HXK4_RAT
ID HXK4_RAT Reviewed; 465 AA.
AC P17712; P17711;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 2.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Hexokinase-4 {ECO:0000305};
DE Short=HK4 {ECO:0000305};
DE EC=2.7.1.1 {ECO:0000269|PubMed:12513690, ECO:0000269|PubMed:6477520};
DE AltName: Full=Glucokinase {ECO:0000303|PubMed:2909525};
DE AltName: Full=Hexokinase type IV {ECO:0000303|PubMed:6477520};
DE Short=HK IV {ECO:0000303|PubMed:6477520};
DE AltName: Full=Hexokinase-D {ECO:0000303|PubMed:6477520};
GN Name=Gck {ECO:0000312|RGD:2670};
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] (ISOFORM 3), AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Liver;
RX PubMed=2909525; DOI=10.1016/s0021-9258(17)31266-8;
RA Andreone T.L., Printz R.L., Pilkis S.J., Magnuson M.A., Granner D.K.;
RT "The amino acid sequence of rat liver glucokinase deduced from cloned
RT cDNA.";
RL J. Biol. Chem. 264:363-369(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND ALTERNATIVE SPLICING.
RC TISSUE=Liver;
RX PubMed=2396986; DOI=10.1042/bj2700261;
RA Hayzer D.J., Iynedjian P.B.;
RT "Alternative splicing of glucokinase mRNA in rat liver.";
RL Biochem. J. 270:261-263(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-15 (ISOFORM 1).
RC TISSUE=Pancreas;
RX PubMed=2550428; DOI=10.1016/s0021-9258(18)71569-x;
RA Magnuson M.A., Shelton K.D.;
RT "An alternate promoter in the glucokinase gene is active in the pancreatic
RT beta cell.";
RL J. Biol. Chem. 264:15936-15942(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-15 (ISOFORM 3).
RX PubMed=2662183; DOI=10.1073/pnas.86.13.4838;
RA Magnuson M.A., Andeone T.L., Printz R.L., Koch S., Granner D.K.;
RT "Rat glucokinase gene: structure and regulation by insulin.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:4838-4842(1989).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-15 (ISOFORM 3).
RX PubMed=2590200; DOI=10.1016/0006-291x(89)91803-2;
RA Noguchi T., Takenaka M., Yamada K., Matsuda T., Hashimoto M., Tanaka T.;
RT "Characterization of the 5' flanking region of rat glucokinase gene.";
RL Biochem. Biophys. Res. Commun. 164:1247-1252(1989).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-166 (ISOFORM 1).
RX PubMed=1999433; DOI=10.1016/s0021-9258(20)64354-x;
RA Hughes S.D., Quaade C., Milburn J.L., Cassidy L., Newgard C.B.;
RT "Expression of normal and novel glucokinase mRNAs in anterior pituitary and
RT islet cells.";
RL J. Biol. Chem. 266:4521-4530(1991).
RN [7]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=6477520; DOI=10.1042/bj2220363;
RA Cardenas M.L., Rabajille E., Niemeyer H.;
RT "Fructose is a good substrate for rat liver 'glucokinase' (hexokinase D).";
RL Biochem. J. 222:363-370(1984).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=3515342; DOI=10.1073/pnas.83.7.1998;
RA Iynedjian P.B., Moebius G., Seitz H.J., Wollheim C.B., Renold A.E.;
RT "Tissue-specific expression of glucokinase: identification of the gene
RT product in liver and pancreatic islets.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:1998-2001(1986).
RN [9]
RP ACTIVITY REGULATION, INTERACTION WITH GCKR, AND SUBCELLULAR LOCATION.
RX PubMed=10456334; DOI=10.1016/s0014-5793(99)00971-0;
RA de la Iglesia N., Veiga-da-Cunha M., Van Schaftingen E., Guinovart J.J.,
RA Ferrer J.C.;
RT "Glucokinase regulatory protein is essential for the proper subcellular
RT localisation of liver glucokinase.";
RL FEBS Lett. 456:332-338(1999).
