MMS4_YEAST
ID MMS4_YEAST Reviewed; 691 AA.
AC P38257; D6VQ99; P38259; Q6B1Z9; Q9URQ2;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 13-APR-2004, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Crossover junction endonuclease MMS4;
DE EC=3.1.22.-;
GN Name=MMS4; Synonyms=SLX2; OrderedLocusNames=YBR098W;
GN ORFNames=YBR0826, YBR0829, YBR100W;
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 [GENOMIC DNA], AND MUTAGENESIS OF GLY-173.
RC STRAIN=S288c / GRF88;
RX PubMed=9604884; DOI=10.1007/s004380050689;
RA Xiao W., Chow B.L., Milo C.N.;
RT "Mms4, a putative transcriptional (co)activator, protects Saccharomyces
RT cerevisiae cells from endogenous and environmental DNA damage.";
RL Mol. Gen. Genet. 257:614-623(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7900426; DOI=10.1002/yea.320101014;
RA Mannhaupt G., Stucka R., Ehnle S., Vetter I., Feldmann H.;
RT "Analysis of a 70 kb region on the right arm of yeast chromosome II.";
RL Yeast 10:1363-1381(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7813418; DOI=10.1002/j.1460-2075.1994.tb06923.x;
RA Feldmann H., Aigle M., Aljinovic G., Andre B., Baclet M.C., Barthe C.,
RA Baur A., Becam A.-M., Biteau N., Boles E., Brandt T., Brendel M.,
RA Brueckner M., Bussereau F., Christiansen C., Contreras R., Crouzet M.,
RA Cziepluch C., Demolis N., Delaveau T., Doignon F., Domdey H.,
RA Duesterhus S., Dubois E., Dujon B., El Bakkoury M., Entian K.-D.,
RA Feuermann M., Fiers W., Fobo G.M., Fritz C., Gassenhuber J., Glansdorff N.,
RA Goffeau A., Grivell L.A., de Haan M., Hein C., Herbert C.J.,
RA Hollenberg C.P., Holmstroem K., Jacq C., Jacquet M., Jauniaux J.-C.,
RA Jonniaux J.-L., Kallesoee T., Kiesau P., Kirchrath L., Koetter P.,
RA Korol S., Liebl S., Logghe M., Lohan A.J.E., Louis E.J., Li Z.Y.,
RA Maat M.J., Mallet L., Mannhaupt G., Messenguy F., Miosga T., Molemans F.,
RA Mueller S., Nasr F., Obermaier B., Perea J., Pierard A., Piravandi E.,
RA Pohl F.M., Pohl T.M., Potier S., Proft M., Purnelle B., Ramezani Rad M.,
RA Rieger M., Rose M., Schaaff-Gerstenschlaeger I., Scherens B.,
RA Schwarzlose C., Skala J., Slonimski P.P., Smits P.H.M., Souciet J.-L.,
RA Steensma H.Y., Stucka R., Urrestarazu L.A., van der Aart Q.J.M.,
RA Van Dyck L., Vassarotti A., Vetter I., Vierendeels F., Vissers S.,
RA Wagner G., de Wergifosse P., Wolfe K.H., Zagulski M., Zimmermann F.K.,
RA Mewes H.-W., Kleine K.;
RT "Complete DNA sequence of yeast chromosome II.";
RL EMBO J. 13:5795-5809(1994).
RN [4]
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 [5]
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 [6]
RP FUNCTION, PROCESSING OF STALLED REPLICATION FORK, AND INTERACTION WITH
RP MUS81.
RX PubMed=11641278; DOI=10.1101/gad.932201;
RA Kaliraman V., Mullen J.R., Fricke W.M., Bastin-Shanower S.A., Brill S.J.;
RT "Functional overlap between Sgs1-Top3 and the Mms4-Mus81 endonuclease.";
RL Genes Dev. 15:2730-2740(2001).
RN [7]
RP FUNCTION, AND INTERACTION WITH MUS81.
RX PubMed=11139495; DOI=10.1093/genetics/157.1.103;
RA Mullen J.R., Kaliraman V., Ibrahim S.S., Brill S.J.;
RT "Requirement for three novel protein complexes in the absence of the Sgs1
RT DNA helicase in Saccharomyces cerevisiae.";
RL Genetics 157:103-118(2001).
RN [8]
RP FUNCTION.
RX PubMed=11779793; DOI=10.1093/genetics/159.4.1511;
RA de los Santos T., Loidl J., Larkin B., Hollingsworth N.M.;
RT "A role for MMS4 in the processing of recombination intermediates during
RT meiosis in Saccharomyces cerevisiae.";
RL Genetics 159:1511-1525(2001).
RN [9]
RP FUNCTION.
