ID DPYD_HUMAN Reviewed; 1025 AA. AC Q12882; A2RRQ2; A2RRQ3; A8K5A2; A8MWG9; Q16694; Q16761; Q96TH1; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 13-NOV-2007, sequence version 2. DT 07-JUL-2009, entry version 99. DE RecName: Full=Dihydropyrimidine dehydrogenase [NADP+]; DE Short=DHPDHase; DE Short=DPD; DE EC=1.3.1.2; DE AltName: Full=Dihydrouracil dehydrogenase; DE AltName: Full=Dihydrothymine dehydrogenase; DE Flags: Precursor; GN Name=DPYD; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Liver; RX MEDLINE=94365020; PubMed=8083224; RA Yokota H., Fernandez-Salguero P., Furuya H., Lin K., McBride O.W., RA Podschun B., Schnackerz K.D., Gonzalez F.J.; RT "cDNA cloning and chromosome mapping of human dihydropyrimidine RT dehydrogenase, an enzyme associated with 5-fluorouracil toxicity and RT congenital thymine uraciluria."; RL J. Biol. Chem. 269:23192-23196(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=97280676; PubMed=9135003; RA Johnson M.R., Wang K., Tillmanns S., Albin N., Diasio R.B.; RT "Structural organization of the human dihydropyrimidine dehydrogenase RT gene."; RL Cancer Res. 57:1660-1663(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=98124145; PubMed=9464498; DOI=10.1016/S0304-3835(97)00377-7; RA Ogura K., Nishiyama T., Takubo H., Kato A., Okuda H., Arakawa K., RA Fukushima M., Nagayama S., Kawaguchi Y., Watabe T.; RT "Suicidal inactivation of human dihydropyrimidine dehydrogenase by RT (E)-5-(2-bromovinyl)uracil derived from the antiviral, sorivudine."; RL Cancer Lett. 122:107-113(1998). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-29. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS VAL-543 AND RP ILE-732. 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 581-635. RC TISSUE=Liver; RX MEDLINE=97047101; PubMed=8892022; DOI=10.1007/BF01799841; RA Vreken P., van Kuilenburg A.B.P., Meinsma R., Smit G.P.A., RA Bakker H.D., de Abreu R.A., van Gennip A.H.; RT "A point mutation in an invariant splice donor site leads to exon RT skipping in two unrelated Dutch patients with dihydropyrimidine RT dehydrogenase deficiency."; RL J. Inherit. Metab. Dis. 19:645-654(1996). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 581-635. RX MEDLINE=97313755; PubMed=9170156; RA Fernandez-Salguero P.M., Sapone A., Wei X., Holt J.R., Jones S., RA Idle J.R., Gonzalez F.J.; RT "Lack of correlation between phenotype and genotype for the RT polymorphically expressed dihydropyrimidine dehydrogenase in a family RT of Pakistani origin."; RL Pharmacogenetics 7:161-163(1997). RN [9] RP CHARACTERIZATION, AND PARTIAL PROTEIN SEQUENCE. RC TISSUE=Liver; RX MEDLINE=92381021; PubMed=1512248; RA Lu Z.-H., Zhang R., Diasio R.B.; RT "Purification and characterization of dihydropyrimidine dehydrogenase RT from human liver."; RL J. Biol. Chem. 267:17102-17109(1992). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-577, AND MASS RP SPECTROMETRY. RX PubMed=18187866; DOI=10.2116/analsci.24.161; RA Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y.; RT "Automated phosphoproteome analysis for cultured cancer cells by two- RT dimensional nanoLC-MS using a calcined titania/C18 biphasic column."; RL Anal. Sci. 24:161-166(2008). RN [11] RP VARIANTS ARG-29; TRP-235 AND HIS-886. RX MEDLINE=98102836; PubMed=9439663; DOI=10.1007/s004390050637; RA Vreken P., van Kuilenburg A.B.P., Meinsma R., van Gennip A.H.; RT "Dihydropyrimidine dehydrogenase (DPD) deficiency: identification and RT expression of missense mutations C29R, R886H and R235W."; RL Hum. Genet. 101:333-338(1997). RN [12] RP VARIANTS ARG-29; TRP-235 AND HIS-886. RX MEDLINE=97411371; PubMed=9266349; DOI=10.1023/A:1005357307122; RA Vreken P., van Kuilenburg A.B.P., Meinsma R., van Gennip A.H.; RT "Identification of novel point mutations in the dihydropyrimidine RT dehydrogenase gene."; RL J. Inherit. Metab. Dis. 20:335-338(1997). RN [13] RP VARIANT [LARGE SCALE ANALYSIS] ARG-29. RX PubMed=18987736; DOI=10.1038/nature07485; RA Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K., RA Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L., RA Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A., RA Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V., RA Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R., RA Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E., RA Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., RA Heath S., Shannon W.D., Nagarajan R., Walter M.J., Link D.C., RA Graubert T.A., DiPersio J.F., Wilson R.K.; RT "DNA sequencing of a cytogenetically normal acute myeloid leukaemia RT genome."; RL Nature 456:66-72(2008). CC -!- FUNCTION: Involved in pyrimidine base degradation. Catalyzes the CC reduction of uracil and thymine. Also involved the degradation of CC the chemotherapeutic drug 5-fluorouracil. CC -!- CATALYTIC ACTIVITY: 5,6-dihydrouracil + NADP(+) = uracil + NADPH. CC -!- COFACTOR: Binds 2 FAD. CC -!- COFACTOR: Binds 2 FMN. CC -!- COFACTOR: Binds 2 4Fe-4S clusters. Contains approximately 33 iron CC atoms per molecule. CC -!- PATHWAY: Amino-acid biosynthesis; beta-alanine biosynthesis. CC -!- SUBUNIT: Homodimer. CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- TISSUE SPECIFICITY: Found in most tissues with greatest activity CC found in liver and peripheral blood mononuclear cells. CC -!- DISEASE: Defects in DPYD are the cause of dihydropyrimidine CC dehydrogenase deficiency (DPYD deficiency) [MIM:274270]; also CC known as hereditary thymine-uraciluria or familial pyrimidinemia. CC DPYD deficiency is a disease characterized by persistent urinary CC excretion of excessive amounts of uracil, thymine and 5- CC hydroxymethyluracil. Patients suffering from this disease show a CC severe reaction to the anticancer drug 5-fluorouracil. This CC reaction includes stomatitis, Leukopenia, thrombocytopenia, hair CC loss, diarrhea, fever, marked weight loss, cerebellar ataxia, and CC neurologic symptoms, progressing to semicoma. CC -!- SIMILARITY: Belongs to the dihydropyrimidine dehydrogenase family. CC -!