DEPD5_HUMAN
ID DEPD5_HUMAN Reviewed; 1603 AA.
AC O75140; A6H8V6; A8MPX9; B4DH93; B9EGN9; Q5K3V5; Q5THY9; Q5THZ0; Q5THZ1;
AC Q5THZ3; Q68DR1; Q6MZX3; Q6PEZ1; Q9UGV8; Q9UH13;
DT 03-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 29-MAY-2013, sequence version 2.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=GATOR complex protein DEPDC5 {ECO:0000305};
DE AltName: Full=DEP domain-containing protein 5 {ECO:0000312|HGNC:HGNC:18423};
GN Name=DEPDC5 {ECO:0000312|HGNC:HGNC:18423};
GN Synonyms=KIAA0645 {ECO:0000312|EMBL:BAA31620.2};
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] (ISOFORMS 1; 4 AND 9).
RC TISSUE=Cerebellum;
RX PubMed=15770670; DOI=10.1002/gcc.20181;
RA Seng T.J., Ichimura K., Liu L., Tingby O., Pearson D.M., Collins V.P.;
RT "Complex chromosome 22 rearrangements in astrocytic tumors identified using
RT microsatellite and chromosome 22 tile path array analysis.";
RL Genes Chromosomes Cancer 43:181-193(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 MRNA] (ISOFORM 8).
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=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 10).
RC TISSUE=Placenta, and Testis;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 571-1603 (ISOFORM 6), AND
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 604-1603 (ISOFORM 9).
RC TISSUE=Fetal brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP FUNCTION, IDENTIFICATION IN GATOR COMPLEX, AND SUBUNIT.
RX PubMed=23723238; DOI=10.1126/science.1232044;
RA Bar-Peled L., Chantranupong L., Cherniack A.D., Chen W.W., Ottina K.A.,
RA Grabiner B.C., Spear E.D., Carter S.L., Meyerson M., Sabatini D.M.;
RT "A Tumor suppressor complex with GAP activity for the Rag GTPases that
RT signal amino acid sufficiency to mTORC1.";
RL Science 340:1100-1106(2013).
RN [10]
RP FUNCTION.
RX PubMed=25457612; DOI=10.1016/j.celrep.2014.10.019;
RA Parmigiani A., Nourbakhsh A., Ding B., Wang W., Kim Y.C., Akopiants K.,
RA Guan K.L., Karin M., Budanov A.V.;
RT "Sestrins inhibit mTORC1 kinase activation through the GATOR complex.";
RL Cell Rep. 9:1281-1291(2014).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-505, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [12]
RP SUBCELLULAR LOCATION.
RX PubMed=28199306; DOI=10.1038/nature21423;
RA Wolfson R.L., Chantranupong L., Wyant G.A., Gu X., Orozco J.M., Shen K.,
RA Condon K.J., Petri S., Kedir J., Scaria S.M., Abu-Remaileh M.,
RA Frankel W.N., Sabatini D.M.;
RT "KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to
RT regulate mTORC1.";
RL Nature 543:438-442(2017).
RN [13]
RP FUNCTION, INTERACTION WITH KLHL22, DOMAIN, UBIQUITINATION BY KLHL22, AND
RP MUTAGENESIS OF LYS-447; LYS-710; LYS-1065; LYS-1088; SER-1188; THR-1189;
RP SER-1195; SER-1201; TYR-1203; SER-1207; THR-1223; THR-1241; SER-1244;
RP THR-1250; TYR-1253; TYR-1256 AND LYS-1574.
RX PubMed=29769719; DOI=10.1038/s41586-018-0128-9;
RA Chen J., Ou Y., Yang Y., Li W., Xu Y., Xie Y., Liu Y.;
RT "KLHL22 activates amino-acid-dependent mTORC1 signalling to promote
RT tumorigenesis and ageing.";
RL Nature 557:585-589(2018).
RN [14]
RP INVOLVEMENT IN FFEVF1, AND VARIANTS FFEVF1 ASP-214; PRO-542; PRO-1081;
RP PHE-1154 AND GLN-1268.
RX PubMed=26505888; DOI=10.1002/ana.24547;
RG Epilepsy Electroclinical Study Group;
RA Ricos M.G., Hodgson B.L., Pippucci T., Saidin A., Ong Y.S., Heron S.E.,
RA Licchetta L., Bisulli F., Bayly M.A., Hughes J., Baldassari S., Palombo F.,
RA Santucci M., Meletti S., Berkovic S.F., Rubboli G., Thomas P.Q.,
RA Scheffer I.E., Tinuper P., Geoghegan J., Schreiber A.W., Dibbens L.M.;
RT "Mutations in the mammalian target of rapamycin pathway regulators NPRL2
RT and NPRL3 cause focal epilepsy.";
RL Ann. Neurol. 79:120-131(2016).
