APEX2_HUMAN
ID APEX2_HUMAN Reviewed; 518 AA.
AC Q9UBZ4; Q9Y5X7;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=DNA-(apurinic or apyrimidinic site) endonuclease 2;
DE EC=3.1.11.2 {ECO:0000250|UniProtKB:P27695};
DE AltName: Full=AP endonuclease XTH2;
DE AltName: Full=APEX nuclease 2;
DE AltName: Full=APEX nuclease-like 2;
DE AltName: Full=Apurinic-apyrimidinic endonuclease 2;
DE Short=AP endonuclease 2;
GN Name=APEX2; Synonyms=APE2, APEXL2, XTH2;
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 [MRNA], FUNCTION, INTERACTION WITH PCNA, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Leukemia;
RX PubMed=11376153; DOI=10.1093/nar/29.11.2349;
RA Tsuchimoto D., Sakai Y., Sakumi K., Nishioka K., Sasaki M., Fujiwara T.,
RA Nakabeppu Y.;
RT "Human APE2 protein is mostly localized in the nuclei and to some extent in
RT the mitochondria, while nuclear APE2 is partly associated with
RT proliferating cell nuclear antigen.";
RL Nucleic Acids Res. 29:2349-2360(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung tumor;
RA Luna L., Rognes T., Henriksen A.C., Bjoras M., Seeberg E.;
RT "Putative human AP endonuclease XTH2.";
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Bone marrow;
RA Akiyama K., Sarker A.H., Yao M., Tsutsui K., Seki S.;
RT "cDNA cloning and characterization of human APEX nuclease-like 2 (APEXL2)
RT protein.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung tumor;
RA Hadi M.Z., Erzberger J.P., Ramirez M.H., Thelen M.P., Wilson D.M. III;
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT CYS-141.
RG NIEHS SNPs program;
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [8]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF ASP-277.
RX PubMed=16687656; DOI=10.1093/nar/gkl259;
RA Burkovics P., Szukacsov V., Unk I., Haracska L.;
RT "Human Ape2 protein has a 3'-5' exonuclease activity that acts
RT preferentially on mismatched base pairs.";
RL Nucleic Acids Res. 34:2508-2515(2006).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-396 AND PHE-397.
RX PubMed=19443450; DOI=10.1093/nar/gkp357;
RA Burkovics P., Hajdu I., Szukacsov V., Unk I., Haracska L.;
RT "Role of PCNA-dependent stimulation of 3'-phosphodiesterase and 3'-5'
RT exonuclease activities of human Ape2 in repair of oxidative DNA damage.";
RL Nucleic Acids Res. 37:4247-4255(2009).
RN [11]
RP VARIANTS TYR-269 AND HIS-392.
RX PubMed=20843780; DOI=10.1093/nar/gkq750;
RA Wang W., Shen P., Thiyagarajan S., Lin S., Palm C., Horvath R.,
RA Klopstock T., Cutler D., Pique L., Schrijver I., Davis R.W., Mindrinos M.,
RA Speed T.P., Scharfe C.;
RT "Identification of rare DNA variants in mitochondrial disorders with
RT improved array-based sequencing.";
RL Nucleic Acids Res. 39:44-58(2011).
CC -!- FUNCTION: Functions as a weak apurinic/apyrimidinic (AP)
CC endodeoxyribonuclease in the DNA base excision repair (BER) pathway of
CC DNA lesions induced by oxidative and alkylating agents. Initiates
CC repair of AP sites in DNA by catalyzing hydrolytic incision of the
CC phosphodiester backbone immediately adjacent to the damage, generating
CC a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl
CC ends. Also displays double-stranded DNA 3'-5' exonuclease, 3'-
CC phosphodiesterase activities. Shows robust 3'-5' exonuclease activity
CC on 3'-recessed heteroduplex DNA and is able to remove mismatched
CC nucleotides preferentially. Shows fairly strong 3'-phosphodiesterase
CC activity involved in the removal of 3'-damaged termini formed in DNA by
CC oxidative agents. In the nucleus functions in the PCNA-dependent BER
CC pathway. Required for somatic hypermutation (SHM) and DNA cleavage step
CC of class switch recombination (CSR) of immunoglobulin genes. Required
CC for proper cell cycle progression during proliferation of peripheral
CC lymphocytes. {ECO:0000269|PubMed:11376153, ECO:0000269|PubMed:16687656,
CC ECO:0000269|PubMed:19443450}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Exonucleolytic cleavage in the 3'- to 5'-direction to yield
CC nucleoside 5'-phosphates.; EC=3.1.11.2;
CC Evidence={ECO:0000250|UniProtKB:P27695};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC Note=Probably binds two magnesium or manganese ions per subunit.
