Full text data of AASDHPPT
AASDHPPT
[Confidence: low (only semi-automatic identification from reviews)]
L-aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase; 2.7.8.- (4'-phosphopantetheinyl transferase; Alpha-aminoadipic semialdehyde dehydrogenase-phosphopantetheinyl transferase; AASD-PPT; LYS5 ortholog)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
L-aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase; 2.7.8.- (4'-phosphopantetheinyl transferase; Alpha-aminoadipic semialdehyde dehydrogenase-phosphopantetheinyl transferase; AASD-PPT; LYS5 ortholog)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9NRN7
ID ADPPT_HUMAN Reviewed; 309 AA.
AC Q9NRN7; B2R6D1; Q9C068; Q9P0Q3; Q9UG80; Q9Y389;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 08-NOV-2005, sequence version 2.
DT 22-JAN-2014, entry version 95.
DE RecName: Full=L-aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase;
DE EC=2.7.8.-;
DE AltName: Full=4'-phosphopantetheinyl transferase;
DE AltName: Full=Alpha-aminoadipic semialdehyde dehydrogenase-phosphopantetheinyl transferase;
DE Short=AASD-PPT;
DE AltName: Full=LYS5 ortholog;
GN Name=AASDHPPT; ORFNames=CGI-80, HAH-P, HSPC223, x0005;
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], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11286508; DOI=10.1006/mgme.2000.3138;
RA Praphanphoj V., Sacksteder K.A., Gould S.J., Thomas G.H.,
RA Geraghty M.T.;
RT "Identification of the alpha-aminoadipic semialdehyde dehydrogenase-
RT phosphopantetheinyl transferase gene, the human ortholog of the yeast
RT LYS5 gene.";
RL Mol. Genet. Metab. 72:336-342(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for
RT 300 previously undefined genes expressed in CD34+ hematopoietic
RT stem/progenitor cells.";
RL Genome Res. 10:1546-1560(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Adrenal gland;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H.,
RA Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J.,
RA Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M.,
RA Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal
RT axis and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Dendritic cell;
RA Li N., Peng Y., Li Y., Gu W., Han Z., Fu G., Chen Z.;
RT "Novel genes expressed in human dendritic cell.";
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Tongue;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Urinary bladder, and Uterus;
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 99-309.
RC TISSUE=Kidney;
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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [10]
RP PROTEIN SEQUENCE OF 235-246, AND MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (MAR-2007) to UniProtKB.
RN [11]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, COFACTOR, MASS SPECTROMETRY,
RP AND TISSUE SPECIFICITY.
RX PubMed=12815048; DOI=10.1074/jbc.M305459200;
RA Joshi A.K., Zhang L., Rangan V.S., Smith S.;
RT "Cloning, expression, and characterization of a human 4'-
RT phosphopantetheinyl transferase with broad substrate specificity.";
RL J. Biol. Chem. 278:33142-33149(2003).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-258, AND MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-258, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-258, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
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.,
RA Buerckstuemmer T., 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 [16]
RP X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 14-309 IN COMPLEXES WITH
RP COENZYME A; MAGNESIUM IONS AND FASN, FUNCTION, BIOPHYSICOCHEMICAL
RP PROPERTIES, COFACTOR, AND MUTAGENESIS OF ARG-47; ARG-86; HIS-111;
RP GLN-112; ASP-129; GLU-181 AND LYS-185.
RX PubMed=18022563; DOI=10.1016/j.chembiol.2007.10.013;
RA Bunkoczi G., Pasta S., Joshi A., Wu X., Kavanagh K.L., Smith S.,
RA Oppermann U.;
RT "Mechanism and substrate recognition of human holo ACP synthase.";
RL Chem. Biol. 14:1243-1253(2007).
CC -!- FUNCTION: Catalyzes the post-translational modification of target
CC proteins by phosphopantetheine. Can transfer the 4'-
CC phosphopantetheine moiety from coenzyme A to a serine residue of a
CC broad range of acceptors, such as the acyl carrier domain of FASN.
CC -!- CATALYTIC ACTIVITY: CoA-[4'-phosphopantetheine] + apo-[acyl-
CC carrier-protein] = adenosine 3',5'-bisphosphate + holo-[acyl-
CC carrier-protein].
