SIR5_HUMAN
ID SIR5_HUMAN Reviewed; 310 AA.
AC Q9NXA8; B4DFM4; B4DYJ5; F5H5Z9; Q5T294; Q5T295; Q9Y6E6;
DT 31-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=NAD-dependent protein deacylase sirtuin-5, mitochondrial {ECO:0000255|HAMAP-Rule:MF_03160};
DE EC=2.3.1.- {ECO:0000255|HAMAP-Rule:MF_03160, ECO:0000269|PubMed:22076378, ECO:0000269|PubMed:24703693, ECO:0000269|PubMed:29180469};
DE AltName: Full=Regulatory protein SIR2 homolog 5 {ECO:0000255|HAMAP-Rule:MF_03160};
DE AltName: Full=SIR2-like protein 5 {ECO:0000255|HAMAP-Rule:MF_03160};
DE Flags: Precursor;
GN Name=SIRT5 {ECO:0000255|HAMAP-Rule:MF_03160}; Synonyms=SIR2L5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=10381378; DOI=10.1006/bbrc.1999.0897;
RA Frye R.A.;
RT "Characterization of five human cDNAs with homology to the yeast SIR2 gene:
RT Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-
RT ribosyltransferase activity.";
RL Biochem. Biophys. Res. Commun. 260:273-279(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3 AND 4).
RC TISSUE=Amygdala, Hepatoblastoma, and Testis;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Eye;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=16079181; DOI=10.1091/mbc.e05-01-0033;
RA Michishita E., Park J.Y., Burneskis J.M., Barrett J.C., Horikawa I.;
RT "Evolutionarily conserved and nonconserved cellular localizations and
RT functions of human SIRT proteins.";
RL Mol. Biol. Cell 16:4623-4635(2005).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18680753; DOI=10.1016/j.jmb.2008.07.048;
RA Schlicker C., Gertz M., Papatheodorou P., Kachholz B., Becker C.F.W.,
RA Steegborn C.;
RT "Substrates and regulation mechanisms for the human mitochondrial sirtuins
RT Sirt3 and Sirt5.";
RL J. Mol. Biol. 382:790-801(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), AND SUBCELLULAR LOCATION (ISOFORMS
RP 1 AND 2).
RX PubMed=21143562; DOI=10.1111/j.1365-2443.2010.01475.x;
RA Matsushita N., Yonashiro R., Ogata Y., Sugiura A., Nagashima S., Fukuda T.,
RA Inatome R., Yanagi S.;
RT "Distinct regulation of mitochondrial localization and stability of two
RT human Sirt5 isoforms.";
RL Genes Cells 16:190-202(2011).
RN [11]
RP FUNCTION, NAD-BINDING, AND MUTAGENESIS OF HIS-158.
RX PubMed=21908771; DOI=10.1074/mcp.m111.012658;
RA Peng C., Lu Z., Xie Z., Cheng Z., Chen Y., Tan M., Luo H., Zhang Y., He W.,
RA Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C., Dai J.,
RA Verdin E., Ye Y., Zhao Y.;
RT "The first identification of lysine malonylation substrates and its
RT regulatory enzyme.";
RL Mol. Cell. Proteomics 10:M111.012658.01-M111.012658.12(2011).
RN [12]
RP ACTIVITY REGULATION, AND MUTAGENESIS OF THR-69 AND ARG-105.
RX PubMed=23028781; DOI=10.1371/journal.pone.0045098;
RA Fischer F., Gertz M., Suenkel B., Lakshminarasimhan M., Schutkowski M.,
RA Steegborn C.;
RT "Sirt5 deacylation activities show differential sensitivities to
RT nicotinamide inhibition.";
RL PLoS ONE 7:E45098-E45098(2012).
RN [13]
RP FUNCTION.
RX PubMed=24140062; DOI=10.1016/j.bbrc.2013.10.033;
RA Lin Z.F., Xu H.B., Wang J.Y., Lin Q., Ruan Z., Liu F.B., Jin W.,
RA Huang H.H., Chen X.;
RT "SIRT5 desuccinylates and activates SOD1 to eliminate ROS.";
RL Biochem. Biophys. Res. Commun. 441:191-195(2013).
