CNOT6_HUMAN
ID CNOT6_HUMAN Reviewed; 557 AA.
AC Q9ULM6; A7MD46; D3DWR0;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-APR-2004, sequence version 2.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=CCR4-NOT transcription complex subunit 6;
DE EC=3.1.13.4 {ECO:0000269|PubMed:11889047, ECO:0000269|PubMed:20065043};
DE AltName: Full=CCR4 carbon catabolite repression 4-like;
DE AltName: Full=Carbon catabolite repressor protein 4 homolog;
DE AltName: Full=Cytoplasmic deadenylase;
GN Name=CNOT6; Synonyms=CCR4, CCR4a, KIAA1194;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=10574462; DOI=10.1093/dnares/6.5.337;
RA Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:337-345(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH CNOT7 AND CNOT8.
RX PubMed=11747467; DOI=10.1186/1471-2164-2-9;
RA Dupressoir A., Morel A.-P., Barbot W., Loireau M.-P., Corbo L.,
RA Heidmann T.;
RT "Identification of four families of yCCR4- and Mg2+-dependent endonuclease-
RT related proteins in higher eukaryotes, and characterization of orthologs of
RT yCCR4 with a conserved leucine-rich repeat essential for hCAF1/hPOP2
RT binding.";
RL BMC Genomics 2:9-9(2001).
RN [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=11889047; DOI=10.1093/emboj/21.6.1414;
RA Chen J., Chiang Y.-C., Denis C.L.;
RT "CCR4, a 3'-5' poly(A) RNA and ssDNA exonuclease, is the catalytic
RT component of the cytoplasmic deadenylase.";
RL EMBO J. 21:1414-1426(2002).
RN [6]
RP INTERACTION WITH UNR.
RX PubMed=15314026; DOI=10.1101/gad.1219104;
RA Chang T.-C., Yamashita A., Chen C.-Y.A., Yamashita Y., Zhu W., Durdan S.,
RA Kahvejian A., Sonenberg N., Shyu A.-B.;
RT "UNR, a new partner of poly(A)-binding protein, plays a key role in
RT translationally coupled mRNA turnover mediated by the c-fos major coding-
RT region determinant.";
RL Genes Dev. 18:2010-2023(2004).
RN [7]
RP INTERACTION WITH ZFP36L1.
RX PubMed=15687258; DOI=10.1101/gad.1282305;
RA Lykke-Andersen J., Wagner E.;
RT "Recruitment and activation of mRNA decay enzymes by two ARE-mediated decay
RT activation domains in the proteins TTP and BRF-1.";
RL Genes Dev. 19:351-361(2005).
RN [8]
RP FUNCTION, AND INTERACTION WITH ZNF335.
RX PubMed=18180299; DOI=10.1074/jbc.m706986200;
RA Garapaty S., Mahajan M.A., Samuels H.H.;
RT "Components of the CCR4-NOT complex function as nuclear hormone receptor
RT coactivators via association with the NRC-interacting Factor NIF-1.";
RL J. Biol. Chem. 283:6806-6816(2008).
RN [9]
RP IDENTIFICATION IN THE CCR4-NOT COMPLEX, AND COMPOSITION OF THE CCR4-NOT
RP COMPLEX.
RX PubMed=19558367; DOI=10.1042/bj20090500;
RA Lau N.C., Kolkman A., van Schaik F.M., Mulder K.W., Pijnappel W.W.,
RA Heck A.J., Timmers H.T.;
RT "Human Ccr4-Not complexes contain variable deadenylase subunits.";
RL Biochem. J. 422:443-453(2009).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF GLU-240.
RX PubMed=20065043; DOI=10.1128/mcb.01481-09;
RA Piao X., Zhang X., Wu L., Belasco J.G.;
RT "CCR4-NOT deadenylates mRNA associated with complexes in human cells.";
RL Mol. Cell. Biol. 30:1486-1494(2010).
RN [11]
RP FUNCTION.
