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UniProtKB - Q9UKM7 (MA1B1_HUMAN)

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Protein

Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase

Gene

MAN1B1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man9GlcNAc2 to produce Man8GlcNAc2, but at high enzyme concentrations, as found in the ER quality control compartment (ERQC), it further trims the carbohydrates to Man5-6GlcNAc2.2 Publications

Caution

It is uncertain whether Met-1 or Met-37 is the initiator.Curated

Catalytic activityi

Hydrolysis of the terminal (1->2)-linked alpha-D-mannose residues in the oligo-mannose oligosaccharide Man9(GlcNAc)2.3 Publications

Cofactori

Ca2+By similarity

Enzyme regulationi

Inhibited by both 1-deoxymannojirimycin (dMNJ) and kifunensine.1 Publication

Kineticsi

  1. KM=0.4 mM for Man9GlcNAc21 Publication

    pH dependencei

    Optimum pH is between 6.5 and 6.9.1 Publication

    Pathwayi: protein glycosylation

    This protein is involved in the pathway protein glycosylation, which is part of Protein modification.By similarity
    View all proteins of this organism that are known to be involved in the pathway protein glycosylation and in Protein modification.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei330Proton donorCurated1
    Active sitei463Curated1
    Active sitei570Proton donorBy similarity1
    Active sitei599Curated1
    Metal bindingi688CalciumBy similarity1

    GO - Molecular functioni

    • calcium ion binding Source: UniProtKB
    • mannosyl-oligosaccharide 1,2-alpha-mannosidase activity Source: UniProtKB
    View the complete GO annotation on QuickGO ...

    GO - Biological processi

    • endoplasmic reticulum mannose trimming Source: ParkinsonsUK-UCL
    • mannose trimming involved in glycoprotein ERAD pathway Source: ParkinsonsUK-UCL
    • N-glycan processing Source: GO_Central
    • oligosaccharide metabolic process Source: ProtInc
    • protein alpha-1,2-demannosylation Source: ParkinsonsUK-UCL
    • protein glycosylation Source: UniProtKB-UniPathway
    • trimming of first mannose on A branch Source: Reactome
    • trimming of second mannose on A branch Source: Reactome
    • trimming of terminal mannose on B branch Source: ParkinsonsUK-UCL
    • trimming of terminal mannose on C branch Source: Reactome
    • ubiquitin-dependent ERAD pathway Source: UniProtKB
    View the complete GO annotation on QuickGO ...

    Keywordsi

    Molecular functionGlycosidase, Hydrolase
    LigandCalcium, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS11144-MONOMER
    BRENDAi3.2.1.113 2681
    ReactomeiR-HSA-4793950 Defective MAN1B1 causes MRT15
    R-HSA-901032 ER Quality Control Compartment (ERQC)
    SABIO-RKiQ9UKM7
    UniPathwayiUPA00378

    Protein family/group databases

    CAZyiGH47 Glycoside Hydrolase Family 47

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase (EC:3.2.1.1133 Publications)
    Alternative name(s):
    ER alpha-1,2-mannosidase
    ER mannosidase 1
    Short name:
    ERMan1
    Man9GlcNAc2-specific-processing alpha-mannosidase
    Mannosidase alpha class 1B member 1
    Gene namesi
    Name:MAN1B1
    ORF Names:UNQ747/PRO1477
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
    Proteomesi
    • UP000005640 Componenti: Chromosome 9

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000177239.14
    HGNCiHGNC:6823 MAN1B1
    MIMi604346 gene
    neXtProtiNX_Q9UKM7

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini1 – 84CytoplasmicSequence analysisAdd BLAST84
    Transmembranei85 – 105Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
    Topological domaini106 – 699LumenalSequence analysisAdd BLAST594

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Mental retardation, autosomal recessive 15 (MRT15)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.
    See also OMIM:614202
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_066592334R → C in MRT15; results in about 1300-fold decrease in activity. 1 PublicationCorresponds to variant dbSNP:rs387906886EnsemblClinVar.1
    Natural variantiVAR_066593397E → K in MRT15; disrupts stable protein expression. 1 PublicationCorresponds to variant dbSNP:rs387906885EnsemblClinVar.1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi330E → Q: About 44-fold reduction in K(cat), slight reduction in K(m), about 100-fold increase in binding affinity for Man(9)GlcnAc(2) but no change in binding affinity for the inhibitor, dMNJ. Even further greater reduction in K(cat) and increase in K(m); when associated with Q-599. 1 Publication1
    Mutagenesisi463D → N: Some reduction in K(cat) but no change in K(m), abolishes almost all binding to Man(9)GlcnAc(2) but reduced binding to the inhibitor dMNJ by about 73-fold. Further reduction in K(m) but slight increase in K(m); when associated with Q-599. 1 Publication1
    Mutagenesisi524H → A: About 4-fold reduction in K(cat). 1 Publication1
    Mutagenesisi599E → Q: Very significant reduction in K(cat), 4-fold weaker binding affinity for Man(9)GlcnAc(2) but about 1000-fold reduction in binding affinity for the inhibitor, dMNJ. Significant reductions in K(cat) and slight increase in K(m); when associated with E-330 or N-463. 1 Publication1