RN [14]
RP INTERACTION WITH PCCA.
RX PubMed=23438705; DOI=10.1016/j.mito.2013.02.002;
RA Wirth M., Karaca S., Wenzel D., Ho L., Tishkoff D., Lombard D.B.,
RA Verdin E., Urlaub H., Jedrusik-Bode M., Fischle W.;
RT "Mitochondrial SIRT4-type proteins in Caenorhabditis elegans and mammals
RT interact with pyruvate carboxylase and other acetylated biotin-dependent
RT carboxylases.";
RL Mitochondrion 13:705-720(2013).
RN [15]
RP SUBCELLULAR LOCATION.
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-158.
RX PubMed=24703693; DOI=10.1016/j.cmet.2014.03.014;
RA Tan M., Peng C., Anderson K.A., Chhoy P., Xie Z., Dai L., Park J., Chen Y.,
RA Huang H., Zhang Y., Ro J., Wagner G.R., Green M.F., Madsen A.S.,
RA Schmiesing J., Peterson B.S., Xu G., Ilkayeva O.R., Muehlbauer M.J.,
RA Braulke T., Muehlhausen C., Backos D.S., Olsen C.A., McGuire P.J.,
RA Pletcher S.D., Lombard D.B., Hirschey M.D., Zhao Y.;
RT "Lysine glutarylation is a protein posttranslational modification regulated
RT by SIRT5.";
RL Cell Metab. 19:605-617(2014).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [18]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-158.
RX PubMed=29180469; DOI=10.1158/0008-5472.can-17-1912;
RA Yang X., Wang Z., Li X., Liu B., Liu M., Liu L., Chen S., Ren M., Wang Y.,
RA Yu M., Wang B., Zou J., Zhu W.G., Yin Y., Gu W., Luo J.;
RT "SHMT2 desuccinylation by SIRT5 drives cancer cell proliferation.";
RL Cancer Res. 78:372-386(2018).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 34-302 IN COMPLEX WITH NAD AND
RP ZINC IONS.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human sirtuin homolog 5 in complex with NAD.";
RL Submitted (FEB-2006) to the PDB data bank.
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.06 ANGSTROMS) OF 34-302 IN COMPLEXES WITH ZINC
RP IONS; SURAMIN AND ADP-RIBOSE, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND
RP SUBUNIT.
RX PubMed=17355872; DOI=10.1016/j.str.2007.02.002;
RA Schuetz A., Min J., Antoshenko T., Wang C.-L., Allali-Hassani A., Dong A.,
RA Loppnau P., Vedadi M., Bochkarev A., Sternglanz R., Plotnikov A.N.;
RT "Structural basis of inhibition of the human NAD+-dependent deacetylase
RT SIRT5 by suramin.";
RL Structure 15:377-389(2007).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 34-302 IN COMPLEX WITH NAD; ZINC
RP IONS AND SUCCINYLATED PEPTIDE, COFACTOR, ACTIVE SITE, BIOPHYSICOCHEMICAL
RP PROPERTIES, FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF TYR-102;
RP ARG-105 AND HIS-158.
RX PubMed=22076378; DOI=10.1126/science.1207861;
RA Du J., Zhou Y., Su X., Yu J.J., Khan S., Jiang H., Kim J., Woo J.,
RA Kim J.H., Choi B.H., He B., Chen W., Zhang S., Cerione R.A., Auwerx J.,
RA Hao Q., Lin H.;
RT "Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase.";
RL Science 334:806-809(2011).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 34-302 IN COMPLEX WITH NAD; ZINC
RP IONS AND SUCCINYLATED PEPTIDE, AND REACTION MECHANISM.
