Reviewed, UniProtKB/Swiss-Prot O00754 (MA2B1_HUMAN)

Names and origin

Protein names

Recommended name:
    Lysosomal alpha-mannosidase
      Short name=Laman
    EC=3.2.1.24
Alternative name(s):
    Lysosomal acid alpha-mannosidase
    Mannosidase alpha class 2B member 1
      Short name=Mannosidase, alpha B
Cleaved into the following 5 chains:
    1- Recommended name:
            Lysosomal alpha-mannosidase A peptide
    2- Recommended name:
            Lysosomal alpha-mannosidase B peptide
    3- Recommended name:
            Lysosomal alpha-mannosidase C peptide
    4- Recommended name:
            Lysosomal alpha-mannosidase D peptide
    5- Recommended name:
            Lysosomal alpha-mannosidase E peptide

Gene names

Name:	MAN2B1
Synonyms:	LAMAN, MANB

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1011 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover. Cleaves all known types of alpha-mannosidic linkages.
Catalytic activity	Hydrolysis of terminal, non-reducing alpha-D-mannose residues in alpha-D-mannosides.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subcellular location	Lysosome.
Post-translational modification	First processed into 3 peptides of 70 kDa, 42 kDa (D) and 13/15 kDa (E). The 70 kDa peptide is further processed into three peptides (A, B and C). The A, B and C peptides are disulfide-linked. Heavily glycosylated. Ref.7 Ref.9
Involvement in disease	Defects in MAN2B1 are the cause of lysosomal alpha-mannosidosis (AM) [MIM:248500]. AM is a lysosomal storage disease characterized by accumulation of unbranched oligosaccharide chains. This accumulation is expressed histologically as cytoplasmic vacuolation predominantly in the CNS and parenchymatous organs. Depending on the clinical findings at the age of onset, a severe infantile (type I) and a mild juvenile (type II) form of alpha-mannosidosis are recognized. There is considerable variation in the clinical expression with mental retardation, recurrent infections, impaired hearing and Hurler-like skeletal changes being the most consistent abnormalities. Ref.2 Ref.10 Ref.11 Ref.12 Ref.13
Sequence similarities	Belongs to the glycosyl hydrolase 38 family.

