ID SIX1_MOUSE Reviewed; 284 AA. AC Q62231; Q8CIL7; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 13-APR-2004, sequence version 2. DT 27-MAR-2024, entry version 188. DE RecName: Full=Homeobox protein SIX1; DE AltName: Full=Sine oculis homeobox homolog 1; GN Name=Six1; 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] OF 12-284. RC STRAIN=C57BL/6J; TISSUE=Embryo; RX PubMed=7720577; DOI=10.1242/dev.121.3.693; RA Oliver G., Wehr R., Jenkins N.A., Copeland N.G., Cheyette B.N.R., RA Hartenstein V., Zipursky S.L., Gruss P.; RT "Homeobox genes and connective tissue patterning."; RL Development 121:693-705(1995). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=FVB/N; TISSUE=Salivary gland; 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 [3] RP FUNCTION. RX PubMed=11978764; DOI=10.1093/hmg/11.9.1045; RA Sato S., Nakamura M., Cho D.H., Tapscott S.J., Ozaki H., Kawakami K.; RT "Identification of transcriptional targets for Six5: implication for the RT pathogenesis of myotonic dystrophy type 1."; RL Hum. Mol. Genet. 11:1045-1058(2002). RN [4] RP DNA-BINDING. RX PubMed=9826681; DOI=10.1073/pnas.95.24.14220; RA Spitz F., Demignon J., Porteu A., Kahn A., Concordet J.P., Daegelen D., RA Maire P.; RT "Expression of myogenin during embryogenesis is controlled by Six/sine RT oculis homeoproteins through a conserved MEF3 binding site."; RL Proc. Natl. Acad. Sci. U.S.A. 95:14220-14225(1998). RN [5] RP FUNCTION, AND INTERACTION WITH EYA3. RX PubMed=12215533; DOI=10.1128/mcb.22.19.6759-6766.2002; RA Ikeda K., Watanabe Y., Ohto H., Kawakami K.; RT "Molecular interaction and synergistic activation of a promoter by Six, RT Eya, and Dach proteins mediated through CREB binding protein."; RL Mol. Cell. Biol. 22:6759-6766(2002). RN [6] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=12668636; DOI=10.1242/dev.00440; RA Laclef C., Hamard G., Demignon J., Souil E., Houbron C., Maire P.; RT "Altered myogenesis in Six1-deficient mice."; RL Development 130:2239-2252(2003). RN [7] RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE. RX PubMed=12783782; DOI=10.1242/dev.00536; RA Xu P.X., Zheng W., Huang L., Maire P., Laclef C., Silvius D.; RT "Six1 is required for the early organogenesis of mammalian kidney."; RL Development 130:3085-3094(2003). RN [8] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=12834866; DOI=10.1016/s0925-4773(03)00065-0; RA Laclef C., Souil E., Demignon J., Maire P.; RT "Thymus, kidney and craniofacial abnormalities in Six 1 deficient mice."; RL Mech. Dev. 120:669-679(2003). RN [9] RP FUNCTION, DISRUPTION PHENOTYPE, AND INTERACTION WITH DACH1. RX PubMed=14628042; DOI=10.1038/nature02083; RA Li X., Oghi K.A., Zhang J., Krones A., Bush K.T., Glass C.K., Nigam S.K., RA Aggarwal A.K., Maas R., Rose D.W., Rosenfeld M.G.; RT "Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional RT effects in mammalian organogenesis."; RL Nature 426:247-254(2003). RN [10] RP ERRATUM OF PUBMED:14628042. RA Li X., Oghi K.A., Zhang J., Krones A., Bush K.T., Glass C.K., Nigam S.K., RA Aggarwal A.K., Maas R., Rose D.W., Rosenfeld M.G.; RL Nature 427:265-265(2004). RN [11] RP FUNCTION, AND DEVELOPMENTAL STAGE. RX PubMed=14695375; DOI=10.1242/dev.00943; RA Ozaki H., Nakamura K., Funahashi J., Ikeda K., Yamada G., Tokano H., RA Okamura H.O., Kitamura K., Muto S., Kotaki H., Sudo K., Horai R., RA Iwakura Y., Kawakami K.; RT "Six1 controls patterning of the mouse otic vesicle."; RL Development 131:551-562(2004). RN [12] RP INTERACTION WITH EYA1. RX PubMed=15141091; DOI=10.1073/pnas.0308475101; RA Ruf R.G., Xu P.