COAC_HUMAN
ID COAC_HUMAN Reviewed; 204 AA.
AC Q96CD2; Q96SX0; Q9HC17;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Phosphopantothenoylcysteine decarboxylase;
DE Short=PPC-DC;
DE EC=4.1.1.36 {ECO:0000269|PubMed:11923312, ECO:0000269|PubMed:15581364};
DE AltName: Full=CoaC;
GN Name=PPCDC; Synonyms=COAC; ORFNames=MDS018, UNQ9365/PRO34154;
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 [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Hematopoietic stem cell;
RA Huang C., Qian B., Tu Y., Gu W., Wang Y., Han Z., Chen Z.;
RT "Novel genes expressed in hematopoietic stem/progenitor cells from
RT myelodysplastic syndrome patients.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [5]
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 [6]
RP IDENTIFICATION, FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=11923312; DOI=10.1074/jbc.m201708200;
RA Daugherty M., Polanuyer B., Farrell M., Scholle M., Lykidis A.,
RA de Crecy-Lagard V., Osterman A.;
RT "Complete reconstitution of the human coenzyme A biosynthetic pathway via
RT comparative genomics.";
RL J. Biol. Chem. 277:21431-21439(2002).
RN [7]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, CATALYTIC ACTIVITY, AND
RP MUTAGENESIS OF CYS-173.
RX PubMed=15581364; DOI=10.1021/bi048340a;
RA Strauss E., Zhai H., Brand L.A., McLafferty F.W., Begley T.P.;
RT "Mechanistic studies on phosphopantothenoylcysteine decarboxylase: trapping
RT of an enethiolate intermediate with a mechanism-based inactivating agent.";
RL Biochemistry 43:15520-15533(2004).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.91 ANGSTROMS) IN COMPLEX WITH FMN, SUBUNIT, AND
RP COFACTOR.
RX PubMed=14501115; DOI=10.1107/s0907444903016214;
RA Manoj N., Ealick S.E.;
RT "Unusual space-group pseudosymmetry in crystals of human
RT phosphopantothenoylcysteine decarboxylase.";
RL Acta Crystallogr. D 59:1762-1766(2003).
CC -!- FUNCTION: Catalyzes the decarboxylation of the cysteine moiety of 4-
CC phosphopantothenoylcysteine to form 4'-phosphopantotheine and this
CC reaction forms part of the biosynthesis of coenzyme A.
CC {ECO:0000269|PubMed:11923312, ECO:0000269|PubMed:15581364}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + N-[(R)-4-phosphopantothenoyl]-L-cysteine = (R)-4'-
CC phosphopantetheine + CO2; Xref=Rhea:RHEA:16793, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:59458, ChEBI:CHEBI:61723; EC=4.1.1.36;
CC Evidence={ECO:0000269|PubMed:11923312, ECO:0000269|PubMed:15581364};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16794;
CC Evidence={ECO:0000305|PubMed:11923312};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000269|PubMed:14501115};
CC Note=Binds 1 FMN per subunit. {ECO:0000269|PubMed:14501115};
CC -!- PATHWAY: Cofactor biosynthesis; coenzyme A biosynthesis; CoA from (R)-
CC pantothenate: step 3/5. {ECO:0000269|PubMed:11923312}.
CC -!- SUBUNIT: Homotrimer. {ECO:0000269|PubMed:14501115}.
CC -!- INTERACTION:
CC Q96CD2; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-724333, EBI-742054;
CC Q96CD2; Q6PIV2: FOXR1; NbExp=10; IntAct=EBI-724333, EBI-10253815;
CC Q96CD2; Q93015-2: NAA80; NbExp=3; IntAct=EBI-724333, EBI-12126220;
CC Q96CD2; Q96HA8: NTAQ1; NbExp=6; IntAct=EBI-724333, EBI-741158;
CC Q96CD2; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-724333, EBI-742388;
CC Q96CD2; Q96CD2: PPCDC; NbExp=5; IntAct=EBI-724333, EBI-724333;
CC Q96CD2; Q13427: PPIG; NbExp=3; IntAct=EBI-724333, EBI-396072;
CC Q96CD2; O76064: RNF8; NbExp=3; IntAct=EBI-724333, EBI-373337;
CC Q96CD2; Q8N9Q2: SREK1IP1; NbExp=3; IntAct=EBI-724333, EBI-10268630;
CC Q96CD2; Q96PF1: TGM7; NbExp=3; IntAct=EBI-724333, EBI-12029034;
CC Q96CD2; Q99757: TXN2; NbExp=6; IntAct=EBI-724333, EBI-2932492;
CC Q96CD2; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-724333, EBI-10180829;
CC Q96CD2; Q9UNY5: ZNF232; NbExp=6; IntAct=EBI-724333, EBI-749023;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96CD2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96CD2-2; Sequence=VSP_044802;
CC -!- MISCELLANEOUS: [Isoform 2]: The Met-1 codon is associated with a
CC polymorphism (dbSNP:rs2304899) that replaces the initiation ATG codon
CC by an ATA codon. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the HFCD (homooligomeric flavin containing Cys
CC decarboxylase) superfamily. {ECO:0000305}.
