SMCR8_HUMAN
ID SMCR8_HUMAN Reviewed; 937 AA.
AC Q8TEV9; A5PKZ5; Q3ZCN0; Q6PJL3;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Guanine nucleotide exchange protein SMCR8 {ECO:0000305};
DE AltName: Full=Smith-Magenis syndrome chromosomal region candidate gene 8 protein {ECO:0000312|HGNC:HGNC:17921};
GN Name=SMCR8 {ECO:0000312|HGNC:HGNC:17921};
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), AND TISSUE SPECIFICITY.
RX PubMed=11997338; DOI=10.1101/gr.73702;
RA Bi W., Yan J., Stankiewicz P., Park S.-S., Walz K., Boerkoel C.F.,
RA Potocki L., Shaffer L.G., Devriendt K., Nowaczyk M.J.M., Inoue K.,
RA Lupski J.R.;
RT "Genes in a refined Smith-Magenis syndrome critical deletion interval on
RT chromosome 17p11.2 and the syntenic region of the mouse.";
RL Genome Res. 12:713-728(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS LEU-524
RP AND HIS-556.
RC TISSUE=Eye;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-471, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-498, AND IDENTIFICATION BY
RP 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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-498, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [7]
RP FUNCTION.
RX PubMed=20562859; DOI=10.1038/nature09204;
RA Behrends C., Sowa M.E., Gygi S.P., Harper J.W.;
RT "Network organization of the human autophagy system.";
RL Nature 466:68-76(2010).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-468; SER-471; SER-492 AND
RP SER-498, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [9]
RP DOMAIN ARCHITECTURE.
RX PubMed=23248642; DOI=10.3389/fgene.2012.00283;
RA Zhang D., Iyer L.M., He F., Aravind L.;
RT "Discovery of novel DENN proteins: implications for the evolution of
RT eukaryotic intracellular membrane structures and human disease.";
RL Front. Genet. 3:283-283(2012).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-417; SER-489; SER-492;
RP SER-498 AND SER-790, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11]
RP FUNCTION, IDENTIFICATION IN THE C9ORF72-SMCR8 COMPLEX, AND SUBCELLULAR
RP LOCATION.
RX PubMed=27193190; DOI=10.1186/s40478-016-0324-5;
RA Sullivan P.M., Zhou X., Robins A.M., Paushter D.H., Kim D., Smolka M.B.,
RA Hu F.;
RT "The ALS/FTLD associated protein C9orf72 associates with SMCR8 and WDR41 to
RT regulate the autophagy-lysosome pathway.";
RL Acta Neuropathol. Commun. 4:51-51(2016).
RN [12]
RP FUNCTION, IDENTIFICATION IN THE C9ORF72-SMCR8 COMPLEX, PHOSPHORYLATION AT
RP SER-402 AND THR-796, AND MUTAGENESIS OF SER-402 AND THR-796.
RX PubMed=27103069; DOI=10.15252/embj.201593350;
RA Sellier C., Campanari M.L., Julie Corbier C., Gaucherot A.,
RA Kolb-Cheynel I., Oulad-Abdelghani M., Ruffenach F., Page A., Ciura S.,
RA Kabashi E., Charlet-Berguerand N.;
RT "Loss of C9ORF72 impairs autophagy and synergizes with polyQ Ataxin-2 to
RT induce motor neuron dysfunction and cell death.";
RL EMBO J. 35:1276-1297(2016).
RN [13]
RP FUNCTION, IDENTIFICATION IN THE C9ORF72-SMCR8 COMPLEX, AND INTERACTION WITH
RP C9ORF72.
RX PubMed=27559131; DOI=10.1091/mbc.e16-01-0003;
RA Amick J., Roczniak-Ferguson A., Ferguson S.M.;
RT "C9orf72 binds SMCR8, localizes to lysosomes, and regulates mTORC1
RT signaling.";
RL Mol. Biol. Cell 27:3040-3051(2016).
RN [14]
RP FUNCTION, IDENTIFICATION IN THE C9ORF72-SMCR8 COMPLEX, AND INTERACTION WITH
RP C9ORF72.
RX PubMed=27617292; DOI=10.1126/sciadv.1601167;
RA Yang M., Liang C., Swaminathan K., Herrlinger S., Lai F., Shiekhattar R.,
RA Chen J.F.;
RT "A C9ORF72/SMCR8-containing complex regulates ULK1 and plays a dual role in
RT autophagy.";
RL Sci. Adv. 2:E1601167-E1601167(2016).
RN [15]
RP FUNCTION, IDENTIFICATION IN THE C9ORF72-SMCR8 COMPLEX, AND SUBCELLULAR
RP LOCATION.