RX PubMed=22767592; DOI=10.1074/jbc.m112.384511;
RA Zhou Y., Zhang H., He B., Du J., Lin H., Cerione R.A., Hao Q.;
RT "The bicyclic intermediate structure provides insights into the
RT desuccinylation mechanism of human sirtuin 5 (SIRT5).";
RL J. Biol. Chem. 287:28307-28314(2012).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) OF 36-302 IN COMPLEX WITH CARBA-NAD
RP AND ZINC IONS.
RX PubMed=22849721; DOI=10.1021/jo301067e;
RA Szczepankiewicz B.G., Dai H., Koppetsch K.J., Qian D., Jiang F., Mao C.,
RA Perni R.B.;
RT "Synthesis of carba-NAD and the structures of its ternary complexes with
RT SIRT3 and SIRT5.";
RL J. Org. Chem. 77:7319-7329(2012).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 34-302 IN COMPLEX WITH PROTEIN
RP PEPTIDE; ZINC IONS AND RESVERATROL, AND ACTIVITY REGULATION.
RX PubMed=23185430; DOI=10.1371/journal.pone.0049761;
RA Gertz M., Nguyen G.T., Fischer F., Suenkel B., Schlicker C., Franzel B.,
RA Tomaschewski J., Aladini F., Becker C., Wolters D., Steegborn C.;
RT "A molecular mechanism for direct sirtuin activation by resveratrol.";
RL PLoS ONE 7:E49761-E49761(2012).
CC -!- FUNCTION: NAD-dependent lysine demalonylase, desuccinylase and
CC deglutarylase that specifically removes malonyl, succinyl and glutaryl
CC groups on target proteins (PubMed:21908771, PubMed:22076378,
CC PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to
CC the regulation of blood ammonia levels during prolonged fasting: acts
CC by mediating desuccinylation and deglutarylation of CPS1, thereby
CC increasing CPS1 activity in response to elevated NAD levels during
CC fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating
CC its desuccinylation, leading to reduced reactive oxygen species
CC (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation
CC (PubMed:29180469). Modulates ketogenesis through the desuccinylation
CC and activation of HMGCS2 (By similarity). Has weak NAD-dependent
CC protein deacetylase activity; however this activity may not be
CC physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS)
CC and a number of other proteins in vitro such as UOX.
CC {ECO:0000250|UniProtKB:Q8K2C6, ECO:0000269|PubMed:18680753,
CC ECO:0000269|PubMed:21908771, ECO:0000269|PubMed:22076378,
CC ECO:0000269|PubMed:24140062, ECO:0000269|PubMed:24703693,
CC ECO:0000269|PubMed:29180469}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-malonyl-L-lysyl-[protein] + NAD(+) = 2''-O-malonyl-
CC ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
CC Xref=Rhea:RHEA:47672, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:11878,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:87831, ChEBI:CHEBI:87833;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03160,
CC ECO:0000269|PubMed:22076378};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-succinyl-L-lysyl-[protein] + NAD(+) = 2''-O-
CC succinyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
CC Xref=Rhea:RHEA:47668, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:11877,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:87830, ChEBI:CHEBI:87832;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03160,
CC ECO:0000269|PubMed:22076378, ECO:0000269|PubMed:29180469};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-glutaryl-L-lysyl-[protein] + NAD(+) = 2''-O-
CC glutaryl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
CC Xref=Rhea:RHEA:47664, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:11875,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:87828, ChEBI:CHEBI:87829;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03160,
CC ECO:0000269|PubMed:24703693};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03160,
CC ECO:0000269|PubMed:22076378};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|HAMAP-Rule:MF_03160,
CC ECO:0000269|PubMed:22076378};
CC -!- ACTIVITY REGULATION: Inhibited by suramin. NAD-dependent lysine
