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Q9UKM7 (MA1B1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (8) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase

EC=3.2.1.113
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 names
Name:MAN1B1
ORF Names:UNQ747/PRO1477
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length699 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6 Ref.7

Catalytic activity

Hydrolysis of the terminal (1->2)-linked alpha-D-mannose residues in the oligo-mannose oligosaccharide Man9(GlcNAc)2. Ref.2 Ref.6 Ref.9

Cofactor

Calcium.

Enzyme regulation

Inhibited by both 1-deoxymannojirimycin (dMNJ) and kifunensine. Ref.2

Pathway

Protein modification; protein glycosylation.

Subcellular location

Endoplasmic reticulum membrane; Single-pass type II membrane protein Ref.2.

Tissue specificity

Widely expressed. Ref.1 Ref.2

Involvement in disease

Mental retardation, autosomal recessive 15 (MRT15) [MIM:614202]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Sequence similarities

Belongs to the glycosyl hydrolase 47 family.

Caution

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

Biophysicochemical properties

Kinetic parameters:

KM=0.4 mM for Man9GlcNAc2 Ref.1

pH dependence:

Optimum pH is between 6.5 and 6.9.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 699699Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase
PRO_0000210314

Regions

Topological domain1 – 8484Cytoplasmic Potential
Transmembrane85 – 10521Helical; Signal-anchor for type II membrane protein; Potential
Topological domain106 – 699594Lumenal Potential
Compositional bias39 – 457Poly-Pro

Sites

Active site3301Proton donor Probable
Active site4631 Probable
Active site5991 Probable

Amino acid modifications

Disulfide bond527 ↔ 556 Ref.8

Natural variations

Natural variant591N → S. Ref.1 Ref.2 Ref.3 Ref.5
Corresponds to variant rs968733 [ dbSNP | Ensembl ].
VAR_055841
Natural variant3341R → C in MRT15; results in about 1300-fold decrease in activity. Ref.10
VAR_066592
Natural variant3971E → K in MRT15; disrupts stable protein expression. Ref.10
VAR_066593

Experimental info

Mutagenesis3301E → 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. Ref.9
Mutagenesis4631D → 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. Ref.9
Mutagenesis5241H → A: About 4-fold reduction in K(cat). Ref.9
Mutagenesis5991E → 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. Ref.9
Sequence conflict2041T → A in AAD45504. Ref.2
Sequence conflict2231S → P in AAD45504. Ref.2

Secondary structure

.................................................................................. 699
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9UKM7 [UniParc].

Last modified March 7, 2006. Version 2.
Checksum: B8BF3BE333D90261

FASTA69979,580
        10         20         30         40         50         60 
MAACEGRRSG ALGSSQSDFL TPPVGGAPWA VATTVVMYPP PPPPPHRDFI SVTLSFGENY 

        70         80         90        100        110        120 
DNSKSWRRRS CWRKWKQLSR LQRNMILFLL AFLLFCGLLF YINLADHWKA LAFRLEEEQK 

       130        140        150        160        170        180 
MRPEIAGLKP ANPPVLPAPQ KADTDPENLP EISSQKTQRH IQRGPPHLQI RPPSQDLKDG 

       190        200        210        220        230        240 
TQEEATKRQE APVDPRPEGD PQRTVISWRG AVIEPEQGTE LPSRRAEVPT KPPLPPARTQ 

       250        260        270        280        290        300 
GTPVHLNYRQ KGVIDVFLHA WKGYRKFAWG HDELKPVSRS FSEWFGLGLT LIDALDTMWI 

       310        320        330        340        350        360 
LGLRKEFEEA RKWVSKKLHF EKDVDVNLFE STIRILGGLL SAYHLSGDSL FLRKAEDFGN 

       370        380        390        400        410        420 
RLMPAFRTPS KIPYSDVNIG TGVAHPPRWT SDSTVAEVTS IQLEFRELSR LTGDKKFQEA 

       430        440        450        460        470        480 
VEKVTQHIHG LSGKKDGLVP MFINTHSGLF THLGVFTLGA RADSYYEYLL KQWIQGGKQE 

       490        500        510        520        530        540 
TQLLEDYVEA IEGVRTHLLR HSEPSKLTFV GELAHGRFSA KMDHLVCFLP GTLALGVYHG 

       550        560        570        580        590        600 
LPASHMELAQ ELMETCYQMN RQMETGLSPE IVHFNLYPQP GRRDVEVKPA DRHNLLRPET 

       610        620        630        640        650        660 
VESLFYLYRV TGDRKYQDWG WEILQSFSRF TRVPSGGYSS INNVQDPQKP EPRDKMESFF 

