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P49641

- MA2A2_HUMAN

UniProt

P49641 - MA2A2_HUMAN

Protein

Alpha-mannosidase 2x

Gene

MAN2A2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 135 (01 Oct 2014)
      Sequence version 3 (21 Sep 2011)
      Previous versions | rss
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    Functioni

    Catalyzes the first committed step in the biosynthesis of complex N-glycans. It controls conversion of high mannose to complex N-glycans; the final hydrolytic step in the N-glycan maturation pathway.

    Catalytic activityi

    Hydrolysis of the terminal (1->3)- and (1->6)-linked alpha-D-mannose residues in the mannosyl-oligosaccharide Man5(GlcNAc)3.

    Cofactori

    Binds 1 zinc ion per subunit.By similarity

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi175 – 1751ZincBy similarity
    Metal bindingi177 – 1771ZincBy similarity
    Active sitei289 – 2891NucleophileBy similarity
    Metal bindingi289 – 2891ZincBy similarity
    Metal bindingi569 – 5691ZincBy similarity

    GO - Molecular functioni

    1. carbohydrate binding Source: InterPro
    2. hydrolase activity, hydrolyzing N-glycosyl compounds Source: Ensembl
    3. mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase activity Source: UniProtKB-EC
    4. zinc ion binding Source: InterPro

    GO - Biological processi

    1. cellular protein metabolic process Source: Reactome
    2. mannose metabolic process Source: InterPro
    3. post-translational protein modification Source: Reactome
    4. protein N-linked glycosylation via asparagine Source: Reactome

    Keywords - Molecular functioni

    Glycosidase, Hydrolase

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    BioCyciMetaCyc:HS11961-MONOMER.
    ReactomeiREACT_25302. Reactions specific to the complex N-glycan synthesis pathway.
    UniPathwayiUPA00378.

    Protein family/group databases

    CAZyiGH38. Glycoside Hydrolase Family 38.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Alpha-mannosidase 2x (EC:3.2.1.114)
    Alternative name(s):
    Alpha-mannosidase IIx
    Short name:
    Man IIx
    Mannosidase alpha class 2A member 2
    Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase
    Gene namesi
    Name:MAN2A2
    Synonyms:MANA2X
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 15

    Organism-specific databases

    HGNCiHGNC:6825. MAN2A2.

    Subcellular locationi

    GO - Cellular componenti

    1. Golgi membrane Source: Reactome
    2. integral component of membrane Source: UniProtKB-KW

    Keywords - Cellular componenti

    Golgi apparatus, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA30574.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 11501150Alpha-mannosidase 2xPRO_0000206905Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi95 – 951N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi305 – 3051N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1093 – 10931N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1131 – 11311N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    MaxQBiP49641.
    PaxDbiP49641.
    PRIDEiP49641.

    PTM databases

    PhosphoSiteiP49641.

    Expressioni

    Gene expression databases

    ArrayExpressiP49641.
    BgeeiP49641.
    CleanExiHS_MAN2A2.
    GenevestigatoriP49641.

    Organism-specific databases

    HPAiHPA017226.

    Interactioni

    Subunit structurei

    Homodimer; disulfide-linked.By similarity

    Protein-protein interaction databases

    BioGridi110295. 7 interactions.
    IntActiP49641. 6 interactions.
    MINTiMINT-1369139.
    STRINGi9606.ENSP00000353655.

    Structurei

    3D structure databases

    ProteinModelPortaliP49641.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 55CytoplasmicSequence Analysis
    Topological domaini27 – 796770LumenalSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei6 – 2621Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the glycosyl hydrolase 38 family.Curated

    Keywords - Domaini

    Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0383.
    HOGENOMiHOG000293253.
    HOVERGENiHBG052390.
    KOiK01231.
    OMAiYLEPMEI.
    PhylomeDBiP49641.
    TreeFamiTF313152.

