MA2A2_HUMAN
ID MA2A2_HUMAN Reviewed; 1150 AA.
AC P49641; A6NH12; A8K1E8; Q13754;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 21-SEP-2011, sequence version 3.
DT 03-AUG-2022, entry version 191.
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Melanoma;
RX PubMed=8524845; DOI=10.1073/pnas.92.25.11766;
RA Misago M., Liao Y.-F., Kudo S., Eto S., Mattei M.-G., Moremen K.W.,
RA Fukuda M.N.;
RT "Molecular cloning and expression of cDNAs encoding human alpha-mannosidase
RT II and a previously unrecognized alpha-mannosidase IIx isozyme.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:11766-11770(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Testis;
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 [5]
RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
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 -!- 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 (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q8BRK9}.
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=3;
CC Comment=Additional isoforms seem to exist.;
CC Name=3;
CC IsoId=P49641-3; Sequence=Displayed;
CC Name=1; Synonyms=Long;
CC IsoId=P49641-1; Sequence=VSP_041732, VSP_041734;
CC Name=2; Synonyms=Short;
CC IsoId=P49641-2; Sequence=VSP_041733;
CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 38 family. {ECO:0000305}.
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DR EMBL; D55649; BAA09510.1; -; mRNA.
DR EMBL; L28821; AAA92022.1; -; mRNA.
DR EMBL; AK289863; BAF82552.1; -; mRNA.
DR EMBL; AC067986; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC068831; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC136448; AAI36449.1; -; mRNA.
DR CCDS; CCDS32332.1; -. [P49641-3]
DR RefSeq; NP_006113.2; NM_006122.3. [P49641-3]
DR RefSeq; XP_016877674.1; XM_017022185.1. [P49641-3]
DR AlphaFoldDB; P49641; -.
DR SMR; P49641; -.
DR BioGRID; 110295; 143.
DR IntAct; P49641; 26.
DR STRING; 9606.ENSP00000452948; -.
DR CAZy; GH38; Glycoside Hydrolase Family 38.
DR GlyGen; P49641; 7 sites, 3 O-linked glycans (3 sites).
DR iPTMnet; P49641; -.
DR PhosphoSitePlus; P49641; -.
DR SwissPalm; P49641; -.
DR BioMuta; MAN2A2; -.
DR DMDM; 347595795; -.
DR EPD; P49641; -.
DR jPOST; P49641; -.
DR MassIVE; P49641; -.
DR MaxQB; P49641; -.
DR PaxDb; P49641; -.
DR PeptideAtlas; P49641; -.
DR PRIDE; P49641; -.
DR ProteomicsDB; 56037; -. [P49641-3]
DR ProteomicsDB; 56038; -. [P49641-1]
DR ProteomicsDB; 56039; -. [P49641-2]
DR Antibodypedia; 2725; 91 antibodies from 16 providers.
DR DNASU; 4122; -.
DR Ensembl; ENST00000360468.7; ENSP00000353655.3; ENSG00000196547.15. [P49641-3]
DR Ensembl; ENST00000559717.6; ENSP00000452948.1; ENSG00000196547.15. [P49641-3]
DR GeneID; 4122; -.
DR KEGG; hsa:4122; -.
DR MANE-Select; ENST00000559717.6; ENSP00000452948.1; NM_006122.4; NP_006113.2.
DR UCSC; uc002bqc.4; human. [P49641-3]
DR CTD; 4122; -.
DR DisGeNET; 4122; -.
DR GeneCards; MAN2A2; -.
DR HGNC; HGNC:6825; MAN2A2.
DR HPA; ENSG00000196547; Low tissue specificity.
DR MIM; 600988; gene.
DR neXtProt; NX_P49641; -.
DR OpenTargets; ENSG00000196547; -.
DR PharmGKB; PA30574; -.
DR VEuPathDB; HostDB:ENSG00000196547; -.
DR eggNOG; KOG1958; Eukaryota.
DR GeneTree; ENSGT01030000234638; -.
DR InParanoid; P49641; -.
DR OMA; GEMEIMQ; -.
DR OrthoDB; 1101882at2759; -.
DR PhylomeDB; P49641; -.
DR TreeFam; TF313152; -.
DR BioCyc; MetaCyc:HS11961-MON; -.
DR PathwayCommons; P49641; -.
DR Reactome; R-HSA-6811438; Intra-Golgi traffic.
DR Reactome; R-HSA-975578; Reactions specific to the complex N-glycan synthesis pathway.
DR SignaLink; P49641; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 4122; 10 hits in 1079 CRISPR screens.
DR ChiTaRS; MAN2A2; human.
DR GenomeRNAi; 4122; -.
DR Pharos; P49641; Tbio.
