MANA_DICDI
ID MANA_DICDI Reviewed; 1010 AA.
AC P34098; Q54DI0;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 04-DEC-2007, sequence version 2.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Lysosomal alpha-mannosidase;
DE Short=Laman;
DE EC=3.2.1.24;
DE AltName: Full=Alpha-D-mannoside mannohydrolase;
DE AltName: Full=Alpha-mannosidase A;
DE Contains:
DE RecName: Full=Alpha-mannosidase 60 kDa subunit;
DE Contains:
DE RecName: Full=Alpha-mannosidase 58 kDa subunit;
DE Flags: Precursor;
GN Name=manA; ORFNames=DDB_G0292206;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 41-63 AND
RP 596-612.
RX PubMed=1740448; DOI=10.1016/s0021-9258(19)50624-x;
RA Schatzle J., Bush J., Cardelli J.;
RT "Molecular cloning and characterization of the structural gene coding for
RT the developmentally regulated lysosomal enzyme, alpha-mannosidase, in
RT Dictyostelium discoideum.";
RL J. Biol. Chem. 267:4000-4007(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of terminal, non-reducing alpha-D-mannose residues
CC in alpha-D-mannosides.; EC=3.2.1.24;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- SUBUNIT: Tetramer of equimolar amounts of 60 and 58 kDa subunits.
CC -!- SUBCELLULAR LOCATION: [Alpha-mannosidase 60 kDa subunit]: Lysosome.
CC Note=A few precursors are secreted. The mature 58 and 60 kDa subunits
CC are lysosomal.
CC -!- SUBCELLULAR LOCATION: [Alpha-mannosidase 58 kDa subunit]: Lysosome.
CC -!- INDUCTION: Via a protein termed prestarvation factor which is produced
CC and secreted by both growing and developing cells.
CC -!- PTM: First cleaved into the mature 58 kDa subunit and an intermediate
CC 82 kDa subunit. The latter is then cleaved to its mature 60 kDa subunit
CC form. These events occur in multiple intracellular compartments. The 60
CC kDa subunit may form one or more intramolecular disulfide bonds.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 38 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA33224.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; M82822; AAA33224.1; ALT_FRAME; Genomic_DNA.
DR EMBL; AAFI02000188; EAL61313.1; -; Genomic_DNA.
DR PIR; A42265; A42265.
DR RefSeq; XP_629747.1; XM_629745.1.
DR AlphaFoldDB; P34098; -.
DR SMR; P34098; -.
DR BioGRID; 1253579; 1.
DR STRING; 44689.DDB0201569; -.
DR CAZy; GH38; Glycoside Hydrolase Family 38.
DR PaxDb; P34098; -.
DR PRIDE; P34098; -.
DR EnsemblProtists; EAL61313; EAL61313; DDB_G0292206.
DR GeneID; 8628576; -.
DR KEGG; ddi:DDB_G0292206; -.
DR dictyBase; DDB_G0292206; manA.
DR eggNOG; KOG1959; Eukaryota.
DR HOGENOM; CLU_004690_2_0_1; -.
DR InParanoid; P34098; -.
DR OMA; LEFIWRP; -.
DR PhylomeDB; P34098; -.
DR Reactome; R-DDI-6798695; Neutrophil degranulation.
DR Reactome; R-DDI-8853383; Lysosomal oligosaccharide catabolism.
DR PRO; PR:P34098; -.
DR Proteomes; UP000002195; Chromosome 6.
DR GO; GO:0032009; C:early phagosome; IDA:dictyBase.
DR GO; GO:0005764; C:lysosome; IDA:dictyBase.
DR GO; GO:0004559; F:alpha-mannosidase activity; IDA:dictyBase.
DR GO; GO:0030246; F:carbohydrate binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006013; P:mannose metabolic process; IEA:InterPro.
DR GO; GO:0036211; P:protein modification process; ISS:dictyBase.
DR GO; GO:0030587; P:sorocarp development; HMP:dictyBase.
DR Gene3D; 1.20.1270.50; -; 2.
DR Gene3D; 2.60.40.1180; -; 1.
DR Gene3D; 3.20.110.10; -; 1.
DR InterPro; IPR011013; Gal_mutarotase_sf_dom.
DR InterPro; IPR011330; Glyco_hydro/deAcase_b/a-brl.
DR InterPro; IPR011682; Glyco_hydro_38_C.
DR InterPro; IPR015341; Glyco_hydro_38_cen.
DR InterPro; IPR037094; Glyco_hydro_38_cen_sf.
DR InterPro; IPR000602; Glyco_hydro_38_N.
DR InterPro; IPR027291; Glyco_hydro_38_N_sf.
