CI072_HUMAN
ID CI072_HUMAN Reviewed; 481 AA.
AC Q96LT7; A8K5W0; D3DRK6; G8I0B6; Q6NUS9;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Guanine nucleotide exchange factor C9orf72 {ECO:0000305};
GN Name=C9orf72 {ECO:0000312|HGNC:HGNC:28337};
GN Synonyms=DENND9 {ECO:0000312|HGNC:HGNC:28337},
GN DENNL72 {ECO:0000312|HGNC:HGNC:28337};
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], INVOLVEMENT IN FTDALS1, SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RC TISSUE=Frontal cortex;
RX PubMed=21944778; DOI=10.1016/j.neuron.2011.09.011;
RA Dejesus-Hernandez M., Mackenzie I.R., Boeve B.F., Boxer A.L., Baker M.,
RA Rutherford N.J., Nicholson A.M., Finch N.A., Flynn H., Adamson J.,
RA Kouri N., Wojtas A., Sengdy P., Hsiung G.Y., Karydas A., Seeley W.W.,
RA Josephs K.A., Coppola G., Geschwind D.H., Wszolek Z.K., Feldman H.,
RA Knopman D.S., Petersen R.C., Miller B.L., Dickson D.W., Boylan K.B.,
RA Graff-Radford N.R., Rademakers R.;
RT "Expanded GGGGCC hexanucleotide repeat in noncoding region of C9orf72
RT causes chromosome 9p-linked FTD and ALS.";
RL Neuron 72:245-256(2011).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 318-418 (ISOFORM 1).
RC TISSUE=Brain, and 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=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 [6]
RP PATHOLOGICAL MECHANISM.
RX PubMed=24132570; DOI=10.1007/s00401-013-1189-3;
RA Mori K., Arzberger T., Graesser F.A., Gijselinck I., May S., Rentzsch K.,
RA Weng S.M., Schludi M.H., van der Zee J., Cruts M., Van Broeckhoven C.,
RA Kremmer E., Kretzschmar H.A., Haass C., Edbauer D.;
RT "Bidirectional transcripts of the expanded C9orf72 hexanucleotide repeat
RT are translated into aggregating dipeptide repeat proteins.";
RL Acta Neuropathol. 126:881-893(2013).
RN [7]
RP FUNCTION IN ENDOSOMAL TRAFFICKING, INTERACTION WITH RAB GTPASES; HNRNPA1;
RP HNRNPA2B1 AND UBQLN2, AND SUBCELLULAR LOCATION.
RX PubMed=24549040; DOI=10.1093/hmg/ddu068;
RA Farg M.A., Sundaramoorthy V., Sultana J.M., Yang S., Atkinson R.A.,
RA Levina V., Halloran M.A., Gleeson P.A., Blair I.P., Soo K.Y., King A.E.,
RA Atkin J.D.;
RT "C9ORF72, implicated in amytrophic lateral sclerosis and frontotemporal
RT dementia, regulates endosomal trafficking.";
RL Hum. Mol. Genet. 23:3579-3595(2014).
RN [8]
RP ERRATUM OF PUBMED:24549040.
RX PubMed=28973528; DOI=10.1093/hmg/ddx309;
RA Farg M.A., Sundaramoorthy V., Sultana J.M., Yang S., Atkinson R.A.K.,
RA Levina V., Halloran M.A., Gleeson P.A., Blair I.P., Soo K.Y., King A.E.,
RA Atkin J.D.;
RL Hum. Mol. Genet. 26:4093-4094(2017).
RN [9]
RP PATHOLOGICAL MECHANISM.
RX PubMed=24598541; DOI=10.1038/nature13124;
RA Haeusler A.R., Donnelly C.J., Periz G., Simko E.A., Shaw P.G., Kim M.S.,
RA Maragakis N.J., Troncoso J.C., Pandey A., Sattler R., Rothstein J.D.,
RA Wang J.;
RT "C9orf72 nucleotide repeat structures initiate molecular cascades of
RT disease.";
RL Nature 507:195-200(2014).
RN [10]
RP DOMAIN ARCHITECTURE.
RX PubMed=23329412; DOI=10.1093/bioinformatics/bts725;
RA Levine T.P., Daniels R.D., Gatta A.T., Wong L.H., Hayes M.J.;
RT "The product of C9orf72, a gene strongly implicated in neurodegeneration,
RT is structurally related to DENN Rab-GEFs.";
RL Bioinformatics 29:499-503(2013).
RN [11]
RP SUBCELLULAR LOCATION (ISOFORMS 1 AND 2).
