MA2A1_MOUSE
ID MA2A1_MOUSE Reviewed; 1150 AA.
AC P27046; B9EHS6;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Alpha-mannosidase 2;
DE EC=3.2.1.114 {ECO:0000250|UniProtKB:P28494};
DE AltName: Full=Golgi alpha-mannosidase II;
DE Short=AMan II;
DE Short=Man II;
DE AltName: Full=Mannosidase alpha class 2A member 1;
DE AltName: Full=Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase;
GN Name=Man2a1; Synonyms=Mana2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC STRAIN=BALB/cJ;
RX PubMed=1757461; DOI=10.1083/jcb.115.6.1521;
RA Moremen K.W., Robbins P.W.;
RT "Isolation, characterization, and expression of cDNAs encoding murine
RT alpha-mannosidase II, a Golgi enzyme that controls conversion of high
RT mannose to complex N-glycans.";
RL J. Cell Biol. 115:1521-1534(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-80 AND SER-82, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-80 AND SER-82, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Catalyzes the first committed step in the biosynthesis of
CC complex N-glycans. It controls conversion of high mannose to complex N-
CC glycans; the final hydrolytic step in the N-glycan maturation pathway.
CC {ECO:0000250|UniProtKB:P28494}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H2O + N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[alpha-
CC D-Man-(1->3)-[alpha-D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-
CC (1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-L-asparaginyl-[protein] =
CC 2 alpha-D-mannopyranose + N(4)-{beta-D-GlcNAc-(1->2)-alpha-D-Man-
CC (1->3)-[alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-
CC beta-D-GlcNAc}-L-asparaginyl-[protein]; Xref=Rhea:RHEA:56052,
CC Rhea:RHEA-COMP:14368, Rhea:RHEA-COMP:14369, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:28729, ChEBI:CHEBI:60615, ChEBI:CHEBI:60625;
CC EC=3.2.1.114; Evidence={ECO:0000250|UniProtKB:P28494};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q29451};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q29451};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC -!- SUBUNIT: Homodimer; disulfide-linked.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane; Single-pass type II
CC membrane protein.
CC -!- TISSUE SPECIFICITY: All tissues, mostly in adrenal and thymus.
CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:P28494}.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 38 family. {ECO:0000305}.
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DR EMBL; X61172; CAA43480.1; -; mRNA.
DR EMBL; BC138371; AAI38372.1; -; mRNA.
DR EMBL; BC138372; AAI38373.1; -; mRNA.
DR CCDS; CCDS28938.1; -.
DR PIR; A41641; A41641.
DR RefSeq; NP_032575.2; NM_008549.2.
DR AlphaFoldDB; P27046; -.
DR SMR; P27046; -.
DR BioGRID; 201304; 2.
DR IntAct; P27046; 2.
DR STRING; 10090.ENSMUSP00000083928; -.
DR CAZy; GH38; Glycoside Hydrolase Family 38.
DR GlyGen; P27046; 3 sites.
DR iPTMnet; P27046; -.
DR PhosphoSitePlus; P27046; -.
DR SwissPalm; P27046; -.
DR EPD; P27046; -.
DR jPOST; P27046; -.
DR MaxQB; P27046; -.
DR PaxDb; P27046; -.
DR PeptideAtlas; P27046; -.
DR PRIDE; P27046; -.
DR ProteomicsDB; 291990; -.
DR Antibodypedia; 13482; 190 antibodies from 30 providers.
DR DNASU; 17158; -.
DR Ensembl; ENSMUST00000086723; ENSMUSP00000083928; ENSMUSG00000024085.
DR GeneID; 17158; -.
DR KEGG; mmu:17158; -.
DR UCSC; uc008dfy.1; mouse.
DR CTD; 4124; -.
DR MGI; MGI:104669; Man2a1.
DR VEuPathDB; HostDB:ENSMUSG00000024085; -.
DR eggNOG; KOG1958; Eukaryota.
DR GeneTree; ENSGT01030000234638; -.
DR HOGENOM; CLU_004690_1_0_1; -.
DR InParanoid; P27046; -.
DR OMA; HHEVNVQ; -.
DR OrthoDB; 1101882at2759; -.
DR PhylomeDB; P27046; -.
DR TreeFam; TF313152; -.
DR BRENDA; 3.2.1.114; 3474.
DR Reactome; R-MMU-975578; Reactions specific to the complex N-glycan synthesis pathway.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 17158; 4 hits in 73 CRISPR screens.
DR ChiTaRS; Man2a1; mouse.
DR PRO; PR:P27046; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; P27046; protein.
DR Bgee; ENSMUSG00000024085; Expressed in stroma of bone marrow and 239 other tissues.
DR ExpressionAtlas; P27046; baseline and differential.
DR Genevisible; P27046; MM.
DR GO; GO:0005801; C:cis-Golgi network; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0005797; C:Golgi medial cisterna; ISO:MGI.
DR GO; GO:0000139; C:Golgi membrane; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004559; F:alpha-mannosidase activity; IBA:GO_Central.
