CDH1_YEAST
ID CDH1_YEAST Reviewed; 566 AA.
AC P53197; D6VUD5;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=APC/C activator protein CDH1;
DE AltName: Full=CDC20 homolog 1;
DE AltName: Full=Homolog of CDC twenty 1;
GN Name=CDH1; Synonyms=HCT1; OrderedLocusNames=YGL003C;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169869;
RA Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J.,
RA Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M.,
RA Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L.,
RA Coblenz A., Coglievina M., Coissac E., Defoor E., Del Bino S., Delius H.,
RA Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P.,
RA Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M.,
RA Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A.,
RA Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K.,
RA Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P.,
RA Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E.,
RA Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K.,
RA Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A.,
RA Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S.,
RA Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M.,
RA Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C.,
RA Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M.,
RA Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M.,
RA Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y.,
RA Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L.,
RA Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D.,
RA Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F.,
RA Zaccaria P., Zimmermann M., Zollner A., Kleine K.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII.";
RL Nature 387:81-84(1997).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [4]
RP ASSOCIATION WITH THE APC/C COMPLEX, PHOSPHORYLATION BY CDC28, AND
RP MUTAGENESIS OF THR-12; SER-16; SER-42; THR-157; SER-169; THR-173; THR-176;
RP SER-227 AND SER-239.
RX PubMed=9831566; DOI=10.1126/science.282.5394.1721;
RA Zachariae W., Schwab M., Nasmyth K., Seufert W.;
RT "Control of cyclin ubiquitination by CDK-regulated binding of Hct1 to the
RT anaphase promoting complex.";
RL Science 282:1721-1724(1998).
RN [5]
RP DEPHOSPHORYLATION BY CDC14.
RX PubMed=10074450; DOI=10.1016/s0960-9822(99)80111-0;
RA Jaspersen S.L., Charles J.F., Morgan D.O.;
RT "Inhibitory phosphorylation of the APC regulator Hct1 is controlled by the
RT kinase Cdc28 and the phosphatase Cdc14.";
RL Curr. Biol. 9:227-236(1999).
RN [6]
RP FUNCTION AS SPINDLE CHECKPOINT TARGET.
RX PubMed=10329618; DOI=10.1093/emboj/18.10.2707;
RA Alexandru G., Zachariae W., Schleiffer A., Nasmyth K.;
RT "Sister chromatid separation and chromosome re-duplication are regulated by
RT different mechanisms in response to spindle damage.";
RL EMBO J. 18:2707-2721(1999).
RN [7]
RP FUNCTION, INTERACTION WITH CLB2; CLB3 AND CDC5, AND DOMAIN C-BOX MOTIF.
RX PubMed=11566880; DOI=10.1093/emboj/20.18.5165;
RA Schwab M., Neutzner M., Moecker D., Seufert W.;
RT "Yeast Hct1 recognizes the mitotic cyclin Clb2 and other substrates of the
RT ubiquitin ligase APC.";
RL EMBO J. 20:5165-5175(2001).
RN [8]
RP INTERACTION WITH HSL1.
RX PubMed=11562348; DOI=10.1101/gad.917901;
RA Burton J.L., Solomon M.J.;
RT "D box and KEN box motifs in budding yeast Hsl1p are required for APC-
RT mediated degradation and direct binding to Cdc20p and Cdh1p.";
RL Genes Dev. 15:2381-2395(2001).
RN [9]
RP FUNCTION IN ASE1 AND CDC20 DEGRADATION.
RX PubMed=11448992; DOI=10.1083/jcb.200102007;
RA Huang J.N., Park I., Ellingson E., Littlepage L.E., Pellman D.;
RT "Activity of the APC(Cdh1) form of the anaphase-promoting complex persists
RT until S phase and prevents the premature expression of Cdc20p.";
RL J. Cell Biol. 154:85-94(2001).
RN [10]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH MSN5 AND PSE1.
RX PubMed=12456658; DOI=10.1093/emboj/cdf634;
RA Jaquenoud M., van Drogen F., Peter M.;
RT "Cell cycle-dependent nuclear export of Cdh1p may contribute to the
RT inactivation of APC/C(Cdh1).";
RL EMBO J. 21:6515-6526(2002).
