MAN2B1

Protein identityUniProt · HPA

UniProt accession

O00754

Gene

MAN2B1

Ensembl

ENSG00000104774

Chromosome

19

Canonical length

1011 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Vesicles

Secretome location

Intracellular and membrane

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes an enzyme that hydrolyzes terminal, non-reducing alpha-D-mannose residues in alpha-D-mannosides. Its activity is necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover and it is member of family 38 of glycosyl hydrolases. The full length protein is processed in two steps. First, a 49 aa leader sequence is cleaved off and the remainder of the protein is processed into 3 peptides of 70 kDa, 42 kDa (D) and 13/15 kDa (E). Next, the 70 kDa peptide is further processed into three peptides (A, B and C). The A, B and C peptides are disulfide-linked. Defects in this gene have been associated with lysosomal alpha-mannosidosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010]

Canonical amino-acid sequenceUniProt

1011 residues, UniProt reviewed canonical sequence.

>O00754|MAN2B1
     1  MGAYARASGV CARGCLDSAG PWTMSRALRP PLPPLCFFLL LLAAAGARAG GYETCPTVQP
    61  NMLNVHLLPH THDDVGWLKT VDQYFYGIKN DIQHAGVQYI LDSVISALLA DPTRRFIYVE
   121  IAFFSRWWHQ QTNATQEVVR DLVRQGRLEF ANGGWVMNDE AATHYGAIVD QMTLGLRFLE
   181  DTFGNDGRPR VAWHIDPFGH SREQASLFAQ MGFDGFFFGR LDYQDKWVRM QKLEMEQVWR
   241  ASTSLKPPTA DLFTGVLPNG YNPPRNLCWD VLCVDQPLVE DPRSPEYNAK ELVDYFLNVA
   301  TAQGRYYRTN HTVMTMGSDF QYENANMWFK NLDKLIRLVN AQQAKGSSVH VLYSTPACYL
   361  WELNKANLTW SVKHDDFFPY ADGPHQFWTG YFSSRPALKR YERLSYNFLQ VCNQLEALVG
   421  LAANVGPYGS GDSAPLNEAM AVLQHHDAVS GTSRQHVAND YARQLAAGWG PCEVLLSNAL
   481  ARLRGFKDHF TFCQQLNISI CPLSQTAARF QVIVYNPLGR KVNWMVRLPV SEGVFVVKDP
   541  NGRTVPSDVV IFPSSDSQAH PPELLFSASL PALGFSTYSV AQVPRWKPQA RAPQPIPRRS
   601  WSPALTIENE HIRATFDPDT GLLMEIMNMN QQLLLPVRQT FFWYNASIGD NESDQASGAY
   661  IFRPNQQKPL PVSRWAQIHL VKTPLVQEVH QNFSAWCSQV VRLYPGQRHL ELEWSVGPIP
   721  VGDTWGKEVI SRFDTPLETK GRFYTDSNGR EILERRRDYR PTWKLNQTEP VAGNYYPVNT
   781  RIYITDGNMQ LTVLTDRSQG GSSLRDGSLE LMVHRRLLKD DGRGVSEPLM ENGSGAWVRG
   841  RHLVLLDTAQ AAAAGHRLLA EQEVLAPQVV LAPGGGAAYN LGAPPRTQFS GLRRDLPPSV
   901  HLLTLASWGP EMVLLRLEHQ FAVGEDSGRN LSAPVTLNLR DLFSTFTITR LQETTLVANQ
   961  LREAASRLKW TTNTGPTPHQ TPYQLDPANI TLEPMEIRTF LASVQWKEVD G

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MAN2B1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.22

Highest tissue expression

79 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MAN2B1.

Disease | AllUniProt

Conditions MAN2B1 is implicated in, by any mechanism.

• Mannosidosis, alpha B, lysosomal (MANSA) MIM:248500

Disease | GeneticClinVar

361 pathogenic / likely-pathogenic of 1,939 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Deficiency of alpha-mannosidase
• Inborn genetic diseases
• MAN2B1-related disorder
• Intellectual disability
• Ovarian serous cystadenocarcinoma

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.97

gnomAD pLI

0

gnomAD missense Z

1.15

DepMap mean gene effect

-0.17

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• glycoprotein catabolic process
• learning or memory
• mannose metabolic process

Molecular functions

• alpha-mannosidase activity
• carbohydrate binding
• metal ion binding

Cellular components

• azurophil granule lumen
• extracellular exosome
• extracellular region
• extracellular space
• lysosomal lumen
• lysosome
• nucleoplasm

Protein domainsUniProt · Pfam · InterPro

• Glycoside hydrolase family 38, N-terminal domain
• Galactose mutarotase-like domain superfamily
• Glycoside hydrolase/deacetylase, beta/alpha-barrel
• Glycosyl hydrolase family 38, C-terminal
• Glycosyl hydrolase, all-beta
• Glycoside hydrolase family 38, central domain
• Glycoside hydrolase 38, N-terminal domain superfamily
• Glycoside hydrolase families 57/38, central domain superfamily
• Glycoside hydrolase family 38, central domain superfamily
• Glycosyl hydrolases family 38, C-terminal domain
• Lysosomal alpha-mannosidase-like, central domain
• Glycosyl Hydrolase Family 38
• Glycosyl hydrolases family 38 N-terminal domain
• Glycosyl hydrolases family 38 C-terminal domain
• Alpha mannosidase middle domain
• Glycosyl hydrolases family 38 C-terminal beta sandwich domain
• Lysosomal alpha-mannosidase-like, central domain

KeywordsUniProt

• Disulfide bond
• Glycoprotein
• Glycosidase
• Hydrolase
• Lysosome
• Metal-binding
• Secreted
• Signal
• Zinc
• Zymogen

InteractionsUniProt · HPA

Protein binding partners of MAN2B1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• FBXO6