ID VPRBP_HUMAN Reviewed; 1507 AA. AC Q9Y4B6; Q2YD74; Q8TBD9; Q9HCA1; Q9UG37; DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot. DT 15-MAY-2007, sequence version 3. DT 05-OCT-2010, entry version 71. DE RecName: Full=Protein VPRBP; DE AltName: Full=DDB1- and CUL4-associated factor 1; DE AltName: Full=HIV-1 Vpr-binding protein; DE Short=VprBP; DE AltName: Full=Vpr-interacting protein; GN Name=VPRBP; Synonyms=DCAF1, KIAA0800, RIP; 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 [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX MEDLINE=99087487; PubMed=9872452; DOI=10.1093/dnares/5.5.277; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A., RA Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XI. RT The complete sequences of 100 new cDNA clones from brain which code RT for large proteins in vitro."; RL DNA Res. 5:277-286(1998). RN [2] RP SEQUENCE REVISION. RX MEDLINE=22158633; PubMed=12168954; DOI=10.1093/dnares/9.3.99; RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.; RT "Construction of expression-ready cDNA clones for KIAA genes: manual RT curation of 330 KIAA cDNA clones."; RL DNA Res. 9:99-106(2002). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). RC TISSUE=B-cell, and Skin; 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 [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 107-1507, PROTEIN SEQUENCE OF 1174-1186 RP AND 1328-1343, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND RP INTERACTION WITH HIV-1 VPR. RX PubMed=11223251; DOI=10.1016/S0378-1119(00)00583-7; RA Zhang S., Feng Y., Narayan O., Zhao L.-J.; RT "Cytoplasmic retention of HIV-1 regulatory protein Vpr by protein- RT protein interaction with a novel human cytoplasmic protein VprBP."; RL Gene 263:131-140(2001). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 375-1507. 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., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [6] RP INTERACTION WITH HIV-1 VPR. RX PubMed=8195203; RA Zhao L.-J., Mukherjee S., Narayan O.; RT "Biochemical mechanism of HIV-I Vpr function. Specific interaction RT with a cellular protein."; RL J. Biol. Chem. 269:15577-15582(1994). RN [7] RP INTERACTION WITH DDB1. RX PubMed=16949367; DOI=10.1016/j.molcel.2006.08.010; RA Jin J., Arias E.E., Chen J., Harper J.W., Walter J.C.; RT "A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, RT which is required for S phase destruction of the replication factor RT Cdt1."; RL Mol. Cell 23:709-721(2006). RN [8] RP FUNCTION. RX PubMed=17314515; RA Le Rouzic E., Belaiedouni N., Estrabaud E., Morel M., Rain J.-C., RA Transy C., Margottin-Goguet F.; RT "HIV1 Vpr arrests the cell cycle by recruiting DCAF1/VprBP, a receptor RT of the Cul4-DDB1 ubiquitin ligase."; RL Cell Cycle 6:182-188(2007). RN [9] RP FUNCTION. RX PubMed=17620334; DOI=10.1074/jbc.M703955200; RA Wen X., Duus K.M., Friedrich T.D., de Noronha C.M.; RT "The HIV1 protein Vpr acts to promote G2 cell cycle arrest by engaging RT a DDB1 and Cullin4A-containing ubiquitin ligase complex using RT VprBP/DCAF1 as an adaptor."; RL J. Biol. Chem. 282:27046-27057(2007). RN [10] RP COMPONENT OF E3 UBIQUITIN-PROTEIN LIGASE COMPLEX, INTERACTION WITH RP HIV-1 VPR, AND FUNCTION. RX PubMed=17626091; DOI=10.1128/JVI.01380-07; RA Tan L., Ehrlich E., Yu X.F.; RT "DDB1 and Cul4A are required for human immunodeficiency virus type 1 RT Vpr-induced G2 arrest."; RL J. Virol. 