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   27-MAR-2024, entry version 141.
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   GlyCosmos; Q8BRK9; 2 sites, No reported glycans.
DR   GlyGen; Q8BRK9; 2 sites.
DR   iPTMnet; Q8BRK9; -.
DR   PhosphoSitePlus; Q8BRK9; -.
DR   EPD; Q8BRK9; -.
DR   MaxQB; Q8BRK9; -.
DR   PaxDb; 10090-ENSMUSP00000095949; -.
DR   PeptideAtlas; Q8BRK9; -.
DR   ProteomicsDB; 287285; -. [Q8BRK9-1]
DR   ProteomicsDB; 287286; -. [Q8BRK9-2]
DR   Pumba; Q8BRK9; -.
DR   Antibodypedia; 2725; 106 antibodies from 17 providers.
DR   DNASU; 140481; -.
DR   Ensembl; ENSMUST00000098346.5; ENSMUSP00000095949.4; ENSMUSG00000038886.11. [Q8BRK9-1]
DR   GeneID; 140481; -.
DR   KEGG; mmu:140481; -.
DR   UCSC; uc009iap.2; mouse. [Q8BRK9-1]
DR   UCSC; uc009iar.2; mouse. [Q8BRK9-2]
DR   AGR; MGI:2150656; -.
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; GHQWLKY; -.
DR   OrthoDB; 5474711at2759; -.
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 77 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 220 other cell types or tissues.
DR   ExpressionAtlas; Q8BRK9; baseline and differential.
DR   GO; GO:0000139; C:Golgi membrane; IBA:GO_Central.
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:0006486; P:protein glycosylation; IEA:UniProtKB-UniPathway.
DR   Gene3D; 3.20.110.10; Glycoside hydrolase 38, N terminal domain; 1.
DR   Gene3D; 1.20.1270.50; Glycoside hydrolase family 38, central domain; 1.
DR   Gene3D; 2.60.40.1180; Golgi alpha-mannosidase II; 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   PANTHER; PTHR11607; ALPHA-MANNOSIDASE; 1.
DR   PANTHER; PTHR11607:SF57; ALPHA-MANNOSIDASE 2X; 1.
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; SSF88688; Families 57/38 glycoside transferase middle domain; 1.
DR   SUPFAM; SSF74650; Galactose mutarotase-like; 1.
DR   SUPFAM; SSF88713; Glycoside hydrolase/deacetylase; 1.
DR   Genevisible; Q8BRK9; MM.
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
//