RN [15]
RP INVOLVEMENT IN FFEVF1, AND VARIANT FFEVF1 ARG-1065.
RX PubMed=27173016; DOI=10.1111/epi.13391;
RA Weckhuysen S., Marsan E., Lambrecq V., Marchal C., Morin-Brureau M.,
RA An-Gourfinkel I., Baulac M., Fohlen M., Kallay Zetchi C., Seeck M.,
RA de la Grange P., Dermaut B., Meurs A., Thomas P., Chassoux F., Leguern E.,
RA Picard F., Baulac S.;
RT "Involvement of GATOR complex genes in familial focal epilepsies and focal
RT cortical dysplasia.";
RL Epilepsia 57:994-1003(2016).
RN [16]
RP VARIANTS FFEVF1 VAL-452; ARG-1073 AND LEU-1104, AND INVOLVEMENT IN FFEVF1.
RX PubMed=23542697; DOI=10.1038/ng.2599;
RA Dibbens L.M., de Vries B., Donatello S., Heron S.E., Hodgson B.L.,
RA Chintawar S., Crompton D.E., Hughes J.N., Bellows S.T., Klein K.M.,
RA Callenbach P.M., Corbett M.A., Gardner A.E., Kivity S., Iona X.,
RA Regan B.M., Weller C.M., Crimmins D., O'Brien T.J., Guerrero-Lopez R.,
RA Mulley J.C., Dubeau F., Licchetta L., Bisulli F., Cossette P., Thomas P.Q.,
RA Gecz J., Serratosa J., Brouwer O.F., Andermann F., Andermann E.,
RA van den Maagdenberg A.M., Pandolfo M., Berkovic S.F., Scheffer I.E.;
RT "Mutations in DEPDC5 cause familial focal epilepsy with variable foci.";
RL Nat. Genet. 45:546-551(2013).
RN [17]
RP VARIANT FFEVF1 GLN-485, AND TISSUE SPECIFICITY.
RX PubMed=23542701; DOI=10.1038/ng.2601;
RA Ishida S., Picard F., Rudolf G., Noe E., Achaz G., Thomas P., Genton P.,
RA Mundwiller E., Wolff M., Marescaux C., Miles R., Baulac M., Hirsch E.,
RA Leguern E., Baulac S.;
RT "Mutations of DEPDC5 cause autosomal dominant focal epilepsies.";
RL Nat. Genet. 45:552-555(2013).
RN [18]
RP VARIANTS FFEVF1 ILE-90 AND LEU-272.
RX PubMed=24591017; DOI=10.1002/ana.24127;
RA Lal D., Reinthaler E.M., Schubert J., Muhle H., Riesch E., Kluger G.,
RA Jabbari K., Kawalia A., Baumel C., Holthausen H., Hahn A., Feucht M.,
RA Neophytou B., Haberlandt E., Becker F., Altmuller J., Thiele H.,
RA Lemke J.R., Lerche H., Nurnberg P., Sander T., Weber Y., Zimprich F.,
RA Neubauer B.A.;
RT "DEPDC5 mutations in genetic focal epilepsies of childhood.";
RL Ann. Neurol. 75:788-792(2014).
RN [19]
RP VARIANT FFEVF1 MET-864.
RX PubMed=24283814; DOI=10.1111/cge.12311;
RA Martin C., Meloche C., Rioux M.F., Nguyen D.K., Carmant L., Andermann E.,
RA Gravel M., Cossette P.;
RT "A recurrent mutation in DEPDC5 predisposes to focal epilepsies in the
RT French-Canadian population.";
RL Clin. Genet. 86:570-574(2014).
RN [20]
RP VARIANTS FFEVF1 ILE-90; LEU-272; VAL-452; GLN-485; MET-864; ARG-1073 AND
RP GLY-1162, CHARACTERIZATION OF VARIANTS FFEVF1 ILE-90; LEU-272; VAL-452;
RP GLN-485; MET-864; ARG-1073 AND GLY-1162, AND IDENTIFICATION IN GATOR
RP COMPLEX.
RX PubMed=25366275; DOI=10.1002/humu.22723;
RA van Kranenburg M., Hoogeveen-Westerveld M., Nellist M.;
RT "Preliminary functional assessment and classification of DEPDC5 variants
RT associated with focal epilepsy.";
RL Hum. Mutat. 36:200-209(2015).
CC -!- FUNCTION: As a component of the GATOR1 complex functions as an
CC inhibitor of the amino acid-sensing branch of the TORC1 pathway. The
CC GATOR1 complex strongly increases GTP hydrolysis by RRAGA and RRAGB
CC within RRAGC-containing heterodimers, thereby deactivating RRAGs,
CC releasing mTORC1 from lysosomal surface and inhibiting mTORC1
CC signaling. The GATOR1 complex is negatively regulated by GATOR2 the
CC other GATOR subcomplex in this amino acid-sensing branch of the TORC1
CC pathway. {ECO:0000269|PubMed:23723238, ECO:0000269|PubMed:25457612,
CC ECO:0000269|PubMed:29769719}.