CC desuccinylase activity is inhibited by physiological nicotinamide
CC concentrations, while deacetylase activity is not. In contrast,
CC resveratrol activates deacetylase activity, while inhibiting
CC desuccinylase activity. {ECO:0000269|PubMed:17355872,
CC ECO:0000269|PubMed:23028781, ECO:0000269|PubMed:23185430}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.1 uM for a synthetic histone H3K9 malonyllysine peptide
CC {ECO:0000269|PubMed:22076378};
CC KM=5.8 uM for a synthetic histone H3K9 succinyllysine peptide
CC {ECO:0000269|PubMed:22076378};
CC KM=8.7 uM for a synthetic GLUD1 peptide malonylated at 'Lys-503'
CC {ECO:0000269|PubMed:22076378};
CC KM=14 uM for a synthetic GLUD1 peptide succinylated at 'Lys-503'
CC {ECO:0000269|PubMed:22076378};
CC KM=150 uM for a synthetic ACSS1 peptide malonylated at 'Lys-628'
CC {ECO:0000269|PubMed:22076378};
CC KM=450 uM for a synthetic ACSS1 peptide succinylated at 'Lys-628'
CC {ECO:0000269|PubMed:22076378};
CC -!- SUBUNIT: Interacts with CPS1 (By similarity). Interacts with PCCA
CC (PubMed:23438705). Monomer (PubMed:17355872). Homodimer
CC (PubMed:17355872). Forms homodimers upon suramin binding
CC (PubMed:17355872). {ECO:0000250|UniProtKB:Q8K2C6,
CC ECO:0000269|PubMed:17355872, ECO:0000269|PubMed:22076378,
CC ECO:0000269|PubMed:22767592, ECO:0000269|PubMed:22849721,
CC ECO:0000269|PubMed:23185430, ECO:0000269|PubMed:23438705,
CC ECO:0000269|Ref.19}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane
CC space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also
CC present extramitochondrially, with a fraction present in the cytosol
CC and very small amounts also detected in the nucleus.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm
CC {ECO:0000269|PubMed:21143562}. Mitochondrion {ECO:0000255|HAMAP-
CC Rule:MF_03160, ECO:0000269|PubMed:21143562}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion {ECO:0000255|HAMAP-
CC Rule:MF_03160, ECO:0000269|PubMed:21143562}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9NXA8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NXA8-2; Sequence=VSP_008730, VSP_008731;
CC Name=3;
CC IsoId=Q9NXA8-3; Sequence=VSP_042292;
CC Name=4;
CC IsoId=Q9NXA8-4; Sequence=VSP_042291;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:10381378}.
CC -!- DOMAIN: In contrast to class I sirtuins, class III sirtuins have only
CC weak deacetylase activity. Difference in substrate specificity is
CC probably due to a larger hydrophobic pocket with 2 residues (Tyr-102
CC and Arg-105) that bind to malonylated and succinylated substrates and
CC define the specificity (PubMed:22076378).
CC {ECO:0000269|PubMed:22076378}.
CC -!- MISCELLANEOUS: The mechanism of demalonylation and desuccinylation
CC involves the presence of a 1',2'-cyclic intermediate, suggesting that
CC sirtuins use the ADP-ribose-peptidylamidate mechanism to remove acyl
CC groups from substrate lysine residues. {ECO:0000305|PubMed:22767592}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class III subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03160}.
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DR EMBL; AF083110; AAD40853.1; -; mRNA.
DR EMBL; AK000355; BAA91107.1; -; mRNA.
DR EMBL; AK294162; BAG57485.1; -; mRNA.
DR EMBL; AK302467; BAG63757.1; -; mRNA.
DR EMBL; AM393414; CAL38292.1; -; mRNA.
DR EMBL; AL441883; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471087; EAW55332.1; -; Genomic_DNA.
DR EMBL; BC000126; AAH00126.1; -; mRNA.
DR CCDS; CCDS4526.1; -. [Q9NXA8-1]
DR CCDS; CCDS4527.1; -. [Q9NXA8-2]
DR CCDS; CCDS54966.1; -. [Q9NXA8-3]
DR CCDS; CCDS56398.1; -. [Q9NXA8-4]
DR RefSeq; NP_001180196.1; NM_001193267.2. [Q9NXA8-3]
DR RefSeq; NP_001229756.1; NM_001242827.1. [Q9NXA8-4]
DR RefSeq; NP_036373.1; NM_012241.4. [Q9NXA8-1]
DR RefSeq; NP_112534.1; NM_031244.3. [Q9NXA8-2]
DR RefSeq; XP_005249025.1; XM_005248968.4.
