ID FOXO4_HUMAN Reviewed; 505 AA. AC P98177; B7WPJ7; O43821; Q13720; Q3KPF1; Q8TDK9; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 25-JUL-2006, sequence version 5. DT 05-OCT-2010, entry version 109. DE RecName: Full=Forkhead box protein O4; DE AltName: Full=Fork head domain transcription factor AFX1; GN Name=FOXO4; Synonyms=AFX, AFX1, MLLT7; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Blood; RX MEDLINE=98001080; PubMed=9341872; DOI=10.1007/s004390050553; RA Peters U., Haberhausen G., Kostrzewa M., Nolte D., Mueller U.; RT "AFX1 and p54nrb: fine mapping, genomic structure, and exclusion as RT candidate genes of X-linked dystonia parkinsonism."; RL Hum. Genet. 100:569-572(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX MEDLINE=97163401; PubMed=9010221; DOI=10.1038/sj.onc.1200814; RA Borkhardt A., Repp R., Haas O.A., Leis T., Harbott J., Kreuder J., RA Hammermann J., Henn T., Lampert F.; RT "Cloning and characterization of AFX, the gene that fuses to MLL in RT acute leukemias with a t(X;11)(q13;q23)."; RL Oncogene 14:195-202(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ZETA). RX MEDLINE=21864263; PubMed=11779849; DOI=10.1074/jbc.M106091200; RA Yang Z., Whelan J., Babb R., Bowen B.R.; RT "An mRNA splice variant of the AFX gene with altered transcriptional RT activity."; RL J. Biol. Chem. 277:8068-8075(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S., RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., RA Williams G., Williams L., Williamson A., Williamson H., Wilming L., RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP CHROMOSOMAL TRANSLOCATION. RC TISSUE=Bone marrow; RX MEDLINE=95118921; PubMed=7529552; DOI=10.1002/gcc.2870110203; RA Parry P., Wei Y., Evans G.; RT "Cloning and characterization of the t(X;11) breakpoint from a RT leukemic cell line identify a new member of the forkhead gene RT family."; RL Genes Chromosomes Cancer 11:79-84(1994). RN [8] RP FUNCTION, PHOSPHORYLATION AT SER-197 AND SER-262, AND MUTAGENESIS OF RP SER-197 AND SER-262. RX PubMed=10217147; DOI=10.1038/19328; RA Kops G.J.P.L., de Ruiter N.D., De Vries-Smits A.M.M., Powell D.R., RA Bos J.L., Burgering B.M.T.; RT "Direct control of the forkhead transcription factor AFX by protein RT kinase B."; RL Nature 398:630-634(1999). RN [9] RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-197 AND SER-262, AND RP MUTAGENESIS OF THR-32; SER-197 AND SER-262. RX PubMed=10518537; DOI=10.1073/pnas.96.21.11836; RA Takaishi H., Konishi H., Matsuzaki H., Ono Y., Shirai Y., Saito N., RA Kitamura T., Ogawa W., Kasuga M., Kikkawa U., Nishizuka Y.; RT "Regulation of nuclear translocation of forkhead transcription factor RT AFX by protein kinase B."; RL Proc. Natl. Acad. Sci. U.S.A. 96:11836-11841(1999). RN [10] RP FUNCTION. RX PubMed=10783894; DOI=10.1038/35008115; RA Medema R.H., Kops G.J.P.L., Bos J.L., Burgering B.M.T.; RT "AFX-like forkhead transcription factors mediate cell-cycle regulation RT by Ras and PKB through p27kip1."; RL Nature 404:782-787(2000). RN [11] RP FUNCTION. RX PubMed=12761217; DOI=10.1074/jbc.M302042200; RA Tang T.T.-L., Lasky L.A.; RT "The forkhead transcription factor FOXO4 induces the down-regulation RT of hypoxia-inducible factor 1 alpha by a von Hippel-Lindau protein- RT independent mechanism."; RL J. Biol. Chem. 278:30125-30135(2003). RN [12] RP FUNCTION, INTERACTION WITH CBP AND SIRT1, AND ACETYLATION. RX PubMed=15126506; DOI=10.1074/jbc.M401138200; RA van der Horst A., Tertoolen L.G.J., de Vries-Smits L.M.M., Frye R.A., RA Medema R.H., Burgering B.M.T.; RT "FOXO4 is acetylated upon peroxide stress and deacetylated by the RT longevity protein hSir2(SIRT1)."; RL J. Biol. Chem. 279:28873-28879(2004). RN [13] RP INTERACTION WITH YWHAZ, AND SUBCELLULAR LOCATION. RX PubMed=16114898; DOI=10.1021/bi050618r; RA Obsilova V., Vecer J., Herman P., Pabianova A., Sulc M., Teisinger J., RA Boura E., Obsil T.; RT "14-3-3 protein interacts with nuclear localization sequence of RT forkhead transcription factor FoxO4."; RL Biochemistry 44:11608-11617(2005). RN [14] RP FUNCTION, AND INTERACTION WITH MYOCD AND SRF. RX PubMed=16054032; DOI=10.1016/j.devcel.2005.05.017; RA Liu Z.