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DR EMBL; AF182419; AAG14955.1; -; mRNA.
DR EMBL; AY358848; AAQ89207.1; -; mRNA.
DR EMBL; AK027491; BAB55151.1; -; mRNA.
DR EMBL; AC015720; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC014409; AAH14409.1; -; mRNA.
DR CCDS; CCDS10275.1; -. [Q96CD2-1]
DR RefSeq; NP_001288030.1; NM_001301101.1.
DR RefSeq; NP_001288031.1; NM_001301102.1.
DR RefSeq; NP_001288032.1; NM_001301103.1.
DR RefSeq; NP_001288033.1; NM_001301104.1.
DR RefSeq; NP_001288034.1; NM_001301105.1.
DR RefSeq; NP_068595.3; NM_021823.4. [Q96CD2-1]
DR PDB; 1QZU; X-ray; 2.91 A; A/B/C/D=1-204.
DR PDBsum; 1QZU; -.
DR AlphaFoldDB; Q96CD2; -.
DR SMR; Q96CD2; -.
DR BioGRID; 121921; 16.
DR IntAct; Q96CD2; 16.
DR MINT; Q96CD2; -.
DR STRING; 9606.ENSP00000343190; -.
DR DrugBank; DB03247; Flavin mononucleotide.
DR DrugBank; DB03738; Pantothenoylaminoethenethiol.
DR GlyGen; Q96CD2; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96CD2; -.
DR PhosphoSitePlus; Q96CD2; -.
DR BioMuta; PPCDC; -.
DR DMDM; 296434457; -.
DR EPD; Q96CD2; -.
DR jPOST; Q96CD2; -.
DR MassIVE; Q96CD2; -.
DR MaxQB; Q96CD2; -.
DR PaxDb; Q96CD2; -.
DR PeptideAtlas; Q96CD2; -.
DR PRIDE; Q96CD2; -.
DR ProteomicsDB; 76180; -. [Q96CD2-1]
DR ProteomicsDB; 76181; -. [Q96CD2-2]
DR Antibodypedia; 14730; 115 antibodies from 19 providers.
DR DNASU; 60490; -.
DR Ensembl; ENST00000342932.8; ENSP00000343190.3; ENSG00000138621.12. [Q96CD2-1]
DR GeneID; 60490; -.
DR KEGG; hsa:60490; -.
DR MANE-Select; ENST00000342932.8; ENSP00000343190.3; NM_021823.5; NP_068595.3.
DR UCSC; uc002azo.4; human. [Q96CD2-1]
DR CTD; 60490; -.
DR DisGeNET; 60490; -.
DR GeneCards; PPCDC; -.
DR HGNC; HGNC:28107; PPCDC.
DR HPA; ENSG00000138621; Low tissue specificity.
DR MIM; 609854; gene.
DR neXtProt; NX_Q96CD2; -.
DR OpenTargets; ENSG00000138621; -.
DR PharmGKB; PA142671157; -.
DR VEuPathDB; HostDB:ENSG00000138621; -.
DR eggNOG; KOG0672; Eukaryota.
DR GeneTree; ENSGT00440000038107; -.
DR HOGENOM; CLU_033319_3_2_1; -.
DR InParanoid; Q96CD2; -.
DR OMA; NTRMYDH; -.
DR OrthoDB; 1225808at2759; -.
DR PhylomeDB; Q96CD2; -.
DR TreeFam; TF315740; -.
DR BioCyc; MetaCyc:HS13735-MON; -.
DR PathwayCommons; Q96CD2; -.
DR Reactome; R-HSA-196783; Coenzyme A biosynthesis.