-X., Silvius D., Otto E.A., Beekmann F., Muerb U.T., RA Kumar S., Neuhaus T.J., Kemper M.J., Raymond R.M. Jr., Brophy P.D., RA Berkman J., Gattas M., Hyland V., Ruf E.-M., Schwartz C., Chang E.H., RA Smith R.J.H., Stratakis C.A., Weil D., Petit C., Hildebrandt F.; RT "SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1- RT SIX1-DNA complexes."; RL Proc. Natl. Acad. Sci. U.S.A. 101:8090-8095(2004). RN [13] RP FUNCTION. RX PubMed=16488997; DOI=10.1158/0008-5472.can-05-2360; RA Yu Y., Davicioni E., Triche T.J., Merlino G.; RT "The homeoprotein six1 transcriptionally activates multiple protumorigenic RT genes but requires ezrin to promote metastasis."; RL Cancer Res. 66:1982-1989(2006). RN [14] RP DISRUPTION PHENOTYPE. RX PubMed=21884692; DOI=10.1016/j.ydbio.2011.08.010; RA Richard A.F., Demignon J., Sakakibara I., Pujol J., Favier M., RA Strochlic L., Le Grand F., Sgarioto N., Guernec A., Schmitt A., Cagnard N., RA Huang R., Legay C., Guillet-Deniau I., Maire P.; RT "Genesis of muscle fiber-type diversity during mouse embryogenesis relies RT on Six1 and Six4 gene expression."; RL Dev. Biol. 359:303-320(2011). RN [15] RP FUNCTION, AND INTERACTION WITH CEBPA; CEBPB AND EBF2. RX PubMed=27923061; DOI=10.1371/journal.pgen.1006474; RA Brunmeir R., Wu J., Peng X., Kim S.Y., Julien S.G., Zhang Q., Xie W., RA Xu F.; RT "Comparative Transcriptomic and Epigenomic Analyses Reveal New Regulators RT of Murine Brown Adipogenesis."; RL PLoS Genet. 12:E1006474-E1006474(2016). CC -!- FUNCTION: Transcription factor that is involved in the regulation of CC cell proliferation, apoptosis and embryonic development CC (PubMed:12215533, PubMed:12668636, PubMed:12834866, PubMed:14628042, CC PubMed:14695375). Plays an important role in the development of several CC organs, including kidney, muscle and inner ear (PubMed:12668636, CC PubMed:12783782, PubMed:12834866, PubMed:14628042, PubMed:14695375). CC Depending on context, functions as a transcriptional repressor or CC activator (PubMed:14628042). Lacks an activation domain, and requires CC interaction with EYA family members for transcription activation (By CC similarity). Mediates nuclear translocation of EYA1 and EYA2 (By CC similarity). Binds the 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 CC element in the MYOG promoter and CIDEA enhancer (By similarity). CC Regulates the expression of numerous genes, including MYC, CCNA1, CCND1 CC and EZR (PubMed:16488997). Acts as an activator of the IGFBP5 promoter, CC probably coactivated by EYA2 (PubMed:11978764). Repression of precursor CC cell proliferation in myoblasts is switched to activation through CC recruitment of EYA3 to the SIX1-DACH1 complex (PubMed:14628042). During CC myogenesis, seems to act together with EYA2 and DACH2. Regulates the CC expression of CCNA1 (By similarity). Promotes brown adipocyte CC differentiation (PubMed:27923061). {ECO:0000250|UniProtKB:Q15475, CC ECO:0000269|PubMed:11978764, ECO:0000269|PubMed:12215533, CC ECO:0000269|PubMed:12668636, ECO:0000269|PubMed:12783782, CC ECO:0000269|PubMed:12834866, ECO:0000269|PubMed:14628042, CC ECO:0000269|PubMed:14695375, ECO:0000269|PubMed:16488997, CC ECO:0000269|PubMed:27923061}. CC -!- SUBUNIT: Interacts with DACH1 (PubMed:14628042). Interacts with EYA1 CC (PubMed:15141091). Interacts with EYA2 (By similarity). Interacts with CC CDH1 (By similarity). Interacts with TBX18 (By similarity). Interacts CC with CEBPA (PubMed:27923061). Interacts with CEBPB (PubMed:27923061). CC Interacts with EBF2 (PubMed:27923061). {ECO:0000250|UniProtKB:Q15475, CC ECO:0000269|PubMed:14628042, ECO:0000269|PubMed:15141091, CC ECO:0000269|PubMed:27923061}. CC -!