CDT1_MOUSE
ID CDT1_MOUSE Reviewed; 557 AA.
AC Q8R4E9; Q8BUQ1; Q8BX29; Q8R3V0; Q8R4E8;
DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=DNA replication factor Cdt1;
DE AltName: Full=Double parked homolog;
DE Short=DUP;
DE AltName: Full=Retroviral insertion site 2 protein;
GN Name=Cdt1 {ECO:0000303|PubMed:11850834};
GN Synonyms=Ris2 {ECO:0000312|MGI:MGI:1914427};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAL82630.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, AND DEVELOPMENTAL
RP STAGE.
RC STRAIN=129/Sv {ECO:0000312|EMBL:AAL82630.1};
RX PubMed=11850834; DOI=10.1038/sj.onc.1205175;
RA Arentson E., Faloon P., Seo J., Moon E., Studts J.M., Fremont D.H.,
RA Choi K.;
RT "Oncogenic potential of the DNA replication licensing protein CDT1.";
RL Oncogene 21:1150-1158(2002).
RN [2] {ECO:0000305, ECO:0000312|EMBL:BAC22085.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INTERACTION WITH GMNN; MCM6 AND
RP ORC2.
RX PubMed=12192004; DOI=10.1074/jbc.m206202200;
RA Yanagi K., Mizuno T., You Z., Hanaoka F.;
RT "Mouse geminin inhibits not only Cdt1-MCM6 interactions but also a novel
RT intrinsic Cdt1 DNA binding activity.";
RL J. Biol. Chem. 277:40871-40880(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryonic stem cell, and Fetal head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4] {ECO:0000312|EMBL:AAH48076.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland {ECO:0000312|EMBL:AAH24485.1}, and
RC Olfactory epithelium {ECO:0000312|EMBL:AAH48076.1};
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 [5] {ECO:0000305}
RP FUNCTION, PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=14993212; DOI=10.1074/jbc.m313175200;
RA Sugimoto N., Tatsumi Y., Tsurumi T., Matsukage A., Kiyono T., Nishitani H.,
RA Fujita M.;
RT "Cdt1 phosphorylation by cyclin A-dependent kinases negatively regulates
RT its function without affecting geminin binding.";
RL J. Biol. Chem. 279:19691-19697(2004).
RN [6]
RP INTERACTION WITH GMNN AND MCM6.
RX PubMed=15811859; DOI=10.1074/jbc.C500070200;
RA Yanagi K., Mizuno T., Tsuyama T., Tada S., Iida Y., Sugimoto A., Eki T.,
RA Enomoto T., Hanaoka F.;
RT "Caenorhabditis elegans geminin homologue participates in cell cycle
RT regulation and germ line development.";
RL J. Biol. Chem. 280:19689-19694(2005).
RN [7] {ECO:0000305}
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 172-368, AND INTERACTION WITH
RP GMNN.
RX PubMed=15286659; DOI=10.1038/nature02813;
RA Lee C., Hong B., Choi J.M., Kim Y., Watanabe S., Ishimi Y., Enomoto T.,
RA Tada S., Kim Y., Cho Y.;
RT "Structural basis for inhibition of the replication licensing factor Cdt1
RT by geminin.";
RL Nature 430:913-917(2004).
CC -!- FUNCTION: Required for both DNA replication and mitosis. DNA
CC replication licensing factor, required for pre-replication complex
CC assembly. Cooperates with CDC6 and the origin recognition complex (ORC)
CC during G1 phase of the cell cycle to promote the loading of the mini-
CC chromosome maintenance (MCM) complex onto DNA to generate pre-
CC replication complexes (pre-RC). Required also for mitosis by promoting
CC stable kinetochore-microtubule attachments (By similarity). Potential
CC oncogene (PubMed:11850834). {ECO:0000250|UniProtKB:Q9H211,
CC ECO:0000269|PubMed:11850834, ECO:0000269|PubMed:12192004,
CC ECO:0000269|PubMed:14993212}.
CC -!- SUBUNIT: Interacts with GMNN; the interaction inhibits the binding of
CC the MCM complex to origins of replication (PubMed:12192004,
CC PubMed:15811859). Interacts with MCM6 (PubMed:15811859). Interacts with
CC CDC6; are mutually dependent on one another for loading MCM complexes
CC onto chromatin (By similarity). Interacts with PCNA (By similarity).
CC Interacts with LRWD1 during G1 phase and during mitosis (By
CC similarity). Interacts with NDC80 subunit of the NDC80 complex; leading
CC to kinetochore localization (By similarity). Interacts with KAT7 (By
CC similarity). Interacts with ubiquitin-binding protein FAF1; the
CC interaction is likely to promote CDT1 degradation (By similarity).
