|
|
|
|
|
|
Description:
Exonuclease 1 (EC 3.1.-.-) (hExo1) (Exonuclease I) (hExoI).
Molecular weight: 94103
View which proteins in this organism that is involved with DNA Repair;
classified after biological processes (using data from the GOA project):
DNA repair( GO:0006281 ) base-excision repair( GO:0006284 ) nucleotide-excision repair (and GO:0045001, a synonym)( GO:0006289 )
Important dates:
24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
24-JAN-2006, sequence version 2.
07-MAR-2006, entry version 27.
Phylogenetic order:
Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Primates Catarrhini Hominidae Homo.
To calculate the pI (Isoelectric point - the pH where a protein has a neutral charge),
go to this page and enter the protein ID (e.g 3MG_ECOLI): http://us.expasy.org/tools/pi_tool.html
Links to references in other databases for protein EXO1_HUMAN:
Keywords:
Alternative splicing; Direct protein sequencing; DNA damage; DNA excision; DNA repair; DNA-binding; Endonuclease; Excision nuclease; Exonuclease; Hydrolase; Immune response; Meiosis; Nuclear protein; Nuclease; Phosphorylation; Polymorphism.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH MSH2, TISSUE
RP SPECIFICITY, AND VARIANTS ARG-354; LYS-589; GLY-670; CYS-723 AND
RP LEU-757.
RX MEDLINE=99002645; PubMed=9788596;
RA Schmutte C., Marinescu R.C., Sadoff M.M., Guerrette S., Overhauser J.,
RA Fishel R.;
RT "Human exonuclease I interacts with the mismatch repair protein
RT hMSH2.";
RL Cancer Res. 58:4537-4542(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], ALTERNATIVE SPLICING, TISSUE
RP SPECIFICITY, AND VARIANTS ARG-354; LYS-589; GLY-670 AND CYS-723.
RX MEDLINE=99040637; PubMed=9823303;
RA Tishkoff D.X., Amin N.S., Viars C.S., Arden K.C., Kolodner R.D.;
RT "Identification of a human gene encoding a homologue of Saccharomyces
RT cerevisiae EXO1, an exonuclease implicated in mismatch repair and
RT recombination.";
RL Cancer Res. 58:5027-5031(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], ALTERNATIVE SPLICING,
RP FUNCTION, TISSUE SPECIFICITY, AND VARIANTS ARG-354; LYS-589; GLY-670
RP AND CYS-723.
RC TISSUE=Sperm;
RX MEDLINE=98352212; PubMed=9685493; DOI=10.1093/nar/26.16.3762;
RA Wilson D.M. III, Carney J.P., Coleman M.A., Adamson A.W.,
RA Christensen M., Lamerdin J.E.;
RT "Hex1: a new human Rad2 nuclease family member with homology to yeast
RT exonuclease 1.";
RL Nucleic Acids Res. 26:3762-3768(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF 1-7
RP (ISOFORMS 1/2), FUNCTION, AND VARIANTS ARG-354; LYS-589; GLY-670 AND
RP CYS-723.
RX MEDLINE=99292759; PubMed=10364235; DOI=10.1074/jbc.274.25.17893;
RA Qiu J., Qian Y., Chen V., Guan M.-X., Shen B.;
RT "Human exonuclease 1 functionally complements its yeast homologues in
RT DNA recombination, RNA primer removal, and mutation avoidance.";
RL J. Biol. Chem. 274:17893-17900(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-76; GLY-93;
RP SER-279; SER-299; ARG-354; ASN-428; MET-439; TYR-456; MET-458;
RP LEU-460; THR-503; LYS-589; GLN-634; GLY-670; CYS-723; LEU-757 AND
RP GLU-759.
RA Rieder M.J., Livingston R.J., Daniels M.R., Montoya M.A., Chung M.-W.,
RA Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D.,
RA Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A.;
RT "NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department
RT of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS
RP GLY-670 AND CYS-723.
RC TISSUE=Skin;
RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899;
RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G.,
RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D.,
RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K.,
RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F.,
RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L.,
RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E.,
RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C.,
RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J.,
RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H.,
RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W.,
RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A.,
RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A.,
RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G.,
RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C.,
RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M.,
RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E.,
RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.;
RT "Generation and initial analysis of more than 15,000 full-length human
RT and mouse cDNA sequences.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 175-846 (ISOFORM 1), AND
RP VARIANTS LYS-589; GLY-670 AND CYS-723.
RC TISSUE=Testis;
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP FUNCTION.
