ID HCN1_MOUSE Reviewed; 910 AA. AC O88704; O54899; Q9D613; DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 14-OCT-2015, entry version 145. DE RecName: Full=Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1; DE AltName: Full=Brain cyclic nucleotide-gated channel 1; DE Short=BCNG-1; DE AltName: Full=Hyperpolarization-activated cation channel 2; DE Short=HAC-2; GN Name=Hcn1; Synonyms=Bcng1, Hac2; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND GLYCOSYLATION. RC STRAIN=C57BL/6J; TISSUE=Brain; RX PubMed=9405696; DOI=10.1073/pnas.94.26.14815; RA Santoro B., Grant S.G.N., Bartsch D., Kandel E.R.; RT "Interactive cloning with the SH3 domain of N-src identifies a new RT brain specific ion channel protein, with homology to eag and cyclic RT nucleotide-gated channels."; RL Proc. Natl. Acad. Sci. U.S.A. 94:14815-14820(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=BALB/c; TISSUE=Brain; RX PubMed=9634236; DOI=10.1038/31255; RA Ludwig A., Zong X., Jeglitsch M., Hofmann F., Biel M.; RT "A family of hyperpolarization-activated cation channels."; RL Nature 393:587-591(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 377-910. RC STRAIN=C57BL/6J; TISSUE=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., RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E., RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., RA 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., RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., RA Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] RP FUNCTION, SUBCELLULAR LOCATION, AND ENZYME REGULATION. RX PubMed=9630217; DOI=10.1016/S0092-8674(00)81434-8; RA Santoro B., Liu D.T., Yao H., Bartsch D., Kandel E.R., RA Siegelbaum S.A., Tibbs G.R.; RT "Identification of a gene encoding a hyperpolarization-activated RT 'pacemaker' channel of brain."; RL Cell 93:717-729(1998). RN [5] RP INTERACTION WITH KCNE2. RX PubMed=11420311; DOI=10.1161/hh1201.093511; RA Yu H., Wu J., Potapova I., Wymore R.T., Holmes B., Zuckerman J., RA Pan Z., Wang H., Shi W., Robinson R.B., El-Maghrabi M.R., Benjamin W., RA Dixon J.E., McKinnon D., Cohen I.S., Wymore R.; RT "MinK-related peptide 1: a beta subunit for the HCN ion channel RT subunit family enhances expression and speeds activation."; RL Circ. Res. 88:E84-E87(2001). RN [6] RP FUNCTION, SUBCELLULAR LOCATION, AND ENZYME REGULATION. RX PubMed=11459060; DOI=10.1038/35081088; RA Wainger B.J., DeGennaro M., Santoro B., Siegelbaum S.A., Tibbs G.R.; RT "Molecular mechanism of cAMP modulation of HCN pacemaker channels."; RL Nature 411:805-810(2001). RN [7] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=11675786; DOI=10.1038/35098087; RA Stevens D.R., Seifert R., Bufe B., Mueller F., Kremmer E., Gauss R., RA Meyerhof W., Kaupp U.B., Lindemann B.; RT "Hyperpolarization-activated channels HCN1 and HCN4 mediate responses RT to sour stimuli."; RL Nature 413:631-635(2001). RN [8] RP INTERACTION WITH HCN2, AND MUTAGENESIS