ID   PDX1_MOUSE              Reviewed;         284 AA.
AC   P52946; Q3ZB03;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   27-MAR-2024, entry version 195.
DE   RecName: Full=Pancreas/duodenum homeobox protein 1;
DE   AltName: Full=Insulin promoter factor 1;
DE            Short=IPF-1;
DE   AltName: Full=Islet/duodenum homeobox 1;
DE            Short=IDX-1;
DE   AltName: Full=Somatostatin-transactivating factor 1;
DE            Short=STF-1;
GN   Name=Pdx1; Synonyms=Ipf1;
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]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=7901001; DOI=10.1002/j.1460-2075.1993.tb06109.x;
RA   Ohlsson H., Karlsson K., Edlund T.;
RT   "IPF1, a homeodomain-containing transactivator of the insulin gene.";
RL   EMBO J. 12:4251-4259(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Cecum;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH MEIS2 AND PBX1.
RX   PubMed=9710595; DOI=10.1128/mcb.18.9.5109;
RA   Swift G.H., Liu Y., Rose S.D., Bischof L.J., Steelman S., Buchberg A.M.,
RA   Wright C.V., MacDonald R.J.;
RT   "An endocrine-exocrine switch in the activity of the pancreatic homeodomain
RT   protein PDX1 through formation of a trimeric complex with PBX1b and MRG1
RT   (MEIS2).";
RL   Mol. Cell. Biol. 18:5109-5120(1998).
RN   [5]
RP   FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH MEIS2 AND PBX1.
RX   PubMed=11279116; DOI=10.1074/jbc.m100678200;
RA   Liu Y., MacDonald R.J., Swift G.H.;
RT   "DNA binding and transcriptional activation by a PDX1.PBX1b.MEIS2b trimer
RT   and cooperation with a pancreas-specific basic helix-loop-helix complex.";
RL   J. Biol. Chem. 276:17985-17993(2001).
RN   [6]
RP   INTERACTION WITH SPOP.
RC   STRAIN=BALB/cJ; TISSUE=Pancreas;
RX   PubMed=15121856; DOI=10.1128/mcb.24.10.4372-4383.2004;
RA   Liu A., Desai B.M., Stoffers D.A.;
RT   "Identification of PCIF1, a POZ domain protein that inhibits PDX-1 (MODY4)
RT   transcriptional activity.";
RL   Mol. Cell. Biol. 24:4372-4383(2004).
RN   [7]
RP   FUNCTION, AND INDUCTION.
RX   PubMed=12219087; DOI=10.1038/ng890;
RA   Nakae J., Biggs W.H. III, Kitamura T., Cavenee W.K., Wright C.V.,
RA   Arden K.C., Accili D.;
RT   "Regulation of insulin action and pancreatic beta-cell function by mutated
RT   alleles of the gene encoding forkhead transcription factor Foxo1.";
RL   Nat. Genet. 32:245-253(2002).
RN   [8]
RP   SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-152, AND MUTAGENESIS OF
RP   THR-152.
RX   PubMed=17052199; DOI=10.1042/bst0340791;
RA   An R., da Silva Xavier G., Hao H.X., Semplici F., Rutter J., Rutter G.A.;
RT   "Regulation by Per-Arnt-Sim (PAS) kinase of pancreatic duodenal homeobox-1
RT   nuclear import in pancreatic beta-cells.";
RL   Biochem. Soc. Trans. 34:791-793(2006).
RN   [9]
RP   PHOSPHORYLATION AT SER-269 BY HIPK2, AND MUTAGENESIS OF SER-269.
RX   PubMed=20637728; DOI=10.1016/j.bbrc.2010.07.035;
RA   An R., da Silva Xavier G., Semplici F., Vakhshouri S., Hao H.X., Rutter J.,
RA   Pagano M.A., Meggio F., Pinna L.A., Rutter G.A.;
RT   "Pancreatic and duodenal homeobox 1 (PDX1) phosphorylation at serine-269 is
RT   HIPK2-dependent and affects PDX1 subnuclear localization.";
RL   Biochem. Biophys. Res. Commun. 399:155-161(2010).
