ID MAGI2_HUMAN Reviewed; 1455 AA. AC Q86UL8; A4D1C1; A7E2C3; O60434; O60510; Q86UI7; Q9NP44; Q9UDQ5; Q9UDU1; DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot. DT 07-FEB-2006, sequence version 3. DT 27-MAR-2024, entry version 195. DE RecName: Full=Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2; DE AltName: Full=Atrophin-1-interacting protein 1; DE Short=AIP-1; DE AltName: Full=Atrophin-1-interacting protein A; DE AltName: Full=Membrane-associated guanylate kinase inverted 2; DE Short=MAGI-2; GN Name=MAGI2; Synonyms=ACVRINP1, AIP1, KIAA0705; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND INTERACTION RP WITH DRPLA. RC TISSUE=Brain; RX PubMed=9647693; DOI=10.1006/mcne.1998.0677; RA Wood J.D., Yuan J., Margolis R.L., Colomer V., Duan K., Kushi J., RA Kaminsky Z., Kleiderlein J.J. Jr., Sharp A.H., Ross C.A.; RT "Atrophin-1, the DRPLA gene product, interacts with two families of WW RT domain-containing proteins."; RL Mol. Cell. Neurosci. 11:149-160(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=9734811; DOI=10.1093/dnares/5.3.169; RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., RA Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. X. The RT complete sequences of 100 new cDNA clones from brain which can code for RT large proteins in vitro."; RL DNA Res. 5:169-176(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D., RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., RA Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PTEN. RX PubMed=10760291; DOI=10.1073/pnas.97.8.4233; RA Wu X., Hepner K., Castelino-Prabhu S., Do D., Kaye M.B., Yuan X.-J., RA Wood J., Ross C., Sawyers C.L., Whang Y.E.; RT "Evidence for regulation of the PTEN tumor suppressor by a membrane- RT localized multi-PDZ domain containing scaffold protein MAGI-2."; RL Proc. Natl. Acad. Sci. U.S.A. 97:4233-4238(2000). RN [7] RP INTERACTION WITH PTEN. RX PubMed=11707428; DOI=10.1074/jbc.c100556200; RA Vazquez F., Grossman S.R., Takahashi Y., Rokas M.V., Nakamura N., RA Sellers W.R.; RT "Phosphorylation of the PTEN tail acts as an inhibitory switch by RT preventing its recruitment into a protein complex."; RL J. Biol. Chem. 276:48627-48630(2001). RN [8] RP INTERACTION WITH DDN. RX PubMed=16464232; DOI=10.1111/j.1471-4159.2006.03679.x; RA Kremerskothen J., Kindler S., Finger I., Veltel S., Barnekow A.; RT "Postsynaptic recruitment of Dendrin depends on both dendritic mRNA RT transport and synaptic anchoring."; RL J. Neurochem. 96:1659-1666(2006). RN [9] RP IDENTIFICATION IN A COMPLEX WITH IGSF9B AND NLGN2. RX PubMed=23751499; DOI=10.1083/jcb.201209132; RA Woo J., Kwon S.K., Nam J., Choi S., Takahashi H., Krueger D., Park J., RA Lee Y., Bae J.Y., Lee D., Ko J., Kim H., Kim M.H., Bae Y.C., Chang S., RA Craig A.M., Kim E.; RT "The adhesion protein IgSF9b is coupled to neuroligin 2 via S-SCAM to RT promote inhibitory synapse development."; RL J. Cell Biol. 201:929-944(2013). RN [10] RP INTERACTION WITH USH1G. RX PubMed=24608321; DOI=10.1093/hmg/ddu104; RA Bauss K., Knapp B., Jores P., Roepman R., Kremer H., Wijk E.V., Maerker T., RA Wolfrum U.; RT "Phosphorylation of the Usher syndrome 1G protein SANS controls Magi2- RT mediated endocytosis."; RL Hum. Mol. Genet. 23:3923-3942(2014). RN [11] RP STRUCTURE BY NMR OF 412-1230. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the PDZ domains of human atrophin-1 interacting RT protein 1 (KIAA0705 protein)."; RL Submitted (FEB-2004) to the PDB data bank. RN [12] RP INVOLVEMENT IN NPHS15. RX PubMed=27932480; DOI=10.1681/asn.2016040387; RG NephroS; RG UK study of Nephrotic Syndrome; RA Bierzynska A., Soderquest K., Dean P., Colby E., Rollason R., Jones C., RA Inward C.D., McCarthy H.J., Simpson M.A., Lord G.M., Williams M., RA Welsh G.I., Koziell A.B., Saleem M.A.; RT "MAGI2 mutations cause congenital nephrotic syndrome."; RL J. Am. Soc. Nephrol. 28:1614-1621(2017). CC -!- FUNCTION: Seems to act as a scaffold molecule at synaptic junctions by CC assembling neurotransmitter receptors and cell adhesion proteins (By CC similarity). Plays a role in nerve growth factor (NGF)-induced CC recruitment of RAPGEF2 to late endosomes and neurite outgrowth (By CC similarity). May play a role in regulating activin-mediated signaling CC in neuronal cells (By similarity). Enhances the ability of PTEN to CC suppress AKT1 activation (PubMed:10760291). Plays a role in receptor- CC mediated clathrin-dependent endocytosis which is required for CC ciliogenesis (By similarity). {ECO:0000250|UniProtKB:O88382, CC ECO:0000250|UniProtKB:Q9WVQ1, ECO:0000269|PubMed:10760291}. CC -!- SUBUNIT: Interacts (via its WW domains) with DRPLA (PubMed:9647693). CC Interacts (via its second PDZ domain) with PTEN (via unphosphorylated CC C-terminus); this interaction diminishes the degradation rate of PTEN CC (PubMed:10760291, PubMed:11707428). Interacts (via guanylate kinase CC domain) with DLGAP1 (By similarity). Interacts (via the PDZ domains) CC with GRIN2A, GRID2 and NLGN1 (By similarity). Interacts with CTNND2, CC CTNNB1, MAGUIN-1, ACVR2A, SMAD2 and SMAD3 (By similarity). Part of a CC complex consisting of MAGI2/ARIP1, ACVR2A, ACVR1B and SMAD3 (By CC similarity). May interact with HTR2A (By similarity). Interacts with CC IGSF9, RAPGEF2 and HTR4 (By similarity). Identified in a complex with CC ACTN4, CASK, IQGAP1, NPHS1, SPTAN1 and SPTBN1 (By similarity). Found in CC a complex, at least composed of KIDINS220, MAGI2, NTRK1 and RAPGEF2; CC the complex is mainly formed at late endosomes in a NGF-dependent CC manner (By similarity). Interacts with RAPGEF2; the interaction occurs CC before or after nerve growth factor (NGF) stimulation (By similarity). CC Interacts (via PDZ domain) with KIDINS220 (via C-terminal domain) (By CC similarity). Interacts with DDN (PubMed:16464232). Interacts with DLL1 CC (By similarity). Found in a complex with IGSF9B and NLGN2; the CC interaction with IGSF9B is mediated via the PDZ 5 and PDZ 6 domains, CC while the interaction with NLGN2 is mediated via the WW1, WW2 and PDZ2 CC domains (PubMed:23751499). Interacts (via PDZ 6 domain) with USH1G (via CC SAM domain); the interaction is triggered by phosphorylation of USH1G CC by CK2 and negatively regulates MAGI2-mediated endocytosis CC (PubMed:24608321). {ECO:0000250|UniProtKB:O88382, CC ECO:0000250|UniProtKB:Q9WVQ1, ECO:0000269|PubMed:10760291, CC ECO:0000269|PubMed:11707428, ECO:0000269|PubMed:16464232, CC ECO:0000269|PubMed:23751499, ECO:0000269|PubMed:24608321, CC ECO:0000269|PubMed:9647693}. CC -!