DEFM_HUMAN
ID DEFM_HUMAN Reviewed; 243 AA.
AC Q9HBH1; Q8WUN6;
DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Peptide deformylase, mitochondrial {ECO:0000303|PubMed:19236878};
DE EC=3.5.1.88 {ECO:0000269|PubMed:19236878};
DE AltName: Full=Polypeptide deformylase;
DE Flags: Precursor;
GN Name=PDF {ECO:0000303|PubMed:19236878};
GN Synonyms=PDF1A {ECO:0000303|PubMed:11060042};
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].
RX PubMed=11060042; DOI=10.1093/emboj/19.21.5916;
RA Giglione C., Serero A., Pierre M., Boisson B., Meinnel T.;
RT "Identification of eukaryotic peptide deformylases reveals universality of
RT N-terminal protein processing mechanisms.";
RL EMBO J. 19:5916-5929(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Lonetto M.A., Zhu Y., Li X., Southan C.;
RT "A human homolog of bacterial peptide deformylases.";
RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-11.
RC TISSUE=Placenta;
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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP TRANSIT PEPTIDE CLEAVAGE SITE.
RX PubMed=14532271; DOI=10.1074/jbc.m309770200;
RA Serero A., Giglione C., Sardini A., Martinez-Sanz J., Meinnel T.;
RT "An unusual peptide deformylase features in the human mitochondrial N-
RT terminal methionine excision pathway.";
RL J. Biol. Chem. 278:52953-52963(2003).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=15489958; DOI=10.1172/jci200422269;
RA Lee M.D., She Y., Soskis M.J., Borella C.P., Gardner J.R., Hayes P.A.,
RA Dy B.M., Heaney M.L., Philips M.R., Bornmann W.G., Sirotnak F.M.,
RA Scheinberg D.A.;
RT "Human mitochondrial peptide deformylase, a new anticancer target of
RT actinonin-based antibiotics.";
RL J. Clin. Invest. 114:1107-1116(2004).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 64-243 IN COMPLEX WITH SUBSTRATE
RP ANALOG AND COBALT ION, FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP METAL-BINDING SITES, SUBSTRATE-BINDING SITES, AND SUBUNIT.
RX PubMed=19236878; DOI=10.1016/j.jmb.2009.02.032;
RA Escobar-Alvarez S., Goldgur Y., Yang G., Ouerfelli O., Li Y.,
RA Scheinberg D.A.;
RT "Structure and activity of human mitochondrial peptide deformylase, a novel
RT cancer target.";
RL J. Mol. Biol. 387:1211-1228(2009).
CC -!- FUNCTION: Removes the formyl group from the N-terminal Met of newly
CC synthesized proteins. {ECO:0000269|PubMed:14532271,
CC ECO:0000269|PubMed:15489958, ECO:0000269|PubMed:19236878}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-terminal N-formyl-L-methionyl-[peptide] = formate + N-
CC terminal L-methionyl-[peptide]; Xref=Rhea:RHEA:24420, Rhea:RHEA-
CC COMP:10639, Rhea:RHEA-COMP:10640, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15740, ChEBI:CHEBI:49298, ChEBI:CHEBI:64731; EC=3.5.1.88;
CC Evidence={ECO:0000269|PubMed:14532271, ECO:0000269|PubMed:15489958,
CC ECO:0000269|PubMed:19236878};
CC -!- COFACTOR:
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000305|PubMed:19236878};
CC Note=Binds 1 Co(2+) ion. {ECO:0000305|PubMed:19236878};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:19236878}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14532271,
CC ECO:0000269|PubMed:15489958}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:14532271}.
CC -!- SIMILARITY: Belongs to the polypeptide deformylase family.
CC {ECO:0000305}.
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DR EMBL; AF239156; AAG33968.1; -; mRNA.
DR EMBL; AF322879; AAK15624.1; -; mRNA.
DR EMBL; BC019912; AAH19912.1; -; mRNA.
DR CCDS; CCDS10875.1; -.
