PINK1_PEDHC
ID PINK1_PEDHC Reviewed; 575 AA.
AC E0W1I1;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2010, sequence version 1.
DT 03-AUG-2022, entry version 57.
DE RecName: Full=Serine/threonine-protein kinase Pink1, mitochondrial {ECO:0000303|PubMed:22645651};
DE EC=2.7.11.1 {ECO:0000269|PubMed:22645651, ECO:0000269|PubMed:29160309};
DE AltName: Full=PTEN-induced putative kinase 1 {ECO:0000303|PubMed:22645651};
DE Flags: Precursor;
GN Name=Pink1 {ECO:0000303|PubMed:22645651};
GN ORFNames=Phum_PHUM577390 {ECO:0000312|EMBL:EEB19487.1};
OS Pediculus humanus subsp. corporis (Body louse).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Paraneoptera; Psocodea; Phthiraptera; Anoplura; Pediculidae;
OC Pediculus.
OX NCBI_TaxID=121224 {ECO:0000312|Proteomes:UP000009046};
RN [1] {ECO:0000312|Proteomes:UP000009046}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=USDA {ECO:0000312|Proteomes:UP000009046};
RX PubMed=20566863; DOI=10.1073/pnas.1003379107;
RA Kirkness E.F., Haas B.J., Sun W., Braig H.R., Perotti M.A., Clark J.M.,
RA Lee S.H., Robertson H.M., Kennedy R.C., Elhaik E., Gerlach D.,
RA Kriventseva E.V., Elsik C.G., Graur D., Hill C.A., Veenstra J.A.,
RA Walenz B., Tubio J.M., Ribeiro J.M., Rozas J., Johnston J.S., Reese J.T.,
RA Popadic A., Tojo M., Raoult D., Reed D.L., Tomoyasu Y., Krause E.,
RA Mittapalli O., Margam V.M., Li H.M., Meyer J.M., Johnson R.M.,
RA Romero-Severson J., Vanzee J.P., Alvarez-Ponce D., Vieira F.G., Aguade M.,
RA Guirao-Rico S., Anzola J.M., Yoon K.S., Strycharz J.P., Unger M.F.,
RA Christley S., Lobo N.F., Seufferheld M.J., Wang N., Dasch G.A.,
RA Struchiner C.J., Madey G., Hannick L.I., Bidwell S., Joardar V., Caler E.,
RA Shao R., Barker S.C., Cameron S., Bruggner R.V., Regier A., Johnson J.,
RA Viswanathan L., Utterback T.R., Sutton G.G., Lawson D., Waterhouse R.M.,
RA Venter J.C., Strausberg R.L., Berenbaum M.R., Collins F.H., Zdobnov E.M.,
RA Pittendrigh B.R.;
RT "Genome sequences of the human body louse and its primary endosymbiont
RT provide insights into the permanent parasitic lifestyle.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:12168-12173(2010).
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, PHOSPHORYLATION, AND MUTAGENESIS OF
RP ASP-357.
RX PubMed=22645651; DOI=10.1098/rsob.110012;
RA Woodroof H.I., Pogson J.H., Begley M., Cantley L.C., Deak M.,
RA Campbell D.G., van Aalten D.M., Whitworth A.J., Alessi D.R., Muqit M.M.;
RT "Discovery of catalytically active orthologues of the Parkinson's disease
RT kinase PINK1: analysis of substrate specificity and impact of mutations.";
RL Open Biol. 1:110012-110012(2011).
RN [3] {ECO:0000305}
RP FUNCTION.
RX PubMed=26161729; DOI=10.1038/nature14879;
RA Wauer T., Simicek M., Schubert A., Komander D.;
RT "Mechanism of phospho-ubiquitin-induced PARKIN activation.";
RL Nature 524:370-374(2015).
RN [4] {ECO:0000305}
RP ERRATUM OF PUBMED:26161729.
RX PubMed=26416742; DOI=10.1038/nature15531;
RA Wauer T., Simicek M., Schubert A., Komander D.;
RL Nature 526:728-728(2015).