    Keywords - Diseasei

    Disease mutation, Mental retardation

    Organism-specific databases

    DisGeNETi11253
    MalaCardsiMAN1B1
    MIMi614202 phenotype
    OpenTargetsiENSG00000177239
    Orphaneti88616 Autosomal recessive non-syndromic intellectual disability
    397941 MAN1B1-CDG
    PharmGKBiPA30572

    Chemistry databases

    ChEMBLiCHEMBL2308
    DrugBankiDB03206 Duvoglustat
    DB02742 Kifunensine
    DB02422 Methyl-2-S-(Alpha-D-Mannopyranosyl)-2-Thio-Alpha-D-Mannopyranoside

    Polymorphism and mutation databases

    BioMutaiMAN1B1
    DMDMi93195043

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002103141 – 699Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidaseAdd BLAST699

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Disulfide bondi527 ↔ 5561 Publication

    Keywords - PTMi

    Disulfide bond

    Proteomic databases

    EPDiQ9UKM7
    MaxQBiQ9UKM7
    PaxDbiQ9UKM7
    PeptideAtlasiQ9UKM7
    PRIDEiQ9UKM7
    ProteomicsDBi84820

    PTM databases

    iPTMnetiQ9UKM7
    PhosphoSitePlusiQ9UKM7
    SwissPalmiQ9UKM7

    Expressioni

    Tissue specificityi

    Widely expressed.2 Publications

    Gene expression databases

    BgeeiENSG00000177239
    CleanExiHS_MAN1B1
    ExpressionAtlasiQ9UKM7 baseline and differential
    GenevisibleiQ9UKM7 HS

    Organism-specific databases

    HPAiHPA051516

    Interactioni

    Protein-protein interaction databases

    BioGridi116414, 7 interactors
    IntActiQ9UKM7, 4 interactors
    MINTiQ9UKM7
    STRINGi9606.ENSP00000360645

    Chemistry databases

    BindingDBiQ9UKM7

    Structurei

    Secondary structure

    1699
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi244 – 246Combined sources3
    Helixi248 – 267Combined sources20
    Beta strandi271 – 275Combined sources5
    Turni276 – 279Combined sources4
    Beta strandi280 – 282Combined sources3
    Beta strandi284 – 287Combined sources4
    Helixi289 – 300Combined sources12
    Helixi304 – 317Combined sources14
    Beta strandi325 – 327Combined sources3
    Helixi328 – 346Combined sources19
    Helixi349 – 362Combined sources14
    Helixi363 – 366Combined sources4
    Beta strandi368 – 370Combined sources3
    Beta strandi375 – 378Combined sources4
    Turni379 – 381Combined sources3
    Beta strandi391 – 394Combined sources4
    Helixi395 – 399Combined sources5
    Helixi402 – 412Combined sources11
    Helixi416 – 429Combined sources14
    Beta strandi441 – 444Combined sources4
    Turni445 – 447Combined sources3
    Beta strandi450 – 452Combined sources3
    Turni460 – 462Combined sources3
    Helixi463 – 475Combined sources13
    Helixi481 – 497Combined sources17
    Beta strandi499 – 501Combined sources3
    Turni503 – 505Combined sources3
    Beta strandi508 – 510Combined sources3
    Beta strandi512 – 514Combined sources3
    Beta strandi517 – 519Combined sources3
    Beta strandi521 – 523Combined sources3
    Helixi524 – 527Combined sources4
    Helixi528 – 538Combined sources11
    Helixi543 – 561Combined sources19
    Beta strandi563 – 566Combined sources4
    Beta strandi570 – 573Combined sources4
    Beta strandi584 – 586Combined sources3
    Helixi589 – 591Combined sources3
    Helixi599 – 611Combined sources13
    Helixi615 – 630Combined sources16
    Helixi659 – 662Combined sources4
    Helixi664 – 672Combined sources9
    Turni676 – 679Combined sources4
    Turni681 – 683Combined sources3
    Beta strandi684 – 686Combined sources3
    Beta strandi692 – 694Combined sources3

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    		PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1FMIX-ray1.90A243-697[»]
    1FO2X-ray2.38A243-699[»]
    1FO3X-ray1.75A243-699[»]
    1X9DX-ray1.41A172-699[»]
    5KIJX-ray1.65A245-696[»]
    5KK7X-ray1.73A/B245-699[»]
    ProteinModelPortaliQ9UKM7
    SMRiQ9UKM7
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9UKM7

    Family & Domainsi

    Compositional bias

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Compositional biasi39 – 45Poly-Pro7

