ID SMG8_HUMAN Reviewed; 991 AA. AC Q8ND04; Q8N5U5; Q8TDN0; Q9H5P5; Q9NVQ1; DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2002, sequence version 1. DT 27-MAR-2024, entry version 145. DE RecName: Full=Nonsense-mediated mRNA decay factor SMG8 {ECO:0000312|HGNC:HGNC:25551}; DE AltName: Full=Amplified in breast cancer gene 2 protein {ECO:0000303|Ref.1}; DE AltName: Full=Protein smg-8 homolog; GN Name=SMG8; Synonyms=ABC2, C17orf71; 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). RA Wu G.G., Couch F.J.; RT "Cloning and characterization of three novel amplified and overexpressed RT genes from breast cancer."; RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Adipose tissue; 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 MRNA] (ISOFORM 1). RC TISSUE=Testis; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 265-991 (ISOFORM 1), AND RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 5-991 (ISOFORM 3). RC TISSUE=Brain, and Colon; 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-469, 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 [8] RP FUNCTION, PHOSPHORYLATION, IDENTIFICATION BY MASS SPECTROMETRY, AND RP IDENTIFICATION IN THE SMG1C COMPLEX. RX PubMed=19417104; DOI=10.1101/gad.1767209; RA Yamashita A., Izumi N., Kashima I., Ohnishi T., Saari B., Katsuhata Y., RA Muramatsu R., Morita T., Iwamatsu A., Hachiya T., Kurata R., Hirano H., RA Anderson P., Ohno S.; RT "SMG-8 and SMG-9, two novel subunits of the SMG-1 complex, regulate RT remodeling of the mRNA surveillance complex during nonsense-mediated mRNA RT decay."; RL Genes Dev. 23:1091-1105(2009). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP INTERACTION WITH SMG1 AND SMG9, AND ELECTRON MICROSCOPY OF THE SMG1C RP COMPLEX. RX PubMed=21245168; DOI=10.1101/gad.606911; RA Arias-Palomo E., Yamashita A., Fernandez I.S., Nunez-Ramirez R., Bamba Y., RA Izumi N., Ohno S., Llorca O.; RT "The nonsense-mediated mRNA decay SMG-1 kinase is regulated by large-scale RT conformational changes controlled by SMG-8."; RL Genes Dev. 25:153-164(2011). RN [12] RP SUBUNIT. RX PubMed=20817927; DOI=10.1093/nar/gkq749; RA Fernandez I.S., Yamashita A., Arias-Palomo E., Bamba Y., Bartolome R.A., RA Canales M.A., Teixido J., Ohno S., Llorca O.; RT "Characterization of SMG-9, an essential component of the nonsense-mediated RT mRNA decay SMG1C complex."; RL Nucleic Acids Res. 39:347-358(2011). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-668, AND IDENTIFICATION BY RP 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 [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-115; SER-668; SER-742 AND RP SER-895, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [15] RP IDENTIFICATION BY 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 [16] RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-898, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Colon carcinoma; RX PubMed=24129315; DOI=10.1074/mcp.o113.027870; RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M., RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V., RA Bedford M.T., Comb M.J.; RT "Immunoaffinity enrichment and mass spectrometry analysis of protein RT methylation."; RL Mol. Cell. Proteomics 13:372-387(2014). RN [17] RP INTERACTION WITH SMG1. RX PubMed=33205750; DOI=10.7554/elife.63042; RA Lopez-Perrote A., Hug N., Gonzalez-Corpas A., Rodriguez