DLG4_HUMAN
ID DLG4_HUMAN Reviewed; 724 AA.
AC P78352; B7Z1S1; G5E939; Q92941; Q9UKK8;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 02-AUG-2005, sequence version 3.
DT 03-AUG-2022, entry version 238.
DE RecName: Full=Disks large homolog 4;
DE AltName: Full=Postsynaptic density protein 95 {ECO:0000305};
DE Short=PSD-95 {ECO:0000303|PubMed:20962234};
DE AltName: Full=Synapse-associated protein 90;
DE Short=SAP-90;
DE Short=SAP90;
GN Name=DLG4 {ECO:0000312|HGNC:HGNC:2903}; Synonyms=PSD95;
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 2).
RC TISSUE=Mammary gland;
RX PubMed=9286702; DOI=10.1006/geno.1997.4848;
RA Stathakis D.G., Hoover K.B., You Z., Bryant P.J.;
RT "Human postsynaptic density-95 (PSD95): location of the gene (DLG4) and
RT possible function in nonneural as well as in neural tissues.";
RL Genomics 44:71-82(1997).
RN [2]
RP SEQUENCE REVISION.
RA Stathakis D.G., Hoover K.H., You Z., Bryant P.J.;
RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10582582; DOI=10.1046/j.1471-4159.1999.0732250.x;
RA Stathakis D.G., Udar N., Sandgren O., Andreasson S., Bryant P.J., Small K.,
RA Forsman-Semb K.;
RT "Genomic organization of human DLG4, the gene encoding postsynaptic density
RT 95.";
RL J. Neurochem. 73:2250-2265(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cerebellum;
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 [5]
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 [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 84-398.
RC TISSUE=Brain;
RA Brenman J.E., Bredt D.S., Parkinson J.F., Manzana W.P., McClary J.A.;
RL Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP INTERACTION WITH KCNA1; KCNA2; KCNA3 AND KCNA4.
RX PubMed=7477295; DOI=10.1038/378085a0;
RA Kim E., Niethammer M., Rothschild A., Jan Y.N., Sheng M.;
RT "Clustering of Shaker-type K+ channels by interaction with a family of
RT membrane-associated guanylate kinases.";
RL Nature 378:85-88(1995).
RN [9]
RP INTERACTION WITH NLGN1; NLGN2 AND NLGN3.
RX PubMed=9278515; DOI=10.1126/science.277.5331.1511;
RA Irie M., Hata Y., Takeuchi M., Ichtchenko K., Toyoda A., Hirao K.,
RA Takai Y., Rosahl T.W., Suedhof T.C.;
RT "Binding of neuroligins to PSD-95.";
RL Science 277:1511-1515(1997).
RN [10]
RP INTERACTION WITH KIF13B.
RX PubMed=10859302; DOI=10.1074/jbc.m000715200;
RA Hanada T., Lin L., Tibaldi E.V., Reinherz E.L., Chishti A.H.;
RT "GAKIN, a novel kinesin-like protein associates with the human homologue of
RT the Drosophila discs large tumor suppressor in T lymphocytes.";
RL J. Biol. Chem. 275:28774-28784(2000).
RN [11]
RP INTERACTION WITH ERBB4.
RX PubMed=10725395; DOI=10.1073/pnas.97.7.3596;
RA Garcia R.A., Vasudevan K., Buonanno A.;
RT "The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at
RT neuronal synapses.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:3596-3601(2000).
RN [12]
RP ALTERNATIVE SPLICING, SUBCELLULAR LOCATION, AND INTERACTION WITH CASK AND
RP HGS.
RX PubMed=12151521; DOI=10.1523/jneurosci.22-15-06415.2002;
RA Chetkovich D.M., Bunn R.C., Kuo S.-H., Kawasaki Y., Kohwi M., Bredt D.S.;
RT "Postsynaptic targeting of alternative postsynaptic density-95 isoforms by
RT distinct mechanisms.";
RL J. Neurosci. 22:6415-6425(2002).
RN [13]
RP INTERACTION WITH LRFN1; LRFN2 AND LRFN4.
RX PubMed=16630835; DOI=10.1016/j.neuron.2006.04.005;
RA Ko J., Kim S., Chung H.S., Kim K., Han K., Kim H., Jun H., Kaang B.-K.,
RA Kim E.;
RT "SALM synaptic cell adhesion-like molecules regulate the differentiation of
RT excitatory synapses.";
RL Neuron 50:233-245(2006).
RN [14]
RP INTERACTION WITH FRMPD4.
RX PubMed=19118189; DOI=10.1523/jneurosci.3112-08.2008;
RA Lee H.W., Choi J., Shin H., Kim K., Yang J., Na M., Choi S.Y., Kang G.B.,
RA Eom S.H., Kim H., Kim E.;
RT "Preso, a novel PSD-95-interacting FERM and PDZ domain protein that
RT regulates dendritic spine morphogenesis.";
RL J. Neurosci. 28:14546-14556(2008).
RN [15]
RP INTERACTION WITH ABR AND BCR.
RX PubMed=20962234; DOI=10.1523/jneurosci.1711-10.2010;
RA Oh D., Han S., Seo J., Lee J.R., Choi J., Groffen J., Kim K., Cho Y.S.,
RA Choi H.S., Shin H., Woo J., Won H., Park S.K., Kim S.Y., Jo J.,
RA Whitcomb D.J., Cho K., Kim H., Bae Y.C., Heisterkamp N., Choi S.Y., Kim E.;
RT "Regulation of synaptic Rac1 activity, long-term potentiation maintenance,
RT and learning and memory by BCR and ABR Rac GTPase-activating proteins.";
RL J. Neurosci. 30:14134-14144(2010).