OF GLY-349; TYR-350 AND RP GLY-351. RX PubMed=12089064; DOI=10.1161/01.RES.0000024390.97889.C6; RA Xue T., Marban E., Li R.A.; RT "Dominant-negative suppression of HCN1- and HCN2-encoded pacemaker RT currents by an engineered HCN1 construct: insights into structure- RT function relationships and multimerization."; RL Circ. Res. 90:1267-1273(2002). RN [9] RP FUNCTION, AND INTERACTION WITH HCN2. RX PubMed=12034718; DOI=10.1074/jbc.M200504200; RA Proenza C., Tran N., Angoli D., Zahynacz K., Balcar P., Accili E.A.; RT "Different roles for the cyclic nucleotide binding domain and amino RT terminus in assembly and expression of hyperpolarization-activated, RT cyclic nucleotide-gated channels."; RL J. Biol. Chem. 277:29634-29642(2002). RN [10] RP MUTAGENESIS OF CYS-303 AND CYS-318. RX PubMed=12351622; DOI=10.1074/jbc.M204915200; RA Xue T., Li R.A.; RT "An external determinant in the S5-P linker of the pacemaker (HCN) RT channel identified by sulfhydryl modification."; RL J. Biol. Chem. 277:46233-46242(2002). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and RT expression."; RL Cell 143:1174-1189(2010). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 390-592 IN COMPLEX WITH CAMP, RP FUNCTION, SUBCELLULAR LOCATION, NUCLEOTIDE-BINDING, ENZYME REGULATION, RP MUTAGENESIS OF ARG-538, AND SUBUNIT. RX PubMed=22006928; DOI=10.1074/jbc.M111.297606; RA Lolicato M., Nardini M., Gazzarrini S., Moller S., Bertinetti D., RA Herberg F.W., Bolognesi M., Martin H., Fasolini M., Bertrand J.A., RA Arrigoni C., Thiel G., Moroni A.; RT "Tetramerization dynamics of C-terminal domain underlies isoform- RT specific cAMP gating in hyperpolarization-activated cyclic nucleotide- RT gated channels."; RL J. Biol. Chem. 286:44811-44820(2011). CC -!- FUNCTION: Hyperpolarization-activated ion channel exhibiting weak CC selectivity for potassium over sodium ions. Contributes to the CC native pacemaker currents in heart (If) and in neurons (Ih). May CC mediate responses to sour stimuli. {ECO:0000269|PubMed:11459060, CC ECO:0000269|PubMed:11675786, ECO:0000269|PubMed:12034718, CC ECO:0000269|PubMed:22006928, ECO:0000269|PubMed:9630217}. CC -!- ENZYME REGULATION: Activated by cAMP, and at 10-100 times higher CC concentrations, also by cGMP. cAMP binding causes a conformation CC change that leads to the assembly of an active tetramer and CC channel opening. Compared to other family members, cAMP has less CC stimulatory effect on HCN1 because part of the molecules already CC contain bound cAMP and form homotetramers when cAMP levels are CC low. {ECO:0000269|PubMed:11459060, ECO:0000269|PubMed:22006928, CC ECO:0000269|PubMed:9630217}. CC -!- SUBUNIT: Homotetramer. Heterotetramer with HCN2. The potassium CC channel is composed of a homo- or heterotetrameric complex of CC pore-forming subunits. Interacts with KCNE2. Interacts with the CC SH3 domain of CSK. {ECO:0000269|PubMed:11420311, CC ECO:0000269|PubMed:12034718, ECO:0000269|PubMed:12089064, CC ECO:0000269|PubMed:22006928}. CC -!