CC -!- SUBUNIT: Within the GATOR complex, component of the GATOR1 subcomplex,
CC made of DEPDC5, NPRL2 and NPRL3. GATOR1 mediates the strong interaction
CC of the GATOR complex with RRAGA/RRAGC and RRAGB/RRAGC heterodimers.
CC Interacts (via DEP domain) with KLHL22; the interaction depends on
CC amino acid availability (PubMed:29769719).
CC {ECO:0000269|PubMed:23723238, ECO:0000269|PubMed:25366275,
CC ECO:0000269|PubMed:29769719}.
CC -!- INTERACTION:
CC O75140-2; P49368: CCT3; NbExp=3; IntAct=EBI-12366971, EBI-356673;
CC O75140-2; Q6W0C5: DPPA3; NbExp=3; IntAct=EBI-12366971, EBI-12082590;
CC O75140-2; Q13257: MAD2L1; NbExp=3; IntAct=EBI-12366971, EBI-78203;
CC O75140-2; Q9UI95: MAD2L2; NbExp=3; IntAct=EBI-12366971, EBI-77889;
CC O75140-2; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12366971, EBI-16439278;
CC O75140-2; Q96QG7: MTMR9; NbExp=3; IntAct=EBI-12366971, EBI-744593;
CC O75140-2; Q9BSW7: SYT17; NbExp=3; IntAct=EBI-12366971, EBI-745392;
CC O75140-2; O75604: USP2; NbExp=3; IntAct=EBI-12366971, EBI-743272;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P61460}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:P61460}. Lysosome membrane
CC {ECO:0000269|PubMed:28199306}. Note=Localization to lysosomes is amino
CC acid-independent. {ECO:0000269|PubMed:28199306}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Name=10;
CC IsoId=O75140-10; Sequence=Displayed;
CC Name=2;
CC IsoId=O75140-2; Sequence=VSP_014933, VSP_014934;
CC Name=4;
CC IsoId=O75140-4; Sequence=VSP_014938;
CC Name=5;
CC IsoId=O75140-5; Sequence=VSP_014941;
CC Name=6;
CC IsoId=O75140-6; Sequence=VSP_014936, VSP_014939, VSP_014940;
CC Name=8;
CC IsoId=O75140-8; Sequence=VSP_014936, VSP_014938;
CC Name=9;
CC IsoId=O75140-9; Sequence=VSP_014937;
CC Name=1;
CC IsoId=O75140-1; Sequence=VSP_014937, VSP_014938;
CC -!- TISSUE SPECIFICITY: Expressed in developing and adult brain.
CC {ECO:0000269|PubMed:23542701}.
CC -!- DOMAIN: The DEP domain mediates the interaction with KLHL22.
CC {ECO:0000269|PubMed:29769719}.
CC -!- PTM: Ubiquitinated. Amino acid-induced 'Lys-48'-linked
CC polyubiquitination of DEPDC5 by the BCR(KLHL22) ubiquitin ligase
CC complex leads to DEPDC5 proteasomal degradation and inhibition of the
CC GATOR1 complex (PubMed:29769719). Ubiquitination may occur at multiple
CC lysines (PubMed:29769719). {ECO:0000269|PubMed:29769719}.
CC -!- DISEASE: Epilepsy, familial focal, with variable foci 1 (FFEVF1)
CC [MIM:604364]: An autosomal dominant form of epilepsy characterized by
CC focal seizures arising from different cortical regions in different
CC family members. Many patients have an aura and show automatisms during
CC the seizures, whereas others may have nocturnal seizures. There is
CC often secondary generalization. Some patients show abnormal interictal
CC EEG, and some patients may have intellectual disability or autism
CC spectrum disorders. Seizure onset usually occurs in the first or second
CC decades, although later onset has been reported, and there is
CC phenotypic variability within families. Penetrance of the disorder is
CC incomplete. {ECO:0000269|PubMed:23542697, ECO:0000269|PubMed:23542701,
CC ECO:0000269|PubMed:24283814, ECO:0000269|PubMed:24591017,
CC ECO:0000269|PubMed:25366275, ECO:0000269|PubMed:26505888,
CC ECO:0000269|PubMed:27173016}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Note=Inactivating mutations and truncating deletions in the
CC genes encoding GATOR1 proteins, including DEPDC5, are detected in
CC glioblastoma and ovarian tumors and are associated with loss of
CC heterozygosity events. Inactivation of GATOR1 proteins promotes
CC constitutive localization of mTORC1 to the lysosomal membrane and
CC blocks mTORC1 inactivation following amino acid withdrawal
CC (PubMed:23723238). {ECO:0000269|PubMed:23723238}.
