HDAC4_RAT
ID HDAC4_RAT Reviewed; 1077 AA.
AC Q99P99;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-2007, sequence version 2.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Histone deacetylase 4;
DE Short=HD4;
DE EC=3.5.1.98;
GN Name=Hdac4;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 55-208.
RC STRAIN=Wistar; TISSUE=Testis;
RA Wilquet V., Chavez M., Korbers R., Geerts A.;
RT "Expression pattern of rat histone deacetylases.";
RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP INTERACTION WITH BTBD14B.
RX PubMed=16033423; DOI=10.1111/j.1471-4159.2005.03206.x;
RA Korutla L., Wang P.J., Mackler S.A.;
RT "The POZ/BTB protein NAC1 interacts with two different histone deacetylases
RT in neuronal-like cultures.";
RL J. Neurochem. 94:786-793(2005).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-563 AND SER-630, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Responsible for the deacetylation of lysine residues on the
CC N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone
CC deacetylation gives a tag for epigenetic repression and plays an
CC important role in transcriptional regulation, cell cycle progression
CC and developmental events. Histone deacetylases act via the formation of
CC large multiprotein complexes. Involved in muscle maturation via its
CC interaction with the myocyte enhancer factors such as MEF2A, MEF2C and
CC MEF2D. Deacetylates HSPA1A and HSPA1B at 'Lys-77' leading to their
CC preferential binding to co-chaperone STUB1.
CC {ECO:0000250|UniProtKB:P56524}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-acetyl-L-lysyl-[histone] = acetate + L-lysyl-
CC [histone]; Xref=Rhea:RHEA:58196, Rhea:RHEA-COMP:9845, Rhea:RHEA-
CC COMP:11338, ChEBI:CHEBI:15377, ChEBI:CHEBI:29969, ChEBI:CHEBI:30089,
CC ChEBI:CHEBI:61930; EC=3.5.1.98;
CC -!- SUBUNIT: Homodimer. Homodimerization via its N-terminal domain.
CC Interacts with HDAC7. Interacts with MEF2A, MEF2C, MEF2D, MORC2 and
CC NR2C1. Interacts with a 14-3-3 chaperone protein in a phosphorylation
CC dependent manner. Interacts with KDM5B and AHRR (By similarity).
CC Interacts with BTBD14B (PubMed:16033423). Interacts with MYOCD.
CC Interacts (via PxLPxI/L motif) with ANKRA2 (via ankyrin repeats).
CC Interacts with CUL7 (as part of the 3M complex); negatively regulated
CC by ANKRA2. Interacts with EP300 in the presence of TFAP2C. Interacts
CC with HSPA1A and HSPA1B leading to their deacetylation at 'Lys-77' (By
CC similarity). Interacts with ZBTB7B; the interaction allows the
CC recruitment of HDAC4 on CD8 loci for deacetylation and possible
CC inhibition of CD8 genes expression (By similarity). Interacts with
CC DHX36 (By similarity). Interacts with SIK3; this interaction leads to
CC HDAC4 retention in the cytoplasm (By similarity).
CC {ECO:0000250|UniProtKB:P56524, ECO:0000250|UniProtKB:Q6NZM9,
CC ECO:0000269|PubMed:16033423}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Shuttles between the
CC nucleus and the cytoplasm. Upon muscle cells differentiation, it
CC accumulates in the nuclei of myotubes, suggesting a positive role of
CC nuclear HDAC4 in muscle differentiation. The export to cytoplasm
CC depends on the interaction with a 14-3-3 chaperone protein and is due
CC to its phosphorylation at Ser-245, Ser-466 and Ser-630 by CaMK4 and
CC SIK1. The nuclear localization probably depends on sumoylation (By
CC similarity). Interaction with SIK3 leads to HDAC4 retention in the
CC cytoplasm (By similarity). Interacts with ZNF638 (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:Q6NZM9}.
CC -!- DOMAIN: The nuclear export sequence mediates the shuttling between the
CC nucleus and the cytoplasm. {ECO:0000250}.
CC -!- DOMAIN: The PxLPxI/L motif mediates interaction with ankyrin repeats of
CC ANKRA2. {ECO:0000250|UniProtKB:P56524}.
CC -!- PTM: Phosphorylated by CaMK4 at Ser-245, Ser-466 and Ser-630.
CC Phosphorylation at other residues by CaMK2D is required for the
CC interaction with 14-3-3. Phosphorylation at Ser-349, within the
CC PxLPxI/L motif, impairs the binding of ANKRA2 but generates a high-
CC affinity docking site for 14-3-3 (By similarity).
CC {ECO:0000250|UniProtKB:P56524}.
CC -!- PTM: Sumoylation on Lys-557 is promoted by the E3 SUMO-protein ligase
CC RANBP2, and prevented by phosphorylation by CaMK4.
CC -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 2
CC subfamily. {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; AABR03067902; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03068091; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03070452; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF321132; AAK11185.1; -; mRNA.
DR RefSeq; NP_445901.1; NM_053449.1.
DR AlphaFoldDB; Q99P99; -.