RN [5] {ECO:0007744|PDB:6EQI}
RP X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 143-575 IN COMPLEX WITH
RP UBIQUITIN, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, PHOSPHORYLATION AT
RP SER-202; SER-204 AND THR-305, AND MUTAGENESIS OF TYR-198; 202-SER--SER-204;
RP PRO-268; GLY-281; 282-ARG-ASN-283; ASP-379 AND GLY-382.
RX PubMed=29160309; DOI=10.1038/nature24645;
RA Schubert A.F., Gladkova C., Pardon E., Wagstaff J.L., Freund S.M.V.,
RA Steyaert J., Maslen S.L., Komander D.;
RT "Structure of PINK1 in complex with its substrate ubiquitin.";
RL Nature 552:51-56(2017).
CC -!- FUNCTION: Acts as a serine/threonine-protein kinase (PubMed:22645651,
CC PubMed:26161729, PubMed:29160309). Exhibits a substrate preference for
CC proline at position P+1 and a general preference at several residues
CC for basic residues such as arginine (By similarity). Also exhibits
CC moderate preferences for a phosphotyrosine at position P-3 and a
CC tryptophan at P-5 (By similarity). Protects against mitochondrial
CC dysfunction during cellular stress by phosphorylating mitochondrial
CC proteins such as park and likely Drp1, to coordinate mitochondrial
CC quality control mechanisms that remove and replace dysfunctional
CC mitochondrial components (PubMed:26161729). Depending on the severity
CC of mitochondrial damage and/or dysfunction, activity ranges from
CC preventing apoptosis and stimulating mitochondrial biogenesis to
CC regulating mitochondrial dynamics and eliminating severely damaged
CC mitochondria via mitophagy (By similarity). Appears to be particularly
CC important in maintaining the physiology and function of cells with high
CC energy demands that are undergoing stress or altered metabolic
CC environment, including spermatids, muscle cells and neurons such as the
CC dopaminergic (DA) neurons (By similarity). Mediates the translocation
CC and activation of park at the outer membrane (OMM) of
CC dysfunctional/depolarized mitochondria (PubMed:26161729). At the OMM of
CC damaged mitochondria, phosphorylates pre-existing polyubiquitin chains,
CC the Pink1-phosphorylated polyubiquitin then recruits park from the
CC cytosol to the OMM where park is fully activated by phosphorylation at
CC 'Ser-94' by Pink1 (By similarity). When cellular stress results in
CC irreversible mitochondrial damage, functions with park to promote the
CC clearance of dysfunctional and/or depolarized mitochondria by selective
CC autophagy (mitophagy) (By similarity). The Pink1-park pathway also
CC promotes fission and/or inhibits fusion of damaged mitochondria, by
CC phosphorylating and thus promoting the park-dependent degradation of
CC proteins involved in mitochondrial fusion/fission such as Marf, Opa1
CC and fzo (By similarity). This prevents the refusion of unhealthy
CC mitochondria with the mitochondrial network or initiates mitochondrial
CC fragmentation facilitating their later engulfment by autophagosomes (By
CC similarity). Also likely to promote mitochondrial fission independently
CC of park and Atg7-mediated mitophagy, via the phosphorylation and
CC activation of Drp1 (By similarity). Regulates motility of damaged
CC mitochondria by phosphorylating Miro which likely promotes its park-
CC dependent degradation by the proteasome; in motor neurons, this
CC inhibits mitochondrial intracellular anterograde transport along the
CC axons which probably increases the chance of the mitochondria being
CC eliminated in the soma (By similarity). The Pink1-park pathway is also
CC involved in mitochondrial regeneration processes such as promoting
CC mitochondrial biogenesis, activating localized mitochondrial repair,
CC promoting selective turnover of mitochondrial proteins and initiating
CC the mitochondrial import of endogenous proteins (By similarity).
