SLX5_YEAST
ID SLX5_YEAST Reviewed; 619 AA.
AC P32828; D6VRX6;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=E3 ubiquitin-protein ligase complex SLX5-SLX8 subunit SLX5;
DE EC=2.3.2.27 {ECO:0000269|PubMed:18032921};
DE AltName: Full=Hexose metabolism-related protein HEX3;
DE AltName: Full=RING-type E3 ubiquitin transferase SLX5 {ECO:0000305};
DE AltName: Full=Synthetic lethal of unknown function protein 5;
GN Name=SLX5; Synonyms=HEX3; OrderedLocusNames=YDL013W; ORFNames=D2875;
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].
RA Costanzo G., Sternglanz R.;
RL Submitted (JAN-1993) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169867;
RA Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G.,
RA Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C.,
RA Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F.,
RA Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M.,
RA Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T.,
RA Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C.,
RA Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S.,
RA Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L.,
RA Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H.,
RA Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M.,
RA Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M.,
RA Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A.,
RA Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G.,
RA Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E.,
RA Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S.,
RA Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D.,
RA Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V.,
RA Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E.,
RA Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M.,
RA Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D.,
RA Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A.,
RA Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R.,
RA Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T.,
RA Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L.,
RA Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E.,
RA Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L.,
RA Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M.,
RA Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K.,
RA Mewes H.-W., Zollner A., Zaccaria P.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV.";
RL Nature 387:75-78(1997).
RN [3]
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 [4]
RP FUNCTION IN DEGRADATION OF SUMOYLATED PROTEINS, AND INTERACTION WITH SLX8.
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 [5]
RP FUNCTION IN STABILIZATION OF DNA DAMAGE.
RX PubMed=16325482; DOI=10.1016/j.dnarep.2005.10.010;
RA Zhang C., Roberts T.M., Yang J., Desai R., Brown G.W.;
RT "Suppression of genomic instability by SLX5 and SLX8 in Saccharomyces
RT cerevisiae.";
RL DNA Repair 5:336-346(2006).
RN [6]
RP FUNCTION IN STABILIZATION OF DNA DAMAGE.
RX PubMed=16387868; DOI=10.1534/genetics.105.052811;
RA Wang Z., Jones G.M., Prelich G.;
RT "Genetic analysis connects SLX5 and SLX8 to the SUMO pathway in
RT Saccharomyces cerevisiae.";
RL Genetics 172:1499-1509(2006).
RN [7]
RP UBIQUITIN-PROTEIN LIGASE ACTIVITY, FUNCTION IN STIMULATION OF UBIQUITIN
RP CONJUGASTING ENZYMES, AND INTERACTION WITH SLX8.
RX PubMed=18032921; DOI=10.4161/cc.6.22.4882;
RA Ii T., Fung J., Mullen J.R., Brill S.J.;
RT "The yeast Slx5-Slx8 DNA integrity complex displays ubiquitin ligase
RT activity.";
RL Cell Cycle 6:2800-2809(2007).
RN [8]
RP FUNCTION IN DEGRADATION OF SUMOYLATED PROTEINS, AND INTERACTION WITH SLX8.
RX PubMed=17669696; DOI=10.1016/j.dnarep.2007.06.004;
RA Ii T., Mullen J.R., Slagle C.E., Brill S.J.;
RT "Stimulation of in vitro sumoylation by Slx5-Slx8: evidence for a
RT functional interaction with the SUMO pathway.";
RL DNA Repair 6:1679-1691(2007).
RN [9]
RP FUNCTION IN DEGRADATION OF SUMOYLATED PROTEINS, AND INTERACTION WITH SLX8.
RX PubMed=17848550; DOI=10.1074/jbc.m706025200;
RA Xie Y., Kerscher O., Kroetz M.B., McConchie H.F., Sung P., Hochstrasser M.;
RT "The yeast Hex3.Slx8 heterodimer is a ubiquitin ligase stimulated by
RT substrate sumoylation.";
RL J. Biol. Chem. 282:34176-34184(2007).
RN [10]
RP FUNCTION IN NEGATIVE REGULATION OF RECOMBINATION.
RX PubMed=17591698; DOI=10.1128/mcb.00787-07;
RA Burgess R.C., Rahman S., Lisby M., Rothstein R., Zhao X.;
RT "The Slx5-Slx8 complex affects sumoylation of DNA repair proteins and
RT negatively regulates recombination.";
RL Mol. Cell. Biol. 27:6153-6162(2007).
RN [11]
RP FUNCTION IN DEGRADATION OF SUMOYLATED PROTEINS.
RX PubMed=18499666; DOI=10.1074/jbc.m802690200;
RA Mullen J.R., Brill S.J.;
RT "Activation of the Slx5-Slx8 ubiquitin ligase by poly-small ubiquitin-like
RT modifier conjugates.";
RL J. Biol. Chem. 283:19912-19921(2008).