CC {ECO:0000250};
CC -!- ACTIVITY REGULATION: 3'-5' exonuclease activity is activated by sodium
CC and manganese. 3'-5' exonuclease and 3'-phosphodiesterase activities
CC are stimulated in presence of PCNA.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 6.0-8.0. {ECO:0000269|PubMed:16687656};
CC -!- SUBUNIT: Interacts with PCNA; this interaction is triggered by reactive
CC oxygen species and increased by misincorporation of uracil in nuclear
CC DNA. {ECO:0000269|PubMed:11376153}.
CC -!- INTERACTION:
CC Q9UBZ4; Q13064: MKRN3; NbExp=3; IntAct=EBI-742588, EBI-2340269;
CC Q9UBZ4; Q63HK5: TSHZ3; NbExp=3; IntAct=EBI-742588, EBI-9053916;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Mitochondrion {ECO:0000305}.
CC Note=Together with PCNA, is redistributed in discrete nuclear foci in
CC presence of oxidative DNA damaging agents.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain and kidney. Weakly
CC expressed in the fetal brain. {ECO:0000269|PubMed:11376153}.
CC -!- SIMILARITY: Belongs to the DNA repair enzymes AP/ExoA family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/apex2/";
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; AB049211; BAB13764.1; -; mRNA.
DR EMBL; AJ011311; CAB45242.1; -; mRNA.
DR EMBL; AB021260; BAA78422.1; -; mRNA.
DR EMBL; AF119046; AAD43041.1; -; mRNA.
DR EMBL; AY884244; AAW56941.1; -; Genomic_DNA.
DR EMBL; AL020991; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002959; AAH02959.1; -; mRNA.
DR CCDS; CCDS14365.1; -.
DR RefSeq; NP_055296.2; NM_014481.3.
DR AlphaFoldDB; Q9UBZ4; -.
DR SMR; Q9UBZ4; -.
DR BioGRID; 118124; 30.
DR IntAct; Q9UBZ4; 28.
DR STRING; 9606.ENSP00000364126; -.
DR iPTMnet; Q9UBZ4; -.
DR PhosphoSitePlus; Q9UBZ4; -.
DR BioMuta; APEX2; -.
DR DMDM; 73921676; -.
DR EPD; Q9UBZ4; -.
DR jPOST; Q9UBZ4; -.
DR MassIVE; Q9UBZ4; -.
DR MaxQB; Q9UBZ4; -.
DR PaxDb; Q9UBZ4; -.
DR PeptideAtlas; Q9UBZ4; -.
DR PRIDE; Q9UBZ4; -.
DR ProteomicsDB; 84104; -.
DR Antibodypedia; 26902; 163 antibodies from 24 providers.
DR DNASU; 27301; -.
DR Ensembl; ENST00000374987.4; ENSP00000364126.3; ENSG00000169188.5.
DR GeneID; 27301; -.
DR KEGG; hsa:27301; -.
DR MANE-Select; ENST00000374987.4; ENSP00000364126.3; NM_014481.4; NP_055296.2.
DR UCSC; uc004dtz.5; human.
DR CTD; 27301; -.
DR DisGeNET; 27301; -.
DR GeneCards; APEX2; -.
DR HGNC; HGNC:17889; APEX2.
DR HPA; ENSG00000169188; Low tissue specificity.
DR MIM; 300773; gene.
DR neXtProt; NX_Q9UBZ4; -.
DR OpenTargets; ENSG00000169188; -.
DR PharmGKB; PA38474; -.
DR VEuPathDB; HostDB:ENSG00000169188; -.
DR eggNOG; KOG1294; Eukaryota.
DR GeneTree; ENSGT00530000063540; -.
DR HOGENOM; CLU_010374_3_0_1; -.
DR InParanoid; Q9UBZ4; -.
DR OMA; FIWSSDW; -.
DR OrthoDB; 1352540at2759; -.
DR PhylomeDB; Q9UBZ4; -.
DR TreeFam; TF328442; -.
DR BRENDA; 4.2.99.18; 2681.
DR PathwayCommons; Q9UBZ4; -.
DR SignaLink; Q9UBZ4; -.
DR BioGRID-ORCS; 27301; 56 hits in 707 CRISPR screens.
DR ChiTaRS; APEX2; human.
DR GenomeRNAi; 27301; -.
DR Pharos; Q9UBZ4; Tbio.
DR PRO; PR:Q9UBZ4; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q9UBZ4; protein.
DR Bgee; ENSG00000169188; Expressed in endometrium epithelium and 164 other tissues.
DR ExpressionAtlas; Q9UBZ4; baseline and differential.
DR Genevisible; Q9UBZ4; HS.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003906; F:DNA-(apurinic or apyrimidinic site) endonuclease activity; IBA:GO_Central.
DR GO; GO:0008311; F:double-stranded DNA 3'-5' exodeoxyribonuclease activity; IBA:GO_Central.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0008081; F:phosphoric diester hydrolase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006284; P:base-excision repair; IBA:GO_Central.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW.
DR Gene3D; 3.60.10.10; -; 1.
DR InterPro; IPR004808; AP_endonuc_1.