CC Involved in mitochondrial biogenesis by promoting the park-dependent
CC ubiquitination of transcriptional repressor Paris which leads to its
CC subsequent proteasomal degradation and allows activation of the
CC transcription factor srl (By similarity). Functions with park to
CC promote localized mitochondrial repair by activating the translation of
CC specific nuclear-encoded mitochondrial RNAs (nc-mtRNAs) on the
CC mitochondrial surface, including several key electron transport chain
CC component nc-mtRNAs (By similarity). During oogenesis, phosphorylates
CC and inactivates larp on the membrane of defective mitochondria, thus
CC impairing local translation and mtDNA replication and consequently,
CC reducing transmission of deleterious mtDNA mutations to the mature
CC oocyte (By similarity). {ECO:0000250|UniProtKB:D6WMX4,
CC ECO:0000250|UniProtKB:Q0KHV6, ECO:0000269|PubMed:22645651,
CC ECO:0000269|PubMed:26161729, ECO:0000269|PubMed:29160309}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:22645651, ECO:0000269|PubMed:29160309};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:22645651,
CC ECO:0000269|PubMed:29160309};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:22645651, ECO:0000269|PubMed:29160309};
CC Note=Binds 2 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:D6WMX4};
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:Q0KHV6}; Single-pass membrane protein
CC {ECO:0000255}. Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:Q0KHV6}; Single-pass membrane protein
CC {ECO:0000255}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q0KHV6}.
CC Note=Localizes mostly in mitochondrion, and the smaller proteolytic
CC processed fragment localizes in the cytosol as well (By similarity).
CC When mitochondria are damaged, defective and/or enriched with
CC deleterious mtDNA mutations, Pink1 import is arrested which induces its
CC accumulation on the outer mitochondrial membrane where it acquires
CC kinase activity (By similarity). {ECO:0000250|UniProtKB:Q0KHV6}.
CC -!- PTM: Proteolytically cleaved. In healthy cells, the precursor is
CC continuously imported into mitochondria where it is proteolytically
CC cleaved into its short form by the mitochondrial rhomboid protease rho-
CC 7 (8231301). The short form is then released into the cytosol where it
CC rapidly undergoes proteasome-dependent degradation. In unhealthy cells,
CC when cellular stress conditions lead to the loss of mitochondrial
CC membrane potential, mitochondrial import is impaired leading to the
CC precursor accumulating on the outer mitochondrial membrane (OMM).
CC {ECO:0000250|UniProtKB:Q0KHV6}.
CC -!- PTM: Autophosphorylated (PubMed:22645651, PubMed:29160309).
CC Autophosphorylated on Ser-202, which activates kinase activity
CC (PubMed:29160309). Loss of mitochondrial membrane potential results in
CC the precursor accumulating on the outer mitochondrial membrane (OMM)
CC where it is activated by autophosphorylation at Ser-202 (By
CC similarity). Autophosphorylation is sufficient and essential for
CC selective recruitment of park to depolarized mitochondria, likely via
CC Pink1-dependent phosphorylation of polyubiquitin chains (By
CC similarity). Also autophosphorylated at Ser-204 and Thr-305
CC (PubMed:29160309). {ECO:0000250|UniProtKB:Q0KHV6,
CC ECO:0000269|PubMed:22645651, ECO:0000269|PubMed:29160309}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. {ECO:0000305}.
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DR EMBL; AAZO01007021; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; DS235870; EEB19487.1; -; Genomic_DNA.
DR RefSeq; XP_002432225.1; XM_002432180.1.
DR PDB; 6EQI; X-ray; 3.10 A; C=143-575.
DR PDB; 7T3X; X-ray; 3.53 A; A=115-575.
DR PDB; 7T4K; EM; 3.25 A; A/B=115-575.
DR PDB; 7T4L; EM; 3.28 A; A/B=115-575.
DR PDB; 7T4M; EM; 2.48 A; A/B/C/D/E/F/G/H/I/J/K/L=115-575.
DR PDB; 7T4N; EM; 2.35 A; A/B=115-575.
DR PDBsum; 6EQI; -.
DR PDBsum; 7T3X; -.
DR PDBsum; 7T4K; -.
DR PDBsum; 7T4L; -.
DR PDBsum; 7T4M; -.
DR PDBsum; 7T4N; -.
DR SMR; E0W1I1; -.
DR STRING; 121225.PHUM577390-PA; -.
DR ABCD; E0W1I1; 1 sequenced antibody.
DR EnsemblMetazoa; PHUM577390-RA; PHUM577390-PA; PHUM577390.
DR GeneID; 8239562; -.