DR PDB; 2B4Y; X-ray; 1.90 A; A/B/C/D=34-302.
DR PDB; 2NYR; X-ray; 2.06 A; A/B=34-302.
DR PDB; 3RIG; X-ray; 2.00 A; A/B=34-302.
DR PDB; 3RIY; X-ray; 1.55 A; A/B=34-302.
DR PDB; 4F4U; X-ray; 2.00 A; A/B=34-302.
DR PDB; 4F56; X-ray; 1.70 A; A/B=34-302.
DR PDB; 4G1C; X-ray; 1.94 A; A/B=36-302.
DR PDB; 4HDA; X-ray; 2.60 A; A/B=34-302.
DR PDB; 5BWL; X-ray; 1.55 A; A=33-302.
DR PDB; 5XHS; X-ray; 2.19 A; A=34-302.
DR PDB; 6ACE; X-ray; 1.98 A; A=36-302.
DR PDB; 6ACL; X-ray; 1.92 A; A=36-302.
DR PDB; 6ACO; X-ray; 1.71 A; A=34-302.
DR PDB; 6ACP; X-ray; 2.30 A; A=36-302.
DR PDB; 6EQS; X-ray; 1.32 A; A/B/C/D=34-302.
DR PDB; 6LJK; X-ray; 1.39 A; A=34-302.
DR PDB; 6LJM; X-ray; 1.78 A; A=34-302.
DR PDB; 6LJN; X-ray; 1.80 A; A=34-302.
DR PDBsum; 2B4Y; -.
DR PDBsum; 2NYR; -.
DR PDBsum; 3RIG; -.
DR PDBsum; 3RIY; -.
DR PDBsum; 4F4U; -.
DR PDBsum; 4F56; -.
DR PDBsum; 4G1C; -.
DR PDBsum; 4HDA; -.
DR PDBsum; 5BWL; -.
DR PDBsum; 5XHS; -.
DR PDBsum; 6ACE; -.
DR PDBsum; 6ACL; -.
DR PDBsum; 6ACO; -.
DR PDBsum; 6ACP; -.
DR PDBsum; 6EQS; -.
DR PDBsum; 6LJK; -.
DR PDBsum; 6LJM; -.
DR PDBsum; 6LJN; -.
DR AlphaFoldDB; Q9NXA8; -.
DR SMR; Q9NXA8; -.
DR BioGRID; 116980; 58.
DR IntAct; Q9NXA8; 20.
DR STRING; 9606.ENSP00000476228; -.
DR BindingDB; Q9NXA8; -.
DR ChEMBL; CHEMBL2163183; -.
DR DrugBank; DB03478; 2'-O-Acetyl Adenosine-5-Diphosphoribose.
DR DrugBank; DB02059; Adenosine-5-Diphosphoribose.
DR DrugBank; DB15493; Cambinol.
DR DrugBank; DB02701; Nicotinamide.
DR DrugBank; DB04786; Suramin.
DR DrugCentral; Q9NXA8; -.
DR GuidetoPHARMACOLOGY; 2711; -.
DR iPTMnet; Q9NXA8; -.
DR PhosphoSitePlus; Q9NXA8; -.
DR BioMuta; SIRT5; -.
DR DMDM; 38258652; -.
DR EPD; Q9NXA8; -.
DR jPOST; Q9NXA8; -.
DR MassIVE; Q9NXA8; -.
DR MaxQB; Q9NXA8; -.
DR PaxDb; Q9NXA8; -.
DR PeptideAtlas; Q9NXA8; -.
DR PRIDE; Q9NXA8; -.
DR ProteomicsDB; 83064; -. [Q9NXA8-1]
DR ProteomicsDB; 83065; -. [Q9NXA8-2]
DR ProteomicsDB; 83066; -. [Q9NXA8-3]
DR ProteomicsDB; 83067; -. [Q9NXA8-4]
DR ABCD; Q9NXA8; 5 sequenced antibodies.