CC -!- COFACTOR: Binds 1 magnesium ion.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.44 mM for magnesium;
CC KM=0.025 mM for coenzyme A;
CC -!- SUBUNIT: Monomer. Interacts with FASN.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Detected in heart, skeletal muscle, placenta,
CC testis, brain, pancreas, liver and kidney.
CC -!- SIMILARITY: Belongs to the P-Pant transferase superfamily. AcpS
CC family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD34075.1; Type=Frameshift; Positions=34, 63;
CC Sequence=AAF86879.1; Type=Erroneous initiation;
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DR EMBL; AF302110; AAG30872.1; -; mRNA.
DR EMBL; AF151838; AAD34075.1; ALT_FRAME; mRNA.
DR EMBL; AF151057; AAF36143.1; -; mRNA.
DR EMBL; AF136978; AAG49439.1; -; mRNA.
DR EMBL; AF201943; AAF86879.1; ALT_INIT; mRNA.
DR EMBL; AK312529; BAG35428.1; -; mRNA.
DR EMBL; CH471065; EAW67078.1; -; Genomic_DNA.
DR EMBL; BC015470; AAH15470.1; -; mRNA.
DR EMBL; BC016728; AAH16728.1; -; mRNA.
DR EMBL; AL050073; CAB43257.1; -; mRNA.
DR PIR; T08733; T08733.
DR RefSeq; NP_056238.2; NM_015423.2.
DR UniGene; Hs.524009; -.
DR PDB; 2BYD; X-ray; 2.00 A; A=14-309.
DR PDB; 2C43; X-ray; 1.93 A; A=14-309.
DR PDB; 2CG5; X-ray; 2.70 A; A=14-309.
DR PDBsum; 2BYD; -.
DR PDBsum; 2C43; -.
DR PDBsum; 2CG5; -.
DR ProteinModelPortal; Q9NRN7; -.
DR SMR; Q9NRN7; 14-289.
DR IntAct; Q9NRN7; 6.
DR MINT; MINT-5005661; -.
DR STRING; 9606.ENSP00000278618; -.
DR PhosphoSite; Q9NRN7; -.
DR DMDM; 81170356; -.
DR PaxDb; Q9NRN7; -.
DR PeptideAtlas; Q9NRN7; -.
DR PRIDE; Q9NRN7; -.
DR DNASU; 60496; -.
DR Ensembl; ENST00000278618; ENSP00000278618; ENSG00000149313.
DR GeneID; 60496; -.
DR KEGG; hsa:60496; -.
DR UCSC; uc001pjc.1; human.
DR CTD; 60496; -.
DR GeneCards; GC11P105982; -.
DR HGNC; HGNC:14235; AASDHPPT.
DR HPA; HPA026687; -.
DR MIM; 607756; gene.
DR neXtProt; NX_Q9NRN7; -.
DR PharmGKB; PA24368; -.
DR eggNOG; COG2091; -.
DR HOGENOM; HOG000265195; -.
DR HOVERGEN; HBG080822; -.
DR InParanoid; Q9NRN7; -.
DR KO; K06133; -.
DR OMA; SPRGKPY; -.
DR BioCyc; MetaCyc:HS14278-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR SABIO-RK; Q9NRN7; -.
DR EvolutionaryTrace; Q9NRN7; -.
DR GeneWiki; AASDHPPT; -.
DR GenomeRNAi; 60496; -.
DR NextBio; 65403; -.
DR PRO; PR:Q9NRN7; -.
DR ArrayExpress; Q9NRN7; -.
DR Bgee; Q9NRN7; -.
DR CleanEx; HS_AASDHPPT; -.
DR Genevestigator; Q9NRN7; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0008897; F:holo-[acyl-carrier-protein] synthase activity; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0009059; P:macromolecule biosynthetic process; IEA:InterPro.
DR GO; GO:0015939; P:pantothenate metabolic process; TAS:Reactome.
DR Gene3D; 3.90.470.20; -; 2.
DR InterPro; IPR008278; 4-PPantetheinyl_Trfase_SF.
DR Pfam; PF01648; ACPS; 1.
DR SUPFAM; SSF56214; SSF56214; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Cytoplasm; Direct protein sequencing;
KW Magnesium; Metal-binding; Phosphoprotein; Reference proteome;
KW Transferase.
FT CHAIN 1 309 L-aminoadipate-semialdehyde
FT dehydrogenase-phosphopantetheinyl
FT transferase.
