ADCY6_RAT
ID ADCY6_RAT Reviewed; 1166 AA.
AC Q03343;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Adenylate cyclase type 6;
DE EC=4.6.1.1 {ECO:0000269|PubMed:1409703, ECO:0000269|PubMed:15385642, ECO:0000269|PubMed:17110384, ECO:0000269|PubMed:21606183, ECO:0000269|PubMed:9391159};
DE AltName: Full=ATP pyrophosphate-lyase 6;
DE AltName: Full=Adenylate cyclase type VI;
DE Short=ACVI;
DE AltName: Full=Adenylyl cyclase 6;
DE Short=AC6 {ECO:0000303|PubMed:9391159};
DE AltName: Full=Ca(2+)-inhibitable adenylyl cyclase;
GN Name=Adcy6;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1332969; DOI=10.1016/s0021-9258(18)35842-3;
RA Krupinski J., Lehman T.C., Frankenfield C.D., Zwaagstra J.C., Watson P.A.;
RT "Molecular diversity in the adenylylcyclase family. Evidence for eight
RT forms of the enzyme and cloning of type VI.";
RL J. Biol. Chem. 267:24858-24862(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=1409703; DOI=10.1073/pnas.89.20.9809;
RA Premont R.T., Chen J., Ma H.-W., Ponnapalli M., Iyengar R.;
RT "Two members of a widely expressed subfamily of hormone-stimulated adenylyl
RT cyclases.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:9809-9813(1992).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION, ACTIVITY
RP REGULATION, MUTAGENESIS OF SER-660, AND PHOSPHORYLATION AT SER-660.
RX PubMed=9391159; DOI=10.1073/pnas.94.25.14100;
RA Chen Y., Harry A., Li J., Smit M.J., Bai X., Magnusson R., Pieroni J.P.,
RA Weng G., Iyengar R.;
RT "Adenylyl cyclase 6 is selectively regulated by protein kinase A
RT phosphorylation in a region involved in Galphas stimulation.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:14100-14104(1997).
RN [4]
RP PHOSPHORYLATION AT SER-554; SER-660 AND THR-917, AND MUTAGENESIS OF
RP SER-311; SER-554; SER-660 AND THR-917.
RX PubMed=11877398; DOI=10.1074/jbc.m111537200;
RA Lin T.-H., Lai H.-L., Kao Y.-Y., Sun C.-N., Hwang M.-J., Chern Y.;
RT "Protein kinase C inhibits type VI adenylyl cyclase by phosphorylating the
RT regulatory N domain and two catalytic C1 and C2 domains.";
RL J. Biol. Chem. 277:15721-15728(2002).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, PHOSPHORYLATION BY RAF1,
RP INTERACTION WITH RAF1, AND ACTIVITY REGULATION.
RX PubMed=15385642; DOI=10.1124/mol.66.4.921;
RA Ding Q., Gros R., Gray I.D., Taussig R., Ferguson S.S., Feldman R.D.;
RT "Raf kinase activation of adenylyl cyclases: isoform-selective
RT regulation.";
RL Mol. Pharmacol. 66:921-928(2004).
RN [6]
RP CATALYTIC ACTIVITY, FUNCTION, ACTIVITY REGULATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=17110384; DOI=10.1074/jbc.m607522200;
RA Gao X., Sadana R., Dessauer C.W., Patel T.B.;
RT "Conditional stimulation of type V and VI adenylyl cyclases by G protein
RT betagamma subunits.";
RL J. Biol. Chem. 282:294-302(2007).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RX PubMed=21606183; DOI=10.1093/cvr/cvr137;
RA Nelson C.P., Rainbow R.D., Brignell J.L., Perry M.D., Willets J.M.,
RA Davies N.W., Standen N.B., Challiss R.A.;
RT "Principal role of adenylyl cyclase 6 in K? channel regulation and
RT vasodilator signalling in vascular smooth muscle cells.";
RL Cardiovasc. Res. 91:694-702(2011).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-53 AND SER-574, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Catalyzes the formation of the signaling molecule cAMP
CC downstream of G protein-coupled receptors (PubMed:1409703,
CC PubMed:15385642, PubMed:17110384, PubMed:21606183). Functions in
CC signaling cascades downstream of beta-adrenergic receptors in the heart
CC and in vascular smooth muscle cells (PubMed:21606183). Functions in
CC signaling cascades downstream of the vasopressin receptor in the kidney
CC and has a role in renal water reabsorption. Functions in signaling
CC cascades downstream of PTH1R and plays a role in regulating renal
CC phosphate excretion. Functions in signaling cascades downstream of the
CC VIP and SCT receptors in pancreas and contributes to the regulation of
CC pancreatic amylase and fluid secretion (By similarity). Signaling
