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O88382 (MAGI2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2
Alternative name(s):
Atrophin-1-interacting protein 1
Short name=AIP-1
Membrane-associated guanylate kinase inverted 2
Short name=MAGI-2
Synaptic-scaffolding molecule
Short name=S-SCAM
Gene names
Name:Magi2
Synonyms:Acvrinp1, Aip1, Sscam
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1277 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Seems to act as scaffold molecule at synaptic junctions by assembling neurotransmitter receptors and cell adhesion proteins. May play a role in regulating activin-mediated signaling in neuronal cells. Enhances the ability of PTEN to suppress AKT1 activation By similarity. Plays a role in nerve growth factor (NGF)-induced recruitment of RAPGEF2 to late endosomes and neurite outgrowth. Ref.1 Ref.11

Subunit structure

Interacts (via its WW domains) with DRPLA By similarity. Interacts with CTNNB1, ACVR2A, SMAD2 and SMAD3 By similarity. Part of a complex consisting of AIP1, ACVR2A, ACVR1B and SMAD3 By similarity. May interact with HTR2A and IGSF9 By similarity. Interacts with HTR4 By similarity. Interacts (via guanylate kinase domain) with DLGAP1. Interacts (via PDZ domains) with GRIN2A, GRID2 and NLGN1. Interacts with CTNND2 and MAGUIN-1. Interacts (via its second PDZ domain) with PTEN (via unphosphorylated C-terminus); this interaction diminishes the degradation rate of PTEN. Found in a complex, at least composed of KIDINS220, MAGI2, NTRK1 and RAPGEF2; the complex is mainly formed at late endosomes in a NGF-dependent manner. Interacts with RAPGEF2; the interaction occurs before or after nerve growth factor (NGF) stimulation. Isoform 1 interacts (via PDZ domain) with KIDINS220 isoform 2 (via C-terminal domain). Interacts with DDN. Identified in a complex with ACTN4, CASK, IQGAP1, NPHS1, SPTAN1 and SPTBN1. Ref.1 Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11

Subcellular location

Cytoplasm. Late endosome. Cell junctionsynapsesynaptosome. Cell membrane; Peripheral membrane protein. Note: Membrane-associated in synaptosomes. Localized diffusely in the cytoplasm before nerve growth factor (NGF) stimulation. Recruted to late endosomes after NGF stimulation. Ref.1 Ref.11

Tissue specificity

Expressed in the foot process layer of podocytes of the kidney glomeruli but not in tubules (at protein level). Expressed in the brain. Ref.1 Ref.8

Developmental stage

Expressed during the late capillary loop stage of glomerulogenesis. First detected in junctional complexes in podocytes after their migration to the base of cells. Up-regulated upon foot process differentiation. Ref.8

Sequence similarities

Belongs to the MAGUK family.

Contains 1 guanylate kinase-like domain.

Contains 5 PDZ (DHR) domains.

Contains 2 WW domains.

Ontologies

Keywords
   Biological processNeurogenesis
   Cellular componentCell junction
Cell membrane
Cytoplasm
Endosome
Membrane
Synapse
Synaptosome
   Coding sequence diversityAlternative splicing
   DomainRepeat
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processSMAD protein signal transduction

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to nerve growth factor stimulus

Inferred from direct assay Ref.11. Source: UniProtKB

cytoplasmic transport

Inferred from mutant phenotype Ref.11. Source: UniProtKB

glomerular filtration

Inferred by curator Ref.8. Source: UniProtKB

glomerular visceral epithelial cell development

Inferred from expression pattern Ref.8. Source: UniProtKB

mitotic cell cycle arrest

Inferred from direct assay PubMed 17880912. Source: UniProtKB

negative regulation of activin receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell migration

Inferred from direct assay PubMed 17880912. Source: UniProtKB

negative regulation of cell proliferation

Inferred from direct assay PubMed 17880912. Source: UniProtKB

negative regulation of protein kinase B signaling

Inferred from sequence or structural similarity. Source: UniProtKB

nerve growth factor signaling pathway

Inferred from direct assay Ref.11. Source: UniProtKB

positive regulation of neuron projection development

Inferred from mutant phenotype Ref.11. Source: UniProtKB

positive regulation of phosphoprotein phosphatase activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of receptor internalization