CC   -!- FUNCTION: Activates insulin and somatostatin gene transcription. Key
CC       regulator of islet peptide hormone expression but also responsible for
CC       the development of the pancreas, most probably by determining
CC       maturation and differentiation of common pancreatic precursor cells in
CC       the developing gut. As part of a PDX1:PBX1b:MEIS2b complex in
CC       pancreatic acinar cells is involved in the transcriptional activation
CC       of the ELA1 enhancer; the complex binds to the enhancer B element and
CC       cooperates with the transcription factor 1 complex (PTF1) bound to the
CC       enhancer A element. Binds the DNA sequence 5'-CC[CT]TAATGGG-3'.
CC       {ECO:0000269|PubMed:11279116, ECO:0000269|PubMed:12219087,
CC       ECO:0000269|PubMed:9710595}.
CC   -!- SUBUNIT: Interacts with the basic helix-loop-helix domains of TCF3(E47)
CC       and NEUROD1 and with HMG-I(Y). Interacts with the methyltransferase
CC       SETD7 (By similarity). Interacts with SPOP. Part of a PDX1:PBX1b:MEIS2b
CC       complex. {ECO:0000250, ECO:0000269|PubMed:11279116,
CC       ECO:0000269|PubMed:15121856, ECO:0000269|PubMed:9710595}.
CC   -!- INTERACTION:
CC       P52946; P13405: Rb1; NbExp=2; IntAct=EBI-7128945, EBI-971782;
CC       P52946; Q6ZWS8: Spop; NbExp=5; IntAct=EBI-7128945, EBI-7128920;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108,
CC       ECO:0000269|PubMed:17052199}. Cytoplasm, cytosol
CC       {ECO:0000269|PubMed:17052199}.
CC   -!- TISSUE SPECIFICITY: Duodenum and pancreas (Langerhans islet beta cells
CC       and small subsets of endocrine non-beta-cells, at low levels in acinar
CC       cells).
CC   -!- DEVELOPMENTAL STAGE: At 8.5 dpc, detected in the gut epithelium from
CC       which the pancreatic buds are formed. Transient expression in
CC       pancreatic ducts, endocrine and acinar cells. Down-regulated around
CC       10.5 dpc when expression becomes restricted to differentiated beta-
CC       cells.
CC   -!- INDUCTION: Expression is repressed by FOXO1 in pancreatic beta-cells.
CC       {ECO:0000269|PubMed:12219087}.
CC   -!- DOMAIN: The Antp-type hexapeptide mediates heterodimerization with PBX
CC       on a regulatory element of the somatostatin promoter. {ECO:0000250}.
CC   -!- DOMAIN: The homeodomain, which contains the nuclear localization
CC       signal, not only mediates DNA-binding, but also acts as a protein-
CC       protein interaction domain for TCF3(E47), NEUROD1 and HMG-I(Y).
CC       {ECO:0000250}.
CC   -!- PTM: Phosphorylated by the SAPK2 pathway at high intracellular glucose
CC       concentration. Phosphorylated by HIPK2 on Ser-269 upon glucose
CC       accumulation. This phosphorylation mediates subnuclear localization
CC       shifting. Phosphorylation by PASK may lead to translocation into the
CC       cytosol. {ECO:0000269|PubMed:17052199, ECO:0000269|PubMed:20637728}.
CC   -!- SIMILARITY: Belongs to the Antp homeobox family. IPF1/XlHbox-8
CC       subfamily. {ECO:0000305}.
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; X74342; CAA52389.1; -; mRNA.
DR   EMBL; AK020261; BAB32045.1; -; mRNA.
DR   EMBL; BC103572; AAI03573.1; -; mRNA.
DR   EMBL; BC103581; AAI03582.1; -; mRNA.
DR   EMBL; BC103582; AAI03583.1; -; mRNA.
DR   EMBL; BC105642; AAI05643.1; -; mRNA.
DR   CCDS; CCDS39398.1; -.
DR   PIR; S39581; S39581.
DR   RefSeq; NP_032840.1; NM_008814.3.
DR   AlphaFoldDB; P52946; -.
DR   SMR; P52946; -.
DR   BioGRID; 202101; 5.
DR   CORUM; P52946; -.
DR   IntAct; P52946; 2.
DR   MINT; P52946; -.
DR   STRING; 10090.ENSMUSP00000082729; -.
DR   GlyGen; P52946; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P52946; -.
DR   PhosphoSitePlus; P52946; -.
DR   PaxDb; 10090-ENSMUSP00000082729; -.
DR   PeptideAtlas; P52946; -.
