ID MPP4_HUMAN Reviewed; 637 AA. AC Q96JB8; C9IZK4; Q53TT3; Q6ZNH6; Q96Q43; Q96Q44; DT 10-JAN-2003, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 2. DT 24-JAN-2024, entry version 184. DE RecName: Full=MAGUK p55 subfamily member 4; DE AltName: Full=Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 5 protein; DE AltName: Full=Discs large homolog 6; GN Name=MPP4; Synonyms=ALS2CR5, DLG6; 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 VARIANT RP SER-44. RC TISSUE=Retina; RX PubMed=11414766; DOI=10.1006/geno.2001.6559; RA Stoehr H., Weber B.H.F.; RT "Cloning and characterization of the human retina-specific gene MPP4, a RT novel member of the p55 subfamily of MAGUK proteins."; RL Genomics 74:377-384(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), AND VARIANT SER-44. RC TISSUE=Brain; RX PubMed=11586298; DOI=10.1038/ng1001-166; RA Hadano S., Hand C.K., Osuga H., Yanagisawa Y., Otomo A., Devon R.S., RA Miyamoto N., Showguchi-Miyata J., Okada Y., Singaraja R., Figlewicz D.A., RA Kwiatkowski T., Hosler B.A., Sagie T., Skaug J., Nasir J., Brown R.H. Jr., RA Scherer S.W., Rouleau G.A., Hayden M.R., Ikeda J.-E.; RT "A gene encoding a putative GTPase regulator is mutated in familial RT amyotrophic lateral sclerosis 2."; RL Nat. Genet. 29:166-173(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND VARIANT SER-44. RC TISSUE=Teratocarcinoma; 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=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [5] RP IDENTIFICATION (ISOFORM 5), AND TISSUE SPECIFICITY. RX PubMed=12384283; DOI=10.1016/s0378-1119(02)00872-7; RA Conte I., Lestingi M., den Hollander A., Miano M.G., Alfano G., Circolo D., RA Pugliese M., Testa F., Simonelli F., Rinaldi E., Baiget M., Banfi S., RA Ciccodicola A.; RT "Characterization of MPP4, a gene highly expressed in photoreceptor cells, RT and mutation analysis in retinitis pigmentosa."; RL Gene 297:33-38(2002). RN [6] RP INTERACTION WITH CRB1 AND PALS1, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=15914641; DOI=10.1167/iovs.04-1417; RA Kantardzhieva A., Gosens I., Alexeeva S., Punte I.M., Versteeg I., RA Krieger E., Neefjes-Mol C.A., den Hollander A.I., Letteboer S.J.F., RA Klooster J., Cremers F.P.M., Roepman R., Wijnholds J.; RT "MPP5 recruits MPP4 to the CRB1 complex in photoreceptors."; RL Invest. Ophthalmol. Vis. Sci. 46:2192-2201(2005). RN [7] RP TISSUE SPECIFICITY. RX PubMed=15558731; DOI=10.1002/cne.20367; RA Stoehr H., Molday L.L., Molday R.S., Weber B.H.F., Biedermann B., RA Reichenbach A., Kraemer F.; RT "Membrane-associated guanylate kinase proteins MPP4 and MPP5 associate with RT Veli3 at distinct intercellular junctions of the neurosensory retina."; RL J. Comp. Neurol. 481:31-41(2005). RN [8] RP INTERACTION WITH FASLG. RX PubMed=19807924; DOI=10.1186/1471-2172-10-53; RA Voss M., Lettau M., Janssen O.; RT "Identification of SH3 domain interaction partners of human FasL (CD178) by RT phage display screening."; RL BMC Immunol. 10:53-53(2009). CC -!- FUNCTION: May play a role in retinal photoreceptors development. CC {ECO:0000250}. CC -!- SUBUNIT: Interacts with MPDZ. May interact with GRIA2 (By similarity). CC Forms a complex with CRB1 and PALS1. Interacts with FASLG. CC {ECO:0000250, ECO:0000269|PubMed:15914641, CC ECO:0000269|PubMed:19807924}. CC -!