MA2A2_MOUSE
ID MA2A2_MOUSE Reviewed; 1152 AA.
AC Q8BRK9; Q3UVK1;
DT 21-SEP-2011, integrated into UniProtKB/Swiss-Prot.
DT 21-SEP-2011, sequence version 2.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Alpha-mannosidase 2x;
DE EC=3.2.1.114 {ECO:0000250|UniProtKB:P28494};
DE AltName: Full=Alpha-mannosidase IIx;
DE Short=Man IIx;
DE AltName: Full=Mannosidase alpha class 2A member 2;
DE AltName: Full=Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase;
GN Name=Man2a2; Synonyms=Mana2x;
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Brain cortex, Testis, and Urinary bladder;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Lung, 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).
RN [4]
RP INTERACTION WITH MGAT4D.
RX PubMed=20805325; DOI=10.1083/jcb.201004102;
RA Huang H.H., Stanley P.;
RT "A testis-specific regulator of complex and hybrid N-glycan synthesis.";
RL J. Cell Biol. 190:893-910(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 (By similarity). {ECO:0000250}.
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; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Interacts with
CC MGAT4D. {ECO:0000250, ECO:0000269|PubMed:20805325}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000250}; Single-
CC pass type II membrane protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8BRK9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BRK9-2; Sequence=VSP_041735, VSP_041736;
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 38 family. {ECO:0000305}.
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DR EMBL; AK029913; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK044028; BAC31745.1; -; mRNA.
DR EMBL; AK137205; BAE23268.1; -; mRNA.
DR EMBL; AC136740; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS57556.1; -. [Q8BRK9-1]
DR RefSeq; NP_766491.2; NM_172903.4. [Q8BRK9-1]
DR RefSeq; XP_006540662.1; XM_006540599.3. [Q8BRK9-1]
DR AlphaFoldDB; Q8BRK9; -.
DR SMR; Q8BRK9; -.
DR BioGRID; 228256; 3.
DR IntAct; Q8BRK9; 1.
DR MINT; Q8BRK9; -.
DR STRING; 10090.ENSMUSP00000095949; -.
DR CAZy; GH38; Glycoside Hydrolase Family 38.
DR GlyGen; Q8BRK9; 2 sites.
DR iPTMnet; Q8BRK9; -.
DR PhosphoSitePlus; Q8BRK9; -.
DR EPD; Q8BRK9; -.
DR MaxQB; Q8BRK9; -.
DR PaxDb; Q8BRK9; -.
DR PeptideAtlas; Q8BRK9; -.
DR PRIDE; Q8BRK9; -.
DR ProteomicsDB; 287285; -. [Q8BRK9-1]
DR ProteomicsDB; 287286; -. [Q8BRK9-2]
DR Antibodypedia; 2725; 91 antibodies from 16 providers.
DR DNASU; 140481; -.
DR Ensembl; ENSMUST00000098346; ENSMUSP00000095949; ENSMUSG00000038886. [Q8BRK9-1]
DR GeneID; 140481; -.
DR KEGG; mmu:140481; -.
DR UCSC; uc009iap.2; mouse. [Q8BRK9-1]
DR UCSC; uc009iar.2; mouse. [Q8BRK9-2]
DR CTD; 4122; -.
DR MGI; MGI:2150656; Man2a2.
DR VEuPathDB; HostDB:ENSMUSG00000038886; -.
DR eggNOG; KOG1958; Eukaryota.
DR GeneTree; ENSGT01030000234638; -.
DR HOGENOM; CLU_004690_1_0_1; -.
DR InParanoid; Q8BRK9; -.
DR OMA; GEMEIMQ; -.
DR PhylomeDB; Q8BRK9; -.
DR TreeFam; TF313152; -.
DR Reactome; R-MMU-975578; Reactions specific to the complex N-glycan synthesis pathway.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 140481; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Man2a2; mouse.
DR PRO; PR:Q8BRK9; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q8BRK9; protein.
DR Bgee; ENSMUSG00000038886; Expressed in retinal neural layer and 218 other tissues.
DR ExpressionAtlas; Q8BRK9; baseline and differential.
DR Genevisible; Q8BRK9; MM.
DR GO; GO:0000139; C:Golgi membrane; IBA:GO_Central.
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:0016799; F:hydrolase activity, hydrolyzing N-glycosyl compounds; IDA:MGI.
DR GO; GO:0015923; F:mannosidase activity; IDA:MGI.