-P., Wang Z., Yanagisawa H., Olson E.N.; RT "Phenotypic modulation of smooth muscle cells through interaction of RT Foxo4 and myocardin."; RL Dev. Cell 9:261-270(2005). RN [15] RP PHOSPHORYLATION AT THR-32; SER-197 AND SER-262, AND MUTAGENESIS OF RP THR-32; SER-197 AND SER-262. RX PubMed=16272144; DOI=10.1093/jb/mvi146; RA Matsuzaki H., Ichino A., Hayashi T., Yamamoto T., Kikkawa U.; RT "Regulation of intracellular localization and transcriptional activity RT of FOXO4 by protein kinase B through phosphorylation at the motif RT sites conserved among the FOXO family."; RL J. Biochem. 138:485-491(2005). RN [16] RP PHARMACEUTICAL USE. RX PubMed=15688030; DOI=10.1038/sj.onc.1208352; RA Yang H., Zhao R., Yang H.-Y., Lee M.-H.; RT "Constitutively active FOXO4 inhibits Akt activity, regulates p27 Kip1 RT stability, and suppresses HER2-mediated tumorigenicity."; RL Oncogene 24:1924-1935(2005). RN [17] RP FUNCTION, INTERACTION WITH USP7, UBIQUITINATION, DEUBIQUITINATION BY RP USP7, AND SUBCELLULAR LOCATION. RX PubMed=16964248; DOI=10.1038/ncb1469; RA van der Horst A., de Vries-Smits A.M., Brenkman A.B., van Triest M.H., RA van den Broek N., Colland F., Maurice M.M., Burgering B.M.; RT "FOXO4 transcriptional activity is regulated by monoubiquitination and RT USP7/HAUSP."; RL Nat. Cell Biol. 8:1064-1073(2006). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-111, AND MASS RP SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=18187866; DOI=10.2116/analsci.24.161; RA Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y.; RT "Automated phosphoproteome analysis for cultured cancer cells by two- RT dimensional nanoLC-MS using a calcined titania/C18 biphasic column."; RL Anal. Sci. 24:161-166(2008). RN [19] RP PHOSPHORYLATION AT SER-197 AND SER-200, AND MASS SPECTROMETRY. RA Carrascal M., Abian J.; RL Submitted (JAN-2008) to UniProtKB. RN [20] RP STRUCTURE BY NMR OF 86-211. RX PubMed=10921784; DOI=10.1023/A:1008358816478; RA Weigelt J., Climent I., Dahlman-Wright K., Wikstrom M.; RT "1H, 13C and 15N resonance assignments of the DNA binding domain of RT the human forkhead transcription factor AFX."; RL J. Biomol. NMR 17:181-182(2000). RN [21] RP STRUCTURE BY NMR OF 86-211. RX PubMed=11352721; DOI=10.1021/bi001663w; RA Weigelt J., Climent I., Dahlman-Wright K., Wikstrom M.; RT "Solution structure of the DNA binding domain of the human forkhead RT transcription factor AFX (FOXO4)."; RL Biochemistry 40:5861-5869(2001). CC -!- FUNCTION: Transcription factor involved in the regulation of the CC insulin signaling pathway. Binds to insulin-response elements CC (IREs) and can activate transcription of IGFBP1. Down-regulates CC expression of HIF1A and suppresses hypoxia-induced transcriptional CC activation of HIF1A-modulated genes. Also involved in negative CC regulation of the cell cycle. CC -!- SUBUNIT: Interacts with CBP, MYOCD, SIRT1, SRF and YWHAZ. CC Acetylated by CBP and deacetylated by SIRT1. Binding of YWHAZ CC inhibits DNA-binding. Interacts with USP7; the interaction is CC enhanced in presence of hydrogen peroxide and occurs independently CC of TP53. CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=When CC phosphorylated, translocated from nucleus to cytoplasm. CC Dephosphorylation triggers nuclear translocation. CC Monoubiquitination increases nuclear localization. When CC deubiquitinated, translocated from nucleus to cytoplasm. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=FOXO4a; CC IsoId=P98177-1; Sequence=Displayed; CC Name=Zeta; Synonyms=AFXzeta, FOXO4b; CC IsoId=P98177-2; Sequence=VSP_001552; CC -!- TISSUE SPECIFICITY: Heart, brain, placenta, lung, liver, skeletal CC muscle, kidney and pancreas. Isoform zeta is most abundant in the CC liver, kidney, and pancreas. CC -!- PTM: Acetylation by CBP, which is induced by peroxidase stress, CC inhibits transcriptional activity. Deacetylation by SIRT1 is NAD- CC dependent and stimulates transcriptional activity. CC -!- PTM: Phosphorylation by PKB/AKT1 inhibits transcriptional activity CC and is responsible for cytoplasmic localization. CC -!- PTM: Monoubiquitinated; monoubiquitination is induced by oxidative CC stress and reduced by deacetylase inhibitors; results in its CC relocalization to the nucleus and its increased transcriptional CC activity. Deubiquitinated by USP7; deubiquitination is induced by CC oxidative stress; enhances its interaction with USP7 and CC consequently, deubiquitination; increases its translocation to the CC cytoplasm and inhibits its transcriptional activity. Hydrogene- CC peroxide-induced ubiquitination and USP7-mediated deubiquitination CC have no major effect on its protein stability. CC -!- DISEASE: Note=A chromosomal aberration involving FOXO4 is found in CC acute leukemias. Translocation t(X;11)(q13;q23) with MLL/HRX. The CC result is a rogue activator protein. CC -!- PHARMACEUTICAL: A constitutively active FOXO4 mutant where CC phosphorylation sites Thr-32, Ser-187 and Ser-262 have been CC mutated to alanine may have therapeutic potential in ERBB2/HER2- CC overexpressing cancers as it inhibits ERBB2-mediated cell CC survival, transformation and tumorigenicity. CC -!- SIMILARITY: Contains 1 fork-head DNA-binding domain. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/AFX1ID57.html"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; Y11284; CAA72156.1; -; Genomic_DNA. DR EMBL; Y11285; CAA72156.1; JOINED; Genomic_DNA. DR EMBL; Y11286; CAA72156.1; JOINED; Genomic_DNA. DR EMBL; X93996; CAA63819.1; -; mRNA. DR EMBL; AF384029; AAL85197.1; -; mRNA. DR EMBL; AL590764; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471132; EAX05321.1; -; Genomic_DNA. DR EMBL; BC106761; AAI06762.1; -; mRNA. DR EMBL; U10072; AAA82171.1; ALT_SEQ; mRNA. DR IPI; IPI00024316; -. DR IPI; IPI00220121; -. DR PIR; I38654; I38654. DR RefSeq; NP_001164402.1; -. DR RefSeq; NP_005929.2; -. DR UniGene; Hs.584654; -. DR PDB; 1E17; NMR; -; A=86-211. DR PDB; 3L2C; X-ray; 1.87 A; A=86-187. DR PDBsum; 1E17; -. DR PDBsum; 3L2C; -. DR ProteinModelPortal; P98177; -. DR STRING; P98177; -. DR PhosphoSite; P98177; -. DR PRIDE; P98177; -. DR Ensembl; ENST00000374259; ENSP00000363377; ENSG00000184481. DR GeneID; 4303; -. DR UCSC; uc004dys.1; human. DR UCSC; uc004dyt.1; human. DR CTD; 4303; -. DR GeneCards; GC0XP070316; -. DR H-InvDB; HIX0056173; -. DR HGNC; HGNC:7139; FOXO4. DR MIM; 300033; gene. DR eggNOG; prNOG08232; -. DR HOGENOM; HBG714085; -. DR HOVERGEN; HBG057789; -. DR OMA; FSLQHPG; -. DR OrthoDB; EOG92C0VK; -. DR PhylomeDB; P98177; -. DR Pathway_Interaction_DB; pi3kciaktpathway; Class I PI3K signaling events mediated by Akt. DR Pathway_Interaction_DB; foxopathway; FoxO family signaling. DR Pathway_Interaction_DB; smad2_3nuclearpathway; Regulation of nuclear SMAD2/3 signaling. DR Pathway_Interaction_DB; hdac_classiii_pathway; Signaling events mediated by HDAC Class III. DR Reactome; REACT_11061; Signalling by NGF. DR NextBio; 16943; -. DR ArrayExpress; P98177; -. DR Bgee; P98177; -. DR CleanEx; HS_FOXO4; -. DR Genevestigator; P98177; -. DR GermOnline; ENSG00000184481; Homo sapiens. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0003700; F:transcription factor activity; IDA:UniProtKB. DR GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB. DR GO; GO:0007050; P:cell cycle arrest; IDA:UniProtKB. DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW. DR GO; GO:0000080; P:G1 phase of mitotic cell cycle; IDA:UniProtKB. DR GO; GO:0008286; P:insulin receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW. DR GO; GO:0016525; P:negative regulation of angiogenesis; IDA:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell proliferation; IDA:UniProtKB. DR GO; GO:0051151; P:negative regulation of smooth muscle cell d...; IDA:UniProtKB. DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IDA:UniProtKB. DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; TAS:ProtInc. DR InterPro; IPR001766; TF_fork_head. DR InterPro; IPR018122; TF_fork_head_CS. DR InterPro; IPR011991; WHTH_trsnscrt_rep_DNA-bd. DR Gene3D; G3DSA:1.10.10.10; Wing_hlx_DNA_bd; 1. DR PANTHER; PTHR11829; Fork_box_protein; 1. DR Pfam; PF00250; Fork_head; 1. DR PRINTS; PR00053; FORKHEAD. DR SMART; SM00339; FH; 1. DR PROSITE; PS00657; FORK_HEAD_1; FALSE_NEG. DR PROSITE; PS00658; FORK_HEAD_2; 1. DR PROSITE; PS50039; FORK_HEAD_3; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; KW Cell cycle; Chromosomal rearrangement; Complete proteome; Cytoplasm; KW Developmental protein; Differentiation; DNA-binding; Myogenesis; KW Nucleus; Pharmaceutical; Phosphoprotein; Proto-oncogene; KW Transcription; Transcription regulation; Ubl conjugation. FT CHAIN 1 505 Forkhead box protein O4. FT /FTId=PRO_0000091875. FT DNA_BIND 100 188 Fork-head. FT MOD_RES 32 32 Phosphothreonine; by PKB/AKT1. FT MOD_RES 111 111 Phosphoserine. FT MOD_RES 197 197 Phosphoserine; by PKB/AKT1. FT MOD_RES 200 200 Phosphoserine. FT MOD_RES 262 262 Phosphoserine; by PKB/AKT1. FT VAR_SEQ 58 112 Missing (in isoform Zeta). FT /FTId=VSP_001552. FT MUTAGEN 32 32 T->A: Abolishes phosphorylation. Protein FT is located mainly in cytoplasm and shows FT increased transcriptional activity. FT MUTAGEN 197 197 S->A: Abolishes phosphorylation. Protein FT is located mainly in cytoplasm and shows FT increased transcriptional activity. FT MUTAGEN 262 262 S->A: Abolishes phosphorylation. No FT effect on cellular location or FT transcriptional activity. FT CONFLICT 1 11 MDPGNENSATE -> MRIQPQK (in Ref. 2). FT CONFLICT 25 34 QSRPRSCTWP -> RAVPLLHLA (in Ref. 1; FT CAA72156). FT CONFLICT 74 74 P -> S (in Ref. 2; CAA63819). FT CONFLICT 79 79 G -> A (in Ref. 1; CAA72156). FT CONFLICT 109 109 L -> F (in Ref. 2; CAA63819). FT CONFLICT 422 422 P -> R (in Ref. 2 and 3). FT HELIX 106 116 FT HELIX 124 134 FT HELIX 136 138 FT HELIX 149 160 FT STRAND 164 167 FT STRAND 177 180 SQ SEQUENCE 505 AA; 53684 MW; 0C71C8E2167CEE68 CRC64; MDPGNENSAT EAAAIIDLDP DFEPQSRPRS CTWPLPRPEI ANQPSEPPEV EPDLGEKVHT EGRSEPILLP SRLPEPAGGP QPGILGAVTG PRKGGSRRNA WGNQSYAELI SQAIESAPEK RLTLAQIYEW MVRTVPYFKD KGDSNSSAGW KNSIRHNLSL HSKFIKVHNE ATGKSSWWML NPEGGKSGKA PRRRAASMDS SSKLLRGRSK APKKKPSVLP APPEGATPTS PVGHFAKWSG SPCSRNREEA DMWTTFRPRS SSNASSVSTR LSPLRPESEV LAEEIPASVS SYAGGVPPTL NEGLELLDGL NLTSSHSLLS RSGLSGFSLQ HPGVTGPLHT YSSSLFSPAE GPLSAGEGCF SSSQALEALL TSDTPPPPAD VLMTQVDPIL SQAPTLLLLG GLPSSSKLAT GVGLCPKPLE APGPSSLVPT LSMIAPPPVM ASAPIPKALG TPVLTPPTEA ASQDRMPQDL DLDMYMENLE CDMDNIISDL MDEGEGLDFN FEPDP //