Ontologies

Keywords
Cellular component	Lysosome
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Glycosidase Hydrolase
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	protein deglycosylation Ref.5 Traceable author statement. Source: ProtInc
Cellular component	lysosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	alpha-mannosidase activity Ref.5 Traceable author statement. Source: ProtInc carbohydrate binding Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 49	49
	Chain	50 – 1011	962	Lysosomal alpha-mannosidase		PRO_0000012069
	Chain	50 – 345	296	Lysosomal alpha-mannosidase A peptide		PRO_0000012070
	Chain	346 – 429	84	Lysosomal alpha-mannosidase B peptide		PRO_0000012071
	Chain	430 – 601	172	Lysosomal alpha-mannosidase C peptide		PRO_0000012072
	Chain	602 – 882	281	Lysosomal alpha-mannosidase D peptide		PRO_0000012073
	Chain	883 – 1011	129	Lysosomal alpha-mannosidase E peptide		PRO_0000012074
Sites
	Active site	196	1	Nucleophile By similarity
	Metal binding	72	1	Zinc By similarity
	Metal binding	74	1	Zinc By similarity
	Metal binding	196	1	Zinc By similarity
	Metal binding	446	1	Zinc By similarity
Amino acid modifications
	Glycosylation	133	1	N-linked (GlcNAc...) Potential
	Glycosylation	310	1	N-linked (GlcNAc...) Potential
	Glycosylation	367	1	N-linked (GlcNAc...) Ref.9
	Glycosylation	497	1	N-linked (GlcNAc...) Potential
	Glycosylation	645	1	N-linked (GlcNAc...) Potential
	Glycosylation	651	1	N-linked (GlcNAc...) Potential
	Glycosylation	692	1	N-linked (GlcNAc...) Potential
	Glycosylation	766	1	N-linked (GlcNAc...) Ref.9
	Glycosylation	832	1	N-linked (GlcNAc...) Potential
	Glycosylation	930	1	N-linked (GlcNAc...) Ref.7
	Glycosylation	989	1	N-linked (GlcNAc...) Potential
	Disulfide bond	55 ↔ 358		By similarity
	Disulfide bond	268 ↔ 273		By similarity
	Disulfide bond	412 ↔ 472		By similarity
	Disulfide bond	493 ↔ 501		By similarity
Natural variations
	Natural variant	72	1	H → L in AM; type II. Ref.2 Ref.10		VAR_003338
	Natural variant	200	1	H → L in AM; no residual enzyme activity. Ref.13		VAR_026412
	Natural variant	250	1	A → S: dbSNP rs3745650.		VAR_049209
	Natural variant	278	1	L → V: dbSNP rs1054486. Ref.11		VAR_003339
	Natural variant	312	1	T → I: dbSNP rs1054487. Ref.11		VAR_003340
	Natural variant	337	1	R → Q: dbSNP rs1133330. Ref.11		VAR_003341
	Natural variant	355	1	T → P in AM. Ref.11		VAR_003342
	Natural variant	356	1	P → R in AM; type I. Ref.10		VAR_003343