RX PubMed=26174152; DOI=10.1002/ana.24469;
RA Xiao S., MacNair L., McGoldrick P., McKeever P.M., McLean J.R., Zhang M.,
RA Keith J., Zinman L., Rogaeva E., Robertson J.;
RT "Isoform-specific antibodies reveal distinct subcellular localizations of
RT C9orf72 in amyotrophic lateral sclerosis.";
RL Ann. Neurol. 78:568-583(2015).
RN [12]
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 [13]
RP FUNCTION, AND IDENTIFICATION IN THE C9ORF72-SMCR8 COMPLEX.
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 [14]
RP FUNCTION, AND INTERACTION WITH ATG13; RAB1A; RB1CC1 AND ULK1.
RX PubMed=27334615; DOI=10.15252/embj.201694401;
RA Webster C.P., Smith E.F., Bauer C.S., Moller A., Hautbergue G.M.,
RA Ferraiuolo L., Myszczynska M.A., Higginbottom A., Walsh M.J.,
RA Whitworth A.J., Kaspar B.K., Meyer K., Shaw P.J., Grierson A.J.,
RA De Vos K.J.;
RT "The C9orf72 protein interacts with Rab1a and the ULK1 complex to regulate
RT initiation of autophagy.";
RL EMBO J. 35:1656-1676(2016).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN THE C9ORF72-SMCR8
RP COMPLEX, AND INTERACTION WITH SMCR8.
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 [16]
RP FUNCTION, INTERACTION WITH COFILIN, AND SUBCELLULAR LOCATION.
RX PubMed=27723745; DOI=10.1038/nn.4407;
RA Sivadasan R., Hornburg D., Drepper C., Frank N., Jablonka S., Hansel A.,
RA Lojewski X., Sterneckert J., Hermann A., Shaw P.J., Ince P.G., Mann M.,
RA Meissner F., Sendtner M.;
RT "C9ORF72 interaction with cofilin modulates actin dynamics in motor
RT neurons.";
RL Nat. Neurosci. 19:1610-1618(2016).
RN [17]
RP FUNCTION, IDENTIFICATION IN THE C9ORF72-SMCR8 COMPLEX, AND INTERACTION WITH
RP SMCR8.
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 [18]
RP FUNCTION, AND IDENTIFICATION IN THE C9ORF72-SMCR8 COMPLEX.
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 [19]
RP FUNCTION (ISOFORMS 1 AND 2), AND SUBCELLULAR LOCATION.
RX PubMed=27037575; DOI=10.1007/s12035-016-9850-1;
RA Maharjan N., Kuenzli C., Buthey K., Saxena S.;
RT "C9ORF72 regulates stress granule formation and its deficiency impairs
RT stress granule assembly, hypersensitizing cells to stress.";
RL Mol. Neurobiol. 54:3062-3077(2017).
RN [20] {ECO:0007744|PDB:6LT0}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS) IN THE C9ORF72-SMCR8
RP COMPLEX, FUNCTION, AND INTERACTION WITH SMCR8.
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).
RN [21]
RP INVOLVEMENT IN FTDALS1, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=21944779; DOI=10.1016/j.neuron.2011.09.010;
RA Renton A.E., Majounie E., Waite A., Simon-Sanchez J., Rollinson S.,
RA Gibbs J.R., Schymick J.C., Laaksovirta H., van Swieten J.C.,
RA Myllykangas L., Kalimo H., Paetau A., Abramzon Y., Remes A.M.,
RA Kaganovich A., Scholz S.W., Duckworth J., Ding J., Harmer D.W.,
RA Hernandez D.G., Johnson J.O., Mok K., Ryten M., Trabzuni D.,
RA Guerreiro R.J., Orrell R.W., Neal J., Murray A., Pearson J., Jansen I.E.,
RA Sondervan D., Seelaar H., Blake D., Young K., Halliwell N., Callister J.B.,
RA Toulson G., Richardson A., Gerhard A., Snowden J., Mann D., Neary D.,
RA Nalls M.A., Peuralinna T., Jansson L., Isoviita V.M., Kaivorinne A.L.,
RA Holtta-Vuori M., Ikonen E., Sulkava R., Benatar M., Wuu J., Chio A.,
RA Restagno G., Borghero G., Sabatelli M., Heckerman D., Rogaeva E.,
RA Zinman L., Rothstein J.D., Sendtner M., Drepper C., Eichler E.E., Alkan C.,
RA Abdullaev Z., Pack S.D., Dutra A., Pak E., Hardy J., Singleton A.,
RA Williams N.M., Heutink P., Pickering-Brown S., Morris H.R., Tienari P.J.,
RA Traynor B.J.;
RT "A hexanucleotide repeat expansion in C9orf72 is the cause of chromosome
RT 9p21-linked ALS-FTD.";
RL Neuron 72:257-268(2011).