RN [16]
RP INTERACTION WITH DGKI.
RX PubMed=21119615; DOI=10.1038/emboj.2010.286;
RA Yang J., Seo J., Nair R., Han S., Jang S., Kim K., Han K., Paik S.K.,
RA Choi J., Lee S., Bae Y.C., Topham M.K., Prescott S.M., Rhee J.S.,
RA Choi S.Y., Kim E.;
RT "DGKiota regulates presynaptic release during mGluR-dependent LTD.";
RL EMBO J. 30:165-180(2011).
RN [17]
RP INTERACTION WITH ADGRB1.
RX PubMed=23782696; DOI=10.1074/jbc.m113.489757;
RA Stephenson J.R., Paavola K.J., Schaefer S.A., Kaur B., Van Meir E.G.,
RA Hall R.A.;
RT "Brain-specific angiogenesis inhibitor-1 signaling, regulation, and
RT enrichment in the postsynaptic density.";
RL J. Biol. Chem. 288:22248-22256(2013).
RN [18]
RP PALMITOYLATION.
RX PubMed=26701913; DOI=10.7554/elife.11306;
RA Lin D.T., Conibear E.;
RT "ABHD17 proteins are novel protein depalmitoylases that regulate N-Ras
RT palmitate turnover and subcellular localization.";
RL Elife 4:E11306-E11306(2015).
RN [19]
RP INTERACTION WITH GPR85.
RX PubMed=25780553; DOI=10.1186/s13229-015-0012-5;
RA Fujita-Jimbo E., Tanabe Y., Yu Z., Kojima K., Mori M., Li H., Iwamoto S.,
RA Yamagata T., Momoi M.Y., Momoi T.;
RT "The association of GPR85 with PSD-95-neuroligin complex and autism
RT spectrum disorder: a molecular analysis.";
RL Mol. Autism 6:17-17(2015).
RN [20]
RP FUNCTION, AND INTERACTION WITH ZDHHC5.
RX PubMed=26334723; DOI=10.1038/ncomms9200;
RA Brigidi G.S., Santyr B., Shimell J., Jovellar B., Bamji S.X.;
RT "Activity-regulated trafficking of the palmitoyl-acyl transferase DHHC5.";
RL Nat. Commun. 6:8200-8200(2015).
RN [21]
RP INTERACTION WITH ADAM22.
RX PubMed=27066583; DOI=10.1212/nxg.0000000000000046;
RA Muona M., Fukata Y., Anttonen A.K., Laari A., Palotie A., Pihko H.,
RA Loennqvist T., Valanne L., Somer M., Fukata M., Lehesjoki A.E.;
RT "Dysfunctional ADAM22 implicated in progressive encephalopathy with
RT cortical atrophy and epilepsy.";
RL Neurol. Genet. 2:E46-E46(2016).
RN [22]
RP INVOLVEMENT IN MRD62, AND VARIANTS MRD62 309-ARG--LEU-724 DEL AND
RP 368-ARG--LEU-724 DEL.
RX PubMed=27479843; DOI=10.1038/nn.4352;
RA Lelieveld S.H., Reijnders M.R., Pfundt R., Yntema H.G., Kamsteeg E.J.,
RA de Vries P., de Vries B.B., Willemsen M.H., Kleefstra T., Loehner K.,
RA Vreeburg M., Stevens S.J., van der Burgt I., Bongers E.M., Stegmann A.P.,
RA Rump P., Rinne T., Nelen M.R., Veltman J.A., Vissers L.E., Brunner H.G.,
RA Gilissen C.;
RT "Meta-analysis of 2,104 trios provides support for 10 new genes for
RT intellectual disability.";
RL Nat. Neurosci. 19:1194-1196(2016).
RN [23]
RP INVOLVEMENT IN MRD62.
RX PubMed=29460436; DOI=10.1111/cge.13243;
RA Moutton S., Bruel A.L., Assoum M., Chevarin M., Sarrazin E., Goizet C.,
RA Guerrot A.M., Charollais A., Charles P., Heron D., Faudet A., Houcinat N.,
RA Vitobello A., Tran-Mau-Them F., Philippe C., Duffourd Y.,
RA Thauvin-Robinet C., Faivre L.;
RT "Truncating variants of the DLG4 gene are responsible for intellectual
RT disability with marfanoid features.";
RL Clin. Genet. 93:1172-1178(2018).
RN [24]
RP STRUCTURE BY NMR OF 105-197, AND INTERACTION WITH GRIK2; KCNA4 AND CRIPT.
RX PubMed=11744724; DOI=10.1074/jbc.m109453200;
RA Piserchio A., Pellegrini M., Mehta S., Blackman S.M., Garcia E.P.,
RA Marshall J., Mierke D.F.;
RT "The PDZ1 domain of SAP90. Characterization of structure and binding.";
RL J. Biol. Chem. 277:6967-6973(2002).