CC -!- MISCELLANEOUS: [Isoform 6]: 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 IML1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA31620.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAG27890.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
CC Sequence=CAH18159.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AJ698950; CAG27889.1; -; mRNA.
DR EMBL; AJ698951; CAG27890.1; ALT_SEQ; mRNA.
DR EMBL; AJ704764; CAG28924.1; -; mRNA.
DR EMBL; AB014545; BAA31620.2; ALT_INIT; mRNA.
DR EMBL; AK294987; BAG58054.1; -; mRNA.
DR EMBL; AC005004; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL022331; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z83856; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z82190; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471095; EAW59996.1; -; Genomic_DNA.
DR EMBL; BC057797; AAH57797.1; -; mRNA.
DR EMBL; BC136612; AAI36613.1; -; mRNA.
DR EMBL; BC146766; AAI46767.1; -; mRNA.
DR EMBL; BX640828; CAE45904.1; -; mRNA.
DR EMBL; CR749304; CAH18159.1; ALT_INIT; mRNA.
DR CCDS; CCDS43006.1; -. [O75140-1]
DR CCDS; CCDS43007.1; -. [O75140-2]
DR CCDS; CCDS46692.1; -. [O75140-9]
DR CCDS; CCDS56229.1; -. [O75140-8]
DR CCDS; CCDS74849.1; -. [O75140-10]
DR CCDS; CCDS87017.1; -. [O75140-4]
DR PIR; T00376; T00376.
DR RefSeq; NP_001007189.1; NM_001007188.2. [O75140-2]
DR RefSeq; NP_001129501.1; NM_001136029.2. [O75140-9]
DR RefSeq; NP_001229825.1; NM_001242896.1. [O75140-10]
DR RefSeq; NP_001229826.1; NM_001242897.1. [O75140-8]
DR RefSeq; NP_055477.1; NM_014662.4. [O75140-1]
DR RefSeq; XP_005261919.1; XM_005261862.1.
DR RefSeq; XP_011528859.1; XM_011530557.2. [O75140-9]
DR RefSeq; XP_011528860.1; XM_011530558.2.
DR RefSeq; XP_011528861.1; XM_011530559.2.
DR RefSeq; XP_011528865.1; XM_011530563.2. [O75140-8]
DR RefSeq; XP_016884598.1; XM_017029109.1.
DR RefSeq; XP_016884599.1; XM_017029110.1.
DR RefSeq; XP_016884600.1; XM_017029111.1.
DR PDB; 6CES; EM; 4.00 A; D=1-1603.
DR PDB; 6CET; EM; 4.40 A; D=1-1603.
DR PDB; 7T3A; EM; 4.00 A; A=1-1603.
DR PDB; 7T3B; EM; 3.90 A; A=1-1603.
DR PDB; 7T3C; EM; 4.00 A; A=1-1603.
DR PDBsum; 6CES; -.
DR PDBsum; 6CET; -.
DR PDBsum; 7T3A; -.
DR PDBsum; 7T3B; -.
DR PDBsum; 7T3C; -.
DR AlphaFoldDB; O75140; -.
DR SMR; O75140; -.
DR BioGRID; 115034; 65.
DR ComplexPortal; CPX-6226; GATOR1 complex.
DR CORUM; O75140; -.
DR DIP; DIP-62050N; -.
DR IntAct; O75140; 25.
DR MINT; O75140; -.
DR STRING; 9606.ENSP00000383105; -.
DR GlyGen; O75140; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O75140; -.
DR PhosphoSitePlus; O75140; -.
DR BioMuta; DEPDC5; -.
DR EPD; O75140; -.
DR jPOST; O75140; -.
DR MassIVE; O75140; -.
DR MaxQB; O75140; -.
DR PaxDb; O75140; -.
DR PeptideAtlas; O75140; -.
DR PRIDE; O75140; -.
DR ProteomicsDB; 1924; -.
DR ProteomicsDB; 49795; -. [O75140-10]
DR ProteomicsDB; 49796; -. [O75140-2]
DR ProteomicsDB; 49798; -. [O75140-4]
DR ProteomicsDB; 49799; -. [O75140-5]
DR ProteomicsDB; 49800; -. [O75140-6]
DR ProteomicsDB; 49802; -. [O75140-8]
DR ABCD; O75140; 1 sequenced antibody.
DR Antibodypedia; 65139; 75 antibodies from 20 providers.
DR DNASU; 9681; -.
