MA2A1_RAT
ID MA2A1_RAT Reviewed; 1148 AA.
AC P28494; G3V7Y9;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 29-OCT-2014, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Alpha-mannosidase 2;
DE EC=3.2.1.114 {ECO:0000269|PubMed:1885615};
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 46-521, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=2748583; DOI=10.1073/pnas.86.14.5276;
RA Moremen K.W.;
RT "Isolation of a rat liver Golgi mannosidase II clone by mixed
RT oligonucleotide-primed amplification of cDNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:5276-5280(1989).
RN [4]
RP PROTEIN SEQUENCE OF 156-171 AND 243-256, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=2246269; DOI=10.1016/s0021-9258(17)45462-7;
RA Baron M.D., Garoff H.;
RT "Mannosidase II and the 135-kDa Golgi-specific antigen recognized
RT monoclonal antibody 53FC3 are the same dimeric protein.";
RL J. Biol. Chem. 265:19928-19931(1990).
RN [5]
RP PROTEIN SEQUENCE OF 107-136 AND 478-496, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP GLYCOSYLATION.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=1885615; DOI=10.1016/s0021-9258(18)55384-9;
RA Moremen K.W., Touster O., Robbins P.W.;
RT "Novel purification of the catalytic domain of Golgi alpha-mannosidase II.
RT Characterization and comparison with the intact enzyme.";
RL J. Biol. Chem. 266:16876-16885(1991).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-80 AND SER-82, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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:0000303|PubMed:1885615}.
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:0000269|PubMed:1885615};
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 -!- ACTIVITY REGULATION: Inhibited by swainsonine.
CC {ECO:0000269|PubMed:1885615}.
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000303|PubMed:1885615}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000269|PubMed:1885615,
CC ECO:0000269|PubMed:2246269}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:1885615, ECO:0000269|PubMed:2246269,
CC ECO:0000269|PubMed:2748583}; Single-pass type II membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Liver. {ECO:0000269|PubMed:1885615,
CC ECO:0000269|PubMed:2748583}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:1885615}.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 38 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AABR06062074; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06062075; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473997; EDL91825.1; -; Genomic_DNA.
DR EMBL; M24353; AAA66457.1; -; mRNA.
DR PIR; A33901; A33901.
DR RefSeq; NP_037111.2; NM_012979.2.
DR AlphaFoldDB; P28494; -.
DR SMR; P28494; -.
DR IntAct; P28494; 2.
DR MINT; P28494; -.
DR STRING; 10116.ENSRNOP00000020767; -.
DR BindingDB; P28494; -.
DR ChEMBL; CHEMBL2257; -.
DR CAZy; GH38; Glycoside Hydrolase Family 38.
DR GlyGen; P28494; 1 site.
DR iPTMnet; P28494; -.
DR PhosphoSitePlus; P28494; -.
DR jPOST; P28494; -.
DR PaxDb; P28494; -.
DR PeptideAtlas; P28494; -.
DR PRIDE; P28494; -.
DR Ensembl; ENSRNOT00000020767; ENSRNOP00000020767; ENSRNOG00000015439.
DR GeneID; 25478; -.
DR KEGG; rno:25478; -.
DR UCSC; RGD:3038; rat.
DR CTD; 4124; -.
DR RGD; 3038; Man2a1.
DR eggNOG; KOG1958; Eukaryota.
DR GeneTree; ENSGT01030000234638; -.
DR HOGENOM; CLU_004690_1_0_1; -.
DR InParanoid; P28494; -.
DR OMA; HHEVNVQ; -.
DR OrthoDB; 1101882at2759; -.
DR TreeFam; TF313152; -.
DR Reactome; R-RNO-975578; Reactions specific to the complex N-glycan synthesis pathway.
DR UniPathway; UPA00378; -.
DR PRO; PR:P28494; -.
DR Proteomes; UP000002494; Chromosome 9.
DR Proteomes; UP000234681; Chromosome 9.
DR Bgee; ENSRNOG00000015439; Expressed in ovary and 19 other tissues.
DR ExpressionAtlas; P28494; baseline and differential.
DR Genevisible; P28494; RN.
DR GO; GO:0005801; C:cis-Golgi network; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0005797; C:Golgi medial cisterna; ISO:RGD.
DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
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; ISO:RGD.
DR GO; GO:0016799; F:hydrolase activity, hydrolyzing N-glycosyl compounds; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0015923; F:mannosidase activity; ISO:RGD.