RN [22]
RP INVOLVEMENT IN FTDALS1.
RX PubMed=22936364; DOI=10.1002/humu.22211;
RA Garcia-Redondo A., Dols-Icardo O., Rojas-Garcia R., Esteban-Perez J.,
RA Cordero-Vazquez P., Munoz-Blanco J.L., Catalina I., Gonzalez-Munoz M.,
RA Varona L., Sarasola E., Povedano M., Sevilla T., Guerrero A., Pardo J.,
RA de Munain A.L., Marquez-Infante C., de Rivera F.J., Pastor P., Jerico I.,
RA de Arcaya A.A., Mora J.S., Clarimon J., Gonzalo-Martinez J.F.,
RA Juarez-Rufian A., Atencia G., Jimenez-Bautista R., Moran Y., Mascias J.,
RA Hernandez-Barral M., Kapetanovic S., Garcia-Barcina M., Alcala C., Vela A.,
RA Ramirez-Ramos C., Galan L., Perez-Tur J., Quintans B., Sobrido M.J.,
RA Fernandez-Torron R., Poza J.J., Gorostidi A., Paradas C., Villoslada P.,
RA Larrode P., Capablo J.L., Pascual-Calvet J., Goni M., Morgado Y.,
RA Guitart M., Moreno-Laguna S., Rueda A., Martin-Estefania C., Cemillan C.,
RA Blesa R., Lleo A.;
RT "Analysis of the C9orf72 gene in patients with amyotrophic lateral
RT sclerosis in Spain and different populations worldwide.";
RL Hum. Mutat. 34:79-82(2013).
RN [23]
RP INVOLVEMENT IN FTDALS1.
RX PubMed=30366907; DOI=10.1101/gad.315564.118;
RA Liu Y., Wang T., Ji Y.J., Johnson K., Liu H., Johnson K., Bailey S.,
RA Suk Y., Lu Y.N., Liu M., Wang J.;
RT "A C9orf72-CARM1 axis regulates lipid metabolism under glucose starvation-
RT induced nutrient stress.";
RL Genes Dev. 32:1380-1397(2018).
CC -!- FUNCTION: Component of the C9orf72-SMCR8 complex, a complex that has
CC guanine nucleotide exchange factor (GEF) activity and regulates
CC autophagy (PubMed:27193190, PubMed:27103069, PubMed:27617292,
CC PubMed:28195531, PubMed:32303654). In the complex, C9orf72 and SMCR8
CC probably constitute the catalytic subunits that promote the exchange of
CC GDP to GTP, converting inactive GDP-bound RAB8A and RAB39B into their
CC active GTP-bound form, thereby promoting autophagosome maturation
CC (PubMed:27103069). The C9orf72-SMCR8 complex also acts as a regulator
CC of autophagy initiation by interacting with the ULK1/ATG1 kinase
CC complex and modulating its protein kinase activity (PubMed:27617292).
CC As part of the C9orf72-SMCR8 complex, stimulates RAB8A and RAB11A
CC GTPase activity in vitro (PubMed:32303654). Positively regulates
CC initiation of autophagy by regulating the RAB1A-dependent trafficking
CC of the ULK1/ATG1 kinase complex to the phagophore which leads to
CC autophagosome formation (PubMed:27334615). Acts as a regulator of
CC mTORC1 signaling by promoting phosphorylation of mTORC1 substrates
CC (PubMed:27559131). Plays a role in endosomal trafficking
CC (PubMed:24549040). May be involved in regulating the maturation of
CC phagosomes to lysosomes (By similarity). Promotes the lysosomal
CC localization and lysosome-mediated degradation of CARM1 which leads to
CC inhibition of starvation-induced lipid metabolism (By similarity).
CC Regulates actin dynamics in motor neurons by inhibiting the GTP-binding
CC activity of ARF6, leading to ARF6 inactivation (PubMed:27723745). This
CC reduces the activity of the LIMK1 and LIMK2 kinases which are
CC responsible for phosphorylation and inactivation of cofilin, leading to
CC CFL1/cofilin activation (PubMed:27723745). Positively regulates axon
CC extension and axon growth cone size in spinal motor neurons
CC (PubMed:27723745). Required for SMCR8 protein expression and
CC localization at pre- and post-synaptic compartments in the forebrain,
CC also regulates protein abundance of RAB3A and GRIA1/GLUR1 in post-
CC synaptic compartments in the forebrain and hippocampus (By similarity).