RN [11]
RP PHOSPHORYLATION BY CDC28.
RX PubMed=14574415; DOI=10.1038/nature02062;
RA Ubersax J.A., Woodbury E.L., Quang P.N., Paraz M., Blethrow J.D., Shah K.,
RA Shokat K.M., Morgan D.O.;
RT "Targets of the cyclin-dependent kinase Cdk1.";
RL Nature 425:859-864(2003).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-213, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
CC -!- FUNCTION: Activator protein that regulates the ubiquitin ligase
CC activity and substrate specificity of the anaphase promoting
CC complex/cyclosome (APC/C). During telophase and in the subsequent G1
CC phase of the cell cycle, recognizes and binds proteins containing a
CC destruction box (D-box) and an additional degradation signal termed the
CC KEN box including ASE1, CDC20, the B-type cyclins CLB2 and CLB3, the
CC polo-like kinase CDC5 and HSL1, and recruits them in a C-box-dependent
CC manner to the APC/C for ubiquitination and subsequent proteolysis.
CC Required for exit from mitosis, cytokinesis and formation of
CC prereplicative complexes in G1. Probably is the target of a BUB2-
CC dependent spindle checkpoint pathway. {ECO:0000269|PubMed:10329618,
CC ECO:0000269|PubMed:11448992, ECO:0000269|PubMed:11566880}.
CC -!- SUBUNIT: Associates with the APC/C complex. Interacts with CLB2, CLB3,
CC CDC5, HSL1, MSN5 and PSE1. {ECO:0000269|PubMed:11562348,
CC ECO:0000269|PubMed:11566880, ECO:0000269|PubMed:12456658}.
CC -!- INTERACTION:
CC P53197; Q08981: ACM1; NbExp=8; IntAct=EBI-23684, EBI-2345174;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12456658}. Nucleus
CC {ECO:0000269|PubMed:12456658}. Note=Nuclear import and export are
CC mediated by the importin PSE1 and the exportin MSN5.
CC -!- DOMAIN: The C-box is required for the association with the APC/C
CC complex. {ECO:0000250}.
CC -!- PTM: Phosphorylated at multiple sites by CDC28, probably in its CLB5
CC bound form, in S, G2 and M phase of the cell cycle, thereby blocking
CC the association of CDH1 to the APC/C and promoting nuclear export of
CC CDH1 by MSN5. Dephosphorylated and activated by CDC14 in late anaphase,
CC which may be necessary for PSE1-dependent nuclear localization.
CC {ECO:0000269|PubMed:14574415, ECO:0000269|PubMed:9831566}.
CC -!- SIMILARITY: Belongs to the WD repeat CDC20/Fizzy family. {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; Z72525; CAA96703.1; -; Genomic_DNA.
DR EMBL; AY693078; AAT93097.1; -; Genomic_DNA.
DR EMBL; BK006941; DAA08096.1; -; Genomic_DNA.
DR PIR; S64005; S64005.
DR RefSeq; NP_011512.1; NM_001180868.1.
DR PDB; 4BH6; X-ray; 2.90 A; A/B/C/D/E/F/G/H=241-548.
DR PDB; 5A31; EM; 4.30 A; R=246-546.
DR PDBsum; 4BH6; -.
DR PDBsum; 5A31; -.
DR AlphaFoldDB; P53197; -.
DR SMR; P53197; -.
DR BioGRID; 33242; 351.
DR ComplexPortal; CPX-761; Anaphase-Promoting Complex, CDH1 variant.
DR DIP; DIP-5915N; -.
DR ELM; P53197; -.
DR IntAct; P53197; 22.
DR MINT; P53197; -.
DR STRING; 4932.YGL003C; -.
DR iPTMnet; P53197; -.
DR MaxQB; P53197; -.
DR PaxDb; P53197; -.
DR PRIDE; P53197; -.
DR EnsemblFungi; YGL003C_mRNA; YGL003C; YGL003C.
DR GeneID; 852881; -.