- INTERACTION: CC Self; NbExp=2; IntAct=EBI-8766347, EBI-8766347; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11459060, CC ECO:0000269|PubMed:22006928, ECO:0000269|PubMed:9630217}; Multi- CC pass membrane protein {ECO:0000269|PubMed:11459060, CC ECO:0000269|PubMed:22006928, ECO:0000269|PubMed:9630217}. CC -!- TISSUE SPECIFICITY: Predominantly expressed in brain. Highly CC expressed in apical dendrites of pyramidal neurons in the cortex, CC in the layer corresponding to the stratum lacunosum-moleculare in CC the hippocampus and in axons of basket cells in the cerebellum. CC Expressed in a subset of elongated cells in taste buds. CC {ECO:0000269|PubMed:11675786, ECO:0000269|PubMed:9405696}. CC -!- DOMAIN: The segment S4 is probably the voltage-sensor and is CC characterized by a series of positively charged amino acids at CC every third position. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:9405696}. CC -!- MISCELLANEOUS: Inhibited by extracellular cesium ions. CC -!- SIMILARITY: Belongs to the potassium channel HCN family. CC {ECO:0000305}. CC -!- SIMILARITY: Contains 1 cyclic nucleotide-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00060}. CC -!- SEQUENCE CAUTION: CC Sequence=AK014722; Type=Frameshift; Positions=381; Evidence={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; AF028737; AAC53518.1; -; mRNA. DR EMBL; AJ225123; CAA12407.1; -; mRNA. DR EMBL; AK014722; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS26793.1; -. DR RefSeq; NP_034538.2; NM_010408.3. DR RefSeq; XP_006517592.1; XM_006517529.2. DR RefSeq; XP_011242925.1; XM_011244623.1. DR UniGene; Mm.343429; -. DR PDB; 3U0Z; X-ray; 2.90 A; A/B=390-592. DR PDBsum; 3U0Z; -. DR ProteinModelPortal; O88704; -. DR SMR; O88704; 390-588. DR BioGrid; 200252; 2. DR MINT; MINT-154994; -. DR STRING; 10090.ENSMUSP00000006991; -. DR BindingDB; O88704; -. DR ChEMBL; CHEMBL1250401; -. DR GuidetoPHARMACOLOGY; 400; -. DR TCDB; 1.A.1.5.2; the voltage-gated ion channel (vic) superfamily. DR PhosphoSite; O88704; -. DR PaxDb; O88704; -. DR PRIDE; O88704; -. DR Ensembl; ENSMUST00000006991; ENSMUSP00000006991; ENSMUSG00000021730. DR GeneID; 15165; -. DR KEGG; mmu:15165; -. DR UCSC; uc007ryo.2; mouse. DR CTD; 348980; -. DR MGI; MGI:1096392; Hcn1. DR eggNOG; COG0664; -. DR GeneTree; ENSGT00760000118772; -. DR HOGENOM; HOG000230717; -. DR HOVERGEN; HBG039489; -. DR InParanoid; O88704; -. DR KO; K04954; -. DR OMA; EVHRSTQ; -. DR OrthoDB; EOG7VMP6X; -. DR PhylomeDB; O88704; -. DR TreeFam; TF318250; -. DR Reactome; R-MMU-1296061; HCN channels. DR NextBio; 287666; -. DR PRO; PR:O88704; -. DR Proteomes; UP000000589; Chromosome 13. DR Bgee; O88704; -. DR Genevisible; O88704; MM. DR GO; GO:0030424; C:axon; IDA:MGI. DR GO; GO:0030425; C:dendrite; IDA:MGI. DR GO; GO:0005887; C:integral component of plasma membrane; IMP:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISO:MGI. DR GO; GO:0030552; F:cAMP