- SIMILARITY: Contains 3 4Fe-4S ferredoxin-type domains. CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.genetests.org/query?gene=DPYD"; 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; U09178; AAA57474.1; -; mRNA. DR EMBL; U20938; AAB51366.1; -; mRNA. DR EMBL; AB003063; BAA89789.1; -; mRNA. DR EMBL; AK291217; BAF83906.1; -; mRNA. DR EMBL; AC091608; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC131777; AAI31778.1; -; mRNA. DR EMBL; BC131778; AAI31779.1; -; mRNA. DR EMBL; X95670; CAA64973.1; -; Genomic_DNA. DR EMBL; U57655; AAB07049.1; -; Genomic_DNA. DR IPI; IPI00029772; -. DR PIR; A54718; A54718. DR RefSeq; NP_000101.2; -. DR UniGene; Hs.335034; -. DR HSSP; Q28943; 1GTE. DR SMR; Q12882; 2-1017. DR PhosphoSite; Q12882; -. DR PRIDE; Q12882; -. DR Ensembl; ENSG00000188641; Homo sapiens. DR GeneID; 1806; -. DR KEGG; hsa:1806; -. DR UCSC; uc001drv.1; human. DR GeneCards; GC01M097255; -. DR H-InvDB; HIX0000804; -. DR HGNC; HGNC:3012; DPYD. DR MIM; 274270; gene+phenotype. DR Orphanet; 1675; Dihydropyrimidine dehydrogenase deficiency. DR PharmGKB; PA145; -. DR HOGENOM; Q12882; -. DR HOVERGEN; Q12882; -. DR BRENDA; 1.3.1.2; 247. DR Reactome; REACT_1698; Metablism of nucleotides. DR DrugBank; DB01101; Capecitabine. DR DrugBank; DB00109; Enfuvirtide. DR NextBio; 7361; -. DR ArrayExpress; Q12882; -. DR Bgee; Q12882; -. DR CleanEx; HS_DPYD; -. DR GermOnline; ENSG00000188641; Homo sapiens. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW. DR GO; GO:0004158; F:dihydroorotate oxidase activity; IEA:InterPro. DR GO; GO:0017113; F:dihydropyrimidine dehydrogenase (NADP+) act...; IDA:UniProtKB. DR GO; GO:0004159; F:dihydrouracil dehydrogenase (NAD+) activity; EXP:Reactome. DR GO; GO:0009055; F:electron carrier activity; IEA:InterPro. DR GO; GO:0050660; F:FAD binding; ISS:UniProtKB. DR GO; GO:0005506; F:iron ion binding; IEA:UniProtKB-KW. DR GO; GO:0050661; F:NADP or NADPH binding; ISS:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0006207; P:'de novo' pyrimidine base biosynthetic process; IEA:InterPro. DR GO; GO:0055114; P:oxidation reduction; IEA:UniProtKB-KW. DR GO; GO:0006145; P:purine base catabolic process; IMP:UniProtKB. DR GO; GO:0006214; P:thymidine catabolic process; IDA:UniProtKB. DR GO; GO:0006210; P:thymine catabolic process; IDA:UniProtKB. DR GO; GO:0006222; P:UMP biosynthetic process; IEA:InterPro. DR GO; GO:0006212; P:uracil catabolic process; IDA:UniProtKB. DR InterPro; IPR017896; 4Fe4S_Fe-S-bd. DR InterPro; IPR001450; 4Fe4S_Fe_S_bd_subgr. DR InterPro; IPR017900; 4Fe4S_Fe_S_CS. DR InterPro; IPR000759; Adrndx_reductase. DR InterPro; IPR013785; Aldolase_TIM. DR InterPro; IPR012135; Dihydroorotate_DH_1_2. DR InterPro; IPR005720; Dihydroorotate_DH_1_core. DR InterPro; IPR013027; FAD_pyr_nucl-diS_OxRdtase. DR InterPro; IPR012285; Fum_reductase_C. DR InterPro; IPR016040; NAD(P)-bd_dom. DR Gene3D; G3DSA:3.20.20.70; Aldolase_TIM; 1. DR Gene3D; G3DSA:1.10.1060.10; Fum_reductase_C; 1. DR Gene3D; G3DSA:3.40.50.720; NAD(P)-bd; 1. DR Pfam; PF01180; DHO_dh; 1. DR Pfam; PF00037; Fer4; 1. DR Pfam; PF07992; Pyr_redox_2; 1. DR PRINTS; PR00419; ADXRDTASE. DR ProDom; PD000139; FAD_pyr_redox; 1. DR TIGRFAMs; TIGR01037; pyrD_sub1_fam; 1. DR PROSITE; PS00198; 4FE4S_FER_1; 1. DR PROSITE; PS51379; 4FE4S_FER_2; 3. PE 1: Evidence at protein level; KW 4Fe-4S; Complete