RN [12]
RP FUNCTION IN TRANSCRIPTIONAL SILENCING, INTERACTION WITH SIR2, AND
RP SUBCELLULAR LOCATION.
RX PubMed=18086879; DOI=10.1128/mcb.01291-07;
RA Darst R.P., Garcia S.N., Koch M.R., Pillus L.;
RT "Slx5 promotes transcriptional silencing and is required for robust growth
RT in the absence of Sir2.";
RL Mol. Cell. Biol. 28:1361-1372(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-29, AND IDENTIFICATION BY
RP 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 [14]
RP FUNCTION IN DEGRADATION OF SUMOYLATED PROTEINS, INTERACTION WITH SLX8, AND
RP SUBCELLULAR LOCATION.
RX PubMed=18948542; DOI=10.1126/science.1162790;
RA Nagai S., Dubrana K., Tsai-Pflugfelder M., Davidson M.B., Roberts T.M.,
RA Brown G.W., Varela E., Hediger F., Gasser S.M., Krogan N.J.;
RT "Functional targeting of DNA damage to a nuclear pore-associated SUMO-
RT dependent ubiquitin ligase.";
RL Science 322:597-602(2008).
RN [15]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19270524; DOI=10.4161/cc.8.7.8123;
RA Cook C.E., Hochstrasser M., Kerscher O.;
RT "The SUMO-targeted ubiquitin ligase subunit Slx5 resides in nuclear foci
RT and at sites of DNA breaks.";
RL Cell Cycle 8:1080-1089(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14 AND SER-29, 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 [17]
RP FUNCTION, DISRUPTION PHENOTYPE, AND SUBCELLULAR LOCATION.
RX PubMed=23785440; DOI=10.1371/journal.pone.0065628;
RA van de Pasch L.A., Miles A.J., Nijenhuis W., Brabers N.A., van Leenen D.,
RA Lijnzaad P., Brown M.K., Ouellet J., Barral Y., Kops G.J., Holstege F.C.;
RT "Centromere binding and a conserved role in chromosome stability for SUMO-
RT dependent ubiquitin ligases.";
RL PLoS ONE 8:E65628-E65628(2013).
RN [18]
RP FUNCTION, INTERACTION WITH KAR9, AND SUBCELLULAR LOCATION.
RX PubMed=26906737; DOI=10.1016/j.devcel.2016.01.011;
RA Schweiggert J., Stevermann L., Panigada D., Kammerer D., Liakopoulos D.;
RT "Regulation of a spindle positioning factor at kinetochores by SUMO-
RT targeted ubiquitin ligases.";
RL Dev. Cell 36:415-427(2016).
RN [19]
RP FUNCTION.
RX PubMed=26960795; DOI=10.1091/mbc.e15-12-0827;
RA Ohkuni K., Takahashi Y., Fulp A., Lawrimore J., Au W.C., Pasupala N.,
RA Levy-Myers R., Warren J., Strunnikov A., Baker R.E., Kerscher O., Bloom K.,
RA Basrai M.A.;
RT "SUMO-targeted ubiquitin ligase (STUbL) Slx5 regulates proteolysis of
RT centromeric histone H3 variant Cse4 and prevents its mislocalization to
RT euchromatin.";
RL Mol. Biol. Cell 0:0-0(2016).
RN [20]
RP FUNCTION.
RX PubMed=30479332; DOI=10.1038/s41467-018-07364-x;
RA Talhaoui I., Bernal M., Mullen J.R., Dorison H., Palancade B., Brill S.J.,
RA Mazon G.;
RT "Slx5-Slx8 ubiquitin ligase targets active pools of the Yen1 nuclease to
RT limit crossover formation.";
RL Nat. Commun. 9:5016-5016(2018).
RN [21]
RP FUNCTION, SUBCELLULAR LOCATION, DNA-BINDING, INTERACTION WITH EUC1, DOMAIN,
RP AND MUTAGENESIS OF 201-SER--LEU-335.
RX PubMed=31015336; DOI=10.15252/embj.2018100368;
RA Hoepfler M., Kern M.J., Straub T., Prytuliak R., Habermann B.H.,
RA Pfander B., Jentsch S.;
RT "Slx5/Slx8-dependent ubiquitin hotspots on chromatin contribute to stress
RT tolerance.";
RL EMBO J. 38:0-0(2019).