CC {ECO:0000250|UniProtKB:Q9H211, ECO:0000269|PubMed:12192004,
CC ECO:0000269|PubMed:15811859}.
CC -!- INTERACTION:
CC Q8R4E9; O88513: Gmnn; NbExp=3; IntAct=EBI-457043, EBI-445922;
CC Q8R4E9; P97311: Mcm6; NbExp=2; IntAct=EBI-457043, EBI-457132;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14993212}.
CC Chromosome, centromere, kinetochore {ECO:0000250|UniProtKB:Q9H211}.
CC Note=Transiently localizes to kinetochores during prometaphase and
CC metaphase. {ECO:0000250|UniProtKB:Q9H211}.
CC -!- DEVELOPMENTAL STAGE: Present during G1 and early S phase of the cell
CC cycle. Degraded during the late S, G2, and M phases.
CC {ECO:0000269|PubMed:11850834}.
CC -!- DOMAIN: The PIP-box K+4 motif mediates both the interaction with PCNA
CC and the recruitment of the DCX(DTL) complex: while the PIP-box
CC interacts with PCNA, the presence of the K+4 submotif, recruits the
CC DCX(DTL) complex, leading to its ubiquitination.
CC {ECO:0000250|UniProtKB:Q9I9A7}.
CC -!- PTM: Two independent E3 ubiquitin ligase complexes, SCF(SKP2) and the
CC DCX(DTL) complex, mediated CDT1 degradation in S phase. Ubiquitinated
CC by the DCX(DTL) complex, in response to DNA damage, leading to its
CC degradation. Ubiquitination by the DCX(DTL) complex is necessary to
CC ensure proper cell cycle regulation and is PCNA-dependent: interacts
CC with PCNA via its PIP-box, while the presence of the containing the
CC 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to
CC its degradation. Phosphorylation at Thr-28 by CDK2 targets CDT1 for
CC ubiquitynation by SCF(SKP2) E3 ubiquitin ligase and subsequent
CC degradation. The interaction with GMNN protects it against
CC ubiquitination. Deubiquitinated by USP37.
CC {ECO:0000250|UniProtKB:Q9H211}.
CC -!- PTM: Phosphorylation by cyclin A-dependent kinases at Thr-28 targets
CC CDT1 for ubiquitynation by SCF(SKP2) E3 ubiquitin ligase and subsequent
CC degradation. Phosphorylated at Thr-28 by MAPK8/JNK1, which blocks
CC replication licensing in response to stress. Binding to GMNN is not
CC affected by phosphorylation (PubMed:14993212).
CC {ECO:0000250|UniProtKB:Q9H211, ECO:0000269|PubMed:14993212}.
CC -!- SIMILARITY: Belongs to the Cdt1 family. {ECO:0000305}.
CC -!- CAUTION: Was originally thought to have DNA binding activity
CC (PubMed:12192004). However, more recent studies show that CDT1 binds
CC DNA indirectly via ORC. {ECO:0000269|PubMed:12192004, ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC38731.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF477481; AAL82630.1; -; mRNA.
DR EMBL; AF477990; AAL88446.1; -; Genomic_DNA.
DR EMBL; AB086655; BAC22085.1; -; mRNA.
DR EMBL; AK028287; BAC25859.1; -; mRNA.
DR EMBL; AK049163; BAC33579.1; -; mRNA.
DR EMBL; AK083015; BAC38731.1; ALT_FRAME; mRNA.
DR EMBL; BC024485; AAH24485.1; -; mRNA.
DR EMBL; BC048076; AAH48076.1; -; mRNA.
DR CCDS; CCDS22741.1; -.
DR RefSeq; NP_080290.3; NM_026014.3.
DR PDB; 2KLO; NMR; -; A=420-557.
DR PDB; 2RQQ; NMR; -; A=450-557.
DR PDB; 2ZXX; X-ray; 2.80 A; C/F=172-368.
DR PDB; 3A4C; X-ray; 1.89 A; A=452-557.
DR PDBsum; 2KLO; -.
DR PDBsum; 2RQQ; -.
DR PDBsum; 2ZXX; -.
DR PDBsum; 3A4C; -.
DR AlphaFoldDB; Q8R4E9; -.
DR SMR; Q8R4E9; -.
DR BioGRID; 211995; 5.
DR IntAct; Q8R4E9; 5.
DR STRING; 10090.ENSMUSP00000006760; -.
DR iPTMnet; Q8R4E9; -.
DR PhosphoSitePlus; Q8R4E9; -.
DR EPD; Q8R4E9; -.
DR MaxQB; Q8R4E9; -.
DR PaxDb; Q8R4E9; -.
DR PeptideAtlas; Q8R4E9; -.
DR PRIDE; Q8R4E9; -.
DR ProteomicsDB; 281303; -.
DR Antibodypedia; 1905; 220 antibodies from 36 providers.