	Natural variant	402	1	E → K in AM. Ref.11		VAR_003344
	Natural variant	413	1	N → S: dbSNP rs35836657. Ref.11		VAR_003345
	Natural variant	453	1	S → Y in AM. Ref.12		VAR_026413
	Natural variant	481	1	A → S: dbSNP rs34544747.		VAR_049210
	Natural variant	714	1	W → R in AM. Ref.11		VAR_003346
	Natural variant	750	1	R → W in AM; type II. Ref.10		VAR_003347
	Natural variant	801	1	G → D in AM; no residual enzyme activity. Ref.13		VAR_026414
	Natural variant	809	1	L → P in AM. Ref.11		VAR_003348
Experimental info
	Sequence conflict	3	1	Missing in AAC51362. Ref.3
	Sequence conflict	186	1	D → V in AAC34130. Ref.2
	Sequence conflict	343	1	Missing in AAB03816. Ref.1
	Sequence conflict	384	1	P → H in AAC50812. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	O00754-1 [UniParc]. Last modified October 31, 2006. Version 3. Checksum: E11C77C19D8BD88C	FASTA	1,011	113,744
	10 20 30 40 50 60 MGAYARASGV CARGCLDSAG PWTMSRALRP PLPPLCFFLL LLAAAGARAG GYETCPTVQP 70 80 90 100 110 120 NMLNVHLLPH THDDVGWLKT VDQYFYGIKN DIQHAGVQYI LDSVISALLA DPTRRFIYVE 130 140 150 160 170 180 IAFFSRWWHQ QTNATQEVVR DLVRQGRLEF ANGGWVMNDE AATHYGAIVD QMTLGLRFLE 190 200 210 220 230 240 DTFGNDGRPR VAWHIDPFGH SREQASLFAQ MGFDGFFFGR LDYQDKWVRM QKLEMEQVWR 250 260 270 280 290 300 ASTSLKPPTA DLFTGVLPNG YNPPRNLCWD VLCVDQPLVE DPRSPEYNAK ELVDYFLNVA 310 320 330 340 350 360 TAQGRYYRTN HTVMTMGSDF QYENANMWFK NLDKLIRLVN AQQAKGSSVH VLYSTPACYL 370 380 390 400 410 420 WELNKANLTW SVKHDDFFPY ADGPHQFWTG YFSSRPALKR YERLSYNFLQ VCNQLEALVG 430 440 450 460 470 480 LAANVGPYGS GDSAPLNEAM AVLQHHDAVS GTSRQHVAND YARQLAAGWG PCEVLLSNAL 490 500 510 520 530 540 ARLRGFKDHF TFCQQLNISI CPLSQTAARF QVIVYNPLGR KVNWMVRLPV SEGVFVVKDP 550 560 570 580 590 600 NGRTVPSDVV IFPSSDSQAH PPELLFSASL PALGFSTYSV AQVPRWKPQA RAPQPIPRRS 610 620 630 640 650 660 WSPALTIENE HIRATFDPDT GLLMEIMNMN QQLLLPVRQT FFWYNASIGD NESDQASGAY 670 680 690 700 710 720 IFRPNQQKPL PVSRWAQIHL VKTPLVQEVH QNFSAWCSQV VRLYPGQRHL ELEWSVGPIP 730 740 750 760 770 780 VGDTWGKEVI SRFDTPLETK GRFYTDSNGR EILERRRDYR PTWKLNQTEP VAGNYYPVNT 790 800 810 820 830 840 RIYITDGNMQ LTVLTDRSQG GSSLRDGSLE LMVHRRLLKD DGRGVSEPLM ENGSGAWVRG 850 860 870 880 890 900 RHLVLLDTAQ AAAAGHRLLA EQEVLAPQVV LAPGGGAAYN LGAPPRTQFS GLRRDLPPSV 910 920 930 940 950 960 HLLTLASWGP EMVLLRLEHQ FAVGEDSGRN LSAPVTLNLR DLFSTFTITR LQETTLVANQ 970 980 990 1000 1010 LREAASRLKW TTNTGPTPHQ TPYQLDPANI TLEPMEIRTF LASVQWKEVD G