CC -!- FUNCTION: Postsynaptic scaffolding protein that plays a critical role
CC in synaptogenesis and synaptic plasticity by providing a platform for
CC the postsynaptic clustering of crucial synaptic proteins. Interacts
CC with the cytoplasmic tail of NMDA receptor subunits and shaker-type
CC potassium channels. Required for synaptic plasticity associated with
CC NMDA receptor signaling. Overexpression or depletion of DLG4 changes
CC the ratio of excitatory to inhibitory synapses in hippocampal neurons.
CC May reduce the amplitude of ASIC3 acid-evoked currents by retaining the
CC channel intracellularly. May regulate the intracellular trafficking of
CC ADR1B. Also regulates AMPA-type glutamate receptor (AMPAR)
CC immobilization at postsynaptic density keeping the channels in an
CC activated state in the presence of glutamate and preventing synaptic
CC depression (By similarity). Under basal conditions, cooperates with FYN
CC to stabilize palmitoyltransferase ZDHHC5 at the synaptic membrane
CC through FYN-mediated phosphorylation of ZDHHC5 and its subsequent
CC inhibition of association with endocytic proteins (PubMed:26334723).
CC {ECO:0000250|UniProtKB:Q62108, ECO:0000269|PubMed:26334723}.
CC -!- SUBUNIT: Interacts through its PDZ domains with ANO2 and NETO1 (By
CC similarity). Interacts through its first two PDZ domains with GRIN2A,
CC GRIN2B, GRIN2C, GRIN2D (By similarity). Interacts with ASIC3 (By
CC similarity). Interacts with SEMA4C (By similarity). Interacts with
CC CXADR (By similarity). Interacts with KCND2 (By similarity). Interacts
CC with SYNGAP1 (By similarity). Interacts with LRRC4 and LRRC4B (By
CC similarity). Interacts with ERBB4 (PubMed:10725395). Interacts with
CC KCNA1, KCNA2, KCNA3 and KCNA4 (PubMed:7477295). Interacts through its
CC first PDZ domain with GRIK2, KCNA4 and CRIPT (PubMed:11744724).
CC Interacts through its second PDZ domain with the PDZ domain of NOS1 or
CC the C-terminus of CAPON (By similarity). Interacts through its third
CC PDZ domain with NLGN1 and CRIPT, and probably with NLGN2 and NLGN3
CC (PubMed:9278515). Interacts through its guanylate kinase-like domain
CC with KIF13B (PubMed:10859302). Interacts through its guanylate kinase-
CC like domain with DLGAP1/GKAP, DLGAP2, DLGAP3, DLGAP4, MAP1A, BEGAIN and
CC SIPA1L1 (By similarity). Isoform 2 interacts through an L27 domain with
CC HGS/HRS and the first L27 domain of CASK (PubMed:12151521). Interacts
CC with ADR1B and ANKS1B (By similarity). May interact with HTR2A (By
CC similarity). Interacts with ADAM22 (PubMed:27066583). Interacts with
CC KLHL17 and LGI1 (By similarity). Interacts with FRMPD4 (via C-terminus)
CC (PubMed:19118189). Interacts with LRFN1, LRFN2 and LRFN4
CC (PubMed:16630835). Interacts (via N-terminal tandem pair of PDZ
CC domains) with GPER1 (via C-terminus tail motif); the interaction is
CC direct and induces the increase of GPER1 protein levels residing at the
CC plasma membrane surface in a estradiol-independent manner (By
CC similarity). Interacts (via N-terminus tandem pair of PDZ domains) with
CC NOS1 (via N-terminal domain) (By similarity). Interacts with SHANK3 (By
CC similarity). Interacts with KCNJ4 (By similarity). Interacts with GPR85
CC (PubMed:25780553). Interacts with CACNG2 and MPP2 (via the SH3-
CC Guanylate kinase-like sub-module) (By similarity). Interacts with
CC ADGRB1 (PubMed:23782696). Found in a complex with PRR7 and GRIN1 (By
CC similarity). Interacts (via PDZ3 domain and to lesser degree via PDZ2
CC domain) with PRR7 (By similarity). Component of the postsynaptic
CC hippocampal AMPA-type glutamate receptor (AMPAR) complex, at least
CC composed of pore forming AMPAR subunits GRIA1, GRIA2 and GRIA3 and
CC AMPAR auxiliary proteins SHISA6 and SHISA7. Interacts (via its first
CC two PDZ domains) with SHISA6 and SHISA7 (via PDZ-binding motif); the
CC interaction is direct (By similarity). Interacts with RPH3A and GRIN2A;
CC this ternary complex regulates NMDA receptor composition at
CC postsynaptic membranes (By similarity). Interacts with ABR and BCR
CC (PubMed:20962234). Interacts with DGKI (via PDZ-binding motif);
CC controls the localization of DGKI to the synapse (PubMed:21119615).
CC Interacts with C9orf72, SMCR8 and RAB39B (By similarity). Interacts
CC with ZDHHC5 (PubMed:26334723). {ECO:0000250|UniProtKB:P31016,
CC ECO:0000250|UniProtKB:Q62108, ECO:0000269|PubMed:10725395,
CC ECO:0000269|PubMed:10859302, ECO:0000269|PubMed:11744724,
CC ECO:0000269|PubMed:12151521, ECO:0000269|PubMed:16630835,
CC ECO:0000269|PubMed:19118189, ECO:0000269|PubMed:20962234,
CC ECO:0000269|PubMed:21119615, ECO:0000269|PubMed:23782696,
CC ECO:0000269|PubMed:25780553, ECO:0000269|PubMed:26334723,
CC ECO:0000269|PubMed:27066583, ECO:0000269|PubMed:7477295,
CC ECO:0000269|PubMed:9278515}.
