ID   MPP3_HUMAN              Reviewed;         585 AA.
AC   Q13368; A0A0C4DGP3; B2R7N0; D3DX47; Q4GX05; Q6PGR3; Q86SV1;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   26-JUN-2007, sequence version 2.
DT   24-JAN-2024, entry version 182.
DE   RecName: Full=MAGUK p55 subfamily member 3 {ECO:0000305};
DE   AltName: Full=Discs large homolog 3;
DE   AltName: Full=Protein MPP3;
GN   Name=MPP3 {ECO:0000303|PubMed:16519681, ECO:0000312|HGNC:HGNC:7221};
GN   Synonyms=DLG3 {ECO:0000303|PubMed:8824795};
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].
RX   PubMed=8824795; DOI=10.1006/geno.1996.0025;
RA   Smith S.A., Holik P., Stevens J., Mazoyer S., Melis R., Williams B.,
RA   White R., Albertsen H.;
RT   "Isolation of a gene (DLG3) encoding a second member of the discs-large
RT   family on chromosome 17q12-q21.";
RL   Genomics 31:145-150(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INTERACTION WITH PALS1 AND
RP   DLG1, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC   TISSUE=Retina;
RX   PubMed=16519681; DOI=10.1111/j.1742-4658.2006.05140.x;
RA   Kantardzhieva A., Alexeeva S., Versteeg I., Wijnholds J.;
RT   "MPP3 is recruited to the MPP5 protein scaffold at the retinal outer
RT   limiting membrane.";
RL   FEBS J. 273:1152-1165(2006).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16625196; DOI=10.1038/nature04689;
RA   Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA   Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA   Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA   Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA   DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA   Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA   Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA   LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA   Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA   Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA   Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA   Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA   Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT   "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT   human lineage.";
RL   Nature 440:1045-1049(2006).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain, and Pancreas;
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   [7]
RP   INTERACTION WITH CADM1.
RX   PubMed=13679854; DOI=10.1038/sj.onc.1206744;
RA   Fukuhara H., Masuda M., Yageta M., Fukami T., Kuramochi M., Maruyama T.,
RA   Kitamura T., Murakami Y.;
RT   "Association of a lung tumor suppressor TSLC1 with MPP3, a human homologue
RT   of Drosophila tumor suppressor Dlg.";
RL   Oncogene 22:6160-6165(2003).
RN   [8]
RP   FUNCTION, INTERACTION WITH CADM1 AND DLG1, AND SUBCELLULAR LOCATION.
RX   PubMed=24503895; DOI=10.1371/journal.pone.0082894;
RA   Murakami S., Sakurai-Yageta M., Maruyama T., Murakami Y.;
RT   "Trans-homophilic interaction of CADM1 activates PI3K by forming a complex
RT   with MAGuK-family proteins MPP3 and Dlg.";
RL   PLoS ONE 9:e82894-e82894(2014).
RN   [9]
RP   ERRATUM OF PUBMED:24503895.
RX   PubMed=25268382; DOI=10.1371/journal.pone.0110062;
RA   Murakami S., Sakurai-Yageta M., Maruyama T., Murakami Y.;
RT   "Trans-homophilic interaction of CADM1 activates PI3K by forming a complex
RT   with MAGuK-family proteins MPP3 and Dlg.";
RL   PLoS ONE 9:e110062-e110062(2014).
CC   -!- FUNCTION: Participates in cell spreading through the phosphoinositide-
CC       3-kinase (PI3K) pathway by connecting CADM1 to DLG1 and the regulatory
CC       subunit of phosphoinositide-3-kinase (PI3K) (PubMed:24503895).
CC       Stabilizes HTR2C at the plasma membrane and prevents its
CC       desensitization. May participates in the maintenance of adherens
CC       junctions (By similarity). {ECO:0000250|UniProtKB:O88910,
CC       ECO:0000269|PubMed:24503895}.