CC Plays a role within the hematopoietic system in restricting
CC inflammation and the development of autoimmunity (By similarity).
CC {ECO:0000250|UniProtKB:Q6DFW0, ECO:0000269|PubMed:24549040,
CC ECO:0000269|PubMed:27103069, ECO:0000269|PubMed:27193190,
CC ECO:0000269|PubMed:27334615, ECO:0000269|PubMed:27559131,
CC ECO:0000269|PubMed:27617292, ECO:0000269|PubMed:27723745,
CC ECO:0000269|PubMed:28195531, ECO:0000269|PubMed:32303654}.
CC -!- FUNCTION: [Isoform 1]: Regulates stress granule assembly in response to
CC cellular stress. {ECO:0000269|PubMed:27037575}.
CC -!- FUNCTION: [Isoform 2]: Does not play a role in regulation of stress
CC granule assembly in response to cellular stress.
CC {ECO:0000269|PubMed:27037575}.
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, PubMed:32303654).
CC The complex is formed of two protomers, each individually consisting of
CC one molecule each of C9orf72, SMCR8 and WDR41 (PubMed:32303654). The
CC protomers homodimerize via an interaction between C9orf72 (via C-
CC terminus) and SMCR8 (via N-terminus) (PubMed:32303654). Within each
CC protomer SMCR8 (via DENN domain) acts as a bridging protein between
CC WDR41 (via C-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:27617292, PubMed:28195531). Interacts
CC with ULK1/ATG1 kinase complex members ULK1, ATG13 and RB1CC1
CC (PubMed:27334615). Interacts with SMCR8; the interaction is direct
CC (PubMed:27559131, PubMed:27617292, PubMed:32303654). Interacts with
CC HNRNPA1, HNRNPA2B1 and UBQLN2 (PubMed:24549040). Interacts with small
CC Rab GTPase RAB1A; the interaction mediates recruitment of RAB1A to the
CC ULK1/ATG1 kinase complex (PubMed:27334615). Also interacts with small
CC Rab GTPase RAB7A (By similarity). Interacts with cofilin
CC (PubMed:27723745). Interacts with GTP-binding proteins ARF1 and ARF6
CC (By similarity). Interacts with the DLG4/PSD-95 (By similarity).
CC Interacts with CARM1 (via PH domain-like fold) (By similarity).
CC {ECO:0000250|UniProtKB:Q6DFW0, ECO:0000269|PubMed:24549040,
CC ECO:0000269|PubMed:27103069, ECO:0000269|PubMed:27193190,
CC ECO:0000269|PubMed:27334615, ECO:0000269|PubMed:27559131,
CC ECO:0000269|PubMed:27617292, ECO:0000269|PubMed:27723745,
CC ECO:0000269|PubMed:28195531, ECO:0000269|PubMed:32303654}.
CC -!- INTERACTION:
CC Q96LT7; P38432: COIL; NbExp=3; IntAct=EBI-2961725, EBI-945751;
CC Q96LT7; O43186: CRX; NbExp=3; IntAct=EBI-2961725, EBI-748171;
CC Q96LT7; P49770: EIF2B2; NbExp=6; IntAct=EBI-2961725, EBI-718773;
CC Q96LT7; Q53XC2: EIF2B2; NbExp=3; IntAct=EBI-2961725, EBI-10288660;
CC Q96LT7; Q9BPX4: EIF2B2; NbExp=3; IntAct=EBI-2961725, EBI-10288788;
CC Q96LT7; Q9NP66: HMG20A; NbExp=3; IntAct=EBI-2961725, EBI-740641;
CC Q96LT7; Q13287: NMI; NbExp=6; IntAct=EBI-2961725, EBI-372942;
CC Q96LT7; O75817: POP7; NbExp=3; IntAct=EBI-2961725, EBI-366574;
CC Q96LT7; Q04864: REL; NbExp=3; IntAct=EBI-2961725, EBI-307352;
CC Q96LT7; Q8TEV9: SMCR8; NbExp=10; IntAct=EBI-2961725, EBI-2961718;
CC Q96LT7; Q17R54: SYN3; NbExp=5; IntAct=EBI-2961725, EBI-12820047;
CC Q96LT7; Q86UV6-2: TRIM74; NbExp=3; IntAct=EBI-2961725, EBI-10259086;
CC Q96LT7; Q9H8Y1: VRTN; NbExp=6; IntAct=EBI-2961725, EBI-12894399;