RN [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=12513690; DOI=10.1042/bj20020728;
RA Monasterio O., Cardenas M.L.;
RT "Kinetic studies of rat liver hexokinase D ('glucokinase') in non-co-
RT operative conditions show an ordered mechanism with MgADP as the last
RT product to be released.";
RL Biochem. J. 371:29-38(2003).
RN [11]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH GCKR.
RX PubMed=16542652; DOI=10.1016/j.febslet.2006.03.009;
RA Arden C., Baltrusch S., Agius L.;
RT "Glucokinase regulatory protein is associated with mitochondria in
RT hepatocytes.";
RL FEBS Lett. 580:2065-2070(2006).
RN [12]
RP INTERACTION WITH MIDN, AND FUNCTION.
RX PubMed=24187134; DOI=10.1074/jbc.m113.526632;
RA Hofmeister-Brix A., Kollmann K., Langer S., Schultz J., Lenzen S.,
RA Baltrusch S.;
RT "Identification of the ubiquitin-like domain of midnolin as a new
RT glucokinase interaction partner.";
RL J. Biol. Chem. 288:35824-35839(2013).
CC -!- FUNCTION: Catalyzes the phosphorylation of hexose, such as D-glucose,
CC D-fructose and D-mannose, to hexose 6-phosphate (D-glucose 6-phosphate,
CC D-fructose 6-phosphate and D-mannose 6-phosphate, respectively)
CC (PubMed:6477520, PubMed:12513690, PubMed:24187134). Compared to other
CC hexokinases, has a weak affinity for D-glucose, and is effective only
CC when glucose is abundant (PubMed:6477520). Mainly expressed in
CC pancreatic beta cells and the liver and constitutes a rate-limiting
CC step in glucose metabolism in these tissues (By similarity). Since
CC insulin secretion parallels glucose metabolism and the low glucose
CC affinity of GCK ensures that it can change its enzymatic activity
CC within the physiological range of glucose concentrations, GCK acts as a
CC glucose sensor in the pancreatic beta cell (By similarity). In
CC pancreas, plays an important role in modulating insulin secretion (By
CC similarity). In liver, helps to facilitate the uptake and conversion of
CC glucose by acting as an insulin-sensitive determinant of hepatic
CC glucose usage (By similarity). Required to provide D-glucose 6-
CC phosphate for the synthesis of glycogen (By similarity). Mediates the
CC initial step of glycolysis by catalyzing phosphorylation of D-glucose
CC to D-glucose 6-phosphate (PubMed:6477520, PubMed:12513690).
CC {ECO:0000250|UniProtKB:P52792, ECO:0000269|PubMed:12513690,
CC ECO:0000269|PubMed:24187134, ECO:0000269|PubMed:6477520}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + D-hexose = ADP + D-hexose 6-phosphate + H(+);
CC Xref=Rhea:RHEA:22740, ChEBI:CHEBI:4194, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61567, ChEBI:CHEBI:456216; EC=2.7.1.1;
CC Evidence={ECO:0000269|PubMed:12513690, ECO:0000269|PubMed:6477520};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22741;
CC Evidence={ECO:0000269|PubMed:12513690, ECO:0000269|PubMed:6477520};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + D-fructose = ADP + D-fructose 6-phosphate + H(+);
CC Xref=Rhea:RHEA:16125, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:37721, ChEBI:CHEBI:61527, ChEBI:CHEBI:456216; EC=2.7.1.1;
CC Evidence={ECO:0000269|PubMed:6477520};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16126;
CC Evidence={ECO:0000269|PubMed:6477520};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + D-glucose = ADP + D-glucose 6-phosphate + H(+);
CC Xref=Rhea:RHEA:17825, ChEBI:CHEBI:4167, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61548, ChEBI:CHEBI:456216; EC=2.7.1.1;
CC Evidence={ECO:0000269|PubMed:12513690, ECO:0000269|PubMed:6477520};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17826;
CC Evidence={ECO:0000269|PubMed:12513690, ECO:0000269|PubMed:6477520};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + D-mannose = ADP + D-mannose 6-phosphate + H(+);
CC Xref=Rhea:RHEA:11028, ChEBI:CHEBI:4208, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:58735, ChEBI:CHEBI:456216; EC=2.7.1.1;
CC Evidence={ECO:0000250|UniProtKB:P35557};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11029;
CC Evidence={ECO:0000250|UniProtKB:P35557};
CC -!- ACTIVITY REGULATION: Subject to allosteric regulation (By similarity).