DR KEGG; sce:YGL003C; -.
DR SGD; S000002971; CDH1.
DR VEuPathDB; FungiDB:YGL003C; -.
DR eggNOG; KOG0305; Eukaryota.
DR GeneTree; ENSGT00950000183104; -.
DR HOGENOM; CLU_014831_4_1_1; -.
DR InParanoid; P53197; -.
DR OMA; WSKNTDE; -.
DR BioCyc; YEAST:G3O-30527-MON; -.
DR Reactome; R-SCE-176407; Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase.
DR Reactome; R-SCE-69656; Cyclin A:Cdk2-associated events at S phase entry.
DR Reactome; R-SCE-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR PRO; PR:P53197; -.
DR Proteomes; UP000002311; Chromosome VII.
DR RNAct; P53197; protein.
DR GO; GO:0005680; C:anaphase-promoting complex; IPI:SGD.
DR GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR GO; GO:0005634; C:nucleus; IDA:SGD.
DR GO; GO:0010997; F:anaphase-promoting complex binding; IBA:GO_Central.
DR GO; GO:0030332; F:cyclin binding; IDA:SGD.
DR GO; GO:1990757; F:ubiquitin ligase activator activity; IDA:SGD.
DR GO; GO:0031145; P:anaphase-promoting complex-dependent catabolic process; IBA:GO_Central.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:1902426; P:deactivation of mitotic spindle assembly checkpoint; IMP:SGD.
DR GO; GO:0010697; P:negative regulation of mitotic spindle pole body separation; IMP:SGD.
DR GO; GO:1905786; P:positive regulation of anaphase-promoting complex-dependent catabolic process; IMP:SGD.
DR GO; GO:0120151; P:positive regulation of mitotic actomyosin contractile ring disassembly; IMP:SGD.
DR GO; GO:0045842; P:positive regulation of mitotic metaphase/anaphase transition; IMP:SGD.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IDA:SGD.
DR GO; GO:1904668; P:positive regulation of ubiquitin protein ligase activity; IDA:SGD.
DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; IDA:SGD.
DR GO; GO:0016567; P:protein ubiquitination; IC:ComplexPortal.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; IC:ComplexPortal.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR024977; Apc4_WD40_dom.
DR InterPro; IPR033010; Cdc20/Fizzy.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR19918; PTHR19918; 1.
DR Pfam; PF12894; ANAPC4_WD40; 1.
DR Pfam; PF00400; WD40; 2.
DR SMART; SM00320; WD40; 5.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 3.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell cycle; Cell division; Cytoplasm; Mitosis; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; WD repeat.
FT CHAIN 1..566
FT /note="APC/C activator protein CDH1"
FT /id="PRO_0000050904"
FT REPEAT 258..298
FT /note="WD 1"
FT REPEAT 300..339
FT /note="WD 2"
FT REPEAT 342..379
FT /note="WD 3"
FT REPEAT 383..422
FT /note="WD 4"
FT REPEAT 425..467
FT /note="WD 5"
FT REPEAT 469..510
FT /note="WD 6"
FT REPEAT 513..552
FT /note="WD 7"
FT REGION 1..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 55..61
FT /note="C-box"
FT COMPBIAS 1..49
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 213
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MUTAGEN 12
FT /note="T->A: Abolishes phosphorylation; when associated
FT with A-16; A-42; A-157; A-169; A-173; A-176; A-227 and A-
FT 239."
FT /evidence="ECO:0000269|PubMed:9831566"
FT MUTAGEN 16
FT /note="S->A: Abolishes phosphorylation; when associated
FT with A-12; A-42; A-157; A-169; A-173; A-176; A-227 and A-
FT 239."
FT /evidence="ECO:0000269|PubMed:9831566"
FT MUTAGEN 42
FT /note="S->A: Abolishes phosphorylation; when associated
FT with A-12; A-16; A-157; A-169; A-173; A-176; A-227 and A-
FT 239."
FT /evidence="ECO:0000269|PubMed:9831566"
FT MUTAGEN 157
FT /note="T->A: Abolishes phosphorylation; when associated
FT with A-12; A-16; A-42; A-169; A-173; A-176; A-227 and A-
FT 239."