CC mediates cAMP-dependent activation of protein kinase PKA
CC (PubMed:21606183). This promotes increased phosphorylation of various
CC proteins, including AKT. Plays a role in regulating cardiac
CC sarcoplasmic reticulum Ca(2+) uptake and storage, and is required for
CC normal heart ventricular contractibility. May contribute to normal
CC heart function (By similarity). Mediates vasodilatation after
CC activation of beta-adrenergic receptors by isoproterenol (By
CC similarity). Contributes to bone cell responses to mechanical stimuli
CC (By similarity). {ECO:0000250|UniProtKB:O43306,
CC ECO:0000250|UniProtKB:Q01341, ECO:0000269|PubMed:1409703,
CC ECO:0000269|PubMed:15385642, ECO:0000269|PubMed:17110384,
CC ECO:0000269|PubMed:21606183}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP = 3',5'-cyclic AMP + diphosphate; Xref=Rhea:RHEA:15389,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:58165; EC=4.6.1.1;
CC Evidence={ECO:0000269|PubMed:1409703, ECO:0000269|PubMed:15385642,
CC ECO:0000269|PubMed:17110384, ECO:0000269|PubMed:21606183,
CC ECO:0000269|PubMed:9391159};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15385642};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:15385642, ECO:0000269|PubMed:9391159};
CC Note=Binds 2 magnesium ions per subunit. Is also active with manganese
CC (in vitro). {ECO:0000250|UniProtKB:P30803};
CC -!- ACTIVITY REGULATION: Activated by forskolin (PubMed:9391159). Inhibited
CC by calcium ions, already at micromolar concentrations (By similarity).
CC Inhibited by adenosine, AMP and their analogs (By similarity).
CC Activated by GNAS (PubMed:9391159, PubMed:17110384). Is further
CC activated by the complex formed by GNB1 and GNG2 (PubMed:17110384).
CC Phosphorylation by RAF1 results in its activation (PubMed:15385642).
CC {ECO:0000250|UniProtKB:P30804, ECO:0000250|UniProtKB:Q01341,
CC ECO:0000269|PubMed:15385642, ECO:0000269|PubMed:17110384}.
CC -!- SUBUNIT: Part of a complex containing AKAP5, ADCY5, PDE4C and PKD2 (By
CC similarity). Interacts with RAF1 (PubMed:15385642). Interacts (via
CC cytoplasmic N-terminus) with GNAS, GNB1 and GNG2 (By similarity).
CC {ECO:0000250|UniProtKB:O43306, ECO:0000250|UniProtKB:Q01341,
CC ECO:0000269|PubMed:15385642}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15385642,
CC ECO:0000269|PubMed:17110384, ECO:0000269|PubMed:9391159}; Multi-pass
CC membrane protein {ECO:0000305}. Cell projection, cilium
CC {ECO:0000250|UniProtKB:Q01341}. Cell projection, stereocilium
CC {ECO:0000250|UniProtKB:Q01341}.
CC -!- TISSUE SPECIFICITY: Detected in brain and kidney (PubMed:1409703).
CC Detected in vascular smooth muscle cells (PubMed:21606183).
CC {ECO:0000269|PubMed:1409703, ECO:0000269|PubMed:21606183}.
CC -!- DOMAIN: The protein contains two modules with six transmembrane helices
CC each; both are required for catalytic activity. Isolated N-terminal or
CC C-terminal guanylate cyclase domains have no catalytic activity, but
CC when they are brought together, enzyme activity is restored. The active
CC site is at the interface of the two domains. Both contribute substrate-
CC binding residues, but the catalytic metal ions are bound exclusively
CC via the N-terminal guanylate cyclase domain.
CC {ECO:0000250|UniProtKB:P26769}.
CC -!- PTM: Phosphorylation by RAF1 increases enzyme activity
CC (PubMed:15385642). Phosphorylation by PKA on Ser-660 inhibits the GNAS-
CC mediated increase in catalytic activity (PubMed:9391159).
CC Phosphorylation by PKC on Ser-554, Ser-660 and Thr-917 inhibits
CC catalytic activity (PubMed:11877398). {ECO:0000269|PubMed:11877398,
CC ECO:0000269|PubMed:15385642, ECO:0000269|PubMed:9391159}.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA40678.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; L01115; AAA40676.1; -; mRNA.
DR EMBL; M96160; AAA40678.1; ALT_INIT; mRNA.
DR PIR; A47202; A47202.
DR RefSeq; NP_036953.4; NM_012821.4.
DR AlphaFoldDB; Q03343; -.
DR SMR; Q03343; -.
DR IntAct; Q03343; 2.
DR STRING; 10116.ENSRNOP00000016624; -.
DR BindingDB; Q03343; -.
DR ChEMBL; CHEMBL2095179; -.
DR DrugCentral; Q03343; -.
