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O88382

- MAGI2_RAT

UniProt

O88382 - MAGI2_RAT

Protein

Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2

Gene

Magi2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 117 (01 Oct 2014)
      Sequence version 1 (01 Nov 1998)
      Previous versions | rss
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    Functioni

    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.By similarity2 Publications

    GO - Molecular functioni

    1. beta-1 adrenergic receptor binding Source: UniProtKB
    2. PDZ domain binding Source: RGD
    3. phosphatase binding Source: UniProtKB
    4. protein binding Source: UniProtKB
    5. protein complex binding Source: RGD
    6. receptor signaling complex scaffold activity Source: UniProtKB
    7. signal transducer activity Source: UniProtKB
    8. SMAD binding Source: UniProtKB
    9. type II activin receptor binding Source: UniProtKB

    GO - Biological processi

    1. cellular response to nerve growth factor stimulus Source: UniProtKB
    2. cytoplasmic transport Source: UniProtKB
    3. glomerular filtration Source: UniProtKB
    4. glomerular visceral epithelial cell development Source: UniProtKB
    5. mitotic cell cycle arrest Source: UniProtKB
    6. negative regulation of activin receptor signaling pathway Source: UniProtKB
    7. negative regulation of cell migration Source: UniProtKB
    8. negative regulation of cell proliferation Source: UniProtKB
    9. negative regulation of protein kinase B signaling Source: UniProtKB
    10. nerve growth factor signaling pathway Source: UniProtKB
    11. positive regulation of neuron projection development Source: UniProtKB
    12. positive regulation of phosphoprotein phosphatase activity Source: UniProtKB
    13. positive regulation of receptor internalization Source: UniProtKB
    14. protein heterooligomerization Source: RGD
    15. receptor clustering Source: RGD
    16. SMAD protein signal transduction Source: UniProtKB

    Keywords - Biological processi

    Neurogenesis

    Names & Taxonomyi

    Protein namesi
    Recommended 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 namesi
    Name:Magi2
    Synonyms:Acvrinp1, Aip1, Sscam
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi621855. Magi2.

    Subcellular locationi

    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.

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. dendrite Source: UniProtKB
    3. late endosome Source: UniProtKB
    4. nucleus Source: UniProtKB
    5. perinuclear region of cytoplasm Source: UniProtKB
    6. plasma membrane Source: UniProtKB
    7. postsynaptic density Source: UniProtKB
    8. protein complex Source: UniProtKB
    9. slit diaphragm Source: UniProtKB
    10. synapse Source: UniProtKB
    11. tight junction Source: UniProtKB

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Cytoplasm, Endosome, Membrane, Synapse, Synaptosome

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 12771277Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2PRO_0000094588Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei362 – 3621PhosphotyrosineBy similarity
    Modified residuei827 – 8271PhosphotyrosineBy similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiO88382.
    PRIDEiO88382.

    PTM databases

    PhosphoSiteiO88382.

    Expressioni

    Tissue specificityi

    Expressed in the foot process layer of podocytes of the kidney glomeruli but not in tubules (at protein level). Expressed in the brain.2 Publications

    Developmental stagei

    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.1 Publication

    Gene expression databases

    GenevestigatoriO88382.

    Interactioni

    Subunit structurei

    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.By similarity10 Publications

    Binary interactionsi

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

    Protein-protein interaction databases

    BioGridi250241. 7 interactions.
    IntActiO88382. 26 interactions.
    MINTiMINT-87246.
    STRINGi10116.ENSRNOP00000036634.

    Structurei

    3D structure databases

    ProteinModelPortaliO88382.
    SMRiO88382. Positions 303-340, 347-395, 412-522, 594-682, 769-865, 916-1021, 1135-1230.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini17 – 10185PDZPROSITE-ProRule annotationAdd
    BLAST
    Domaini109 – 283175Guanylate kinase-likePROSITE-ProRule annotationAdd
    BLAST
    Domaini302 – 33534WW 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini348 – 38134WW 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini426 – 51085PDZ 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini605 – 68379PDZ 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini778 – 86083PDZ 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini920 – 101091PDZ 4PROSITE-ProRule annotationAdd
    BLAST
    Domaini1141 – 122383PDZ 5PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni302 – 38180Interaction with DDNBy similarityAdd
    BLAST

    Sequence similaritiesi

    Belongs to the MAGUK family.Curated
    Contains 1 guanylate kinase-like domain.PROSITE-ProRule annotation
    Contains 5 PDZ (DHR) domains.PROSITE-ProRule annotation
    Contains 2 WW domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiCOG5021.
    HOGENOMiHOG000113463.
    HOVERGENiHBG007091.
    InParanoidiO88382.
    KOiK05629.
    PhylomeDBiO88382.