CC Q96LT7-1; O75143: ATG13; NbExp=5; IntAct=EBI-16693635, EBI-2798775;
CC Q96LT7-1; P62820: RAB1A; NbExp=5; IntAct=EBI-16693635, EBI-716845;
CC Q96LT7-1; Q8TDY2: RB1CC1; NbExp=7; IntAct=EBI-16693635, EBI-1047793;
CC Q96LT7-1; Q8TEV9: SMCR8; NbExp=5; IntAct=EBI-16693635, EBI-2961718;
CC Q96LT7-1; O75385: ULK1; NbExp=5; IntAct=EBI-16693635, EBI-908831;
CC Q96LT7-2; O75143: ATG13; NbExp=4; IntAct=EBI-16693673, EBI-2798775;
CC Q96LT7-2; P62820: RAB1A; NbExp=4; IntAct=EBI-16693673, EBI-716845;
CC Q96LT7-2; Q8TDY2: RB1CC1; NbExp=6; IntAct=EBI-16693673, EBI-1047793;
CC Q96LT7-2; O75385: ULK1; NbExp=4; IntAct=EBI-16693673, EBI-908831;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21944779,
CC ECO:0000269|PubMed:27037575}. Cytoplasm {ECO:0000269|PubMed:21944778,
CC ECO:0000269|PubMed:27037575, ECO:0000269|PubMed:27193190}. Cytoplasm,
CC P-body {ECO:0000269|PubMed:27037575}. Cytoplasm, Stress granule
CC {ECO:0000269|PubMed:27037575}. Endosome {ECO:0000269|PubMed:24549040}.
CC Lysosome {ECO:0000269|PubMed:24549040, ECO:0000269|PubMed:27559131}.
CC Cytoplasmic vesicle, autophagosome {ECO:0000269|PubMed:24549040}.
CC Secreted {ECO:0000269|PubMed:24549040}. Cell projection, axon
CC {ECO:0000269|PubMed:27723745}. Cell projection, growth cone
CC {ECO:0000269|PubMed:27723745}. Perikaryon
CC {ECO:0000250|UniProtKB:Q6DFW0}. Note=Detected in the cytoplasm of
CC neurons from brain tissue (PubMed:21944778). Detected in the nucleus in
CC fibroblasts (PubMed:21944779). During corticogenesis, transitions from
CC being predominantly cytoplasmic to a more even nucleocytoplasmic
CC distribution (By similarity). {ECO:0000250|UniProtKB:Q6DFW0,
CC ECO:0000269|PubMed:21944778, ECO:0000269|PubMed:21944779,
CC ECO:0000269|PubMed:27037575}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Perikaryon
CC {ECO:0000269|PubMed:26174152}. Cell projection, dendrite
CC {ECO:0000269|PubMed:26174152}. Presynapse
CC {ECO:0000250|UniProtKB:Q6DFW0}. Postsynapse
CC {ECO:0000250|UniProtKB:Q6DFW0}. Note=Expressed diffusely throughout the
CC cytoplasm and dendritic processes of cerebellar Purkinje cells. Also
CC expressed diffusely throughout the cytoplasm of spinal motor neurons.
CC {ECO:0000269|PubMed:26174152}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus membrane
CC {ECO:0000269|PubMed:26174152}; Peripheral membrane protein
CC {ECO:0000305}. Nucleus {ECO:0000269|PubMed:26174152}. Note=Detected at
CC the nuclear membrane of cerebellar Purkinje cells and spinal motor
CC neurons. Also shows diffuse nuclear expression in spinal motor neurons.
CC {ECO:0000269|PubMed:26174152}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=C9-L {ECO:0000303|PubMed:26174152}, C9(LF)
CC {ECO:0000303|PubMed:27037575};
CC IsoId=Q96LT7-1; Sequence=Displayed;
CC Name=2; Synonyms=C9-S {ECO:0000303|PubMed:26174152}, C9(SF)
CC {ECO:0000303|PubMed:27037575};
CC IsoId=Q96LT7-2; Sequence=VSP_014745, VSP_014746;
CC -!- TISSUE SPECIFICITY: Both isoforms are widely expressed, including
CC kidney, lung, liver, heart, testis and several brain regions, such as
CC cerebellum. Also expressed in the frontal cortex and in lymphoblasts
CC (at protein level). {ECO:0000269|PubMed:21944778,
CC ECO:0000269|PubMed:21944779}.