FT /FTId=PRO_0000175736.
FT REGION 86 91 Coenzyme A binding.
FT REGION 108 111 Coenzyme A binding.
FT REGION 181 185 Coenzyme A binding.
FT METAL 129 129 Magnesium.
FT METAL 181 181 Magnesium.
FT BINDING 47 47 Coenzyme A.
FT MOD_RES 258 258 Phosphoserine.
FT MUTAGEN 47 47 R->A: Reduces affinity for magnesium 7-
FT fold, and enzyme activity 2-fold.
FT MUTAGEN 86 86 R->A: Reduces affinity for magnesium and
FT coenzyme A, and reduces enzyme activity
FT 7-fold.
FT MUTAGEN 111 111 H->A: Reduces affinity for magnesium 75-
FT fold, and enzyme activity 150-fold.
FT MUTAGEN 112 112 Q->E: Reduces affinity for magnesium 200-
FT fold and abolishes enzyme activity; when
FT associated with Q-181.
FT MUTAGEN 129 129 D->A: Reduces affinity for magnesium 10-
FT fold, and enzyme activity 30000-fold.
FT MUTAGEN 181 181 E->A: Reduces affinity for magnesium 40-
FT fold, and enzyme activity 32000-fold.
FT MUTAGEN 181 181 E->Q: Reduces affinity for magnesium 20-
FT fold, and enzyme activity 6500-fold.
FT MUTAGEN 185 185 K->A: Reduces enzyme activity 2000-fold,
FT with only minor change in the affinity
FT for magnesium and coenzyme A.
FT CONFLICT 136 141 PGRGSI -> FQVVVQF (in Ref. 4; AAG49439).
FT CONFLICT 307 309 TKS -> YKVMMIP (in Ref. 4; AAG49439).
FT STRAND 17 21
FT HELIX 23 25
FT HELIX 30 38
FT HELIX 42 49
FT HELIX 54 74
FT HELIX 79 81
FT STRAND 84 86
FT STRAND 92 94
FT STRAND 102 104
FT STRAND 106 112
FT STRAND 115 132
FT STRAND 137 139
FT HELIX 141 147
FT HELIX 149 151
FT HELIX 154 160
FT STRAND 163 165
FT HELIX 166 187
FT HELIX 190 192
FT HELIX 195 197
FT STRAND 198 201
FT STRAND 203 206
FT STRAND 217 220
FT STRAND 228 236
FT STRAND 239 246
FT STRAND 270 272
FT HELIX 274 277
FT TURN 278 280
FT HELIX 289 291
FT HELIX 298 300
FT TURN 305 307
SQ SEQUENCE 309 AA; 35776 MW; 6263E302600FDDED CRC64;
MVFPAKRFCL VPSMEGVRWA FSCGTWLPSR AEWLLAVRSI QPEEKERIGQ FVFARDAKAA
MAGRLMIRKL VAEKLNIPWN HIRLQRTAKG KPVLAKDSSN PYPNFNFNIS HQGDYAVLAA
EPELQVGIDI MKTSFPGRGS IPEFFHIMKR KFTNKEWETI RSFKDEWTQL DMFYRNWALK
ESFIKAIGVG LGFELQRLEF DLSPLNLDIG QVYKETRLFL DGEEEKEWAF EESKIDEHHF
VAVALRKPDG SRHQDVPSQD DSKPTQRQFT ILNFNDLMSS AVPMTPEDPS FWDCFCFTEE
IPIRNGTKS
//
ID ADPPT_HUMAN Reviewed; 309 AA.
AC Q9NRN7; B2R6D1; Q9C068; Q9P0Q3; Q9UG80; Q9Y389;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 08-NOV-2005, sequence version 2.
DT 22-JAN-2014, entry version 95.