DR   ProteomicsDB; 287995; -.
DR   Antibodypedia; 22687; 1005 antibodies from 39 providers.
DR   DNASU; 18609; -.
DR   Ensembl; ENSMUST00000085591.7; ENSMUSP00000082729.6; ENSMUSG00000029644.8.
DR   GeneID; 18609; -.
DR   KEGG; mmu:18609; -.
DR   UCSC; uc009any.2; mouse.
DR   AGR; MGI:102851; -.
DR   CTD; 3651; -.
DR   MGI; MGI:102851; Pdx1.
DR   VEuPathDB; HostDB:ENSMUSG00000029644; -.
DR   eggNOG; KOG0489; Eukaryota.
DR   GeneTree; ENSGT00940000162542; -.
DR   HOGENOM; CLU_087401_0_0_1; -.
DR   InParanoid; P52946; -.
DR   OMA; HTWKGQW; -.
DR   OrthoDB; 728401at2759; -.
DR   PhylomeDB; P52946; -.
DR   TreeFam; TF326223; -.
DR   BioGRID-ORCS; 18609; 4 hits in 79 CRISPR screens.
DR   PRO; PR:P52946; -.
DR   Proteomes; UP000000589; Chromosome 5.
DR   RNAct; P52946; Protein.
DR   Bgee; ENSMUSG00000029644; Expressed in pancreas primordium and 49 other cell types or tissues.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0016607; C:nuclear speck; IDA:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IC:NTNU_SB.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR   GO; GO:1990841; F:promoter-specific chromatin binding; ISO:MGI.
DR   GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR   GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR   GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl.
DR   GO; GO:0030154; P:cell differentiation; ISO:MGI.
DR   GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR   GO; GO:0048565; P:digestive tract development; IMP:MGI.
DR   GO; GO:0006351; P:DNA-templated transcription; ISO:MGI.
DR   GO; GO:0031018; P:endocrine pancreas development; IMP:MGI.
DR   GO; GO:0035883; P:enteroendocrine cell differentiation; IMP:MGI.
DR   GO; GO:0050673; P:epithelial cell proliferation; IMP:MGI.
DR   GO; GO:0031017; P:exocrine pancreas development; IMP:MGI.
DR   GO; GO:0042593; P:glucose homeostasis; IMP:MGI.
DR   GO; GO:0010255; P:glucose mediated signaling pathway; ISO:MGI.
DR   GO; GO:0006006; P:glucose metabolic process; IDA:MGI.
DR   GO; GO:0030073; P:insulin secretion; ISO:MGI.
DR   GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IMP:MGI.
DR   GO; GO:0001889; P:liver development; IMP:MGI.
DR   GO; GO:0016331; P:morphogenesis of embryonic epithelium; IMP:MGI.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:MGI.
DR   GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISO:MGI.
DR   GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IMP:MGI.
DR   GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:MGI.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR   GO; GO:2000675; P:negative regulation of type B pancreatic cell apoptotic process; IMP:MGI.
DR   GO; GO:0007263; P:nitric oxide mediated signal transduction; ISO:MGI.
DR   GO; GO:0031016; P:pancreas development; IMP:MGI.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:MGI.
DR   GO; GO:0032024; P:positive regulation of insulin secretion; IDA:UniProtKB.
DR   GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:MGI.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR   GO; GO:1904692; P:positive regulation of type B pancreatic cell proliferation; IMP:MGI.
DR   GO; GO:0042127; P:regulation of cell population proliferation; IDA:MGI.
DR   GO; GO:0010468; P:regulation of gene expression; ISO:MGI.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR   GO; GO:0043279; P:response to alkaloid; IEA:Ensembl.
DR   GO; GO:0010157; P:response to chlorate; IEA:Ensembl.
DR   GO; GO:0034097; P:response to cytokine; IEA:Ensembl.
DR   GO; GO:0070542; P:response to fatty acid; IEA:Ensembl.
DR   GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR   GO; GO:0009749; P:response to glucose; ISO:MGI.
DR   GO; GO:0010040; P:response to iron(II) ion; IEA:Ensembl.
DR   GO; GO:0043201; P:response to leucine; IEA:Ensembl.
DR   GO; GO:0035094; P:response to nicotine; IEA:Ensembl.