- INTERACTION: CC Q86UL8; P08588: ADRB1; NbExp=3; IntAct=EBI-311035, EBI-991009; CC Q86UL8-2; Q6IS01: DLGAP1; NbExp=5; IntAct=EBI-12081182, EBI-11961832; CC Q86UL8-2; Q9P1A6-3: DLGAP2; NbExp=3; IntAct=EBI-12081182, EBI-12019838; CC Q86UL8-2; O95886: DLGAP3; NbExp=3; IntAct=EBI-12081182, EBI-1752541; CC Q86UL8-2; Q8NDC4: MORN4; NbExp=3; IntAct=EBI-12081182, EBI-10269566; CC Q86UL8-2; Q5EBL8: PDZD11; NbExp=3; IntAct=EBI-12081182, EBI-1644207; CC Q86UL8-2; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-12081182, EBI-742388; CC Q86UL8-2; P14678-2: SNRPB; NbExp=3; IntAct=EBI-12081182, EBI-372475; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Late endosome CC {ECO:0000250}. Synapse, synaptosome {ECO:0000250}. Cell membrane CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Cytoplasm, CC cytoskeleton, microtubule organizing center, centrosome CC {ECO:0000250|UniProtKB:Q9WVQ1}. Cell projection, cilium CC {ECO:0000250|UniProtKB:Q9WVQ1}. Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome, centriole CC {ECO:0000250|UniProtKB:Q9WVQ1}. Photoreceptor inner segment CC {ECO:0000250|UniProtKB:Q9WVQ1}. Cell projection, cilium, photoreceptor CC outer segment {ECO:0000250|UniProtKB:Q9WVQ1}. Note=Localized diffusely CC in the cytoplasm before nerve growth factor (NGF) stimulation. CC Recruited to late endosomes after NGF stimulation. Membrane-associated CC in synaptosomes (By similarity). {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q86UL8-1; Sequence=Displayed; CC Name=2; CC IsoId=Q86UL8-2; Sequence=VSP_008435; CC -!- TISSUE SPECIFICITY: Specifically expressed in brain. CC {ECO:0000269|PubMed:9647693}. CC -!- DISEASE: Nephrotic syndrome 15 (NPHS15) [MIM:617609]: A form of CC nephrotic syndrome, a renal disease clinically characterized by severe CC proteinuria, resulting in complications such as hypoalbuminemia, CC hyperlipidemia and edema. Kidney biopsies show non-specific histologic CC changes such as focal segmental glomerulosclerosis and diffuse CC mesangial proliferation. NPHS15 is an autosomal recessive form with CC onset in the first months of life. Disease severity is variable. Some CC patients show rapid progression to end-stage renal failure. CC {ECO:0000269|PubMed:27932480}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the MAGUK family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA31680.2; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF038563; AAC05370.1; -; mRNA. DR EMBL; AB014605; BAA31680.2; ALT_INIT; mRNA. DR EMBL; AC004808; AAC23438.1; -; Genomic_DNA. DR EMBL; AC004945; AAC61488.1; -; Genomic_DNA. DR EMBL; AC004990; AAC79151.1; -; Genomic_DNA. DR EMBL; AC005246; AAC25530.1; -; Genomic_DNA. DR EMBL; AC006043; AAD15413.2; -; Genomic_DNA. DR EMBL; AC006324; AAF66080.1; -; Genomic_DNA. DR EMBL; AC007237; AAP21886.1; -; Genomic_DNA. DR EMBL; AC073200; AAP22360.1; -; Genomic_DNA. DR EMBL; CH236949; EAL24194.1; -; Genomic_DNA. DR EMBL; BC150277; AAI50278.1; -; mRNA. DR CCDS; CCDS5594.1; -. [Q86UL8-1] DR CCDS; CCDS75623.1; -. [Q86UL8-2] DR RefSeq; NP_001288057.1; NM_001301128.1. [Q86UL8-2] DR RefSeq; NP_036433.2; NM_012301.3. [Q86UL8-1] DR PDB; 1UEP; NMR; -; A=774-863. DR PDB; 1UEQ; NMR; -; A=412-522. DR PDB; 1UEW; NMR; -; A=915-1015. DR PDB; 1UJV; NMR; -; A=600-682. DR PDB; 1WFV; NMR; -; A=1141-1230. DR PDBsum; 1UEP; -. DR PDBsum; 1UEQ; -. DR PDBsum; 1UEW; -. DR PDBsum; 1UJV; -. DR PDBsum; 1WFV; -. DR AlphaFoldDB; Q86UL8; -. DR