DR SMR; Q99P99; -.
DR BioGRID; 264106; 4.
DR CORUM; Q99P99; -.
DR STRING; 10116.ENSRNOP00000027622; -.
DR BindingDB; Q99P99; -.
DR ChEMBL; CHEMBL2095943; -.
DR DrugCentral; Q99P99; -.
DR iPTMnet; Q99P99; -.
DR PhosphoSitePlus; Q99P99; -.
DR PaxDb; Q99P99; -.
DR PRIDE; Q99P99; -.
DR GeneID; 363287; -.
DR KEGG; rno:363287; -.
DR UCSC; RGD:619979; rat.
DR CTD; 9759; -.
DR RGD; 619979; Hdac4.
DR VEuPathDB; HostDB:ENSRNOG00000020372; -.
DR eggNOG; KOG1343; Eukaryota.
DR HOGENOM; CLU_006530_2_0_1; -.
DR InParanoid; Q99P99; -.
DR OMA; AEESTPX; -.
DR OrthoDB; 1484694at2759; -.
DR PhylomeDB; Q99P99; -.
DR TreeFam; TF106174; -.
DR Reactome; R-RNO-350054; Notch-HLH transcription pathway.
DR Reactome; R-RNO-4090294; SUMOylation of intracellular receptors.
DR Reactome; R-RNO-4551638; SUMOylation of chromatin organization proteins.
DR Reactome; R-RNO-8951936; RUNX3 regulates p14-ARF.
DR PRO; PR:Q99P99; -.
DR Proteomes; UP000002494; Chromosome 9.
DR Bgee; ENSRNOG00000020372; Expressed in frontal cortex and 19 other tissues.
DR Genevisible; Q99P99; RN.
DR GO; GO:0031672; C:A band; IDA:MGI.
DR GO; GO:0042641; C:actomyosin; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0000118; C:histone deacetylase complex; ISO:RGD.
DR GO; GO:0031594; C:neuromuscular junction; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0030017; C:sarcomere; IDA:MGI.
DR GO; GO:0017053; C:transcription repressor complex; ISO:RGD.
DR GO; GO:0030018; C:Z disc; IDA:MGI.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0004407; F:histone deacetylase activity; ISO:RGD.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0030955; F:potassium ion binding; ISO:RGD.
DR GO; GO:1990841; F:promoter-specific chromatin binding; IDA:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0033558; F:protein lysine deacetylase activity; ISO:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0019789; F:SUMO transferase activity; ISO:RGD.
DR GO; GO:0003714; F:transcription corepressor activity; ISO:RGD.
DR GO; GO:0008270; F:zinc ion binding; ISO:RGD.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD.
DR GO; GO:0071374; P:cellular response to parathyroid hormone stimulus; IEP:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
DR GO; GO:0006338; P:chromatin remodeling; ISO:RGD.
DR GO; GO:0016575; P:histone deacetylation; ISO:RGD.
DR GO; GO:0070932; P:histone H3 deacetylation; ISO:RGD.
DR GO; GO:0070933; P:histone H4 deacetylation; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0045820; P:negative regulation of glycolytic process; ISO:RGD.
DR GO; GO:1902894; P:negative regulation of miRNA transcription; ISO:RGD.
DR GO; GO:0010832; P:negative regulation of myotube differentiation; ISO:RGD.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0002076; P:osteoblast development; ISO:RGD.
DR GO; GO:0034983; P:peptidyl-lysine deacetylation; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; IMP:RGD.
DR GO; GO:1902437; P:positive regulation of male mating behavior; IMP:RGD.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:RGD.
DR GO; GO:0033235; P:positive regulation of protein sumoylation; ISO:RGD.
DR GO; GO:1903428; P:positive regulation of reactive oxygen species biosynthetic process; IMP:RGD.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IMP:RGD.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0006476; P:protein deacetylation; ISO:RGD.
DR GO; GO:0010882; P:regulation of cardiac muscle contraction by calcium ion signaling; ISO:RGD.
DR GO; GO:0040029; P:regulation of gene expression, epigenetic; ISO:RGD.
DR GO; GO:0043393; P:regulation of protein binding; ISO:RGD.
DR GO; GO:0048742; P:regulation of skeletal muscle fiber development; ISO:RGD.
DR GO; GO:1902809; P:regulation of skeletal muscle fiber differentiation; IEA:Ensembl.
DR GO; GO:0051153; P:regulation of striated muscle cell differentiation; ISO:RGD.
DR GO; GO:0014894; P:response to denervation involved in regulation of muscle adaptation; ISO:RGD.
DR GO; GO:0070555; P:response to interleukin-1; ISO:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:RGD.
DR GO; GO:0001501; P:skeletal system development; ISO:RGD.
DR Gene3D; 3.40.800.20; -; 1.
DR InterPro; IPR033660; HDAC4/7.
DR InterPro; IPR000286; His_deacetylse.
DR InterPro; IPR023801; His_deacetylse_dom.
DR InterPro; IPR037138; His_deacetylse_dom_sf.
DR InterPro; IPR024643; Hist_deacetylase_Gln_rich_N.