RX PubMed=21233283; DOI=10.1091/mbc.e10-11-0898;
RA Mittal S., Aslam A., Doidge R., Medica R., Winkler G.S.;
RT "The Ccr4a (CNOT6) and Ccr4b (CNOT6L) deadenylase subunits of the human
RT Ccr4-Not complex contribute to the prevention of cell death and
RT senescence.";
RL Mol. Biol. Cell 22:748-758(2011).
CC -!- FUNCTION: Poly(A) nuclease with 3'-5' RNase activity. Catalytic
CC component of the CCR4-NOT complex which is one of the major cellular
CC mRNA deadenylases and is linked to various cellular processes including
CC bulk mRNA degradation, miRNA-mediated repression, translational
CC repression during translational initiation and general transcription
CC regulation. Additional complex functions may be a consequence of its
CC influence on mRNA expression. Involved in mRNA decay mediated by the
CC major-protein-coding determinant of instability (mCRD) of the FOS gene
CC in the cytoplasm. In the presence of ZNF335, enhances ligand-dependent
CC transcriptional activity of nuclear hormone receptors, including RARA.
CC The increase of ligand-dependent ESR1-mediated transcription is much
CC smaller, if any. Mediates cell proliferation and cell survival and
CC prevents cellular senescence. {ECO:0000269|PubMed:11889047,
CC ECO:0000269|PubMed:18180299, ECO:0000269|PubMed:20065043,
CC ECO:0000269|PubMed:21233283}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Exonucleolytic cleavage of poly(A) to 5'-AMP.; EC=3.1.13.4;
CC Evidence={ECO:0000269|PubMed:11889047, ECO:0000269|PubMed:20065043};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q96LI5};
CC Note=Binds 2 magnesium ions, but the ions interact each with only 1 or
CC 2 residues. {ECO:0000250|UniProtKB:Q96LI5};
CC -!- SUBUNIT: Component of the CCR4-NOT complex; distinct complexes seem to
CC exist that differ in the participation of probably mutually exclusive
CC catalytic subunits; the complex contains two deadenylase subunits,
CC CNOT6 or CNOT6L, and CNOT7 or CNOT8 (PubMed:19558367). Interacts with
CC CNOT7 and CNOT8 (PubMed:11747467). Interacts with UNR
CC (PubMed:15314026). Interacts with ZFP36L1 (via N-terminus)
CC (PubMed:15687258). Interacts with ZNF335 (PubMed:18180299).
CC {ECO:0000269|PubMed:11747467, ECO:0000269|PubMed:15314026,
CC ECO:0000269|PubMed:15687258, ECO:0000269|PubMed:18180299,
CC ECO:0000269|PubMed:19558367}.
CC -!- INTERACTION:
CC Q9ULM6; A5YKK6: CNOT1; NbExp=3; IntAct=EBI-2104530, EBI-1222758;
CC Q9ULM6; Q9UIV1: CNOT7; NbExp=2; IntAct=EBI-2104530, EBI-2105113;
CC Q9ULM6; Q9UFF9: CNOT8; NbExp=2; IntAct=EBI-2104530, EBI-742299;
CC Q9ULM6; Q86TB9: PATL1; NbExp=3; IntAct=EBI-2104530, EBI-2562092;
CC Q9ULM6; Q9HCJ0: TNRC6C; NbExp=2; IntAct=EBI-2104530, EBI-6507625;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q96LI5}. Nucleus
CC {ECO:0000250|UniProtKB:Q96LI5}. Note=Predominantly cytoplasmic.
CC {ECO:0000250|UniProtKB:Q96LI5}.
CC -!- SIMILARITY: Belongs to the CCR4/nocturin family. {ECO:0000305}.
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DR EMBL; AB033020; BAA86508.1; -; mRNA.
DR EMBL; CH471165; EAW53752.1; -; Genomic_DNA.
DR EMBL; CH471165; EAW53753.1; -; Genomic_DNA.
DR EMBL; BC152469; AAI52470.1; -; mRNA.