CC   -!- SUBUNIT: Interacts with HTR2C; this interaction stabilizes the receptor
CC       at the plasma membrane and prevents the desensitization of the HTR2C
CC       receptor-mediated calcium response (By similarity). Interacts with
CC       HTR2A (By similarity). Interacts with HTR4 (By similarity). Interacts
CC       (via PDZ domain) with CADM1 (via C-terminus)Interacts (via PDZ domain)
CC       with CADM1; this interaction connects CADM1 with DLG1
CC       (PubMed:24503895). Interacts (via Guanylate kinase-like domain) with
CC       PALS1 (PubMed:16519681). Interacts with DLG1 (via N-terminus); this
CC       interaction connects CADM1 with DLG1 and links CADM1 with the
CC       regulatory subunit of phosphoinositide-3-kinase (PI3K) by forming a
CC       multiprotein complex and participates in cell spreading
CC       (PubMed:24503895, PubMed:16519681). {ECO:0000250|UniProtKB:O88910,
CC       ECO:0000269|PubMed:16519681, ECO:0000269|PubMed:24503895}.
CC   -!- INTERACTION:
CC       Q13368; Q9H0C5: BTBD1; NbExp=3; IntAct=EBI-716157, EBI-935503;
CC       Q13368; O14910: LIN7A; NbExp=5; IntAct=EBI-716157, EBI-2513988;
CC       Q13368; Q9HAP6: LIN7B; NbExp=8; IntAct=EBI-716157, EBI-821335;
CC       Q13368; Q9NUP9: LIN7C; NbExp=7; IntAct=EBI-716157, EBI-1171517;
CC       Q13368; P55347: PKNOX1; NbExp=3; IntAct=EBI-716157, EBI-1373569;
CC       Q13368; Q8N720: ZNF655; NbExp=3; IntAct=EBI-716157, EBI-625509;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24503895}.
CC       Apical cell membrane {ECO:0000269|PubMed:16519681}. Cell junction,
CC       adherens junction {ECO:0000269|PubMed:16519681}. Note=Localized in
CC       apical villi of Mueller glia cells (By similarity). Localized at the
CC       apical membrane in the developing cortex and colocalized with apical
CC       proteins and adherens junction proteins (By similarity). Localized at
CC       the outer limiting membrane (OLM), and outer plexiform (OPL) of retina
CC       (PubMed:16519681). {ECO:0000250|UniProtKB:O88910,
CC       ECO:0000269|PubMed:16519681}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q13368-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q13368-2; Sequence=VSP_061794;
CC   -!- TISSUE SPECIFICITY: Expressed in retina (at protein level) at the
CC       subapical region (SAR) adjacent to adherens junctions at the OLM, and
CC       at the OPL. {ECO:0000269|PubMed:16519681}.
CC   -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC       premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC       decay. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the MAGUK family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH47017.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; U37707; AAB36964.1; -; mRNA.
DR   EMBL; AM050144; CAJ18313.1; -; mRNA.
DR   EMBL; AM050145; CAJ18315.1; -; mRNA.
DR   EMBL; AK313045; BAG35877.1; -; mRNA.
DR   EMBL; AC003098; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471178; EAW51663.1; -; Genomic_DNA.
DR   EMBL; CH471178; EAW51664.1; -; Genomic_DNA.
DR   EMBL; CH471178; EAW51665.1; -; Genomic_DNA.
DR   EMBL; BC047017; AAH47017.1; ALT_INIT; mRNA.
DR   EMBL; BC056865; AAH56865.1; -; mRNA.
DR   CCDS; CCDS42344.1; -. [Q13368-1]
DR   PIR; G02165; G02165.
DR   RefSeq; NP_001317162.1; NM_001330233.1.
DR   RefSeq; NP_001923.2; NM_001932.4. [Q13368-1]
DR   RefSeq; XP_006721978.1; XM_006721915.2. [Q13368-1]
DR   AlphaFoldDB; Q13368; -.
DR   SMR; Q13368; -.
