ID PSME4_HUMAN Reviewed; 1843 AA. AC Q14997; Q1XBG4; Q1XBG5; Q1XBG6; Q2M1Z0; Q6IPR2; Q86XF8; DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot. DT 20-MAR-2007, sequence version 2. DT 02-DEC-2020, entry version 155. DE RecName: Full=Proteasome activator complex subunit 4; DE AltName: Full=Proteasome activator PA200; GN Name=PSME4; Synonyms=KIAA0077; 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 2 AND 3), AND NUCLEOTIDE SEQUENCE RP [MRNA] OF 1-1210 (ISOFORM 1). RA Blickwedehl J., McEvoy S., Wong I., Kousis P., Cresswell P., Liang P., RA Bangia N.; RT "Proteasomes and Proteasome Activator 200kD (PA200) accumulate on chromatin RT in response to ionizing radiation."; RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 104-1843 (ISOFORM 1). RC TISSUE=Brain, Mammary gland, and Skeletal muscle; 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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 46-1843 (ISOFORM 1). RC TISSUE=Bone marrow; RX PubMed=7584044; DOI=10.1093/dnares/1.5.223; RA Nomura N., Nagase T., Miyajima N., Sazuka T., Tanaka A., Sato S., Seki N., RA Kawarabayasi Y., Ishikawa K., Tabata S.; RT "Prediction of the coding sequences of unidentified human genes. II. The RT coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of RT cDNA clones from human cell line KG-1."; RL DNA Res. 1:223-229(1994). RN [4] RP IDENTIFICATION, FUNCTION, SUBUNIT, INTERACTION WITH PROTEASOMES 20S AND RP 26S, PHOSPHORYLATION, AND SUBCELLULAR LOCATION. RX PubMed=12093752; DOI=10.1093/emboj/cdf333; RA Ustrell V., Hoffman L., Pratt G., Rechsteiner M.; RT "PA200, a nuclear proteasome activator involved in DNA repair."; RL EMBO J. 21:3516-3525(2002). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17323924; DOI=10.1021/bi061994u; RA Wang X., Chen C.-F., Baker P.R., Chen P.-L., Kaiser P., Huang L.; RT "Mass spectrometric characterization of the affinity-purified human 26S RT proteasome complex."; RL Biochemistry 46:3553-3565(2007). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1121, 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 [7] RP FUNCTION. RX PubMed=18845680; DOI=10.1073/pnas.0803145105; RA Blickwedehl J., Agarwal M., Seong C., Pandita R.K., Melendy T., Sung P., RA Pandita T.K., Bangia N.; RT "Role for proteasome activator PA200 and postglutamyl proteasome activity RT in genomic stability."; RL Proc. Natl. Acad. Sci. U.S.A. 105:16165-16170(2008). RN [8] 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 [9] RP FUNCTION. RX PubMed=22550082; DOI=10.1158/1541-7786.mcr-11-0493-t; RA Blickwedehl J., Olejniczak S., Cummings R., Sarvaiya N., Mantilla A., RA Chanan-Khan A., Pandita T.K., Schmidt M., Thompson C.B., Bangia N.; RT "The proteasome activator PA200 regulates tumor cell responsiveness to RT glutamine and resistance to ionizing radiation."; RL Mol. Cancer Res. 10:937-944(2012). RN [10] RP FUNCTION, AND MUTAGENESIS OF 1716-ASN-PHE-1717. RX PubMed=23706739; DOI=10.1016/j.cell.2013.04.032; RA Qian M.X., Pang Y., Liu C.H., Haratake K., Du B.Y., Ji D.Y., Wang G.F., RA Zhu Q.Q., Song W., Yu Y., Zhang X.X., Huang H.T., Miao S., Chen L.B., RA Zhang Z.H., Liang Y.N., Liu S., Cha H., Yang D., Zhai Y., Komatsu T., RA Tsuruta F., Li H., Cao C., Li W., Li G.H., Cheng Y., Chiba T., Wang L., RA Goldberg A.L., Shen Y., Qiu X.B.; RT "Acetylation-mediated proteasomal degradation of core histones during DNA RT repair and spermatogenesis."; RL Cell 153:1012-1024(2013). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1121; SER-1614 AND SER-1746, RP 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). CC -!