PMM_DROME
ID PMM_DROME Reviewed; 254 AA.
AC Q9VTZ6;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Phosphomannomutase {ECO:0000305};
DE EC=5.4.2.8 {ECO:0000269|PubMed:26940433};
DE AltName: Full=Phosphomannomutase 2 {ECO:0000250|UniProtKB:O15305};
DE AltName: Full=Phosphomannomutase type 2 {ECO:0000303|PubMed:26940433, ECO:0000312|FlyBase:FBgn0036300};
GN Name=Pmm2 {ECO:0000303|PubMed:26940433, ECO:0000312|FlyBase:FBgn0036300};
GN ORFNames=CG10688 {ECO:0000312|FlyBase:FBgn0036300};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J.W., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.A.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P.W., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J.M., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K.H., Yu C., Lewis S.E., Rubin G.M., Celniker S.E.;
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=26940433; DOI=10.1242/dmm.022939;
RA Parkinson W.M., Dookwah M., Dear M.L., Gatto C.L., Aoki K., Tiemeyer M.,
RA Broadie K.;
RT "Synaptic roles for phosphomannomutase type 2 in a new Drosophila
RT congenital disorder of glycosylation disease model.";
RL Dis. Model. Mech. 9:513-527(2016).
CC -!- FUNCTION: Involved in the synthesis of the GDP-mannose and dolichol-
CC phosphate-mannose required for a number of critical mannosyl transfer
CC reactions (PubMed:26940433). Required for maintaining N-linked
CC glycoprotein glycosylation at the neuromuscular junction (NMJ)
CC synaptomatrix, and thus acts in multiple pathways that prevent NMJ
CC structural overgrowth, restrict synaptic bouton differentiation, and
CC limit NMJ neurotransmission strength, in order to maintain viability,
CC coordinate movement, and in adults ensure correct wing positioning
CC (PubMed:26940433). Acts in the NMJ trans-synaptic Wg pathway via
CC glycosylation of synaptic Mmp2 which enables dlp/wg signaling during
CC development (PubMed:26940433). {ECO:0000269|PubMed:26940433}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=alpha-D-mannose 1-phosphate = D-mannose 6-phosphate;
CC Xref=Rhea:RHEA:11140, ChEBI:CHEBI:58409, ChEBI:CHEBI:58735;
CC EC=5.4.2.8; Evidence={ECO:0000269|PubMed:26940433};
CC -!- PATHWAY: Nucleotide-sugar biosynthesis; GDP-alpha-D-mannose
CC biosynthesis; alpha-D-mannose 1-phosphate from D-fructose 6-phosphate:
CC step 2/2.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q92871}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O35621}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated whole-body knockdown is lethal at
CC larval stage with severe developmental delays (PubMed:26940433). RNAi-
CC mediated whole-body knockdown or combined neural and muscle knockdown,
CC reduces N-linked protein glycosylation at the neuromuscular junction
CC (NMJ) leading to NMJ synaptic overelaboration and decreased amplitude
CC of evoked excitatory junction currents (EJCs) (PubMed:26940433). These
CC structural and functional defects at the NMJ impair coordinated
CC movement needed for viability (PubMed:26940433). Loss of N-linked
CC protein glycosylation at the NMJ, reduces levels of synaptic Mmp2 and
CC thereby the synaptic levels of wg and its coreceptor dlp leading to a
CC down-regulation of the trans-synaptic pathway (PubMed:26940433). RNAi-
CC mediated knockdown either in the neurons or in the muscles, also
CC reduces glycosylation at the NMJ and synaptic overelaboration, however
CC there is no decrease in the amplitude of evoked excitatory junction
CC currents (EJCs) and flies die at the adult stage (PubMed:26940433).
CC Adults display held-out wings and exhibit incoordination which impairs
CC walking or flying (PubMed:26940433). RNAi-mediated knockdown in muscles
CC impairs coordinated movement required for pharate adults to properly
CC eclose, resulting in death (PubMed:26940433).
CC {ECO:0000269|PubMed:26940433}.
CC -!- SIMILARITY: Belongs to the eukaryotic PMM family. {ECO:0000305}.
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DR EMBL; AE014296; AAF49899.1; -; Genomic_DNA.
DR EMBL; BT009926; AAQ22395.1; -; mRNA.
DR RefSeq; NP_648589.1; NM_140332.2.
DR AlphaFoldDB; Q9VTZ6; -.
DR SMR; Q9VTZ6; -.
DR BioGRID; 64785; 1.
DR STRING; 7227.FBpp0075693; -.
DR PaxDb; Q9VTZ6; -.
DR PRIDE; Q9VTZ6; -.
DR DNASU; 39436; -.