CC -!- DISEASE: Frontotemporal dementia and/or amyotrophic lateral sclerosis 1
CC (FTDALS1) [MIM:105550]: An autosomal dominant neurodegenerative
CC disorder characterized by adult onset of frontotemporal dementia and/or
CC amyotrophic lateral sclerosis in an affected individual. There is high
CC intrafamilial variation. Frontotemporal dementia is characterized by
CC frontal and temporal lobe atrophy associated with neuronal loss,
CC gliosis, and dementia. Patients exhibit progressive changes in social,
CC behavioral, and/or language function. Amyotrophic lateral sclerosis is
CC characterized by the death of motor neurons in the brain, brainstem,
CC and spinal cord, resulting in fatal paralysis.
CC {ECO:0000269|PubMed:21944778, ECO:0000269|PubMed:21944779,
CC ECO:0000269|PubMed:22936364, ECO:0000269|PubMed:30366907}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry. In the first intron of the gene, the expansion of a GGGGCC
CC hexanucleotide that can vary from 10 to thousands of repeats,
CC represents the most common genetic cause of both familial and sporadic
CC FTDALS. The hexanucleotide repeat expansion (HRE) is structurally
CC polymorphic and during transcription, is responsible for the formation
CC of RNA and DNA G-quadruplexes resulting in the production of aborted
CC transcripts at the expense of functional transcripts. The accumulation
CC of those aborted transcripts may cause nucleolar stress and indirectly
CC cell death (PubMed:24598541). The expanded GGGGCC repeats are
CC bidirectionally transcribed into repetitive RNA, which forms sense and
CC antisense RNA foci. Remarkably, despite being within a non-coding
CC region, these repetitive RNAs can be translated in every reading frame
CC to form five different dipeptide repeat proteins (DPRs) -- poly-GA,
CC poly-GP, poly-GR, poly-PA and poly-PR -- via a non-canonical mechanism
CC known as repeat-associated non-ATG (RAN) translation. These dipeptide
CC repeat proteins (DPRs) co-aggregate in the characteristic SQSTM1-
CC positive TARDBP negative inclusions found in FTLD/ALS patients with
CC C9orf72 repeat expansion (PubMed:24132570).
CC {ECO:0000269|PubMed:24132570, ECO:0000269|PubMed:24598541}.
CC -!- MISCELLANEOUS: [Isoform 1]: Encoded by 2 transcripts differing in the
CC 5' non-coding region.
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DR EMBL; JN681271; AET41697.1; -; mRNA.
DR EMBL; AK057806; BAB71583.1; -; mRNA.
DR EMBL; AK291425; BAF84114.1; -; mRNA.
DR EMBL; AL451123; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471071; EAW58561.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58558.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58560.1; -; Genomic_DNA.
DR EMBL; BC068445; AAH68445.1; -; mRNA.
DR CCDS; CCDS6522.1; -. [Q96LT7-1]
DR CCDS; CCDS6523.1; -. [Q96LT7-2]
DR RefSeq; NP_001242983.1; NM_001256054.2. [Q96LT7-1]
DR RefSeq; NP_060795.1; NM_018325.4. [Q96LT7-1]
DR RefSeq; NP_659442.2; NM_145005.6. [Q96LT7-2]
DR PDB; 6LT0; EM; 3.20 A; C/F=1-481.
DR PDB; 6V4U; EM; 3.80 A; A=1-481.
DR PDB; 7MGE; EM; 3.94 A; C=1-481.
DR PDB; 7O2W; EM; -; A=1-481.
DR PDBsum; 6LT0; -.
DR PDBsum; 6V4U; -.
DR PDBsum; 7MGE; -.
DR PDBsum; 7O2W; -.
DR AlphaFoldDB; Q96LT7; -.
DR SMR; Q96LT7; -.
DR BioGRID; 128456; 123.
DR ComplexPortal; CPX-3961; C9orf72-SMCR8 complex. [Q96LT7-1]
DR CORUM; Q96LT7; -.
DR IntAct; Q96LT7; 108.
DR MINT; Q96LT7; -.
DR STRING; 9606.ENSP00000482753; -.
DR iPTMnet; Q96LT7; -.
DR PhosphoSitePlus; Q96LT7; -.
DR BioMuta; C9orf72; -.
DR DMDM; 71152412; -.
DR EPD; Q96LT7; -.
DR jPOST; Q96LT7; -.
DR MassIVE; Q96LT7; -.
DR MaxQB; Q96LT7; -.
DR PaxDb; Q96LT7; -.
DR PeptideAtlas; Q96LT7; -.
DR PRIDE; Q96LT7; -.
DR ProteomicsDB; 77248; -. [Q96LT7-1]
DR ProteomicsDB; 77249; -. [Q96LT7-2]
DR Antibodypedia; 10609; 259 antibodies from 32 providers.