RX PubMed=28195531; DOI=10.7554/elife.23063;
RA Jung J., Nayak A., Schaeffer V., Starzetz T., Kirsch A.K., Mueller S.,
RA Dikic I., Mittelbronn M., Behrends C.;
RT "Multiplex image-based autophagy RNAi screening identifies SMCR8 as ULK1
RT kinase activity and gene expression regulator.";
RL Elife 6:0-0(2017).
RN [16] {ECO:0007744|PDB:6LT0}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS) IN THE C9ORF72-SMCR8
RP COMPLEX, FUNCTION, INTERACTION WITH C9ORF72, AND MUTAGENESIS OF ARG-147.
RX PubMed=32303654; DOI=10.1073/pnas.2002110117;
RA Tang D., Sheng J., Xu L., Zhan X., Liu J., Jiang H., Shu X., Liu X.,
RA Zhang T., Jiang L., Zhou C., Li W., Cheng W., Li Z., Wang K., Lu K.,
RA Yan C., Qi S.;
RT "Cryo-EM structure of C9ORF72-SMCR8-WDR41 reveals the role as a GAP for
RT Rab8a and Rab11a.";
RL Proc. Natl. Acad. Sci. U.S.A. 117:9876-9883(2020).
CC -!- FUNCTION: Component of the C9orf72-SMCR8 complex, a complex that has
CC guanine nucleotide exchange factor (GEF) activity and regulates
CC autophagy (PubMed:20562859, PubMed:27193190, PubMed:27103069,
CC PubMed:27559131, PubMed:27617292, PubMed:28195531, PubMed:32303654). In
CC the complex, C9orf72 and SMCR8 probably constitute the catalytic
CC subunits that promote the exchange of GDP to GTP, converting inactive
CC GDP-bound RAB8A and RAB39B into their active GTP-bound form, thereby
CC promoting autophagosome maturation (PubMed:20562859, PubMed:27103069,
CC PubMed:27617292, PubMed:28195531). The C9orf72-SMCR8 complex also acts
CC as a negative regulator of autophagy initiation by interacting with the
CC ULK1/ATG1 kinase complex and inhibiting its protein kinase activity
CC (PubMed:27617292, PubMed:28195531). As part of the C9orf72-SMCR8
CC complex, stimulates RAB8A and RAB11A GTPase activity in vitro
CC (PubMed:32303654). Acts as a regulator of mTORC1 signaling by promoting
CC phosphorylation of mTORC1 substrates (PubMed:27559131,
CC PubMed:28195531). In addition to its activity in the cytoplasm within
CC the C9orf72-SMCR8 complex, SMCR8 also localizes in the nucleus, where
CC it associates with chromatin and negatively regulates expression of
CC suppresses ULK1 and WIPI2 genes (PubMed:28195531).
CC {ECO:0000269|PubMed:20562859, ECO:0000269|PubMed:27103069,
CC ECO:0000269|PubMed:27193190, ECO:0000269|PubMed:27559131,
CC ECO:0000269|PubMed:27617292, ECO:0000269|PubMed:28195531,
CC ECO:0000269|PubMed:32303654}.
CC -!- SUBUNIT: Component of the C9orf72-SMCR8 complex, at least composed of
CC C9orf72, SMCR8 and WDR41 (PubMed:27193190, PubMed:27103069,
CC PubMed:27559131, PubMed:27617292, PubMed:28195531). The complex is
CC formed of two protomers, each individually consisting of one molecule
CC each of C9orf72, SMCR8 and WDR41 (PubMed:32303654). The protomers
CC homodimerize via an interaction between C9orf72 (via C-terminus) and
CC SMCR8 (via N-terminus) (PubMed:32303654). Within each protomer SMCR8
CC (via DENN domain) acts as a bridging protein between WDR41 (via C-
CC terminus and N-terminus) and C9orf72 (via C-terminus)
CC (PubMed:32303654). The C9orf72-SMCR8 complex associates with the
CC ULK1/ATG1 kinase complex (PubMed:28195531). Interacts with C9orf72; the
CC interaction is direct (PubMed:27559131, PubMed:27617292,
CC PubMed:32303654). Interacts with DLG4/PSD-95 (By similarity).
CC {ECO:0000250|UniProtKB:Q3UMB5, ECO:0000269|PubMed:27103069,
CC ECO:0000269|PubMed:27193190, ECO:0000269|PubMed:27559131,
CC ECO:0000269|PubMed:27617292, ECO:0000269|PubMed:28195531,
CC ECO:0000269|PubMed:32303654}.