    Family and domain databases

    Gene3Di2.30.42.10. 6 hits.
    InterProiIPR008145. GK/Ca_channel_bsu.
    IPR008144. Guanylate_kin-like.
    IPR020590. Guanylate_kinase_CS.
    IPR027417. P-loop_NTPase.
    IPR001478. PDZ.
    IPR001202. WW_dom.
    [Graphical view]
    PfamiPF00625. Guanylate_kin. 1 hit.
    PF00595. PDZ. 6 hits.
    PF00397. WW. 2 hits.
    [Graphical view]
    SMARTiSM00072. GuKc. 1 hit.
    SM00228. PDZ. 6 hits.
    SM00456. WW. 2 hits.
    [Graphical view]
    SUPFAMiSSF50156. SSF50156. 6 hits.
    SSF51045. SSF51045. 2 hits.
    SSF52540. SSF52540. 1 hit.
    PROSITEiPS00856. 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]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O88382-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MSKSLKKKSH WTSKVHESVI GRNPEGQLGF ELKGGAENGQ FPYLGEVKPG     50
    KVAYESGSKL VSEELLLEVN ETPVAGLTIR DVLAVIKHCK DPLRLKCVKQ 100
    GGIVDKDLRH YLNLRFQKGS VDHELQQIIR DNLYLRTVPC TTRPHKEGEV 150
    PGVDYIFITV EDFMELEKSG ALLESGTYED NYYGTPKPPA EPAPLLLNVT 200
    DQILPGATPS AEGKRKRNKS VTNMEKASIE PPEEEEEERP VVNGNGVVIT 250
    PESSEHEDKS AGASGETPSQ PYPAPVYSQP EELKDQMDDT KSTKPEENED 300
    SDPLPDNWEM AYTEKGEVYF IDHNTKTTSW LDPRLAKKAK PAEECKENEL 350
    PYGWEKIDDP IYGTYYVDHI NRRTQFENPV LEAKRKLQQH NMPHTELGTK 400
    PLQAPGFREK PLFTRDASQL KGTFLSTTLK KSNMGFGFTI IGGDEPDEFL 450
    QVKSVIPDGP AAQDGKMETG DVIVYINEVC VLGHTHADVV KLFQSVPIGQ 500
    SVNLVLCRGY PLPFDPEDPA NSMVPPLAIM ERPPPVMVNG RHNYETYLEY 550
    ISRTSQSVPD ITDRPPHSLH SMPADGQLDG TYPPPVHDDN VSVASSGATQ 600
    AELMTLTIVK GAKGFGFTIA DSPTGQRVKQ ILDIQGCPGL CEGDLIVEIN 650
    QQNVQNLSHT EVVDILKDCP VGSETSLIIH RGGFFSPWKT PKPMVDRWEN 700
    QGSPQTSLSA PAVPQSLPFP PALHRSSFPD STEAFDPRKP DPYELYEKSR 750
    AIYESRQQVP PRTSFRMDSS GPDYKELDVH LRRMESGFGF RILGGDEPGQ 800
    PILIGAVIAM GSADRDGRLH PGDELVYVDG IPVAGKTHRY VIDLMHHAAR 850
    NGQVNLTVRR KVLCGGEPCP ENGRSPGSVS THHSSPRSDY ATYANSNHAA 900
    PSNNASPPEG FASHSLQTSD VIIHRKENEG FGFVIISSLN RPESGATITV 950
    PHKIGRIIDG SPADRCAKLK VGDRILAVNG QSIINMPHAD IVKLIKDAGL 1000
    SVTLRIIPQE ELNNPTSAPS SEKQSPMAQQ HSPLAQQHSP LAQPSPATPN 1050
    SPVAQPAPPQ PLQLQGHENS YRSEVKARQD VKPDIRQPPF TDYRQPPLDY 1100
    RQPPGGDYSQ PSPLDYRQHS PDTRQYPLSD YRQPQDFDYF TVDMEKGAKG 1150
    FGFSIRGGRE YKMDLYVLRL AEDGPAIRNG RMRVGDQIIE INGESTRDMT 1200
    HARAIELIKS GGRRVRLLLK RGTGQVPEYG MVPSSLSMCM KSDKHGSPYF 1250
    YLLGHPKDTT NPTPGALPLP PPQACRK 1277
    Length:1,277
    Mass (Da):141,072
    Last modified:November 1, 1998 - v1
    Checksum:iE1A435FF35549DF9
    GO
    Isoform 2 (identifier: O88382-2) [UniParc]FASTAAdd to Basket

