Q62696 (DLG1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Disks large homolog 1

Alternative name(s):
Synapse-associated protein 97
Short name=SAP-97
Short name=SAP97

Gene names

Name:	Dlg1
Synonyms:	Dlgh1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	911 AA.
Sequence status	Complete.
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. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels. Functional regulator of Kv1.5 channel By similarity. May play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Ref.9 Ref.10 Ref.11 Ref.16
Subunit structure	Homotetramer Probable. Interacts with KCNF1 By similarity. Interacts with CAMK2. Interacts through its PDZ domains with GRIN2A, KCNA1, KCNA2, KCNA3, KCNA4, KCNA5, KCND2, KCND3, 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 and LRFN2. Interacts with LRFN4 and SFPQ By similarity. Interacts with PTEN. Interacts with FRMPD4 (via C-terminus). Ref.2 Ref.3 Ref.4 Ref.6 Ref.8 Ref.9 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16
Subcellular location	Membrane; Peripheral membrane protein By similarity. Basolateral cell membrane By similarity. Endoplasmic reticulum membrane By similarity. Cell junction › synapse › postsynaptic cell membrane › postsynaptic density By similarity. Cell junction › synapse. Cell membrane › sarcolemma. 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. Ref.1 Ref.5 Ref.6 Ref.10 Ref.16
Tissue specificity	Widely expressed. Strongly expressed in epithelial cells, in the small intestine it is only detected in the vili. Expressed in brain, heart (at protein level), muscle, lung and liver. In the brain it was detected in olfactory bulbs, cerebral cortex, hippocampus, and spinal cord (at protein level). Ref.1 Ref.16
Induction	By BDNF. Ref.7
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	Phosphorylated by MAPK12 By similarity. Phosphorylation of Ser-39 modulates transport to the plasma membrane and phosphorylation of Ser-232 regulates association with GRIN2A. Ref.8 Ref.10
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 Complete proteome Reference proteome
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 positive regulation of potassium ion transport Inferred from mutant phenotype Ref.16. Source: RGD regulation of protein localization Inferred from mutant phenotype PubMed 17635915. Source: RGD
Cellular_component	T-tubule Inferred from direct assay PubMed 11181181. Source: RGD basal plasma membrane Inferred from direct assay Ref.1. Source: RGD cell junction Inferred from electronic annotation. Source: UniProtKB-KW endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell postsynaptic density Traceable author statement PubMed 1127911. Source: UniProtKB postsynaptic membrane Traceable author statement Ref.8. Source: RGD presynaptic membrane Inferred from direct assay Ref.1. Source: RGD
Molecular_function	phosphatase binding Inferred from sequence or structural similarity. Source: UniProtKB protein kinase binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Lrfn2	Q460M5	2	EBI-389325,EBI-877185
Map1a	P34926	2	EBI-389325,EBI-631571
PTEN	P60484	2	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 Ref.10

Modified residue

122

1

Phosphoserine By similarity

Modified residue

158

1

Phosphoserine By similarity

Modified residue

232

1

Phosphoserine; by CaMK2 Ref.8

Modified residue

301

1

Phosphoserine By similarity

Modified residue

398

1

Phosphotyrosine By similarity

Modified residue

567

1

Phosphoserine 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

Experimental info

Mutagenesis

39

1

S → A: No enrichment in postsynaptic density upon CaMK2 activation. Ref.10

Mutagenesis

39

1

S → D: Localizes at the postsynaptic density. Ref.10

Mutagenesis

232

1

S → A: No effect on association with GRIN2B. Ref.8

Mutagenesis

232

1

S → D: Partial loss of association with GRIN2B. Ref.8

Secondary structure

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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