DR Ensembl; ENST00000382111.6; ENSP00000371545.2; ENSG00000100150.20. [O75140-5]
DR Ensembl; ENST00000382112.8; ENSP00000371546.4; ENSG00000100150.20. [O75140-10]
DR Ensembl; ENST00000400242.8; ENSP00000383101.3; ENSG00000100150.20. [O75140-2]
DR Ensembl; ENST00000400248.7; ENSP00000383107.1; ENSG00000100150.20. [O75140-1]
DR Ensembl; ENST00000400249.7; ENSP00000383108.3; ENSG00000100150.20. [O75140-4]
DR Ensembl; ENST00000535622.6; ENSP00000440210.1; ENSG00000100150.20. [O75140-8]
DR Ensembl; ENST00000642696.1; ENSP00000495917.1; ENSG00000100150.20. [O75140-1]
DR Ensembl; ENST00000644331.1; ENSP00000494406.1; ENSG00000100150.20. [O75140-4]
DR Ensembl; ENST00000645711.1; ENSP00000493489.1; ENSG00000100150.20. [O75140-9]
DR Ensembl; ENST00000646755.1; ENSP00000496532.1; ENSG00000100150.20. [O75140-2]
DR Ensembl; ENST00000651528.2; ENSP00000498382.1; ENSG00000100150.20. [O75140-10]
DR GeneID; 9681; -.
DR KEGG; hsa:9681; -.
DR MANE-Select; ENST00000651528.2; ENSP00000498382.1; NM_001242896.3; NP_001229825.1.
DR UCSC; uc003alr.3; human. [O75140-10]
DR CTD; 9681; -.
DR DisGeNET; 9681; -.
DR GeneCards; DEPDC5; -.
DR GeneReviews; DEPDC5; -.
DR HGNC; HGNC:18423; DEPDC5.
DR HPA; ENSG00000100150; Low tissue specificity.
DR MalaCards; DEPDC5; -.
DR MIM; 604364; phenotype.
DR MIM; 614191; gene.
DR neXtProt; NX_O75140; -.
DR OpenTargets; ENSG00000100150; -.
DR Orphanet; 101046; Autosomal dominant epilepsy with auditory features.
DR Orphanet; 98784; Autosomal dominant nocturnal frontal lobe epilepsy.
DR Orphanet; 98820; Familial focal epilepsy with variable foci.
DR PharmGKB; PA134864958; -.
DR VEuPathDB; HostDB:ENSG00000100150; -.
DR eggNOG; KOG3572; Eukaryota.
DR GeneTree; ENSGT00390000016559; -.
DR HOGENOM; CLU_004411_0_0_1; -.
DR InParanoid; O75140; -.
DR OMA; RMYDLQM; -.
DR OrthoDB; 45642at2759; -.
DR PathwayCommons; O75140; -.
DR Reactome; R-HSA-9639288; Amino acids regulate mTORC1.
DR SignaLink; O75140; -.
DR SIGNOR; O75140; -.
DR BioGRID-ORCS; 9681; 38 hits in 1090 CRISPR screens.
DR ChiTaRS; DEPDC5; human.
DR GeneWiki; DEPDC5; -.
DR GenomeRNAi; 9681; -.
DR Pharos; O75140; Tbio.
DR PRO; PR:O75140; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; O75140; protein.
DR Bgee; ENSG00000100150; Expressed in paraflocculus and 149 other tissues.
DR ExpressionAtlas; O75140; baseline and differential.
DR Genevisible; O75140; HS.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:1990130; C:GATOR1 complex; IDA:SGD.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005096; F:GTPase activator activity; IEA:UniProtKB-KW.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:UniProtKB.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IMP:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0032007; P:negative regulation of TOR signaling; IMP:SGD.
DR GO; GO:1904262; P:negative regulation of TORC1 signaling; IMP:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; IBA:GO_Central.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR000591; DEP_dom.
DR InterPro; IPR045838; DEPDC5_CTD.
DR InterPro; IPR027244; IML1.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR13179; PTHR13179; 1.
DR Pfam; PF00610; DEP; 1.
DR Pfam; PF19418; DEPDC5_CTD; 1.
DR Pfam; PF12257; IML1; 1.