CC -!- INTERACTION:
CC P78352; Q9P021: CRIPT; NbExp=5; IntAct=EBI-80389, EBI-946968;
CC P78352; O14490: DLGAP1; NbExp=6; IntAct=EBI-80389, EBI-1753207;
CC P78352; Q15303: ERBB4; NbExp=6; IntAct=EBI-80389, EBI-80371;
CC P78352; Q12879: GRIN2A; NbExp=6; IntAct=EBI-80389, EBI-7249937;
CC P78352; Q13224: GRIN2B; NbExp=3; IntAct=EBI-80389, EBI-2256942;
CC P78352; Q14957: GRIN2C; NbExp=4; IntAct=EBI-80389, EBI-8285963;
CC P78352; Q09470: KCNA1; NbExp=2; IntAct=EBI-80389, EBI-8286599;
CC P78352; P22459: KCNA4; NbExp=2; IntAct=EBI-80389, EBI-631235;
CC P78352; O60333-3: KIF1B; NbExp=4; IntAct=EBI-80389, EBI-465669;
CC P78352; Q07954: LRP1; NbExp=2; IntAct=EBI-80389, EBI-1046087;
CC P78352; Q00987: MDM2; NbExp=3; IntAct=EBI-80389, EBI-389668;
CC P78352; Q15311: RALBP1; NbExp=2; IntAct=EBI-80389, EBI-749285;
CC P78352; O43166: SIPA1L1; NbExp=2; IntAct=EBI-80389, EBI-310678;
CC P78352; P97836-5: Dlgap1; Xeno; NbExp=3; IntAct=EBI-80389, EBI-6269434;
CC P78352; Q8VDU0: Gpsm2; Xeno; NbExp=7; IntAct=EBI-80389, EBI-7575403;
CC P78352; P10499: Kcna1; Xeno; NbExp=2; IntAct=EBI-80389, EBI-631463;
CC P78352; P63142: Kcna2; Xeno; NbExp=2; IntAct=EBI-80389, EBI-631446;
CC P78352; P15384: Kcna3; Xeno; NbExp=2; IntAct=EBI-80389, EBI-631478;
CC P78352; P15385: Kcna4; Xeno; NbExp=9; IntAct=EBI-80389, EBI-631417;
CC P78352; Q8R4I7: Neto1; Xeno; NbExp=2; IntAct=EBI-80389, EBI-2314926;
CC P78352-2; O60260-5: PRKN; NbExp=6; IntAct=EBI-631152, EBI-21251460;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12151521};
CC Lipid-anchor {ECO:0000269|PubMed:12151521}; Cytoplasmic side
CC {ECO:0000269|PubMed:12151521}. Postsynaptic density
CC {ECO:0000250|UniProtKB:P31016}. Synapse {ECO:0000269|PubMed:12151521}.
CC Cytoplasm {ECO:0000250|UniProtKB:P31016}. Cell projection, axon
CC {ECO:0000250|UniProtKB:P31016}. Cell projection, dendritic spine
CC {ECO:0000250|UniProtKB:P31016}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:P31016}. Presynapse
CC {ECO:0000250|UniProtKB:P31016}. Note=High levels in postsynaptic
CC density of neurons in the forebrain. Also in presynaptic region of
CC inhibitory synapses formed by cerebellar basket cells on axon hillocks
CC of Purkinje cells. Suppression of neuronal activity induces synaptic
CC accumulation and clustering of DLG4. {ECO:0000250|UniProtKB:P31016}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=PSD95-alpha;
CC IsoId=P78352-1; Sequence=Displayed;
CC Name=2; Synonyms=PSD95-beta;
CC IsoId=P78352-2; Sequence=VSP_014929;
CC Name=3;
CC IsoId=P78352-3; Sequence=VSP_047247;
CC -!- TISSUE SPECIFICITY: Brain.
CC -!- DOMAIN: The PDZ domain 3 mediates interaction with ADR1B.
CC -!- DOMAIN: The L27 domain near the N-terminus of isoform 2 is required for
CC HGS/HRS-dependent targeting to postsynaptic density.
CC -!- PTM: Palmitoylated (PubMed:26701913). Palmitoylation is required for
CC targeting to postsynaptic density, plasma membrane and synapses (By
CC similarity). Palmitoylation by ZDHHC2 occurs when the synaptic activity
CC decreases and induces DLG4 synaptic clustering (By similarity).
CC Palmitoylation by ZDHHC15 regulates trafficking to the postsynaptic
CC density and function in synaptogenesis (By similarity). Palmitoylation
CC may play a role in glutamate receptor GRIA1 synapse clustering (By
CC similarity). Depalmitoylated by ABHD17A and ABHD17B and to a lesser
CC extent by ABHD17C, ABHD12, ABHD13, LYPLA1 and LYPLA2 (PubMed:26701913).
CC Undergoes rapid synaptic palmitoylation/depalmitoylation cycles during
CC neuronal development which slow down in mature neurons (By similarity).
CC {ECO:0000250|UniProtKB:P31016, ECO:0000269|PubMed:26701913}.
