ARBK1_BOVIN
ID ARBK1_BOVIN Reviewed; 689 AA.
AC P21146;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 1.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Beta-adrenergic receptor kinase 1;
DE Short=Beta-ARK-1;
DE EC=2.7.11.15 {ECO:0000250|UniProtKB:P26817};
DE AltName: Full=G-protein-coupled receptor kinase 2 {ECO:0000250|UniProtKB:P25098};
GN Name=GRK2 {ECO:0000250|UniProtKB:P25098}; Synonyms=ADRBK1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND TISSUE
RP SPECIFICITY.
RX PubMed=2552582; DOI=10.1126/science.2552582;
RA Benovic J.L., Deblasi A., Stone W.C., Caron M.G., Lefkowitz R.J.;
RT "Beta-adrenergic receptor kinase: primary structure delineates a multigene
RT family.";
RL Science 246:235-240(1989).
RN [2]
RP INTERACTION WITH GIT1.
RX PubMed=9826657; DOI=10.1073/pnas.95.24.14082;
RA Premont R.T., Claing A., Vitale N., Freeman J.L.R., Pitcher J.A.,
RA Patton W.A., Moss J., Vaughan M., Lefkowitz R.J.;
RT "Beta2-adrenergic receptor regulation by GIT1, a G protein-coupled receptor
RT kinase-associated ADP ribosylation factor GTPase-activating protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:14082-14087(1998).
RN [3]
RP MUTAGENESIS OF THR-353.
RX PubMed=15157420; DOI=10.1016/s0896-6273(04)00252-1;
RA Fukuto H.S., Ferkey D.M., Apicella A.J., Lans H., Sharmeen T., Chen W.,
RA Lefkowitz R.J., Jansen G., Schafer W.R., Hart A.C.;
RT "G protein-coupled receptor kinase function is essential for chemosensation
RT in C. elegans.";
RL Neuron 42:581-593(2004).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21659505; DOI=10.1074/jbc.m111.234666;
RA Evron T., Philipp M., Lu J., Meloni A.R., Burkhalter M., Chen W.,
RA Caron M.G.;
RT "Growth arrest specific 8 (Gas8) and G protein-coupled receptor kinase 2
RT (GRK2) cooperate in the control of Smoothened signaling.";
RL J. Biol. Chem. 286:27676-27686(2011).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH GNB1 AND GNG2,
RP SUBCELLULAR LOCATION, PH DOMAIN, AND ACTIVITY REGULATION.
RX PubMed=12764189; DOI=10.1126/science.1082348;
RA Lodowski D.T., Pitcher J.A., Capel W.D., Lefkowitz R.J., Tesmer J.J.;
RT "Keeping G proteins at bay: a complex between G protein-coupled receptor
RT kinase 2 and Gbetagamma.";
RL Science 300:1256-1262(2003).
CC -!- FUNCTION: Specifically phosphorylates the agonist-occupied form of the
CC beta-adrenergic and closely related receptors, probably inducing a
CC desensitization of them (By similarity). Key regulator of LPAR1
CC signaling (By similarity). Competes with RALA for binding to LPAR1 thus
CC affecting the signaling properties of the receptor (By similarity).
CC Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner
CC (By similarity). Positively regulates ciliary smoothened (SMO)-
CC dependent Hedgehog (Hh) signaling pathway by facilitating the
CC trafficking of SMO into the cilium and the stimulation of SMO activity
CC (PubMed:21659505). Inhibits relaxation of airway smooth muscle in
CC response to blue light (By similarity). {ECO:0000250|UniProtKB:P25098,
CC ECO:0000250|UniProtKB:Q99MK8, ECO:0000269|PubMed:21659505}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[beta-adrenergic receptor] + ATP = [beta-adrenergic receptor]-
CC phosphate + ADP + H(+); Xref=Rhea:RHEA:19429, Rhea:RHEA-COMP:11222,
CC Rhea:RHEA-COMP:11223, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43176, ChEBI:CHEBI:68546, ChEBI:CHEBI:456216;
CC EC=2.7.11.15; Evidence={ECO:0000250|UniProtKB:P26817};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19430;
CC Evidence={ECO:0000250|UniProtKB:P26817};
CC -!- ACTIVITY REGULATION: In contrast to other AGC family kinases, the
CC catalytic activity is solely regulated by the binding of substrates and
CC ligands, not by phosphorylation of the kinase domain.
CC {ECO:0000269|PubMed:12764189}.
CC -!- SUBUNIT: Interacts with the heterodimer formed by GNB1 and GNG2
CC (PubMed:12764189). Interacts with GIT1 (PubMed:9826657). Interacts
CC with, and phosphorylates chemokine-stimulated CCR5 (By similarity).