Inferred from sequence or structural similarity. Source: UniProtKB

protein heterooligomerization

Inferred from direct assay Ref.2. Source: RGD

receptor clustering

Inferred from direct assay Ref.2. Source: RGD

   Cellular_componentcytoplasm

Inferred from direct assay Ref.11. Source: UniProtKB

dendrite

Inferred from direct assay Ref.4. Source: UniProtKB

late endosome

Inferred from direct assay Ref.11. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from direct assay Ref.6. Source: UniProtKB

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

postsynaptic density

Inferred from direct assay Ref.6. Source: UniProtKB

protein complex

Inferred from direct assay Ref.11. Source: UniProtKB

slit diaphragm

Inferred from direct assay Ref.8. Source: UniProtKB

synapse

Inferred from direct assay Ref.4PubMed 10681527. Source: UniProtKB

tight junction

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionPDZ domain binding

Inferred from physical interaction Ref.2. Source: RGD

SMAD binding

Inferred from sequence or structural similarity. Source: UniProtKB

beta-1 adrenergic receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatase binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.4Ref.6Ref.8Ref.11PubMed 20534871. Source: UniProtKB

protein complex binding

Inferred from physical interaction PubMed 15331416. Source: RGD

receptor signaling complex scaffold activity

Inferred from sequence or structural similarity. Source: UniProtKB

signal transducer activity

Inferred from sequence or structural similarity. Source: UniProtKB

type II activin receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

DDNO948503EBI-696179,EBI-5240523From a different organism.
Dlgap1P978363EBI-696179,EBI-80901
GraspQ8R4T55EBI-696179,EBI-7361884
PTENP604843EBI-696179,EBI-696162From a different organism.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O88382-1)

Also known as: alpha;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O88382-2)

Also known as: beta;

The sequence of this isoform differs from the canonical sequence as follows:
     1-163: Missing.
Isoform 3 (identifier: O88382-3)

Also known as: gamma;

The sequence of this isoform differs from the canonical sequence as follows:
     1-223: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12771277Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2
PRO_0000094588

Regions

Domain17 – 10185PDZ
Domain109 – 283175Guanylate kinase-like
Domain302 – 33534WW 1
Domain348 – 38134WW 2
Domain426 – 51085PDZ 1
Domain605 – 68379PDZ 2
Domain778 – 86083PDZ 3
Domain920 – 101091PDZ 4
Domain1141 – 122383PDZ 5
Region302 – 38180Interaction with DDN By similarity

Amino acid modifications

Modified residue3621Phosphotyrosine By similarity
Modified residue8271Phosphotyrosine By similarity

Natural variations

Alternative sequence1 – 223223Missing in isoform 3.
VSP_008439
Alternative sequence1 – 163163Missing in isoform 2.
VSP_008438

Experimental info

Sequence conflict6451L → F in AAD31015. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (alpha) [UniParc].

Last modified November 1, 1998. Version 1.
Checksum: E1A435FF35549DF9

FASTA1,277141,072
        10         20         30         40         50         60 
MSKSLKKKSH WTSKVHESVI GRNPEGQLGF ELKGGAENGQ FPYLGEVKPG KVAYESGSKL 

        70         80         90        100        110        120 
VSEELLLEVN ETPVAGLTIR DVLAVIKHCK DPLRLKCVKQ GGIVDKDLRH YLNLRFQKGS 

       130        140        150        160        170        180 
VDHELQQIIR DNLYLRTVPC TTRPHKEGEV PGVDYIFITV EDFMELEKSG ALLESGTYED 

       190        200        210        220        230        240 
NYYGTPKPPA EPAPLLLNVT DQILPGATPS AEGKRKRNKS VTNMEKASIE PPEEEEEERP 

       250        260        270        280        290        300 
VVNGNGVVIT PESSEHEDKS AGASGETPSQ PYPAPVYSQP EELKDQMDDT KSTKPEENED 

       310        320        330        340        350        360 
SDPLPDNWEM AYTEKGEVYF IDHNTKTTSW LDPRLAKKAK PAEECKENEL PYGWEKIDDP 

       370        380        390        400        410        420 
IYGTYYVDHI NRRTQFENPV LEAKRKLQQH NMPHTELGTK PLQAPGFREK PLFTRDASQL 

       430        440        450        460        470        480 
KGTFLSTTLK KSNMGFGFTI IGGDEPDEFL QVKSVIPDGP AAQDGKMETG DVIVYINEVC 