Beta strand

583 – 587

5

Turn

593 – 595

3

Beta strand

611 – 616

6

Beta strand

619 – 628

10

Beta strand

638 – 641

4

Helix

643 – 651

9

Beta strand

709 – 717

9

Beta strand

724 – 728

5

Helix

731 – 741

11

Turn

743 – 745

3

Turn

763 – 765

3

Helix

773 – 781

9

Beta strand

785 – 791

7

Beta strand

794 – 799

6

Helix

800 – 807

8

Turn

808 – 810

3

Beta strand

812 – 815

4

Helix

820 – 827

8

Beta strand

833 – 837

5

Helix

842 – 848

7

Helix

854 – 871

18

Helix

872 – 874

3

Beta strand

876 – 879

4

Helix

884 – 898

15

Beta strand

900 – 906

7

Sequences

	Sequence		Length	Mass (Da)
	Q62696 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Binding of PTEN to specific PDZ domains contributes to PTEN protein stability and phosphorylation by microtubule-associated serine/threonine kinases." Valiente M., Andres-Pons A., Gomar B., Torres J., Gil A., Tapparel C., Antonarakis S.E., Pulido R. J. Biol. Chem. 280:28936-28943(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PTEN.
[13]	"A novel family of adhesion-like molecules that interacts with the NMDA receptor." Wang C.Y., Chang K., Petralia R.S., Wang Y.X., Seabold G.K., Wenthold R.J. J. Neurosci. 26:2174-2183(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LRFN2.
[14]	"SALM synaptic cell adhesion-like molecules regulate the differentiation of excitatory synapses." Ko J., Kim S., Chung H.S., Kim K., Han K., Kim H., Jun H., Kaang B.-K., Kim E. Neuron 50:233-245(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LRFN1.
[15]	"Preso, a novel PSD-95-interacting FERM and PDZ domain protein that regulates dendritic spine morphogenesis." Lee H.W., Choi J., Shin H., Kim K., Yang J., Na M., Choi S.Y., Kang G.B., Eom S.H., Kim H., Kim E. J. Neurosci. 28:14546-14556(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FRMPD4.
[16]	"Kv4 potassium channels form a tripartite complex with the anchoring protein SAP97 and CaMKII in cardiac myocytes." El-Haou S., Balse E., Neyroud N., Dilanian G., Gavillet B., Abriel H., Coulombe A., Jeromin A., Hatem S.N. Circ. Res. 104:758-769(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH KCND2; KCND3 AND CAMK2.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U14950 mRNA. Translation: AAA79976.1.

IPI

IPI00207201.

PIR

I56552.

RefSeq

NP_036920.1. NM_012788.1.

UniGene

Rn.89331.

3D structure databases

PDBe
RCSB PDB
PDBj

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	318-409	[»]
2AWW	X-ray	2.21	A/B	318-409	[»]
2AWX	X-ray	1.80	A/B	318-409	[»]
2G2L	X-ray	2.35	A/B	318-409	[»]
2I0I	X-ray	2.80	A/B/C	459-543	[»]
2I0L	X-ray	2.31	A/B	318-401	[»]
3UAT	X-ray	2.70	A	578-911	[»]

ProteinModelPortal

Q62696.

SMR

Q62696. Positions 4-63, 221-313, 318-400, 462-542, 583-911.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q62696. 15 interactions.

MINT

MINT-93379.

STRING

10116.ENSRNOP00000055673.

PTM databases

PhosphoSite

Q62696.

Proteomic databases

PaxDb

Q62696.

PRIDE

Q62696.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

25252.

KEGG

rno:25252.

UCSC

RGD:2505. rat.

Organism-specific databases

CTD

1739.

RGD

2505. Dlg1.

Phylogenomic databases

eggNOG

COG0194.

HOGENOM

HOG000232102.

HOVERGEN

HBG107814.

KO

K12076.

OrthoDB

EOG447FSN.

Gene expression databases

ArrayExpress

Q62696.

Genevestigator

Q62696.

GermOnline

ENSRNOG00000038597. Rattus norvegicus.

Family and domain databases

InterPro

IPR008144. Guanylate_kin.
IPR008145. Guanylate_kin/L-typ_Ca_channel.
IPR020590. Guanylate_kinase_CS.
IPR004172. L27.
IPR015143. L27_1.
IPR016313. M-assoc_guanylate_kinase.
IPR019590. MAGUK_PEST_N.
IPR001478. PDZ.
IPR019583. PDZ_assoc.
IPR011511. SH3_2.
IPR001452. SH3_domain.
[Graphical view]

Pfam

PF00625. Guanylate_kin. 1 hit.
PF09058. L27_1. 1 hit.
PF10608. MAGUK_N_PEST. 1 hit.
PF00595. PDZ. 3 hits.
PF10600. PDZ_assoc. 1 hit.
PF07653. SH3_2. 1 hit.
[Graphical view]

PIRSF

PIRSF001741. MAGUK_DLGH. 1 hit.

SMART

SM00072. GuKc. 1 hit.
SM00569. L27. 1 hit.
SM00228. PDZ. 3 hits.
SM00326. SH3. 1 hit.
[Graphical view]

SUPFAM

SSF50156. PDZ. 3 hits.
SSF50044. SH3. 1 hit.

PROSITE

PS00856. GUANYLATE_KINASE_1. 1 hit.
PS50052. GUANYLATE_KINASE_2. 1 hit.
PS51022. L27. 1 hit.
PS50106. PDZ. 3 hits.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q62696.

NextBio

605875.

Entry information

Entry name

DLG1_RAT

Accession

Primary (citable) accession number: Q62696

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	April 3, 2013
This is version 131 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program