DR InterPro; IPR020847; AP_endonuclease_F1_BS.
DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR InterPro; IPR005135; Endo/exonuclease/phosphatase.
DR InterPro; IPR010666; Znf_GRF.
DR PANTHER; PTHR22748; PTHR22748; 1.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR Pfam; PF06839; zf-GRF; 1.
DR SUPFAM; SSF56219; SSF56219; 1.
DR TIGRFAMs; TIGR00633; xth; 1.
DR PROSITE; PS00726; AP_NUCLEASE_F1_1; 1.
DR PROSITE; PS51435; AP_NUCLEASE_F1_4; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cytoplasm; DNA damage; DNA recombination; DNA repair;
KW DNA-binding; Endonuclease; Exonuclease; Hydrolase; Magnesium;
KW Metal-binding; Mitochondrion; Nuclease; Nucleus; Reference proteome; Zinc;
KW Zinc-finger.
FT CHAIN 1..518
FT /note="DNA-(apurinic or apyrimidinic site) endonuclease 2"
FT /id="PRO_0000200014"
FT ZN_FING 467..515
FT /note="GRF-type"
FT REGION 355..407
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 390..397
FT /note="Required for the colocalization with PCNA in nuclear
FT foci in presence of oxidative-induced DNA damaging agents"
FT ACT_SITE 156
FT /evidence="ECO:0000250"
FT ACT_SITE 197
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT BINDING 8
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 48
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 197
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 199
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 303
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT SITE 199
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT SITE 277
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250"
FT SITE 304
FT /note="Interaction with DNA substrate"
FT /evidence="ECO:0000250"
FT VARIANT 141
FT /note="R -> C (in dbSNP:rs2301416)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_023390"
FT VARIANT 141
FT /note="R -> W (in dbSNP:rs2301416)"
FT /id="VAR_048261"
FT VARIANT 269
FT /note="H -> Y (identified in a patient with mtDNA
FT maintenance disorders; dbSNP:rs145122391)"
FT /evidence="ECO:0000269|PubMed:20843780"
FT /id="VAR_064033"
FT VARIANT 392
FT /note="N -> H (identified in a patient with mtDNA
FT maintenance disorders; dbSNP:rs201964062)"
FT /evidence="ECO:0000269|PubMed:20843780"
FT /id="VAR_064034"
FT MUTAGEN 269
FT /note="H->A: Abolishes AP endodeoxyribonuclease, 3'-5'
FT exonuclease activity and 3'-phosphodiesterase activities."
FT MUTAGEN 277
FT /note="D->A: Abolishes AP endodeoxyribonuclease, 3'-5'
FT exonuclease activity and 3'-phosphodiesterase activities."
FT /evidence="ECO:0000269|PubMed:16687656"
FT MUTAGEN 396
FT /note="Y->A: Reduces 3'-5' exonuclease activity in presence
FT of PCNA. Does not abolish the 3'-5' exonuclease activity.
FT Does only partially redistributes together with PCNA in
FT nuclear foci in presence of oxidative-induced DNA damaging
FT agents."
FT /evidence="ECO:0000269|PubMed:19443450"
FT MUTAGEN 397
FT /note="F->A: Reduces 3'-5' exonuclease activity in presence
FT of PCNA. Does not abolish the 3'-5' exonuclease activity.
FT Does only partially redistributes together with PCNA in
FT nuclear foci in presence of oxidative-induced DNA damaging
FT agents."
FT /evidence="ECO:0000269|PubMed:19443450"
FT CONFLICT 399
FT /note="P -> S (in Ref. 4; AAD43041)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 518 AA; 57401 MW; 08464806153F8832 CRC64;
MLRVVSWNIN GIRRPLQGVA NQEPSNCAAV AVGRILDELD ADIVCLQETK VTRDALTEPL
AIVEGYNSYF SFSRNRSGYS GVATFCKDNA TPVAAEEGLS GLFATQNGDV GCYGNMDEFT
QEELRALDSE GRALLTQHKI RTWEGKEKTL TLINVYCPHA DPGRPERLVF KMRFYRLLQI
RAEALLAAGS HVIILGDLNT AHRPIDHWDA VNLECFEEDP GRKWMDSLLS NLGCQSASHV
GPFIDSYRCF QPKQEGAFTC WSAVTGARHL NYGSRLDYVL GDRTLVIDTF QASFLLPEVM
GSDHCPVGAV LSVSSVPAKQ CPPLCTRFLP EFAGTQLKIL RFLVPLEQSP VLEQSTLQHN
NQTRVQTCQN KAQVRSTRPQ PSQVGSSRGQ KNLKSYFQPS PSCPQASPDI ELPSLPLMSA
LMTPKTPEEK AVAKVVKGQA KTSEAKDEKE LRTSFWKSVL AGPLRTPLCG GHREPCVMRT
VKKPGPNLGR RFYMCARPRG PPTDPSSRCN FFLWSRPS