CC Low glucose and high fructose-6-phosphate triggers association with the
CC inhibitor GCKR followed by sequestration in the nucleus
CC (PubMed:10456334). {ECO:0000250|UniProtKB:P35557,
CC ECO:0000269|PubMed:10456334}.
CC -!- PATHWAY: Carbohydrate metabolism; hexose metabolism.
CC {ECO:0000305|PubMed:12513690, ECO:0000305|PubMed:6477520}.
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC phosphate and glycerone phosphate from D-glucose: step 1/4.
CC {ECO:0000305|PubMed:12513690, ECO:0000305|PubMed:6477520}.
CC -!- SUBUNIT: Monomer (By similarity). Interacts with MIDN; the interaction
CC occurs preferentially at low glucose levels and results in inhibition
CC of hexokinase activity (PubMed:24187134). Interacts with GCKR; leading
CC to sequestration in the nucleus (PubMed:10456334, PubMed:16542652).
CC {ECO:0000250|UniProtKB:P35557, ECO:0000269|PubMed:10456334,
CC ECO:0000269|PubMed:16542652, ECO:0000269|PubMed:24187134}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10456334,
CC ECO:0000269|PubMed:16542652}. Nucleus {ECO:0000269|PubMed:10456334}.
CC Mitochondrion {ECO:0000269|PubMed:16542652}. Note=Under low glucose
CC concentrations, associates with GCKR and the inactive complex is
CC recruited to the hepatocyte nucleus. {ECO:0000269|PubMed:10456334}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=3;
CC Comment=A number of isoforms are produced by alternative promoter
CC usage. The use of alternative promoters apparently enables the type
CC IV hexokinase gene to be regulated by insulin in the liver and
CC glucose in the beta cell. This may constitute an important feedback
CC loop for maintaining glucose homeostasis.
CC {ECO:0000250|UniProtKB:P35557};
CC Name=1;
CC IsoId=P17712-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P17712-2; Sequence=VSP_002078;
CC Name=3;
CC IsoId=P17712-3; Sequence=VSP_002077;
CC -!- TISSUE SPECIFICITY: Expression is restricted to the liver and
CC pancreatic islets (at protein level). {ECO:0000269|PubMed:3515342}.
CC -!- SIMILARITY: Belongs to the hexokinase family. {ECO:0000255|PROSITE-
CC ProRule:PRU01084, ECO:0000305}.
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DR EMBL; J04218; AAA41229.1; -; mRNA.
DR EMBL; M24952; AAA41230.1; -; Genomic_DNA.
DR EMBL; M24943; AAA41230.1; JOINED; Genomic_DNA.
DR EMBL; M24944; AAA41230.1; JOINED; Genomic_DNA.
DR EMBL; M24945; AAA41230.1; JOINED; Genomic_DNA.
DR EMBL; M24947; AAA41230.1; JOINED; Genomic_DNA.
DR EMBL; M24948; AAA41230.1; JOINED; Genomic_DNA.
DR EMBL; M24949; AAA41230.1; JOINED; Genomic_DNA.
DR EMBL; M24950; AAA41230.1; JOINED; Genomic_DNA.
DR EMBL; M24951; AAA41230.1; JOINED; Genomic_DNA.
DR EMBL; M25806; AAA41238.1; -; Genomic_DNA.
DR EMBL; M25807; AAA41239.1; -; mRNA.
DR EMBL; M58759; AAA41236.1; -; mRNA.
DR EMBL; X53588; CAA37657.1; -; mRNA.
DR EMBL; X53590; CAA37660.1; -; Genomic_DNA.
DR EMBL; M30770; AAA41231.1; -; Genomic_DNA.
DR PIR; A31810; A31810.
DR PIR; I84740; I84740.