CC -!- FUNCTION: Component of the SUMO-targeted ubiquitin ligase (STUbL)
CC complex SLX5/SLX8 that mediates ubiquitination and subsequent
CC desumoylation of sumoylated proteins and proteins containing SUMO-like
CC domains for their degradation (PubMed:11139495, PubMed:16325482,
CC PubMed:18032921, PubMed:17669696, PubMed:17848550, PubMed:18499666,
CC PubMed:18948542, PubMed:31015336). The STUbL complex SLX5/SLX8
CC stimulates ubiquitin conjugating enzymes, including UBC1, UBC4, UBC5
CC and UBC13-MMS2, and mediates the proteolytic down-regulation of
CC sumoylated proteins (PubMed:18032921). The STUbL complex SLX5/SLX8 is
CC involved in ubiquitin-mediated degradation of histone variant CSE4,
CC preventing mislocalization to euchromatin (PubMed:26960795). The
CC complex plays an essential role in maintenance of chromosome stability
CC and links SUMO-dependent ubiquitination to a centromere-specific
CC function during mitosis (PubMed:23785440). The complex is involved in
CC proteolysis of spindle positioning protein KAR9 and ensures correct
CC spindle function by regulating levels of microtubule-associated
CC proteins (PubMed:26906737). During replication, the complex helps
CC prevent DNA lesions via recombination and has a role in localizing the
CC DNA damage protein DCD2 (PubMed:16325482, PubMed:17591698). The complex
CC especially ubiquitinates the nuclease YEN1 and prevents persistent
CC accumulation of a fraction of YEN1 associated with sites of activity in
CC late G2/M and helps maintain the balance between pro- and anti-
CC crossover pathways during homologous recombination (PubMed:30479332).
CC It is also involved in ubiquitin-mediated degradation of DNA repair
CC proteins RAD52 and RAD57 (PubMed:18032921). Along with SIR2, promotes
CC silencing of genes at telomeric or ribosomal DNA (rDNA) loci
CC (PubMed:18086879). Finally, the complex is recruited to distinct
CC genomic hotspots of non-H2B protein ubiquitination (ub-hotspots) by the
CC sumoylated transcription factor-like protein EUC1 where it
CC ubiquitinates EUC1 and presumably other targets (PubMed:31015336).
CC {ECO:0000269|PubMed:11139495, ECO:0000269|PubMed:16325482,
CC ECO:0000269|PubMed:17591698, ECO:0000269|PubMed:17669696,
CC ECO:0000269|PubMed:17848550, ECO:0000269|PubMed:18032921,
CC ECO:0000269|PubMed:18086879, ECO:0000269|PubMed:18499666,
CC ECO:0000269|PubMed:18948542, ECO:0000269|PubMed:23785440,
CC ECO:0000269|PubMed:26906737, ECO:0000269|PubMed:26960795,
CC ECO:0000269|PubMed:30479332, ECO:0000269|PubMed:31015336}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:18032921};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:18032921}.
CC -!- SUBUNIT: Component of the heterodimeric SUMO-targeted ubiquitin ligase
CC (STUbL) complex composed of SLX5 and SLX8 (PubMed:11139495,
CC PubMed:18032921, PubMed:17669696, PubMed:17848550, PubMed:18948542).
CC Interacts with sirtuin SIR2 (PubMed:18086879). Interacts with KAR9
CC (PubMed:26906737). Interacts with EUC1 (PubMed:31015336).
CC {ECO:0000269|PubMed:11139495, ECO:0000269|PubMed:17669696,
CC ECO:0000269|PubMed:17848550, ECO:0000269|PubMed:18032921,
CC ECO:0000269|PubMed:18086879, ECO:0000269|PubMed:18948542,
CC ECO:0000269|PubMed:26906737, ECO:0000269|PubMed:31015336}.
CC -!- INTERACTION:
CC P32828; P40072: SLX8; NbExp=2; IntAct=EBI-8276, EBI-22661;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18086879,
CC ECO:0000269|PubMed:18948542, ECO:0000269|PubMed:23785440}. Chromosome
CC {ECO:0000269|PubMed:31015336}. Chromosome, centromere, kinetochore
CC {ECO:0000269|PubMed:26906737}. Chromosome, centromere
CC {ECO:0000269|PubMed:23785440}. Note=Localizes to few distinct genomic
CC hotspots of non-H2B protein ubiquitination (ub-hotspots).
CC {ECO:0000269|PubMed:31015336}.
CC -!- DOMAIN: The region between Ser-201 and Leu-335 is required recruitment
CC of SLX5 to ub-hotspots via interacion with EUC1.
CC {ECO:0000269|PubMed:31015336}.
CC -!- DISRUPTION PHENOTYPE: Leads to severe mitotic defects that include
CC aneuploidy, spindle mispositioning, fish hooks and aberrant spindle
CC kinetics. {ECO:0000269|PubMed:23785440}.
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; L07745; AAA34671.1; -; Genomic_DNA.
DR EMBL; Z48432; CAA88346.1; -; Genomic_DNA.