    Family and domain databases

    Gene3Di1.20.1270.50. 1 hit.
    2.60.40.1180. 1 hit.
    3.20.110.10. 1 hit.
    InterProiIPR011013. Gal_mutarotase_SF_dom.
    IPR011330. Glyco_hydro/deAcase_b/a-brl.
    IPR013780. Glyco_hydro_13_b.
    IPR027291. Glyco_hydro_38/57_N.
    IPR011682. Glyco_hydro_38_C.
    IPR015341. Glyco_hydro_38_cen.
    IPR000602. Glyco_hydro_38_N.
    IPR028995. Glyco_hydro_57/38_cen.
    [Graphical view]
    PfamiPF09261. Alpha-mann_mid. 1 hit.
    PF01074. Glyco_hydro_38. 1 hit.
    PF07748. Glyco_hydro_38C. 1 hit.
    [Graphical view]
    SMARTiSM00872. Alpha-mann_mid. 1 hit.
    [Graphical view]
    SUPFAMiSSF74650. SSF74650. 1 hit.
    SSF88688. SSF88688. 1 hit.
    SSF88713. SSF88713. 1 hit.

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Note: Additional isoforms seem to exist.

    Isoform 3 (identifier: P49641-3) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MKLKKQVTVC GAAIFCVAVF SLYLMLDRVQ HDPTRHQNGG NFPRSQISVL     50
    QNRIEQLEQL LEENHEIISH IKDSVLELTA NAEGPPAMLP YYTVNGSWVV 100
    PPEPRPSFFS ISPQDCQFAL GGRGQKPELQ MLTVSEELPF DNVDGGVWRQ 150
    GFDISYDPHD WDAEDLQVFV VPHSHNDPGW IKTFDKYYTE QTQHILNSMV 200
    SKLQEDPRRR FLWAEVSFFA KWWDNINVQK RAAVRRLVGN GQLEIATGGW 250
    VMPDEANSHY FALIDQLIEG HQWLERNLGA TPRSGWAVDP FGYSSTMPYL 300
    LRRANLTSML IQRVHYAIKK HFAATHSLEF MWRQTWDSDS STDIFCHMMP 350
    FYSYDVPHTC GPDPKICCQF DFKRLPGGRI NCPWKVPPRA ITEANVAERA 400
    ALLLDQYRKK SQLFRSNVLL VPLGDDFRYD KPQEWDAQFF NYQRLFDFFN 450
    SRPNLHVQAQ FGTLSDYFDA LYKRTGVEPG ARPPGFPVLS GDFFSYADRE 500
    DHYWTGYYTS RPFYKSLDRV LEAHLRGAEV LYSLAAAHAR RSGLAGRYPL 550
    SDFTLLTEAR RTLGLFQHHD AITGTAKEAV VVDYGVRLLR SLVNLKQVII 600
    HAAHYLVLGD KETYHFDPEA PFLQVDDTRL SHDALPERTV IQLDSSPRFV 650
    VLFNPLEQER FSMVSLLVNS PRVRVLSEEG QPLAVQISAH WSSATEAVPD 700
    VYQVSVPVRL PALGLGVLQL QLGLDGHRTL PSSVRIYLHG RQLSVSRHEA 750
    FPLRVIDSGT SDFALSNRYM QVWFSGLTGL LKSIRRVDEE HEQQVDMQVL 800
    VYGTRTSKDK SGAYLFLPDG EAKPYVPKEP PVLRVTEGPF FSEVVAYYEH 850
    IHQAVRLYNL PGVEGLSLDI SSLVDIRDYV NKELALHIHT DIDSQGIFFT 900
    DLNGFQVQPR RYLKKLPLQA NFYPMPVMAY IQDAQKRLTL HTAQALGVSS 950
    LKDGQLEVIL DRRLMQDDNR GLGQGLKDNK RTCNRFRLLL ERRTVGSEVQ 1000
    DSHSTSYPSL LSHLTSMYLN APALALPVAR MQLPGPGLRS FHPLASSLPC 1050
    DFHLLNLRTL QAEEDTLPSA ETALILHRKG FDCGLEAKNL GFNCTTSQGK 1100
    VALGSLFHGL DVVFLQPTSL TLLYPLASPS NSTDVYLEPM EIATFRLRLG 1150
    Length:1,150
    Mass (Da):130,539
    Last modified:September 21, 2011 - v3
    Checksum:iBFB3D763A6A55444
    GO
    Isoform 1 (identifier: P49641-1) [UniParc]FASTAAdd to Basket