DR CCDS; CCDS4455.1; -.
DR RefSeq; NP_001290170.1; NM_001303241.1.
DR RefSeq; XP_005266010.1; XM_005265953.1.
DR RefSeq; XP_011532908.1; XM_011534606.1.
DR RefSeq; XP_011532909.1; XM_011534607.1.
DR PDB; 7AX1; X-ray; 3.30 A; A=1-557.
DR PDBsum; 7AX1; -.
DR AlphaFoldDB; Q9ULM6; -.
DR SMR; Q9ULM6; -.
DR BioGRID; 121542; 57.
DR ComplexPortal; CPX-2849; CCR4-NOT mRNA deadenylase complex, CNOT6-CNOT8 variant.
DR ComplexPortal; CPX-707; CCR4-NOT mRNA deadenylase complex, CNOT6-CNOT7 variant.
DR CORUM; Q9ULM6; -.
DR DIP; DIP-46838N; -.
DR IntAct; Q9ULM6; 21.
DR STRING; 9606.ENSP00000377024; -.
DR ChEMBL; CHEMBL3616363; -.
DR iPTMnet; Q9ULM6; -.
DR PhosphoSitePlus; Q9ULM6; -.
DR BioMuta; CNOT6; -.
DR DMDM; 46396033; -.
DR EPD; Q9ULM6; -.
DR jPOST; Q9ULM6; -.
DR MassIVE; Q9ULM6; -.
DR MaxQB; Q9ULM6; -.
DR PaxDb; Q9ULM6; -.
DR PeptideAtlas; Q9ULM6; -.
DR PRIDE; Q9ULM6; -.
DR ProteomicsDB; 85079; -.
DR Antibodypedia; 29603; 156 antibodies from 22 providers.
DR DNASU; 57472; -.
DR Ensembl; ENST00000261951.9; ENSP00000261951.4; ENSG00000113300.13.
DR Ensembl; ENST00000393356.7; ENSP00000377024.1; ENSG00000113300.13.
DR Ensembl; ENST00000618123.4; ENSP00000481893.1; ENSG00000113300.13.
DR MANE-Select; ENST00000261951.9; ENSP00000261951.4; NM_001370472.1; NP_001357401.1.
DR UCSC; uc003mlx.3; human.
DR GeneCards; CNOT6; -.
DR HGNC; HGNC:14099; CNOT6.
DR HPA; ENSG00000113300; Low tissue specificity.
DR MIM; 608951; gene.
DR neXtProt; NX_Q9ULM6; -.
DR OpenTargets; ENSG00000113300; -.
DR PharmGKB; PA26677; -.
DR VEuPathDB; HostDB:ENSG00000113300; -.
DR eggNOG; KOG0620; Eukaryota.
DR GeneTree; ENSGT00940000158978; -.
DR HOGENOM; CLU_016428_4_2_1; -.
DR InParanoid; Q9ULM6; -.
DR OMA; MMEMSSG; -.
DR OrthoDB; 724242at2759; -.
DR PhylomeDB; Q9ULM6; -.
DR TreeFam; TF323175; -.
DR PathwayCommons; Q9ULM6; -.
DR Reactome; R-HSA-429947; Deadenylation of mRNA.
DR Reactome; R-HSA-5617472; Activation of anterior HOX genes in hindbrain development during early embryogenesis.
DR Reactome; R-HSA-6804115; TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain.
DR SignaLink; Q9ULM6; -.
DR SIGNOR; Q9ULM6; -.
DR BioGRID-ORCS; 57472; 18 hits in 1080 CRISPR screens.
DR ChiTaRS; CNOT6; human.
DR GeneWiki; CNOT6; -.
DR GenomeRNAi; 57472; -.
DR Pharos; Q9ULM6; Tbio.
DR PRO; PR:Q9ULM6; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9ULM6; protein.
DR Bgee; ENSG00000113300; Expressed in secondary oocyte and 200 other tissues.
