MF2L2_HUMAN
ID MF2L2_HUMAN Reviewed; 1114 AA.
AC Q86YR7; O94942; Q6P2B8; Q6ZVJ5; Q8N318;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 3.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Probable guanine nucleotide exchange factor MCF2L2;
DE AltName: Full=Dbs-related Rho family guanine nucleotide exchange factor;
DE AltName: Full=MCF2-transforming sequence-like protein 2;
GN Name=MCF2L2; Synonyms=DRG, KIAA0861;
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] (ISOFORM 3), AND VARIANT LEU-359.
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 804-1114 (ISOFORM 4), AND VARIANTS LEU-378; SER-589
RP AND ALA-902.
RC TISSUE=Brain, and Pancreas;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 57-1114 (ISOFORM 1), AND VARIANT ALA-902.
RA Yamauchi J., Miyamoto Y., Itoh H.;
RT "DRG, a novel guanine-nucleotide exchange factor for Rho family.";
RL Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 133-1114 (ISOFORM 1), AND
RP VARIANTS MET-159 AND ALA-902.
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [6]
RP INVOLVEMENT IN NIDDM, AND TISSUE SPECIFICITY.
RX PubMed=18259684; DOI=10.1007/s10038-008-0254-6;
RA Takeuchi F., Ochiai Y., Serizawa M., Yanai K., Kuzuya N., Kajio H.,
RA Honjo S., Takeda N., Kaburagi Y., Yasuda K., Shirasawa S., Sasazuki T.,
RA Kato N.;
RT "Search for type 2 diabetes susceptibility genes on chromosomes 1q, 3q and
RT 12q.";
RL J. Hum. Genet. 53:314-324(2008).
RN [7]
RP VARIANTS [LARGE SCALE ANALYSIS] PRO-254; HIS-622 AND PHE-1039.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Probably functions as a guanine nucleotide exchange factor.
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q86YR7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86YR7-2; Sequence=VSP_033874, VSP_033875;
CC Name=3;
CC IsoId=Q86YR7-3; Sequence=VSP_033872, VSP_033873;
CC Name=4;
CC IsoId=Q86YR7-4; Sequence=VSP_033876;
CC -!- TISSUE SPECIFICITY: Significantly expressed in brain and modestly in
CC pancreas, brain and testis. {ECO:0000269|PubMed:18259684}.
CC -!- DISEASE: Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]:
CC A multifactorial disorder of glucose homeostasis caused by a lack of
CC sensitivity to the body's own insulin. Affected individuals usually
CC have an obese body habitus and manifestations of a metabolic syndrome
CC characterized by diabetes, insulin resistance, hypertension and
CC hypertriglyceridemia. The disease results in long-term complications
CC that affect the eyes, kidneys, nerves, and blood vessels.
CC {ECO:0000269|PubMed:18259684}. Note=Disease susceptibility may be
CC associated with variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the MCF2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAO19651.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK124500; BAC85866.1; -; mRNA.
DR EMBL; AC069417; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC092960; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC104641; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC112647; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC029074; AAH29074.2; -; mRNA.
DR EMBL; BC064632; AAH64632.1; -; mRNA.
DR EMBL; AY172737; AAO19651.1; ALT_INIT; mRNA.
DR EMBL; AB020668; BAA74884.1; -; mRNA.
DR CCDS; CCDS3243.1; -. [Q86YR7-1]
DR RefSeq; NP_055893.3; NM_015078.3. [Q86YR7-1]
DR AlphaFoldDB; Q86YR7; -.
DR SMR; Q86YR7; -.
DR BioGRID; 116728; 35.
DR IntAct; Q86YR7; 22.
DR STRING; 9606.ENSP00000328118; -.
DR iPTMnet; Q86YR7; -.
DR PhosphoSitePlus; Q86YR7; -.
DR BioMuta; MCF2L2; -.
DR DMDM; 317373423; -.
DR MassIVE; Q86YR7; -.
DR PaxDb; Q86YR7; -.
DR PeptideAtlas; Q86YR7; -.
DR PRIDE; Q86YR7; -.