DR SMART; SM00049; DEP; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR PROSITE; PS50186; DEP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Disease variant; Epilepsy;
KW GTPase activation; Lysosome; Membrane; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..1603
FT /note="GATOR complex protein DEPDC5"
FT /id="PRO_0000079865"
FT DOMAIN 1187..1262
FT /note="DEP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00066"
FT REGION 427..450
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 484..527
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 696..720
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1135..1165
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 427..443
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 495..527
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 505
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 556..559
FT /note="DVLE -> EHLG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_014933"
FT VAR_SEQ 560..1603
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_014934"
FT VAR_SEQ 624..701
FT /note="Missing (in isoform 6 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_014936"
FT VAR_SEQ 724..733
FT /note="ILTLSAPPVV -> M (in isoform 1 and isoform 9)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:15770670, ECO:0000303|PubMed:17974005,
FT ECO:0000303|PubMed:9734811"
FT /id="VSP_014937"
FT VAR_SEQ 1089..1110
FT /note="Missing (in isoform 1, isoform 4 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:15770670,
FT ECO:0000303|PubMed:9734811"
FT /id="VSP_014938"
FT VAR_SEQ 1230..1338
FT /note="IMQKMLEEQLITHASGEAWRTFIYGFYFYKIVTDKEPDRVAMQQPATTWHTA
FT GVDDFASFQRKWFEVAFVAEELVHSEIPAFLLPWLPSRPASYASRHSSFSRSFGGRS
FT -> VMQWPCSSPPPPGTQQEWTTSPASSASGLRWPLWQKSSCTLRFLPFSCPGCLTGQP
FT PMQVGTAPLAEVLEDGARRQHF (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_014939"
FT VAR_SEQ 1339..1603
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_014940"
FT VAR_SEQ 1460..1603
FT /note="FEPETYWDRMHLFQEAIAHRFGFVQDKYSASAFNFPAENKPQYIHVTGTVFL
FT QLPYSKRKFSGQQRRRRNSTSSTNQNMFCEERVGYNWAYNTMLTKTWRSSATGDEKFAD
FT RLLKDFTDFCINRDNRLVTFWTSCLEKMHASAP -> LGLYKINILPLLLTSLLRTSLS
FT ISTLQEQCFCSCPTPSASSQGSSGGGGTPPAPPTRTCSARSGSATTGPTTPCSPKHGAP
FT APQGMKSLLIGC (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_014941"
FT VARIANT 90
FT /note="V -> I (in FFEVF1; does not inhibit DEPDC5
FT signaling; does not change kinase activity of mTORC1; does
FT not change association with the GATOR complex; inhibits
FT slightly RRAGA/RRAGC and RRAGB/RRAGC heterodimer formation;
FT dbSNP:rs768456731)"
FT /evidence="ECO:0000269|PubMed:24591017,
FT ECO:0000269|PubMed:25366275"
FT /id="VAR_072363"
FT VARIANT 214
FT /note="H -> D (in FFEVF1; unknown pathological
FT significance; dbSNP:rs886039276)"
FT /evidence="ECO:0000269|PubMed:26505888"
FT /id="VAR_077128"
FT VARIANT 272
FT /note="V -> L (in FFEVF1; does not inhibit DEPDC5
FT signaling; does not change kinase activity of mTORC1; does
FT not change association with the GATOR complex; does not
FT change RRAGA/RRAGC and RRAGB/RRAGC heterodimer formation;
FT dbSNP:rs187334123)"
FT /evidence="ECO:0000269|PubMed:24591017,
FT ECO:0000269|PubMed:25366275"
FT /id="VAR_072364"
FT VARIANT 452
FT /note="A -> V (in FFEVF1; inhibits slightly DEPDC5
FT signaling; stimulates slightly kinase activity of mTORC1;
FT does not change association with the GATOR complex; does
FT not change RRAGA/RRAGC and RRAGB/RRAGC heterodimer
FT formation; dbSNP:rs202226316)"
FT /evidence="ECO:0000269|PubMed:23542697,
FT ECO:0000269|PubMed:25366275"
FT /id="VAR_069263"
FT VARIANT 485
FT /note="R -> Q (in FFEVF1; does not inhibit DEPDC5
FT signaling; stimulates slightly kinase activity of mTORC1;
FT does not change association with the GATOR complex; does
FT not change RRAGA/RRAGC and RRAGB/RRAGC heterodimer
FT formation; dbSNP:rs886039278)"
FT /evidence="ECO:0000269|PubMed:23542701,
FT ECO:0000269|PubMed:25366275"
FT /id="VAR_069264"
FT VARIANT 491
FT /note="S -> T (in dbSNP:rs8138516)"
FT /id="VAR_024338"
FT VARIANT 542
FT /note="Q -> P (in FFEVF1; unknown pathological
FT significance; dbSNP:rs886039279)"
FT /evidence="ECO:0000269|PubMed:26505888"