DR PRO; PR:P49641; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P49641; protein.
DR Bgee; ENSG00000196547; Expressed in right hemisphere of cerebellum and 206 other tissues.
DR ExpressionAtlas; P49641; baseline and differential.
DR Genevisible; P49641; HS.
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; IEA:Ensembl.
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 2: Evidence at transcript level;
KW Alternative splicing; Disulfide bond; Glycoprotein; Glycosidase;
KW Golgi apparatus; Hydrolase; Membrane; Metal-binding; Reference proteome;
KW Signal-anchor; Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1..1150
FT /note="Alpha-mannosidase 2x"
FT /id="PRO_0000206905"
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 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 95
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 305
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1093
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1131
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 783..796
FT /note="SIRRVDEEHEQQVD -> GSGLCFLAEHPKGG (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:8524845"
FT /id="VSP_041732"
FT VAR_SEQ 797..1150
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8524845"
FT /id="VSP_041733"
FT VAR_SEQ 823..906
FT /note="KPYVPKEPPVLRVTEGPFFSEVVAYYEHIHQAVRLYNLPGVEGLSLDISSLV
FT DIRDYVNKELALHIHTDIDSQGIFFTDLNGFQ -> SPTSPRSPPCCVSLKALSSQRWL
FT RTMSTFTRRSGFTICQGWRGCLWTYHPWWTSGTTSTRSWPCTSIQTSTAR (in
FT isoform 1)"
FT /evidence="ECO:0000303|PubMed:8524845"
FT /id="VSP_041734"
FT VARIANT 412
FT /note="Q -> R (in dbSNP:rs2106673)"
FT /id="VAR_047912"
FT VARIANT 665
FT /note="S -> F (in dbSNP:rs1266494)"
FT /id="VAR_047913"
SQ SEQUENCE 1150 AA; 130539 MW; BFB3D763A6A55444 CRC64;
MKLKKQVTVC GAAIFCVAVF SLYLMLDRVQ HDPTRHQNGG NFPRSQISVL QNRIEQLEQL
LEENHEIISH IKDSVLELTA NAEGPPAMLP YYTVNGSWVV PPEPRPSFFS ISPQDCQFAL
GGRGQKPELQ MLTVSEELPF DNVDGGVWRQ GFDISYDPHD WDAEDLQVFV VPHSHNDPGW
IKTFDKYYTE QTQHILNSMV SKLQEDPRRR FLWAEVSFFA KWWDNINVQK RAAVRRLVGN
GQLEIATGGW VMPDEANSHY FALIDQLIEG HQWLERNLGA TPRSGWAVDP FGYSSTMPYL
LRRANLTSML IQRVHYAIKK HFAATHSLEF MWRQTWDSDS STDIFCHMMP FYSYDVPHTC
GPDPKICCQF DFKRLPGGRI NCPWKVPPRA ITEANVAERA ALLLDQYRKK SQLFRSNVLL
VPLGDDFRYD KPQEWDAQFF NYQRLFDFFN SRPNLHVQAQ FGTLSDYFDA LYKRTGVEPG
ARPPGFPVLS GDFFSYADRE DHYWTGYYTS RPFYKSLDRV LEAHLRGAEV LYSLAAAHAR
RSGLAGRYPL SDFTLLTEAR RTLGLFQHHD AITGTAKEAV VVDYGVRLLR SLVNLKQVII
HAAHYLVLGD KETYHFDPEA PFLQVDDTRL SHDALPERTV IQLDSSPRFV VLFNPLEQER
FSMVSLLVNS PRVRVLSEEG QPLAVQISAH WSSATEAVPD VYQVSVPVRL PALGLGVLQL
QLGLDGHRTL PSSVRIYLHG RQLSVSRHEA FPLRVIDSGT SDFALSNRYM QVWFSGLTGL
LKSIRRVDEE HEQQVDMQVL VYGTRTSKDK SGAYLFLPDG EAKPYVPKEP PVLRVTEGPF
FSEVVAYYEH IHQAVRLYNL PGVEGLSLDI SSLVDIRDYV NKELALHIHT DIDSQGIFFT
DLNGFQVQPR RYLKKLPLQA NFYPMPVMAY IQDAQKRLTL HTAQALGVSS LKDGQLEVIL
DRRLMQDDNR GLGQGLKDNK RTCNRFRLLL ERRTVGSEVQ DSHSTSYPSL LSHLTSMYLN
APALALPVAR MQLPGPGLRS FHPLASSLPC DFHLLNLRTL QAEEDTLPSA ETALILHRKG
FDCGLEAKNL GFNCTTSQGK VALGSLFHGL DVVFLQPTSL TLLYPLASPS NSTDVYLEPM
EIATFRLRLG