DR KEGG; phu:Phum_PHUM577390; -.
DR CTD; 8239562; -.
DR VEuPathDB; VectorBase:PHUM577390; -.
DR eggNOG; KOG4158; Eukaryota.
DR HOGENOM; CLU_022208_0_0_1; -.
DR InParanoid; E0W1I1; -.
DR OMA; FGQHARK; -.
DR PhylomeDB; E0W1I1; -.
DR Proteomes; UP000009046; Unplaced.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Autophagy; Cytoplasm; Kinase; Magnesium;
KW Membrane; Metal-binding; Mitochondrion; Mitochondrion inner membrane;
KW Mitochondrion outer membrane; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Transit peptide; Transmembrane; Transmembrane helix.
FT TRANSIT 1..51
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 52..575
FT /note="Serine/threonine-protein kinase Pink1,
FT mitochondrial"
FT /evidence="ECO:0000255"
FT /id="PRO_0000454927"
FT TOPO_DOM 52..94
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT TRANSMEM 95..118
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 119..575
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT ACT_SITE 334
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 193
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 214
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:D6WMX4"
FT BINDING 339
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:D6WMX4"
FT BINDING 357
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:D6WMX4"
FT BINDING 357
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:D6WMX4"
FT MOD_RES 202
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:29160309"
FT MOD_RES 204
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:29160309"
FT MOD_RES 305
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:29160309"
FT MUTAGEN 198
FT /note="Y->E: Abolishes ubiquitin phosphorylation, but has
FT no effect on autophosphorylation."
FT /evidence="ECO:0000269|PubMed:29160309"
FT MUTAGEN 202..204
FT /note="SNS->ANA: Abolishes ubiquitin phosphorylation and
FT displays reduced autophosphorylation."
FT /evidence="ECO:0000269|PubMed:29160309"
FT MUTAGEN 268
FT /note="P->L: Reduced phosphorylation of ubiquitin, but has
FT no effect on autophosphorylation."
FT /evidence="ECO:0000269|PubMed:29160309"
FT MUTAGEN 281
FT /note="G->D: Abolishes ubiquitin phosphorylation and
FT reduces autophosphorylation."
FT /evidence="ECO:0000269|PubMed:29160309"
FT MUTAGEN 282..283
FT /note="RN->AA: Abolishes ubiquitin phosphorylation and
FT displays reduced autophosphorylation."
FT /evidence="ECO:0000269|PubMed:29160309"
FT MUTAGEN 357
FT /note="D->A: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:22645651"
FT MUTAGEN 379
FT /note="D->A: Reduced phosphorylation of ubiquitin, but has
FT no effect on autophosphorylation."
FT /evidence="ECO:0000269|PubMed:29160309"
FT MUTAGEN 382
FT /note="G->V: Abolishes enzyme activity. Loss of ubiquitin
FT phosphorylation and autophosphorylation."
FT /evidence="ECO:0000269|PubMed:29160309"
FT HELIX 120..136
FT /evidence="ECO:0007829|PDB:7T4N"
FT TURN 149..151