DE RecName: Full=L-aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase;
DE EC=2.7.8.-;
DE AltName: Full=4'-phosphopantetheinyl transferase;
DE AltName: Full=Alpha-aminoadipic semialdehyde dehydrogenase-phosphopantetheinyl transferase;
DE Short=AASD-PPT;
DE AltName: Full=LYS5 ortholog;
GN Name=AASDHPPT; ORFNames=CGI-80, HAH-P, HSPC223, x0005;
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], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11286508; DOI=10.1006/mgme.2000.3138;
RA Praphanphoj V., Sacksteder K.A., Gould S.J., Thomas G.H.,
RA Geraghty M.T.;
RT "Identification of the alpha-aminoadipic semialdehyde dehydrogenase-
RT phosphopantetheinyl transferase gene, the human ortholog of the yeast
RT LYS5 gene.";
RL Mol. Genet. Metab. 72:336-342(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for
RT 300 previously undefined genes expressed in CD34+ hematopoietic
RT stem/progenitor cells.";
RL Genome Res. 10:1546-1560(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Adrenal gland;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H.,
RA Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J.,
RA Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M.,
RA Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal
RT axis and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Dendritic cell;
RA Li N., Peng Y., Li Y., Gu W., Han Z., Fu G., Chen Z.;
RT "Novel genes expressed in human dendritic cell.";
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Tongue;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Urinary bladder, and Uterus;
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 99-309.
RC TISSUE=Kidney;
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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [10]
RP PROTEIN SEQUENCE OF 235-246, AND MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (MAR-2007) to UniProtKB.
RN [11]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, COFACTOR, MASS SPECTROMETRY,
RP AND TISSUE SPECIFICITY.
RX PubMed=12815048; DOI=10.1074/jbc.M305459200;
RA Joshi A.K., Zhang L., Rangan V.S., Smith S.;
RT "Cloning, expression, and characterization of a human 4'-
RT phosphopantetheinyl transferase with broad substrate specificity.";
RL J. Biol. Chem. 278:33142-33149(2003).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-258, AND MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-258, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-258, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
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.,
RA Buerckstuemmer T., 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 [16]
RP X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 14-309 IN COMPLEXES WITH
RP COENZYME A; MAGNESIUM IONS AND FASN, FUNCTION, BIOPHYSICOCHEMICAL
RP PROPERTIES, COFACTOR, AND MUTAGENESIS OF ARG-47; ARG-86; HIS-111;
RP GLN-112; ASP-129; GLU-181 AND LYS-185.
RX PubMed=18022563; DOI=10.1016/j.chembiol.2007.10.013;
RA Bunkoczi G., Pasta S., Joshi A., Wu X., Kavanagh K.L., Smith S.,
RA Oppermann U.;
RT "Mechanism and substrate recognition of human holo ACP synthase.";
RL Chem. Biol. 14:1243-1253(2007).
CC -!- FUNCTION: Catalyzes the post-translational modification of target
CC proteins by phosphopantetheine. Can transfer the 4'-
CC phosphopantetheine moiety from coenzyme A to a serine residue of a
CC broad range of acceptors, such as the acyl carrier domain of FASN.
CC -!- CATALYTIC ACTIVITY: CoA-[4'-phosphopantetheine] + apo-[acyl-
CC carrier-protein] = adenosine 3',5'-bisphosphate + holo-[acyl-
CC carrier-protein].
CC -!- COFACTOR: Binds 1 magnesium ion.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.44 mM for magnesium;
CC KM=0.025 mM for coenzyme A;
CC -!- SUBUNIT: Monomer. Interacts with FASN.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Detected in heart, skeletal muscle, placenta,
CC testis, brain, pancreas, liver and kidney.
CC -!- SIMILARITY: Belongs to the P-Pant transferase superfamily. AcpS
CC family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD34075.1; Type=Frameshift; Positions=34, 63;
CC Sequence=AAF86879.1; Type=Erroneous initiation;
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DR EMBL; AF302110; AAG30872.1; -; mRNA.
DR EMBL; AF151838; AAD34075.1; ALT_FRAME; mRNA.
DR EMBL; AF151057; AAF36143.1; -; mRNA.
DR EMBL; AF136978; AAG49439.1; -; mRNA.
DR EMBL; AF201943; AAF86879.1; ALT_INIT; mRNA.
DR EMBL; AK312529; BAG35428.1; -; mRNA.
DR EMBL; CH471065; EAW67078.1; -; Genomic_DNA.
DR EMBL; BC015470; AAH15470.1; -; mRNA.
DR EMBL; BC016728; AAH16728.1; -; mRNA.
DR EMBL; AL050073; CAB43257.1; -; mRNA.
DR PIR; T08733; T08733.
DR RefSeq; NP_056238.2; NM_015423.2.
DR UniGene; Hs.524009; -.
DR PDB; 2BYD; X-ray; 2.00 A; A=14-309.