RX PubMed=12475932; DOI=10.1073/pnas.252652399;
RA Fabre F., Chan A., Heyer W.-D., Gangloff S.;
RT "Alternate pathways involving Sgs1/Top3, Mus81/ Mms4, and Srs2 prevent
RT formation of toxic recombination intermediates from single-stranded gaps
RT created by DNA replication.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16887-16892(2002).
RN [10]
RP ERRATUM OF PUBMED:12475932.
RA Fabre F., Chan A., Heyer W.-D., Gangloff S.;
RL Proc. Natl. Acad. Sci. U.S.A. 100:1462-1462(2002).
RN [11]
RP FUNCTION, INTERACTION WITH MUS81, SUBCELLULAR LOCATION, AND
RP CHARACTERIZATION OF MUTANT ARG-173.
RX PubMed=14642571; DOI=10.1016/j.dnarep.2003.08.013;
RA Fu Y., Xiao W.;
RT "Functional domains required for the Saccharomyces cerevisiae Mus81-Mms4
RT endonuclease complex formation and nuclear localization.";
RL DNA Repair 2:1435-1447(2003).
RN [12]
RP FUNCTION, AND CROSSOVER WITHOUT DOUBLE HOLLIDAY JUNCTION.
RX PubMed=12750322; DOI=10.1093/genetics/164.1.81;
RA de los Santos T., Hunter N., Lee C., Larkin B., Loidl J.,
RA Hollingsworth N.M.;
RT "The Mus81/Mms4 endonuclease acts independently of double-Holliday junction
RT resolution to promote a distinct subset of crossovers during meiosis in
RT budding yeast.";
RL Genetics 164:81-94(2003).
RN [13]
RP FUNCTION.
RX PubMed=12473680; DOI=10.1074/jbc.m210006200;
RA Whitby M.C., Osman F., Dixon J.;
RT "Cleavage of model replication forks by fission yeast Mus81-Eme1 and
RT budding yeast Mus81-Mms4.";
RL J. Biol. Chem. 278:6928-6935(2003).
RN [14]
RP FUNCTION, AND CLEAVAGE SITE SELECTION.
RX PubMed=12724407; DOI=10.1128/mcb.23.10.3487-3496.2003;
RA Bastin-Shanower S.A., Fricke W.M., Mullen J.R., Brill S.J.;
RT "The mechanism of Mus81-Mms4 cleavage site selection distinguishes it from
RT the homologous endonuclease Rad1-Rad10.";
RL Mol. Cell. Biol. 23:3487-3496(2003).
RN [15]
RP FUNCTION, AND CROSSOVER WITHOUT DOUBLE HOLLIDAY JUNCTION.
RX PubMed=14527420; DOI=10.1016/s1097-2765(03)00343-5;
RA Osman F., Dixon J., Doe C.L., Whitby M.C.;
RT "Generating crossovers by resolution of nicked Holliday junctions: a role
RT for Mus81-Eme1 in meiosis.";
RL Mol. Cell 12:761-774(2003).
RN [16]
RP FUNCTION.
RX PubMed=15611158; DOI=10.1534/genetics.104.032912;
RA Argueso J.L., Wanat J., Gemici Z., Alani E.;
RT "Competing crossover pathways act during meiosis in Saccharomyces
RT cerevisiae.";
RL Genetics 168:1805-1816(2004).
RN [17]
RP FUNCTION, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, AND INTERACTION WITH
RP MUS81.
RX PubMed=15590332; DOI=10.1016/j.dnarep.2004.10.001;
RA Fricke W.M., Bastin-Shanower S.A., Brill S.J.;
RT "Substrate specificity of the Saccharomyces cerevisiae Mus81-Mms4
RT endonuclease.";
RL DNA Repair 4:243-251(2005).
RN [18]
RP REVIEW.
RX PubMed=14752007; DOI=10.1101/gad.1165904;
RA Hollingsworth N.M., Brill S.J.;
RT "The Mus81 solution to resolution: generating meiotic crossovers without
RT Holliday junctions.";
RL Genes Dev. 18:117-125(2004).
RN [19]
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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48; SER-49 AND SER-61, AND
RP IDENTIFICATION BY 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).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Interacts with MUS81 to form a DNA structure-specific
CC endonuclease with substrate preference for branched DNA structures with
CC a 5'-end at the branch nick. Typical substrates include 3'-flap
CC structures, D-loops, replication forks with regressed leading strands
CC and nicked Holliday junctions. Cleavage probably occurs approximately
CC half a helical turn upstream of the free 5'-end in these structures.