DR   BioGRID; 110496; 35.
DR   CORUM; Q13368; -.
DR   IntAct; Q13368; 34.
DR   STRING; 9606.ENSP00000381430; -.
DR   iPTMnet; Q13368; -.
DR   PhosphoSitePlus; Q13368; -.
DR   BioMuta; MPP3; -.
DR   DMDM; 150421601; -.
DR   jPOST; Q13368; -.
DR   MassIVE; Q13368; -.
DR   MaxQB; Q13368; -.
DR   PaxDb; 9606-ENSP00000381425; -.
DR   PeptideAtlas; Q13368; -.
DR   ProteomicsDB; 59353; -.
DR   Antibodypedia; 8160; 360 antibodies from 28 providers.
DR   DNASU; 4356; -.
DR   Ensembl; ENST00000398389.9; ENSP00000381425.4; ENSG00000161647.19. [Q13368-1]
DR   Ensembl; ENST00000496503.5; ENSP00000465486.1; ENSG00000161647.19. [Q13368-2]
DR   GeneID; 4356; -.
DR   KEGG; hsa:4356; -.
DR   MANE-Select; ENST00000398389.9; ENSP00000381425.4; NM_001932.6; NP_001923.2.
DR   UCSC; uc002iei.5; human. [Q13368-1]
DR   AGR; HGNC:7221; -.
DR   CTD; 4356; -.
DR   DisGeNET; 4356; -.
DR   GeneCards; MPP3; -.
DR   HGNC; HGNC:7221; MPP3.
DR   HPA; ENSG00000161647; Group enriched (brain, heart muscle).
DR   MIM; 601114; gene.
DR   neXtProt; NX_Q13368; -.
DR   OpenTargets; ENSG00000161647; -.
DR   PharmGKB; PA30926; -.
DR   VEuPathDB; HostDB:ENSG00000161647; -.
DR   eggNOG; KOG0609; Eukaryota.
DR   GeneTree; ENSGT00940000157190; -.
DR   HOGENOM; CLU_001715_5_0_1; -.
DR   InParanoid; Q13368; -.
DR   OMA; IQVVMAK; -.
DR   OrthoDB; 2873706at2759; -.
DR   PhylomeDB; Q13368; -.
DR   TreeFam; TF314263; -.
DR   PathwayCommons; Q13368; -.
DR   SignaLink; Q13368; -.
DR   BioGRID-ORCS; 4356; 36 hits in 1149 CRISPR screens.
DR   GenomeRNAi; 4356; -.
DR   Pharos; Q13368; Tbio.
DR   PRO; PR:Q13368; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; Q13368; Protein.
DR   Bgee; ENSG00000161647; Expressed in apex of heart and 129 other cell types or tissues.
DR   ExpressionAtlas; Q13368; baseline and differential.
DR   GO; GO:0005912; C:adherens junction; ISS:UniProtKB.
DR   GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR   GO; GO:0005911; C:cell-cell junction; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0030165; F:PDZ domain binding; IEA:Ensembl.
DR   CDD; cd00071; GMPK; 1.
DR   CDD; cd00992; PDZ_signaling; 1.
DR   CDD; cd12039; SH3_MPP3; 1.
DR   Gene3D; 2.30.42.10; -; 1.
DR   Gene3D; 1.10.287.650; L27 domain; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR   Gene3D; 2.30.30.40; SH3 Domains; 1.
DR   InterPro; IPR008145; GK/Ca_channel_bsu.
DR   InterPro; IPR008144; Guanylate_kin-like_dom.
DR   InterPro; IPR020590; Guanylate_kinase_CS.
DR   InterPro; IPR014775; L27_C.
DR   InterPro; IPR004172; L27_dom.
DR   InterPro; IPR036892; L27_dom_sf.
DR   InterPro; IPR035604; MPP3_SH3.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR001478; PDZ.
DR   InterPro; IPR036034; PDZ_sf.