DR PDB; 2C43; X-ray; 1.93 A; A=14-309.
DR PDB; 2CG5; X-ray; 2.70 A; A=14-309.
DR PDBsum; 2BYD; -.
DR PDBsum; 2C43; -.
DR PDBsum; 2CG5; -.
DR ProteinModelPortal; Q9NRN7; -.
DR SMR; Q9NRN7; 14-289.
DR IntAct; Q9NRN7; 6.
DR MINT; MINT-5005661; -.
DR STRING; 9606.ENSP00000278618; -.
DR PhosphoSite; Q9NRN7; -.
DR DMDM; 81170356; -.
DR PaxDb; Q9NRN7; -.
DR PeptideAtlas; Q9NRN7; -.
DR PRIDE; Q9NRN7; -.
DR DNASU; 60496; -.
DR Ensembl; ENST00000278618; ENSP00000278618; ENSG00000149313.
DR GeneID; 60496; -.
DR KEGG; hsa:60496; -.
DR UCSC; uc001pjc.1; human.
DR CTD; 60496; -.
DR GeneCards; GC11P105982; -.
DR HGNC; HGNC:14235; AASDHPPT.
DR HPA; HPA026687; -.
DR MIM; 607756; gene.
DR neXtProt; NX_Q9NRN7; -.
DR PharmGKB; PA24368; -.
DR eggNOG; COG2091; -.
DR HOGENOM; HOG000265195; -.
DR HOVERGEN; HBG080822; -.
DR InParanoid; Q9NRN7; -.
DR KO; K06133; -.
DR OMA; SPRGKPY; -.
DR BioCyc; MetaCyc:HS14278-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR SABIO-RK; Q9NRN7; -.
DR EvolutionaryTrace; Q9NRN7; -.
DR GeneWiki; AASDHPPT; -.
DR GenomeRNAi; 60496; -.
DR NextBio; 65403; -.
DR PRO; PR:Q9NRN7; -.
DR ArrayExpress; Q9NRN7; -.
DR Bgee; Q9NRN7; -.
DR CleanEx; HS_AASDHPPT; -.
DR Genevestigator; Q9NRN7; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0008897; F:holo-[acyl-carrier-protein] synthase activity; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0009059; P:macromolecule biosynthetic process; IEA:InterPro.
DR GO; GO:0015939; P:pantothenate metabolic process; TAS:Reactome.
DR Gene3D; 3.90.470.20; -; 2.
DR InterPro; IPR008278; 4-PPantetheinyl_Trfase_SF.
DR Pfam; PF01648; ACPS; 1.
DR SUPFAM; SSF56214; SSF56214; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Cytoplasm; Direct protein sequencing;
KW Magnesium; Metal-binding; Phosphoprotein; Reference proteome;
KW Transferase.
FT CHAIN 1 309 L-aminoadipate-semialdehyde
FT dehydrogenase-phosphopantetheinyl
FT transferase.
FT /FTId=PRO_0000175736.
FT REGION 86 91 Coenzyme A binding.
FT REGION 108 111 Coenzyme A binding.
FT REGION 181 185 Coenzyme A binding.
FT METAL 129 129 Magnesium.
FT METAL 181 181 Magnesium.
FT BINDING 47 47 Coenzyme A.
FT MOD_RES 258 258 Phosphoserine.
FT MUTAGEN 47 47 R->A: Reduces affinity for magnesium 7-
FT fold, and enzyme activity 2-fold.
FT MUTAGEN 86 86 R->A: Reduces affinity for magnesium and
FT coenzyme A, and reduces enzyme activity
FT 7-fold.
FT MUTAGEN 111 111 H->A: Reduces affinity for magnesium 75-
FT fold, and enzyme activity 150-fold.
FT MUTAGEN 112 112 Q->E: Reduces affinity for magnesium 200-
FT fold and abolishes enzyme activity; when
FT associated with Q-181.
FT MUTAGEN 129 129 D->A: Reduces affinity for magnesium 10-
FT fold, and enzyme activity 30000-fold.
FT MUTAGEN 181 181 E->A: Reduces affinity for magnesium 40-
FT fold, and enzyme activity 32000-fold.
FT MUTAGEN 181 181 E->Q: Reduces affinity for magnesium 20-
FT fold, and enzyme activity 6500-fold.