CC May be required in mitosis for the processing of stalled replication
CC fork intermediates arising spontaneously or subsequent to treatment
CC with DNA damaging agents such as methylmethane sulfonate (MMS),
CC camptothecin (CPT) or UV. May be required in meiosis for the repair of
CC meiosis-specific double strand breaks subsequent to single-end invasion
CC (SEI). This involves consecutive cleavage of D-loops and nicked
CC Holliday junctions leading to sister chromatid crossover. In contrast
CC to MSH4-MSH5 dependent crossover, double Holliday junctions do not seem
CC to be involved. Spore formation and viability are severely impaired in
CC deletion strains. {ECO:0000269|PubMed:11139495,
CC ECO:0000269|PubMed:11641278, ECO:0000269|PubMed:11779793,
CC ECO:0000269|PubMed:12473680, ECO:0000269|PubMed:12475932,
CC ECO:0000269|PubMed:12724407, ECO:0000269|PubMed:12750322,
CC ECO:0000269|PubMed:14527420, ECO:0000269|PubMed:14642571,
CC ECO:0000269|PubMed:15590332, ECO:0000269|PubMed:15611158}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15590332};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:15590332};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=31.1 nM for a nicked Holliday junction
CC {ECO:0000269|PubMed:15590332};
CC KM=6.84 nM for a regressed leading strand replication fork
CC {ECO:0000269|PubMed:15590332};
CC KM=4.8 nM for a 3'-flap structure {ECO:0000269|PubMed:15590332};
CC KM=3.45 nM for a nicked duplex {ECO:0000269|PubMed:15590332};
CC KM=14.0 nM for a regressed lagging strand replication fork
CC {ECO:0000269|PubMed:15590332};
CC KM=245 nM for a Y structure {ECO:0000269|PubMed:15590332};
CC KM=173 nM for a double flap structure {ECO:0000269|PubMed:15590332};
CC Vmax=55.6 nmol/min/ng enzyme with a nicked Holliday junction as
CC substrate {ECO:0000269|PubMed:15590332};
CC Vmax=31.3 nmol/min/ng enzyme with a regressed leading strand
CC replication fork as substrate {ECO:0000269|PubMed:15590332};
CC Vmax=24.4 nmol/min/ng enzyme with a 3'-flap structure as substrate
CC {ECO:0000269|PubMed:15590332};
CC Vmax=2.21 nmol/min/ng enzyme with a nicked duplex as substrate
CC {ECO:0000269|PubMed:15590332};
CC Vmax=0.832 nmol/min/ng enzyme with a regressed lagging strand
CC replication fork as subsystrate {ECO:0000269|PubMed:15590332};
CC Vmax=0.0468 nmol/min/ng enzyme with a Y structure as substrate
CC {ECO:0000269|PubMed:15590332};
CC Vmax=0.0879 nmol/min/ng enzyme with a double flap structure as
CC substrate {ECO:0000269|PubMed:15590332};
CC pH dependence:
CC Optimum pH is 8.0 for cleavage of a 3'-flap structure.
CC {ECO:0000269|PubMed:15590332};
CC -!- SUBUNIT: Interacts with MUS81. {ECO:0000269|PubMed:11139495,
CC ECO:0000269|PubMed:11641278, ECO:0000269|PubMed:14642571,
CC ECO:0000269|PubMed:15590332}.
CC -!- INTERACTION:
CC P38257; Q04149: MUS81; NbExp=4; IntAct=EBI-21547, EBI-33508;
CC P38257; P0CS90: SSC1; NbExp=2; IntAct=EBI-21547, EBI-8637;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14642571}.
CC -!- MISCELLANEOUS: Two distinct classes of meiotic crossovers have been
CC demonstrated in budding yeast. Class I crossovers exhibit crossover
CC interference and require MSH4 and MSH5 for their resolution, while
CC class II crossovers exhibit no crossover interference and require MUS81
CC and MMS4. While class I crossovers represent the majority of crossovers
CC in S.cerevisiae, they are virtually absent in S.pombe which lacks
CC orthologs of MSH4 and MSH5.
CC -!- SIMILARITY: Belongs to the EME1/MMS4 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAT92950.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAA55603.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAA85051.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAA85054.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; U14000; AAF06816.1; -; Genomic_DNA.
DR EMBL; X78993; CAA55603.1; ALT_FRAME; Genomic_DNA.
DR EMBL; Z35967; CAA85051.1; ALT_FRAME; Genomic_DNA.
DR EMBL; Z35968; CAA85054.1; ALT_INIT; Genomic_DNA.
DR EMBL; AY692931; AAT92950.1; ALT_FRAME; Genomic_DNA.
DR EMBL; BK006936; DAA07219.1; -; Genomic_DNA.
DR PIR; S45968; S45968.
DR PIR; S48265; S48265.
DR RefSeq; NP_009656.2; NM_001178446.1.
DR AlphaFoldDB; P38257; -.
DR BioGRID; 32804; 229.
DR ComplexPortal; CPX-1670; Deoxyribonuclease complex MUS81-MMS4.
DR DIP; DIP-2927N; -.
DR IntAct; P38257; 9.
DR MINT; P38257; -.