DR ProteomicsDB; 70457; -. [Q86YR7-1]
DR ProteomicsDB; 70458; -. [Q86YR7-2]
DR ProteomicsDB; 70459; -. [Q86YR7-3]
DR ProteomicsDB; 70460; -. [Q86YR7-4]
DR Antibodypedia; 50764; 20 antibodies from 7 providers.
DR DNASU; 23101; -.
DR Ensembl; ENST00000328913.8; ENSP00000328118.3; ENSG00000053524.13. [Q86YR7-1]
DR Ensembl; ENST00000414362.6; ENSP00000414131.2; ENSG00000053524.13. [Q86YR7-3]
DR Ensembl; ENST00000447025.6; ENSP00000388190.2; ENSG00000053524.13. [Q86YR7-2]
DR Ensembl; ENST00000473233.5; ENSP00000420070.1; ENSG00000053524.13. [Q86YR7-4]
DR GeneID; 23101; -.
DR KEGG; hsa:23101; -.
DR MANE-Select; ENST00000328913.8; ENSP00000328118.3; NM_015078.4; NP_055893.4.
DR UCSC; uc003fli.3; human. [Q86YR7-1]
DR CTD; 23101; -.
DR DisGeNET; 23101; -.
DR GeneCards; MCF2L2; -.
DR HGNC; HGNC:30319; MCF2L2.
DR HPA; ENSG00000053524; Tissue enhanced (brain, retina).
DR MalaCards; MCF2L2; -.
DR MIM; 125853; phenotype.
DR neXtProt; NX_Q86YR7; -.
DR OpenTargets; ENSG00000053524; -.
DR PharmGKB; PA134863801; -.
DR VEuPathDB; HostDB:ENSG00000053524; -.
DR eggNOG; KOG4240; Eukaryota.
DR GeneTree; ENSGT00940000161734; -.
DR HOGENOM; CLU_007130_0_0_1; -.
DR InParanoid; Q86YR7; -.
DR OMA; PSHMEFY; -.
DR OrthoDB; 118479at2759; -.
DR PhylomeDB; Q86YR7; -.
DR TreeFam; TF318080; -.
DR PathwayCommons; Q86YR7; -.
DR SignaLink; Q86YR7; -.
DR BioGRID-ORCS; 23101; 5 hits in 1063 CRISPR screens.
DR ChiTaRS; MCF2L2; human.
DR GenomeRNAi; 23101; -.
DR Pharos; Q86YR7; Tbio.
DR PRO; PR:Q86YR7; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q86YR7; protein.
DR Bgee; ENSG00000053524; Expressed in right frontal lobe and 96 other tissues.
DR ExpressionAtlas; Q86YR7; baseline and differential.
DR Genevisible; Q86YR7; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IBA:GO_Central.
DR CDD; cd00160; RhoGEF; 1.
DR CDD; cd00170; SEC14; 1.
DR CDD; cd00176; SPEC; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR001251; CRAL-TRIO_dom.
DR InterPro; IPR036865; CRAL-TRIO_dom_sf.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR018159; Spectrin/alpha-actinin.
DR Pfam; PF13716; CRAL_TRIO_2; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00325; RhoGEF; 1.
DR SMART; SM00516; SEC14; 1.
DR SMART; SM00150; SPEC; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR SUPFAM; SSF52087; SSF52087; 1.
DR PROSITE; PS50191; CRAL_TRIO; 1.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Diabetes mellitus;
KW Guanine-nucleotide releasing factor; Reference proteome.