CC -!- INTERACTION:
CC Q8TEV9; Q96LT7: C9orf72; NbExp=10; IntAct=EBI-2961718, EBI-2961725;
CC Q8TEV9; Q96LT7-1: C9orf72; NbExp=5; IntAct=EBI-2961718, EBI-16693635;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:27193190,
CC ECO:0000269|PubMed:28195531}. Nucleus {ECO:0000269|PubMed:28195531}.
CC Presynapse {ECO:0000250|UniProtKB:Q3UMB5}. Postsynapse
CC {ECO:0000250|UniProtKB:Q3UMB5}. Note=Localizes mainly in the cytoplasm.
CC {ECO:0000269|PubMed:28195531}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8TEV9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TEV9-2; Sequence=VSP_025487;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues tested.
CC {ECO:0000269|PubMed:11997338}.
CC -!- PTM: Phosphorylation by TBK1 is required to promote autophagosome
CC maturation (PubMed:27103069). Phosphorylated by ULK1 (PubMed:27103069).
CC {ECO:0000269|PubMed:27103069}.
CC -!- SIMILARITY: Belongs to the SMCR8 family. {ECO:0000305}.
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DR EMBL; AF467440; AAL78337.1; -; mRNA.
DR EMBL; BC001018; AAH01018.1; ALT_TERM; mRNA.
DR EMBL; BC101116; AAI01117.1; -; mRNA.
DR EMBL; BC101117; AAI01118.1; -; mRNA.
DR EMBL; BC014179; AAH14179.1; ALT_TERM; mRNA.
DR EMBL; BC142680; AAI42681.1; -; mRNA.
DR CCDS; CCDS11195.2; -. [Q8TEV9-1]
DR RefSeq; NP_658988.2; NM_144775.2. [Q8TEV9-1]
DR PDB; 6LT0; EM; 3.20 A; B/E=1-937.
DR PDB; 6V4U; EM; 3.80 A; B=1-937.
DR PDB; 7EL6; X-ray; 2.80 A; A/B=778-787.
DR PDB; 7MGE; EM; 3.94 A; B=1-937.
DR PDB; 7O2W; EM; -; B=1-439, B=620-937.
DR PDBsum; 6LT0; -.
DR PDBsum; 6V4U; -.
DR PDBsum; 7EL6; -.
DR PDBsum; 7MGE; -.
DR PDBsum; 7O2W; -.
DR AlphaFoldDB; Q8TEV9; -.
DR SMR; Q8TEV9; -.
DR BioGRID; 126704; 118.
DR ComplexPortal; CPX-3961; C9orf72-SMCR8 complex.
DR CORUM; Q8TEV9; -.
DR IntAct; Q8TEV9; 26.
DR MINT; Q8TEV9; -.
DR STRING; 9606.ENSP00000385025; -.
DR GlyGen; Q8TEV9; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8TEV9; -.
DR PhosphoSitePlus; Q8TEV9; -.
DR BioMuta; SMCR8; -.
DR DMDM; 147733168; -.
DR EPD; Q8TEV9; -.
DR jPOST; Q8TEV9; -.
DR MassIVE; Q8TEV9; -.
DR MaxQB; Q8TEV9; -.
DR PaxDb; Q8TEV9; -.
DR PeptideAtlas; Q8TEV9; -.
DR PRIDE; Q8TEV9; -.
DR ProteomicsDB; 74504; -. [Q8TEV9-1]
DR ProteomicsDB; 74505; -. [Q8TEV9-2]
DR Antibodypedia; 13526; 40 antibodies from 14 providers.
DR DNASU; 140775; -.
DR Ensembl; ENST00000406438.5; ENSP00000385025.3; ENSG00000176994.11. [Q8TEV9-1]
DR Ensembl; ENST00000639332.2; ENSP00000492062.1; ENSG00000283741.2. [Q8TEV9-1]
DR GeneID; 140775; -.
DR KEGG; hsa:140775; -.
DR MANE-Select; ENST00000406438.5; ENSP00000385025.3; NM_144775.3; NP_658988.2.
DR UCSC; uc002gsy.5; human. [Q8TEV9-1]
DR CTD; 140775; -.
DR DisGeNET; 140775; -.
DR GeneCards; SMCR8; -.
DR HGNC; HGNC:17921; SMCR8.
DR HPA; ENSG00000176994; Low tissue specificity.
DR neXtProt; NX_Q8TEV9; -.
DR OpenTargets; ENSG00000176994; -.
DR PharmGKB; PA38266; -.
DR VEuPathDB; HostDB:ENSG00000176994; -.
DR eggNOG; ENOG502QSW2; Eukaryota.