DR GO; GO:0004572; F:mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:0001889; P:liver development; ISO:RGD.
DR GO; GO:0048286; P:lung alveolus development; ISO:RGD.
DR GO; GO:0006013; P:mannose metabolic process; IEA:InterPro.
DR GO; GO:0007005; P:mitochondrion organization; ISO:RGD.
DR GO; GO:0006491; P:N-glycan processing; IDA:UniProtKB.
DR GO; GO:0050769; P:positive regulation of neurogenesis; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0060042; P:retina morphogenesis in camera-type eye; ISO:RGD.
DR GO; GO:0007033; P:vacuole organization; ISO:RGD.
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 Coiled coil; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Glycosidase; Golgi apparatus; Hydrolase; Membrane; Metal-binding;
KW Phosphoprotein; Reference proteome; Signal-anchor; Transmembrane;
KW Transmembrane helix; Zinc.
FT CHAIN 1..1148
FT /note="Alpha-mannosidase 2"
FT /id="PRO_0000206904"
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..1148
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 1121..1148
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 288
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q29451"
FT BINDING 174
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q29451"
FT BINDING 176
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q29451"
FT BINDING 288
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q29451"
FT BINDING 568
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q29451"
FT MOD_RES 80
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 82
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CARBOHYD 93
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 46
FT /note="G -> GFSPHIIRVERKG (in Ref. 3; AAA66457)"
FT CONFLICT 157
FT /note="A -> G (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 160
FT /note="W -> I (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 244
FT /note="I -> G (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 247
FT /note="G -> K (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 493
FT /note="F -> I (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1148 AA; 131242 MW; 8FEEAA55D4AD068B CRC64;
MKLSRQFTVF GSAIFCVVIF SLYLMLDRGH LDYPRGPRQE GSFPQGQLSI LQEKIDHLER
LLAENNEIIS NIRDSVINLS ESVEDGPRGP AGNASQGSAH LHSAQLALQA DPKDCLFASQ
SGNQHRDVQM LDVYDLIPFD NPDGGVWKQG FDIKYEADEW DREPLQVFVV PHSHNDPGWL
KTFNDYFRDK TQYIFNNMVL KLKEDSSRKF IWSEISYLAK WWDIIDNPKK EAVKSLLQNG
QLEIVTGGWV MADEATTHYF ALIDQLIEGH QWLEKNLGVK PRSGWAIDPF GHSPTMTYLL
KRAGFSHMLI QRVHYSVKKH FSLQKTLEFF WRQNWDLGST TDILCHMMPF YSYDIPHTCG
PDPKICCQFD FKRLPGGRYG CPWGVPPEAI SPGNVQSRAQ MLLDQYRKKS KLFRTKVLLA
PLGDDFRFSE YTEWDLQYRN YEQLFSYMNS QPHLKVKIQF GTLSDYFDAL EKSVAAEKKG
GQSVFPALSG DFFTYADRDD HYWSGYFTSR PFYKRMDRIM ESRLRTAEIL YHLALKQAQK
YKINKFLSSP HYTTLTEARR NLGLFQHHDA ITGTAKDWVV VDYGTRLFQS LNSLEKIIGD
SAFLLILKDK KLYQSDPSKA FLEMDTKQSS QDSLPKKNII QLSAQEPRYL VVYNPFEQER
HSVVSVRVNS ATVKVLSDLG KAVEVQVSAV WKDMRTTSQA AYEVAFLAHL PPLGLKVYKI
LESQSSSSHL ADYFLYNNDG QAESGIFHMK NMVDSGDAIT IENSFLTLGF DRSGLMEKVR
RKEDNKQQEL KVQFLWYGTT NKRDKSGAYL FLPDGQGQPY VSLRTPFVRV TRGRIYSDVT
CFLEHVTHKV RLYHIQGIEG QSMEVSNIVD IRSVHNREIV MRISSKINNQ NRYYTDLNGY
QIQPRRTMAK LPLQANVYPM STMAYIQDAA HRLTLLSAQS LGASSMASGQ IEVFMDRRLM
QDDNRGLGQG VHDNKITANL FRILLEKRNG MNMEEDKKSP VSYPSLLSHM TSAFLNHPFL
PMVLSGQLPS PAIELLSEFR LLQSSLPCDI HLVNLRTIQS KVGKGYSDEA ALILHRKVFD
CQLSSRAMGL PCSTTQGKMS IPKLFNNFAV ESFIPSSLSL MHSPPDAQNT SEVSLSPMEI
STSRIRLR