binding; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0005222; F:intracellular cAMP activated cation channel activity; IMP:UniProtKB. DR GO; GO:0005249; F:voltage-gated potassium channel activity; IMP:UniProtKB. DR GO; GO:0005248; F:voltage-gated sodium channel activity; ISO:MGI. DR GO; GO:0045176; P:apical protein localization; IMP:MGI. DR GO; GO:0071320; P:cellular response to cAMP; IMP:UniProtKB. DR GO; GO:0071805; P:potassium ion transmembrane transport; IMP:UniProtKB. DR GO; GO:0042391; P:regulation of membrane potential; ISO:MGI. DR GO; GO:0046549; P:retinal cone cell development; IMP:MGI. DR GO; GO:0035725; P:sodium ion transmembrane transport; ISO:MGI. DR Gene3D; 2.60.120.10; -; 1. DR InterPro; IPR018490; cNMP-bd-like. DR InterPro; IPR018488; cNMP-bd_CS. DR InterPro; IPR000595; cNMP-bd_dom. DR InterPro; IPR005821; Ion_trans_dom. DR InterPro; IPR013621; Ion_trans_N. DR InterPro; IPR030169; K/Na_HCN1. DR InterPro; IPR003938; K_chnl_volt-dep_EAG/ELK/ERG. DR InterPro; IPR014710; RmlC-like_jellyroll. DR PANTHER; PTHR10217:SF373; PTHR10217:SF373; 1. DR Pfam; PF00027; cNMP_binding; 1. DR Pfam; PF00520; Ion_trans; 1. DR Pfam; PF08412; Ion_trans_N; 1. DR PRINTS; PR01463; EAGCHANLFMLY. DR SMART; SM00100; cNMP; 1. DR SUPFAM; SSF51206; SSF51206; 1. DR PROSITE; PS00888; CNMP_BINDING_1; 1. DR PROSITE; PS50042; CNMP_BINDING_3; 1. PE 1: Evidence at protein level; KW 3D-structure; cAMP; cAMP-binding; Cell membrane; Complete proteome; KW Glycoprotein; Ion channel; Ion transport; Ligand-gated ion channel; KW Membrane; Nucleotide-binding; Phosphoprotein; Potassium; KW Potassium channel; Potassium transport; Reference proteome; Sodium; KW Sodium channel; Sodium transport; Transmembrane; Transmembrane helix; KW Transport; Voltage-gated channel. FT CHAIN 1 910 Potassium/sodium hyperpolarization- FT activated cyclic nucleotide-gated channel FT 1. FT /FTId=PRO_0000054108. FT TOPO_DOM 1 135 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 136 156 Helical; Name=Segment S1. {ECO:0000255}. FT TOPO_DOM 157 162 Extracellular. {ECO:0000255}. FT TRANSMEM 163 183 Helical; Name=Segment S2. {ECO:0000255}. FT TOPO_DOM 184 208 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 209 229 Helical; Name=Segment S3. {ECO:0000255}. FT TOPO_DOM 230 237 Extracellular. {ECO:0000255}. FT TRANSMEM 238 258 Helical; Voltage-sensor; Name=Segment S4. FT {ECO:0000255}. FT TOPO_DOM 259 289 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 290 310 Helical; Name=Segment S5. {ECO:0000255}. FT TOPO_DOM 311 333 Extracellular. {ECO:0000255}. FT INTRAMEM 334 355 Pore-forming; Name=Segment H5. FT {ECO:0000255}. FT TOPO_DOM 356 360 Extracellular. {ECO:0000255}. FT TRANSMEM 361 381 Helical; Name=Segment S6. {ECO:0000255}. FT TOPO_DOM 382 910 Cytoplasmic. {ECO:0000255}. FT NP_BIND 528 531 cAMP. {ECO:0000269|PubMed:22006928}. FT NP_BIND 538 539 cAMP. {ECO:0000269|PubMed:22006928}. FT NP_BIND 579 582 cAMP. {ECO:0000269|PubMed:22006928}. FT