DR GeneTree; ENSGT00390000010052; -.
DR HOGENOM; CLU_013891_0_0_1; -.
DR InParanoid; Q8TEV9; -.
DR OMA; KPVKHWV; -.
DR OrthoDB; 692565at2759; -.
DR PhylomeDB; Q8TEV9; -.
DR TreeFam; TF330880; -.
DR PathwayCommons; Q8TEV9; -.
DR SignaLink; Q8TEV9; -.
DR SIGNOR; Q8TEV9; -.
DR BioGRID-ORCS; 140775; 16 hits in 1080 CRISPR screens.
DR ChiTaRS; SMCR8; human.
DR GenomeRNAi; 140775; -.
DR Pharos; Q8TEV9; Tbio.
DR PRO; PR:Q8TEV9; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q8TEV9; protein.
DR Bgee; ENSG00000176994; Expressed in monocyte and 106 other tissues.
DR Genevisible; Q8TEV9; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:1990316; C:Atg1/ULK1 kinase complex; IDA:HGNC.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR GO; GO:0000785; C:chromatin; IDA:HGNC.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0032045; C:guanyl-nucleotide exchange factor complex; IDA:HGNC.
DR GO; GO:0005654; C:nucleoplasm; IDA:HGNC.
DR GO; GO:0098794; C:postsynapse; ISS:UniProtKB.
DR GO; GO:0098793; C:presynapse; ISS:UniProtKB.
DR GO; GO:0005096; F:GTPase activator activity; IEA:InterPro.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IEA:UniProtKB-KW.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IMP:HGNC.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:1902902; P:negative regulation of autophagosome assembly; IMP:HGNC.
DR GO; GO:0045920; P:negative regulation of exocytosis; IC:ComplexPortal.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:HGNC.
DR GO; GO:0050777; P:negative regulation of immune response; IC:ComplexPortal.
DR GO; GO:0016242; P:negative regulation of macroautophagy; IMP:HGNC.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IMP:HGNC.
DR GO; GO:1901098; P:positive regulation of autophagosome maturation; IMP:HGNC.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IMP:UniProtKB.
DR GO; GO:0032008; P:positive regulation of TOR signaling; IMP:HGNC.
DR GO; GO:0010506; P:regulation of autophagy; IMP:UniProtKB.
DR GO; GO:1903432; P:regulation of TORC1 signaling; IMP:UniProtKB.
DR InterPro; IPR037521; FLCN/SMCR8_DENN.
DR InterPro; IPR037520; Folliculin/SMCR8_longin.
DR Pfam; PF11704; Folliculin; 1.
DR PROSITE; PS51834; DENN_FLCN_SMCR8; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Autophagy; Cell projection; Cytoplasm;
KW Guanine-nucleotide releasing factor; Nucleus; Phosphoprotein;
KW Reference proteome; Synapse; Transcription; Transcription regulation.
FT CHAIN 1..937
FT /note="Guanine nucleotide exchange protein SMCR8"
FT /id="PRO_0000287469"
FT DOMAIN 48..220
FT /note="uDENN FLCN/SMCR8-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01178,
FT ECO:0000305|PubMed:23248642"
FT DOMAIN 318..835
FT /note="cDENN FLCN/SMCR8-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01178,
FT ECO:0000305|PubMed:23248642"
FT DOMAIN 844..910
FT /note="dDENN FLCN/SMCR8-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01178,
FT ECO:0000305|PubMed:23248642"
FT REGION 1..349
FT /note="Required for the homodimerization of the C9orf72-
FT SMCR8 complex"
FT /evidence="ECO:0000269|PubMed:32303654"
FT REGION 274..293
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 384..405
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 564..645
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 862..914
FT /note="Interacts with WDR41 within the C9orf72-SMCR8
FT complex"
FT /evidence="ECO:0000269|PubMed:32303654"
FT COMPBIAS 275..292
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 572..587
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 597..611
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 612..627
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 402
FT /note="Phosphoserine; by TBK1"
FT /evidence="ECO:0000269|PubMed:27103069"
FT MOD_RES 417
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 468
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 471
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 489
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 492
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 498
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 790
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 796
FT /note="Phosphothreonine; by TBK1"
FT /evidence="ECO:0000269|PubMed:27103069"
FT VAR_SEQ 788..937
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11997338"
FT /id="VSP_025487"
FT VARIANT 524
FT /note="P -> L (in dbSNP:rs8080966)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_032309"
FT VARIANT 556
FT /note="R -> H (in dbSNP:rs1563632)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_032310"
FT VARIANT 636
FT /note="N -> S (in dbSNP:rs12449313)"
FT /id="VAR_032311"
FT MUTAGEN 147
FT /note="R->A: Loss of C9ORF72-SMCR8 complex-mediated
FT stimulation of RAB8A and RAB11A GTPase activity."
