MPP4_HUMAN
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 03-AUG-2022, entry version 177.
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}.
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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 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; Q96JB8; -.
DR PeptideAtlas; Q96JB8; -.
DR PRIDE; 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; 57 antibodies from 14 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 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; EAQYWQF; -.
DR OrthoDB; 531106at2759; -.
DR PhylomeDB; Q96JB8; -.
DR TreeFam; TF314263; -.
DR PathwayCommons; Q96JB8; -.
DR SignaLink; Q96JB8; -.
DR BioGRID-ORCS; 58538; 7 hits in 1064 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 81 other tissues.
DR ExpressionAtlas; Q96JB8; baseline and differential.
DR Genevisible; Q96JB8; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0005912; C:adherens junction; IDA:UniProtKB.
DR GO; GO:0005911; C:cell-cell junction; IBA:GO_Central.
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; cd12034; SH3_MPP4; 1.
DR Gene3D; 2.30.42.10; -; 1.
DR Gene3D; 3.40.50.300; -; 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 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; SSF101288; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR SUPFAM; SSF52540; SSF52540; 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; 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