- INTERACTION: CC Q62231; P97767: Eya1; NbExp=3; IntAct=EBI-1368483, EBI-1368503; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q15475}. Cytoplasm CC {ECO:0000250|UniProtKB:Q15475}. CC -!- TISSUE SPECIFICITY: Expressed in phalangeal tendons and in skeletal CC muscle and in head and body mesenchyme. CC -!- DEVELOPMENTAL STAGE: First expressed at 8.2-8.5 dpc of embryo CC development in the anterior head mesoderm and developing pharyngeal CC pouches. Expression in the developing limb begins at 11 dpc and is more CC pronounced dorsally. It progresses into the developing phalanges at CC 13.5 dpc. In the developing inner ear detected in the otic placode and CC the surrounding surface ectoderm at 8.5 dpc. Expression became CC prominent at the invaginating otic pit and the nascent otic vesicle at CC 9.5 dpc. At 10.5 dpc, expression was limited to the ventral half of the CC otic vesicle. Subsequently, the expression became gradually restricted CC to the cochlear region at 11.5 dpc and 12.5 dpc. At later stages CC detected exclusively in the cochlea at 14.5 dpc, and the expression in CC the cochlear duct persisted in the neonate. In the developing kidney, CC is expressed in the uninduced metanephric mesenchyme at 10.5 dpc and in CC the induced mesenchyme around the ureteric bud at 11.5 dpc. At 17.5 dpc CC to P0, expression becomes restricted to a subpopulation of collecting CC tubule epithelial cells. {ECO:0000269|PubMed:12783782, CC ECO:0000269|PubMed:14695375}. CC -!- PTM: Phosphorylated during interphase; becomes hyperphosphorylated CC during mitosis. Hyperphosphorylation impairs binding to promoter CC elements (By similarity). {ECO:0000250}. CC -!- PTM: Ubiquitinated by the anaphase promoting complex (APC), leading to CC its proteasomal degradation. {ECO:0000250}. CC -!- DISRUPTION PHENOTYPE: Perinatal lethality. Mice show failure in renal CC organogenesis, a severe reduction of most migratory hypaxial muscles CC including those of the forelimb, diaphragm and tongue, and severe rib- CC cage deformation. Besides, mice display craniofacial defects, including CC loss of inner ear structures. Pax2, Six2 and Sall1 expression is CC markedly reduced in the metanephric mesenchyme at 10.5 dpc during CC kidney development. Mice lacking both Six1 and Eya1 show defects in CC kidney development, complete absence of hypaxial muscle, severe CC reduction in epaxial muscle and a 5-10-fold by volume smaller pituarity CC than the wild-type gland. {ECO:0000269|PubMed:12668636, CC ECO:0000269|PubMed:12783782, ECO:0000269|PubMed:12834866, CC ECO:0000269|PubMed:14628042, ECO:0000269|PubMed:21884692}. CC -!- SIMILARITY: Belongs to the SIX/Sine oculis homeobox family. CC {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; X80339; CAA56585.1; -; mRNA. DR EMBL; BC023304; AAH23304.1; -; mRNA. DR CCDS; CCDS25973.1; -. DR PIR; S60751; S60751. DR RefSeq; NP_033215.2; NM_009189.3. DR AlphaFoldDB; Q62231; -. DR SMR; Q62231; -. DR BioGRID; 203259; 10. DR CORUM; Q62231; -. DR IntAct; Q62231; 1. DR STRING; 10090.ENSMUSP00000059026; -. DR iPTMnet; Q62231; -. DR PhosphoSitePlus; Q62231; -. DR PaxDb; 10090-ENSMUSP00000059026; -. DR Pumba; Q62231; -. DR Antibodypedia; 39; 248 antibodies from 30 providers. DR DNASU; 20471; -. DR Ensembl; ENSMUST00000050029.8; ENSMUSP00000059026.7; ENSMUSG00000051367.9. DR GeneID; 20471; -. DR KEGG; mmu:20471; -. DR UCSC; uc007nwa.2; mouse. DR