DR EnsemblMetazoa; FBtr0075961; FBpp0075693; FBgn0036300.
DR GeneID; 39436; -.
DR KEGG; dme:Dmel_CG10688; -.
DR UCSC; CG10688-RA; d. melanogaster.
DR CTD; 5373; -.
DR FlyBase; FBgn0036300; Pmm2.
DR VEuPathDB; VectorBase:FBgn0036300; -.
DR eggNOG; KOG3189; Eukaryota.
DR GeneTree; ENSGT00390000002918; -.
DR HOGENOM; CLU_065642_0_1_1; -.
DR InParanoid; Q9VTZ6; -.
DR OMA; VCPIGRQ; -.
DR OrthoDB; 1038583at2759; -.
DR PhylomeDB; Q9VTZ6; -.
DR Reactome; R-DME-446205; Synthesis of GDP-mannose.
DR UniPathway; UPA00126; UER00424.
DR BioGRID-ORCS; 39436; 1 hit in 3 CRISPR screens.
DR GenomeRNAi; 39436; -.
DR PRO; PR:Q9VTZ6; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0036300; Expressed in embryonic/larval hemocyte (Drosophila) and 26 other tissues.
DR Genevisible; Q9VTZ6; DM.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004615; F:phosphomannomutase activity; IBA:GO_Central.
DR GO; GO:0071456; P:cellular response to hypoxia; IMP:FlyBase.
DR GO; GO:0009298; P:GDP-mannose biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006013; P:mannose metabolic process; IBA:GO_Central.
DR GO; GO:0006487; P:protein N-linked glycosylation; IMP:FlyBase.
DR CDD; cd02585; HAD_PMM; 1.
DR Gene3D; 3.30.1240.20; -; 1.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR006379; HAD-SF_hydro_IIB.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR005002; PMM.
DR InterPro; IPR043169; PMM_cap.
DR PANTHER; PTHR10466; PTHR10466; 1.
DR Pfam; PF03332; PMM; 1.
DR SFLD; SFLDF00445; alpha-phosphomannomutase; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR TIGRFAMs; TIGR01484; HAD-SF-IIB; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Isomerase; Magnesium; Metal-binding; Reference proteome.
FT CHAIN 1..254
FT /note="Phosphomannomutase"
FT /id="PRO_0000199699"
FT ACT_SITE 16
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q92871"
FT ACT_SITE 18
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q92871"
FT BINDING 16
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q92871"
FT BINDING 18
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q92871"
FT BINDING 25
FT /ligand="alpha-D-mannose 1-phosphate"
FT /ligand_id="ChEBI:CHEBI:58409"
FT /evidence="ECO:0000250|UniProtKB:Q92871"
FT BINDING 129
FT /ligand="alpha-D-mannose 1-phosphate"
FT /ligand_id="ChEBI:CHEBI:58409"
FT /evidence="ECO:0000250|UniProtKB:Q92871"
FT BINDING 140
FT /ligand="alpha-D-mannose 1-phosphate"
FT /ligand_id="ChEBI:CHEBI:58409"
FT /evidence="ECO:0000250|UniProtKB:Q92871"
FT BINDING 147
FT /ligand="alpha-D-mannose 1-phosphate"
FT /ligand_id="ChEBI:CHEBI:58409"
FT /evidence="ECO:0000250|UniProtKB:Q92871"
FT BINDING 185
FT /ligand="alpha-D-mannose 1-phosphate"
FT /ligand_id="ChEBI:CHEBI:58409"
FT /evidence="ECO:0000250|UniProtKB:Q92871"
FT BINDING 187
FT /ligand="alpha-D-mannose 1-phosphate"
FT /ligand_id="ChEBI:CHEBI:58409"
FT /evidence="ECO:0000250|UniProtKB:Q92871"
FT BINDING 216
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P31353"
FT BINDING 228
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P31353"
FT BINDING 230
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q92871"
FT BINDING 233
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q92871"
SQ SEQUENCE 254 AA; 29667 MW; 716E05E7BB2438BB CRC64;
MTTAALKRDE ILLLFDVDGT LTMPRSVVTP EFEEFFYSRV KPRATIGIVG GSDLEKMFEQ
LNGRKILNEF DFIFPENGLV QIEGGKEVGK QNIIMHLGEE TVKRFINFVL RYLSELDVPI
KRGTFIEFRN GMMNVCPIGR QCTREERNMF AEYDIEHKVR EKMIKDLKQE FADVDLTYSI
GGQISFDVFP HGWDKTYCLR HIEAHYKFKE IHFFGDKTEP GGNDYEIYSD PRTISHRVYT
PKDTQRILTE ILEL