FT /id="VAR_077129"
FT VARIANT 641
FT /note="A -> V (in dbSNP:rs16989528)"
FT /id="VAR_053953"
FT VARIANT 712
FT /note="S -> F (in dbSNP:rs16989535)"
FT /id="VAR_053954"
FT VARIANT 864
FT /note="T -> M (in FFEVF1; inhibits slightly DEPDC5
FT signaling; does not change kinase activity of mTORC1; does
FT not change association with the GATOR complex; does not
FT change RRAGA/RRAGC and RRAGB/RRAGC heterodimer formation;
FT dbSNP:rs564667614)"
FT /evidence="ECO:0000269|PubMed:24283814,
FT ECO:0000269|PubMed:25366275"
FT /id="VAR_072365"
FT VARIANT 1065
FT /note="K -> R (in FFEVF1; unknown pathological
FT significance; dbSNP:rs757609394)"
FT /evidence="ECO:0000269|PubMed:27173016"
FT /id="VAR_077130"
FT VARIANT 1073
FT /note="S -> R (in FFEVF1; inhibits slightly DEPDC5
FT signaling; does not change kinase activity of mTORC1; does
FT not change association with the GATOR complex; does not
FT change RRAGA/RRAGC and RRAGB/RRAGC heterodimer formation;
FT dbSNP:rs754608531)"
FT /evidence="ECO:0000269|PubMed:23542697,
FT ECO:0000269|PubMed:25366275"
FT /id="VAR_069265"
FT VARIANT 1081
FT /note="T -> P (in FFEVF1; unknown pathological
FT significance; dbSNP:rs142540948)"
FT /evidence="ECO:0000269|PubMed:26505888"
FT /id="VAR_077131"
FT VARIANT 1104
FT /note="S -> L (in FFEVF1; unknown pathological
FT significance; dbSNP:rs79027628)"
FT /evidence="ECO:0000269|PubMed:23542697"
FT /id="VAR_069266"
FT VARIANT 1154
FT /note="S -> F (in FFEVF1; unknown pathological
FT significance; dbSNP:rs578244490)"
FT /evidence="ECO:0000269|PubMed:26505888"
FT /id="VAR_077132"
FT VARIANT 1162
FT /note="S -> G (in FFEVF1; does not inhibit DEPDC5
FT signaling; does not change kinase activity of mTORC1; does
FT not change association with the GATOR complex; does not
FT change RRAGA/RRAGC and RRAGB/RRAGC heterodimer formation;
FT dbSNP:rs886039280)"
FT /evidence="ECO:0000269|PubMed:25366275"
FT /id="VAR_072366"
FT VARIANT 1268
FT /note="R -> Q (in FFEVF1; unknown pathological
FT significance; dbSNP:rs886039281)"
FT /evidence="ECO:0000269|PubMed:26505888"
FT /id="VAR_077133"
FT MUTAGEN 447
FT /note="K->R: No effect on ubiquitination. Loss of
FT interaction with KLHL22 and ubiquitination; when associated
FT with R-710, R-1065, R-1088 and R-1574."
FT /evidence="ECO:0000269|PubMed:29769719"
FT MUTAGEN 710
FT /note="K->R: No effect on ubiquitination. Loss of
FT interaction with KLHL22 and ubiquitination; when associated
FT with R-447, R-1065, R-1088 and R-1574."
FT /evidence="ECO:0000269|PubMed:29769719"
FT MUTAGEN 1065
FT /note="K->R: No effect on ubiquitination. Loss of
FT interaction with KLHL22 and ubiquitination; when associated
FT with R-447, R-710, R-1088 and R-1574."
FT /evidence="ECO:0000269|PubMed:29769719"
FT MUTAGEN 1088
FT /note="K->R: No effect on ubiquitination. Loss of
FT interaction with KLHL22 and ubiquitination; when associated
FT with R-447, R-710, R-1065 and R-1574."
FT /evidence="ECO:0000269|PubMed:29769719"
FT MUTAGEN 1188
FT /note="S->A: No effect on interaction with KLHL22."
FT /evidence="ECO:0000269|PubMed:29769719"
FT MUTAGEN 1189
FT /note="T->A: No effect on interaction with KLHL22."
FT /evidence="ECO:0000269|PubMed:29769719"
FT MUTAGEN 1195
FT /note="S->A: No effect on interaction with KLHL22."
FT /evidence="ECO:0000269|PubMed:29769719"
FT MUTAGEN 1201
FT /note="S->A: No effect on interaction with KLHL22."
FT /evidence="ECO:0000269|PubMed:29769719"
FT MUTAGEN 1203
FT /note="Y->A: No effect on interaction with KLHL22."
FT /evidence="ECO:0000269|PubMed:29769719"
FT MUTAGEN 1207
FT /note="S->A: No effect on interaction with KLHL22."
FT /evidence="ECO:0000269|PubMed:29769719"
FT MUTAGEN 1223
FT /note="T->A: No effect on interaction with KLHL22."
FT /evidence="ECO:0000269|PubMed:29769719"
FT MUTAGEN 1241
FT /note="T->A: No effect on interaction with KLHL22."
FT /evidence="ECO:0000269|PubMed:29769719"
FT MUTAGEN 1244
FT /note="S->A: No effect on interaction with KLHL22."
FT /evidence="ECO:0000269|PubMed:29769719"
FT MUTAGEN 1250
FT /note="T->A: No effect on interaction with KLHL22."
FT /evidence="ECO:0000269|PubMed:29769719"
FT MUTAGEN 1253
FT /note="Y->A: No effect on interaction with KLHL22."