DR RefSeq; NP_001257779.1; NM_001270850.1. [P17712-2]
DR RefSeq; NP_036697.1; NM_012565.2. [P17712-3]
DR RefSeq; XP_006251241.1; XM_006251179.3. [P17712-1]
DR AlphaFoldDB; P17712; -.
DR SMR; P17712; -.
DR IntAct; P17712; 2.
DR MINT; P17712; -.
DR STRING; 10116.ENSRNOP00000019625; -.
DR BindingDB; P17712; -.
DR ChEMBL; CHEMBL3882; -.
DR PaxDb; P17712; -.
DR Ensembl; ENSRNOT00000086343; ENSRNOP00000071435; ENSRNOG00000061527. [P17712-3]
DR Ensembl; ENSRNOT00000086474; ENSRNOP00000069954; ENSRNOG00000061527. [P17712-1]
DR GeneID; 24385; -.
DR KEGG; rno:24385; -.
DR UCSC; RGD:2670; rat. [P17712-1]
DR CTD; 2645; -.
DR RGD; 2670; Gck.
DR eggNOG; KOG1369; Eukaryota.
DR GeneTree; ENSGT00950000182787; -.
DR InParanoid; P17712; -.
DR PhylomeDB; P17712; -.
DR BRENDA; 2.7.1.1; 5301.
DR Reactome; R-RNO-170822; Regulation of Glucokinase by Glucokinase Regulatory Protein.
DR Reactome; R-RNO-70171; Glycolysis.
DR SABIO-RK; P17712; -.
DR UniPathway; UPA00109; UER00180.
DR UniPathway; UPA00242; -.
DR PRO; PR:P17712; -.
DR Proteomes; UP000002494; Chromosome 14.
DR Bgee; ENSRNOG00000061527; Expressed in liver and 4 other tissues.
DR ExpressionAtlas; P17712; baseline and differential.
DR GO; GO:0045180; C:basal cortex; IDA:RGD.
DR GO; GO:0005938; C:cell cortex; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0005654; C:nucleoplasm; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0030141; C:secretory granule; IDA:RGD.
DR GO; GO:0043531; F:ADP binding; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IDA:RGD.
DR GO; GO:0008865; F:fructokinase activity; IDA:UniProtKB.
DR GO; GO:0004340; F:glucokinase activity; IDA:UniProtKB.
DR GO; GO:0005536; F:glucose binding; IDA:RGD.
DR GO; GO:0004396; F:hexokinase activity; ISO:RGD.
DR GO; GO:0000287; F:magnesium ion binding; IDA:RGD.
DR GO; GO:0019158; F:mannokinase activity; IDA:UniProtKB.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:RGD.
DR GO; GO:0070509; P:calcium ion import; ISO:RGD.
DR GO; GO:0046835; P:carbohydrate phosphorylation; IDA:RGD.
DR GO; GO:0001678; P:cellular glucose homeostasis; IMP:RGD.
DR GO; GO:0042149; P:cellular response to glucose starvation; IMP:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:BHF-UCL.
DR GO; GO:0044320; P:cellular response to leptin stimulus; IDA:BHF-UCL.
DR GO; GO:0051594; P:detection of glucose; IDA:BHF-UCL.
DR GO; GO:0006003; P:fructose 2,6-bisphosphate metabolic process; IDA:RGD.
DR GO; GO:0006002; P:fructose 6-phosphate metabolic process; IDA:UniProtKB.
DR GO; GO:0051156; P:glucose 6-phosphate metabolic process; IDA:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; IMP:RGD.
DR GO; GO:0006006; P:glucose metabolic process; IDA:RGD.
DR GO; GO:0005978; P:glycogen biosynthetic process; IDA:RGD.
DR GO; GO:0006096; P:glycolytic process; IDA:RGD.
DR GO; GO:0055088; P:lipid homeostasis; IDA:RGD.
DR GO; GO:0006013; P:mannose metabolic process; IDA:UniProtKB.
DR GO; GO:0006739; P:NADP metabolic process; ISO:RGD.
DR GO; GO:0032811; P:negative regulation of epinephrine secretion; IMP:RGD.