DR ExpressionAtlas; Q9ULM6; baseline and differential.
DR Genevisible; Q9ULM6; HS.
DR GO; GO:0030014; C:CCR4-NOT complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0000175; F:3'-5'-exoribonuclease activity; IBA:GO_Central.
DR GO; GO:0004532; F:exoribonuclease activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; IDA:GO_Central.
DR GO; GO:0004535; F:poly(A)-specific ribonuclease activity; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0043928; P:exonucleolytic catabolism of deadenylated mRNA; IDA:UniProtKB.
DR GO; GO:0035195; P:miRNA-mediated gene silencing; TAS:UniProtKB.
DR GO; GO:0070966; P:nuclear-transcribed mRNA catabolic process, no-go decay; IMP:UniProtKB.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; IMP:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0010606; P:positive regulation of cytoplasmic mRNA processing body assembly; IMP:UniProtKB.
DR CDD; cd10313; Deadenylase_CCR4a; 1.
DR Gene3D; 3.60.10.10; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR034966; Cnot6.
DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR InterPro; IPR005135; Endo/exonuclease/phosphatase.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR Pfam; PF13855; LRR_8; 1.
DR SMART; SM00369; LRR_TYP; 3.
DR SUPFAM; SSF56219; SSF56219; 1.
DR PROSITE; PS51450; LRR; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Cytoplasm; Exonuclease; Hydrolase;
KW Leucine-rich repeat; Magnesium; Metal-binding; Nuclease; Nucleus;
KW Reference proteome; Repeat; RNA-binding; RNA-mediated gene silencing;
KW Transcription; Transcription regulation; Translation regulation.
FT CHAIN 1..557
FT /note="CCR4-NOT transcription complex subunit 6"
FT /id="PRO_0000218573"
FT REPEAT 52..73
FT /note="LRR 1"
FT REPEAT 75..96
FT /note="LRR 2"
FT REPEAT 98..120
FT /note="LRR 3"
FT REPEAT 121..143
FT /note="LRR 4"
FT REGION 153..557
FT /note="Nuclease domain"
FT /evidence="ECO:0000250"
FT ACT_SITE 412
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q96LI5"
FT BINDING 240
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q96LI5"
FT BINDING 240
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LI5"
FT BINDING 276
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LI5"
FT BINDING 361
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LI5"
FT BINDING 366
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LI5"
FT BINDING 412
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q96LI5"
FT BINDING 414
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LI5"
FT BINDING 481
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LI5"
FT BINDING 486
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LI5"
FT MUTAGEN 240
FT /note="E->A: Impairs deadenylation and decay of mRNAi-
FT targeted mRNA."
FT /evidence="ECO:0000269|PubMed:20065043"
FT HELIX 19..25
FT /evidence="ECO:0007829|PDB:7AX1"
FT STRAND 33..36
FT /evidence="ECO:0007829|PDB:7AX1"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:7AX1"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:7AX1"