C.F., Serna M., RA Garcia-Martin C., Boskovic J., Fernandez-Leiro R., Caceres J.F., Llorca O.; RT "Regulation of RUVBL1-RUVBL2 AAA-ATPases by the nonsense-mediated mRNA RT decay factor DHX34, as evidenced by Cryo-EM."; RL Elife 9:0-0(2020). RN [18] RP VARIANTS ALKUS ARG-208 AND 839-ARG--GLN-991 DEL, AND INVOLVEMENT IN ALKUS. RX PubMed=33242396; DOI=10.1016/j.ajhg.2020.11.007; RA Alzahrani F., Kuwahara H., Long Y., Al-Owain M., Tohary M., AlSayed M., RA Mahnashi M., Fathi L., Alnemer M., Al-Hamed M.H., Lemire G., Boycott K.M., RA Hashem M., Han W., Al-Maawali A., Al Mahrizi F., Al-Thihli K., Gao X., RA Alkuraya F.S.; RT "Recessive, deleterious variants in SMG8 expand the role of nonsense- RT mediated decay in developmental disorders in humans."; RL Am. J. Hum. Genet. 107:1178-1185(2020). CC -!- FUNCTION: Involved in nonsense-mediated decay (NMD) of mRNAs containing CC premature stop codons. Is recruited by release factors to stalled CC ribosomes together with SMG1 and SMG9 (forming the SMG1C protein kinase CC complex) and, in the SMG1C complex, is required to mediate the CC recruitment of SMG1 to the ribosome:SURF complex and to suppress SMG1 CC kinase activity until the ribosome:SURF complex locates the exon CC junction complex (EJC). Acts as a regulator of kinase activity. CC {ECO:0000269|PubMed:19417104}. CC -!- SUBUNIT: Component of the SMG1C complex composed of SMG1, SMG8 and CC SMG9; the recruitment of SMG8 to SMG1 N-terminus induces a large CC conformational change in the SMG1 C-terminal head domain containing the CC catalytic domain (PubMed:33205750). Forms heterodimers with SMG9; this CC assembly form may represent a SMG1C intermediate form. CC {ECO:0000269|PubMed:19417104, ECO:0000269|PubMed:20817927, CC ECO:0000269|PubMed:33205750}. CC -!- INTERACTION: CC Q8ND04; Q9H0W8: SMG9; NbExp=6; IntAct=EBI-3903643, EBI-2872322; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q8ND04-1; Sequence=Displayed; CC Name=2; Synonyms=ABC2; CC IsoId=Q8ND04-2; Sequence=VSP_028166; CC Name=3; CC IsoId=Q8ND04-3; Sequence=VSP_028164, VSP_028165; CC -!- PTM: Phosphorylated by SMG1. {ECO:0000269|PubMed:19417104}. CC -!- DISEASE: Alzahrani-Kuwahara syndrome (ALKUS) [MIM:619268]: An autosomal CC recessive disorder characterized by severe global developmental delay, CC impaired intellectual function, poor or absent speech, microcephaly, CC and facial dysmorphism. Additional variable features include early- CC onset cataracts, hypotonia, lower limb spasticity, and congenital heart CC malformations. {ECO:0000269|PubMed:33242396}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the SMG8 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH20957.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAA91699.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF349467; AAL83913.1; -; mRNA. DR EMBL; AK001449; BAA91699.1; ALT_INIT; mRNA. DR EMBL; AK026858; BAB15576.1; -; mRNA. DR EMBL; AL834490; CAD39148.1; -; mRNA. DR EMBL; AC099850; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471109; EAW94415.1; -; Genomic_DNA. DR EMBL; BC020957; AAH20957.1; ALT_INIT; mRNA. DR EMBL; BC031604; AAH31604.1; -; mRNA. DR CCDS; CCDS11615.1; -. [Q8ND04-1] DR RefSeq; NP_060619.4; NM_018149.6. [Q8ND04-1] DR PDB; 6L54; EM; 3.43 A; B=1-991. DR PDB; 6SYT; EM; 3.45 A; B=1-991. DR PDB; 6Z3R; EM; 2.97 A; B=1-991. DR PDB; 7PW4; EM; 3.27 