DR DNASU; 203228; -.
DR Ensembl; ENST00000379995.1; ENSP00000369331.1; ENSG00000147894.17. [Q96LT7-2]
DR Ensembl; ENST00000379997.7; ENSP00000369333.3; ENSG00000147894.17. [Q96LT7-2]
DR Ensembl; ENST00000380003.8; ENSP00000369339.3; ENSG00000147894.17. [Q96LT7-1]
DR Ensembl; ENST00000619707.5; ENSP00000482753.1; ENSG00000147894.17. [Q96LT7-1]
DR GeneID; 203228; -.
DR KEGG; hsa:203228; -.
DR MANE-Select; ENST00000380003.8; ENSP00000369339.3; NM_018325.5; NP_060795.1.
DR UCSC; uc003zqq.4; human. [Q96LT7-1]
DR CTD; 203228; -.
DR DisGeNET; 203228; -.
DR GeneCards; C9orf72; -.
DR GeneReviews; C9orf72; -.
DR HGNC; HGNC:28337; C9orf72.
DR HPA; ENSG00000147894; Low tissue specificity.
DR MalaCards; C9orf72; -.
DR MIM; 105550; phenotype.
DR MIM; 614260; gene.
DR neXtProt; NX_Q96LT7; -.
DR OpenTargets; ENSG00000147894; -.
DR Orphanet; 803; Amyotrophic lateral sclerosis.
DR Orphanet; 275864; Behavioral variant of frontotemporal dementia.
DR Orphanet; 275872; Frontotemporal dementia with motor neuron disease.
DR Orphanet; 401901; Huntington disease-like syndrome due to C9ORF72 expansions.
DR Orphanet; 100070; Progressive non-fluent aphasia.
DR Orphanet; 100069; Semantic dementia.
DR PharmGKB; PA134908144; -.
DR VEuPathDB; HostDB:ENSG00000147894; -.
DR eggNOG; ENOG502QSST; Eukaryota.
DR GeneTree; ENSGT00390000005644; -.
DR HOGENOM; CLU_047573_0_0_1; -.
DR InParanoid; Q96LT7; -.
DR OMA; IFGRSFY; -.
DR OrthoDB; 1434762at2759; -.
DR PhylomeDB; Q96LT7; -.
DR TreeFam; TF313315; -.
DR PathwayCommons; Q96LT7; -.
DR SignaLink; Q96LT7; -.
DR SIGNOR; Q96LT7; -.
DR BioGRID-ORCS; 203228; 12 hits in 1063 CRISPR screens.
DR ChiTaRS; C9orf72; human.
DR GenomeRNAi; 203228; -.
DR Pharos; Q96LT7; Tbio.
DR PRO; PR:Q96LT7; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q96LT7; protein.
DR Bgee; ENSG00000147894; Expressed in monocyte and 175 other tissues.
DR ExpressionAtlas; Q96LT7; baseline and differential.
DR Genevisible; Q96LT7; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005776; C:autophagosome; IDA:UniProtKB.
DR GO; GO:0044295; C:axonal growth cone; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0090543; C:Flemming body; IDA:HPA.
DR GO; GO:0032045; C:guanyl-nucleotide exchange factor complex; IDA:HGNC.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0044304; C:main axon; IDA:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000932; C:P-body; IDA:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IDA:UniProtKB.
DR GO; GO:0098794; C:postsynapse; IEA:UniProtKB-SubCell.
DR GO; GO:0098793; C:presynapse; IEA:UniProtKB-SubCell.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IEA:UniProtKB-KW.
DR GO; GO:0031267; F:small GTPase binding; IDA:UniProtKB.
DR GO; GO:0006914; P:autophagy; IMP:UniProtKB.
DR GO; GO:0048675; P:axon extension; IMP:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IMP:UniProtKB.
DR GO; GO:1902774; P:late endosome to lysosome transport; ISS:UniProtKB.
DR GO; GO:0045920; P:negative regulation of exocytosis; IC:ComplexPortal.
DR GO; GO:1904425; P:negative regulation of GTP binding; IEA:Ensembl.
DR GO; GO:0050777; P:negative regulation of immune response; IC:ComplexPortal.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IMP:UniProtKB.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IMP:UniProtKB.
DR GO; GO:0110053; P:regulation of actin filament organization; IMP:UniProtKB.
DR GO; GO:2000785; P:regulation of autophagosome assembly; IMP:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; IMP:UniProtKB.
DR GO; GO:0032880; P:regulation of protein localization; IEA:Ensembl.