CC Interacts with ARRB1 (By similarity). Interacts with LPAR1 and LPAR2
CC (By similarity). Interacts with RALA in response to LPAR1 activation
CC (By similarity). ADRBK1 and RALA mutually inhibit each other's binding
CC to LPAR1 (By similarity). Interacts with ADRB2 (By similarity).
CC {ECO:0000250|UniProtKB:P25098, ECO:0000269|PubMed:12764189,
CC ECO:0000269|PubMed:9826657}.
CC -!- INTERACTION:
CC P21146; Q9UBN7: HDAC6; Xeno; NbExp=3; IntAct=EBI-1036401, EBI-301697;
CC P21146; Q9Z2V5: Hdac6; Xeno; NbExp=2; IntAct=EBI-1036401, EBI-1009256;
CC P21146; Q13635: PTCH1; Xeno; NbExp=4; IntAct=EBI-1036401, EBI-8775406;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12764189,
CC ECO:0000269|PubMed:21659505}. Cell membrane
CC {ECO:0000269|PubMed:12764189}. Postsynapse
CC {ECO:0000250|UniProtKB:P26817}. Presynapse
CC {ECO:0000250|UniProtKB:P26817}.
CC -!- TISSUE SPECIFICITY: Ubiquitous; brain, spleen > heart, lung > kidney.
CC {ECO:0000269|PubMed:2552582}.
CC -!- DOMAIN: The PH domain binds anionic phospholipids and helps recruiting
CC ADRBK1 from the cytoplasm to plasma membrane close to activated
CC receptors. It mediates binding to G protein beta and gamma subunits,
CC competing with G-alpha subunits and other G-betagamma effectors.
CC {ECO:0000269|PubMed:12764189}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. GPRK subfamily. {ECO:0000305}.
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DR EMBL; M34019; AAA30384.1; -; mRNA.
DR PIR; A40088; A40088.
DR RefSeq; NP_777135.1; NM_174710.2.
DR PDB; 1OMW; X-ray; 2.50 A; A=1-689.
DR PDB; 1YM7; X-ray; 4.50 A; A/B/C/D=1-689.
DR PDB; 2BCJ; X-ray; 3.06 A; A=1-689.
DR PDB; 3PSC; X-ray; 2.67 A; A=1-689.
DR PDB; 3PVU; X-ray; 2.48 A; A=1-689.
DR PDB; 3PVW; X-ray; 2.49 A; A=1-689.
DR PDB; 3UZS; X-ray; 4.52 A; A=1-681.
DR PDB; 3UZT; X-ray; 3.51 A; A=1-689.
DR PDB; 5HE0; X-ray; 2.56 A; A=30-670.
DR PDB; 5HE2; X-ray; 2.79 A; A=30-670.
DR PDB; 5HE3; X-ray; 2.74 A; A=30-670.
DR PDB; 5UKM; X-ray; 3.03 A; A=1-689.
DR PDBsum; 1OMW; -.
DR PDBsum; 1YM7; -.
DR PDBsum; 2BCJ; -.
DR PDBsum; 3PSC; -.
DR PDBsum; 3PVU; -.
DR PDBsum; 3PVW; -.
DR PDBsum; 3UZS; -.
DR PDBsum; 3UZT; -.
DR PDBsum; 5HE0; -.
DR PDBsum; 5HE2; -.
DR PDBsum; 5HE3; -.
DR PDBsum; 5UKM; -.
DR AlphaFoldDB; P21146; -.
DR SMR; P21146; -.
DR BioGRID; 159836; 4.
DR DIP; DIP-37856N; -.
DR IntAct; P21146; 5.
DR MINT; P21146; -.
DR STRING; 9913.ENSBTAP00000050806; -.
DR BindingDB; P21146; -.
DR ChEMBL; CHEMBL3711550; -.
DR iPTMnet; P21146; -.
DR PaxDb; P21146; -.
DR PRIDE; P21146; -.
DR Ensembl; ENSBTAT00000055962; ENSBTAP00000050806; ENSBTAG00000005832.
DR GeneID; 282682; -.
DR KEGG; bta:282682; -.
DR CTD; 156; -.
DR VEuPathDB; HostDB:ENSBTAG00000005832; -.
DR VGNC; VGNC:56266; GRK2.
DR eggNOG; KOG0986; Eukaryota.
DR GeneTree; ENSGT00940000161626; -.
DR HOGENOM; CLU_000288_63_41_1; -.
DR InParanoid; P21146; -.
DR OMA; FIQRSPN; -.
DR OrthoDB; 1104340at2759; -.
DR BRENDA; 2.7.11.15; 908.
DR EvolutionaryTrace; P21146; -.