CC -!- PTM: Ubiquitinated by MDM2 in response to NMDA receptor activation,
CC leading to proteasome-mediated degradation of DLG4 which is required
CC for AMPA receptor endocytosis. {ECO:0000250|UniProtKB:P31016}.
CC -!- DISEASE: Intellectual developmental disorder, autosomal dominant 62
CC (MRD62) [MIM:618793]: An autosomal dominant form of intellectual
CC disability, a disorder characterized by significantly below average
CC general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period. MRD62
CC is characterized by mild to moderately impaired intellectual
CC development. {ECO:0000269|PubMed:27479843,
CC ECO:0000269|PubMed:29460436}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the MAGUK family. {ECO:0000305}.
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DR EMBL; U83192; AAC52113.1; -; mRNA.
DR EMBL; AF156495; AAD56173.1; -; Genomic_DNA.
DR EMBL; AK293835; BAH11607.1; -; mRNA.
DR EMBL; AC120057; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471108; EAW90255.1; -; Genomic_DNA.
DR EMBL; U68138; AAB07736.1; ALT_SEQ; mRNA.
DR CCDS; CCDS45599.1; -. [P78352-2]
DR CCDS; CCDS45600.1; -. [P78352-3]
DR CCDS; CCDS82050.1; -. [P78352-1]
DR PIR; T09599; T09599.
DR RefSeq; NP_001122299.1; NM_001128827.2. [P78352-3]
DR RefSeq; NP_001308004.1; NM_001321075.1. [P78352-1]
DR RefSeq; NP_001356.1; NM_001365.4. [P78352-2]
DR PDB; 1KEF; NMR; -; A=62-154.
DR PDB; 2MES; NMR; -; B=1-71.
DR PDB; 3I4W; X-ray; 1.35 A; A/B/C/D=302-403.
DR PDB; 3K82; X-ray; 1.40 A; A=305-402.
DR PDB; 3ZRT; X-ray; 3.40 A; A/B/C/D=61-249.
DR PDB; 5J7J; NMR; -; B=1-19.
DR PDB; 5JXB; X-ray; 2.90 A; A/C=309-413.
DR PDB; 6QJD; X-ray; 1.55 A; A/B/C/D=302-393.
DR PDB; 6QJF; X-ray; 1.50 A; A/B/C/D=302-403.
DR PDB; 6QJG; X-ray; 2.00 A; A/B/C/D=302-403.
DR PDB; 6QJI; X-ray; 1.50 A; A/B/C/D/E/F=305-403.
DR PDB; 6QJJ; X-ray; 1.70 A; A=305-403.
DR PDB; 6QJK; X-ray; 1.05 A; A=305-402.
DR PDB; 6QJL; X-ray; 1.04 A; A/B=302-403.
DR PDB; 6QJN; X-ray; 1.80 A; A/B=302-403.
DR PDB; 6SPV; X-ray; 2.04 A; A=55-249.
DR PDB; 6SPZ; X-ray; 2.08 A; A=55-249.
DR PDBsum; 1KEF; -.
DR PDBsum; 2MES; -.
DR PDBsum; 3I4W; -.
DR PDBsum; 3K82; -.
DR PDBsum; 3ZRT; -.
DR PDBsum; 5J7J; -.
DR PDBsum; 5JXB; -.
DR PDBsum; 6QJD; -.
DR PDBsum; 6QJF; -.
DR PDBsum; 6QJG; -.
DR PDBsum; 6QJI; -.
DR PDBsum; 6QJJ; -.
DR PDBsum; 6QJK; -.
DR PDBsum; 6QJL; -.
DR PDBsum; 6QJN; -.
DR PDBsum; 6SPV; -.
DR PDBsum; 6SPZ; -.
DR AlphaFoldDB; P78352; -.
DR BMRB; P78352; -.
DR SASBDB; P78352; -.
DR SMR; P78352; -.
DR BioGRID; 108086; 135.
DR ComplexPortal; CPX-6186; Scribble cell polarity complex, DLG4-LLGL2-SCRIB variant.
DR ComplexPortal; CPX-6189; Scribble cell polarity complex, DLG4-LLGL1-SCRIB variant.
DR CORUM; P78352; -.
DR DIP; DIP-30919N; -.
DR IntAct; P78352; 79.
DR MINT; P78352; -.
DR STRING; 9606.ENSP00000382428; -.
DR BindingDB; P78352; -.
DR ChEMBL; CHEMBL5666; -.
DR DrugBank; DB00536; Guanidine.
DR DrugBank; DB01972; Guanosine-5'-Monophosphate.
DR MoonDB; P78352; Predicted.
DR TCDB; 8.A.24.1.3; the ezrin/radixin/moesin-binding phosphoprotein 50 (ebp50) family.
DR iPTMnet; P78352; -.
DR PhosphoSitePlus; P78352; -.
DR SwissPalm; P78352; -.
DR BioMuta; DLG4; -.
DR DMDM; 71658825; -.
DR EPD; P78352; -.
DR jPOST; P78352; -.
DR MassIVE; P78352; -.
DR MaxQB; P78352; -.
DR PaxDb; P78352; -.
DR PeptideAtlas; P78352; -.
DR PRIDE; P78352; -.
DR ProteomicsDB; 33819; -.
DR ProteomicsDB; 57584; -. [P78352-1]
DR ProteomicsDB; 57585; -. [P78352-2]
DR ABCD; P78352; 3 sequenced antibodies.