- INTERACTION: CC Q96JB8; P82279: CRB1; NbExp=2; IntAct=EBI-2483346, EBI-1048648; CC Q96JB8; Q8N3R9: PALS1; NbExp=5; IntAct=EBI-2483346, EBI-2513978; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15914641}. CC Note=Detected at the outer limiting membrane (OLM) and in the outer CC plexiform layer (OPL) of the retina. At the OLM, detected apical to the CC adherens junction (AJ). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=Q96JB8-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96JB8-2; Sequence=VSP_003159, VSP_003160; CC Name=3; CC IsoId=Q96JB8-3; Sequence=VSP_003157, VSP_003158; CC Name=4; CC IsoId=Q96JB8-4; Sequence=VSP_003157, VSP_013992, VSP_013993; CC Name=5; CC IsoId=Q96JB8-5; Sequence=VSP_013991; CC -!- TISSUE SPECIFICITY: Expressed in the retina (at protein level). Highly CC expressed in the retina. Lower amounts are detected in brain, testis, CC ARPE-19, RPE/choroid and fetal eye. Isoform 5 is retina-specific. CC {ECO:0000269|PubMed:11414766, ECO:0000269|PubMed:12384283, CC ECO:0000269|PubMed:15558731, ECO:0000269|PubMed:15914641}. CC -!- SIMILARITY: Belongs to the MAGUK family. {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; AF316032; AAK71862.1; -; mRNA. DR EMBL; AB053302; BAB69012.1; -; mRNA. DR EMBL; AB053303; BAB69013.1; -; mRNA. DR EMBL; AK131208; BAD18399.1; -; mRNA. DR EMBL; AC007279; AAY15057.1; -; Genomic_DNA. DR CCDS; CCDS46491.1; -. [Q96JB8-1] DR RefSeq; NP_149055.1; NM_033066.2. [Q96JB8-1] DR AlphaFoldDB; Q96JB8; -. DR SMR; Q96JB8; -. DR BioGRID; 121853; 2. DR CORUM; Q96JB8; -. DR IntAct; Q96JB8; 3. DR STRING; 9606.ENSP00000387278; -. DR GlyCosmos; Q96JB8; 1 site, 1 glycan. DR GlyGen; Q96JB8; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q96JB8; -. DR PhosphoSitePlus; Q96JB8; -. DR BioMuta; MPP4; -. DR DMDM; 296438297; -. DR MassIVE; Q96JB8; -. DR PaxDb; 9606-ENSP00000387278; -. DR PeptideAtlas; Q96JB8; -. DR ProteomicsDB; 76934; -. [Q96JB8-1] DR ProteomicsDB; 76935; -. [Q96JB8-2] DR ProteomicsDB; 76936; -. [Q96JB8-3] DR ProteomicsDB; 76937; -. [Q96JB8-4] DR ProteomicsDB; 76938; -. [Q96JB8-5] DR Antibodypedia; 34145; 62 antibodies from 15 providers. DR DNASU; 58538; -. DR Ensembl; ENST00000315506.11; ENSP00000319363.7; ENSG00000082126.18. [Q96JB8-2] DR Ensembl; ENST00000409474.8; ENSP00000387278.3; ENSG00000082126.18. [Q96JB8-1] DR GeneID; 58538; -. DR KEGG; hsa:58538; -. DR MANE-Select; ENST00000409474.8; ENSP00000387278.3; NM_033066.3; NP_149055.2. DR UCSC; uc002uyk.5; human. [Q96JB8-1] DR AGR; HGNC:13680; -. DR CTD; 58538; -. DR DisGeNET; 58538; -. DR GeneCards; MPP4; -. DR HGNC; HGNC:13680; MPP4. DR HPA; ENSG00000082126; Tissue enriched (retina). DR MalaCards; MPP4; -. DR MIM; 606575; gene. DR neXtProt; NX_Q96JB8; -. DR OpenTargets; ENSG00000082126; -. DR PharmGKB; PA30927; -. DR VEuPathDB; HostDB:ENSG00000082126; -. DR eggNOG; KOG0609; Eukaryota. DR GeneTree; ENSGT00940000156444; -. DR InParanoid; Q96JB8; -. DR OMA; PACWIRP; -. DR OrthoDB; 2873706at2759; -. DR PhylomeDB; Q96JB8; -. DR TreeFam; TF314263; -. DR PathwayCommons; Q96JB8; -. DR SignaLink; Q96JB8; -. DR BioGRID-ORCS; 58538; 8 hits in 1142 CRISPR screens. DR ChiTaRS; MPP4; human. DR GenomeRNAi; 58538; -. DR Pharos; Q96JB8; Tdark. DR PRO; PR:Q96JB8; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q96JB8; Protein. DR Bgee; ENSG00000082126; Expressed in secondary oocyte and 82 other cell types or tissues. DR ExpressionAtlas; Q96JB8; baseline and differential. DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA. DR