DR   GO; GO:0033273; P:response to vitamin; IEA:Ensembl.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR   GO; GO:0007224; P:smoothened signaling pathway; ISO:MGI.
DR   GO; GO:0048863; P:stem cell differentiation; ISO:MGI.
DR   GO; GO:0006366; P:transcription by RNA polymerase II; ISO:MGI.
DR   GO; GO:0060290; P:transdifferentiation; IEA:Ensembl.
DR   GO; GO:0097050; P:type B pancreatic cell apoptotic process; IMP:MGI.
DR   GO; GO:0003309; P:type B pancreatic cell differentiation; IMP:MGI.
DR   GO; GO:0044342; P:type B pancreatic cell proliferation; IMP:MGI.
DR   CDD; cd00086; homeodomain; 1.
DR   Gene3D; 1.10.10.60; Homeodomain-like; 1.
DR   InterPro; IPR009057; Homeobox-like_sf.
DR   InterPro; IPR017995; Homeobox_antennapedia.
DR   InterPro; IPR017970; Homeobox_CS.
DR   InterPro; IPR001356; Homeobox_dom.
DR   InterPro; IPR020479; Homeobox_metazoa.
DR   PANTHER; PTHR45664:SF12; PANCREAS_DUODENUM HOMEOBOX PROTEIN 1; 1.
DR   PANTHER; PTHR45664; PROTEIN ZERKNUELLT 1-RELATED; 1.
DR   Pfam; PF00046; Homeodomain; 1.
DR   PRINTS; PR00025; ANTENNAPEDIA.
DR   PRINTS; PR00024; HOMEOBOX.
DR   SMART; SM00389; HOX; 1.
DR   SUPFAM; SSF46689; Homeodomain-like; 1.
DR   PROSITE; PS00027; HOMEOBOX_1; 1.
DR   PROSITE; PS50071; HOMEOBOX_2; 1.
DR   Genevisible; P52946; MM.
PE   1: Evidence at protein level;
KW   Activator; Cytoplasm; Developmental protein; Diabetes mellitus;
KW   DNA-binding; Homeobox; Nucleus; Phosphoprotein; Reference proteome;
KW   Transcription; Transcription regulation.
FT   CHAIN           1..284
FT                   /note="Pancreas/duodenum homeobox protein 1"
FT                   /id="PRO_0000049149"
FT   DNA_BIND        147..206
FT                   /note="Homeobox"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   REGION          13..73
FT                   /note="Transactivation domain"
FT                   /evidence="ECO:0000250"
FT   REGION          30..116
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          202..284
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           119..124
FT                   /note="Antp-type hexapeptide"
FT   MOTIF           198..204
FT                   /note="Nuclear localization signal"
FT   COMPBIAS        37..51
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         152
FT                   /note="Phosphothreonine; by PASK"
FT                   /evidence="ECO:0000269|PubMed:17052199"
FT   MOD_RES         269
FT                   /note="Phosphoserine; by HIPK2"
FT                   /evidence="ECO:0000269|PubMed:20637728"
FT   MUTAGEN         152
FT                   /note="T->D,E: Displays a more cytosolic distribution."
FT                   /evidence="ECO:0000269|PubMed:17052199"
FT   MUTAGEN         269
FT                   /note="S->A: Reduced phosphorylation by HIPK2."
FT                   /evidence="ECO:0000269|PubMed:20637728"
FT   MUTAGEN         269
FT                   /note="S->E: Abnormal subnuclear localization upon glucose
FT                   accumulation."
FT                   /evidence="ECO:0000269|PubMed:20637728"
SQ   SEQUENCE   284 AA;  30999 MW;  A57D04569D14E3C4 CRC64;
     MNSEEQYYAA TQLYKDPCAF QRGPVPEFSA NPPACLYMGR QPPPPPPPQF TSSLGSLEQG
     SPPDISPYEV PPLASDDPAG AHLHHHLPAQ LGLAHPPPGP FPNGTEPGGL EEPNRVQLPF
     PWMKSTKAHA WKGQWAGGAY TAEPEENKRT RTAYTRAQLL ELEKEFLFNK YISRPRRVEL
     AVMLNLTERH IKIWFQNRRM KWKKEEDKKR SSGTPSGGGG GEEPEQDCAV TSGEELLAVP
     PLPPPGGAVP PGVPAAVREG LLPSGLSVSP QPSSIAPLRP QEPR
//