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human lysosomal alpha-mannosidase: isolation and nucleotide sequence of the full-length cDNA." Nebes V.L., Schmidt M.C. Biochem. Biophys. Res. Commun. 200:239-245(1994) [PubMed: 8166692] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Alpha-mannosidosis: functional cloning of the lysosomal alpha-mannosidase cDNA and identification of a mutation in two affected siblings." Nilssen O., Berg T., Riise H.M.F., Ramachandran U., Evjen G., Hansen G.M., Malm D., Tranebjaerg L., Tollersrud O.-K. Hum. Mol. Genet. 6:717-726(1997) [PubMed: 9158146] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, VARIANT AM LEU-72. Tissue: Lung and Skin.
[3]	"Genomic structure of the human lysosomal alpha-mannosidase gene (MANB)." Riise H.M.F., Berg T., Nilssen O., Romeo G., Tollersrud O.-K., Ceccherini I. Genomics 42:200-207(1997) [PubMed: 9192839] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[5]	"Cloning, expression, purification, and characterization of the human broad specificity lysosomal acid alpha-mannosidase." Liao Y.-F., Lal A., Moremen K.W. J. Biol. Chem. 271:28348-28358(1996) [PubMed: 8910458] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 9-1010. Tissue: Spleen.
[6]	"Partial sequence of the purified protein confirms the identity of cDNA coding for human lysosomal alpha-mannosidase B." Emiliani C., Martino S., Stirling J.L., Maras B., Orlacchio A. Biochem. J. 305:363-366(1995) [PubMed: 7832746] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE.
[7]	"Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry." Zhang H., Li X.-J., Martin D.B., Aebersold R. Nat. Biotechnol. 21:660-666(2003) [PubMed: 12754519] [Abstract] Cited for: GLYCOSYLATION AT ASN-930.
[8]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[9]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-367 AND ASN-766, MASS SPECTROMETRY. Tissue: Liver.
[10]	"Missense and nonsense mutations in the lysosomal alpha-mannosidase gene (MANB) in severe and mild forms of alpha-mannosidosis." Gotoda Y., Wakamatsu N., Kawai H., Nishida Y., Matsumoto T. Am. J. Hum. Genet. 63:1015-1024(1998) [PubMed: 9758606] [Abstract] Cited for: VARIANTS AM LEU-72; ARG-356 AND TRP-750.
[11]	"Spectrum of mutations in alpha-mannosidosis." Berg T., Riise H.M.F., Hansen G.M., Malm D., Tranebjaerg L., Tollersrud O.-K., Nilssen O. Am. J. Hum. Genet. 64:77-88(1999) [PubMed: 9915946] [Abstract] Cited for: VARIANTS AM PRO-355; LYS-402; ARG-714 AND PRO-809, VARIANTS VAL-278; ILE-312; GLN-337 AND SER-413.
[12]	"Alpha-mannosidosis and mutational analysis in a Turkish patient." Oelmez A., Nilssen O., Coskun T., Klenow H. Turk. J. Pediatr. 45:46-50(2003) [PubMed: 12718372] [Abstract] Cited for: VARIANT AM TYR-453.
[13]	"Identification and characterization of five novel MAN2B1 mutations in Italian patients with alpha-mannosidosis." Sbaragli M., Bibi L., Pittis M.G., Balducci C., Heikinheimo P., Ricci R., Antuzzi D., Parini R., Spaccini L., Bembi B., Beccari T. Hum. Mutat. 25:320-320(2005) [PubMed: 15712269] [Abstract] Cited for: VARIANTS AM LEU-200 AND ASP-801, CHARACTERIZATION OF VARIANTS AM LEU-200 AND ASP-801.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	U05572 mRNA. Translation: AAB03816.1. Different initiation. U60266 mRNA. Translation: AAC34130.1. U60899 , U60885, U60886, U60887, U60888, U60889, U60890, U60891, U60892, U60893, U60894, U60895, U60896, U60897, U60898 Genomic DNA. Translation: AAC51362.1. BC000736 mRNA. Translation: AAH00736.1. U68567 mRNA. Translation: AAC50812.1. Different initiation.
IPI	IPI00012989.
RefSeq	NP_000519.2.
UniGene	Hs.356769
3D structure databases
HSSP	HSSP built from PDB template 1O7D based on UniProtKB Q29451.
SMR	O00754. Positions 51-341, 605-874, 885-1006.
ModBase	Search...
Protein-protein interaction databases
STRING	O00754.
Protein family/group databases
CAZy	GH38. Glycoside Hydrolase Family 38.
Proteomic databases
PRIDE	O00754.
Genome annotation databases
Ensembl	ENST00000221363; ENSP00000221363; ENSG00000104774; Homo sapiens. [Genome view] ENST00000433513; ENSP00000390583; ENSG00000104774; Homo sapiens. [Genome view] ENST00000456935; ENSP00000395473; ENSG00000104774; Homo sapiens. [Genome view]
GeneID	4125.
KEGG	hsa:4125.
UCSC	uc002mub.2. human.
Organism-specific databases
CTD	4125.
GeneCards	GC19M012618.
HGNC	HGNC:6826. MAN2B1.
MIM	248500. phenotype. 609458. gene.
Orphanet	61. Alpha-mannosidosis.
PharmGKB	PA30575.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O00754.
HOVERGEN	O00754.
OMA	WRASTSL.
Enzyme and pathway databases
BRENDA	3.2.1.24. 247.
Gene expression databases
ArrayExpress	O00754.
Bgee	O00754.
CleanEx	HS_MAN2B1.
Genevestigator	O00754.
GermOnline	ENSG00000104774. Homo sapiens.
Family and domain databases
InterPro	IPR013780. Glyco_hydro_13_b. IPR011682. Glyco_hydro_38_C. IPR015341. Glyco_hydro_38_central. IPR000602. Glyco_hydro_38_core. [Graphical view]
Gene3D	G3DSA:2.60.40.1180. Glyco_hydro_13_b. 1 hit. G3DSA:3.20.110.10. Glyco_hydro_38_core. 1 hit.
Pfam	PF09261. Alpha-mann_mid. 1 hit. PF01074. Glyco_hydro_38. 1 hit. PF07748. Glyco_hydro_38C. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	16196.
SOURCE	Search...

Entry information

Entry name

MA2B1_HUMAN

Accession

Primary (citable) accession number: O00754
Secondary accession number(s): O15330 , Q16680, Q93094, Q9BW13

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	October 31, 2006
Last modified:	November 3, 2009
This is version 98 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.