SMR; Q86UL8; -. DR BioGRID; 115197; 29. DR CORUM; Q86UL8; -. DR IntAct; Q86UL8; 24. DR MINT; Q86UL8; -. DR STRING; 9606.ENSP00000346151; -. DR TCDB; 8.A.24.1.6; the ezrin/radixin/moesin-binding phosphoprotein 50 (ebp50) family. DR iPTMnet; Q86UL8; -. DR PhosphoSitePlus; Q86UL8; -. DR BioMuta; MAGI2; -. DR DMDM; 88909269; -. DR EPD; Q86UL8; -. DR jPOST; Q86UL8; -. DR MassIVE; Q86UL8; -. DR MaxQB; Q86UL8; -. DR PaxDb; 9606-ENSP00000346151; -. DR PeptideAtlas; Q86UL8; -. DR ProteomicsDB; 69831; -. [Q86UL8-1] DR ProteomicsDB; 69832; -. [Q86UL8-2] DR Antibodypedia; 2880; 300 antibodies from 33 providers. DR DNASU; 9863; -. DR Ensembl; ENST00000354212.9; ENSP00000346151.4; ENSG00000187391.23. [Q86UL8-1] DR Ensembl; ENST00000419488.5; ENSP00000405766.1; ENSG00000187391.23. [Q86UL8-2] DR GeneID; 9863; -. DR KEGG; hsa:9863; -. DR MANE-Select; ENST00000354212.9; ENSP00000346151.4; NM_012301.4; NP_036433.2. DR UCSC; uc003ugx.3; human. [Q86UL8-1] DR AGR; HGNC:18957; -. DR CTD; 9863; -. DR DisGeNET; 9863; -. DR GeneCards; MAGI2; -. DR HGNC; HGNC:18957; MAGI2. DR HPA; ENSG00000187391; Tissue enhanced (brain). DR MalaCards; MAGI2; -. DR MIM; 606382; gene. DR MIM; 617609; phenotype. DR neXtProt; NX_Q86UL8; -. DR OpenTargets; ENSG00000187391; -. DR Orphanet; 656; Genetic steroid-resistant nephrotic syndrome. DR PharmGKB; PA142671484; -. DR VEuPathDB; HostDB:ENSG00000187391; -. DR eggNOG; KOG3209; Eukaryota. DR GeneTree; ENSGT00940000155057; -. DR InParanoid; Q86UL8; -. DR OMA; XYRSEVK; -. DR OrthoDB; 2902917at2759; -. DR PhylomeDB; Q86UL8; -. DR TreeFam; TF316816; -. DR PathwayCommons; Q86UL8; -. DR Reactome; R-HSA-373753; Nephrin family interactions. DR SignaLink; Q86UL8; -. DR SIGNOR; Q86UL8; -. DR BioGRID-ORCS; 9863; 10 hits in 1152 CRISPR screens. DR ChiTaRS; MAGI2; human. DR EvolutionaryTrace; Q86UL8; -. DR GeneWiki; MAGI2; -. DR GenomeRNAi; 9863; -. DR Pharos; Q86UL8; Tbio. DR PRO; PR:Q86UL8; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q86UL8; Protein. DR Bgee; ENSG00000187391; Expressed in calcaneal tendon and 187 other cell types or tissues. DR ExpressionAtlas; Q86UL8; baseline and differential. DR GO; GO:0005923; C:bicellular tight junction; IDA:UniProtKB. DR GO; GO:0005911; C:cell-cell junction; IBA:GO_Central. DR GO; GO:0005814; C:centriole; ISS:UniProtKB. DR GO; GO:0005813; C:centrosome; IEA:UniProtKB-SubCell. DR GO; GO:0097546; C:ciliary base; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0030425; C:dendrite; ISS:UniProtKB. DR GO; GO:0005770; C:late endosome; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB. DR GO; GO:0001917; C:photoreceptor inner segment; ISS:UniProtKB. DR GO; GO:0001750; C:photoreceptor outer segment; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0014069; C:postsynaptic density; ISS:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB. DR GO; GO:0036057; C:slit diaphragm; ISS:UniProtKB. DR GO; GO:0045202; C:synapse; ISS:UniProtKB. DR GO; GO:0031697; F:beta-1 adrenergic receptor binding; IPI:UniProtKB. DR GO; GO:0019902; F:phosphatase binding; IPI:UniProtKB. DR GO; GO:0030159; F:signaling receptor complex adaptor activity; IDA:UniProtKB. DR GO; GO:0046332; F:SMAD binding; ISS:UniProtKB. DR GO; GO:0070699; F:type II activin receptor binding; ISS:UniProtKB. DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; ISS:UniProtKB. DR