DR InterPro; IPR028995; Glyco_hydro_57/38_cen_sf.
DR InterPro; IPR013780; Glyco_hydro_b.
DR Pfam; PF09261; Alpha-mann_mid; 1.
DR Pfam; PF07748; Glyco_hydro_38C; 1.
DR Pfam; PF01074; Glyco_hydro_38N; 1.
DR SMART; SM00872; Alpha-mann_mid; 1.
DR SUPFAM; SSF74650; SSF74650; 1.
DR SUPFAM; SSF88688; SSF88688; 1.
DR SUPFAM; SSF88713; SSF88713; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Glycosidase;
KW Hydrolase; Lysosome; Metal-binding; Reference proteome; Signal; Zinc;
KW Zymogen.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..40
FT /note="Pro I"
FT /evidence="ECO:0000255"
FT /id="PRO_0000012081"
FT CHAIN 41..507
FT /note="Alpha-mannosidase 60 kDa subunit"
FT /id="PRO_0000012082"
FT PROPEP 508..595
FT /note="Pro II"
FT /evidence="ECO:0000255"
FT /id="PRO_0000012083"
FT CHAIN 596..1010
FT /note="Alpha-mannosidase 58 kDa subunit"
FT /id="PRO_0000012084"
FT ACT_SITE 173
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 51
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 53
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 173
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 420
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT SITE 507..508
FT /note="Cleavage; to produce 60 kDa subunit"
FT /evidence="ECO:0000255"
FT SITE 589..590
FT /note="Cleavage; to produce 58 and 82 kDa subunits;
FT alternate"
FT /evidence="ECO:0000305"
FT SITE 593..594
FT /note="Cleavage; to produce 58 and 82 kDa subunits;
FT alternate"
FT /evidence="ECO:0000305"
FT CARBOHYD 68
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 480
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 520
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 528
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 539
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 623
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 760
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 784
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 828
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 954
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 963
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 514..515
FT /note="IP -> TL (in Ref. 1; AAA33224)"
FT /evidence="ECO:0000305"
FT CONFLICT 978
FT /note="D -> Y (in Ref. 1; AAA33224)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1010 AA; 113429 MW; 80C65C941232573F CRC64;
MVIKKLFILI FCLFLIINEI NGKKTKINDI KKSKPKLSST LLNVHIVAHT HDDVGWLKTV
DEYYYGSNMS IAFAGVQYTL DTAITCLLAN PERKFIYVEI AFFQRWWDEQ STTMQNIVKG
LVESGQLEFI NGGYCMNDEA TTYYDDTIDQ MTLGHQFLWE NFGVMPKIGW HIDPFGHSAT
QARIFGQLGF DAFIIGRMDY QDIEARLENK QMEFMWRSTQ STPENQVFTS VLRAMYCTPD
GFNFEQGDDP IQDDPNLFDN NVDSRAEQFT QVALEYATHY RTNNVLIPFG CDFAYLNAQM
YYKNIDKLIA HINSNPDKYG LNLLYSTPSI YIDAVNDANL VWEVKTDDLF PYADNEFSYW
TGYFVSRPAL KGYVRQNNAL LHVVEQMLVT SSNLMPSSRS EQLVDDIVIM REVMGIAQHH
DAVSGTEQQH VADDYAERLS IGNCASLETI NTVVGTLLTA NGNSKSAAAT PTISFCPLLN
QSICPATDPL SSGTSVPVLI YNSLSWTRNE PVRIPIPIAN VTVTSSSNGS ITSQVNQING
TFILEFLATI PPLGYSTYII TSTASDFVEP NSIPAIIIQD EIIVSGGGKI NEKVSYNDPI
ILENDYINVQ FSSQDGSILS ITNKTSGVTS SITQEYIWYN PSVGNDDSAQ CSGAYIFRPV
EDFAYPYNNA TPSVSIIRGE ISSSIRRFWS NEMVQTFRLY SNADHLEVEE IIGPIDISDG
IGKEIVSRYT TTLVTDQTWY SDSQGMEMQK RITNYRPSWN LTVVQPTSGN YVPVNAIAYI
QDPNQSLQFT IVTDRSRGCA SLRDGQLDMM MHRRTLKDDG RGVGQPMNES TQIVTTSKLI
FHDISSYAQS HYRPAALSLS HPLLPMFTTT QQSSNDWNSQ YQGVYSPLTS ASPLPNGLKI
QTLQWLDNQD NTILLRIENI YQIDGQDSQD PQTITLDLST IFSTITITSA TEMNLTGVQK
LSNLSRLKWK TVDGKNYDHK SSSSTKEDSS NGFVFTFSPM QIRTFIITTN