FT /evidence="ECO:0007829|PDB:7T4N"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:7T4N"
FT STRAND 163..167
FT /evidence="ECO:0007829|PDB:6EQI"
FT STRAND 168..178
FT /evidence="ECO:0007829|PDB:7T4N"
FT STRAND 189..198
FT /evidence="ECO:0007829|PDB:7T4N"
FT STRAND 201..203
FT /evidence="ECO:0007829|PDB:7T4K"
FT HELIX 204..214
FT /evidence="ECO:0007829|PDB:7T4N"
FT TURN 215..217
FT /evidence="ECO:0007829|PDB:7T4N"
FT STRAND 221..223
FT /evidence="ECO:0007829|PDB:7T4N"
FT TURN 225..227
FT /evidence="ECO:0007829|PDB:7T4N"
FT TURN 230..235
FT /evidence="ECO:0007829|PDB:7T4N"
FT STRAND 249..255
FT /evidence="ECO:0007829|PDB:7T4N"
FT TURN 258..262
FT /evidence="ECO:0007829|PDB:7T4N"
FT TURN 264..266
FT /evidence="ECO:0007829|PDB:7T4N"
FT HELIX 268..270
FT /evidence="ECO:0007829|PDB:6EQI"
FT TURN 273..275
FT /evidence="ECO:0007829|PDB:6EQI"
FT STRAND 283..291
FT /evidence="ECO:0007829|PDB:7T4N"
FT STRAND 294..296
FT /evidence="ECO:0007829|PDB:7T4N"
FT HELIX 297..303
FT /evidence="ECO:0007829|PDB:7T4N"
FT HELIX 308..327
FT /evidence="ECO:0007829|PDB:7T4N"
FT STRAND 339..343
FT /evidence="ECO:0007829|PDB:7T4N"
FT STRAND 348..350
FT /evidence="ECO:0007829|PDB:7T4N"
FT STRAND 352..355
FT /evidence="ECO:0007829|PDB:7T4N"
FT HELIX 358..360
FT /evidence="ECO:0007829|PDB:7T4N"
FT TURN 365..369
FT /evidence="ECO:0007829|PDB:7T4N"
FT STRAND 370..372
FT /evidence="ECO:0007829|PDB:7T4N"
FT STRAND 384..386
FT /evidence="ECO:0007829|PDB:7T4K"
FT HELIX 389..392
FT /evidence="ECO:0007829|PDB:7T4N"
FT STRAND 397..399
FT /evidence="ECO:0007829|PDB:6EQI"
FT STRAND 401..403
FT /evidence="ECO:0007829|PDB:7T4N"
FT HELIX 407..419
FT /evidence="ECO:0007829|PDB:7T4N"
FT TURN 425..427
FT /evidence="ECO:0007829|PDB:7T4N"
FT TURN 429..431
FT /evidence="ECO:0007829|PDB:7T4N"
FT TURN 435..437
FT /evidence="ECO:0007829|PDB:7T4N"
FT HELIX 440..442
FT /evidence="ECO:0007829|PDB:7T4N"
FT HELIX 452..461
FT /evidence="ECO:0007829|PDB:7T4N"
FT TURN 466..468
FT /evidence="ECO:0007829|PDB:7T4N"
FT HELIX 472..484
FT /evidence="ECO:0007829|PDB:7T4N"
FT HELIX 487..490
FT /evidence="ECO:0007829|PDB:7T4N"
FT STRAND 491..493
FT /evidence="ECO:0007829|PDB:7T4M"
FT HELIX 499..514
FT /evidence="ECO:0007829|PDB:7T4N"
FT HELIX 543..553
FT /evidence="ECO:0007829|PDB:7T4N"
FT HELIX 558..573
FT /evidence="ECO:0007829|PDB:7T4N"
SQ SEQUENCE 575 AA; 65446 MW; 6937F4BC747FF1BE CRC64;
MSLLAYTNLL LQNGRIFRYY KKANIKKFIK KIIKLDLKST PSEASVSRQT FLSTGLNSVK
NAVQLQARKL LINNVLERVT PTLNSDLKKK AAKRLFYGDS APFFALVGVS LASGSGLLTK
DDELEGICWE IREAVSKGKW NDSESENVEQ LQAANLDELD LGEPIAKGCN AVVYSAKLKN
VQSNKLAHQL AVKMMFNYDV ESNSTAILKA MYRETVPAMS YFFNQNLFNI ENISDFKIRL
PPHPNIVRMY SVFADRIPDL QCNKQLYPEA LPPRINPEGS GRNMSLFLVM KRYDCTLKEY
LRDKTPNMRS SILLLSQLLE AVAHMNIHNI SHRDLKSDNI LVDLSEGDAY PTIVITDFGC
CLCDKQNGLV IPYRSEDQDK GGNRALMAPE IANAKPGTFS WLNYKKSDLW AVGAIAYEIF
NIDNPFYDKT MKLLSKSYKE EDLPELPDTI PFIIRNLVSN MLSRSTNKRL DCDVAATVAQ
LYLWAPSSWL KENYTLPNSN EIIQWLLCLS SKVLCERDIT ARNKTNTMSE SVSKAQYKGR
RSLPEYELIA SFLRRVRLHL VRKGLKWIQE LHIYN