A; B=1-991. DR PDB; 7PW5; EM; 3.40 A; B=1-991. DR PDB; 7PW8; EM; 2.82 A; B=1-991. DR PDBsum; 6L54; -. DR PDBsum; 6SYT; -. DR PDBsum; 6Z3R; -. DR PDBsum; 7PW4; -. DR PDBsum; 7PW5; -. DR PDBsum; 7PW8; -. DR AlphaFoldDB; Q8ND04; -. DR EMDB; EMD-0837; -. DR EMDB; EMD-10347; -. DR EMDB; EMD-11063; -. DR EMDB; EMD-13674; -. DR EMDB; EMD-13675; -. DR EMDB; EMD-13678; -. DR EMDB; EMD-2663; -. DR EMDB; EMD-2664; -. DR EMDB; EMD-2665; -. DR EMDB; EMD-2666; -. DR EMDB; EMD-3065; -. DR EMDB; EMD-3066; -. DR EMDB; EMD-3278; -. DR SMR; Q8ND04; -. DR BioGRID; 120480; 126. DR ComplexPortal; CPX-2827; SMG1C protein kinase complex. DR IntAct; Q8ND04; 24. DR STRING; 9606.ENSP00000438748; -. DR GlyGen; Q8ND04; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q8ND04; -. DR PhosphoSitePlus; Q8ND04; -. DR BioMuta; SMG8; -. DR DMDM; 74715258; -. DR EPD; Q8ND04; -. DR jPOST; Q8ND04; -. DR MassIVE; Q8ND04; -. DR MaxQB; Q8ND04; -. DR PaxDb; 9606-ENSP00000438748; -. DR PeptideAtlas; Q8ND04; -. DR ProteomicsDB; 72968; -. [Q8ND04-1] DR ProteomicsDB; 72969; -. [Q8ND04-2] DR ProteomicsDB; 72970; -. [Q8ND04-3] DR Pumba; Q8ND04; -. DR Antibodypedia; 31075; 65 antibodies from 18 providers. DR DNASU; 55181; -. DR Ensembl; ENST00000300917.10; ENSP00000300917.4; ENSG00000167447.13. [Q8ND04-1] DR Ensembl; ENST00000543872.6; ENSP00000438748.2; ENSG00000167447.13. [Q8ND04-1] DR Ensembl; ENST00000578922.1; ENSP00000462119.1; ENSG00000167447.13. [Q8ND04-3] DR GeneID; 55181; -. DR KEGG; hsa:55181; -. DR MANE-Select; ENST00000300917.10; ENSP00000300917.4; NM_018149.7; NP_060619.4. DR UCSC; uc002ixi.4; human. [Q8ND04-1] DR AGR; HGNC:25551; -. DR CTD; 55181; -. DR DisGeNET; 55181; -. DR GeneCards; SMG8; -. DR HGNC; HGNC:25551; SMG8. DR HPA; ENSG00000167447; Low tissue specificity. DR MalaCards; SMG8; -. DR MIM; 613175; gene. DR MIM; 619268; phenotype. DR neXtProt; NX_Q8ND04; -. DR OpenTargets; ENSG00000167447; -. DR PharmGKB; PA142672219; -. DR VEuPathDB; HostDB:ENSG00000167447; -. DR eggNOG; KOG3692; Eukaryota. DR GeneTree; ENSGT00390000018533; -. DR HOGENOM; CLU_008116_0_0_1; -. DR InParanoid; Q8ND04; -. DR OMA; CHIVVYV; -. DR OrthoDB; 73615at2759; -. DR PhylomeDB; Q8ND04; -. DR TreeFam; TF323445; -. DR PathwayCommons; Q8ND04; -. DR Reactome; R-HSA-975957; Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC). DR SignaLink; Q8ND04; -. DR BioGRID-ORCS; 55181; 86 hits in 1166 CRISPR screens. DR ChiTaRS; SMG8; human. DR GenomeRNAi; 55181; -. DR Pharos; Q8ND04; Tdark. DR PRO; PR:Q8ND04; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q8ND04; Protein. DR Bgee; ENSG00000167447; Expressed in secondary oocyte and 193 other cell types or tissues. DR ExpressionAtlas; Q8ND04; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IMP:UniProtKB. DR GO; GO:0045859; P:regulation of protein kinase activity; IMP:UniProtKB. DR InterPro; IPR019354; SMG8-like. DR PANTHER; PTHR13091; AMPLIFIED IN BREAST CANCER 2-RELATED; 1. DR PANTHER; PTHR13091:SF0; NONSENSE-MEDIATED MRNA DECAY FACTOR SMG8; 1. DR Pfam; PF10220; Smg8_Smg9; 1. DR Genevisible; Q8ND04; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cataract; Disease variant; KW Intellectual disability; Methylation; Nonsense-mediated mRNA decay; KW Phosphoprotein; Reference proteome. FT CHAIN 1..991 FT /note="Nonsense-mediated mRNA decay factor SMG8" FT /id="PRO_0000304974" FT REGION 16..41 