REGION 78 129 Involved in subunit assembly. FT {ECO:0000250}. FT COMPBIAS 1 81 Gly-rich. FT COMPBIAS 715 777 Gln-rich. FT COMPBIAS 878 884 Poly-Pro. FT MOD_RES 714 714 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9JKA9}. FT CARBOHYD 327 327 N-linked (GlcNAc...). FT {ECO:0000305|PubMed:9405696}. FT MUTAGEN 303 303 C->S: Abolishes conductivity. FT {ECO:0000269|PubMed:12351622}. FT MUTAGEN 318 318 C->S: Abolishes sensitivity to sulfhydryl FT modification. FT {ECO:0000269|PubMed:12351622}. FT MUTAGEN 349 349 G->A: Abolishes conductivity; when FT associated with A-350 and A-351. FT {ECO:0000269|PubMed:12089064}. FT MUTAGEN 350 350 Y->A: Abolishes conductivity; when FT associated with A-349 and A-351. FT {ECO:0000269|PubMed:12089064}. FT MUTAGEN 351 351 G->A: Abolishes conductivity; when FT associated with A-349 and A-350. FT {ECO:0000269|PubMed:12089064}. FT MUTAGEN 538 538 R->E: Reduces affinity for cAMP and FT impairs tetramerization. FT {ECO:0000269|PubMed:22006928}. FT CONFLICT 42 42 G -> R (in Ref. 1; AAC53518). FT {ECO:0000305}. FT CONFLICT 394 394 R -> S (in Ref. 3; AK014722). FT {ECO:0000305}. FT HELIX 391 410 {ECO:0000244|PDB:3U0Z}. FT HELIX 414 428 {ECO:0000244|PDB:3U0Z}. FT HELIX 435 440 {ECO:0000244|PDB:3U0Z}. FT HELIX 444 454 {ECO:0000244|PDB:3U0Z}. FT HELIX 456 460 {ECO:0000244|PDB:3U0Z}. FT HELIX 463 466 {ECO:0000244|PDB:3U0Z}. FT HELIX 470 478 {ECO:0000244|PDB:3U0Z}. FT STRAND 481 485 {ECO:0000244|PDB:3U0Z}. FT STRAND 490 492 {ECO:0000244|PDB:3U0Z}. FT STRAND 500 506 {ECO:0000244|PDB:3U0Z}. FT STRAND 509 512 {ECO:0000244|PDB:3U0Z}. FT STRAND 519 521 {ECO:0000244|PDB:3U0Z}. FT STRAND 526 528 {ECO:0000244|PDB:3U0Z}. FT HELIX 529 534 {ECO:0000244|PDB:3U0Z}. FT STRAND 540 546 {ECO:0000244|PDB:3U0Z}. FT STRAND 548 554 {ECO:0000244|PDB:3U0Z}. FT HELIX 555 564 {ECO:0000244|PDB:3U0Z}. FT HELIX 567 583 {ECO:0000244|PDB:3U0Z}. SQ SEQUENCE 910 AA; 102432 MW; 56FD5F328DD972E9 CRC64; MEGGGKPNSA SNSRDDGNSV FPSKAPATGP VAADKRLGTP PGGGAAGKEH GNSVCFKVDG GGGEEPAGSF EDAEGPRRQY GFMQRQFTSM LQPGVNKFSL RMFGSQKAVE KEQERVKTAG FWIIHPYSDF RFYWDLIMLI MMVGNLVIIP VGITFFTEQT TTPWIIFNVA SDTVFLLDLI MNFRTGTVNE DSSEIILDPK VIKMNYLKSW FVVDFISSIP VDYIFLIVEK GMDSEVYKTA RALRIVRFTK ILSLLRLLRL SRLIRYIHQW EEIFHMTYDL ASAVVRIFNL IGMMLLLCHW DGCLQFLVPL LQDFPPDCWV SLNEMVNDSW GKQYSYALFK AMSHMLCIGY GAQAPVSMSD LWITMLSMIV GATCYAMFVG HATALIQSLD SSRRQYQEKY KQVEQYMSFH KLPADMRQKI HDYYEHRYQG KIFDEENILS ELNDPLREEI VNFNCRKLVA TMPLFANADP NFVTAMLSKL RFEVFQPGDY IIREGAVGKK MYFIQHGVAG VITKSSKEMK LTDGSYFGEI CLLTKGRRTA SVRADTYCRL YSLSVDNFNE VLEEYPMMRR AFETVAIDRL DRIGKKNSIL LQKFQKDLNT GVFNNQENEI LKQIVKHDRE MVQAIPPINY PQMTALNCTS STTTPTSRMR TQSPPVYTAT SLSHSNLHSP SPSTQTPQPS AILSPCSYTT AVCSPPIQSP LATRTFHYAS PTASQLSLMQ QPQQQLPQSQ VQQTQTQTQQ QQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QQQQQPQTPG SSTPKNEVHK STQALHNTNL TKEVRPLSAS QPSLPHEVST LISRPHPTVG ESLASIPQPV AAVHSTGLQA GSRSTVPQRV TLFRQMSSGA IPPNRGVPPA PPPPAAVQRE SPSVLNTDPD AEKPRFASNL //