DR SABIO-RK; Q96CD2; -.
DR SignaLink; Q96CD2; -.
DR UniPathway; UPA00241; UER00354.
DR BioGRID-ORCS; 60490; 102 hits in 1079 CRISPR screens.
DR ChiTaRS; PPCDC; human.
DR EvolutionaryTrace; Q96CD2; -.
DR GenomeRNAi; 60490; -.
DR Pharos; Q96CD2; Tbio.
DR PRO; PR:Q96CD2; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q96CD2; protein.
DR Bgee; ENSG00000138621; Expressed in blood and 143 other tissues.
DR ExpressionAtlas; Q96CD2; baseline and differential.
DR Genevisible; Q96CD2; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0071513; C:phosphopantothenoylcysteine decarboxylase complex; IBA:GO_Central.
DR GO; GO:0010181; F:FMN binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0004633; F:phosphopantothenoylcysteine decarboxylase activity; IDA:UniProtKB.
DR GO; GO:0015937; P:coenzyme A biosynthetic process; IDA:UniProtKB.
DR Gene3D; 3.40.50.1950; -; 1.
DR InterPro; IPR036551; Flavin_trans-like.
DR InterPro; IPR003382; Flavoprotein.
DR Pfam; PF02441; Flavoprotein; 1.
DR SUPFAM; SSF52507; SSF52507; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coenzyme A biosynthesis; Decarboxylase;
KW Flavoprotein; FMN; Lyase; Reference proteome.
FT CHAIN 1..204
FT /note="Phosphopantothenoylcysteine decarboxylase"
FT /id="PRO_0000182030"
FT ACT_SITE 173
FT /note="Proton donor"
FT /evidence="ECO:0000305|PubMed:15581364"
FT BINDING 59
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:14501115"
FT BINDING 104..107
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:14501115"
FT BINDING 140
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..78
FT /note="MEPKASCPAAAPLMERKFHVLVGVTGSVAALKLPLLVSKLLDIPGLEVAVVT
FT TERAKHFYSPQDIPVTLYSDADEWEI -> M (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_044802"
FT VARIANT 78
FT /note="I -> M (in dbSNP:rs2304899)"
FT /id="VAR_068974"
FT MUTAGEN 173
FT /note="C->S: Loss of activity."
FT /evidence="ECO:0000269|PubMed:15581364"
FT CONFLICT 49
FT /note="A -> S (in Ref. 3; BAB55151)"
FT /evidence="ECO:0000305"
FT STRAND 16..24
FT /evidence="ECO:0007829|PDB:1QZU"
FT HELIX 28..31
FT /evidence="ECO:0007829|PDB:1QZU"
FT HELIX 33..40
FT /evidence="ECO:0007829|PDB:1QZU"
FT STRAND 46..52
FT /evidence="ECO:0007829|PDB:1QZU"
FT HELIX 55..58
FT /evidence="ECO:0007829|PDB:1QZU"
FT HELIX 62..64
FT /evidence="ECO:0007829|PDB:1QZU"
FT HELIX 72..77
FT /evidence="ECO:0007829|PDB:1QZU"
FT HELIX 87..92
FT /evidence="ECO:0007829|PDB:1QZU"
FT STRAND 96..103
FT /evidence="ECO:0007829|PDB:1QZU"
FT HELIX 105..112
FT /evidence="ECO:0007829|PDB:1QZU"
FT HELIX 119..125
FT /evidence="ECO:0007829|PDB:1QZU"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:1QZU"
FT HELIX 141..144
FT /evidence="ECO:0007829|PDB:1QZU"
FT HELIX 149..157
FT /evidence="ECO:0007829|PDB:1QZU"
FT HELIX 186..191
FT /evidence="ECO:0007829|PDB:1QZU"
SQ SEQUENCE 204 AA; 22395 MW; 9E59683480032894 CRC64;
MEPKASCPAA APLMERKFHV LVGVTGSVAA LKLPLLVSKL LDIPGLEVAV VTTERAKHFY
SPQDIPVTLY SDADEWEIWK SRSDPVLHID LRRWADLLLV APLDANTLGK VASGICDNLL
TCVMRAWDRS KPLLFCPAMN TAMWEHPITA QQVDQLKAFG YVEIPCVAKK LVCGDEGLGA
MAEVGTIVDK VKEVLFQHSG FQQS