DR Antibodypedia; 1930; 866 antibodies from 50 providers.
DR DNASU; 1742; -.
DR Ensembl; ENST00000302955.11; ENSP00000307471.6; ENSG00000132535.22. [P78352-3]
DR Ensembl; ENST00000399506.9; ENSP00000382425.2; ENSG00000132535.22. [P78352-1]
DR Ensembl; ENST00000648172.8; ENSP00000497806.3; ENSG00000132535.22. [P78352-2]
DR GeneID; 1742; -.
DR KEGG; hsa:1742; -.
DR MANE-Select; ENST00000399506.9; ENSP00000382425.2; NM_001321075.3; NP_001308004.1.
DR UCSC; uc002get.5; human. [P78352-1]
DR CTD; 1742; -.
DR DisGeNET; 1742; -.
DR GeneCards; DLG4; -.
DR HGNC; HGNC:2903; DLG4.
DR HPA; ENSG00000132535; Group enriched (brain, pituitary gland, retina).
DR MalaCards; DLG4; -.
DR MIM; 602887; gene.
DR MIM; 618793; phenotype.
DR neXtProt; NX_P78352; -.
DR OpenTargets; ENSG00000132535; -.
DR PharmGKB; PA27359; -.
DR VEuPathDB; HostDB:ENSG00000132535; -.
DR eggNOG; KOG0708; Eukaryota.
DR GeneTree; ENSGT00940000157956; -.
DR HOGENOM; CLU_001715_4_2_1; -.
DR InParanoid; P78352; -.
DR OMA; SISESQX; -.
DR OrthoDB; 807583at2759; -.
DR PhylomeDB; P78352; -.
DR TreeFam; TF323171; -.
DR PathwayCommons; P78352; -.
DR Reactome; R-HSA-1236394; Signaling by ERBB4.
DR Reactome; R-HSA-399719; Trafficking of AMPA receptors.
DR Reactome; R-HSA-438066; Unblocking of NMDA receptors, glutamate binding and activation.
DR Reactome; R-HSA-442982; Ras activation upon Ca2+ influx through NMDA receptor.
DR Reactome; R-HSA-447038; NrCAM interactions.
DR Reactome; R-HSA-451308; Activation of Ca-permeable Kainate Receptor.
DR Reactome; R-HSA-5625900; RHO GTPases activate CIT.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-HSA-5682910; LGI-ADAM interactions.
DR Reactome; R-HSA-6794361; Neurexins and neuroligins.
DR Reactome; R-HSA-8849932; Synaptic adhesion-like molecules.
DR Reactome; R-HSA-9609736; Assembly and cell surface presentation of NMDA receptors.
DR Reactome; R-HSA-9617324; Negative regulation of NMDA receptor-mediated neuronal transmission.
DR Reactome; R-HSA-9620244; Long-term potentiation.
DR SignaLink; P78352; -.
DR SIGNOR; P78352; -.
DR BioGRID-ORCS; 1742; 12 hits in 1080 CRISPR screens.
DR ChiTaRS; DLG4; human.
DR EvolutionaryTrace; P78352; -.
DR GeneWiki; DLG4; -.
DR GenomeRNAi; 1742; -.
DR Pharos; P78352; Tchem.
DR PRO; PR:P78352; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P78352; protein.
DR Bgee; ENSG00000132535; Expressed in right hemisphere of cerebellum and 120 other tissues.
DR ExpressionAtlas; P78352; baseline and differential.
DR Genevisible; P78352; HS.
DR GO; GO:0005912; C:adherens junction; IC:ComplexPortal.
DR GO; GO:0032281; C:AMPA glutamate receptor complex; ISS:BHF-UCL.
DR GO; GO:0099031; C:anchored component of postsynaptic density membrane; IEA:Ensembl.
DR GO; GO:0030054; C:cell junction; ISS:BHF-UCL.
DR GO; GO:0044300; C:cerebellar mossy fiber; IEA:Ensembl.
DR GO; GO:0030863; C:cortical cytoskeleton; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0032839; C:dendrite cytoplasm; ISS:BHF-UCL.
DR GO; GO:0043197; C:dendritic spine; ISS:ParkinsonsUK-UCL.
DR GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:BHF-UCL.
DR GO; GO:0060076; C:excitatory synapse; ISS:BHF-UCL.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:BHF-UCL.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0044224; C:juxtaparanode region of axon; ISS:BHF-UCL.
DR GO; GO:0031594; C:neuromuscular junction; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0044306; C:neuron projection terminus; ISS:BHF-UCL.
DR GO; GO:0044309; C:neuron spine; ISS:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0014069; C:postsynaptic density; ISS:UniProtKB.
DR GO; GO:0098839; C:postsynaptic density membrane; IBA:GO_Central.
DR GO; GO:0045211; C:postsynaptic membrane; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IDA:BHF-UCL.
DR GO; GO:0097060; C:synaptic membrane; ISS:ARUK-UCL.
DR GO; GO:0008021; C:synaptic vesicle; ISS:BHF-UCL.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IEA:Ensembl.
DR GO; GO:0033130; F:acetylcholine receptor binding; ISS:BHF-UCL.
DR GO; GO:0031697; F:beta-1 adrenergic receptor binding; ISS:BHF-UCL.
DR GO; GO:0031698; F:beta-2 adrenergic receptor binding; IEA:Ensembl.