       490        500        510        520        530        540 
VLGHTHADVV KLFQSVPIGQ SVNLVLCRGY PLPFDPEDPA NSMVPPLAIM ERPPPVMVNG 

       550        560        570        580        590        600 
RHNYETYLEY ISRTSQSVPD ITDRPPHSLH SMPADGQLDG TYPPPVHDDN VSVASSGATQ 

       610        620        630        640        650        660 
AELMTLTIVK GAKGFGFTIA DSPTGQRVKQ ILDIQGCPGL CEGDLIVEIN QQNVQNLSHT 

       670        680        690        700        710        720 
EVVDILKDCP VGSETSLIIH RGGFFSPWKT PKPMVDRWEN QGSPQTSLSA PAVPQSLPFP 

       730        740        750        760        770        780 
PALHRSSFPD STEAFDPRKP DPYELYEKSR AIYESRQQVP PRTSFRMDSS GPDYKELDVH 

       790        800        810        820        830        840 
LRRMESGFGF RILGGDEPGQ PILIGAVIAM GSADRDGRLH PGDELVYVDG IPVAGKTHRY 

       850        860        870        880        890        900 
VIDLMHHAAR NGQVNLTVRR KVLCGGEPCP ENGRSPGSVS THHSSPRSDY ATYANSNHAA 

       910        920        930        940        950        960 
PSNNASPPEG FASHSLQTSD VIIHRKENEG FGFVIISSLN RPESGATITV PHKIGRIIDG 

       970        980        990       1000       1010       1020 
SPADRCAKLK VGDRILAVNG QSIINMPHAD IVKLIKDAGL SVTLRIIPQE ELNNPTSAPS 

      1030       1040       1050       1060       1070       1080 
SEKQSPMAQQ HSPLAQQHSP LAQPSPATPN SPVAQPAPPQ PLQLQGHENS YRSEVKARQD 

      1090       1100       1110       1120       1130       1140 
VKPDIRQPPF TDYRQPPLDY RQPPGGDYSQ PSPLDYRQHS PDTRQYPLSD YRQPQDFDYF 

      1150       1160       1170       1180       1190       1200 
TVDMEKGAKG FGFSIRGGRE YKMDLYVLRL AEDGPAIRNG RMRVGDQIIE INGESTRDMT 

      1210       1220       1230       1240       1250       1260 
HARAIELIKS GGRRVRLLLK RGTGQVPEYG MVPSSLSMCM KSDKHGSPYF YLLGHPKDTT 

      1270 
NPTPGALPLP PPQACRK 

« Hide

Isoform 2 (beta) [UniParc].

Checksum: 7B1BA3E0049DBD30
Show »

FASTA1,114122,766
Isoform 3 (gamma) [UniParc].

Checksum: 718C43F950E5365E
Show »