    Also known as: beta

    The sequence of this isoform differs from the canonical sequence as follows:
         1-163: Missing.

    Show »
    Length:1,114
    Mass (Da):122,766
    Checksum:i7B1BA3E0049DBD30
    GO
    Isoform 3 (identifier: O88382-3) [UniParc]FASTAAdd to Basket

    Also known as: gamma

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

    Show »
    Length:1,054
    Mass (Da):116,325
    Checksum:i718C43F950E5365E
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti645 – 6451L → F in AAD31015. (PubMed:10644767)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 223223Missing in isoform 3. CuratedVSP_008439Add
    BLAST
    Alternative sequencei1 – 163163Missing in isoform 2. 1 PublicationVSP_008438Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF034863 mRNA. Translation: AAC31124.1.
    AF130819 mRNA. Translation: AAD31015.1.
    PIRiT14152.
    RefSeqiNP_446073.1. NM_053621.1. [O88382-1]
    UniGeneiRn.205058.

    Genome annotation databases

    GeneIDi113970.
    KEGGirno:113970.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF034863 mRNA. Translation: AAC31124.1 .
    AF130819 mRNA. Translation: AAD31015.1 .
    PIRi T14152.
    RefSeqi NP_446073.1. NM_053621.1. [O88382-1 ]
    UniGenei Rn.205058.

    3D structure databases

    ProteinModelPortali O88382.
    SMRi O88382. Positions 303-340, 347-395, 412-522, 594-682, 769-865, 916-1021, 1135-1230.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 250241. 7 interactions.
    IntActi O88382. 26 interactions.
    MINTi MINT-87246.
    STRINGi 10116.ENSRNOP00000036634.

    PTM databases

    PhosphoSitei O88382.

    Proteomic databases

    PaxDbi O88382.
    PRIDEi O88382.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 113970.
    KEGGi rno:113970.

    Organism-specific databases

    CTDi 9863.
    RGDi 621855. Magi2.

    Phylogenomic databases

    eggNOGi COG5021.
    HOGENOMi HOG000113463.
    HOVERGENi HBG007091.
    InParanoidi O88382.
    KOi K05629.
    PhylomeDBi O88382.

    Miscellaneous databases

    NextBioi 618109.
    PROi O88382.

    Gene expression databases

    Genevestigatori O88382.

    Family and domain databases

    Gene3Di 2.30.42.10. 6 hits.
    InterProi IPR008145. GK/Ca_channel_bsu.
    IPR008144. Guanylate_kin-like.
    IPR020590. Guanylate_kinase_CS.
    IPR027417. P-loop_NTPase.
    IPR001478. PDZ.
    IPR001202. WW_dom.
    [Graphical view ]
    Pfami PF00625. Guanylate_kin. 1 hit.
    PF00595. PDZ. 6 hits.
    PF00397. WW. 2 hits.
    [Graphical view ]
    SMARTi SM00072. GuKc. 1 hit.
    SM00228. PDZ. 6 hits.
    SM00456. WW. 2 hits.
    [Graphical view ]
    SUPFAMi SSF50156. SSF50156. 6 hits.
    SSF51045. SSF51045. 2 hits.
    SSF52540. SSF52540. 1 hit.
    PROSITEi PS00856. 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 ]
    ProtoNeti Search...

    Publicationsi

    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.

    Entry informationi

    Entry nameiMAGI2_RAT
    AccessioniPrimary (citable) accession number: O88382
    Secondary accession number(s): Q9R271
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 3, 2003
    Last sequence update: November 1, 1998
    Last modified: October 1, 2014
    This is version 117 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3