RX MEDLINE=20076443; PubMed=10608837; DOI=10.1074/jbc.274.53.37763;
RA Lee B.-I., Wilson D.M. III;
RT "The RAD2 domain of human exonuclease 1 exhibits 5' to 3' exonuclease
RT and flap structure-specific endonuclease activities.";
RL J. Biol. Chem. 274:37763-37769(1999).
RN [10]
RP INTERACTION WITH MSH2, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX MEDLINE=20316168; PubMed=10856833; DOI=10.1016/S0921-8777(00)00012-4;
RA Rasmussen L.J., Rasmussen M., Lee B.-I., Rasmussen A.K.,
RA Wilson D.M. III, Nielsen F.C., Bisgaard H.C.;
RT "Identification of factors interacting with hMSH2 in the fetal liver
RT utilizing the yeast two-hybrid system. In vivo interaction through the
RT C-terminal domains of hEXO1 and hMSH2 and comparative expression
RT analysis.";
RL Mutat. Res. 460:41-52(2000).
RN [11]
RP INTERACTIONS WITH MLH1; MSH2 AND MSH3.
RX PubMed=11427529; DOI=10.1074/jbc.M102670200;
RA Schmutte C., Sadoff M.M., Shim K.-S., Acharya S., Fishel R.;
RT "The interaction of DNA mismatch repair proteins with human
RT exonuclease I.";
RL J. Biol. Chem. 276:33011-33018(2001).
RN [12]
RP INTERACTIONS WITH MLH1 AND MSH2, AND SUBCELLULAR LOCATION.
RX PubMed=11429708; DOI=10.1038/sj/onc/1204467;
RA Jaeger A.C., Rasmussen M., Bisgaard H.C., Singh K.K., Nielsen F.C.,
RA Rasmussen L.J.;
RT "HNPCC mutations in the human DNA mismatch repair gene hMLH1 influence
RT assembly of hMutLalpha and hMLH1-hEXO1 complexes.";
RL Oncogene 20:3590-3595(2001).
RN [13]
RP FUNCTION, INTERACTIONS WITH MLH1 AND MSH2, CHARACTERIZATION OF
RP VARIANTS LYS-109; ARG-410; SER-640; GLU-759 AND LEU-770, AND
RP MUTAGENESIS OF PRO-640; GLY-759 AND PRO-770.
RA Sun X., Zheng L., Shen B.;
RT "Functional alterations of human exonuclease 1 mutants identified in
RT atypical hereditary nonpolyposis colorectal cancer syndrome.";
RL Cancer Res. 62:6026-6030(2002).
RN [14]
RP FUNCTION.
RX PubMed=11809771; DOI=10.1074/jbc.M111854200;
RA Genschel J., Bazemore L.R., Modrich P.;
RT "Human exonuclease I is required for 5' and 3' mismatch repair.";
RL J. Biol. Chem. 277:13302-13311(2002).
RN [15]
RP FUNCTION, DNA-BINDING, AND MUTAGENESIS OF ASP-78; ASP-173 AND ASP-225.
RX MEDLINE=21831089; PubMed=11842105; DOI=10.1093/nar/30.4.942;
RA Lee B.-I., Nguyen L.H., Barsky D., Fernandes M., Wilson D.M. III;
RT "Molecular interactions of human Exo1 with DNA.";
RL Nucleic Acids Res. 30:942-949(2002).
RN [16]
RP INVOLVEMENT IN COLORECTAL CANCER.
RX MEDLINE=22984782; PubMed=14623461; DOI=10.1016/S0165-4608(03)00196-1;
RA Alam N.A., Gorman P., Jaeger E.E.M., Kelsell D., Leigh I.M.,
RA Ratnavel R., Murdoch M.E., Houlston R.S., Aaltonen L.A.,
RA Roylance R.R., Tomlinson I.P.M.;
RT "Germline deletions of EXO1 do not cause colorectal tumors and lesions
RT which are null for EXO1 do not have microsatellite instability.";
RL Cancer Genet. Cytogenet. 147:121-127(2003).
RN [17]
RP FUNCTION, AND INTERACTION WITH WRN.
RX PubMed=12704184; DOI=10.1074/jbc.M212798200;
RA Sharma S., Sommers J.A., Driscoll H.C., Uzdilla L.A., Wilson T.M.,
RA Brosh R.M. Jr.;
RT "The exonucleolytic and endonucleolytic cleavage activities of human
RT exonuclease 1 are stimulated by an interaction with the carboxyl-
RT terminal region of the Werner syndrome protein.";
RL J. Biol. Chem. 278:23487-23496(2003).
RN [18]
RP FUNCTION.