GO; GO:0072583; P:clathrin-dependent endocytosis; ISS:UniProtKB. DR GO; GO:0032926; P:negative regulation of activin receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0030336; P:negative regulation of cell migration; ISS:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB. DR GO; GO:0051898; P:negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:UniProtKB. DR GO; GO:0038180; P:nerve growth factor signaling pathway; ISS:UniProtKB. DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW. DR GO; GO:0003402; P:planar cell polarity pathway involved in axis elongation; NAS:UniProtKB. DR GO; GO:0072015; P:podocyte development; ISS:UniProtKB. DR GO; GO:0010976; P:positive regulation of neuron projection development; ISS:UniProtKB. DR GO; GO:0032516; P:positive regulation of phosphoprotein phosphatase activity; IDA:UniProtKB. DR GO; GO:0002092; P:positive regulation of receptor internalization; IDA:UniProtKB. DR GO; GO:0043113; P:receptor clustering; ISS:UniProtKB. DR GO; GO:0007165; P:signal transduction; IBA:GO_Central. DR GO; GO:0060395; P:SMAD protein signal transduction; ISS:UniProtKB. DR CDD; cd00992; PDZ_signaling; 6. DR CDD; cd00201; WW; 2. DR Gene3D; 2.20.70.10; -; 2. DR Gene3D; 2.30.42.10; -; 6. DR Gene3D; 3.30.63.10; Guanylate Kinase phosphate binding domain; 1. DR InterPro; IPR008145; GK/Ca_channel_bsu. DR InterPro; IPR008144; Guanylate_kin-like_dom. DR InterPro; IPR020590; Guanylate_kinase_CS. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR001478; PDZ. DR InterPro; IPR036034; PDZ_sf. DR InterPro; IPR001202; WW_dom. DR InterPro; IPR036020; WW_dom_sf. DR PANTHER; PTHR10316; MEMBRANE ASSOCIATED GUANYLATE KINASE-RELATED; 1. DR PANTHER; PTHR10316:SF27; MEMBRANE-ASSOCIATED GUANYLATE KINASE, WW AND PDZ DOMAIN-CONTAINING PROTEIN 2; 1. DR Pfam; PF00625; Guanylate_kin; 1. DR Pfam; PF16663; MAGI_u1; 1. DR Pfam; PF00595; PDZ; 6. DR Pfam; PF00397; WW; 1. DR SMART; SM00072; GuKc; 1. DR SMART; SM00228; PDZ; 6. DR SMART; SM00456; WW; 2. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR SUPFAM; SSF50156; PDZ domain-like; 6. DR SUPFAM; SSF51045; WW domain; 2. DR PROSITE; PS00856; GUANYLATE_KINASE_1; 1. DR PROSITE; PS50052; GUANYLATE_KINASE_2; 1. DR PROSITE; PS50106; PDZ; 6. DR PROSITE; PS01159; WW_DOMAIN_1; 2. DR PROSITE; PS50020; WW_DOMAIN_2; 2. DR Genevisible; Q86UL8; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Cell projection; KW Cytoplasm; Cytoskeleton; Endocytosis; Endosome; Membrane; Neurogenesis; KW Phosphoprotein; Reference proteome; Repeat; Synapse; Synaptosome. FT CHAIN 1..1455 FT /note="Membrane-associated guanylate kinase, WW and PDZ FT domain-containing protein 2" FT /id="PRO_0000094586" FT DOMAIN 17..101 FT /note="PDZ 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT DOMAIN 109..283 FT /note="Guanylate kinase-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00100" FT DOMAIN 302..335 FT /note="WW 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224" FT DOMAIN 348..381 FT /note="WW 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224" FT DOMAIN 426..510 FT /note="PDZ 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT DOMAIN 605..683 FT /note="PDZ 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT DOMAIN 778..860 FT /note="PDZ 