DR DNASU; 67177; -.
DR Ensembl; ENSMUST00000006760; ENSMUSP00000006760; ENSMUSG00000006585.
DR GeneID; 67177; -.
DR KEGG; mmu:67177; -.
DR UCSC; uc009ntd.1; mouse.
DR CTD; 81620; -.
DR MGI; MGI:1914427; Cdt1.
DR VEuPathDB; HostDB:ENSMUSG00000006585; -.
DR eggNOG; KOG4762; Eukaryota.
DR GeneTree; ENSGT00390000012337; -.
DR HOGENOM; CLU_023373_1_0_1; -.
DR InParanoid; Q8R4E9; -.
DR OMA; DRVKEHH; -.
DR OrthoDB; 648388at2759; -.
DR PhylomeDB; Q8R4E9; -.
DR TreeFam; TF101159; -.
DR Reactome; R-MMU-68867; Assembly of the pre-replicative complex.
DR Reactome; R-MMU-68949; Orc1 removal from chromatin.
DR Reactome; R-MMU-68962; Activation of the pre-replicative complex.
DR Reactome; R-MMU-69052; Switching of origins to a post-replicative state.
DR BioGRID-ORCS; 67177; 19 hits in 78 CRISPR screens.
DR ChiTaRS; Cdt1; mouse.
DR EvolutionaryTrace; Q8R4E9; -.
DR PRO; PR:Q8R4E9; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q8R4E9; protein.
DR Bgee; ENSMUSG00000006585; Expressed in fetal liver hematopoietic progenitor cell and 221 other tissues.
DR Genevisible; Q8R4E9; MM.
DR GO; GO:0000776; C:kinetochore; ISO:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0070182; F:DNA polymerase binding; IBA:GO_Central.
DR GO; GO:0051315; P:attachment of mitotic spindle microtubules to kinetochore; ISS:UniProtKB.
DR GO; GO:0051301; P:cell division; ISO:MGI.
DR GO; GO:0007059; P:chromosome segregation; ISS:UniProtKB.
DR GO; GO:1902426; P:deactivation of mitotic spindle assembly checkpoint; ISO:MGI.
DR GO; GO:0000076; P:DNA replication checkpoint signaling; IDA:UniProtKB.
DR GO; GO:0071163; P:DNA replication preinitiation complex assembly; ISO:MGI.
DR GO; GO:0051383; P:kinetochore organization; ISO:MGI.
DR GO; GO:0000278; P:mitotic cell cycle; ISO:MGI.
DR GO; GO:0045786; P:negative regulation of cell cycle; ISO:MGI.
DR GO; GO:2000104; P:negative regulation of DNA-templated DNA replication; ISO:MGI.
DR GO; GO:1905341; P:negative regulation of protein localization to kinetochore; ISO:MGI.
DR GO; GO:0035563; P:positive regulation of chromatin binding; ISO:MGI.
DR GO; GO:0045740; P:positive regulation of DNA replication; ISO:MGI.
DR GO; GO:2000105; P:positive regulation of DNA-templated DNA replication; ISO:MGI.
DR GO; GO:1905342; P:positive regulation of protein localization to kinetochore; ISO:MGI.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISO:MGI.
DR GO; GO:0033044; P:regulation of chromosome organization; ISO:MGI.
DR GO; GO:1902595; P:regulation of DNA replication origin binding; ISO:MGI.
DR GO; GO:0030174; P:regulation of DNA-templated DNA replication initiation; IDA:UniProtKB.
DR GO; GO:0033262; P:regulation of nuclear cell cycle DNA replication; IDA:MGI.
DR GO; GO:0072708; P:response to sorbitol; ISO:MGI.
DR CDD; cd08767; Cdt1_c; 1.
DR CDD; cd08674; Cdt1_m; 1.
DR Gene3D; 1.10.10.1420; -; 1.
DR InterPro; IPR045173; Cdt1.
DR InterPro; IPR032054; Cdt1_C.
DR InterPro; IPR038090; Cdt1_C_WH_dom_sf.
DR InterPro; IPR014939; CDT1_Gemini-bd-like.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR28637; PTHR28637; 1.
DR Pfam; PF08839; CDT1; 1.
DR Pfam; PF16679; CDT1_C; 1.