    Also known as: Long

    The sequence of this isoform differs from the canonical sequence as follows:
         783-796: SIRRVDEEHEQQVD → GSGLCFLAEHPKGG
         823-906: KPYVPKEPPV...IFFTDLNGFQ → SPTSPRSPPC...CTSIQTSTAR

    Show »
    Length:1,139
    Mass (Da):128,915
    Checksum:iC16551A585F7F7FA
    GO
    Isoform 2 (identifier: P49641-2) [UniParc]FASTAAdd to Basket

    Also known as: Short

    The sequence of this isoform differs from the canonical sequence as follows:
         797-1150: Missing.

    Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

    Show »
    Length:796
    Mass (Da):91,059
    Checksum:iFDAC30CA17B00E6E
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti412 – 4121Q → R.
    Corresponds to variant rs2106673 [ dbSNP | Ensembl ].
    VAR_047912
    Natural varianti665 – 6651S → F.
    Corresponds to variant rs1266494 [ dbSNP | Ensembl ].
    VAR_047913

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei783 – 79614SIRRV…EQQVD → GSGLCFLAEHPKGG in isoform 1. 1 PublicationVSP_041732Add
    BLAST
    Alternative sequencei797 – 1150354Missing in isoform 2. 1 PublicationVSP_041733Add
    BLAST
    Alternative sequencei823 – 90684KPYVP…LNGFQ → SPTSPRSPPCCVSLKALSSQ RWLRTMSTFTRRSGFTICQG WRGCLWTYHPWWTSGTTSTR SWPCTSIQTSTAR in isoform 1. 1 PublicationVSP_041734Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D55649 mRNA. Translation: BAA09510.1.
    L28821 mRNA. Translation: AAA92022.1.
    AK289863 mRNA. Translation: BAF82552.1.
    AC067986 Genomic DNA. No translation available.
    AC068831 Genomic DNA. No translation available.
    BC136448 mRNA. Translation: AAI36449.1.
    CCDSiCCDS32332.1. [P49641-3]
    RefSeqiNP_006113.2. NM_006122.2. [P49641-3]
    UniGeneiHs.116459.

    Genome annotation databases

    EnsembliENST00000360468; ENSP00000353655; ENSG00000196547. [P49641-3]
    ENST00000558161; ENSP00000452631; ENSG00000196547.
    ENST00000559717; ENSP00000452948; ENSG00000196547. [P49641-3]
    GeneIDi4122.
    KEGGihsa:4122.
    UCSCiuc002bqc.3. human. [P49641-3]

    Polymorphism databases

    DMDMi347595795.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D55649 mRNA. Translation: BAA09510.1 .
    L28821 mRNA. Translation: AAA92022.1 .
    AK289863 mRNA. Translation: BAF82552.1 .
    AC067986 Genomic DNA. No translation available.
    AC068831 Genomic DNA. No translation available.
    BC136448 mRNA. Translation: AAI36449.1 .
    CCDSi CCDS32332.1. [P49641-3 ]
    RefSeqi NP_006113.2. NM_006122.2. [P49641-3 ]
    UniGenei Hs.116459.

    3D structure databases

    ProteinModelPortali P49641.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 110295. 7 interactions.
    IntActi P49641. 6 interactions.
    MINTi MINT-1369139.
    STRINGi 9606.ENSP00000353655.

    Chemistry

    BindingDBi P49641.