DR GO; GO:0004572; F:mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006013; P:mannose metabolic process; IEA:InterPro.
DR GO; GO:0006491; P:N-glycan processing; IBA:GO_Central.
DR GO; GO:0006517; P:protein deglycosylation; IBA:GO_Central.
DR GO; GO:0006486; P:protein glycosylation; IEA:UniProtKB-UniPathway.
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 Alternative splicing; Coiled coil; Disulfide bond; Glycoprotein;
KW Glycosidase; Golgi apparatus; Hydrolase; Membrane; Metal-binding;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix;
KW Zinc.
FT CHAIN 1..1152
FT /note="Alpha-mannosidase 2x"
FT /id="PRO_0000412634"
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..796
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT COILED 43..74
FT /evidence="ECO:0000255"
FT ACT_SITE 289
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 175
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 177
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 289
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 569
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT CARBOHYD 225
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 305
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 783..827
FT /note="SIRRVDEEQEQQMELEFLVYGTRTSKDKSGAYLFLPDSEAKPYVP -> VKG
FT QARGGGEGPEEGMGVRGLVDSCSCSHVPSCLSPDSQRFGCEH (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_041735"
FT VAR_SEQ 828..1152
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_041736"
FT CONFLICT 97
FT /note="S -> T (in Ref. 1; AK029913)"
FT /evidence="ECO:0000305"
FT CONFLICT 1111
FT /note="G -> S (in Ref. 1; BAE23268)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1152 AA; 130649 MW; 8A6274E9671F92DF CRC64;
MKLKKQVTVC GAAIFCVAVF SLYLMLDRVQ HDPARHQNGG NFPRSQISVL QNRIEQLEQL
LEENHDIISR IKDSVLELTA NAEGPPALLP YHTANGSWAV LPEPRPSFFS VSPQDCQFAL
GGRGQKPELQ MLTVSEDLPF DNVEGGVWRQ GFDISYSPND WDTEDLQVFV VPHSHNDPGW
IKTFDKYYTE QTQHILNSMV SKLQEDPRRR FLWAEVSFFA KWWDNISAQK RAAVRRLVGN
GQLEIATGGW VMPDEANSHY FALVDQLIEG HQWLERNLGA TPRSGWAVDP FGHSSTMPYL
LRRANLTSML IQRVHYAIKK HFAATHSLEF MWRQMWDSDS STDIFCHMMP FYSYDVPHTC
GPDPKICCQF DFKRLPGGRI NCPWKVPPRA ITEANVADRA ALLLDQYRKK SRLFRSNVLL
VPLGDDFRYD KPQEWDAQFF NYQRLFDFLN SKPEFHVQAQ FGTLSEYFDA LYKRTGVEPG
ARPPGFPVLS GDFFSYADRE DHYWTGYYTS RPFYKSLDRV LEAHLRGAEI LYSLALAHAR
RSGLAGQYPL SDFALLTEAR RTLGLFQHHD AITGTAKEAV VVDYGVRLLR SLVSLKQVII
NAAHYLVLGD QETYSFDPGT PFLQMDDSRV SHDALPERTV IRLDSSPRFV VVFNPLEQER
LSVVSLLVNS PRVRVLSEEG QPLSVQISVH WSSATDMVPD VYQVSVPVRL PGLGLGVLQL
QPDLDGPYTL QSSVRVYLNG VKLSVSRQSA FPVRVVDSGA SDFAISNRYM QVWFSGLTGL
LKSIRRVDEE QEQQMELEFL VYGTRTSKDK SGAYLFLPDS EAKPYVPKKP PVLRVTEGPF
FSEVAVYYEH FHQVIRLYNL PGVEGLSLDM SFQVDIRDYV NKELALRIHT DIDSQGTFFT
DLNGFQIQPR QYLKKLPLQA NFYPMPVMAY IQDSQRRLTL HTAQALGVSS LGNGQLEVIL
DRRLMQDDNR GLGQGLKDNK ITCNRFRLLL ERRTTMSPEV HQEQERSTSY PSLLSHLTSM
YLSTPPLVLP VAKRQGTSPA LRSFHPLASP LPCDFHLLNL RMLPAEDTLP ATDSALILHR
KGFDCGLEAK NLGFNCTTSQ GKLALGSLFH GLDVTFLQPT SLTLLYPLAS PSNSTDISLE
PMEISTFRLR LG
