DHYSP_TRYB2
ID DHYSP_TRYB2 Reviewed; 342 AA.
AC Q4GZD1;
DT 15-FEB-2017, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2005, sequence version 1.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=Deoxyhypusine synthase regulatory subunit {ECO:0000305};
DE AltName: Full=Inactive deoxyhypusine synthase {ECO:0000303|PubMed:23525104};
GN Name=DHSp {ECO:0000303|PubMed:23525104};
GN ORFNames=TB927.1.870 {ECO:0000312|EMBL:CAJ16007.1};
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 {ECO:0000312|Proteomes:UP000008524};
RX PubMed=12907729; DOI=10.1093/nar/gkg674;
RA Hall N., Berriman M., Lennard N.J., Harris B.R., Hertz-Fowler C.,
RA Bart-Delabesse E.N., Gerrard C.S., Atkin R.J., Barron A.J., Bowman S.,
RA Bray-Allen S.P., Bringaud F., Clark L.N., Corton C.H., Cronin A.,
RA Davies R., Doggett J., Fraser A., Grueter E., Hall S., Harper A.D.,
RA Kay M.P., Leech V., Mayes R., Price C., Quail M.A., Rabbinowitsch E.,
RA Reitter C., Rutherford K., Sasse J., Sharp S., Shownkeen R., MacLeod A.,
RA Taylor S., Tweedie A., Turner C.M., Tait A., Gull K., Barrell B.,
RA Melville S.E.;
RT "The DNA sequence of chromosome I of an African trypanosome: gene content,
RT chromosome organisation, recombination and polymorphism.";
RL Nucleic Acids Res. 31:4864-4873(2003).
RN [2] {ECO:0000312|Proteomes:UP000008524}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=927/4 GUTat10.1 {ECO:0000312|Proteomes:UP000008524};
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 [3] {ECO:0000305}
RP FUNCTION, 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: Required for the activation and stability of deoxyhypusine
CC synthase DHSc. Required for cell growth and survival.
CC {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 -!- 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}.
CC -!- CAUTION: Lacks the conserved active site Lys, and therefore lacks
CC catalytic activity. {ECO:0000269|PubMed:23525104}.
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DR EMBL; AL929603; CAJ16007.1; -; Genomic_DNA.
DR RefSeq; XP_001218790.1; XM_001218789.1.
DR PDB; 6DFT; X-ray; 3.50 A; B/D/F/H/J/L=1-342.
DR PDBsum; 6DFT; -.
DR AlphaFoldDB; Q4GZD1; -.
DR SMR; Q4GZD1; -.
DR STRING; 5691.CAJ16007; -.
DR PaxDb; Q4GZD1; -.
DR GeneID; 4357125; -.
DR KEGG; tbr:TB927.1.870; -.
DR VEuPathDB; TriTrypDB:Tb927.1.870; -.
DR eggNOG; KOG2924; Eukaryota.
DR InParanoid; Q4GZD1; -.
DR OMA; EARSWGK; -.
DR BRENDA; 2.5.1.46; 6520.
DR UniPathway; UPA00354; -.
DR Proteomes; UP000008524; Chromosome 1.
DR GO; GO:1902494; C:catalytic complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:GeneDB.
DR GO; GO:0034038; F:deoxyhypusine synthase activity; IBA:GO_Central.
DR GO; GO:0008047; F:enzyme activator activity; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI: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; IBA:GO_Central.
DR GO; GO:0043085; P:positive regulation of catalytic activity; 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; -; 1.
DR InterPro; IPR002773; Deoxyhypusine_synthase.
DR InterPro; IPR036982; Deoxyhypusine_synthase_sf.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR PANTHER; PTHR11703; PTHR11703; 1.
DR Pfam; PF01916; DS; 1.
DR SUPFAM; SSF52467; SSF52467; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hypusine biosynthesis; NAD; Reference proteome.
FT CHAIN 1..342
FT /note="Deoxyhypusine synthase regulatory subunit"
FT /id="PRO_0000438977"
FT BINDING 72..76
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P49366"
FT BINDING 98..100
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P49366"
FT BINDING 104
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P49366"
FT BINDING 213
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P49366"
FT BINDING 282..283
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P49366"
FT BINDING 316..317
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P49366"
FT HELIX 16..20
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 24..33
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 35..37
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 40..58
FT /evidence="ECO:0007829|PDB:6DFT"
FT STRAND 59..63
FT /evidence="ECO:0007829|PDB:6DFT"
FT STRAND 65..70
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 72..76
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 79..88
FT /evidence="ECO:0007829|PDB:6DFT"
FT STRAND 93..96
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 100..107
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 122..127
FT /evidence="ECO:0007829|PDB:6DFT"
FT STRAND 130..133
FT /evidence="ECO:0007829|PDB:6DFT"
FT STRAND 136..139
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 140..164
FT /evidence="ECO:0007829|PDB:6DFT"
FT STRAND 166..169
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 172..186
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 190..193
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 195..201
FT /evidence="ECO:0007829|PDB:6DFT"
FT STRAND 212..214
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 215..224
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 236..245
FT /evidence="ECO:0007829|PDB:6DFT"
FT STRAND 254..260
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 263..271
FT /evidence="ECO:0007829|PDB:6DFT"
FT STRAND 275..281
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 285..287
FT /evidence="ECO:0007829|PDB:6DFT"
FT STRAND 289..292
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 295..300
FT /evidence="ECO:0007829|PDB:6DFT"
FT STRAND 309..315
FT /evidence="ECO:0007829|PDB:6DFT"
FT HELIX 317..325
FT /evidence="ECO:0007829|PDB:6DFT"
SQ SEQUENCE 342 AA; 37378 MW; 1A6BF07664635C44 CRC64;
MSGVPFPSRV IGDLDYSNLL NIGQEEAIRC VLNAYPNIGL EATNLGRARR IVQRALNDNG
MDGNKVMLAY TSNLISSGLR DTFACLAREN RIGAVVTTAG GVEEDVIKCL GDTLVGDFAL
NDHALRNNGL NRVGNLLVPN DNYRNFEDFF VPLLRRLHEQ QRDSRWTTKT TPSQIIAEIG
AALESVRPND CGSSLIYWCY RNDIPVFSPA FTDGSMGDMI YFYNYSRKGL VVDPVPDVRR
LRQLGCKSTN VGRITCIVLG AGLPKHHLLR NVQADAVVYV TTGSDADGCE SSCNVMADRA
NGLLSPNCDV VRVHGDATII SPLLLLRSSD GKEKVGVRED GN