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT DOMAIN 920..1010 FT /note="PDZ 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT DOMAIN 1147..1229 FT /note="PDZ 6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT REGION 205..306 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 302..381 FT /note="Interaction with DDN" FT /evidence="ECO:0000269|PubMed:16464232" FT REGION 869..913 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1011..1136 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1231..1455 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 282..301 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 874..913 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1011..1042 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1043..1057 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1069..1085 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1285..1323 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 362 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q9WVQ1" FT MOD_RES 686 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O88382" FT MOD_RES 827 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q9WVQ1" FT MOD_RES 884 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O88382" FT MOD_RES 885 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O88382" FT MOD_RES 1014 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9WVQ1" FT VAR_SEQ 757..771 FT /note="QQVPPRTSFRMDSSG -> R (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:9734811" FT /id="VSP_008435" FT CONFLICT 1234 FT /note="E -> Q (in Ref. 1; AAC05370)" FT /evidence="ECO:0000305" FT CONFLICT 1250 FT /note="G -> C (in Ref. 1; AAC05370)" FT /evidence="ECO:0000305" FT CONFLICT 1291 FT /note="E -> K (in Ref. 1; AAC05370)" FT /evidence="ECO:0000305" FT CONFLICT 1383 FT /note="P -> L (in Ref. 1; AAC05370)" FT /evidence="ECO:0000305" FT CONFLICT 1389..1394 FT /note="FAGPGG -> SADPAD (in Ref. 1; AAC05370)" FT /evidence="ECO:0000305" FT CONFLICT 1401 FT /note="E -> A (in Ref. 1; AAC05370)" FT /evidence="ECO:0000305" FT CONFLICT 1411 FT /note="G -> A (in Ref. 1; AAC05370)" FT /evidence="ECO:0000305" FT CONFLICT 1414..1415 FT /note="PG -> SV (in Ref. 1; AAC05370)" FT /evidence="ECO:0000305" FT CONFLICT 1420 FT /note="G -> A (in Ref. 1; AAC05370)" FT /evidence="ECO:0000305" FT CONFLICT 1423 FT /note="P -> A (in Ref. 1; AAC05370)" FT /evidence="ECO:0000305" FT CONFLICT 1426 FT /note="K -> R (in Ref. 1; AAC05370)" FT /evidence="ECO:0000305" FT CONFLICT 1429 FT /note="V -> G (in Ref. 1; AAC05370)" FT /evidence="ECO:0000305" FT CONFLICT 1437 FT /note="P -> R (in Ref. 1; AAC05370)" FT /evidence="ECO:0000305" FT STRAND 415..417 FT /evidence="ECO:0007829|PDB:1UEQ" FT STRAND 422..430 FT /evidence="ECO:0007829|PDB:1UEQ" FT STRAND 437..441 FT /evidence="ECO:0007829|PDB:1UEQ" FT STRAND 444..447 FT /evidence="ECO:0007829|PDB:1UEQ" FT STRAND 451..455 FT /evidence="ECO:0007829|PDB:1UEQ" FT HELIX 460..463 FT /evidence="ECO:0007829|PDB:1UEQ" FT STRAND 472..476 FT /evidence="ECO:0007829|PDB:1UEQ" FT HELIX 486..494 FT /evidence="ECO:0007829|PDB:1UEQ" FT STRAND 501..509 FT /evidence="ECO:0007829|PDB:1UEQ" FT STRAND 604..609 FT /evidence="ECO:0007829|PDB:1UJV" FT STRAND 612..622 FT /evidence="ECO:0007829|PDB:1UJV" FT STRAND 625..632 FT /evidence="ECO:0007829|PDB:1UJV" FT HELIX 