DR   InterPro; IPR036028; SH3-like_dom_sf.
DR   InterPro; IPR001452; SH3_domain.
DR   PANTHER; PTHR23122:SF33; MAGUK P55 SUBFAMILY MEMBER 3; 1.
DR   PANTHER; PTHR23122; MEMBRANE-ASSOCIATED GUANYLATE KINASE MAGUK; 1.
DR   Pfam; PF00625; Guanylate_kin; 1.
DR   Pfam; PF02828; L27; 2.
DR   Pfam; PF00595; PDZ; 1.
DR   Pfam; PF07653; SH3_2; 1.
DR   SMART; SM00072; GuKc; 1.
DR   SMART; SM00569; L27; 2.
DR   SMART; SM00228; PDZ; 1.
DR   SMART; SM00326; SH3; 1.
DR   SUPFAM; SSF101288; L27 domain; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR   SUPFAM; SSF50156; PDZ domain-like; 1.
DR   SUPFAM; SSF50044; SH3-domain; 1.
DR   PROSITE; PS00856; GUANYLATE_KINASE_1; 1.
DR   PROSITE; PS50052; GUANYLATE_KINASE_2; 1.
DR   PROSITE; PS51022; L27; 2.
DR   PROSITE; PS50106; PDZ; 1.
DR   PROSITE; PS50002; SH3; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell junction; Cell membrane; Membrane;
KW   Phosphoprotein; Reference proteome; Repeat; SH3 domain.
FT   CHAIN           1..585
FT                   /note="MAGUK p55 subfamily member 3"
FT                   /id="PRO_0000094575"
FT   DOMAIN          6..60
FT                   /note="L27 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00365"
FT   DOMAIN          61..118
FT                   /note="L27 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00365"
FT   DOMAIN          137..212
FT                   /note="PDZ"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT   DOMAIN          226..296
FT                   /note="SH3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT   DOMAIN          385..570
FT                   /note="Guanylate kinase-like"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00100"
FT   MOD_RES         307
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O88954"
FT   VAR_SEQ         316..585
FT                   /note="Missing (in isoform 2)"
FT                   /id="VSP_061794"
FT   VARIANT         585
FT                   /note="R -> G (in dbSNP:rs17742683)"
FT                   /id="VAR_050014"
FT   CONFLICT        37
FT                   /note="V -> D (in Ref. 1; AAB36964)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   585 AA;  66152 MW;  782DAE54096A4993 CRC64;
     MPVLSEDSGL HETLALLTSQ LRPDSNHKEE MGFLRDVFSE KSLSYLMKIH EKLRYYERQS
     PTPVLHSAVA LAEDVMEELQ AASVHSDERE LLQLLSTPHL RAVLMVHDTV AQKNFDPVLP
     PLPDNIDEDF DEESVKIVRL VKNKEPLGAT IRRDEHSGAV VVARIMRGGA ADRSGLVHVG
     DELREVNGIA VLHKRPDEIS QILAQSQGSI TLKIIPATQE EDRLKESKVF MRALFHYNPR
     EDRAIPCQEA GLPFQRRQVL EVVSQDDPTW WQAKRVGDTN LRAGLIPSKG FQERRLSYRR
     AAGTLPSPQS LRKPPYDQPC DKETCDCEGY LKGHYVAGLR RSFRLGCRER LGGSQEGKMS
     SGAESPELLT YEEVARYQHQ PGERPRLVVL IGSLGARLHE LKQKVVAENP QHFGVAVPHT
     TRPRKSHEKE GVEYHFVSKQ AFEADLHHNK FLEHGEYKEN LYGTSLEAIQ AVMAKNKVCL
     VDVEPEALKQ LRTSEFKPYI IFVKPAIQEK RKTPPMSPAC EDTAAPFDEQ QQEMAASAAF
     IDRHYGHLVD AVLVKEDLQG AYSQLKVVLE KLSKDTHWVP VSWVR
//