FT HELIX 68..72
FT /evidence="ECO:0007829|PDB:7AX1"
FT HELIX 92..95
FT /evidence="ECO:0007829|PDB:7AX1"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:7AX1"
FT HELIX 114..118
FT /evidence="ECO:0007829|PDB:7AX1"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:7AX1"
FT HELIX 134..141
FT /evidence="ECO:0007829|PDB:7AX1"
FT HELIX 145..160
FT /evidence="ECO:0007829|PDB:7AX1"
FT STRAND 174..176
FT /evidence="ECO:0007829|PDB:7AX1"
FT STRAND 186..195
FT /evidence="ECO:0007829|PDB:7AX1"
FT TURN 204..206
FT /evidence="ECO:0007829|PDB:7AX1"
FT HELIX 212..215
FT /evidence="ECO:0007829|PDB:7AX1"
FT HELIX 217..231
FT /evidence="ECO:0007829|PDB:7AX1"
FT STRAND 234..240
FT /evidence="ECO:0007829|PDB:7AX1"
FT HELIX 243..248
FT /evidence="ECO:0007829|PDB:7AX1"
FT HELIX 250..255
FT /evidence="ECO:0007829|PDB:7AX1"
FT TURN 256..258
FT /evidence="ECO:0007829|PDB:7AX1"
FT HELIX 274..278
FT /evidence="ECO:0007829|PDB:7AX1"
FT STRAND 284..288
FT /evidence="ECO:0007829|PDB:7AX1"
FT TURN 289..291
FT /evidence="ECO:0007829|PDB:7AX1"
FT STRAND 296..299
FT /evidence="ECO:0007829|PDB:7AX1"
FT HELIX 311..320
FT /evidence="ECO:0007829|PDB:7AX1"
FT STRAND 327..334
FT /evidence="ECO:0007829|PDB:7AX1"
FT STRAND 354..361
FT /evidence="ECO:0007829|PDB:7AX1"
FT HELIX 366..368
FT /evidence="ECO:0007829|PDB:7AX1"
FT HELIX 369..393
FT /evidence="ECO:0007829|PDB:7AX1"
FT STRAND 407..412
FT /evidence="ECO:0007829|PDB:7AX1"
FT HELIX 420..426
FT /evidence="ECO:0007829|PDB:7AX1"
FT STRAND 427..431
FT /evidence="ECO:0007829|PDB:7AX1"
FT HELIX 435..440
FT /evidence="ECO:0007829|PDB:7AX1"
FT HELIX 446..449
FT /evidence="ECO:0007829|PDB:7AX1"
FT STRAND 461..463
FT /evidence="ECO:0007829|PDB:7AX1"
FT TURN 471..475
FT /evidence="ECO:0007829|PDB:7AX1"
FT STRAND 476..478
FT /evidence="ECO:0007829|PDB:7AX1"
FT STRAND 480..482
FT /evidence="ECO:0007829|PDB:7AX1"
FT STRAND 491..496
FT /evidence="ECO:0007829|PDB:7AX1"
FT TURN 497..499
FT /evidence="ECO:0007829|PDB:7AX1"
FT STRAND 500..506
FT /evidence="ECO:0007829|PDB:7AX1"
FT HELIX 511..516
FT /evidence="ECO:0007829|PDB:7AX1"
FT STRAND 521..524
FT /evidence="ECO:0007829|PDB:7AX1"
FT STRAND 529..531
FT /evidence="ECO:0007829|PDB:7AX1"
FT STRAND 536..541
FT /evidence="ECO:0007829|PDB:7AX1"
SQ SEQUENCE 557 AA; 63307 MW; DA9FF7A059BFB583 CRC64;
MPKEKYEPPD PRRMYTIMSS EEAANGKKSH WAELEISGKV RSLSASLWSL THLTALHLSD
NSLSRIPSDI AKLHNLVYLD LSSNKIRSLP AELGNMVSLR ELHLNNNLLR VLPFELGKLF
QLQTLGLKGN PLTQDILNLY QEPDGTRRLL NYLLDNLSGT AKRITTEQPP PRSWIMLQEP
DRTRPTALFS VMCYNVLCDK YATRQLYGYC PSWALNWDYR KKAIIQEILS CNADIVSLQE
VETEQYYSFF LVELKERGYN GFFSPKSRAR TMSEQERKHV DGCAIFFKTE KFTLVQKHTV
EFNQLAMANS EGSEAMLNRV MTKDNIGVAV LLELRKESIE MPSGKPHLGT EKQLILVANA
HMHWDPEYSD VKLVQTMMFL SEVKNIIDKA SRNLKSSVLG EFGTIPLVLC ADLNSLPDSG
VVEYLSTGGV ETNHKDFKEL RYNESLTNFS CHGKNGTTNG RITHGFKLQS AYESGLMPYT
NYTFDFKGII DYIFYSKPQL NTLGILGPLD HHWLVENNIS GCPHPLIPSD HFSLFAQLEL
LLPFLPQVNG IHLPGRR