FT /evidence="ECO:0000269|PubMed:29769719"
FT MUTAGEN 1256
FT /note="Y->A: No effect on interaction with KLHL22."
FT /evidence="ECO:0000269|PubMed:29769719"
FT MUTAGEN 1574
FT /note="K->R: No effect on ubiquitination. Loss of
FT ubiquitination; when associated with R-447, R-710, R-1065
FT and R-1088."
FT /evidence="ECO:0000269|PubMed:29769719"
FT CONFLICT 1365
FT /note="D -> G (in Ref. 7; CAH18159)"
FT /evidence="ECO:0000305"
FT CONFLICT 1430
FT /note="L -> P (in Ref. 7; CAH18159)"
FT /evidence="ECO:0000305"
FT CONFLICT 1561
FT /note="S -> G (in Ref. 7; CAH18159)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1603 AA; 181264 MW; 19664228B566A080 CRC64;
MRTTKVYKLV IHKKGFGGSD DELVVNPKVF PHIKLGDIVE IAHPNDEYSP LLLQVKSLKE
DLQKETISVD QTVTQVFRLR PYQDVYVNVV DPKDVTLDLV ELTFKDQYIG RGDMWRLKKS
LVSTCAYITQ KVEFAGIRAQ AGELWVKNEK VMCGYISEDT RVVFRSTSAM VYIFIQMSCE
MWDFDIYGDL YFEKAVNGFL ADLFTKWKEK NCSHEVTVVL FSRTFYDAKS VDEFPEINRA
SIRQDHKGRF YEDFYKVVVQ NERREEWTSL LVTIKKLFIQ YPVLVRLEQA EGFPQGDNST
SAQGNYLEAI NLSFNVFDKH YINRNFDRTG QMSVVITPGV GVFEVDRLLM ILTKQRMIDN
GIGVDLVCMG EQPLHAVPLF KLHNRSAPRD SRLGDDYNIP HWINHSFYTS KSQLFCNSFT
PRIKLAGKKP ASEKAKNGRD TSLGSPKESE NALPIQVDYD AYDAQVFRLP GPSRAQCLTT
CRSVRERESH SRKSASSCDV SSSPSLPSRT LPTEEVRSQA SDDSSLGKSA NILMIPHPHL
HQYEVSSSLG YTSTRDVLEN MMEPPQRDSS APGRFHVGSA ESMLHVRPGG YTPQRALINP
FAPSRMPMKL TSNRRRWMHT FPVGPSGEAI QIHHQTRQNM AELQGSGQRD PTHSSAELLE
LAYHEAAGRH SNSRQPGDGM SFLNFSGTEE LSVGLLSNSG AGMNPRTQNK DSLEDSVSTS
PDPILTLSAP PVVPGFCCTV GVDWKSLTTP ACLPLTTDYF PDRQGLQNDY TEGCYDLLPE
ADIDRRDEDG VQMTAQQVFE EFICQRLMQG YQIIVQPKTQ KPNPAVPPPL SSSPLYSRGL
VSRNRPEEED QYWLSMGRTF HKVTLKDKMI TVTRYLPKYP YESAQIHYTY SLCPSHSDSE
FVSCWVEFSH ERLEEYKWNY LDQYICSAGS EDFSLIESLK FWRTRFLLLP ACVTATKRIT
EGEAHCDIYG DRPRADEDEW QLLDGFVRFV EGLNRIRRRH RSDRMMRKGT AMKGLQMTGP
ISTHSLESTA PPVGKKGTSA LSALLEMEAS QKCLGEQQAA VHGGKSSAQS AESSSVAMTP
TYMDSPRKDG AFFMEFVRSP RTASSAFYPQ VSVDQTATPM LDGTSLGICT GQSMDRGNSQ
TFGNSQNIGE QGYSSTNSSD SSSQQLVASS LTSSSTLTEI LEAMKHPSTG VQLLSEQKGL
SPYCFISAEV VHWLVNHVEG IQTQAMAIDI MQKMLEEQLI THASGEAWRT FIYGFYFYKI
VTDKEPDRVA MQQPATTWHT AGVDDFASFQ RKWFEVAFVA EELVHSEIPA FLLPWLPSRP
ASYASRHSSF SRSFGGRSQA AALLAATVPE QRTVTLDVDV NNRTDRLEWC SCYYHGNFSL
NAAFEIKLHW MAVTAAVLFE MVQGWHRKAT SCGFLLVPVL EGPFALPSYL YGDPLRAQLF
IPLNISCLLK EGSEHLFDSF EPETYWDRMH LFQEAIAHRF GFVQDKYSAS AFNFPAENKP
QYIHVTGTVF LQLPYSKRKF SGQQRRRRNS TSSTNQNMFC EERVGYNWAY NTMLTKTWRS
SATGDEKFAD RLLKDFTDFC INRDNRLVTF WTSCLEKMHA SAP