DR Antibodypedia; 10177; 671 antibodies from 44 providers.
DR DNASU; 23408; -.
DR Ensembl; ENST00000359782.8; ENSP00000352830.3; ENSG00000124523.17. [Q9NXA8-3]
DR Ensembl; ENST00000379262.8; ENSP00000368564.4; ENSG00000124523.17. [Q9NXA8-2]
DR Ensembl; ENST00000397350.7; ENSP00000380509.3; ENSG00000124523.17. [Q9NXA8-1]
DR Ensembl; ENST00000606117.2; ENSP00000476228.1; ENSG00000124523.17. [Q9NXA8-1]
DR Ensembl; ENST00000680151.1; ENSP00000505086.1; ENSG00000124523.17. [Q9NXA8-1]
DR Ensembl; ENST00000680432.1; ENSP00000505496.1; ENSG00000124523.17. [Q9NXA8-1]
DR Ensembl; ENST00000680707.1; ENSP00000505469.1; ENSG00000124523.17. [Q9NXA8-2]
DR GeneID; 23408; -.
DR KEGG; hsa:23408; -.
DR MANE-Select; ENST00000606117.2; ENSP00000476228.1; NM_012241.5; NP_036373.1.
DR UCSC; uc003naw.4; human. [Q9NXA8-1]
DR CTD; 23408; -.
DR DisGeNET; 23408; -.
DR GeneCards; SIRT5; -.
DR HGNC; HGNC:14933; SIRT5.
DR HPA; ENSG00000124523; Low tissue specificity.
DR MIM; 604483; gene.
DR neXtProt; NX_Q9NXA8; -.
DR OpenTargets; ENSG00000124523; -.
DR PharmGKB; PA37938; -.
DR VEuPathDB; HostDB:ENSG00000124523; -.
DR eggNOG; KOG2684; Eukaryota.
DR GeneTree; ENSGT00940000156080; -.
DR HOGENOM; CLU_023643_3_1_1; -.
DR InParanoid; Q9NXA8; -.
DR OMA; SMQVYPA; -.
DR OrthoDB; 1459156at2759; -.
DR PhylomeDB; Q9NXA8; -.
DR TreeFam; TF106183; -.
DR BRENDA; 2.3.1.B43; 2681.
DR PathwayCommons; Q9NXA8; -.
DR Reactome; R-HSA-2151201; Transcriptional activation of mitochondrial biogenesis.
DR SABIO-RK; Q9NXA8; -.
DR SignaLink; Q9NXA8; -.
DR SIGNOR; Q9NXA8; -.
DR BioGRID-ORCS; 23408; 14 hits in 1096 CRISPR screens.
DR ChiTaRS; SIRT5; human.
DR EvolutionaryTrace; Q9NXA8; -.
DR GeneWiki; SIRT5; -.
DR GenomeRNAi; 23408; -.
DR Pharos; Q9NXA8; Tchem.
DR PRO; PR:Q9NXA8; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9NXA8; protein.
DR Bgee; ENSG00000124523; Expressed in diaphragm and 202 other tissues.
DR ExpressionAtlas; Q9NXA8; baseline and differential.
DR Genevisible; Q9NXA8; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; TAS:UniProtKB.
DR GO; GO:0003950; F:NAD+ ADP-ribosyltransferase activity; TAS:ProtInc.
DR GO; GO:0070403; F:NAD+ binding; IDA:UniProtKB.
DR GO; GO:0034979; F:NAD-dependent protein deacetylase activity; TAS:Reactome.
DR GO; GO:0061697; F:protein-glutaryllysine deglutarylase activity; IDA:UniProtKB.
DR GO; GO:0036054; F:protein-malonyllysine demalonylase activity; IDA:UniProtKB.
DR GO; GO:0036055; F:protein-succinyllysine desuccinylase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0007005; P:mitochondrion organization; TAS:Reactome.
DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IEA:Ensembl.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IDA:UniProtKB.
DR GO; GO:0036047; P:peptidyl-lysine demalonylation; IDA:UniProtKB.
DR GO; GO:0036049; P:peptidyl-lysine desuccinylation; IDA:UniProtKB.
DR GO; GO:0006471; P:protein ADP-ribosylation; ISS:GO_Central.
DR GO; GO:0006476; P:protein deacetylation; IDA:UniProtKB.
DR GO; GO:0061698; P:protein deglutarylation; IDA:UniProtKB.
DR GO; GO:0036046; P:protein demalonylation; IDA:UniProtKB.
DR GO; GO:0036048; P:protein desuccinylation; IDA:UniProtKB.
DR GO; GO:0010566; P:regulation of ketone biosynthetic process; ISS:UniProtKB.
DR GO; GO:0031667; P:response to nutrient levels; IEA:Ensembl.
DR CDD; cd01412; SIRT5_Af1_CobB; 1.
DR Gene3D; 3.30.1600.10; -; 1.
DR HAMAP; MF_01121; Sirtuin_ClassIII; 1.
DR IDEAL; IID00502; -.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR003000; Sirtuin.
DR InterPro; IPR026591; Sirtuin_cat_small_dom_sf.
DR InterPro; IPR027546; Sirtuin_class_III.
DR InterPro; IPR026590; Ssirtuin_cat_dom.
DR Pfam; PF02146; SIR2; 1.
DR SUPFAM; SSF52467; SSF52467; 1.
DR PROSITE; PS50305; SIRTUIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Metal-binding;
KW Mitochondrion; NAD; Nucleus; Reference proteome; Transferase;
KW Transit peptide; Zinc.
FT TRANSIT 1..36
FT /note="Mitochondrion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT CHAIN 37..310
FT /note="NAD-dependent protein deacylase sirtuin-5,
FT mitochondrial"
FT /id="PRO_0000110266"
FT DOMAIN 41..309
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT ACT_SITE 158
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160,
FT ECO:0000269|PubMed:22076378, ECO:0000269|PubMed:29180469"
FT BINDING 58..77
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160,
FT ECO:0000269|PubMed:22076378, ECO:0000269|PubMed:22767592,
FT ECO:0000269|Ref.19"
FT BINDING 102
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 105
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 140..143
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160,
FT ECO:0000269|PubMed:22076378, ECO:0000269|PubMed:22767592,
FT ECO:0000269|Ref.19"
FT BINDING 166
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 169
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 207
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 212
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160"
FT BINDING 249..251
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160,
FT ECO:0000269|PubMed:22076378, ECO:0000269|PubMed:22767592,
FT ECO:0000269|Ref.19"
FT BINDING 275..277
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160,
FT ECO:0000269|PubMed:22076378, ECO:0000269|PubMed:22767592,
FT ECO:0000269|Ref.19"
FT BINDING 293
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03160,
FT ECO:0000269|PubMed:22076378, ECO:0000269|PubMed:22767592,
FT ECO:0000269|Ref.19"
FT VAR_SEQ 1..108
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042291"
FT VAR_SEQ 189..206
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042292"
FT VAR_SEQ 286..299
FT /note="RFHFQGPCGTTLPE -> SHLISISSLIIIKN (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_008730"
FT VAR_SEQ 300..310
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_008731"
FT VARIANT 285
FT /note="F -> L (in dbSNP:rs9464003)"
FT /id="VAR_029042"
FT VARIANT 305
FT /note="E -> G (in dbSNP:rs34162626)"
FT /id="VAR_051980"
FT MUTAGEN 69
FT /note="T->A: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:23028781"
FT MUTAGEN 102
FT /note="Y->F: Increases the KM for desuccinylation."
FT /evidence="ECO:0000269|PubMed:22076378"
FT MUTAGEN 105
FT /note="R->M: Increases the KM for desuccinylation. Does not
FT affect deacetylase activity."