DR GlyGen; Q03343; 2 sites.
DR iPTMnet; Q03343; -.
DR PhosphoSitePlus; Q03343; -.
DR SwissPalm; Q03343; -.
DR PaxDb; Q03343; -.
DR PRIDE; Q03343; -.
DR GeneID; 25289; -.
DR KEGG; rno:25289; -.
DR UCSC; RGD:2035; rat.
DR CTD; 112; -.
DR RGD; 2035; Adcy6.
DR eggNOG; KOG3619; Eukaryota.
DR InParanoid; Q03343; -.
DR PhylomeDB; Q03343; -.
DR Reactome; R-RNO-163615; PKA activation.
DR Reactome; R-RNO-170660; Adenylate cyclase activating pathway.
DR Reactome; R-RNO-170670; Adenylate cyclase inhibitory pathway.
DR Reactome; R-RNO-400042; Adrenaline,noradrenaline inhibits insulin secretion.
DR Reactome; R-RNO-418597; G alpha (z) signalling events.
DR Reactome; R-RNO-5610787; Hedgehog 'off' state.
DR PRO; PR:Q03343; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005929; C:cilium; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; IDA:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:BHF-UCL.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0031528; C:microvillus membrane; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0032420; C:stereocilium; IEA:UniProtKB-SubCell.
DR GO; GO:0004016; F:adenylate cyclase activity; IDA:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008294; F:calcium- and calmodulin-responsive adenylate cyclase activity; IDA:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019901; F:protein kinase binding; IPI:BHF-UCL.
DR GO; GO:0005080; F:protein kinase C binding; ISO:RGD.
DR GO; GO:0097110; F:scaffold protein binding; ISO:RGD.
DR GO; GO:0005102; F:signaling receptor binding; IPI:RGD.
DR GO; GO:0000149; F:SNARE binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0097746; P:blood vessel diameter maintenance; ISO:RGD.
DR GO; GO:0006171; P:cAMP biosynthetic process; IDA:RGD.
DR GO; GO:0071870; P:cellular response to catecholamine stimulus; ISO:RGD.
DR GO; GO:1904322; P:cellular response to forskolin; ISS:UniProtKB.
DR GO; GO:0071380; P:cellular response to prostaglandin E stimulus; ISO:RGD.
DR GO; GO:1904117; P:cellular response to vasopressin; ISS:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; IEP:RGD.
DR GO; GO:0007212; P:dopamine receptor signaling pathway; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0072660; P:maintenance of protein location in plasma membrane; IMP:ParkinsonsUK-UCL.
DR GO; GO:0010977; P:negative regulation of neuron projection development; IMP:ParkinsonsUK-UCL.
DR GO; GO:0035811; P:negative regulation of urine volume; ISS:UniProtKB.
DR GO; GO:0003091; P:renal water homeostasis; ISS:UniProtKB.
DR CDD; cd07302; CHD; 1.
DR Gene3D; 3.30.70.1230; -; 2.
DR InterPro; IPR001054; A/G_cyclase.
DR InterPro; IPR018297; A/G_cyclase_CS.
DR InterPro; IPR032628; AC_N.
DR InterPro; IPR030672; Adcy.
DR InterPro; IPR009398; Adcy_conserved_dom.
DR InterPro; IPR029787; Nucleotide_cyclase.
DR Pfam; PF16214; AC_N; 1.
DR Pfam; PF06327; DUF1053; 1.
DR Pfam; PF00211; Guanylate_cyc; 2.
DR PIRSF; PIRSF039050; Ade_cyc; 1.
DR SMART; SM00044; CYCc; 2.
DR SUPFAM; SSF55073; SSF55073; 2.
DR PROSITE; PS00452; GUANYLATE_CYCLASE_1; 2.
DR PROSITE; PS50125; GUANYLATE_CYCLASE_2; 2.
PE 1: Evidence at protein level;
KW ATP-binding; cAMP biosynthesis; Cell membrane; Cell projection; Cilium;
KW Glycoprotein; Lyase; Magnesium; Manganese; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..1166
FT /note="Adenylate cyclase type 6"
FT /id="PRO_0000195701"
FT TOPO_DOM 1..149
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 150..166
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 179..195
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 212..228
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 237..253
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 257..273
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 287..303
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 304..671
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 672..689
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 700..716
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 741..757
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 758..817
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 818..834
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 837..853
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 895..911
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 912..1166
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT BINDING 382..387
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 382
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 382
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 383
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 424..426
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 426
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 426
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 470
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 1029
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1103..1105
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1110..1114
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1150
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT MOD_RES 53
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 554
FT /note="Phosphoserine; by PKC; in vitro"
FT /evidence="ECO:0000269|PubMed:11877398"
FT MOD_RES 574
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 660
FT /note="Phosphoserine; by PKA; in vitro"
FT /evidence="ECO:0000269|PubMed:9391159"
FT MOD_RES 660
FT /note="Phosphoserine; by PKC; in vitro"
FT /evidence="ECO:0000269|PubMed:11877398"
FT MOD_RES 917
FT /note="Phosphothreonine; by PKC; in vitro"
FT /evidence="ECO:0000269|PubMed:11877398"
FT CARBOHYD 791
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 876
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 311
FT /note="S->A: No effect on phosphorylation by PKC."