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 82..127 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 279..299 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 653..722 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 671..685 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 686..709 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 115 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 469 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 668 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 742 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 895 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 898 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT VAR_SEQ 588 FT /note="E -> S (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_028164" FT VAR_SEQ 589..991 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_028165" FT VAR_SEQ 945 FT /note="T -> TLPPDGLWVLRFPYAYGLREDLVSPXGKKQEIP (in isoform FT 2)" FT /evidence="ECO:0000303|Ref.1" FT /id="VSP_028166" FT VARIANT 208 FT /note="H -> R (in ALKUS)" FT /evidence="ECO:0000269|PubMed:33242396" FT /id="VAR_085550" FT VARIANT 280 FT /note="P -> L (in dbSNP:rs8068240)" FT /id="VAR_035137" FT VARIANT 839..991 FT /note="Missing (in ALKUS)" FT /evidence="ECO:0000269|PubMed:33242396" FT /id="VAR_085551" FT CONFLICT 278 FT /note="E -> V (in Ref. 2; BAB15576)" FT /evidence="ECO:0000305" FT CONFLICT 411 FT /note="R -> W (in Ref. 2; BAB15576)" FT /evidence="ECO:0000305" FT CONFLICT 488 FT /note="F -> L (in Ref. 1; AAL83913)" FT /evidence="ECO:0000305" FT CONFLICT 491 FT /note="I -> F (in Ref. 1; AAL83913)" FT /evidence="ECO:0000305" FT CONFLICT 493 FT /note="T -> P (in Ref. 1; AAL83913)" FT /evidence="ECO:0000305" FT CONFLICT 520 FT /note="T -> P (in Ref. 1; AAL83913)" FT /evidence="ECO:0000305" FT CONFLICT 522 FT /note="T -> P (in Ref. 1; AAL83913)" FT /evidence="ECO:0000305" FT CONFLICT 532 FT /note="L -> R (in Ref. 1; AAL83913)" FT /evidence="ECO:0000305" FT HELIX 7..11 FT /evidence="ECO:0007829|PDB:7PW8" FT HELIX 40..42 FT /evidence="ECO:0007829|PDB:7PW8" FT STRAND 48..54 FT /evidence="ECO:0007829|PDB:7PW8" FT STRAND 58..61 FT /evidence="ECO:0007829|PDB:6Z3R" FT HELIX 63..71 FT /evidence="ECO:0007829|PDB:7PW8" FT STRAND 72..74 FT /evidence="ECO:0007829|PDB:6Z3R" FT STRAND 137..143 FT /evidence="ECO:0007829|PDB:7PW8" FT TURN 144..147 FT /evidence="ECO:0007829|PDB:7PW8" FT STRAND 148..154 FT /evidence="ECO:0007829|PDB:7PW8" FT HELIX 159..171 FT /evidence="ECO:0007829|PDB:7PW8" FT HELIX 182..203 FT /evidence="ECO:0007829|PDB:7PW8" FT STRAND 208..218 FT /evidence="ECO:0007829|PDB:7PW8" FT HELIX 222..234 FT /evidence="ECO:0007829|PDB:7PW8" FT HELIX 238..244 FT /evidence="ECO:0007829|PDB:7PW8" FT STRAND 246..248 FT /evidence="ECO:0007829|PDB:7PW8" FT HELIX 252..257 FT /evidence="ECO:0007829|PDB:7PW8" FT STRAND 258..261 FT /evidence="ECO:0007829|PDB:7PW8" FT STRAND 264..270 FT /evidence="ECO:0007829|PDB:7PW8" FT HELIX 296..314 FT /evidence="ECO:0007829|PDB:7PW8" FT TURN 322..324 FT /evidence="ECO:0007829|PDB:7PW8" FT STRAND 325..328 FT /evidence="ECO:0007829|PDB:6SYT" FT STRAND 331..333 FT /evidence="ECO:0007829|PDB:7PW8" FT STRAND 336..339 FT /evidence="ECO:0007829|PDB:7PW8" FT STRAND 343..345 FT /evidence="ECO:0007829|PDB:7PW8" FT HELIX 347..358 FT /evidence="ECO:0007829|PDB:7PW8" FT HELIX 410..422 FT /evidence="ECO:0007829|PDB:7PW8" FT STRAND 432..434 FT /evidence="ECO:0007829|PDB:7PW8" FT HELIX 445..457 FT /evidence="ECO:0007829|PDB:7PW8" FT HELIX 478..482 FT /evidence="ECO:0007829|PDB:7PW8" FT HELIX 483..485 FT /evidence="ECO:0007829|PDB:6L54" FT HELIX 489..508 FT /evidence="ECO:0007829|PDB:7PW8" FT HELIX 524..538 FT /evidence="ECO:0007829|PDB:7PW8" FT HELIX 544..557 FT /evidence="ECO:0007829|PDB:7PW8" FT STRAND 578..580 FT /evidence="ECO:0007829|PDB:7PW5" FT STRAND 594..596 FT /evidence="ECO:0007829|PDB:7PW5" FT STRAND 606..610 FT /evidence="ECO:0007829|PDB:7PW5" FT STRAND 617..621 FT /evidence="ECO:0007829|PDB:7PW5" FT HELIX 626..630 FT /evidence="ECO:0007829|PDB:7PW5" FT HELIX 632..638 FT /evidence="ECO:0007829|PDB:7PW5" FT TURN 639..644 FT /evidence="ECO:0007829|PDB:7PW5" FT STRAND 645..648 FT /evidence="ECO:0007829|PDB:7PW5" FT STRAND 656..659 FT /evidence="ECO:0007829|PDB:7PW5" FT STRAND 743..749 FT /evidence="ECO:0007829|PDB:7PW5" FT STRAND 761..763 FT /evidence="ECO:0007829|PDB:7PW5" FT STRAND 767..772 FT /evidence="ECO:0007829|PDB:7PW5" FT HELIX 774..776 FT /evidence="ECO:0007829|PDB:7PW5" FT TURN 779..781 FT /evidence="ECO:0007829|PDB:7PW5" FT STRAND 796..801 FT /evidence="ECO:0007829|PDB:7PW5" FT HELIX 839..841 FT /evidence="ECO:0007829|PDB:7PW5" FT STRAND 842..853 FT /evidence="ECO:0007829|PDB:7PW5" FT STRAND 858..863 FT /evidence="ECO:0007829|PDB:7PW5" FT STRAND 872..874 FT /evidence="ECO:0007829|PDB:7PW5" FT HELIX 879..883 FT /evidence="ECO:0007829|PDB:7PW5" FT STRAND 887..892 FT /evidence="ECO:0007829|PDB:7PW5" FT STRAND 898..901 FT /evidence="ECO:0007829|PDB:7PW5" FT STRAND 904..914 FT /evidence="ECO:0007829|PDB:7PW5" FT STRAND 916..923 FT /evidence="ECO:0007829|PDB:7PW5" FT STRAND 927..931 FT /evidence="ECO:0007829|PDB:7PW5" FT STRAND 940..942 FT /evidence="ECO:0007829|PDB:7PW5" FT STRAND 944..946 FT /evidence="ECO:0007829|PDB:7PW5" FT STRAND 948..955 FT /evidence="ECO:0007829|PDB:7PW5" FT STRAND 958..962 FT /evidence="ECO:0007829|PDB:7PW5" FT STRAND 965..967 FT /evidence="ECO:0007829|PDB:7PW5" FT HELIX 976..978 FT /evidence="ECO:0007829|PDB:7PW5" FT STRAND 979..981 FT /evidence="ECO:0007829|PDB:7PW5" FT STRAND 985..990 FT /evidence="ECO:0007829|PDB:7PW5" SQ SEQUENCE 991 AA; 109684 MW; 9D8168B171179CFF CRC64; MAGPVSLRDL LMGASAWMGS ESPGGSPTEG GGSAAGGPEP PWREDEICVV GIFGKTALRL NSEKFSLVNT VCDRQVFPLF RHQDPGDPGP GIRTEAGAVG EAGGAEDPGA AAGGSVRGSG AVAEGNRTEA GSQDYSLLQA YYSQESKVLY LLLTSICDNS QLLRACRALQ SGEAGGGLSL PHAEAHEFWK HQEKLQCLSL LYLFSVCHIL LLVHPTCSFD ITYDRVFRAL DGLRQKVLPL LKTAIKDCPV GKDWKLNCRP CPPRLLFLFQ LNGALKVEPP RNQDPAHPDK PKKHSPKRRL QHALEDQIYR IFRKSRVLTN QSINCLFTVP ANQAFVYIVP GSQEEDPVGM LLDQLRSHCT VKDPESLLVP APLSGPRRYQ VMRQHSRQQL SFHIDSSSSS SSGQLVDFTL REFLWQHVEL VLSKKGFDDS VGRNPQPSHF ELPTYQKWIS AASKLYEVAI DGKEEDLGSP TGELTSKILS SIKVLEGFLD IDTKFSENRC QKALPMAHSA YQSNLPHNYT MTVHKNQLAQ ALRVYSQHAR GPAFHKYAMQ LHEDCYKFWS NGHQLCEERS LTDQHCVHKF HSLPKSGEKP EADRNPPVLY HNSRARSTGA CNCGRKQAPR DDPFDIKAAN YDFYQLLEEK CCGKLDHINF PVFEPSTPDP APAKNESSPA PPDSDADKLK EKEPQTQGES TSLSLALSLG QSTDSLGTYP ADPQAGGDNP EVHGQVEVKT EKRPNFVDRQ ASTVEYLPGM LHSNCPKGLL PKFSSWSLVK LGPAKSYNFH TGLDQQGFIP GTNYLMPWDI VIRTRAEDEG DLDTNSWPAP NKAIPGKRSA VVMGRGRRRD DIARAFVGFE YEDSRGRRFM CSGPDKVMKV MGSGPKESAL KALNSDMPLY ILSSSQGRGL KPHYAQLMRL FVVVPDAPLQ IILMPQVQPG PPPCPVFYPE KQEITLPPDG LWVLRFPYAY VTERGPCFPP KENVQLMSYK VLRGVLKAVT Q //