- FUNCTION: Associated component of the proteasome that specifically CC recognizes acetylated histones and promotes ATP- and ubiquitin- CC independent degradation of core histones during spermatogenesis and DNA CC damage response. Recognizes and binds acetylated histones via its CC bromodomain-like (BRDL) region and activates the proteasome by opening CC the gated channel for substrate entry. Binds to the core proteasome via CC its C-terminus, which occupies the same binding sites as the CC proteasomal ATPases, opening the closed structure of the proteasome via CC an active gating mechanism. Component of the spermatoproteasome, a form CC of the proteasome specifically found in testis: binds to acetylated CC histones and promotes degradation of histones, thereby participating CC actively to the exchange of histones during spermatogenesis. Also CC involved in DNA damage response in somatic cells, by promoting CC degradation of histones following DNA double-strand breaks. CC {ECO:0000269|PubMed:12093752, ECO:0000269|PubMed:18845680, CC ECO:0000269|PubMed:22550082, ECO:0000269|PubMed:23706739}. CC -!- SUBUNIT: Homodimer. Interacts with the 20S and 26S proteasomes. CC Component of the spermatoproteasome, a form of the proteasome CC specifically found in testis. {ECO:0000269|PubMed:12093752}. CC -!- INTERACTION: CC Q14997; Q13137: CALCOCO2; NbExp=3; IntAct=EBI-1236916, EBI-739580; CC Q14997; Q86Y26: NUTM1; NbExp=3; IntAct=EBI-1236916, EBI-10178410; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250}. Nucleus CC {ECO:0000269|PubMed:12093752}. Nucleus speckle {ECO:0000250}. CC Note=Found in nuclear foci following treatment with ionizing radiation, CC but not with ultraviolet irradiation or H(2)O(2). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q14997-1; Sequence=Displayed; CC Name=2; CC IsoId=Q14997-2; Sequence=VSP_023878; CC Name=3; CC IsoId=Q14997-3; Sequence=VSP_023877, VSP_023879; CC Name=4; CC IsoId=Q14997-4; Sequence=VSP_023876; CC -!- DOMAIN: The bromodomain-like (BRDL) region specifically recognizes and CC binds acetylated histones. {ECO:0000269|PubMed:23706739}. CC -!- SIMILARITY: Belongs to the BLM10 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAI12170.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAI13669.1; Type=Erroneous initiation; 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; AY894754; AAX83869.1; -; mRNA. DR EMBL; AY894755; AAX83870.1; -; mRNA. DR EMBL; AY894756; AAX83871.1; -; mRNA. DR EMBL; BC043602; AAH43602.1; -; mRNA. DR EMBL; BC071768; AAH71768.1; -; mRNA. DR EMBL; BC112169; AAI12170.1; ALT_INIT; mRNA. DR EMBL; BC113668; AAI13669.1; ALT_INIT; mRNA. DR EMBL; D38521; BAA07526.1; -; mRNA. DR CCDS; CCDS33197.2; -. [Q14997-1] DR RefSeq; NP_055429.2; NM_014614.2. [Q14997-1] DR PDB; 6KWX; EM; 3.75 A; A=1-1843. DR PDB; 6KWY; EM; 2.72 A; c=1-1843. DR PDB; 6REY; EM; 3.00 A; c/d=1-1843. DR PDBsum; 6KWX; -. DR PDBsum; 6KWY; -. DR PDBsum; 6REY; -. DR SMR; Q14997; -. DR BioGRID; 116807; 49. DR DIP; DIP-38203N; -. DR IntAct; Q14997; 30. DR MINT; Q14997; -. DR STRING; 9606.ENSP00000384211; -. DR iPTMnet; Q14997; -. DR PhosphoSitePlus; Q14997; -. DR BioMuta; PSME4; -. DR DMDM; 134034993; -. DR EPD; Q14997; -. DR jPOST; Q14997; -. DR MassIVE; Q14997; -. DR MaxQB; Q14997; -. DR PaxDb; Q14997; -. DR PeptideAtlas; Q14997; -. DR PRIDE; Q14997; -. DR ProteomicsDB; 60286; -. [Q14997-1] DR ProteomicsDB; 60287; -. [Q14997-2] DR ProteomicsDB; 60288; -. [Q14997-3] DR ProteomicsDB; 60289; -. [Q14997-4] DR Antibodypedia; 30226; 100 antibodies. DR Ensembl; ENST00000404125; ENSP00000384211; ENSG00000068878. [Q14997-1] DR GeneID; 23198; -. DR KEGG; hsa:23198; -. DR UCSC; uc002rxp.2; human. [Q14997-1] DR CTD; 23198; -. DR DisGeNET; 23198; -. DR EuPathDB; HostDB:ENSG00000068878.14; -. DR GeneCards; PSME4; -. DR HGNC; HGNC:20635; PSME4. DR HPA; ENSG00000068878; Tissue enhanced (skeletal). DR MIM; 607705; gene. DR neXtProt; NX_Q14997; -. DR OpenTargets; ENSG00000068878; -. DR PharmGKB; PA134872587; -. DR eggNOG; KOG1851; Eukaryota. DR GeneTree; ENSGT00390000011433; -. DR HOGENOM; CLU_000772_2_0_1; -. DR InParanoid; Q14997; -. DR OMA; GKDWSDE; -. DR OrthoDB; 83617at2759; -. DR PhylomeDB; Q14997; -. DR TreeFam; TF106237; -. DR PathwayCommons; Q14997; -. DR Reactome; R-HSA-1169091; Activation of NF-kappaB in B cells. DR Reactome; R-HSA-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha. DR Reactome; R-HSA-1236974; ER-Phagosome pathway. DR Reactome; R-HSA-1236978; Cross-presentation of soluble exogenous antigens (endosomes). DR Reactome; R-HSA-174113; SCF-beta-TrCP mediated degradation of Emi1. DR Reactome; R-HSA-174154; APC/C:Cdc20 mediated degradation of Securin. DR Reactome; R-HSA-174178; APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1. DR Reactome; R-HSA-174184; Cdc20:Phospho-APC/C mediated degradation of Cyclin A. DR Reactome; R-HSA-180534; Vpu mediated degradation of CD4. DR Reactome; R-HSA-180585; Vif-mediated degradation of APOBEC3G. DR Reactome; R-HSA-195253; Degradation of beta-catenin by the destruction complex. DR Reactome; R-HSA-202424; Downstream TCR signaling. DR Reactome; R-HSA-211733; Regulation of activated PAK-2p34 by proteasome mediated degradation. DR Reactome; R-HSA-2467813; Separation of Sister Chromatids. DR Reactome; R-HSA-2871837; FCERI mediated NF-kB activation. DR Reactome; R-HSA-349425; Autodegradation of the E3 ubiquitin ligase COP1. DR Reactome; R-HSA-350562; Regulation of ornithine decarboxylase (ODC). DR Reactome; R-HSA-382556; ABC-family proteins mediated transport. DR Reactome; R-HSA-450408; AUF1 (hnRNP D0) binds and destabilizes mRNA. DR Reactome; R-HSA-4608870; Asymmetric localization of PCP proteins. DR Reactome; R-HSA-4641257; Degradation of AXIN. DR Reactome; R-HSA-4641258; Degradation of DVL. DR Reactome; R-HSA-5358346; Hedgehog ligand biogenesis. DR Reactome; R-HSA-5362768; Hh mutants that don't undergo autocatalytic processing are degraded by ERAD. DR Reactome; R-HSA-5607761; Dectin-1 mediated noncanonical NF-kB signaling. DR Reactome; R-HSA-5607764; CLEC7A (Dectin-1) signaling. DR Reactome; R-HSA-5610780; Degradation of GLI1 by the proteasome. DR Reactome; R-HSA-5610783; Degradation of GLI2 by the proteasome. DR Reactome; R-HSA-5610785; GLI3 is processed to GLI3R by the proteasome. DR Reactome; R-HSA-5632684; Hedgehog 'on' state. DR Reactome; R-HSA-5658442; Regulation of RAS by GAPs. DR Reactome; R-HSA-5668541; TNFR2 non-canonical NF-kB pathway. DR Reactome; R-HSA-5676590; NIK-->noncanonical NF-kB signaling. DR Reactome; R-HSA-5678895; Defective CFTR causes cystic fibrosis. DR Reactome; R-HSA-5687128; MAPK6/MAPK4 signaling. DR Reactome; R-HSA-5689603; UCH proteinases. DR Reactome; R-HSA-5689880; Ub-specific processing proteases. DR Reactome; R-HSA-68827; CDT1 association with the CDC6:ORC:origin complex. DR Reactome; R-HSA-68949; Orc1 removal from chromatin. DR Reactome; R-HSA-69017; CDK-mediated phosphorylation and removal of Cdc6. DR Reactome; R-HSA-69481; G2/M Checkpoints. DR Reactome; R-HSA-69601; Ubiquitin Mediated Degradation of Phosphorylated Cdc25A. DR Reactome; R-HSA-75815; Ubiquitin-dependent degradation of Cyclin D. DR Reactome; R-HSA-8852276; The role of GTSE1 in G2/M progression after G2 checkpoint. DR Reactome; R-HSA-8854050; FBXL7 down-regulates AURKA during mitotic entry and in early mitosis. DR Reactome; R-HSA-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs. DR Reactome; R-HSA-8939902; Regulation of RUNX2 expression and activity. DR Reactome; R-HSA-8948751; Regulation of PTEN stability and activity. DR Reactome; R-HSA-8951664; Neddylation. DR Reactome; R-HSA-9010553; Regulation of expression of SLITs and ROBOs. DR Reactome; R-HSA-9020702; Interleukin-1 signaling. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR BioGRID-ORCS; 23198; 11 hits in 847 CRISPR screens. DR ChiTaRS; PSME4; human. DR GeneWiki; PSME4; -. DR GenomeRNAi; 23198; -. DR Pharos; Q14997; Tdark. DR PRO; PR:Q14997; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q14997; protein. DR Bgee; ENSG00000068878; Expressed in epithelium of mammary gland and 246 other tissues. DR ExpressionAtlas; Q14997; baseline and differential. DR Genevisible; Q14997; HS. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; HDA:UniProtKB. DR GO; GO:1990111; C:spermatoproteasome complex; ISS:UniProtKB. DR GO; GO:0070577; F:lysine-acetylated histone binding; ISS:UniProtKB. DR GO; GO:0016504; F:peptidase activator activity; ISS:UniProtKB. DR GO; GO:0070628; F:proteasome binding; IBA:GO_Central. DR GO; GO:0031145; P:anaphase-promoting complex-dependent catabolic process; TAS:Reactome. DR GO; GO:0002479; P:antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent; TAS:Reactome. DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB. DR GO; GO:0006281; P:DNA repair; ISS:UniProtKB. DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome. DR GO; GO:0070498; P:interleukin-1-mediated signaling pathway; TAS:Reactome. DR GO; GO:0000165; P:MAPK cascade; TAS:Reactome. DR GO; GO:0007275; P:multicellular organism development; IEA:UniProtKB-KW. DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; TAS:Reactome. DR GO; GO:0010972; P:negative regulation of G2/M transition of mitotic cell cycle; TAS:Reactome. DR GO; GO:0038061; P:NIK/NF-kappaB signaling; TAS:Reactome. DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; TAS:Reactome. DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome. DR GO; GO:0010499; P:proteasomal ubiquitin-independent protein catabolic process; ISS:UniProtKB. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; TAS:Reactome. DR GO; GO:0016579; P:protein deubiquitination; TAS:Reactome. DR GO; GO:0000209; P:protein polyubiquitination; TAS:Reactome. DR GO; GO:0006521; P:regulation of cellular amino acid metabolic process; TAS:Reactome. DR GO; GO:1902036; P:regulation of hematopoietic stem cell differentiation; TAS:Reactome. DR GO; GO:1901990; P:regulation of mitotic cell cycle phase transition; TAS:Reactome. DR GO; GO:0043488; P:regulation of mRNA stability; TAS:Reactome. DR GO; GO:0061418; P:regulation of transcription from RNA polymerase II promoter in response to hypoxia; TAS:Reactome. DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; TAS:Reactome. DR GO; GO:0035093; P:spermatogenesis, exchange of chromosomal proteins; ISS:UniProtKB. DR GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; TAS:Reactome. DR GO; GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome. DR GO; GO:0055085; P:transmembrane transport; TAS:Reactome. DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; TAS:Reactome. DR GO; GO:0060071; P:Wnt signaling pathway, planar cell polarity pathway; TAS:Reactome. DR Gene3D; 1.25.10.10; -; 1. DR InterPro; IPR011989; ARM-like. DR InterPro; IPR016024; ARM-type_fold. DR InterPro; IPR032430; Blm10_mid. DR InterPro; IPR035309; PSME4. DR InterPro; IPR021843; PSME4_C. DR PANTHER; PTHR32170; PTHR32170; 1. DR Pfam; PF16507; BLM10_mid; 1. DR Pfam; PF11919; DUF3437; 1. DR SUPFAM; SSF48371; SSF48371; 2. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Developmental protein; KW Differentiation; DNA damage; DNA repair; Nucleus; Phosphoprotein; KW Polymorphism; Proteasome; Reference proteome; Repeat; Spermatogenesis. FT CHAIN 1..1843 FT /note="Proteasome activator complex subunit 4" FT /id="PRO_0000280718" FT REPEAT 475..519 FT /note="HEAT 1" FT REPEAT 998..1037 FT /note="HEAT 2" FT REPEAT 1179..1217 FT /note="HEAT 3" FT REPEAT 1354..1392 FT /note="HEAT 4" FT REPEAT 1636..1674 FT /note="HEAT 5" FT REPEAT 1680..1718 FT /note="HEAT 6" FT REGION 1650..1738 FT /note="Bromodomain-like (BRDL)" FT MOD_RES 1121 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:23186163" FT MOD_RES 1614 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:23186163" FT MOD_RES 1746 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:23186163" FT VAR_SEQ 1..1628 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_023876" FT VAR_SEQ 1..856 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|Ref.1" FT /id="VSP_023877" FT VAR_SEQ 1..625 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.1" FT /id="VSP_023878" FT VAR_SEQ 857..871 FT /note="YDLSRENHREVIATV -> MGENLAKKIMFFLLI (in isoform 3)" FT /evidence="ECO:0000303|Ref.1" FT /id="VSP_023879" FT VARIANT 872 FT /note="I -> V (in dbSNP:rs2302878)" FT /id="VAR_031189" FT VARIANT 1371 FT /note="S -> T (in dbSNP:rs805408)" FT /id="VAR_031190" FT VARIANT 1825 FT /note="T -> A (in dbSNP:rs35903236)" FT /id="VAR_059755" FT MUTAGEN 1716..1717 FT /note="NF->TS: Abolihes binding to acetylated histones." FT /evidence="ECO:0000269|PubMed:23706739" FT CONFLICT 217 FT /note="F -> V (in Ref. 1; AAX83871)" FT /evidence="ECO:0000305" FT CONFLICT 710 FT /note="C -> R (in Ref. 1; AAX83871)" FT /evidence="ECO:0000305" FT CONFLICT 984 FT /note="N -> S (in Ref. 1; AAX83871)" FT /evidence="ECO:0000305" FT CONFLICT 1401 FT /note="L -> F (in Ref. 2; AAH43602)" FT /evidence="ECO:0000305" FT STRAND 29..31 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 33..35 FT /evidence="ECO:0000244|PDB:6KWY" FT TURN 39..42 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 43..65 FT /evidence="ECO:0000244|PDB:6KWY" FT TURN 68..71 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 72..86 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 92..104 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 113..127 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 130..132 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 135..137 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 143..150 FT /evidence="ECO:0000244|PDB:6KWY" FT TURN 158..161 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 167..169 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 170..180 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 181..183 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 188..192 FT /evidence="ECO:0000244|PDB:6KWY" FT TURN 193..195 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 197..199 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 206..217 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 224..229 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 231..233 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 235..244 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 250..265 FT /evidence="ECO:0000244|PDB:6KWY" FT TURN 267..269 FT /evidence="ECO:0000244|PDB:6REY" FT TURN 273..275 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 276..286 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 292..294 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 298..300 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 303..305 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 308..318 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 326..336 FT /evidence="ECO:0000244|PDB:6KWY" FT TURN 338..341 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 343..345 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 350..371 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 384..386 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 390..408 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 415..427 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 429..438 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 440..443 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 451..461 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 464..467 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 477..480 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 481..487 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 489..491 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 497..507 FT /evidence="ECO:0000244|PDB:6KWY" FT TURN 508..513 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 520..525 FT /evidence="ECO:0000244|PDB:6REY" FT HELIX 531..537 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 540..543 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 544..547 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 549..559 FT /evidence="ECO:0000244|PDB:6KWY" FT TURN 577..583 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 584..595 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 599..615 FT /evidence="ECO:0000244|PDB:6KWY" FT TURN 620..622 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 623..637 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 639..657 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 661..665 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 672..683 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 689..691 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 696..699 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 702..705 FT /evidence="ECO:0000244|PDB:6KWY" FT TURN 711..713 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 715..729 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 732..734 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 743..746 FT /evidence="ECO:0000244|PDB:6REY" FT TURN 747..749 FT /evidence="ECO:0000244|PDB:6REY" FT HELIX 752..754 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 762..764 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 774..787 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 789..799 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 807..823 FT /evidence="ECO:0000244|PDB:6KWY" FT TURN 825..827 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 837..839 FT /evidence="ECO:0000244|PDB:6REY" FT STRAND 859..861 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 864..882 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 889..900 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 904..906 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 908..924 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 932..934 FT /evidence="ECO:0000244|PDB:6REY" FT HELIX 937..953 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 963..975 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 976..978 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 980..994 FT /evidence="ECO:0000244|PDB:6KWY" FT TURN 1001..1003 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1005..1008 FT /evidence="ECO:0000244|PDB:6KWY" FT TURN 1009..1012 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 1014..1016 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1021..1032 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 1035..1037 FT /evidence="ECO:0000244|PDB:6REY" FT STRAND 1040..1042 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 1044..1046 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1049..1058 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 1062..1064 FT /evidence="ECO:0000244|PDB:6REY" FT HELIX 1070..1086 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1100..1105 FT /evidence="ECO:0000244|PDB:6KWY" FT TURN 1122..1126 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1127..1135 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1138..1154 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1161..1172 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 1177..1179 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1183..1191 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1198..1214 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 1221..1224 FT /evidence="ECO:0000244|PDB:6REY" FT TURN 1226..1228 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 1240..1242 FT /evidence="ECO:0000244|PDB:6KWY" FT TURN 1244..1246 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1247..1249 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1260..1264 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 1271..1273 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 1281..1286 FT /evidence="ECO:0000244|PDB:6REY" FT TURN 1289..1291 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 1299..1302 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1306..1313 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1316..1325 FT /evidence="ECO:0000244|PDB:6KWY" FT TURN 1332..1334 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1339..1351 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1356..1367 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1374..1389 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1390..1392 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1395..1414 FT /evidence="ECO:0000244|PDB:6KWY" FT TURN 1418..1420 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1421..1431 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 1433..1435 FT /evidence="ECO:0000244|PDB:6KWY" FT TURN 1437..1439 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1442..1447 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 1451..1453 FT /evidence="ECO:0000244|PDB:6REY" FT HELIX 1460..1474 FT /evidence="ECO:0000244|PDB:6KWY" FT TURN 1475..1477 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1480..1490 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1491..1493 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 1494..1496 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1499..1512 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1530..1540 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1542..1544 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1568..1584 FT /evidence="ECO:0000244|PDB:6KWY" FT TURN 1585..1587 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 1588..1590 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 1596..1599 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1600..1604 FT /evidence="ECO:0000244|PDB:6KWY" FT TURN 1616..1618 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1619..1630 FT /evidence="ECO:0000244|PDB:6KWY" FT TURN 1636..1638 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1639..1648 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 1651..1653 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1655..1670 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1673..1677 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1680..1693 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1699..1714 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1722..1732 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 1742..1744 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1756..1771 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1781..1789 FT /evidence="ECO:0000244|PDB:6KWY" FT STRAND 1792..1794 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1798..1812 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1817..1820 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1821..1823 FT /evidence="ECO:0000244|PDB:6KWY" FT HELIX 1826..1833 FT /evidence="ECO:0000244|PDB:6KWY" FT TURN 1840..1842 FT /evidence="ECO:0000244|PDB:6REY" SQ SEQUENCE 1843 AA; 211334 MW; 2D2C3A594E4FA4E7 CRC64; MEPAERAGVG EPPEPGGRPE PGPRGFVPQK EIVYNKLLPY AERLDAESDL QLAQIKCNLG RAVQLQELWP GGLFWTRKLS TYIRLYGRKF SKEDHVLFIK LLYELVSIPK LEISMMQGFA RLLINLLKKK ELLSRADLEL PWRPLYDMVE RILYSKTEHL GLNWFPNSVE NILKTLVKSC RPYFPADATA EMLEEWRPLM CPFDVTMQKA ITYFEIFLPT SLPPELHHKG FKLWFDELIG LWVSVQNLPQ WEGQLVNLFA RLATDNIGYI DWDPYVPKIF TRILRSLNLP VGSSQVLVPR FLTNAYDIGH AVIWITAMMG GPSKLVQKHL AGLFNSITSF YHPSNNGRWL NKLMKLLQRL PNSVVRRLHR ERYKKPSWLT PVPDSHKLTD QDVTDFVQCI IQPVLLAMFS KTGSLEAAQA LQNLALMRPE LVIPPVLERT YPALETLTEP HQLTATLSCV IGVARSLVSG GRWFPEGPTH MLPLLMRALP GVDPNDFSKC MITFQFIATF STLVPLVDCS SVLQERNDLT EVERELCSAT AEFEDFVLQF MDRCFGLIES STLEQTREET ETEKMTHLES LVELGLSSTF STILTQCSKE IFMVALQKVF NFSTSHIFET RVAGRMVADM CRAAVKCCPE ESLKLFVPHC CSVITQLTMN DDVLNDEELD KELLWNLQLL SEITRVDGRK LLLYREQLVK ILQRTLHLTC KQGYTLSCNL LHHLLRSTTL IYPTEYCSVP GGFDKPPSEY FPIKDWGKPG DLWNLGIQWH VPSSEEVSFA FYLLDSFLQP ELVKLQHCGD GKLEMSRDDI LQSLTIVHNC LIGSGNLLPP LKGEPVTNLV PSMVSLEETK LYTGLEYDLS RENHREVIAT VIRKLLNHIL DNSEDDTKSL FLIIKIIGDL LQFQGSHKHE FDSRWKSFNL VKKSMENRLH GKKQHIRALL IDRVMLQHEL RTLTVEGCEY KKIHQDMIRD LLRLSTSSYS QVRNKAQQTF FAALGAYNFC CRDIIPLVLE FLRPDRQGVT QQQFKGALYC LLGNHSGVCL ANLHDWDCIV QTWPAIVSSG LSQAMSLEKP SIVRLFDDLA EKIHRQYETI GLDFTIPKSC VEIAELLQQS KNPSINQILL SPEKIKEGIK RQQEKNADAL RNYENLVDTL LDGVEQRNLP WKFEHIGIGL LSLLLRDDRV LPLRAIRFFV ENLNHDAIVV RKMAISAVAG ILKQLKRTHK KLTINPCEIS GCPKPTQIIA GDRPDNHWLH YDSKTIPRTK KEWESSCFVE KTHWGYYTWP KNMVVYAGVE EQPKLGRSRE DMTEAEQIIF DHFSDPKFVE QLITFLSLED RKGKDKFNPR RFCLFKGIFR NFDDAFLPVL KPHLEHLVAD SHESTQRCVA EIIAGLIRGS KHWTFEKVEK LWELLCPLLR TALSNITVET YNDWGACIAT SCESRDPRKL HWLFELLLES PLSGEGGSFV DACRLYVLQG GLAQQEWRVP ELLHRLLKYL EPKLTQVYKN VRERIGSVLT YIFMIDVSLP NTTPTISPHV PEFTARILEK LKPLMDVDEE IQNHVMEENG IGEEDERTQG IKLLKTILKW LMASAGRSFS TAVTEQLQLL PLFFKIAPVE NDNSYDELKR DAKLCLSLMS QGLLYPHQVP LVLQVLKQTA RSSSWHARYT VLTYLQTMVF YNLFIFLNNE DAVKDIRWLV ISLLEDEQLE VREMAATTLS GLLQCNFLTM DSPMQIHFEQ LCKTKLPKKR KRDPGSVGDT IPSAELVKRH AGVLGLGACV LSSPYDVPTW MPQLLMNLSA HLNDPQPIEM TVKKTLSNFR RTHHDNWQEH KQQFTDDQLL VLTDLLVSPC YYA //