DR GO; GO:0031748; F:D1 dopamine receptor binding; ISS:BHF-UCL.
DR GO; GO:0005109; F:frizzled binding; IEA:Ensembl.
DR GO; GO:0019865; F:immunoglobulin binding; IEA:Ensembl.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; ISS:BHF-UCL.
DR GO; GO:0019900; F:kinase binding; IDA:MGI.
DR GO; GO:0019894; F:kinesin binding; IEA:Ensembl.
DR GO; GO:0097109; F:neuroligin family protein binding; ISS:BHF-UCL.
DR GO; GO:0031812; F:P2Y1 nucleotide receptor binding; ISS:BHF-UCL.
DR GO; GO:0030165; F:PDZ domain binding; ISS:BHF-UCL.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0019903; F:protein phosphatase binding; ISS:BHF-UCL.
DR GO; GO:0044877; F:protein-containing complex binding; ISS:BHF-UCL.
DR GO; GO:0097110; F:scaffold protein binding; ISS:BHF-UCL.
DR GO; GO:0098919; F:structural constituent of postsynaptic density; IEA:Ensembl.
DR GO; GO:0097113; P:AMPA glutamate receptor clustering; ISS:BHF-UCL.
DR GO; GO:0098609; P:cell-cell adhesion; IBA:GO_Central.
DR GO; GO:0035865; P:cellular response to potassium ion; ISS:ARUK-UCL.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0060997; P:dendritic spine morphogenesis; ISS:BHF-UCL.
DR GO; GO:0045184; P:establishment of protein localization; IDA:BHF-UCL.
DR GO; GO:0045197; P:establishment or maintenance of epithelial cell apical/basal polarity; IC:ComplexPortal.
DR GO; GO:0007612; P:learning; TAS:ProtInc.
DR GO; GO:0035641; P:locomotory exploration behavior; IEA:Ensembl.
DR GO; GO:0002091; P:negative regulation of receptor internalization; ISS:BHF-UCL.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0050885; P:neuromuscular process controlling balance; IEA:Ensembl.
DR GO; GO:0099645; P:neurotransmitter receptor localization to postsynaptic specialization membrane; IEA:Ensembl.
DR GO; GO:1904719; P:positive regulation of AMPA glutamate receptor clustering; IEA:Ensembl.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISS:BHF-UCL.
DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; ISS:BHF-UCL.
DR GO; GO:0150012; P:positive regulation of neuron projection arborization; ISS:ARUK-UCL.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; ISS:ARUK-UCL.
DR GO; GO:0050806; P:positive regulation of synaptic transmission; ISS:BHF-UCL.
DR GO; GO:0098970; P:postsynaptic neurotransmitter receptor diffusion trapping; IBA:GO_Central.
DR GO; GO:0035418; P:protein localization to synapse; IDA:BHF-UCL.
DR GO; GO:0065003; P:protein-containing complex assembly; IDA:BHF-UCL.
DR GO; GO:0043113; P:receptor clustering; IBA:GO_Central.
DR GO; GO:0097120; P:receptor localization to synapse; ISS:BHF-UCL.
DR GO; GO:2000821; P:regulation of grooming behavior; IEA:Ensembl.
DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; ISS:BHF-UCL.
DR GO; GO:2000310; P:regulation of NMDA receptor activity; ISS:BHF-UCL.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0035176; P:social behavior; IEA:Ensembl.
DR GO; GO:0016188; P:synaptic vesicle maturation; ISS:BHF-UCL.
DR GO; GO:0071625; P:vocalization behavior; IEA:Ensembl.
DR Gene3D; 2.30.42.10; -; 3.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR016313; DLG1-like.
DR InterPro; IPR019590; DLG1_PEST_dom.
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; IPR019583; PDZ_assoc.
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; PF10608; MAGUK_N_PEST; 1.
DR Pfam; PF00595; PDZ; 3.
DR Pfam; PF10600; PDZ_assoc; 1.
DR Pfam; PF00018; SH3_1; 1.
DR PIRSF; PIRSF001741; MAGUK_DLGH; 1.
DR SMART; SM00072; GuKc; 1.
DR SMART; SM01277; MAGUK_N_PEST; 1.
DR SMART; SM00228; PDZ; 3.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF50156; SSF50156; 3.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00856; GUANYLATE_KINASE_1; 1.
DR PROSITE; PS50052; GUANYLATE_KINASE_2; 1.
DR PROSITE; PS50106; PDZ; 3.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cell projection;
KW Cytoplasm; Disease variant; Intellectual disability; Lipoprotein; Membrane;
KW Palmitate; Phosphoprotein; Reference proteome; Repeat; SH3 domain; Synapse;
KW Ubl conjugation.