DR Proteomes; UP000009136; Chromosome 29.
DR Bgee; ENSBTAG00000005832; Expressed in temporal cortex and 106 other tissues.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:BHF-UCL.
DR GO; GO:0016020; C:membrane; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0098794; C:postsynapse; IEA:UniProtKB-SubCell.
DR GO; GO:0098793; C:presynapse; IEA:UniProtKB-SubCell.
DR GO; GO:0031694; F:alpha-2A adrenergic receptor binding; IPI:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0047696; F:beta-adrenergic receptor kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0031755; F:Edg-2 lysophosphatidic acid receptor binding; ISS:UniProtKB.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IBA:GO_Central.
DR GO; GO:0004703; F:G protein-coupled receptor kinase activity; IDA:BHF-UCL.
DR GO; GO:0004672; F:protein kinase activity; IDA:CAFA.
DR GO; GO:0060048; P:cardiac muscle contraction; IMP:BHF-UCL.
DR GO; GO:0002029; P:desensitization of G protein-coupled receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0007213; P:G protein-coupled acetylcholine receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0002031; P:G protein-coupled receptor internalization; IDA:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISS:AgBase.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0006886; P:intracellular protein transport; IMP:BHF-UCL.
DR GO; GO:1901081; P:negative regulation of relaxation of smooth muscle; ISS:UniProtKB.
DR GO; GO:0045988; P:negative regulation of striated muscle contraction; IMP:BHF-UCL.
DR GO; GO:0003108; P:negative regulation of the force of heart contraction by chemical signal; IMP:BHF-UCL.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IEA:Ensembl.
DR GO; GO:1903566; P:positive regulation of protein localization to cilium; IMP:UniProtKB.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:CAFA.
DR GO; GO:0009966; P:regulation of signal transduction; IMP:BHF-UCL.
DR GO; GO:0002026; P:regulation of the force of heart contraction; IBA:GO_Central.
DR GO; GO:0007217; P:tachykinin receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0046718; P:viral entry into host cell; IEA:Ensembl.
DR GO; GO:0019079; P:viral genome replication; IEA:Ensembl.
DR Gene3D; 1.10.167.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR000239; GPCR_kinase.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR016137; RGS.
DR InterPro; IPR036305; RGS_sf.
DR InterPro; IPR044926; RGS_subdomain_2.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00615; RGS; 1.
DR PRINTS; PR00717; GPCRKINASE.
DR SMART; SM00233; PH; 1.
DR SMART; SM00315; RGS; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF48097; SSF48097; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS50132; RGS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell membrane; Cell projection; Cytoplasm;
KW Direct protein sequencing; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Synapse; Transferase.
FT CHAIN 1..689
FT /note="Beta-adrenergic receptor kinase 1"
FT /id="PRO_0000085626"
FT DOMAIN 54..175
FT /note="RGS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00171"
FT DOMAIN 191..453
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 454..521
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT DOMAIN 558..652
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 1..190
FT /note="N-terminal"
FT REGION 454..689
FT /note="C-terminal"
FT ACT_SITE 317
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 197..205
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 220
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 3
FT /note="Required for receptor phosphorylation"
FT /evidence="ECO:0000250|UniProtKB:P25098"
FT SITE 4
FT /note="Required for receptor phosphorylation"
FT /evidence="ECO:0000250|UniProtKB:P25098"
FT SITE 10
FT /note="Required for receptor phosphorylation"
FT /evidence="ECO:0000250|UniProtKB:P25098"
FT MOD_RES 670
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P25098"
FT MUTAGEN 353
FT /note="T->I: Dramatic increase in GRK2 protein levels."