AGR; MGI:102780; -. DR CTD; 6495; -. DR MGI; MGI:102780; Six1. DR VEuPathDB; HostDB:ENSMUSG00000051367; -. DR eggNOG; KOG0775; Eukaryota. DR GeneTree; ENSGT00940000156487; -. DR HOGENOM; CLU_046914_2_0_1; -. DR InParanoid; Q62231; -. DR OMA; YKAHYVE; -. DR OrthoDB; 602349at2759; -. DR PhylomeDB; Q62231; -. DR TreeFam; TF315545; -. DR BioGRID-ORCS; 20471; 1 hit in 80 CRISPR screens. DR PRO; PR:Q62231; -. DR Proteomes; UP000000589; Chromosome 12. DR RNAct; Q62231; Protein. DR Bgee; ENSMUSG00000051367; Expressed in lumbar dorsal root ganglion and 169 other cell types or tissues. DR ExpressionAtlas; Q62231; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005730; C:nucleolus; ISO:MGI. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI. DR GO; GO:0003682; F:chromatin binding; IGI:MGI. DR GO; GO:0003677; F:DNA binding; ISO:MGI. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI. 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:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI. 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:0000976; F:transcription cis-regulatory region binding; ISO:MGI. DR GO; GO:0001223; F:transcription coactivator binding; ISO:MGI. DR GO; GO:0048856; P:anatomical structure development; IGI:MGI. DR GO; GO:0035909; P:aorta morphogenesis; IGI:MGI. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IGI:MGI. DR GO; GO:1905243; P:cellular response to 3,3',5-triiodo-L-thyronine; ISO:MGI. DR GO; GO:0090103; P:cochlea morphogenesis; IMP:MGI. DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IGI:MGI. DR GO; GO:0048704; P:embryonic skeletal system morphogenesis; IGI:MGI. DR GO; GO:0086100; P:endothelin receptor signaling pathway; IMP:MGI. DR GO; GO:0030855; P:epithelial cell differentiation; IMP:MGI. DR GO; GO:0021610; P:facial nerve morphogenesis; IMP:MGI. DR GO; GO:0061197; P:fungiform papilla morphogenesis; IMP:UniProtKB. DR GO; GO:0010467; P:gene expression; IMP:MGI. DR GO; GO:0048699; P:generation of neurons; IMP:UniProtKB. DR GO; GO:0048839; P:inner ear development; IMP:UniProtKB. DR GO; GO:0042472; P:inner ear morphogenesis; IGI:MGI. DR GO; GO:0001822; P:kidney development; IMP:UniProtKB. DR GO; GO:0072198; P:mesenchymal cell proliferation involved in ureter development; IGI:MGI. DR GO; GO:0072172; P:mesonephric tubule formation; IMP:UniProtKB. DR GO; GO:0072075; P:metanephric mesenchyme development; IMP:UniProtKB. DR GO; GO:0042474; P:middle ear morphogenesis; IMP:MGI. DR GO; GO:0051451; P:myoblast migration; IGI:MGI. DR GO; GO:0051450; P:myoblast proliferation; IGI:MGI. DR GO; GO:0061055; P:myotome development; IMP:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0014033; P:neural crest cell differentiation; IGI:MGI. DR GO; GO:0022008; P:neurogenesis; IMP:UniProtKB. DR GO; GO:0048665; P:neuron fate specification; IGI:MGI. DR GO; GO:0007219; P:Notch signaling pathway; IMP:MGI. DR GO; GO:0030910; P:olfactory placode formation; IMP:UniProtKB. DR GO; GO:0001759; P:organ induction; IMP:MGI. DR GO; GO:0071599; P:otic vesicle development; IMP:MGI. DR GO; GO:0003151; P:outflow tract morphogenesis; IGI:MGI. DR GO; GO:0007389; P:pattern specification process; IMP:MGI. DR GO; GO:0060037; P:pharyngeal system development; IMP:UniProtKB. DR GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; IMP:UniProtKB. DR GO; GO:0090336; P:positive regulation of brown fat cell differentiation; IMP:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:2000729; P:positive regulation of mesenchymal cell proliferation involved in ureter development; IGI:MGI. DR GO; GO:2000288; P:positive regulation of myoblast proliferation; IGI:MGI. DR GO; GO:0072513; P:positive regulation of secondary heart field cardioblast proliferation; IGI:MGI. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0072107; P:positive regulation of ureteric bud formation; IMP:UniProtKB. DR GO; GO:0034504; P:protein localization to nucleus; ISO:MGI. DR GO; GO:0072095; P:regulation of branch elongation involved in ureteric bud branching; IMP:UniProtKB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:MGI. DR GO; GO:0050678; P:regulation of epithelial cell proliferation; IMP:UniProtKB. DR GO; GO:0010468; P:regulation of gene expression; IGI:MGI. DR GO; GO:0045664; P:regulation of neuron differentiation; IMP:MGI. DR GO; GO:0032880; P:regulation of protein localization; IGI:MGI. DR GO; GO:2001014; P:regulation of skeletal muscle cell differentiation; IDA:UniProtKB. DR GO; GO:0014857; P:regulation of skeletal muscle cell proliferation; IBA:GO_Central. DR GO; GO:0014842; P:regulation of skeletal muscle satellite cell proliferation; IDA:UniProtKB. DR GO; GO:0008582; P:regulation of synaptic assembly at neuromuscular junction; IGI:MGI. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0007605; P:sensory perception of sound; IMP:MGI. DR GO; GO:0048741; P:skeletal muscle fiber development; IBA:GO_Central. DR GO; GO:0007519; P:skeletal muscle tissue development; IMP:UniProtKB. DR GO; GO:0048705; P:skeletal system morphogenesis; IMP:MGI. DR GO; GO:0007382; P:specification of segmental identity, maxillary segment; IMP:MGI. DR GO; GO:0048538; P:thymus development; IMP:MGI. DR GO; GO:0030878; P:thyroid gland development; IMP:MGI. DR GO; GO:0043586; P:tongue development; IMP:UniProtKB. DR GO; GO:0061551; P:trigeminal ganglion development; IMP:UniProtKB. DR GO; GO:0072193; P:ureter smooth muscle cell differentiation; IMP:MGI. DR GO; GO:0001657; P:ureteric bud development; IMP:MGI. DR CDD; cd00086; homeodomain; 1. DR Gene3D; 1.10.10.60; Homeodomain-like; 1. DR InterPro; IPR009057; Homeobox-like_sf. DR InterPro; IPR017970; Homeobox_CS. DR InterPro; IPR001356; Homeobox_dom. DR InterPro; IPR008422; Homeobox_KN_domain. DR InterPro; IPR031701; SIX1_SD. DR PANTHER; PTHR10390; HOMEOBOX PROTEIN SIX; 1. DR PANTHER; PTHR10390:SF13; HOMEOBOX PROTEIN SIX1; 1. DR Pfam; PF05920; Homeobox_KN; 1. DR Pfam; PF16878; SIX1_SD; 1. 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; Q62231; MM. PE 1: Evidence at protein level; KW Activator; Apoptosis; Cytoplasm; Developmental protein; DNA-binding; KW Homeobox; Nucleus; Phosphoprotein; Reference proteome; Repressor; KW Transcription; Transcription regulation; Ubl conjugation. FT CHAIN 1..284 FT /note="Homeobox protein SIX1" FT /id="PRO_0000049296" FT DNA_BIND 124..183 FT /note="Homeobox" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108" FT REGION 168..284 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 173..192 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 193..209 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 217..284 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CONFLICT 12..14 FT /note="EQV -> GQG (in Ref. 1; CAA56585)" FT /evidence="ECO:0000305" SQ SEQUENCE 284 AA; 32210 MW; 4A6F88000FB9F8EB CRC64; MSMLPSFGFT QEQVACVCEV LQQGGNLERL GRFLWSLPAC DHLHKNESVL KAKAVVAFHR GNFRELYKIL ESHQFSPHNH PKLQQLWLKA HYVEAEKLRG RPLGAVGKYR VRRKFPLPRT IWDGEETSYC FKEKSRGVLR EWYAHNPYPS PREKRELAEA TGLTTTQVSN WFKNRRQRDR AAEAKERENT ENNNSSSNKQ NQLSPLEGGK PLMSSSEEEF SPPQSPDQNS VLLLQSNMGH ARSSNYSLPG LTASQPSHGL QAHQHQLQDS LLGPLTSSLV DLGS //