DR GO; GO:0045721; P:negative regulation of gluconeogenesis; ISS:UniProtKB.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:RGD.
DR GO; GO:0045725; P:positive regulation of glycogen biosynthetic process; ISS:UniProtKB.
DR GO; GO:0045821; P:positive regulation of glycolytic process; IDA:RGD.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IDA:RGD.
DR GO; GO:0042327; P:positive regulation of phosphorylation; IDA:RGD.
DR GO; GO:0050796; P:regulation of insulin secretion; ISO:RGD.
DR GO; GO:0043266; P:regulation of potassium ion transport; ISO:RGD.
DR GO; GO:0009749; P:response to glucose; IEP:RGD.
DR GO; GO:0019932; P:second-messenger-mediated signaling; IDA:RGD.
DR InterPro; IPR043129; ATPase_NBD.
DR InterPro; IPR039073; GCK_chordate.
DR InterPro; IPR001312; Hexokinase.
DR InterPro; IPR019807; Hexokinase_BS.
DR InterPro; IPR022673; Hexokinase_C.
DR InterPro; IPR022672; Hexokinase_N.
DR PANTHER; PTHR19443; PTHR19443; 1.
DR PANTHER; PTHR19443:SF3; PTHR19443:SF3; 1.
DR Pfam; PF00349; Hexokinase_1; 1.
DR Pfam; PF03727; Hexokinase_2; 1.
DR SUPFAM; SSF53067; SSF53067; 2.
DR PROSITE; PS00378; HEXOKINASE_1; 1.
DR PROSITE; PS51748; HEXOKINASE_2; 1.
PE 1: Evidence at protein level;
KW Allosteric enzyme; Alternative promoter usage; Alternative splicing;
KW ATP-binding; Cytoplasm; Direct protein sequencing; Glycolysis; Kinase;
KW Mitochondrion; Nucleotide-binding; Nucleus; Reference proteome;
KW Transferase.
FT CHAIN 1..465
FT /note="Hexokinase-4"
FT /id="PRO_0000197595"
FT DOMAIN 10..454
FT /note="Hexokinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 67..203
FT /note="Hexokinase small subdomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 204..443
FT /note="Hexokinase large subdomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT BINDING 78..83
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 151..152
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P35557"
FT BINDING 168..169
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P35557"
FT BINDING 204..205
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P35557"
FT BINDING 228
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P35557"
FT BINDING 231
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P35557"
FT BINDING 256
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P35557"
FT BINDING 290
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P35557"
FT BINDING 295..296
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P35557"
FT BINDING 332..336
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P35557"
FT BINDING 411..415
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P35557"
FT VAR_SEQ 1..15
FT /note="MLDDRARMEATKKEK -> MAMDTTRCGAQLLTL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:2909525"
FT /id="VSP_002077"
FT VAR_SEQ 122..138
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_002078"
SQ SEQUENCE 465 AA; 52116 MW; 65B36673DF9297BE CRC64;
MLDDRARMEA TKKEKVEQIL AEFQLQEEDL KKVMSRMQKE MDRGLRLETH EEASVKMLPT
YVRSTPEGSE VGDFLSLDLG GTNFRVMLVK VGEGEAGQWS VKTKHQMYSI PEDAMTGTAE
MLFDYISECI SDFLDKHQMK HKKLPLGFTF SFPVRHEDLD KGILLNWTKG FKASGAEGNN
IVGLLRDAIK RRGDFEMDVV AMVNDTVATM ISCYYEDRQC EVGMIVGTGC NACYMEEMQN
VELVEGDEGR MCVNTEWGAF GDSGELDEFL LEYDRMVDES SANPGQQLYE KIIGGKYMGE
LVRLVLLKLV DENLLFHGEA SEQLRTRGAF ETRFVSQVES DSGDRKQIHN ILSTLGLRPS
VTDCDIVRRA CESVSTRAAH MCSAGLAGVI NRMRESRSED VMRITVGVDG SVYKLHPSFK
ERFHASVRRL TPNCEITFIE SEEGSGRGAA LVSAVACKKA CMLAQ