FT /evidence="ECO:0000269|PubMed:15157420"
FT HELIX 39..48
FT /evidence="ECO:0007829|PDB:3PVU"
FT TURN 49..51
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 55..59
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 62..75
FT /evidence="ECO:0007829|PDB:3PVU"
FT TURN 77..79
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 80..93
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 98..112
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 114..118
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 126..137
FT /evidence="ECO:0007829|PDB:3PVU"
FT TURN 143..146
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 147..158
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 160..167
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 169..182
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 188..190
FT /evidence="ECO:0007829|PDB:5HE0"
FT STRAND 191..199
FT /evidence="ECO:0007829|PDB:3PVU"
FT STRAND 201..210
FT /evidence="ECO:0007829|PDB:3PVU"
FT TURN 211..213
FT /evidence="ECO:0007829|PDB:3PVU"
FT STRAND 216..223
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 224..230
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 233..244
FT /evidence="ECO:0007829|PDB:3PVU"
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:3PVU"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:3PVU"
FT STRAND 257..262
FT /evidence="ECO:0007829|PDB:3PVU"
FT STRAND 264..272
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 279..286
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 291..310
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 320..322
FT /evidence="ECO:0007829|PDB:3PVU"
FT STRAND 323..325
FT /evidence="ECO:0007829|PDB:3PVU"
FT STRAND 327..329
FT /evidence="ECO:0007829|PDB:1OMW"
FT STRAND 331..333
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 336..338
FT /evidence="ECO:0007829|PDB:5HE2"
FT STRAND 343..345
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 354..356
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 359..362
FT /evidence="ECO:0007829|PDB:3PVU"
FT STRAND 363..365
FT /evidence="ECO:0007829|PDB:5HE0"
FT HELIX 371..386
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 393..395
FT /evidence="ECO:0007829|PDB:5HE3"
FT HELIX 399..406
FT /evidence="ECO:0007829|PDB:3PVU"
FT STRAND 415..417
FT /evidence="ECO:0007829|PDB:1OMW"
FT HELIX 419..428
FT /evidence="ECO:0007829|PDB:3PVU"
FT TURN 433..435
FT /evidence="ECO:0007829|PDB:3PVU"
FT TURN 437..439
FT /evidence="ECO:0007829|PDB:3PVU"
FT STRAND 440..442
FT /evidence="ECO:0007829|PDB:3PVW"
FT HELIX 444..448
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 451..453
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 458..462
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 502..504
FT /evidence="ECO:0007829|PDB:3PVU"
FT TURN 505..508
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 514..522
FT /evidence="ECO:0007829|PDB:3PVU"
FT TURN 523..525
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 526..546
FT /evidence="ECO:0007829|PDB:3PVU"
FT TURN 553..558
FT /evidence="ECO:0007829|PDB:3PVU"
FT STRAND 561..567
FT /evidence="ECO:0007829|PDB:3PVU"
FT TURN 571..573
FT /evidence="ECO:0007829|PDB:5HE0"
FT STRAND 577..584
FT /evidence="ECO:0007829|PDB:3PVU"
FT STRAND 587..591
FT /evidence="ECO:0007829|PDB:3PVU"
FT STRAND 593..595
FT /evidence="ECO:0007829|PDB:3PVU"
FT STRAND 599..602
FT /evidence="ECO:0007829|PDB:3PVU"
FT TURN 603..605
FT /evidence="ECO:0007829|PDB:3PVU"
FT STRAND 606..614
FT /evidence="ECO:0007829|PDB:3PVU"
FT STRAND 617..624
FT /evidence="ECO:0007829|PDB:3PVU"
FT TURN 625..627
FT /evidence="ECO:0007829|PDB:3PVW"
FT STRAND 629..633
FT /evidence="ECO:0007829|PDB:3PVU"
FT HELIX 637..660
FT /evidence="ECO:0007829|PDB:3PVU"
FT TURN 662..664
FT /evidence="ECO:0007829|PDB:3PVU"
SQ SEQUENCE 689 AA; 79647 MW; 4AB95DB5E630B9DA CRC64;
MADLEAVLAD VSYLMAMEKS KATPAARASK KILLPEPSIR SVMQKYLEDR GEVTFEKIFS
QKLGYLLFRD FCLKHLEEAK PLVEFYEEIK KYEKLETEEE RLVCSREIFD TYIMKELLAC
SHPFSKSAIE HVQGHLVKKQ VPPDLFQPYI EEICQNLRGD VFQKFIESDK FTRFCQWKNV
ELNIHLTMND FSVHRIIGRG GFGEVYGCRK ADTGKMYAMK CLDKKRIKMK QGETLALNER
IMLSLVSTGD CPFIVCMSYA FHTPDKLSFI LDLMNGGDLH YHLSQHGVFS EADMRFYAAE
IILGLEHMHN RFVVYRDLKP ANILLDEHGH VRISDLGLAC DFSKKKPHAS VGTHGYMAPE
VLQKGVAYDS SADWFSLGCM LFKLLRGHSP FRQHKTKDKH EIDRMTLTMA VELPDSFSPE
LRSLLEGLLQ RDVNRRLGCL GRGAQEVKES PFFRSLDWQM VFLQKYPPPL IPPRGEVNAA
DAFDIGSFDE EDTKGIKLLD SDQELYRNFP LTISERWQQE VAETVFDTIN AETDRLEARK
KTKNKQLGHE EDYALGKDCI MHGYMSKMGN PFLTQWQRRY FYLFPNRLEW RGEGEAPQSL
LTMEEIQSVE ETQIKERKCL LLKIRGGKQF VLQCDSDPEL VQWKKELRDA YREAQQLVQR
VPKMKNKPRS PVVELSKVPL IQRGSANGL