DR EMBL; Z74061; CAA98570.1; -; Genomic_DNA.
DR EMBL; BK006938; DAA11836.1; -; Genomic_DNA.
DR PIR; S30780; S30780.
DR RefSeq; NP_010271.3; NM_001180072.3.
DR AlphaFoldDB; P32828; -.
DR BioGRID; 32041; 893.
DR ComplexPortal; CPX-3179; Slx5-Slx8 SUMO-targeted ubiquitin ligase (STUbL) complex.
DR DIP; DIP-727N; -.
DR IntAct; P32828; 28.
DR MINT; P32828; -.
DR STRING; 4932.YDL013W; -.
DR iPTMnet; P32828; -.
DR MaxQB; P32828; -.
DR PaxDb; P32828; -.
DR PRIDE; P32828; -.
DR TopDownProteomics; P32828; -.
DR EnsemblFungi; YDL013W_mRNA; YDL013W; YDL013W.
DR GeneID; 851549; -.
DR KEGG; sce:YDL013W; -.
DR SGD; S000002171; SLX5.
DR VEuPathDB; FungiDB:YDL013W; -.
DR eggNOG; ENOG502QTIW; Eukaryota.
DR HOGENOM; CLU_445559_0_0_1; -.
DR InParanoid; P32828; -.
DR OMA; RCFARID; -.
DR BioCyc; YEAST:G3O-29443-MON; -.
DR UniPathway; UPA00143; -.
DR PRO; PR:P32828; -.
DR Proteomes; UP000002311; Chromosome IV.
DR RNAct; P32828; protein.
DR GO; GO:0000775; C:chromosome, centromeric region; IDA:SGD.
DR GO; GO:0000776; C:kinetochore; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IDA:SGD.
DR GO; GO:0033768; C:SUMO-targeted ubiquitin ligase complex; IDA:SGD.
DR GO; GO:0032183; F:SUMO binding; IDA:SGD.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IMP:SGD.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:SGD.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0016925; P:protein sumoylation; IMP:SGD.
DR GO; GO:0016567; P:protein ubiquitination; IDA:SGD.
DR GO; GO:0000723; P:telomere maintenance; IMP:SGD.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:SGD.
DR InterPro; IPR038886; E3_SLX5/Rfp1.
DR PANTHER; PTHR28042; PTHR28042; 1.
PE 1: Evidence at protein level;
KW Centromere; Chromosome; DNA damage; DNA repair; Kinetochore; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Transferase; Ubl conjugation pathway.
FT CHAIN 1..619
FT /note="E3 ubiquitin-protein ligase complex SLX5-SLX8
FT subunit SLX5"
FT /id="PRO_0000083954"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 63..90
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 201..335
FT /note="EUC1 interaction domain"
FT /evidence="ECO:0000269|PubMed:31015336"
FT COMPBIAS 72..88
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 29
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956,
FT ECO:0007744|PubMed:19779198"
FT MUTAGEN 201..335
FT /note="Missing: Leads to loss of SLX5 recruitment to ub-
FT hotspots."
FT /evidence="ECO:0000269|PubMed:31015336"
SQ SEQUENCE 619 AA; 71071 MW; 75846FEA93A65AE9 CRC64;
MHSDTNGRTK SNNSPSDNNP NETVILIDSD KEEDASIREA NLPVRLYPDR RVGRRRDALN
RFVRSDSRSR NSQRTHITAS SERPDFQANN DDITIIREVG RFFGDDGPID PSAHYVDLDQ
EPGSETLETP RTIQVDNTNG YLNDNGNNNE SDDGLTIVEE RTTRPRVTLN LPGGERLEVT
ATTTDIPIRR SFEFQEDLGA SRRQLLRRSA TRARNLFVDR SDENDEDWTD DTHNLPEAIQ
RARRESRMRM SRRIAERQRR VQQQRVSSDE NISTSIRLQS IRERIQSYTP DIRSAFHRAE
SLHEFRSILQ NVAPITLQEC EEELMALFTE FRNQLLQNWA IDRVRNTQEE ALRLHREALE
RQERTAGRVF HRGTLRESIT NYLNFNGEDG FLSRLWSGPA LSDADEERHT QNIIDMIQER
EERERDVVMK NLMNKTRAQQ EEFEARAASL PEGYSASFDT TPKMKLDITK NGKEETIIVT
DDDLAKTLED IPVCCLCGAE LGVGIPDDFT GISQKDRGVS FEGLVSKYKF HCPYQTLARP
SMLDRDLSKR TFIASCGHAF CGRCFARIDN AKKKSKMPKK KLAQLKGSAH PDNYGPKLCP
ADSCKKLIRS RGRLKEVYF