proteome; Cytoplasm; Direct protein sequencing; KW Disease mutation; FAD; Flavoprotein; FMN; Iron; Iron-sulfur; KW Metal-binding; NADP; Oxidoreductase; Phosphoprotein; Polymorphism; KW Repeat. FT PROPEP 1 3 FT /FTId=PRO_0000021114. FT CHAIN 4 1025 Dihydropyrimidine dehydrogenase [NADP+]. FT /FTId=PRO_0000021115. FT DOMAIN 69 100 4Fe-4S ferredoxin-type 1. FT DOMAIN 944 976 4Fe-4S ferredoxin-type 2. FT DOMAIN 978 1007 4Fe-4S ferredoxin-type 3. FT NP_BIND 335 351 NADP (Potential). FT NP_BIND 471 481 FAD (Potential). FT REGION 661 678 Uracil binding (Potential). FT METAL 953 953 Iron-sulfur 1 (4Fe-4S) (Potential). FT METAL 956 956 Iron-sulfur 1 (4Fe-4S) (Potential). FT METAL 959 959 Iron-sulfur 1 (4Fe-4S) (Potential). FT METAL 963 963 Iron-sulfur 1 (4Fe-4S) (Potential). FT METAL 986 986 Iron-sulfur 2 (4Fe-4S) (Potential). FT METAL 989 989 Iron-sulfur 2 (4Fe-4S) (Potential). FT METAL 992 992 Iron-sulfur 2 (4Fe-4S) (Potential). FT METAL 996 996 Iron-sulfur 2 (4Fe-4S) (Potential). FT MOD_RES 577 577 Phosphoserine. FT VARIANT 29 29 C -> R (in allele DPYD*9A and allele FT DPYD*9B; loss of activity; FT dbSNP:rs1801265). FT /FTId=VAR_005173. FT VARIANT 166 166 M -> V (in dbSNP:rs2297595). FT /FTId=VAR_054034. FT VARIANT 235 235 R -> W (in allele DPYD*8; loss of FT activity; dbSNP:rs1801266). FT /FTId=VAR_005174. FT VARIANT 534 534 S -> N (in allele DPYD*4; low activity; FT dbSNP:rs1801158). FT /FTId=VAR_005175. FT VARIANT 543 543 I -> V (in allele DPYD*5; FT dbSNP:rs1801159). FT /FTId=VAR_005176. FT VARIANT 732 732 V -> I (in dbSNP:rs1801160). FT /FTId=VAR_014760. FT VARIANT 886 886 R -> H (in allele DPYD*9B; 25% of FT activity; dbSNP:rs1801267). FT /FTId=VAR_005177. FT VARIANT 995 995 V -> F (in allele DPYD*10; low activity; FT dbSNP:rs1801268). FT /FTId=VAR_005178. FT CONFLICT 845 845 E -> G (in Ref. 4; BAF83906). FT CONFLICT 910 910 N -> S (in Ref. 1; AAA57474). FT CONFLICT 1024 1024 V -> G (in Ref. 6; AAI31779). SQ SEQUENCE 1025 AA; 111401 MW; 0201943955AB2C21 CRC64; MAPVLSKDSA DIESILALNP RTQTHATLCS TSAKKLDKKH WKRNPDKNCF NCEKLENNFD DIKHTTLGER GALREAMRCL KCADAPCQKS CPTNLDIKSF ITSIANKNYY GAAKMIFSDN PLGLTCGMVC PTSDLCVGGC NLYATEEGPI NIGGLQQFAT EVFKAMSIPQ IRNPSLPPPE KMSEAYSAKI ALFGAGPASI SCASFLARLG YSDITIFEKQ EYVGGLSTSE IPQFRLPYDV VNFEIELMKD LGVKIICGKS LSVNEMTLST LKEKGYKAAF IGIGLPEPNK DAIFQGLTQD QGFYTSKDFL PLVAKGSKAG MCACHSPLPS IRGVVIVLGA GDTAFDCATS ALRCGARRVF IVFRKGFVNI RAVPEEMELA KEEKCEFLPF LSPRKVIVKG GRIVAMQFVR TEQDETGKWN EDEDQMVHLK ADVVISAFGS VLSDPKVKEA LSPIKFNRWG LPEVDPETMQ TSEAWVFAGG DVVGLANTTV ESVNDGKQAS WYIHKYVQSQ YGASVSAKPE LPLFYTPIDL VDISVEMAGL KFINPFGLAS ATPATSTSMI RRAFEAGWGF ALTKTFSLDK DIVTNVSPRI IRGTTSGPMY GPGQSSFLNI ELISEKTAAY WCQSVTELKA DFPDNIVIAS IMCSYNKNDW TELAKKSEDS GADALELNLS CPHGMGERGM GLACGQDPEL VRNICRWVRQ AVQIPFFAKL TPNVTDIVSI ARAAKEGGAN GVTATNTVSG LMGLKSDGTP WPAVGIAKRT TYGGVSGTAI RPIALRAVTS IARALPGFPI LATGGIDSAE SGLQFLHSGA SVLQVCSAIQ NQDFTVIEDY CTGLKALLYL KSIEELQDWD GQSPATVSHQ KGKPVPRIAE LMDKKLPSFG PYLEQRKKII AENKIRLKEQ NVAFSPLKRN CFIPKRPIPT IKDVIGKALQ YLGTFGELSN VEQVVAMIDE EMCINCGKCY MTCNDSGYQA IQFDPETHLP TITDTCTGCT LCLSVCPIVD CIKMVSRTTP YEPKRGVPLS VNPVC //