       670        680        690 
LGETLKYLFL LFSDDPNLLS LDAYVFNTEA HPLPIWTPA 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and expression of a specific human alpha1,2-mannosidase that trims Man9GlcNAc2 to Man8GlcNAc2 isomer B during N-glycan biosynthesis."
Tremblay L.O., Herscovics A.
Glycobiology 9:1073-1078(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, VARIANT SER-59.
Tissue: Fetal brain, Liver, Placenta and Testis.
[2]"Identification, expression, and characterization of a cDNA encoding human endoplasmic reticulum mannosidase I, the enzyme that catalyzes the first mannose trimming step in mammalian Asn-linked oligosaccharide biosynthesis."
Gonzalez D.S., Karaveg K., Vandersall-Nairn A.S., Lal A., Moremen K.W.
J. Biol. Chem. 274:21375-21386(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 37-699, TISSUE SPECIFICITY, ENZYME ACTIVITY, ENZYME REGULATION, SUBCELLULAR LOCATION, VARIANT SER-59.
[3]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-59.
[4]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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], VARIANT SER-59.
Tissue: Lung and Placenta.
[6]"The specificity of the yeast and human class I ER alpha 1,2-mannosidases involved in ER quality control is not as strict previously reported."
Herscovics A., Romero P.A., Tremblay L.O.
Glycobiology 12:14G-15G(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY.
[7]"Endoplasmic reticulum (ER) mannosidase I is compartmentalized and required for N-glycan trimming to Man5-6GlcNAc2 in glycoprotein ER-associated degradation."
Avezov E., Frenkel Z., Ehrlich M., Herscovics A., Lederkremer G.Z.
Mol. Biol. Cell 19:216-225(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"Structural basis for catalysis and inhibition of N-glycan processing class I alpha 1,2-mannosidases."
Vallee F., Karaveg K., Herscovics A., Moremen K.W., Howell P.L.
J. Biol. Chem. 275:41287-41298(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 243-699, DISULFIDE BOND.
[9]"Mechanism of class 1 (glycosylhydrolase family 47) {alpha}-mannosidases involved in N-glycan processing and endoplasmic reticulum quality control."
Karaveg K., Siriwardena A., Tempel W., Liu Z.J., Glushka J., Wang B.C., Moremen K.W.
J. Biol. Chem. 280:16197-16207(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.41 ANGSTROMS) OF 172-699 IN COMPLEX WITH A THIO-DISACCHARIDE SUBSTRATE ANALOG, ENZYME ACTIVITY, MUTAGENESIS OF GLU-330; ASP-463; HIS-524 AND GLU-599.
[10]"Mutations in the alpha 1,2-mannosidase gene, MAN1B1, cause autosomal-recessive intellectual disability."
Rafiq M.A., Kuss A.W., Puettmann L., Noor A., Ramiah A., Ali G., Hu H., Kerio N.A., Xiang Y., Garshasbi M., Khan M.A., Ishak G.E., Weksberg R., Ullmann R., Tzschach A., Kahrizi K., Mahmood K., Naeem F. expand/collapse author list , Ayub M., Moremen K.W., Vincent J.B., Ropers H.H., Ansar M., Najmabadi H.
Am. J. Hum. Genet. 89:176-182(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MRT15 CYS-334 AND LYS-397, CHARACTERIZATION OF VARIANTS MRT15 CYS-334 AND LYS-397.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF148509 mRNA. Translation: AAF03215.1.
AF145732 mRNA. Translation: AAD45504.1.
AY358465 mRNA. Translation: AAQ88830.1.
AL929554, AL807752 Genomic DNA. Translation: CAH72887.1.
AL807752, AL929554 Genomic DNA. Translation: CAI12781.1.
BC002953 mRNA. Translation: AAH02953.1.
BC006079 mRNA. Translation: AAH06079.1.
RefSeqNP_057303.2. NM_016219.4.
UniGeneHs.279881.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1FMIX-ray1.90A243-697[»]
1FO2X-ray2.38A243-699[»]
1FO3X-ray1.75A243-699[»]
1X9DX-ray1.41A172-699[»]
ProteinModelPortalQ9UKM7.
SMRQ9UKM7. Positions 243-697.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116414. 4 interactions.
IntActQ9UKM7. 2 interactions.
MINTMINT-6610355.
STRING9606.ENSP00000360645.

Chemistry

BindingDBQ9UKM7.
ChEMBLCHEMBL2308.

Protein family/group databases

CAZyGH47. Glycoside Hydrolase Family 47.

PTM databases

PhosphoSiteQ9UKM7.

Polymorphism databases

DMDM93195043.

Proteomic databases

PaxDbQ9UKM7.
PRIDEQ9UKM7.

Protocols and materials databases

DNASU11253.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000371589; ENSP00000360645; ENSG00000177239.
GeneID11253.
KEGGhsa:11253.
UCSCuc004cld.3. human.

Organism-specific databases

CTD11253.
GeneCardsGC09P139981.
H-InvDBHIX0035043.
HGNCHGNC:6823. MAN1B1.
HPAHPA051516.
MIM604346. gene.
614202. phenotype.
neXtProtNX_Q9UKM7.
Orphanet88616. Autosomal recessive nonsyndromic intellectual deficit.
PharmGKBPA30572.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG300315.
HOGENOMHOG000181987.
HOVERGENHBG052389.
KOK01230.
OMAYAQVETG.
OrthoDBEOG7ZGX2S.
PhylomeDBQ9UKM7.
TreeFamTF354274.

Enzyme and pathway databases

BRENDA3.2.1.113. 2681.
ReactomeREACT_17015. Metabolism of proteins.
UniPathwayUPA00378.

Gene expression databases

ArrayExpressQ9UKM7.
BgeeQ9UKM7.
CleanExHS_MAN1B1.
GenevestigatorQ9UKM7.

Family and domain databases

Gene3D1.50.10.50. 1 hit.
InterProIPR001382. Glyco_hydro_47.
[Graphical view]
PANTHERPTHR11742. PTHR11742. 1 hit.
PfamPF01532. Glyco_hydro_47. 1 hit.
[Graphical view]
PRINTSPR00747. GLYHDRLASE47.
SUPFAMSSF48225. SSF48225. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ9UKM7.
GeneWikiMAN1B1.
GenomeRNAi11253.
NextBio42822.
PROQ9UKM7.
SOURCESearch...

Entry information

Entry nameMA1B1_HUMAN
AccessionPrimary (citable) accession number: Q9UKM7
Secondary accession number(s): Q5VSG3, Q9BRS9, Q9Y5K7
Entry history
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: March 7, 2006
Last modified: March 19, 2014
This is version 136 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM

Glycosyl hydrolases

Classification of glycosyl hydrolase families and list of entries