FT MUTAGEN 402
FT /note="S->A: Impaired autophagosome maturation; when
FT associated with A-796."
FT /evidence="ECO:0000269|PubMed:27103069"
FT MUTAGEN 402
FT /note="S->D: Phosphomimetic mutant; able to promote
FT autophagosome maturation; when associated with D-796."
FT /evidence="ECO:0000269|PubMed:27103069"
FT MUTAGEN 796
FT /note="T->A: Impaired autophagosome maturation; when
FT associated with A-402."
FT /evidence="ECO:0000269|PubMed:27103069"
FT MUTAGEN 796
FT /note="T->D: Phosphomimetic mutant; able to promote
FT autophagosome maturation; when associated with D-402."
FT /evidence="ECO:0000269|PubMed:27103069"
FT STRAND 60..63
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 85..88
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 97..100
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 103..105
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:7O2W"
FT STRAND 115..117
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 130..137
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:7O2W"
FT HELIX 147..149
FT /evidence="ECO:0007829|PDB:7O2W"
FT STRAND 153..160
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 162..166
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 169..173
FT /evidence="ECO:0007829|PDB:6LT0"
FT TURN 174..179
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 180..187
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 215..219
FT /evidence="ECO:0007829|PDB:7O2W"
FT HELIX 225..248
FT /evidence="ECO:0007829|PDB:7O2W"
FT HELIX 315..330
FT /evidence="ECO:0007829|PDB:7O2W"
FT HELIX 331..344
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 350..364
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 368..371
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 702..714
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 717..719
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 721..729
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 732..736
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 740..750
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 751..753
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 757..761
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 778..784
FT /evidence="ECO:0007829|PDB:7EL6"
FT HELIX 796..800
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 801..803
FT /evidence="ECO:0007829|PDB:6LT0"
FT TURN 812..815
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 816..819
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 826..830
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 841..863
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 865..868
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 872..874
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 877..890
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 898..915
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 918..921
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 933..935
FT /evidence="ECO:0007829|PDB:6LT0"
SQ SEQUENCE 937 AA; 105022 MW; 53A4EF9B3107248F CRC64;
MISAPDVVAF TKEEEYEEEP YNEPALPEEY SVPLFPFASQ GANPWSKLSG AKFSRDFILI
SEFSEQVGPQ PLLTIPNDTK VFGTFDLNYF SLRIMSVDYQ ASFVGHPPGS AYPKLNFVED
SKVVLGDSKE GAFAYVHHLT LYDLEARGFV RPFCMAYISA DQHKIMQQFQ ELSAEFSRAS
ECLKTGNRKA FAGELEKKLK DLDYTRTVLH TETEIQKKAN DKGFYSSQAI EKANELASVE
KSIIEHQDLL KQIRSYPHRK LKGHDLCPGE MEHIQDQASQ ASTTSNPDES ADTDLYTCRP
AYTPKLIKAK STKCFDKKLK TLEELCDTEY FTQTLAQLSH IEHMFRGDLC YLLTSQIDRA
LLKQQHITNF LFEDFVEVDD RMVEKQESIP SKPSQDRPPS SSLEECPIPK VLISVGSYKS
SVESVLIKME QELGDEEYKE VEVTELSSFD PQENLDYLDM DMKGSISSGE SIEVLGTEKS
TSVLSKSDSQ ASLTVPLSPQ VVRSKAVSHR TISEDSIEVL STCPSEALIP DDFKASYPSA
INEEESYPDG NEGAIRFQAS ISPPELGETE EGSIENTPSQ IDSSCCIGKE SDGQLVLPST
PAHTHSDEDG VVSSPPQRHR QKDQGFRVDF SVENANPSSR DNSCEGFPAY ELDPSHLLAS
RDISKTSLDN YSDTTSYVSS VASTSSDRIP SAYPAGLSSD RHKKRAGQNA LKFIRQYPFA
HPAIYSLLSG RTLVVLGEDE AIVRKLVTAL AIFVPSYGCY AKPVKHWASS PLHIMDFQKW
KLIGLQRVAS PAGAGTLHAL SRYSRYTSIL DLDNKTLRCP LYRGTLVPRL ADHRTQIKRG
STYYLHVQSM LTQLCSKAFL YTFCHHLHLP THDKETEELV ASRQMSFLKL TLGLVNEDVR
VVQYLAELLK LHYMQESPGT SHPMLRFDYV PSFLYKI