GO; GO:0005912; C:adherens junction; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0035418; P:protein localization to synapse; ISM:UniProtKB. DR CDD; cd00071; GMPK; 1. DR CDD; cd00992; PDZ_signaling; 1. DR CDD; cd12034; SH3_MPP4; 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; IPR035600; MPP4_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:SF34; MAGUK P55 SUBFAMILY MEMBER 4; 1. DR PANTHER; PTHR23122; MEMBRANE-ASSOCIATED GUANYLATE KINASE MAGUK; 1. DR Pfam; PF00625; Guanylate_kin; 1. DR Pfam; PF02828; L27; 1. DR Pfam; PF00595; PDZ; 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. DR Genevisible; Q96JB8; HS. PE 1: Evidence at protein level; KW Alternative splicing; Coiled coil; Cytoplasm; Reference proteome; Repeat; KW SH3 domain. FT CHAIN 1..637 FT /note="MAGUK p55 subfamily member 4" FT /id="PRO_0000094577" FT DOMAIN 24..80 FT /note="L27 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00365" FT DOMAIN 87..137 FT /note="L27 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00365" FT DOMAIN 154..235 FT /note="PDZ" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT DOMAIN 242..312 FT /note="SH3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 427..616 FT /note="Guanylate kinase-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00100" FT REGION 1..22 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 568..621 FT /evidence="ECO:0000255" FT VAR_SEQ 93..164 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000305" FT /id="VSP_013991" FT VAR_SEQ 121..164 FT /note="Missing (in isoform 3 and isoform 4)" FT /evidence="ECO:0000303|PubMed:11586298, FT ECO:0000303|PubMed:14702039" FT /id="VSP_003157" FT VAR_SEQ 245..257 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11586298" FT /id="VSP_003159" FT VAR_SEQ 311..637 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:11586298" FT /id="VSP_003158" FT VAR_SEQ 311..337 FT /note="KQREFWWSQPYQPHTCLKSTLSISMEE -> WSFALVAQAGVQWHYLDSLQP FT LPPGFKRFSCLSLPRSWDYI (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_013992" FT VAR_SEQ 332..363 FT /note="SISMEEEDDMKIDEKCVEADEETFESEELSED -> Y (in isoform FT 2)" FT /evidence="ECO:0000303|PubMed:11586298" FT /id="VSP_003160" FT VAR_SEQ 358..362 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_013993" FT VARIANT 44 FT /note="G -> S (in dbSNP:rs6725443)" FT /evidence="ECO:0000269|PubMed:11414766, FT ECO:0000269|PubMed:11586298, ECO:0000269|PubMed:14702039" FT /id="VAR_022643" FT VARIANT 562 FT /note="V -> I (in dbSNP:rs11894115)" FT /id="VAR_050015" FT CONFLICT 5 FT /note="D -> G (in Ref. 3; BAD18399)" FT /evidence="ECO:0000305" SQ SEQUENCE 637 AA; 72779 MW; B180AE8635E32CDD CRC64; MIQSDKGADP PDKKDMKLST ATNPQNGLSQ ILRLVLQELS LFYGRDVNGV CLLYDLLHSP WLQALLKIYD CLQEFKEKKL VPATPHAQVL SYEVVELLRE TPTSPEIQEL RQMLQAPHFK ALLSAHDTIA QKDFEPLLPP LPDNIPESEE AMRIVCLVKN QQPLGATIKR HEMTGDILVA RIIHGGLAER SGLLYAGDKL VEVNGVSVEG LDPEQVIHIL AMSRGTIMFK VVPVSDPPVN SQQMVYVRAM TEYWPQEDPD IPCMDAGLPF QKGDILQIVD QNDALWWQAR KISDPATCAG LVPSNHLLKR KQREFWWSQP YQPHTCLKST LSISMEEEDD MKIDEKCVEA DEETFESEEL SEDKEEFVGY GQKFFIAGFR RSMRLCRRKS HLSPLHASVC CTGSCYSAVG APYEEVVRYQ RRPSDKYRLI VLMGPSGVGV NELRRQLIEF NPSHFQSAVP HTTRTKKSYE MNGREYHYVS KETFENLIYS HRMLEYGEYK GHLYGTSVDA VQTVLVEGKI CVMDLEPQDI QGVRTHELKP YVIFIKPSNM RCMKQSRKNA KVITDYYVDM KFKDEDLQEM ENLAQRMETQ FGQFFDHVIV NDSLHDACAQ LLSAIQKAQE EPQWVPATWI SSDTESQ //