FT CHAIN 1..1114
FT /note="Probable guanine nucleotide exchange factor MCF2L2"
FT /id="PRO_0000337087"
FT DOMAIN 11..193
FT /note="CRAL-TRIO"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00056"
FT REPEAT 323..428
FT /note="Spectrin"
FT DOMAIN 619..822
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 834..954
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 530..614
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 962..1114
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 545..563
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 569..614
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 962..979
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 993..1014
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1035..1058
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1059..1084
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 622..628
FT /note="RIIRDLL -> YSSQYFK (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_033872"
FT VAR_SEQ 629..1114
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_033873"
FT VAR_SEQ 706..711
FT /note="KEDLQI -> VSLYSQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033874"
FT VAR_SEQ 712..1114
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033875"
FT VAR_SEQ 1075..1114
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033876"
FT VARIANT 159
FT /note="T -> M (in dbSNP:rs12632177)"
FT /evidence="ECO:0000269|PubMed:10048485"
FT /id="VAR_043587"
FT VARIANT 254
FT /note="L -> P (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_043588"
FT VARIANT 277
FT /note="N -> S (in dbSNP:rs13082605)"
FT /id="VAR_043589"
FT VARIANT 359
FT /note="I -> L (in dbSNP:rs7639705)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_043590"
FT VARIANT 378
FT /note="Q -> L (in dbSNP:rs2293203)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_043591"
FT VARIANT 589
FT /note="F -> S (in dbSNP:rs3732602)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_043592"
FT VARIANT 622
FT /note="R -> H (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs767614039)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_043593"
FT VARIANT 772
FT /note="F -> L (in dbSNP:rs9826325)"
FT /id="VAR_043594"
FT VARIANT 902
FT /note="T -> A (in dbSNP:rs6804951)"
FT /evidence="ECO:0000269|PubMed:10048485,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.4"
FT /id="VAR_043595"
FT VARIANT 1015
FT /note="M -> T (in dbSNP:rs35070271)"
FT /id="VAR_043596"
FT VARIANT 1039
FT /note="L -> F (in a breast cancer sample; somatic mutation;
FT dbSNP:rs1560327395)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_043597"
FT CONFLICT 373
FT /note="P -> S (in Ref. 4; AAO19651 and 5; BAA74884)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1114 AA; 126993 MW; CB1F04EC485C746D CRC64;
MLSCLKEEMP PQELTRRLAT VITHVDEIMQ QEVRPLMAVE IIEQLHRQFA ILSGGRGEDG
APIITFPEFS GFKHIPDEDF LNVMTYLTSI PSVEAASIGF IVVIDRRRDK WSSVKASLTR
IAVAFPGNLQ LIFILRPSRF IQRTFTDIGI KYYRNEFKTK VPIIMVNSVS DLHGYIDKSQ
LTRELGGTLE YRHGQWVNHR TAIENFALTL KTTAQMLQTF GSCLATAELP RSMLSTEDLL
MSHTRQRDKL QDELKLLGKQ GTTLLSCIQE PATKCPNSKL NLNQLENVTT MERLLVQLDE
TEKAFSHFWS EHHLKLNQCL QLQHFEHDFC KAKLALDNLL EEQAEFTGIG DSVMHVEQIL
KEHKKLEEKS QEPLEKAQLL ALVGDQLIQS HHYAADAIRP RCVELRHLCD DFINGNKKKW
DILGKSLEFH RQLDKVSQWC EAGIYLLASQ AVDKCQSREG VDIALNDIAT FLGTVKEYPL
LSPKEFYNEF ELLLTLDAKA KAQKVLQRLD DVQEIFHKRQ VSLMKLAAKQ TRPVQPVAPH
PESSPKWVSS KTSQPSTSVP LARPLRTSEE PYTETELNSR GKEDDETKFE VKSEEIFESH
HERGNPELEQ QARLGDLSPR RRIIRDLLET EEIYIKEIKS IIDGYITPMD FIWLKHLIPD
VLQNNKDFLF GNIRELYEFH NRTFLKELEK CAENPELLAH CFLKRKEDLQ IYFKYHKNLP
RARAIWQECQ DCAYFGVCQR QLDHNLPLFK YLKGPSQRLI KYQMLLKGLL DFESPEDMEI
DPGELGGSAK DGPKRTKDSA FSTELQQALA VIEDLIKSCE LAVDLAAVTE CPDDIGKLGK
LLLHGPFSVW TIHKDRYKMK DLIRFKPSQR QIYLFERGIV FCKIRMEPGD QGLSPHYSFK
KTMKLMTLSI RQLGRGSHRK FEIASRNGLE KYILQAASKE IRDCWFSEIS KLLMEQQNNI
KDQGNPQFEM STSKGSGAGS GPWIKNMERA TTSKEDPASS TGGIKGCSSR EFSSMDTFED
CEGAEDMEKE SSALSLAGLF QSDDSHETCS SKSAFLERGE SSQGEKEERD EEETATRSTE
EERAGASTGR LAPAGATAGF QARALRPRTS AQES