RX MEDLINE=23001081; PubMed=14636568; DOI=10.1016/S1097-2765(03)00428-3;
RA Genschel J., Modrich P.;
RT "Mechanism of 5'-directed excision in human mismatch repair.";
RL Mol. Cell 12:1077-1086(2003).
RN [19]
RP FUNCTION, INTERACTION WITH PCNA, AND MUTAGENESIS OF ASP-173.
RX PubMed=15225546; DOI=10.1016/j.molcel.2004.06.016;
RA Dzantiev L., Constantin N., Genschel J., Iyer R.R., Burgers P.M.,
RA Modrich P.;
RT "A defined human system that supports bidirectional mismatch-provoked
RT excision.";
RL Mol. Cell 15:31-41(2004).
RN [20]
RP FUNCTION, INTERACTIONS WITH MLH1 AND MSH2, AND SUBCELLULAR LOCATION.
RX PubMed=14676842; DOI=10.1038/sj.onc.1207265;
RA Nielsen F.C., Jaeger A.C., Luetzen A., Bundgaard J.R., Rasmussen L.J.;
RT "Characterization of human exonuclease 1 in complex with mismatch
RT repair proteins, subcellular localization and association with PCNA.";
RL Oncogene 23:1457-1468(2004).
RN [21]
RP PHOSPHORYLATION SITE SER-598.
RX PubMed=15302935; DOI=10.1073/pnas.0404720101;
RA Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J.,
RA Li J., Cohn M.A., Cantley L.C., Gygi S.P.;
RT "Large-scale characterization of HeLa cell nuclear phosphoproteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004).
RN [22]
RP FUNCTION.
RX PubMed=16143102; DOI=10.1016/j.cell.2005.06.027;
RA Zhang Y., Yuan F., Presnell S.R., Tian K., Gao Y., Tomkinson A.E.,
RA Gu L., Li G.-M.;
RT "Reconstitution of 5'-directed human mismatch repair in a purified
RT system.";
RL Cell 122:693-705(2005).
RN [23]
RP FUNCTION, AND INTERACTION WITH RECQL.
RX PubMed=15886194; DOI=10.1074/jbc.M500265200;
RA Doherty K.M., Sharma S., Uzdilla L.A., Wilson T.M., Cui S.,
RA Vindigni A., Brosh R.M. Jr.;
RT "RECQ1 helicase interacts with human mismatch repair factors that
RT regulate genetic recombination.";
RL J. Biol. Chem. 280:28085-28094(2005).
RN [24]
RP VARIANTS ALA-27; LYS-109; ARG-410; GLY-610; ALA-640; SER-640; GLU-759
RP AND LEU-770.
RA Wu Y., Berends M.J.W., Post J.G., Mensink R.G.J., Verlind E.,
RA Van Der Sluis T., Kempinga C., Sijmons R.H., van der Zee A.G.J.,
RA Hollema H., Kleibeuker J.H., Buys C.H.C.M., Hofstra R.M.W.;
RT "Germline mutations of EXO1 gene in patients with hereditary
RT nonpolyposis colorectal cancer (HNPCC) and atypical HNPCC forms.";
RL Gastroenterology 120:1580-1587(2001).
RN [25]
RP VARIANTS SER-137; ARG-410; CYS-438; GLY-610; ALA-640; SER-640; GLU-759
RP AND VAL-827.
RA Jagmohan-Changur S., Poikonen T., Vilkki S., Launonen V., Wikman F.,
RA Orntoft T.F., Moeller P., Vasen H., Tops C., Kolodner R.D.,
RA Mecklin J.-P., Jaervinen H., Bevan S., Houlston R.S., Aaltonen L.A.,
RA Fodde R., Wijnen J., Karhu A.;
RT "EXO1 variants occur commonly in normal population: evidence against a
RT role in hereditary nonpolyposis colorectal cancer.";
RL Cancer Res. 63:154-158(2003).
RN [26]
RP VARIANTS MET-439; GLY-670; PRO-726 AND LEU-757.
RX PubMed=14756672; DOI=10.1111/j.1399-0004.2004.00214.x;
RA Thompson E., Meldrum C.J., Crooks R., McPhillips M., Thomas L.,
RA Spigelman A.D., Scott R.J.;
RT "Hereditary non-polyposis colorectal cancer and the role of hPMS2 and
RT hEXO1 mutations.";
RL Clin. Genet. 65:215-225(2004).
RN [27]
RP VARIANTS MET-439 AND LEU-757.
RX PubMed=15550454; DOI=10.1093/carcin/bgh335;
RA Yamamoto H., Hanafusa H., Ouchida M., Yano M., Suzuki H., Murakami M.,
RA Aoe M., Shimizu N., Nakachi K., Shimizu K.;
RT "Single nucleotide polymorphisms in the EXO1 gene and risk of
RT colorectal cancer in a Japanese population.";
RL Carcinogenesis 26:411-416(2005).