DR SMART; SM01075; CDT1; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell cycle; Centromere; Chromosome; DNA replication;
KW DNA-binding; Kinetochore; Nucleus; Phosphoprotein; Proto-oncogene;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..557
FT /note="DNA replication factor Cdt1"
FT /id="PRO_0000191620"
FT REGION 20..113
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 163..203
FT /note="Interaction with GMNN"
FT /evidence="ECO:0000250|UniProtKB:Q9H211"
FT REGION 397..427
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 463..557
FT /note="Interaction with LRWD1"
FT /evidence="ECO:0000250|UniProtKB:Q9H211"
FT MOTIF 1..25
FT /note="PIP-box K+4 motif"
FT /evidence="ECO:0000250|UniProtKB:Q9H211"
FT MOTIF 65..67
FT /note="Cyclin-binding motif"
FT /evidence="ECO:0000250|UniProtKB:Q9H211"
FT COMPBIAS 81..104
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 405..422
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 28
FT /note="Phosphothreonine; by MAPK8"
FT /evidence="ECO:0000250|UniProtKB:Q9H211"
FT MOD_RES 30
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H211"
FT MOD_RES 107
FT /note="Phosphoserine; by MAPK8"
FT /evidence="ECO:0000250|UniProtKB:Q9H211"
FT MOD_RES 392
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H211"
FT CONFLICT 4
FT /note="S -> G (in Ref. 3; BAC33579)"
FT /evidence="ECO:0000305"
FT CONFLICT 211
FT /note="R -> H (in Ref. 1; AAL88446)"
FT /evidence="ECO:0000305"
FT CONFLICT 258
FT /note="T -> M (in Ref. 1; AAL88446)"
FT /evidence="ECO:0000305"
FT HELIX 182..185
FT /evidence="ECO:0007829|PDB:2ZXX"
FT HELIX 188..190
FT /evidence="ECO:0007829|PDB:2ZXX"
FT HELIX 201..222
FT /evidence="ECO:0007829|PDB:2ZXX"
FT HELIX 229..240
FT /evidence="ECO:0007829|PDB:2ZXX"
FT HELIX 246..255
FT /evidence="ECO:0007829|PDB:2ZXX"
FT HELIX 257..259
FT /evidence="ECO:0007829|PDB:2ZXX"
FT STRAND 260..266
FT /evidence="ECO:0007829|PDB:2ZXX"
FT HELIX 277..279
FT /evidence="ECO:0007829|PDB:2ZXX"
FT STRAND 280..286
FT /evidence="ECO:0007829|PDB:2ZXX"
FT HELIX 300..326
FT /evidence="ECO:0007829|PDB:2ZXX"
FT STRAND 329..331
FT /evidence="ECO:0007829|PDB:2ZXX"
FT HELIX 337..339
FT /evidence="ECO:0007829|PDB:2ZXX"
FT HELIX 349..351
FT /evidence="ECO:0007829|PDB:2ZXX"
FT HELIX 432..446
FT /evidence="ECO:0007829|PDB:2KLO"
FT HELIX 454..478
FT /evidence="ECO:0007829|PDB:3A4C"
FT STRAND 481..486
FT /evidence="ECO:0007829|PDB:3A4C"
FT HELIX 487..496
FT /evidence="ECO:0007829|PDB:3A4C"
FT TURN 499..501
FT /evidence="ECO:0007829|PDB:2KLO"
FT HELIX 504..517
FT /evidence="ECO:0007829|PDB:3A4C"
FT TURN 519..521
FT /evidence="ECO:0007829|PDB:3A4C"
FT STRAND 522..527
FT /evidence="ECO:0007829|PDB:3A4C"
FT STRAND 530..535
FT /evidence="ECO:0007829|PDB:3A4C"
FT HELIX 541..554
FT /evidence="ECO:0007829|PDB:3A4C"
SQ SEQUENCE 557 AA; 61510 MW; BFBA4E6DB5ABC1E6 CRC64;
MAQSRVTDFY ACRRPGLTTP RAKSICLTPS PGGLVAPAFT RSSSRKRARP PAEPGSDQPA
PLARRRLRLP GLDSCPSSLP EPSSPAEPSP PADPSPPADP GSPVCPSPVK RTKSTTVYVG
QQPGKIPSED SVSELQSCLR RARKLGAQAR ALRARVQENA VEPSTPDAKV PTEQPCVEKA
PAYQRFHALA QPGLPGLVLP YKYQVLVEMF RSMDTIVSML HNRSETVTFA KVKQGVQEMM
RKRFEERNVG QIKTVYPTSY RFRQECNVPT FKDSIKRSDY QLTIEPLLGQ EAGGATQLTA
TCLLQRRQVF RQNLVERVKE QHKVFLASLN PPMAVPDDQL TRWHPRFNVD EVPDIEPAEL
PQPPVTEKLT TAQEVLARAR SLMTPKMEKA LSNLALRSAE PGSPGTSTPP LPATPPATPP
AASPSALKGV SQALLERIRA KEVQKQLARM TRCPEQELRL QRLERLPELA RVLRNVFVSE
RKPALTMEVV CARMVDSCQT ALSPGEMEKH LVLLAELLPD WLSLHRIRTD TYVKLDKAVD
LAGLTARLAH HVHAEGL