FT /evidence="ECO:0000269|PubMed:9831566"
FT MUTAGEN 169
FT /note="S->A: Abolishes phosphorylation; when associated
FT with A-12; A-16; A-42; A-157; A-173; A-176; A-227 and A-
FT 239."
FT /evidence="ECO:0000269|PubMed:9831566"
FT MUTAGEN 173
FT /note="T->A: Abolishes phosphorylation; when associated
FT with A-12; A-16; A-42; A-157; A-169; A-176; A-227 and A-
FT 239."
FT /evidence="ECO:0000269|PubMed:9831566"
FT MUTAGEN 176
FT /note="T->A: Abolishes phosphorylation; when associated
FT with A-12; A-16; A-42; A-157; A-169; A-173; A-227 and A-
FT 239."
FT /evidence="ECO:0000269|PubMed:9831566"
FT MUTAGEN 227
FT /note="S->A: Abolishes phosphorylation; when associated
FT with A-12; A-16; A-42; A-157; A-169; A-173; A-176 and A-
FT 239."
FT /evidence="ECO:0000269|PubMed:9831566"
FT MUTAGEN 239
FT /note="S->A: Abolishes phosphorylation; when associated
FT with A-12; A-16; A-42; A-157; A-169; A-173; A-176 and A-
FT 227."
FT /evidence="ECO:0000269|PubMed:9831566"
FT STRAND 252..256
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 269..271
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 275..281
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 284..289
FT /evidence="ECO:0007829|PDB:4BH6"
FT TURN 290..292
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 295..300
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 305..310
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 314..321
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 326..330
FT /evidence="ECO:0007829|PDB:4BH6"
FT TURN 331..334
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 335..340
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 347..353
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 356..364
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 366..370
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 373..376
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 378..381
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 388..393
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 395..397
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 399..404
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 409..413
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 420..423
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 430..435
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 437..439
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 442..447
FT /evidence="ECO:0007829|PDB:4BH6"
FT TURN 449..451
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 453..458
FT /evidence="ECO:0007829|PDB:4BH6"
FT TURN 459..462
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 463..469
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 474..479
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 481..484
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 486..490
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 497..500
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 502..504
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 507..511
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 518..523
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 527..534
FT /evidence="ECO:0007829|PDB:4BH6"
FT TURN 535..537
FT /evidence="ECO:0007829|PDB:4BH6"
FT STRAND 538..543
FT /evidence="ECO:0007829|PDB:4BH6"
SQ SEQUENCE 566 AA; 62821 MW; DA6DE5545607906B CRC64;
MSTNLNPFMN NTPSSSPLKG SESKRVSKRP ISSSSSASLL SSPSRRSRPS TVYGDRYIPS
RTDIDFNSIV SISSMASVPA LNPSSTEDQV EYQKERQAHE TYNTLLKNEL FGEMLSKDTV
GSESSIDRIK NTRPSTRGNV HAENTTRHGY ELERVSTPPP EAAGLEEFSP HSTPVTPRRL
FTSQQDEITR PSSNSVRGAS LLTYQQRKGR RLSAASLLQS QFFDSMSPVR PDSKQLLLSP
GKQFRQIAKV PYRVLDAPSL ADDFYYSLID WSSTDVLAVA LGKSIFLTDN NTGDVVHLCD
TENEYTSLSW IGAGSHLAVG QANGLVEIYD VMKRKCIRTL SGHIDRVACL SWNNHVLTSG
SRDHRILHRD VRMPDPFFET IESHTQEVCG LKWNVADNKL ASGGNDNVVH VYEGTSKSPI
LTFDEHKAAV KAMAWSPHKR GVLATGGGTA DRRLKIWNVN TSIKMSDIDS GSQICNMVWS
KNTNELVTSH GYSKYNLTLW DCNSMDPIAI LKGHSFRVLH LTLSNDGTTV VSGAGDETLR
YWKLFDKPKA KVQPNSLIFD AFNQIR