DR STRING; 4932.YBR098W; -.
DR iPTMnet; P38257; -.
DR MaxQB; P38257; -.
DR PaxDb; P38257; -.
DR PRIDE; P38257; -.
DR EnsemblFungi; YBR098W_mRNA; YBR098W; YBR098W.
DR GeneID; 852395; -.
DR KEGG; sce:YBR098W; -.
DR SGD; S000000302; MMS4.
DR VEuPathDB; FungiDB:YBR098W; -.
DR eggNOG; ENOG502RY0Q; Eukaryota.
DR HOGENOM; CLU_023637_0_0_1; -.
DR InParanoid; P38257; -.
DR OMA; SHMEFIN; -.
DR BioCyc; YEAST:G3O-29062-MON; -.
DR Reactome; R-SCE-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR PRO; PR:P38257; -.
DR Proteomes; UP000002311; Chromosome II.
DR RNAct; P38257; protein.
DR GO; GO:1905347; C:endodeoxyribonuclease complex; IPI:ComplexPortal.
DR GO; GO:0048476; C:Holliday junction resolvase complex; IDA:SGD.
DR GO; GO:0043596; C:nuclear replication fork; IDA:ComplexPortal.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:SGD.
DR GO; GO:0006281; P:DNA repair; IMP:SGD.
DR GO; GO:0006265; P:DNA topological change; IGI:SGD.
DR GO; GO:0006302; P:double-strand break repair; IBA:GO_Central.
DR GO; GO:0031573; P:mitotic intra-S DNA damage checkpoint signaling; IBA:GO_Central.
DR GO; GO:0007131; P:reciprocal meiotic recombination; IMP:SGD.
DR GO; GO:0010520; P:regulation of reciprocal meiotic recombination; IGI:SGD.
DR GO; GO:0031297; P:replication fork processing; IBA:GO_Central.
DR GO; GO:0000712; P:resolution of meiotic recombination intermediates; IGI:SGD.
DR InterPro; IPR006166; ERCC4_domain.
DR InterPro; IPR033310; Mms4/EME1/EME2.
DR PANTHER; PTHR21077; PTHR21077; 1.
DR Pfam; PF02732; ERCC4; 1.
DR SMART; SM00891; ERCC4; 1.
PE 1: Evidence at protein level;
KW Acetylation; Coiled coil; DNA damage; DNA recombination; DNA repair;
KW Endonuclease; Hydrolase; Magnesium; Manganese; Meiosis; Metal-binding;
KW Nuclease; Nucleus; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..691
FT /note="Crossover junction endonuclease MMS4"
FT /id="PRO_0000096516"
FT REGION 201..240
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 598..691
FT /note="Interaction with MUS81"
FT COILED 364..391
FT /evidence="ECO:0000255"
FT COILED 507..529
FT /evidence="ECO:0000255"
FT COMPBIAS 214..229
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 48
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 49
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 61
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MUTAGEN 173
FT /note="G->R: In allele MMS4-1; loss of activity."
FT /evidence="ECO:0000269|PubMed:9604884"
SQ SEQUENCE 691 AA; 78764 MW; 3B3918DD3B2E7E0C CRC64;
MSQIVDFVED KDSRNDASIQ IIDGPSNVEI IALSESMDQD ECKRAHVSSA EMIPSSPQRK
SVSNDVENVD LNKSIELSAP FFQDISISKL DDFSTTVNSI IDSSLRNENN AKGNAKKLLD
DLISDEWSAD LESSGKKHNK SQYNLRDIAE KWGVQSLKNP EPIAVDCEYK TQGIGKTNSD
ISDSPKSQIG AADILFDFPL SPVKHENPTE EKHNSIANEN SSPDNSLKPA GKQNHGEDGT
SMAKRVYNKG EDEQEHLPKG KKRTIALSRT LINSTKLPDT VELNLSKFLD SSDSITTDVL
STPAKGSNIV RTGSQPIFSN ANCFQEAKRS KTLTAEDPKC TKNTAREVSQ LENYIAYGQY
YTREDSKNKI RHLLKENKNA FKRVNQIYRD NIKARSQMII EFSPSLLQLF KKGDSDLQQQ
LAPAVVQSSY NDSMPLLRFL RKCDSIYDFS NDFYYPCDPK IVEENVLILY YDAQEFFEQY
TSQKKELYRK IRFFSKNGKH VILILSDINK LKRAIFQLEN EKYKARVEQR LSGTEEALRP
RSKKSSQVGK LGIKKFDLEQ RLRFIDREWH VKIHTVNSHM EFINSLPNLV SLIGKQRMDP
AIRYMKYAHL NVKSAQDSTE TLKKTFHQIG RMPEMKANNV VSLYPSFQSL LEDIEKGRLQ
SDNEGKYLMT EAVEKRLYKL FTCTDPNDTI E