634..636 FT /evidence="ECO:0007829|PDB:1UJV" FT STRAND 645..649 FT /evidence="ECO:0007829|PDB:1UJV" FT HELIX 659..668 FT /evidence="ECO:0007829|PDB:1UJV" FT STRAND 673..680 FT /evidence="ECO:0007829|PDB:1UJV" FT STRAND 774..777 FT /evidence="ECO:0007829|PDB:1UEP" FT STRAND 780..787 FT /evidence="ECO:0007829|PDB:1UEP" FT STRAND 790..792 FT /evidence="ECO:0007829|PDB:1UEP" FT STRAND 803..807 FT /evidence="ECO:0007829|PDB:1UEP" FT HELIX 814..816 FT /evidence="ECO:0007829|PDB:1UEP" FT STRAND 824..828 FT /evidence="ECO:0007829|PDB:1UEP" FT HELIX 838..851 FT /evidence="ECO:0007829|PDB:1UEP" FT STRAND 853..861 FT /evidence="ECO:0007829|PDB:1UEP" FT STRAND 919..924 FT /evidence="ECO:0007829|PDB:1UEW" FT STRAND 933..936 FT /evidence="ECO:0007829|PDB:1UEW" FT STRAND 953..957 FT /evidence="ECO:0007829|PDB:1UEW" FT HELIX 964..966 FT /evidence="ECO:0007829|PDB:1UEW" FT STRAND 974..978 FT /evidence="ECO:0007829|PDB:1UEW" FT TURN 983..985 FT /evidence="ECO:0007829|PDB:1UEW" FT HELIX 988..997 FT /evidence="ECO:0007829|PDB:1UEW" FT TURN 998..1000 FT /evidence="ECO:0007829|PDB:1UEW" FT STRAND 1001..1006 FT /evidence="ECO:0007829|PDB:1UEW" FT STRAND 1156..1159 FT /evidence="ECO:0007829|PDB:1WFV" FT STRAND 1162..1164 FT /evidence="ECO:0007829|PDB:1WFV" FT TURN 1165..1168 FT /evidence="ECO:0007829|PDB:1WFV" FT STRAND 1169..1172 FT /evidence="ECO:0007829|PDB:1WFV" FT HELIX 1181..1185 FT /evidence="ECO:0007829|PDB:1WFV" FT STRAND 1193..1197 FT /evidence="ECO:0007829|PDB:1WFV" FT HELIX 1207..1217 FT /evidence="ECO:0007829|PDB:1WFV" FT STRAND 1219..1221 FT /evidence="ECO:0007829|PDB:1WFV" FT STRAND 1223..1226 FT /evidence="ECO:0007829|PDB:1WFV" SQ SEQUENCE 1455 AA; 158754 MW; 93E170D070A70A9C CRC64; MSKSLKKKSH WTSKVHESVI GRNPEGQLGF ELKGGAENGQ FPYLGEVKPG KVAYESGSKL VSEELLLEVN ETPVAGLTIR DVLAVIKHCK DPLRLKCVKQ GGIVDKDLRH YLNLRFQKGS VDHELQQIIR DNLYLRTVPC TTRPHKEGEV PGVDYIFITV EDFMELEKSG ALLESGTYED NYYGTPKPPA EPAPLLLNVT DQILPGATPS AEGKRKRNKS VSNMEKASIE PPEEEEEERP VVNGNGVVVT PESSEHEDKS AGASGEMPSQ PYPAPVYSQP EELKEQMDDT KPTKPEDNEE PDPLPDNWEM AYTEKGEVYF IDHNTKTTSW LDPRLAKKAK PPEECKENEL PYGWEKIDDP IYGTYYVDHI NRRTQFENPV LEAKRKLQQH NMPHTELGTK PLQAPGFREK PLFTRDASQL KGTFLSTTLK KSNMGFGFTI IGGDEPDEFL QVKSVIPDGP AAQDGKMETG DVIVYINEVC VLGHTHADVV KLFQSVPIGQ SVNLVLCRGY PLPFDPEDPA NSMVPPLAIM ERPPPVMVNG RHNYETYLEY ISRTSQSVPD ITDRPPHSLH SMPTDGQLDG TYPPPVHDDN VSMASSGATQ AELMTLTIVK GAQGFGFTIA DSPTGQRVKQ ILDIQGCPGL CEGDLIVEIN QQNVQNLSHT EVVDILKDCP IGSETSLIIH RGGFFSPWKT PKPIMDRWEN QGSPQTSLSA PAIPQNLPFP PALHRSSFPD STEAFDPRKP DPYELYEKSR AIYESRQQVP PRTSFRMDSS GPDYKELDVH LRRMESGFGF RILGGDEPGQ PILIGAVIAM GSADRDGRLH PGDELVYVDG IPVAGKTHRY VIDLMHHAAR NGQVNLTVRR KVLCGGEPCP ENGRSPGSVS THHSSPRSDY ATYTNSNHAA PSSNASPPEG FASHSLQTSD VVIHRKENEG FGFVIISSLN RPESGSTITV PHKIGRIIDG SPADRCAKLK VGDRILAVNG QSIINMPHAD IVKLIKDAGL SVTLRIIPQE ELNSPTSAPS SEKQSPMAQQ SPLAQQSPLA QPSPATPNSP IAQPAPPQPL QLQGHENSYR SEVKARQDVK PDIRQPPFTD YRQPPLDYRQ PPGGDYQQPP PLDYRQPPLL DYRQHSPDTR QYPLSDYRQP QDFDYFTVDM EKGAKGFGFS IRGGREYKMD LYVLRLAEDG PAIRNGRMRV GDQIIEINGE STRDMTHARA IELIKSGGRR VRLLLKRGTG QVPEYDEPAP WSSPAAAAPG LPEVGVSLDD GLAPFSPSHP APPSDPSHQI SPGPTWDIKR EHDVRKPKEL SACGQKKQRL GEQRERSASP QRAARPRLEE APGGQGRPEA GRPASEARAP GLAAADAADA ARAGGKEAPR AAAGSELCRR EGPGAAPAFA GPGGGGSGAL EAEGRAGARA GPRPGPRPPG GAPARKAAVA PGPWKVPGSD KLPSVLKPGA SAASR //