DR GO; GO:1903432; P:regulation of TORC1 signaling; IMP:UniProtKB.
DR GO; GO:0034063; P:stress granule assembly; IMP:UniProtKB.
DR InterPro; IPR027819; C9orf72.
DR PANTHER; PTHR31855; PTHR31855; 1.
DR Pfam; PF15019; C9orf72-like; 1.
DR PROSITE; PS51835; DENN_C9ORF72; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Amyotrophic lateral sclerosis;
KW Autophagy; Cell projection; Cytoplasm; Cytoplasmic vesicle; Endosome;
KW Guanine-nucleotide releasing factor; Lysosome; Membrane; Neurodegeneration;
KW Nucleus; Reference proteome; Secreted; Synapse.
FT CHAIN 1..481
FT /note="Guanine nucleotide exchange factor C9orf72"
FT /id="PRO_0000089711"
FT DOMAIN 23..194
FT /note="uDENN C9ORF72-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01179"
FT DOMAIN 200..343
FT /note="cDENN C9ORF72-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01179"
FT DOMAIN 370..464
FT /note="dDENN C9ORF72-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01179"
FT REGION 461..481
FT /note="Required for the homodimerization of the C9orf72-
FT SMCR8 complex"
FT /evidence="ECO:0000269|PubMed:32303654"
FT VAR_SEQ 222
FT /note="N -> K (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_014745"
FT VAR_SEQ 223..481
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_014746"
FT VARIANT 207
FT /note="N -> S (in dbSNP:rs17769294)"
FT /id="VAR_050827"
FT STRAND 14..17
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 20..23
FT /evidence="ECO:0007829|PDB:7O2W"
FT STRAND 44..47
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 57..67
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 81..87
FT /evidence="ECO:0007829|PDB:6LT0"
FT TURN 88..91
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 92..98
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 102..106
FT /evidence="ECO:0007829|PDB:7O2W"
FT STRAND 111..117
FT /evidence="ECO:0007829|PDB:6LT0"
FT TURN 122..124
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 125..127
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 128..147
FT /evidence="ECO:0007829|PDB:6LT0"
FT TURN 155..157
FT /evidence="ECO:0007829|PDB:7O2W"
FT HELIX 168..171
FT /evidence="ECO:0007829|PDB:7O2W"
FT HELIX 174..192
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 201..203
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 208..211
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 213..215
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 216..229
FT /evidence="ECO:0007829|PDB:6LT0"
FT TURN 230..232
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 234..237
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 242..251
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 252..254
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 257..262
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 268..270
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 279..281
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 285..288
FT /evidence="ECO:0007829|PDB:7O2W"
FT HELIX 295..299
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 301..303
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 306..309
FT /evidence="ECO:0007829|PDB:6LT0"
FT TURN 310..313
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 314..316
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 321..336
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 376..384
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 385..387
FT /evidence="ECO:0007829|PDB:7O2W"
FT HELIX 394..419
FT /evidence="ECO:0007829|PDB:6LT0"
FT STRAND 422..425
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 430..436
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 442..454
FT /evidence="ECO:0007829|PDB:6LT0"
FT HELIX 459..463
FT /evidence="ECO:0007829|PDB:6LT0"
FT TURN 465..467
FT /evidence="ECO:0007829|PDB:7O2W"
SQ SEQUENCE 481 AA; 54328 MW; B36C5576B3D268CE CRC64;
MSTLCPPPSP AVAKTEIALS GKSPLLAATF AYWDNILGPR VRHIWAPKTE QVLLSDGEIT
FLANHTLNGE ILRNAESGAI DVKFFVLSEK GVIIVSLIFD GNWNGDRSTY GLSIILPQTE
LSFYLPLHRV CVDRLTHIIR KGRIWMHKER QENVQKIILE GTERMEDQGQ SIIPMLTGEV
IPVMELLSSM KSHSVPEEID IADTVLNDDD IGDSCHEGFL LNAISSHLQT CGCSVVVGSS
AEKVNKIVRT LCLFLTPAER KCSRLCEAES SFKYESGLFV QGLLKDSTGS FVLPFRQVMY
APYPTTHIDV DVNTVKQMPP CHEHIYNQRR YMRSELTAFW RATSEEDMAQ DTIIYTDESF
TPDLNIFQDV LHRDTLVKAF LDQVFQLKPG LSLRSTFLAQ FLLVLHRKAL TLIKYIEDDT
QKGKKPFKSL RNLKIDLDLT AEGDLNIIMA LAEKIKPGLH SFIFGRPFYT SVQERDVLMT
F