    Sequence similaritiesi

    Belongs to the glycosyl hydrolase 47 family.Curated

    Keywords - Domaini

    Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG2431 Eukaryota
    ENOG410XP04 LUCA
    GeneTreeiENSGT00390000016529
    HOGENOMiHOG000181987
    HOVERGENiHBG052389
    InParanoidiQ9UKM7
    KOiK01230
    OMAiDHLTCYL
    OrthoDBiEOG091G0342
    PhylomeDBiQ9UKM7
    TreeFamiTF354274

    Family and domain databases

    Gene3Di1.50.10.10, 1 hit
    InterProiView protein in InterPro
    IPR012341 6hp_glycosidase-like_sf
    IPR001382 Glyco_hydro_47
    IPR036026 Seven-hairpin_glycosidases
    PfamiView protein in Pfam
    PF01532 Glyco_hydro_47, 1 hit
    PRINTSiPR00747 GLYHDRLASE47
    SUPFAMiSSF48225 SSF48225, 1 hit

    Sequencei

    Sequence statusi: Complete.

    Q9UKM7-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MAACEGRRSG ALGSSQSDFL TPPVGGAPWA VATTVVMYPP PPPPPHRDFI 
            60         70         80         90        100
    SVTLSFGENY DNSKSWRRRS CWRKWKQLSR LQRNMILFLL AFLLFCGLLF 
           110        120        130        140        150
    YINLADHWKA LAFRLEEEQK MRPEIAGLKP ANPPVLPAPQ KADTDPENLP 
           160        170        180        190        200
    EISSQKTQRH IQRGPPHLQI RPPSQDLKDG TQEEATKRQE APVDPRPEGD 
           210        220        230        240        250
    PQRTVISWRG AVIEPEQGTE LPSRRAEVPT KPPLPPARTQ GTPVHLNYRQ 
           260        270        280        290        300
    KGVIDVFLHA WKGYRKFAWG HDELKPVSRS FSEWFGLGLT LIDALDTMWI 
           310        320        330        340        350
    LGLRKEFEEA RKWVSKKLHF EKDVDVNLFE STIRILGGLL SAYHLSGDSL 
           360        370        380        390        400
    FLRKAEDFGN RLMPAFRTPS KIPYSDVNIG TGVAHPPRWT SDSTVAEVTS 
           410        420        430        440        450
    IQLEFRELSR LTGDKKFQEA VEKVTQHIHG LSGKKDGLVP MFINTHSGLF 
           460        470        480        490        500
    THLGVFTLGA RADSYYEYLL KQWIQGGKQE TQLLEDYVEA IEGVRTHLLR 
           510        520        530        540        550
    HSEPSKLTFV GELAHGRFSA KMDHLVCFLP GTLALGVYHG LPASHMELAQ 
           560        570        580        590        600
    ELMETCYQMN RQMETGLSPE IVHFNLYPQP GRRDVEVKPA DRHNLLRPET 
           610        620        630        640        650
    VESLFYLYRV TGDRKYQDWG WEILQSFSRF TRVPSGGYSS INNVQDPQKP 
           660        670        680        690 
    EPRDKMESFF LGETLKYLFL LFSDDPNLLS LDAYVFNTEA HPLPIWTPA
    Length:699
    Mass (Da):79,580
    Last modified:March 7, 2006 - v2
    Checksum:iB8BF3BE333D90261
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti204T → A in AAD45504 (PubMed:10409699).Curated1
    Sequence conflicti223S → P in AAD45504 (PubMed:10409699).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_05584159N → S4 PublicationsCorresponds to variant dbSNP:rs968733EnsemblClinVar.1
    Natural variantiVAR_066592334R → C in MRT15; results in about 1300-fold decrease in activity. 1 PublicationCorresponds to variant dbSNP:rs387906886EnsemblClinVar.1
    Natural variantiVAR_066593397E → K in MRT15; disrupts stable protein expression. 1 PublicationCorresponds to variant dbSNP:rs387906885EnsemblClinVar.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    		AF148509 mRNA Translation: AAF03215.1
    AF145732 mRNA Translation: AAD45504.1
    AY358465 mRNA Translation: AAQ88830.1
    AL929554 Genomic DNA No translation available.
    AL807752 Genomic DNA No translation available.
    BC002953 mRNA Translation: AAH02953.1
    BC006079 mRNA Translation: AAH06079.1
    CCDSiCCDS7029.1
    RefSeqiNP_057303.2, NM_016219.4
    UniGeneiHs.279881

    Genome annotation databases

    EnsembliENST00000371589; ENSP00000360645; ENSG00000177239
    GeneIDi11253
    KEGGihsa:11253
    UCSCiuc004cld.3 human

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiMA1B1_HUMAN
    AccessioniPrimary (citable) accession number: Q9UKM7
    Secondary accession number(s): Q5VSG3, Q9BRS9, Q9Y5K7
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 16, 2001
    Last sequence update: March 7, 2006
    Last modified: June 20, 2018
    This is version 178 of the entry and version 2 of the sequence. See 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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Glycosyl hydrolases
      Classification of glycosyl hydrolase families and list of entries
    2. Human chromosome 9
      Human chromosome 9: 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    8. SIMILARITY comments
      Index of protein domains and families

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