FT MUTAGEN 185 185 K->A: Reduces enzyme activity 2000-fold,
FT with only minor change in the affinity
FT for magnesium and coenzyme A.
FT CONFLICT 136 141 PGRGSI -> FQVVVQF (in Ref. 4; AAG49439).
FT CONFLICT 307 309 TKS -> YKVMMIP (in Ref. 4; AAG49439).
FT STRAND 17 21
FT HELIX 23 25
FT HELIX 30 38
FT HELIX 42 49
FT HELIX 54 74
FT HELIX 79 81
FT STRAND 84 86
FT STRAND 92 94
FT STRAND 102 104
FT STRAND 106 112
FT STRAND 115 132
FT STRAND 137 139
FT HELIX 141 147
FT HELIX 149 151
FT HELIX 154 160
FT STRAND 163 165
FT HELIX 166 187
FT HELIX 190 192
FT HELIX 195 197
FT STRAND 198 201
FT STRAND 203 206
FT STRAND 217 220
FT STRAND 228 236
FT STRAND 239 246
FT STRAND 270 272
FT HELIX 274 277
FT TURN 278 280
FT HELIX 289 291
FT HELIX 298 300
FT TURN 305 307
SQ SEQUENCE 309 AA; 35776 MW; 6263E302600FDDED CRC64;
MVFPAKRFCL VPSMEGVRWA FSCGTWLPSR AEWLLAVRSI QPEEKERIGQ FVFARDAKAA
MAGRLMIRKL VAEKLNIPWN HIRLQRTAKG KPVLAKDSSN PYPNFNFNIS HQGDYAVLAA
EPELQVGIDI MKTSFPGRGS IPEFFHIMKR KFTNKEWETI RSFKDEWTQL DMFYRNWALK
ESFIKAIGVG LGFELQRLEF DLSPLNLDIG QVYKETRLFL DGEEEKEWAF EESKIDEHHF
VAVALRKPDG SRHQDVPSQD DSKPTQRQFT ILNFNDLMSS AVPMTPEDPS FWDCFCFTEE
IPIRNGTKS
//
MIM
607756
*RECORD*
*FIELD* NO
607756
*FIELD* TI
*607756 ALPHA-AMINOADIPATE SEMIALDEHYDE DEHYDROGENASE-PHOSPHOPANTETHEINYL
TRANSFERASE; AASDHPPT
read more;;AASDPPT;;
LYS5, S. CEREVISIAE, HOMOLOG OF;;
CGI-80;;
DKFZP566E2346
*FIELD* TX
DESCRIPTION
In mammals, L-lysine is first catabolized to alpha-aminoadipate
semialdehyde by the bifunctional enzyme alpha-aminoadipate semialdehyde
synthase (AASS; 605113), followed by a conversion to alpha-aminoadipate
(AAA) by alpha-aminoadipate semialdehyde dehydrogenase (AASDH). In S.
cerevisiae, which synthesize rather than degrade lysine, the latter
activity requires 2 distinct genes. LYS2 encodes the alpha-aminoadipate
reductase activity, while LYS5 encodes a phosphopantetheinyl transferase
activity that is required to activate LYS2 protein.
CLONING
Praphanphoj et al. (2001) identified a full-length human cDNA homologous
to the yeast LYS5 gene. The cDNA contains an open reading frame of 930
basepairs predicted to encode 309 amino acids, and the human protein is
26% identical to its yeast counterpart. Northern blot analysis detected
a single transcript of approximately 3 kb in all tissues except testis,
where there was an additional transcript of 1.5 kb. Expression is
highest in brain followed by heart and skeletal muscle, and to a lesser
extent in liver.
MAPPING
By FISH, Praphanphoj et al. (2001) mapped the human AASDPPT gene to
chromosome 11q22.
GENE FUNCTION
Praphanphoj et al. (2001) used complementation studies in a yeast
knockout of LYS5 to demonstrate that the human homolog encodes
alpha-aminoadipate dehydrogenase-phosphopantetheinyl transferase
activity. Kasahara and Kato (2003) fed mice a lysine-rich diet
(containing 2,000-fold more free lysine than normal) and found that
blood concentrations of lysine and 2-aminoadipic acid (AAA) were
markedly increased. The level of U26, or mouse aminoadipic
6-semialdehyde dehydrogenase (AASDH), in the liver and heart of
lysine-loaded mice was significantly higher than in control mice. Mouse
AASS and Lys5 transcripts were also increased in the lysine-loaded mice.