FASTA1,054116,325

References

[1]"A novel multiple PDZ domain-containing molecule interacting with N-methyl-d-aspartate receptors and neuronal cell adhesion proteins."
Hirao K., Hata Y., Ide N., Takeuchi M., Irie M., Yao I., Deguchi M., Toyoda A., Suedhof T.C., Takai Y.
J. Biol. Chem. 273:21105-21110(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH DLGAP1; NLGN1 AND GRIN2A.
[2]"Three isoforms of synaptic scaffolding molecule and their characterization: multimerization between the isoforms and their interaction with N-methyl-D-aspartate receptors and SAP90/PSD-95-associated protein."
Hirao K., Hata Y., Yao I., Deguchi M., Kawabe H., Mizoguchi A., Takai Y.
J. Biol. Chem. 275:2966-2972(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING (ISOFORM 3).
[3]"Interaction of S-SCAM with neural plakophilin-related Armadillo-repeat protein/delta-catenin."
Ide N., Hata Y., Deguchi M., Hirao K., Yao I., Takai Y.
Biochem. Biophys. Res. Commun. 256:456-461(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CTNND2.
[4]"nRap GEP: a novel neural GDP/GTP exchange protein for rap1 small G protein that interacts with synaptic scaffolding molecule (S-SCAM)."
Ohtsuka T., Hata Y., Ide N., Yasuda T., Inoue E., Inoue T., Mizoguchi A., Takai Y.
Biochem. Biophys. Res. Commun. 265:38-44(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAPGEF2.
[5]"MAGUIN, a novel neuronal membrane-associated guanylate kinase-interacting protein."
Yao I., Hata Y., Ide N., Hirao K., Deguchi M., Nishioka H., Mizoguchi A., Takai Y.
J. Biol. Chem. 274:11889-11896(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAGUIN-1.
[6]"PKC regulates the delta2 glutamate receptor interaction with S-SCAM/MAGI-2 protein."
Yap C.C., Muto Y., Kishida H., Hashikawa T., Yano R.
Biochem. Biophys. Res. Commun. 301:1122-1128(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GRID2.
[7]"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.
[8]"Cell junction-associated proteins IQGAP1, MAGI-2, CASK, spectrins, and alpha-actinin are components of the nephrin multiprotein complex."
Lehtonen S., Ryan J.J., Kudlicka K., Iino N., Zhou H., Farquhar M.G.
Proc. Natl. Acad. Sci. U.S.A. 102:9814-9819(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH ACTN4; CASK; IQGAP1; NPHS1; SPTAN1 AND SPTBN1, IDENTIFICATION BY MASS SPECTROMETRY, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
Strain: Sprague-Dawley.
Tissue: Renal glomerulus.
[9]"CIN85 is localized at synapses and forms a complex with S-SCAM via dendrin."
Kawata A., Iida J., Ikeda M., Sato Y., Mori H., Kansaku A., Sumita K., Fujiwara N., Rokukawa C., Hamano M., Hirabayashi S., Hata Y.
J. Biochem. 139:931-939(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DDN.
[10]"Postsynaptic recruitment of Dendrin depends on both dendritic mRNA transport and synaptic anchoring."
Kremerskothen J., Kindler S., Finger I., Veltel S., Barnekow A.
J. Neurochem. 96:1659-1666(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DDN.
[11]"Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth."
Hisata S., Sakisaka T., Baba T., Yamada T., Aoki K., Matsuda M., Takai Y.
J. Cell Biol. 178:843-860(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH KIDINS220; RAPGEF2 AND NTRK1, INTERACTION WITH RAPGEF2 AND KIDINS220, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF034863 mRNA. Translation: AAC31124.1.
AF130819 mRNA. Translation: AAD31015.1.
PIRT14152.
RefSeqNP_446073.1. NM_053621.1. [O88382-1]
UniGeneRn.205058.

3D structure databases

ProteinModelPortalO88382.
SMRO88382. Positions 303-340, 347-395, 412-522, 594-682, 769-865, 916-1021, 1135-1230.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid250241. 7 interactions.
IntActO88382. 26 interactions.
MINTMINT-87246.
STRING10116.ENSRNOP00000036634.

PTM databases

PhosphoSiteO88382.

Proteomic databases

PaxDbO88382.
PRIDEO88382.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID113970.
KEGGrno:113970.

Organism-specific databases

CTD9863.
RGD621855. Magi2.

Phylogenomic databases

eggNOGCOG5021.
HOGENOMHOG000113463.
HOVERGENHBG007091.
InParanoidO88382.
KOK05629.
PhylomeDBO88382.

Gene expression databases

GenevestigatorO88382.

Family and domain databases

Gene3D2.30.42.10. 6 hits.
InterProIPR008145. GK/Ca_channel_bsu.
IPR008144. Guanylate_kin-like.
IPR020590. Guanylate_kinase_CS.
IPR027417. P-loop_NTPase.
IPR001478. PDZ.
IPR001202. WW_dom.
[Graphical view]
PfamPF00625. Guanylate_kin. 1 hit.
PF00595. PDZ. 6 hits.
PF00397. WW. 2 hits.
[Graphical view]
SMARTSM00072. GuKc. 1 hit.
SM00228. PDZ. 6 hits.
SM00456. WW. 2 hits.
[Graphical view]
SUPFAMSSF50156. SSF50156. 6 hits.
SSF51045. SSF51045. 2 hits.
SSF52540. SSF52540. 1 hit.
PROSITEPS00856. GUANYLATE_KINASE_1. 1 hit.
PS50052. GUANYLATE_KINASE_2. 1 hit.
PS50106. PDZ. 6 hits.
PS01159. WW_DOMAIN_1. 2 hits.
PS50020. WW_DOMAIN_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio618109.
PROO88382.

Entry information

Entry nameMAGI2_RAT
AccessionPrimary (citable) accession number: O88382
Secondary accession number(s): Q9R271
Entry history
Integrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: November 1, 1998
Last modified: June 11, 2014
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families