81:10822-10830(2007). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, AND INTERACTION WITH RP HIV-1 VPR. RX PubMed=17630831; DOI=10.1371/journal.ppat.0030085; RA Belzile J.P., Duisit G., Rougeau N., Mercier J., Finzi A., Cohen E.A.; RT "HIV-1 Vpr-mediated G2 arrest involves the DDB1-CUL4A[VPRBP] E3 RT ubiquitin ligase."; RL PLoS Pathog. 3:E85-E85(2007). RN [12] RP FUNCTION, AND COMPONENT OF DDA1-DDB1-VRPBP/DCAF1 COMPLEX. RX PubMed=17609381; DOI=10.1073/pnas.0702102104; RA Hrecka K., Gierszewska M., Srivastava S., Kozaczkiewicz L., RA Swanson S.K., Florens L., Washburn M.P., Skowronski J.; RT "Lentiviral Vpr usurps Cul4-DDB1[VprBP] E3 ubiquitin ligase to RT modulate cell cycle."; RL Proc. Natl. Acad. Sci. U.S.A. 104:11778-11783(2007). RN [13] RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-280, AND MASS RP SPECTROMETRY. RC TISSUE=Mammary cancer; RX PubMed=17370265; DOI=10.1002/pmic.200600410; RA Denis N.J., Vasilescu J., Lambert J.-P., Smith J.C., Figeys D.; RT "Tryptic digestion of ubiquitin standards reveals an improved strategy RT for identifying ubiquitinated proteins by mass spectrometry."; RL Proteomics 7:868-874(2007). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY, COMPONENT OF THE RP CUL4A-RBX1-DDB1-VPRBP/DCAF1 COMPLEX, AND FUNCTION. RX PubMed=17559673; DOI=10.1186/1743-422X-4-57; RA DeHart J.L., Zimmerman E.S., Ardon O., Monteiro-Filho C.M., RA Arganaraz E.R., Planelles V.; RT "HIV-1 Vpr activates the G2 checkpoint through manipulation of the RT ubiquitin proteasome system."; RL Virol. J. 4:57-57(2007). RN [15] RP FUNCTION. RX PubMed=18524771; DOI=10.1074/jbc.M710298200; RA Le Rouzic E., Morel M., Ayinde D., Belaidouni N., Letienne J., RA Transy C., Margottin-Goguet F.; RT "Assembly with the Cul4A-DDB1[DCAF1] ubiquitin ligase protects HIV-1 RT Vpr from proteasomal degradation."; RL J. Biol. Chem. 283:21686-21692(2008). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-895, AND MASS RP SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., RA Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for RT efficient phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [17] RP FUNCTION, INTERACTION WITH DDB1, COMPONENT OF THE RP CUL4A-RBX1-DDB1-VPRBP/DCAF1 COMPLEX, AND CHROMATIN ASSOCIATION. RX PubMed=18606781; DOI=10.1128/MCB.00232-08; RA McCall C.M., Miliani de Marval P.L., Chastain P.D. II, Jackson S.C., RA He Y.J., Kotake Y., Cook J.G., Xiong Y.; RT "Human immunodeficiency virus type 1 Vpr-binding protein VprBP, a WD40 RT protein associated with the DDB1-CUL4 E3 ubiquitin ligase, is RT essential for DNA replication and embryonic development."; RL Mol. Cell. Biol. 28:5621-5633(2008). RN [18] RP FUNCTION, AND INTERACTION WITH NF2. RX PubMed=18332868; DOI=10.1038/onc.2008.44; RA Huang J., Chen J.; RT "VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for RT degradation."; RL Oncogene 27:4056-4064(2008). RN [19] RP FUNCTION, AND INTERACTION WITH HIV-2 VPX. RX PubMed=18464893; DOI=10.1371/journal.ppat.1000059; RA Srivastava S., Swanson S.K., Manel N., Florens L., Washburn M.P., RA Skowronski J.; RT "Lentiviral Vpx accessory factor targets VprBP/DCAF1 substrate adaptor RT for cullin 4 E3 ubiquitin ligase to enable macrophage infection."; RL PLoS Pathog. 