Kasahara and Kato (2003) concluded that U26, as well as AASS and LYS5,
is involved in the lysine degradation pathway in mice. They found that
pyrroloquinoline quinone (PQQ) is a crucial redox cofactor in this
reaction and qualifies as a newcomer to the B group of vitamins.
*FIELD* RF
1. Kasahara, T.; Kato, T.: A new redox-cofactor vitamin for mammals. Nature 422:
832 only, 2003.
2. Praphanphoj, V.; Sacksteder, K. A.; Gould, S. J.; Thomas, G. H.;
Geraghty, M. T.: Identification of the alpha-aminoadipic semialdehyde
dehydrogenase-phosphopantetheinyl transferase gene, the human ortholog
of the yeast LYS5 gene. Molec. Genet. Metab. 72: 336-342, 2001.
*FIELD* CD
Ada Hamosh: 5/7/2003
*FIELD* ED
alopez: 05/07/2003
*RECORD*
*FIELD* NO
607756
*FIELD* TI
*607756 ALPHA-AMINOADIPATE SEMIALDEHYDE DEHYDROGENASE-PHOSPHOPANTETHEINYL
TRANSFERASE; AASDHPPT
read more;;AASDPPT;;
LYS5, S. CEREVISIAE, HOMOLOG OF;;
CGI-80;;
DKFZP566E2346
*FIELD* TX
DESCRIPTION
In mammals, L-lysine is first catabolized to alpha-aminoadipate
semialdehyde by the bifunctional enzyme alpha-aminoadipate semialdehyde
synthase (AASS; 605113), followed by a conversion to alpha-aminoadipate
(AAA) by alpha-aminoadipate semialdehyde dehydrogenase (AASDH). In S.
cerevisiae, which synthesize rather than degrade lysine, the latter
activity requires 2 distinct genes. LYS2 encodes the alpha-aminoadipate
reductase activity, while LYS5 encodes a phosphopantetheinyl transferase
activity that is required to activate LYS2 protein.
CLONING
Praphanphoj et al. (2001) identified a full-length human cDNA homologous
to the yeast LYS5 gene. The cDNA contains an open reading frame of 930
basepairs predicted to encode 309 amino acids, and the human protein is
26% identical to its yeast counterpart. Northern blot analysis detected
a single transcript of approximately 3 kb in all tissues except testis,
where there was an additional transcript of 1.5 kb. Expression is
highest in brain followed by heart and skeletal muscle, and to a lesser
extent in liver.
MAPPING
By FISH, Praphanphoj et al. (2001) mapped the human AASDPPT gene to
chromosome 11q22.
GENE FUNCTION
Praphanphoj et al. (2001) used complementation studies in a yeast
knockout of LYS5 to demonstrate that the human homolog encodes
alpha-aminoadipate dehydrogenase-phosphopantetheinyl transferase
activity. Kasahara and Kato (2003) fed mice a lysine-rich diet
(containing 2,000-fold more free lysine than normal) and found that
blood concentrations of lysine and 2-aminoadipic acid (AAA) were
markedly increased. The level of U26, or mouse aminoadipic
6-semialdehyde dehydrogenase (AASDH), in the liver and heart of
lysine-loaded mice was significantly higher than in control mice. Mouse
AASS and Lys5 transcripts were also increased in the lysine-loaded mice.
Kasahara and Kato (2003) concluded that U26, as well as AASS and LYS5,
is involved in the lysine degradation pathway in mice. They found that
pyrroloquinoline quinone (PQQ) is a crucial redox cofactor in this
reaction and qualifies as a newcomer to the B group of vitamins.
*FIELD* RF
1. Kasahara, T.; Kato, T.: A new redox-cofactor vitamin for mammals. Nature 422:
832 only, 2003.
2. Praphanphoj, V.; Sacksteder, K. A.; Gould, S. J.; Thomas, G. H.;
Geraghty, M. T.: Identification of the alpha-aminoadipic semialdehyde
dehydrogenase-phosphopantetheinyl transferase gene, the human ortholog
of the yeast LYS5 gene. Molec. Genet. Metab. 72: 336-342, 2001.
*FIELD* CD
Ada Hamosh: 5/7/2003
*FIELD* ED
alopez: 05/07/2003