FT /evidence="ECO:0000269|PubMed:11877398"
FT MUTAGEN 554
FT /note="S->A: Reduces phosphorylation by PKC and PKC-
FT mediated inhibition."
FT /evidence="ECO:0000269|PubMed:11877398"
FT MUTAGEN 660
FT /note="S->A: Abolishes phosphorylation by PKA and PKA-
FT mediated down-regulation of enzyme activity."
FT /evidence="ECO:0000269|PubMed:9391159"
FT MUTAGEN 660
FT /note="S->A: Reduces phosphorylation by PKC and PKC-
FT mediated inhibition."
FT /evidence="ECO:0000269|PubMed:11877398"
FT MUTAGEN 917
FT /note="T->A: Reduces phosphorylation by PKC, abolishes PKC-
FT mediated inhibition."
FT /evidence="ECO:0000269|PubMed:11877398"
FT CONFLICT 80
FT /note="K -> E (in Ref. 2; AAA40678)"
FT /evidence="ECO:0000305"
FT CONFLICT 130
FT /note="R -> P (in Ref. 2; AAA40678)"
FT /evidence="ECO:0000305"
FT CONFLICT 538
FT /note="G -> A (in Ref. 2; AAA40678)"
FT /evidence="ECO:0000305"
FT CONFLICT 790
FT /note="I -> L (in Ref. 2; AAA40678)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1166 AA; 130506 MW; 5042C650546E4E79 CRC64;
MSWFSGLLVP KVDERKTAWG ERNGQKRPRQ ATRARGFCAP RYMSCLKNVE PPSPTPAART
RCPWQDEAFI RRAGPGRGVK LGLRSVALGF DDTEVTTPMG TAEVAPDTSP RSGPSCWHRL
AQVFQSKQFR SAKLERLYQR YFFQMNQSSL TLLMAVLVLL MAVLLTFHAA PALPQPAYVA
LLTCASVLFV VLMVVCNRHS FRQDSMWVVS YVVLGILAAV QVGGALAANP RSPSAGLWCP
VFFVYITYTL LPIRMRAAVL SGLGLSTLHL ILAWHLNNGD PFLWKQLGAN VVLFLCTNAI
GVCTHYPAEV SQRQAFQETR GYIQARLHLQ HENRQQERLL LSVLPQHVAM EMKEDINTKK
EDMMFHKIYI QKHDNVSILF ADIEGFTSLA SQCTAQELVM TLNELFARFD KLAAENHCLR
IKILGDCYYC VSGLPEARAD HAHCCVEMGV DMIEAISLVR EVTGVNVNMR VGIHSGRVHC
GVLGLRKWQF DVWSNDVTLA NHMEAGGRAG RIHITRATLQ YLNGDYEVEP GRGGERNGYL
KEQCIETFLI LGASQKRKEE KAMLVKLQRT RANSMEGLMP RWVPDRAFSR TKDSKAFRQM
GIDDSSKENR GAQDALNPED EVDEFLGRAI DARSIDQLRK DHVRRFLLTF QREDLEKKYS
RKVDPRFGAY VACALLVFCF ICFIQFLVFP HSALILGIYA GIFLLLLVTV LICAVCSCGS
FFPNALQRLS RSIVRSRVHS TAVGVFSVLL VFISAIANMF TCSHTPLRTC AARMLNLTPS
DVTACHLRQI NYSLGLEAPL CEGTAPTCSF PEYFVGSVLL SLLASSVFLH ISSIGKLVMT
FVLGFIYLLL LLLGPPATIF DNYDLLLSVH GLASSNETFD GLDCPAVGRV ALKYMTPVIL
LVFALALYLH AQQVESTARL DFLWKLQATG EKEEMEELQA YNRRLLHNIL PKDVAAHFLA
RERRNDELYY QSCECVAVMF ASIANFSEFY VELEANNEGV ECLRLLNEII ADFDEIISEE
RFRQLEKIKT IGSTYMAASG LNASTYDQVG RSHITALADY AMRLMEQMKH INEHSFNNFQ
MKIGLNMGPV VAGVIGARKP QYDIWGNTVN VSSRMDSTGV PDRIQVTTDL YQVLAAKGYQ
LECRGVVKVK GKGEMTTYFL NGGPSS