DR InterPro; IPR017320; Histone_deAcase_II_euk.
DR InterPro; IPR023696; Ureohydrolase_dom_sf.
DR PANTHER; PTHR45364; PTHR45364; 1.
DR PANTHER; PTHR45364:SF3; PTHR45364:SF3; 1.
DR Pfam; PF12203; HDAC4_Gln; 1.
DR Pfam; PF00850; Hist_deacetyl; 1.
DR PIRSF; PIRSF037911; HDAC_II_euk; 1.
DR PRINTS; PR01270; HDASUPER.
DR SUPFAM; SSF52768; SSF52768; 1.
PE 1: Evidence at protein level;
KW Chromatin regulator; Coiled coil; Cytoplasm; Hydrolase; Isopeptide bond;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Repressor;
KW Transcription; Transcription regulation; Ubl conjugation; Zinc.
FT CHAIN 1..1077
FT /note="Histone deacetylase 4"
FT /id="PRO_0000281034"
FT REGION 117..312
FT /note="Interaction with MEF2A"
FT /evidence="ECO:0000250"
FT REGION 132..167
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 204..225
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 239..327
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 508..530
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 542..582
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 623..646
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 653..1077
FT /note="Histone deacetylase"
FT /evidence="ECO:0000250"
FT REGION 1052..1077
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 66..169
FT /evidence="ECO:0000255"
FT MOTIF 348..353
FT /note="PxLPxI/L motif; mediates interaction with ANKRA2 and
FT 14-3-3 proteins"
FT /evidence="ECO:0000250|UniProtKB:P56524"
FT MOTIF 1044..1077
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 132..166
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 204..224
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 239..278
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 290..327
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 515..530
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1061..1077
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 796
FT /evidence="ECO:0000250"
FT BINDING 665
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 667
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 673
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 744
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT MOD_RES 209
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6NZM9"
FT MOD_RES 245
FT /note="Phosphoserine; by CaMK4 and SIK1"
FT /evidence="ECO:0000250|UniProtKB:P56524"
FT MOD_RES 349
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P56524"
FT MOD_RES 466
FT /note="Phosphoserine; by CaMK4 and SIK1"
FT /evidence="ECO:0000250|UniProtKB:P56524"
FT MOD_RES 563
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 630
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 631
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P56524"
FT CROSSLNK 557
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
SQ SEQUENCE 1077 AA; 118652 MW; 88127299D9962DBA CRC64;
MSSQSHPDGL SGRDQPVELL NPARVNHMPS TVDVATALPL QVAPAAVPMD LRLDHQFSLP
LEPALREQQL QQELLALKQK QQIQRQILIA EFQRQHEQLS RQHEAQLHEH IKQQQEMLAM
KHQQELLEHQ RKLERHRQEQ ELEKQHREQK LQQLKNKEKG KESAVASTEV KMKLQEFVLN
KKKALAHRNL NHCMSSDPRY WYGKTQHSSL DQSSPPQSGV SASYNHPVLG MYDAKDDFPL
RKTASEPNLK LRSRLKQKVA ERRSSPLLRR KDGPVATALK KRPLDVTDSA CSSAPGSGPS
SPNSSSGNVS TENGIAPTVP STPAETSLAH RLVTREGSVA PLPLYTSPSL PNITLGLPAT
GPAAGAAGQQ DAERLALPAL QQRISLFPGT HLTPYLSTSP LERDGGAAHN PLLQHMVLLE
QPPTQTPLVT GLGALPLHTQ SLVGADRVSP SIHKLRQHRP LGRTQSAPLP QNAQALQHLV
IQQQHQQFLE KHKQQFQQQQ LHLSKMISKP SEPPRQPESH PEETEEELRE HQALLDEPYL
DRLPGQKEPS LAGVQVKQEP IESEEEEVEA TREAEPSQRP ATEQELLFRQ QALLLEQQRI
HQLRNYQASM EAAGIPVSFG SHRPLSRAQS SPASATFPMS VQEPPTKPRF TTGLVYDTLM
LKHQCTCGNT NSHPEHAGRI QSIWSRLQET GLRGKCECIR GRKATLEELQ TVHSEAHTLL
YGTNPLNRQK LDSSLTSVFV RLPCGGVGVD SDTIWNEVHS SGAARLAVGC VVELVFKVAT
GELKNGFAVV RPPGHHAEES TPMGFCYFNS VAIAAKLLQQ RLNVSKILIV DWDVHHGNGT
QQAFYNDPNV LYMSLHRYDD GNFFPGSGAP DEVGTGPGVG FNVNMAFTGG LDPPMGDAEY
LAAFRTVVMP IANEFAPDVV LVSSGFDAVE GHPTPLGGYN LSAKCFGYLT KQLMGLAGGR
IVLALEGGHD LTAICDASEA CVSALLGNEL EPLPEKVLHQ RPNANAVHSM EKVMGIHSEY
WRCLQRLSPT VGHSLIEAQK CENEEAETVT AMASLSVGVK PAEKRSEEEP MEEEPPL