Feature:
CHAIN 1 846 Exonuclease 1.
/FTId=PRO_0000154039.
REGION 1 99 N-domain.
REGION 129 387 Interaction with MSH3.
REGION 138 229 I-domain.
REGION 388 490 Interaction with MLH1.
REGION 600 846 Interaction with MSH2.
REGION 787 846 Interaction with MLH1.
MOD_RES 598 598 Phosphoserine.
VARSPLIC 803 803 D -> F (in isoform 2).
/FTId=VSP_017029.
VARSPLIC 804 846 Missing (in isoform 2).
/FTId=VSP_017030.
VARIANT 27 27 V -> A.
/FTId=VAR_024966.
VARIANT 76 76 V -> I (in dbSNP:4149864).
/FTId=VAR_024967.
VARIANT 93 93 R -> G (in dbSNP:4149865).
/FTId=VAR_024968.
VARIANT 109 109 E -> K (abrogates exonuclease activity).
/FTId=VAR_024969.
VARIANT 137 137 A -> S.
/FTId=VAR_024970.
VARIANT 279 279 N -> S (in dbSNP:4149909).
/FTId=VAR_024971.
VARIANT 299 299 N -> S (in dbSNP:4149910).
/FTId=VAR_024972.
VARIANT 354 354 H -> R (in dbSNP:735943).
/FTId=VAR_024973.
VARIANT 410 410 L -> R (abrogates exonuclease activity).
/FTId=VAR_024974.
VARIANT 428 428 D -> N (in dbSNP:4149962).
/FTId=VAR_024975.
VARIANT 438 438 F -> C.
/FTId=VAR_024976.
VARIANT 439 439 T -> M (may be associated with an
increased risk of colorectal cancer;
dbSNP:4149963).
/FTId=VAR_024977.
VARIANT 456 456 S -> Y (in dbSNP:4149964).
/FTId=VAR_024978.
VARIANT 458 458 V -> M (in dbSNP:4149965).
/FTId=VAR_024979.
VARIANT 460 460 V -> L (in dbSNP:4149966).
/FTId=VAR_024980.
VARIANT 503 503 R -> T (in dbSNP:4149967).
/FTId=VAR_024981.
VARIANT 589 589 E -> K (in dbSNP:1047840).
/FTId=VAR_024982.
VARIANT 610 610 S -> G (in dbSNP:12122770).
/FTId=VAR_024983.
VARIANT 634 634 R -> Q (in dbSNP:4149978).
/FTId=VAR_024984.
VARIANT 640 640 P -> A.
/FTId=VAR_024985.
VARIANT 640 640 P -> S (reduces interaction with MSH2).
/FTId=VAR_024986.
VARIANT 670 670 E -> G (in dbSNP:1776148 and
dbSNP:17856209).
/FTId=VAR_024987.
VARIANT 723 723 R -> C (in dbSNP:1635498 and
dbSNP:17850203).
/FTId=VAR_024988.
VARIANT 726 726 H -> P.
/FTId=VAR_024989.
VARIANT 757 757 P -> L (may be associated with a reduced
risk of colorectal cancer; dbSNP:9350).
/FTId=VAR_024990.
VARIANT 759 759 G -> E (reduces interaction with MSH2;
dbSNP:4150001).
/FTId=VAR_024991.
VARIANT 770 770 P -> L (reduces interaction with MSH2).
/FTId=VAR_024992.
VARIANT 827 827 A -> V.
/FTId=VAR_024993.
MUTAGEN 78 78 D->A: Abrogates double-stranded DNA
exonuclease activity and endonuclease
activity against 5' overhanging flap
structures. Also reduces DNA-binding to
5' overhanging flap structures.
MUTAGEN 173 173 D->A: Abrogates double-stranded DNA
exonuclease activity and endonuclease
activity against 5' overhanging flap
structures. No effect on DNA-binding to
5' overhanging flap structures.
MUTAGEN 225 225 D->A: Abrogates double-stranded DNA
exonuclease activity and endonuclease
activity against 5' overhanging flap
structures. Also enhances DNA-binding to
5' overhanging flap structures.
MUTAGEN 640 640 P->S: Abrogates interaction with MSH2;
when associated with P-770.
MUTAGEN 759 759 G->E: Abrogates interaction with MSH2;
when associated with P-770.
MUTAGEN 770 770 P->L: Abrogates interaction with MSH2;
when associated with S-640 or E-759.