    Protein family/group databases

    CAZyi GH38. Glycoside Hydrolase Family 38.

    PTM databases

    PhosphoSitei P49641.

    Polymorphism databases

    DMDMi 347595795.

    Proteomic databases

    MaxQBi P49641.
    PaxDbi P49641.
    PRIDEi P49641.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000360468 ; ENSP00000353655 ; ENSG00000196547 . [P49641-3 ]
    ENST00000558161 ; ENSP00000452631 ; ENSG00000196547 .
    ENST00000559717 ; ENSP00000452948 ; ENSG00000196547 . [P49641-3 ]
    GeneIDi 4122.
    KEGGi hsa:4122.
    UCSCi uc002bqc.3. human. [P49641-3 ]

    Organism-specific databases

    CTDi 4122.
    GeneCardsi GC15P091447.
    H-InvDB HIX0202164.
    HGNCi HGNC:6825. MAN2A2.
    HPAi HPA017226.
    MIMi 600988. gene.
    neXtProti NX_P49641.
    PharmGKBi PA30574.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0383.
    HOGENOMi HOG000293253.
    HOVERGENi HBG052390.
    KOi K01231.
    OMAi YLEPMEI.
    PhylomeDBi P49641.
    TreeFami TF313152.

    Enzyme and pathway databases

    UniPathwayi UPA00378 .
    BioCyci MetaCyc:HS11961-MONOMER.
    Reactomei REACT_25302. Reactions specific to the complex N-glycan synthesis pathway.

    Miscellaneous databases

    ChiTaRSi MAN2A2. human.
    GenomeRNAii 4122.
    NextBioi 16184.
    PROi P49641.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P49641.
    Bgeei P49641.
    CleanExi HS_MAN2A2.
    Genevestigatori P49641.

    Family and domain databases

    Gene3Di 1.20.1270.50. 1 hit.
    2.60.40.1180. 1 hit.
    3.20.110.10. 1 hit.
    InterProi IPR011013. Gal_mutarotase_SF_dom.
    IPR011330. Glyco_hydro/deAcase_b/a-brl.
    IPR013780. Glyco_hydro_13_b.
    IPR027291. Glyco_hydro_38/57_N.
    IPR011682. Glyco_hydro_38_C.
    IPR015341. Glyco_hydro_38_cen.
    IPR000602. Glyco_hydro_38_N.
    IPR028995. Glyco_hydro_57/38_cen.
    [Graphical view ]
    Pfami PF09261. Alpha-mann_mid. 1 hit.
    PF01074. Glyco_hydro_38. 1 hit.
    PF07748. Glyco_hydro_38C. 1 hit.
    [Graphical view ]
    SMARTi SM00872. Alpha-mann_mid. 1 hit.
    [Graphical view ]
    SUPFAMi SSF74650. SSF74650. 1 hit.
    SSF88688. SSF88688. 1 hit.
    SSF88713. SSF88713. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Molecular cloning and expression of cDNAs encoding human alpha-mannosidase II and a previously unrecognized alpha-mannosidase IIx isozyme."
      Misago M., Liao Y.-F., Kudo S., Eto S., Mattei M.-G., Moremen K.W., Fukuda M.N.
      Proc. Natl. Acad. Sci. U.S.A. 92:11766-11770(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
      Tissue: Melanoma.
    2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
      Tissue: Brain.
    3. "Analysis of the DNA sequence and duplication history of human chromosome 15."
      Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A.
      , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
      Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
      Tissue: Testis.
    5. Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).

    Entry informationi

    Entry nameiMA2A2_HUMAN
    AccessioniPrimary (citable) accession number: P49641
    Secondary accession number(s): A6NH12, A8K1E8, Q13754
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: September 21, 2011
    Last modified: October 1, 2014
    This is version 135 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Glycosyl hydrolases
      Classification of glycosyl hydrolase families and list of entries
    2. Human chromosome 15
      Human chromosome 15: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3