DHYSC_TRYB2
ID DHYSC_TRYB2 Reviewed; 461 AA.
AC Q38BX0;
DT 15-FEB-2017, integrated into UniProtKB/Swiss-Prot.
DT 22-NOV-2005, sequence version 1.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=Deoxyhypusine synthase {ECO:0000303|PubMed:23525104};
DE EC=2.5.1.46 {ECO:0000269|PubMed:23525104};
GN Name=DHSc {ECO:0000303|PubMed:23525104};
GN ORFNames=Tb10.70.4900 {ECO:0000312|EMBL:EAN77700.1};
OS Trypanosoma brucei brucei (strain 927/4 GUTat10.1).
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Trypanosoma.
OX NCBI_TaxID=185431 {ECO:0000312|Proteomes:UP000008524};
RN [1] {ECO:0000312|Proteomes:UP000008524}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=927/4 GUTat10.1;
RX PubMed=16020726; DOI=10.1126/science.1112642;
RA Berriman M., Ghedin E., Hertz-Fowler C., Blandin G., Renauld H.,
RA Bartholomeu D.C., Lennard N.J., Caler E., Hamlin N.E., Haas B., Bohme U.,
RA Hannick L., Aslett M.A., Shallom J., Marcello L., Hou L., Wickstead B.,
RA Alsmark U.C.M., Arrowsmith C., Atkin R.J., Barron A.J., Bringaud F.,
RA Brooks K., Carrington M., Cherevach I., Chillingworth T.J., Churcher C.,
RA Clark L.N., Corton C.H., Cronin A., Davies R.M., Doggett J., Djikeng A.,
RA Feldblyum T., Field M.C., Fraser A., Goodhead I., Hance Z., Harper D.,
RA Harris B.R., Hauser H., Hostetler J., Ivens A., Jagels K., Johnson D.,
RA Johnson J., Jones K., Kerhornou A.X., Koo H., Larke N., Landfear S.,
RA Larkin C., Leech V., Line A., Lord A., Macleod A., Mooney P.J., Moule S.,
RA Martin D.M., Morgan G.W., Mungall K., Norbertczak H., Ormond D., Pai G.,
RA Peacock C.S., Peterson J., Quail M.A., Rabbinowitsch E., Rajandream M.A.,
RA Reitter C., Salzberg S.L., Sanders M., Schobel S., Sharp S., Simmonds M.,
RA Simpson A.J., Tallon L., Turner C.M., Tait A., Tivey A.R., Van Aken S.,
RA Walker D., Wanless D., Wang S., White B., White O., Whitehead S.,
RA Woodward J., Wortman J., Adams M.D., Embley T.M., Gull K., Ullu E.,
RA Barry J.D., Fairlamb A.H., Opperdoes F., Barrell B.G., Donelson J.E.,
RA Hall N., Fraser C.M., Melville S.E., El-Sayed N.M.A.;
RT "The genome of the African trypanosome Trypanosoma brucei.";
RL Science 309:416-422(2005).
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, SUBUNIT, AND DISRUPTION PHENOTYPE.
RX PubMed=23525104; DOI=10.1074/jbc.m113.461137;
RA Nguyen S., Jones D.C., Wyllie S., Fairlamb A.H., Phillips M.A.;
RT "Allosteric activation of trypanosomatid deoxyhypusine synthase by a
RT catalytically dead paralog.";
RL J. Biol. Chem. 288:15256-15267(2013).
CC -!- FUNCTION: In association with the non-catalytic regulatory subunit
CC DHSp, catalyzes the NAD-dependent oxidative cleavage of spermidine and
CC the subsequent transfer of the butylamine moiety of spermidine to the
CC epsilon-amino group of a specific lysine residue of the eIF5A precursor
CC protein to form the intermediate deoxyhypusine residue. Regulates
CC protein levels of its regulatory subunit DHSp. Required for cell growth
CC and survival. {ECO:0000269|PubMed:23525104}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[eIF5A protein]-L-lysine + spermidine = [eIF5A protein]-
CC deoxyhypusine + propane-1,3-diamine; Xref=Rhea:RHEA:33299, Rhea:RHEA-
CC COMP:10143, Rhea:RHEA-COMP:10144, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57484, ChEBI:CHEBI:57834, ChEBI:CHEBI:82657; EC=2.5.1.46;
CC Evidence={ECO:0000269|PubMed:23525104};
CC -!- COFACTOR:
CC Name=NAD(+); Xref=ChEBI:CHEBI:57540;
CC Evidence={ECO:0000269|PubMed:23525104};
CC Note=The binding sites for NAD(+) are contained in the regulatory
CC subunit DHSp. {ECO:0000305};
CC -!- ACTIVITY REGULATION: Allosterically activated by DHSp. Inhibited by
CC spermididine analog N1-guanyl-1,7-diamineoheptane (GC7).
CC {ECO:0000269|PubMed:23525104}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=82 uM for NAD(+) (at 37 degrees Celsius when bound to regulatory
CC subunit DHSp) {ECO:0000269|PubMed:23525104};
CC KM=0.7 uM for IF5A (at 37 degrees Celsius when bound to regulatory
CC subunit DHSp) {ECO:0000269|PubMed:23525104};
CC KM=43 uM for spermidine (at 37 degrees Celsius when bound to
CC regulatory subunit DHSp) {ECO:0000269|PubMed:23525104};
CC -!- PATHWAY: Protein modification; eIF5A hypusination.
CC {ECO:0000269|PubMed:23525104}.
CC -!- SUBUNIT: Heterotetramer formed by a homodimer of the non-catalytic
CC regulatory subunit DHSp and a homodimer of the catalytic subunit DHSc
CC where DHSc appears to bind spermidine and DHSp appears to bind NAD(+).