FT CHAIN 1..724
FT /note="Disks large homolog 4"
FT /id="PRO_0000094560"
FT DOMAIN 65..151
FT /note="PDZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 160..246
FT /note="PDZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 313..393
FT /note="PDZ 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 428..498
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 534..709
FT /note="Guanylate kinase-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00100"
FT REGION 15..35
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 73
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62108"
FT MOD_RES 142
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62108"
FT MOD_RES 240
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q62108"
FT MOD_RES 295
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31016"
FT MOD_RES 415
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62108"
FT MOD_RES 418
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62108"
FT MOD_RES 420
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q62108"
FT MOD_RES 422
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62108"
FT MOD_RES 425
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62108"
FT MOD_RES 449
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31016"
FT MOD_RES 480
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62108"
FT MOD_RES 580
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q62108"
FT MOD_RES 606
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62108"
FT MOD_RES 654
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31016"
FT MOD_RES 715
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q62108"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P31016"
FT LIPID 5
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P31016"
FT VAR_SEQ 1..10
FT /note="MDCLCIVTTK -> MSQRPRAPRSALWLLAPPLLRWAPPLLTVLHSDLFQAL
FT LDILDYYEASLSESQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9286702"
FT /id="VSP_014929"
FT VAR_SEQ 51..53
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_047247"
FT VARIANT 309..724
FT /note="Missing (in MRD62)"
FT /evidence="ECO:0000269|PubMed:27479843"
FT /id="VAR_083773"
FT VARIANT 368..724
FT /note="Missing (in MRD62)"
FT /evidence="ECO:0000269|PubMed:27479843"
FT /id="VAR_083774"
FT HELIX 2..15
FT /evidence="ECO:0007829|PDB:2MES"
FT STRAND 61..69
FT /evidence="ECO:0007829|PDB:6SPV"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:1KEF"
FT STRAND 76..85
FT /evidence="ECO:0007829|PDB:6SPV"
FT STRAND 87..90
FT /evidence="ECO:0007829|PDB:1KEF"
FT STRAND 94..99
FT /evidence="ECO:0007829|PDB:6SPV"
FT HELIX 104..108
FT /evidence="ECO:0007829|PDB:6SPV"
FT STRAND 116..120
FT /evidence="ECO:0007829|PDB:6SPV"
FT STRAND 126..128
FT /evidence="ECO:0007829|PDB:1KEF"
FT HELIX 130..138
FT /evidence="ECO:0007829|PDB:6SPV"
FT STRAND 142..151
FT /evidence="ECO:0007829|PDB:6SPV"
FT STRAND 157..164
FT /evidence="ECO:0007829|PDB:6SPV"
FT STRAND 171..176
FT /evidence="ECO:0007829|PDB:6SPV"
FT STRAND 178..180
FT /evidence="ECO:0007829|PDB:3ZRT"
FT STRAND 189..194
FT /evidence="ECO:0007829|PDB:6SPV"
FT HELIX 199..203
FT /evidence="ECO:0007829|PDB:6SPV"
FT STRAND 211..215
FT /evidence="ECO:0007829|PDB:6SPV"
FT HELIX 225..233
FT /evidence="ECO:0007829|PDB:6SPV"
FT STRAND 237..245
FT /evidence="ECO:0007829|PDB:6SPV"
FT STRAND 312..317
FT /evidence="ECO:0007829|PDB:6QJL"
FT STRAND 324..331
FT /evidence="ECO:0007829|PDB:6QJL"
FT STRAND 334..341
FT /evidence="ECO:0007829|PDB:6QJL"
FT STRAND 343..345
FT /evidence="ECO:0007829|PDB:5JXB"
FT HELIX 346..350
FT /evidence="ECO:0007829|PDB:6QJL"
FT STRAND 357..362
FT /evidence="ECO:0007829|PDB:6QJL"
FT HELIX 372..380
FT /evidence="ECO:0007829|PDB:6QJL"
FT STRAND 384..392
FT /evidence="ECO:0007829|PDB:6QJL"
FT HELIX 394..400
FT /evidence="ECO:0007829|PDB:6QJL"
FT CONFLICT P78352-2:46
FT /note="E -> V (in Ref. 3; AAD56173)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 724 AA; 80495 MW; 7922D3F220F9A101 CRC64;
MDCLCIVTTK KYRYQDEDTP PLEHSPAHLP NQANSPPVIV NTDTLEAPGY ELQVNGTEGE
MEYEEITLER GNSGLGFSIA GGTDNPHIGD DPSIFITKII PGGAAAQDGR LRVNDSILFV
NEVDVREVTH SAAVEALKEA GSIVRLYVMR RKPPAEKVME IKLIKGPKGL GFSIAGGVGN
QHIPGDNSIY VTKIIEGGAA HKDGRLQIGD KILAVNSVGL EDVMHEDAVA ALKNTYDVVY
LKVAKPSNAY LSDSYAPPDI TTSYSQHLDN EISHSSYLGT DYPTAMTPTS PRRYSPVAKD
LLGEEDIPRE PRRIVIHRGS TGLGFNIVGG EDGEGIFISF ILAGGPADLS GELRKGDQIL
SVNGVDLRNA SHEQAAIALK NAGQTVTIIA QYKPEEYSRF EAKIHDLREQ LMNSSLGSGT
ASLRSNPKRG FYIRALFDYD KTKDCGFLSQ ALSFRFGDVL HVIDASDEEW WQARRVHSDS
ETDDIGFIPS KRRVERREWS RLKAKDWGSS SGSQGREDSV LSYETVTQME VHYARPIIIL
GPTKDRANDD LLSEFPDKFG SCVPHTTRPK REYEIDGRDY HFVSSREKME KDIQAHKFIE
AGQYNSHLYG TSVQSVREVA EQGKHCILDV SANAVRRLQA AHLHPIAIFI RPRSLENVLE
INKRITEEQA RKAFDRATKL EQEFTECFSA IVEGDSFEEI YHKVKRVIED LSGPYIWVPA
RERL