DR RefSeq; NP_071736.1; NM_022341.1.
DR PDB; 3G5K; X-ray; 1.70 A; A/B/C/D=64-243.
DR PDB; 3G5P; X-ray; 1.70 A; A/B/C/D=64-243.
DR PDBsum; 3G5K; -.
DR PDBsum; 3G5P; -.
DR AlphaFoldDB; Q9HBH1; -.
DR SMR; Q9HBH1; -.
DR BioGRID; 122085; 110.
DR IntAct; Q9HBH1; 47.
DR STRING; 9606.ENSP00000288022; -.
DR BindingDB; Q9HBH1; -.
DR ChEMBL; CHEMBL4647; -.
DR DrugBank; DB04310; 2-[(Formyl-Hydroxy-Amino)-Methyl]-Heptanoic Acid [1-(2-Hydroxymethyl-Pyrrolidine-1-Carbonyl)-2-Methyl-Propyl]-Amide.
DR DrugBank; DB04368; Bb-3497.
DR SwissPalm; Q9HBH1; -.
DR BioMuta; PDF; -.
DR DMDM; 17433054; -.
DR EPD; Q9HBH1; -.
DR jPOST; Q9HBH1; -.
DR MassIVE; Q9HBH1; -.
DR MaxQB; Q9HBH1; -.
DR PaxDb; Q9HBH1; -.
DR PeptideAtlas; Q9HBH1; -.
DR PRIDE; Q9HBH1; -.
DR ProteomicsDB; 81550; -.
DR Antibodypedia; 56384; 175 antibodies from 22 providers.
DR DNASU; 64146; -.
DR Ensembl; ENST00000288022.2; ENSP00000288022.1; ENSG00000258429.2.
DR GeneID; 64146; -.
DR KEGG; hsa:64146; -.
DR MANE-Select; ENST00000288022.2; ENSP00000288022.1; NM_022341.2; NP_071736.1.
DR UCSC; uc002ewx.1; human.
DR CTD; 64146; -.
DR DisGeNET; 64146; -.
DR GeneCards; PDF; -.
DR HGNC; HGNC:30012; PDF.
DR HPA; ENSG00000258429; Tissue enhanced (liver).
DR MIM; 618720; gene.
DR neXtProt; NX_Q9HBH1; -.
DR OpenTargets; ENSG00000258429; -.
DR PharmGKB; PA144596394; -.
DR VEuPathDB; HostDB:ENSG00000258429; -.
DR eggNOG; KOG3137; Eukaryota.
DR GeneTree; ENSGT00390000018698; -.
DR HOGENOM; CLU_061901_5_1_1; -.
DR InParanoid; Q9HBH1; -.
DR OMA; ILYPMRI; -.
DR PhylomeDB; Q9HBH1; -.
DR TreeFam; TF323637; -.
DR BRENDA; 3.5.1.88; 2681.
DR PathwayCommons; Q9HBH1; -.
DR SABIO-RK; Q9HBH1; -.
DR SignaLink; Q9HBH1; -.
DR BioGRID-ORCS; 64146; 12 hits in 1076 CRISPR screens.
DR EvolutionaryTrace; Q9HBH1; -.
DR GeneWiki; PDF_(gene); -.
DR GenomeRNAi; 64146; -.
DR Pharos; Q9HBH1; Tchem.
DR PRO; PR:Q9HBH1; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9HBH1; protein.
DR Bgee; ENSG00000258429; Expressed in adult mammalian kidney and 96 other tissues.
DR ExpressionAtlas; Q9HBH1; baseline and differential.
DR Genevisible; Q9HBH1; HS.
DR GO; GO:0005739; C:mitochondrion; IDA:HGNC-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042586; F:peptide deformylase activity; IDA:UniProtKB.
DR GO; GO:0043686; P:co-translational protein modification; IBA:GO_Central.
DR GO; GO:0031365; P:N-terminal protein amino acid modification; IDA:HGNC-UCL.