CC {ECO:0000269|PubMed:23525104}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes cell growth arrest
CC followed by death, loss of DHSp expression and a failure to sustain
CC infection in mice. {ECO:0000269|PubMed:23525104}.
CC -!- SIMILARITY: Belongs to the deoxyhypusine synthase family.
CC {ECO:0000305}.
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DR EMBL; CM000208; EAN77700.1; -; Genomic_DNA.
DR RefSeq; XP_822528.1; XM_817435.1.
DR PDB; 6DFT; X-ray; 3.50 A; A/C/E/G/I/K=1-461.
DR PDBsum; 6DFT; -.
DR AlphaFoldDB; Q38BX0; -.
DR SMR; Q38BX0; -.
DR STRING; 5691.EAN77700; -.
DR PaxDb; Q38BX0; -.
DR GeneID; 3662232; -.
DR KEGG; tbr:Tb10.70.4900; -.
DR VEuPathDB; TriTrypDB:Tb927.10.2750; -.
DR eggNOG; KOG2924; Eukaryota.
DR InParanoid; Q38BX0; -.
DR OMA; ANLMGTG; -.
DR BRENDA; 2.5.1.46; 6520.
DR UniPathway; UPA00354; -.
DR Proteomes; UP000008524; Chromosome 10.
DR GO; GO:1902494; C:catalytic complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:GeneDB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0034038; F:deoxyhypusine synthase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0044403; P:biological process involved in symbiotic interaction; IMP:UniProtKB.
DR GO; GO:0008612; P:peptidyl-lysine modification to peptidyl-hypusine; IDA:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0051290; P:protein heterotetramerization; IDA:UniProtKB.
DR GO; GO:0008216; P:spermidine metabolic process; IDA:UniProtKB.
DR Gene3D; 3.40.910.10; -; 2.
DR InterPro; IPR002773; Deoxyhypusine_synthase.
DR InterPro; IPR036982; Deoxyhypusine_synthase_sf.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR PANTHER; PTHR11703; PTHR11703; 3.
DR Pfam; PF01916; DS; 2.
DR SUPFAM; SSF52467; SSF52467; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hypusine biosynthesis; Membrane; NAD; Reference proteome;
KW Signal-anchor; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..461
FT /note="Deoxyhypusine synthase"
FT /evidence="ECO:0000305"
FT /id="PRO_0000438976"
FT TRANSMEM 428..448
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 418
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P49366"
FT BINDING 166..167
FT /ligand="spermidine"
FT /ligand_id="ChEBI:CHEBI:57834"
FT /evidence="ECO:0000250|UniProtKB:P49366"
FT BINDING 331
FT /ligand="spermidine"
FT /ligand_id="ChEBI:CHEBI:57834"
FT /evidence="ECO:0000250|UniProtKB:P49366"
FT BINDING 377
FT /ligand="spermidine"
FT /ligand_id="ChEBI:CHEBI:57834"
FT /evidence="ECO:0000250|UniProtKB:P49366"
FT BINDING 403..405
FT /ligand="spermidine"
FT /ligand_id="ChEBI:CHEBI:57834"
FT /evidence="ECO:0000250|UniProtKB:P49366"
FT BINDING 412..418
FT /ligand="spermidine"
FT /ligand_id="ChEBI:CHEBI:57834"
FT /evidence="ECO:0000250|UniProtKB:P49366"
FT HELIX 37..43
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 44..46
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 49..64
FT /evidence="ECO:0007829|PDB:6DFT"
FT STRAND 88..90
FT /evidence="ECO:0007829|PDB:6DFT"
FT STRAND 92..97
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 99..102
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 106..115
FT /evidence="ECO:0007829|PDB:6DFT"
FT STRAND 124..128
FT /evidence="ECO:0007829|PDB:6DFT"
FT STRAND 157..160
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 164..173
FT /evidence="ECO:0007829|PDB:6DFT"
FT STRAND 205..214
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 223..248
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 265..286
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 293..304
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 308..315
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 324..326
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 329..337
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 349..360
FT /evidence="ECO:0007829|PDB:6DFT"
FT STRAND 363..371
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 374..384
FT /evidence="ECO:0007829|PDB:6DFT"
FT TURN 385..387
FT /evidence="ECO:0007829|PDB:6DFT"
FT STRAND 389..395
FT /evidence="ECO:0007829|PDB:6DFT"
FT TURN 405..407
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 410..416
FT /evidence="ECO:0007829|PDB:6DFT"
FT STRAND 418..427
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 432..442
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 444..453
FT /evidence="ECO:0007829|PDB:6DFT"
SQ SEQUENCE 461 AA; 50170 MW; C4DD29BF6C115D80 CRC64;
MAELAKSAVL VSSCTDDLLG DAKQVVVGPN QEDLHSAEAV LNRYSTVGFQ ASNLARAFSI
CEMMLTPQSP SPSLMPTEGD QASESPVMVQ PTLFVGVTAN LFGTGCREAI RFLCTECVPL
PNGVEPATPL DDMAGISCDG TGALKPSPCD SRALIHVLVV SGGAMEHDIR RACESYKLSR
DGAEEEGEQF HHPVERDRSR SKGTDCHFGN VRYNSSGVAS RNLFSCVMRC LVKRLAEAQR
KEKANREAAP IPEAYYDVCS WAITPSTLWY MAGLWMADIF TEALQETGEV TDEKVASEEG
LKRAKSTVLY WAARNGVPIF SPSLTDGDIM EFILTAGDTG VPLLQLDLVA DIHRLNRLAM
RSRRTGMMIL GGGVVKHHVC NANLMRNGAD YAVFLNNAQE FDGSDAGARP GEAVSWGKLR
LDSTAVKVYS EVTIVFPLIV VHVFVAWVRM MRSKGKENIR S