4:E1000059-E1000059(2008). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-888; SER-895; SER-898 RP AND THR-902, AND MASS SPECTROMETRY. 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 [21] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RA Colinge J., Superti-Furga G., Bennett K.L.; RL Submitted (OCT-2008) to UniProtKB. RN [22] RP FUNCTION, AND INTERACTION WITH HIV-2 VPX. RX PubMed=19264781; DOI=10.1128/JVI.00187-09; RA Bergamaschi A., Ayinde D., David A., Le Rouzic E., Morel M., RA Collin G., Descamps D., Damond F., Brun-Vezinet F., Nisole S., RA Margottin-Goguet F., Pancino G., Transy C.; RT "The human immunodeficiency virus type 2 Vpx protein usurps the CUL4A- RT DDB1 DCAF1 ubiquitin ligase to overcome a postentry block in RT macrophage infection."; RL J. Virol. 83:4854-4860(2009). RN [23] RP INTERACTION WITH HIV-1 VPR. RX PubMed=19838296; DOI=10.1371/journal.pone.0007514; RA Jacquot G., Le Rouzic E., Maidou-Peindara P., Maizy M., Lefrere J.J., RA Daneluzzi V., Monteiro-Filho C.M., Hong D., Planelles V., RA Morand-Joubert L., Benichou S.; RT "Characterization of the molecular determinants of primary HIV-1 Vpr RT proteins: impact of the Q65R and R77Q substitutions on Vpr RT functions."; RL PLoS ONE 4:E7514-E7514(2009). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-895 AND SER-1000, AND RP MASS SPECTROMETRY. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [25] RP IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND RP INTERACTION WITH NF2. RX PubMed=20178741; DOI=10.1016/j.cell.2010.01.029; RA Li W., You L., Cooper J., Schiavon G., Pepe-Caprio A., Zhou L., RA Ishii R., Giovannini M., Hanemann C.O., Long S.B., RA Erdjument-Bromage H., Zhou P., Tempst P., Giancotti F.G.; RT "Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin RT ligase CRL4(DCAF1) in the nucleus."; RL Cell 140:477-490(2010). RN [26] RP FUNCTION. RX PubMed=19923175; DOI=10.1128/JVI.01437-09; RA Gramberg T., Sunseri N., Landau N.R.; RT "Evidence for an activation domain at the amino terminus of simian RT immunodeficiency virus Vpx."; RL J. Virol. 84:1387-1396(2010). CC -!- FUNCTION: Component of the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 CC ubiquitin-protein ligase complex, VprBP/DCAF1 may function as the CC substrate recognition module within this complex. For example, CC VprBP/DCAF1 targets NF2 to the E3 ubiquitin-ligase complex for CC ubiquitination and subsequent proteasome-dependent degradation. In CC case of infection by HIV-1 virus, it is recruited by HIV-1 Vpr in CC order to hijack the CUL4A-RBX1-DDB1 function leading to arrest the CC cell cycle in G2 phase, and also to protect the viral protein from CC proteasomal degradation by another E3 ubiquitin