FT /evidence="ECO:0000269|PubMed:22076378,
FT ECO:0000269|PubMed:23028781"
FT MUTAGEN 158
FT /note="H->A: Abolishes desuccinylation and deglutarylation
FT activity."
FT /evidence="ECO:0000269|PubMed:21908771,
FT ECO:0000269|PubMed:22076378, ECO:0000269|PubMed:24703693,
FT ECO:0000269|PubMed:29180469"
FT CONFLICT 53
FT /note="I -> M (in Ref. 2; BAG63757)"
FT /evidence="ECO:0000305"
FT HELIX 40..49
FT /evidence="ECO:0007829|PDB:6EQS"
FT STRAND 51..57
FT /evidence="ECO:0007829|PDB:6EQS"
FT HELIX 60..63
FT /evidence="ECO:0007829|PDB:6EQS"
FT TURN 64..66
FT /evidence="ECO:0007829|PDB:6EQS"
FT HELIX 72..75
FT /evidence="ECO:0007829|PDB:6EQS"
FT HELIX 82..85
FT /evidence="ECO:0007829|PDB:6EQS"
FT HELIX 88..93
FT /evidence="ECO:0007829|PDB:6EQS"
FT HELIX 95..109
FT /evidence="ECO:0007829|PDB:6EQS"
FT HELIX 116..130
FT /evidence="ECO:0007829|PDB:6EQS"
FT STRAND 134..139
FT /evidence="ECO:0007829|PDB:6EQS"
FT HELIX 145..148
FT /evidence="ECO:0007829|PDB:6EQS"
FT STRAND 152..156
FT /evidence="ECO:0007829|PDB:6EQS"
FT STRAND 159..166
FT /evidence="ECO:0007829|PDB:6EQS"
FT TURN 167..169
FT /evidence="ECO:0007829|PDB:6EQS"
FT STRAND 172..174
FT /evidence="ECO:0007829|PDB:6EQS"
FT STRAND 178..181
FT /evidence="ECO:0007829|PDB:6EQS"
FT HELIX 182..184
FT /evidence="ECO:0007829|PDB:6EQS"
FT STRAND 190..193
FT /evidence="ECO:0007829|PDB:4HDA"
FT HELIX 201..203
FT /evidence="ECO:0007829|PDB:6EQS"
FT TURN 210..212
FT /evidence="ECO:0007829|PDB:6EQS"
FT STRAND 215..220
FT /evidence="ECO:0007829|PDB:6EQS"
FT HELIX 229..241
FT /evidence="ECO:0007829|PDB:6EQS"
FT STRAND 243..249
FT /evidence="ECO:0007829|PDB:6EQS"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:5BWL"
FT HELIX 257..259
FT /evidence="ECO:0007829|PDB:6EQS"
FT HELIX 260..266
FT /evidence="ECO:0007829|PDB:6EQS"
FT STRAND 271..277
FT /evidence="ECO:0007829|PDB:6EQS"
FT HELIX 282..284
FT /evidence="ECO:0007829|PDB:6EQS"
FT STRAND 285..291
FT /evidence="ECO:0007829|PDB:6EQS"
FT HELIX 293..300
FT /evidence="ECO:0007829|PDB:6EQS"
SQ SEQUENCE 310 AA; 33881 MW; 022DA32CDB43AC3A CRC64;
MRPLQIVPSR LISQLYCGLK PPASTRNQIC LKMARPSSSM ADFRKFFAKA KHIVIISGAG
VSAESGVPTF RGAGGYWRKW QAQDLATPLA FAHNPSRVWE FYHYRREVMG SKEPNAGHRA
IAECETRLGK QGRRVVVITQ NIDELHRKAG TKNLLEIHGS LFKTRCTSCG VVAENYKSPI
CPALSGKGAP EPGTQDASIP VEKLPRCEEA GCGGLLRPHV VWFGENLDPA ILEEVDRELA
HCDLCLVVGT SSVVYPAAMF APQVAARGVP VAEFNTETTP ATNRFRFHFQ GPCGTTLPEA
LACHENETVS