DR GO; GO:0030246; F:carbohydrate binding; IEA:InterPro.
DR GO; GO:0016787; F:hydrolase activity; IDA:MGI.
DR GO; GO:0016799; F:hydrolase activity, hydrolyzing N-glycosyl compounds; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0015923; F:mannosidase activity; IDA:MGI.
DR GO; GO:0004572; F:mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase activity; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IGI:MGI.
DR GO; GO:0001889; P:liver development; IGI:MGI.
DR GO; GO:0048286; P:lung alveolus development; IGI:MGI.
DR GO; GO:0006013; P:mannose metabolic process; IEA:InterPro.
DR GO; GO:0007005; P:mitochondrion organization; IGI:MGI.
DR GO; GO:0006491; P:N-glycan processing; IGI:MGI.
DR GO; GO:0050769; P:positive regulation of neurogenesis; IMP:MGI.
DR GO; GO:0006517; P:protein deglycosylation; IBA:GO_Central.
DR GO; GO:0006486; P:protein glycosylation; IEA:UniProtKB-UniPathway.
DR GO; GO:0007585; P:respiratory gaseous exchange by respiratory system; IGI:MGI.
DR GO; GO:0060042; P:retina morphogenesis in camera-type eye; IMP:MGI.
DR GO; GO:0007033; P:vacuole organization; IGI:MGI.
DR Gene3D; 1.20.1270.50; -; 1.
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 Golgi apparatus; Hydrolase; Membrane; Metal-binding; Phosphoprotein;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix;
KW Zinc.
FT CHAIN 1..1150
FT /note="Alpha-mannosidase 2"
FT /id="PRO_0000206903"
FT TOPO_DOM 1..5
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 6..26
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 27..1150
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT ACT_SITE 288
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 174
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 176
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 288
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 568
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT MOD_RES 80
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 82
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT CARBOHYD 78
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 93
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1129
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 673
FT /note="V -> G (in Ref. 1; CAA43480)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1150 AA; 131631 MW; 5CDD9DD388DF5BC6 CRC64;
MKLSRQFTVF GSAIFCVVIF SLYLMLDRGH LDYPRGPRQE GSFPQGQLSI LQEKIDHLER
LLAENNEIIS NIRDSVINLS ESVEDGPRGS PGNASQGSIH LHSPQLALQA DPRDCLFASQ
SGSQPRDVQM LDVYDLIPFD NPDGGVWKQG FDIKYEADEW DHEPLQVFVV PHSHNDPGWL
KTFNDYFRDK TQYIFNNMVL KLKEDSSRKF MWSEISYLAK WWDIIDIPKK EAVKSLLQNG
QLEIVTGGWV MPDEATPHYF ALIDQLIEGH QWLEKNLGVK PRSGWAIDPF GHSPTMAYLL
KRAGFSHMLI QRVHYAIKKH FSLHKTLEFF WRQNWDLGSA TDILCHMMPF YSYDIPHTCG
PDPKICCQFD FKRLPGGRYG CPWGVPPEAI SPGNVQSRAQ MLLDQYRKKS KLFRTKVLLA
PLGDDFRFSE YTEWDLQCRN YEQLFSYMNS QPHLKVKIQF GTLSDYFDAL EKAVAAEKKS
SQSVFPALSG DFFTYADRDD HYWSGYFTSR PFYKRMDRIM ESRIRAAEIL YQLALKQAQK
YKINKFLSSP HYTTLTEARR NLGLFQHHDA ITGTAKDWVV VDYGTRLFQS LNSLEKIIGD
SAFLLILKDK KLYQSDPSKA FLEMDTKQSS QDSLPQKIII QLSAQEPRYL VVYNPFEQER
HSVVSIRVNS ATVKVLSDSG KPVEVQVSAV WNDMRTISQA AYEVSFLAHI PPLGLKVFKI
LESQSSSSHL ADYVLYNNDG LAENGIFHVK NMVDAGDAIT IENPFLAIWF DRSGLMEKVR
RKEDSRQHEL KVQFLWYGTT NKRDKSGAYL FLPDGQGQPY VSLRPPFVRV TRGRIYSDVT
CFLEHVTHKV RLYNIQGIEG QSMEVSNIVN IRNVHNREIV MRISSKINNQ NRYYTDLNGY
QIQPRRTMSK LPLQANVYPM CTMAYIQDAE HRLTLLSAQS LGASSMASGQ IEVFMDRRLM
QDDNRGLGQG VHDNKITANL FRILLEKRSA VNMEEEKKSP VSYPSLLSHM TSSFLNHPFL
PMVLSGQLPS PAFELLSEFP LLQSSLPCDI HLVNLRTIQS KMGKGYSDEA ALILHRKGFD
CQFSSRGIGL PCSTTQGKMS VLKLFNKFAV ESLVPSSLSL MHSPPDAQNM SEVSLSPMEI
STFRIRLRWT