ligase. In case of CC infection by HIV-2 virus, it is recruited by HIV-2 Vpx in order to CC hijack the CUL4A-RBX1-DDB1 function leading to enhanced efficiency CC of macrophage infection and promotion of the replication of CC cognate primate lentiviruses in cells of monocyte/macrophage CC lineage. Associated with chromatin in a DDB1-independent and cell CC cycle-dependent manner, VprBP/DCAF1 is recruited to chromatin as CC DNA is being replicated and is released from chromatin before CC mitosis. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Component of the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 CC ubiquitin-protein ligase complex that could interact with HIV-1 CC virus Vpr protein and HIV-2 virus Vpx protein. Interacts directly CC with DDB1. Also forms a ternary complex with DDA1 and DDB1. CC Interacts with NF2 (via FERM domain). Component of EDD/UBR5-DDB1- CC VprBP/DCAF1 E3 ubiquitin-protein ligase complex. CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9Y4B6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9Y4B6-2; Sequence=VSP_025498; CC Note=No experimental confirmation available; CC Name=3; CC IsoId=Q9Y4B6-3; Sequence=VSP_025499; CC Note=No experimental confirmation available; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. CC -!- DOMAIN: The DWD boxes are required for interaction with DDB1. CC -!- SIMILARITY: Belongs to the VPRBP/DCAF1 family. CC -!- SIMILARITY: Contains 1 LisH domain. CC -!- SIMILARITY: Contains 5 WD repeats. CC -!- SEQUENCE CAUTION: CC Sequence=BAA34520.2; Type=Erroneous initiation; 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; AB018343; BAA34520.2; ALT_INIT; mRNA. DR EMBL; BC022792; AAH22792.1; -; mRNA. DR EMBL; BC110371; AAI10372.1; -; mRNA. DR EMBL; AL080145; CAB45738.1; -; mRNA. DR EMBL; AF061935; AAG27134.1; -; mRNA. DR IPI; IPI00181396; -. DR IPI; IPI00329528; -. DR IPI; IPI00794498; -. DR PIR; T12529; T12529. DR RefSeq; NP_001165375.1; -. DR RefSeq; NP_055518.1; -. DR UniGene; Hs.716623; -. DR ProteinModelPortal; Q9Y4B6; -. DR SMR; Q9Y4B6; 1092-1293. DR IntAct; Q9Y4B6; 8. DR STRING; Q9Y4B6; -. DR PhosphoSite; Q9Y4B6; -. DR PRIDE; Q9Y4B6; -. DR Ensembl; ENST00000273612; ENSP00000273612; ENSG00000145041. DR GeneID; 9730; -. DR UCSC; uc003dbe.1; human. DR UCSC; uc003dbf.1; human. DR CTD; 9730; -. DR GeneCards; GC03M051409; -. DR H-InvDB; HIX0003330; -. DR HGNC; HGNC:30911; VPRBP. DR PharmGKB; PA142670621; -. DR eggNOG; prNOG16074; -. DR HOGENOM; HBG717452; -. DR HOVERGEN; HBG108659; -. DR InParanoid; Q9Y4B6; -. DR NextBio; 36604; -. DR ArrayExpress; Q9Y4B6; -. DR Bgee; Q9Y4B6; -. DR CleanEx; HS_VPRBP; -. DR Genevestigator; Q9Y4B6; -. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005515; F:protein binding; IPI:UniProtKB. DR GO; GO:0044419; P:interspecies interaction between organisms; IEA:UniProtKB-KW. DR InterPro; IPR016024; ARM-type_fold. DR InterPro; IPR006594; LisH_dimerisation. DR InterPro; IPR011046; WD40_repeat-like_dom. DR SMART; SM00667; LisH; 1. DR SUPFAM; SSF48371; ARM-type_fold; 1. DR SUPFAM; SSF50978; WD40_like; 1. DR PROSITE; PS50896; LISH; 1. DR PROSITE; PS00678; WD_REPEATS_1; FALSE_NEG. DR PROSITE; PS50082; WD_REPEATS_2; FALSE_NEG. DR PROSITE; PS50294; WD_REPEATS_REGION; FALSE_NEG. PE 1: Evidence at protein level; KW Alternative splicing; Complete proteome; Cytoplasm; KW Direct protein sequencing; Host-virus interaction; Isopeptide bond; KW Nucleus; Phosphoprotein; Polymorphism; Repeat; Ubl conjugation; KW Ubl conjugation pathway; WD repeat. FT CHAIN 1 1507 Protein VPRBP. FT /FTId=PRO_0000287473. FT DOMAIN 846 878 LisH. FT REPEAT 1091 1130 WD 1. FT REPEAT 1133 1174 WD 2. FT REPEAT 1176 1213 WD 3. FT REPEAT 1215 1247 WD 4. FT REPEAT 1248 1290 WD 5. FT REGION 1091 1174 WD repeat-like region. FT REGION 1418 1507 Interaction with NF2. FT MOTIF 1242 1249 DWD box 1 (By similarity). FT MOTIF 1278 1285 DWD box 2 (By similarity). FT COMPBIAS 1396 1500 Asp/Glu-rich (acidic). FT MOD_RES 888 888 Phosphothreonine. FT MOD_RES 895 895 Phosphoserine. FT MOD_RES 898 898 Phosphoserine. FT MOD_RES 902 902 Phosphothreonine. FT MOD_RES 1000 1000 Phosphoserine. FT CROSSLNK 280 280 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT VAR_SEQ 87 87 Missing (in isoform 2). FT /FTId=VSP_025498. FT VAR_SEQ 225 673 Missing (in isoform 3). FT /FTId=VSP_025499. FT VARIANT 267 267 N -> D (in dbSNP:rs3749318). FT /FTId=VAR_051486. FT VARIANT 378 378 L -> F (in dbSNP:rs17712228). FT /FTId=VAR_051487. FT VARIANT 1031 1031 L -> P (in dbSNP:rs9835229). FT /FTId=VAR_051488. SQ SEQUENCE 1507 AA; 169007 MW; 7E71AB2CAC4962C5 CRC64; MTTVVVHVDS KAELTTLLEQ WEKEHGSGQD MVPILTRMSQ LIEKETEEYR KGDPDPFDDR HPGRADPECM LGHLLRILFK NDDFMNALVN AYVMTSREPP LNTAACRLLL DIMPGLETAV VFQEKEGIVE NLFKWAREAD QPLRTYSTGL LGGAMENQDI AANYRDENSQ LVAIVLRRLR ELQLQEVALR QENKRPSPRK LSSEPLLPLD EEAVDMDYGD MAVDVVDGDQ EEASGDMEIS FHLDSGHKTS SRVNSTTKPE DGGLKKNKSA KQGDRENFRK AKQKLGFSSS DPDRMFVELS NSSWSEMSPW VIGTNYTLYP MTPAIEQRLI LQYLTPLGEY QELLPIFMQL GSRELMMFYI DLKQTNDVLL TFEALKHLAS LLLHNKFATE FVAHGGVQKL LEIPRPSMAA TGVSMCLYYL SYNQDAMERV CMHPHNVLSD VVNYTLWLME CSHASGCCHA TMFFSICFSF RAVLELFDRY DGLRRLVNLI STLEILNLED QGALLSDDEI FASRQTGKHT CMALRKYFEA HLAIKLEQVK QSLQRTEGGI LVHPQPPYKA CSYTHEQIVE MMEFLIEYGP AQLYWEPAEV FLKLSCVQLL LQLISIACNW KTYYARNDTV RFALDVLAIL TVVPKIQLQL AESVDVLDEA GSTVSTVGIS IILGVAEGEF FIHDAEIQKS ALQIIINCVC GPDNRISSIG KFISGTPRRK LPQNPKSSEH TLAKMWNVVQ SNNGIKVLLS LLSIKMPITD ADQIRALACK ALVGLSRSST VRQIISKLPL FSSCQIQQLM KEPVLQDKRS DHVKFCKYAA ELIERVSGKP LLIGTDVSLA RLQKADVVAQ SRISFPEKEL LLLIRNHLIS KGLGETATVL TKEADLPMTA ASHSSAFTPV TAAASPVSLP RTPRIANGIA TRLGSHAAVG ASAPSAPTAH PQPRPPQGPL ALPGPSYAGN SPLIGRISFI RERPSPCNGR KIRVLRQKSD HGAYSQSPAI KKQLDRHLPS PPTLDSIITE YLREQHARCK NPVATCPPFS LFTPHQCPEP KQRRQAPINF TSRLNRRASF PKYGGVDGGC FDRHLIFSRF RPISVFREAN EDESGFTCCA FSARERFLML GTCTGQLKLY NVFSGQEEAS YNCHNSAITH LEPSRDGSLL LTSATWSQPL SALWGMKSVF DMKHSFTEDH YVEFSKHSQD RVIGTKGDIA HIYDIQTGNK LLTLFNPDLA NNYKRNCATF NPTDDLVLND GVLWDVRSAQ AIHKFDKFNM NISGVFHPNG LEVIINTEIW DLRTFHLLHT VPALDQCRVV FNHTGTVMYG AMLQADDEDD LMEERMKSPF GSSFRTFNAT DYKPIATIDV KRNIFDLCTD TKDCYLAVIE NQGSMDALNM DTVCRLYEVG RQRLAEDEDE EEDQEEEEQE EEDDDEDDDD TDDLDELDTD QLLEAELEED DNNENAGEDG DNDFSPSDEE LANLLEEGED GEDEDSDADE EVELILGDTD SSDNSDLEDD IILSLNE //