Comments:
-!- FUNCTION: 5'->3' double-stranded DNA exonuclease which may also
possess a cryptic 3'->5' double-stranded DNA exonuclease activity.
Functions in DNA mismatch repair (MMR) to excise mismatch-
containing DNA tracts directed by strand breaks located either 5'
or 3' to the mismatch. Also exhibits endonuclease activity against
5' overhanging flap structures similar to those generated by
displacement synthesis when DNA polymerase encounters the 5' end
of a downstream Okazaki fragment. Required for somatic
hypermutation (SHM) and class switch recombination (CSR) of
immunoglobulin genes. Essential for male and female meiosis.
-!- SUBUNIT: Interacts with the MLH1-PMS2 heterodimer via MLH1.
Interacts with MSH3. Interacts with the MSH2-MSH6 heterodimer via
MSH2, and this interaction may increase the processivity of the
5'->3' exonuclease activity. Interacts with PCNA, and this
interaction may both stimulate the cryptic 3'->5' exonuclease
activity and suppress the 5'->3' exonuclease activity. Interacts
with WRN, and this interaction stimulates both the 5'->3'
exonuclease activity and cleavage of 5' overhanging flap
structures. Interacts with RECQL/RECQ1, and this interaction
stimulates cleavage of 5' overhanging flap structures.
-!- SUBCELLULAR LOCATION: Nuclear. Colocalizes with PCNA to discrete
nuclear foci in S-phase.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1; Synonyms=B;
IsoId=Q9UQ84-1; Sequence=Displayed;
Name=2; Synonyms=A;
IsoId=Q9UQ84-4; Sequence=VSP_017029, VSP_017030;
-!- TISSUE SPECIFICITY: Highly expressed in bone marrow, testis and
thymus. Expressed at lower levels in colon, lymph nodes, ovary,
placenta, prostate, small intestine, spleen and stomach.
-!- DEVELOPMENTAL STAGE: Highly expressed in fetal liver and at lower
levels in fetal brain, heart, kidney, spleen and thymus.
-!- POLYMORPHISM: Most naturally occurring variants in this protein
are not associated with familial disposition to hereditary non-
polyposis colorectal cancer (HNPCC). Furthermore, germline
deletions involving this locus are not associated with clinically
manifested colorectal tumors.
-!- SIMILARITY: Belongs to the XPG/RAD2 endonuclease family. EXO1
subfamily.
-!- CAUTION: Ref.4 sequence differs from that shown due to a
frameshift in position 793.
-----------------------------------------------------------------------
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
Distributed under the Creative Commons Attribution-NoDerivs License
-----------------------------------------------------------------------
Sequence length: 846
MGIQGLLQFI KEASEPIHVR KYKGQVVAVD TYCWLHKGAI ACAEKLAKGE PTDRYVGFCM
KFVNMLLSHG IKPILVFDGC TLPSKKEVER SRRERRQANL LKGKQLLREG KVSEARECFT
RSINITHAMA HKVIKAARSQ GVDCLVAPYE ADAQLAYLNK AGIVQAIITE DSDLLAFGCK
KVILKMDQFG NGLEIDQARL GMCRQLGDVF TEEKFRYMCI LSGCDYLSSL RGIGLAKACK
VLRLANNPDI VKVIKKIGHY LKMNITVPED YINGFIRANN TFLYQLVFDP IKRKLIPLNA
YEDDVDPETL SYAGQYVDDS IALQIALGNK DINTFEQIDD YNPDTAMPAH SRSHSWDDKT
CQKSANVSSI WHRNYSPRPE SGTVSDAPQL KENPSTVGVE RVISTKGLNL PRKSSIVKRP
RSAELSEDDL LSQYSLSFTK KTKKNSSEGN KSLSFSEVFV PDLVNGPTNK KSVSTPPRTR
NKFATFLQRK NEESGAVVVP GTRSRFFCSS DSTDCVSNKV SIQPLDETAV TDKENNLHES
EYGDQEGKRL VDTDVARNSS DDIPNNHIPG DHIPDKATVF TDEESYSFES SKFTRTISPP
TLGTLRSCFS WSGGLGDFSR TPSPSPSTAL QQFRRKSDSP TSLPENNMSD VSQLKSEESS
DDESHPLREE ACSSQSQESG EFSLQSSNAS KLSQCSSKDS DSEESDCNIK LLDSQSDQTS
KLRLSHFSKK DTPLRNKVPG LYKSSSADSL STTKIKPLGP ARASGLSKKP ASIQKRKHHN
AENKPGLQIK LNELWKNFGF KKDSEKLPPC KKPLSPVRDN IQLTPEAEED IFNKPECGRV
QRAIFQ