KQCEPVQPGN PWESGSLSSA AVTSESLPGG LSPPVEKYRY QDEEVLPSER 130 140 150 160 170 180 ISPQVPNEVL GPELVHVSEK SLSEIENVHG FVSHSHISPI KPTEAVPPSS PIVPVTPALP 190 200 210 220 230 240 VPAESPVVLP STPQANPPPV LVNTDSLETP TYVNGTDADY EYEEITLERG NSGLGFSIAG 250 260 270 280 290 300 GTDNPHIGDD SSIFITKIIT GGAAAQDGRL RVNDCILRVN EADVRDVTHS KAVEALKEAG 310 320 330 340 350 360 SIVRLYVKRR KAFRKNHEIK LIKGPKGLGF SIAGGVGNQH IPGDNSIYVT KIIEGGAAHK 370 380 390 400 410 420 DGKLQIGDKL LAVNSVCLEE VTHEEAVTAL KNTSDFVYLK AAKPTSMYIN DGYAPPDITN 430 440 450 460 470 480 SSSQSVDNHV SPSSYLGQTP ASPARYSPIS KAVLGDDEIT REPRKVVLHR GSTGLGFNIV 490 500 510 520 530 540 GGEDGEGIFI SFILAGGPAD LSGELRKGDR IISVNSVDLR AASHEQAAAA LKNAGQAVTI 550 560 570 580 590 600 VAQYRPEEYS RFEAKIHDLR ETMMNSSVSS GSGSLRTSQK RSLYVRALFD YDKTKDSGLP 610 620 630 640 650 660 SQGLNFKFGD ILHVINASDD EWWQARQVTP DGESDEVGVI PSKRRVEKKE RARLKTVKFN 670 680 690 700 710 720 SKTRGDKGEI PDDMGSKGLK HVTSNASDSE SSYHEYGCSK GGQEEYVLSY EPVNQQEVNY 730 740 750 760 770 780 TRPVIILGPM KDRVNDDLIS EFPDKFGSCV PHTTRPKRDY EVDGRDYHFV TSREQMEKDI 790 800 810 820 830 840 QEHKFIEAGQ YNNHLYGTSV QSVRAVAEKG KHCILDVSGN AIKRLQIAQL YPISIFIKPK 850 860 870 880 890 900 SMENIMEMNK RLTDEQARKT FERAVRLEQE FTEHFTAIVQ GDTLEDIYNQ VKQIIEEQSG 910 PYIWVPAKEK L

References

[1]	"Molecular characterization and spatial distribution of SAP97, a novel presynaptic protein homologous to SAP90 and the Drosophila discs-large tumor suppressor protein." Mueller B.M., Kistner U., Veh R.W., Cases-Langhoff C., Becker B., Gundelfinger E.D., Garner C.C. J. Neurosci. 15:2354-2366(1995) [PubMed: 7891172] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION. Tissue: Brain.
[2]	"SAPAPs. A family of PSD-95/SAP90-associated proteins localized at postsynaptic density." Takeuchi M., Hata Y., Hirao K., Toyoda A., Irie M., Takai Y. J. Biol. Chem. 272:11943-11951(1997) [PubMed: 9115257] [Abstract] Cited for: INTERACTION WITH DLGAP1; DLGAP2; DLGAP3 AND DLGAP4.
[3]	"SAP97 is associated with the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit." Leonard A.S., Davare M.A., Horne M.C., Garner C.C., Hell J.W. J. Biol. Chem. 273:19518-19524(1998) [PubMed: 9677374] [Abstract] Cited for: INTERACTION WITH GRIA1.
[4]	"Localization of postsynaptic density-93 to dendritic microtubules and interaction with microtubule-associated protein 1A." Brenman J.E., Topinka J.R., Cooper E.C., McGee A.W., Rosen J., Milroy T., Ralston H.J., Bredt D.S. J. Neurosci. 18:8805-8813(1998) [PubMed: 9786987] [Abstract] Cited for: INTERACTION WITH MAP1A.
[5]	"PSD-95 and SAP97 exhibit distinct mechanisms for regulating K(+) channel surface expression and clustering." Tiffany A.M., Manganas L.N., Kim E., Hsueh Y.P., Sheng M., Trimmer J.S. J. Cell Biol. 148:147-158(2000) [PubMed: 10629225] [Abstract] Cited for: SUBCELLULAR LOCATION.
[6]	"A novel and conserved protein-protein interaction domain of mammalian Lin-2/CASK binds and recruits SAP97 to the lateral surface of epithelia." Lee S., Fan S., Makarova O., Straight S., Margolis B. Mol. Cell. Biol. 22:1778-1791(2002) [PubMed: 11865057] [Abstract] Cited for: INTERACTION WITH CASK, SUBCELLULAR LOCATION.
[7]	"Brain-derived neurotrophic factor signal enhances and maintains the expression of AMPA receptor-associated PDZ proteins in developing cortical neurons." Jourdi H., Iwakura Y., Narisawa-Saito M., Ibaraki K., Xiong H., Watanabe M., Hayashi Y., Takei N., Nawa H. Dev. Biol. 263:216-230(2003) [PubMed: 14597197] [Abstract] Cited for: INDUCTION BY BDNF.
[8]	"CaMKII-dependent phosphorylation regulates SAP97/NR2A interaction." Gardoni F., Mauceri D., Fiorentini C., Bellone C., Missale C., Cattabeni F., Di Luca M. J. Biol. Chem. 278:44745-44752(2003) [PubMed: 12933808] [Abstract] Cited for: MUTAGENESIS OF SER-232, PHOSPHORYLATION AT SER-232, INTERACTION WITH GRIN2A.
[9]	"A multiprotein trafficking complex composed of SAP97, CASK, Veli, and Mint1 is associated with inward rectifier Kir2 potassium channels." Leonoudakis D., Conti L.R., Radeke C.M., McGuire L.M., Vandenberg C.A. J. Biol. Chem. 279:19051-19063(2004) [PubMed: 14960569] [Abstract] Cited for: INTERACTION WITH CASK; LIN7A; LIN7B; LIN7C; APBA1 AND KCNJ12, FUNCTION.
[10]	"Calcium/calmodulin-dependent protein kinase II phosphorylation drives synapse-associated protein 97 into spines." Mauceri D., Cattabeni F., Di Luca M., Gardoni F. J. Biol. Chem. 279:23813-23821(2004) [PubMed: 15044483] [Abstract] Cited for: MUTAGENESIS OF SER-39, PHOSPHORYLATION AT SER-39, SUBCELLULAR LOCATION, FUNCTION.
[11]	"Quaternary structure, protein dynamics, and synaptic function of SAP97 controlled by L27 domain interactions." Nakagawa T., Futai K., Lashuel H.A., Lo I., Okamoto K., Walz T., Hayashi Y., Sheng M. Neuron 44:453-467(2004) [PubMed: 15504326] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

U14950 mRNA. Translation: AAA79976.1.

PIR

I56552.

RefSeq

NP_036920.1.

UniGene

Rn.89331

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1RSO	NMR	-	A/C	4-63	[»]
1ZOK	NMR	-	A	221-313	[»]
2AWU	X-ray	2.44	A/B	318-410	[»]
2AWW	X-ray	2.21	A/B	318-410	[»]
2AWX	X-ray	1.80	A/B	318-410	[»]
2G2L	X-ray	2.35	A/B	318-410	[»]
2I0I	X-ray	2.80	A/B/C	459-543	[»]
2I0L	X-ray	2.31	A/B	318-401	[»]

SMR

Q62696. Positions 454-554.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q62696.

PTM databases