DR GO; GO:0018206; P:peptidyl-methionine modification; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:HGNC-UCL.
DR GO; GO:0006412; P:translation; IEA:UniProtKB-KW.
DR CDD; cd00487; Pep_deformylase; 1.
DR Gene3D; 3.90.45.10; -; 1.
DR HAMAP; MF_00163; Pep_deformylase; 1.
DR InterPro; IPR023635; Peptide_deformylase.
DR InterPro; IPR036821; Peptide_deformylase_sf.
DR PANTHER; PTHR10458; PTHR10458; 1.
DR Pfam; PF01327; Pep_deformylase; 1.
DR PRINTS; PR01576; PDEFORMYLASE.
DR SUPFAM; SSF56420; SSF56420; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cobalt; Hydrolase; Metal-binding; Mitochondrion;
KW Protein biosynthesis; Reference proteome; Transit peptide.
FT TRANSIT 1..39
FT /note="Mitochondrion"
FT /evidence="ECO:0000305|PubMed:14532271"
FT CHAIN 40..243
FT /note="Peptide deformylase, mitochondrial"
FT /id="PRO_0000006729"
FT REGION 165..175
FT /note="Hydrophobic dimerization interface"
FT /evidence="ECO:0000269|PubMed:19236878"
FT ACT_SITE 215
FT /evidence="ECO:0000250|UniProtKB:P0A6K3"
FT BINDING 71
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19236878"
FT BINDING 169
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19236878"
FT BINDING 171
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19236878"
FT BINDING 172
FT /ligand="Co(2+)"
FT /ligand_id="ChEBI:CHEBI:48828"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:19236878"
FT BINDING 214
FT /ligand="Co(2+)"
FT /ligand_id="ChEBI:CHEBI:48828"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:19236878"
FT BINDING 218
FT /ligand="Co(2+)"
FT /ligand_id="ChEBI:CHEBI:48828"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:19236878"
FT VARIANT 11
FT /note="W -> R (in dbSNP:rs8057004)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_060122"
FT HELIX 73..75
FT /evidence="ECO:0007829|PDB:3G5K"
FT HELIX 84..86
FT /evidence="ECO:0007829|PDB:3G5K"
FT HELIX 90..105
FT /evidence="ECO:0007829|PDB:3G5K"
FT STRAND 109..112
FT /evidence="ECO:0007829|PDB:3G5K"
FT HELIX 113..116
FT /evidence="ECO:0007829|PDB:3G5K"
FT STRAND 120..127
FT /evidence="ECO:0007829|PDB:3G5K"
FT HELIX 129..133
FT /evidence="ECO:0007829|PDB:3G5K"
FT HELIX 137..143
FT /evidence="ECO:0007829|PDB:3G5K"
FT STRAND 148..170
FT /evidence="ECO:0007829|PDB:3G5K"
FT STRAND 178..193
FT /evidence="ECO:0007829|PDB:3G5K"
FT STRAND 199..205
FT /evidence="ECO:0007829|PDB:3G5K"
FT HELIX 206..219
FT /evidence="ECO:0007829|PDB:3G5K"
FT HELIX 224..226
FT /evidence="ECO:0007829|PDB:3G5K"
FT HELIX 230..232
FT /evidence="ECO:0007829|PDB:3G5K"
SQ SEQUENCE 243 AA; 27013 MW; B15A3456F0F8D689 CRC64;
MARLWGALSL WPLWAAVPWG GAAAVGVRAC SSTAAPDGVE GPALRRSYWR HLRRLVLGPP
EPPFSHVCQV GDPVLRGVAA PVERAQLGGP ELQRLTQRLV QVMRRRRCVG LSAPQLGVPR
QVLALELPEA LCRECPPRQR ALRQMEPFPL RVFVNPSLRV LDSRLVTFPE GCESVAGFLA
CVPRFQAVQI SGLDPNGEQV VWQASGWAAR IIQHEMDHLQ GCLFIDKMDS RTFTNVYWMK
VND
