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P49641 (MA2A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:MAN2A2
Synonyms:MANA2X
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1150 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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 activity

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

Cofactor

Binds 1 zinc ion per subunit By similarity.

Pathway

Protein modification; protein glycosylation.

Subunit structure

Homodimer; disulfide-linked By similarity.

Subcellular location

Golgi apparatus membrane; Single-pass type II membrane protein By similarity.

Sequence similarities

Belongs to the glycosyl hydrolase 38 family.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 3 (identifier: P49641-3)

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.
Isoform 1 (identifier: P49641-1)

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
Isoform 2 (identifier: P49641-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11501150Alpha-mannosidase 2x
PRO_0000206905

Regions

Topological domain1 – 55Cytoplasmic Potential
Transmembrane6 – 2621Helical; Signal-anchor for type II membrane protein; Potential
Topological domain27 – 796770Lumenal Potential

Sites

Active site2891Nucleophile By similarity
Metal binding1751Zinc By similarity
Metal binding1771Zinc By similarity
Metal binding2891Zinc By similarity
Metal binding5691Zinc By similarity

Amino acid modifications

Glycosylation951N-linked (GlcNAc...) Potential
Glycosylation3051N-linked (GlcNAc...) Potential
Glycosylation10931N-linked (GlcNAc...) Potential
Glycosylation11311N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence783 – 79614SIRRV…EQQVD → GSGLCFLAEHPKGG in isoform 1.
VSP_041732
Alternative sequence797 – 1150354Missing in isoform 2.
VSP_041733
Alternative sequence823 – 90684KPYVP…LNGFQ → SPTSPRSPPCCVSLKALSSQ RWLRTMSTFTRRSGFTICQG WRGCLWTYHPWWTSGTTSTR SWPCTSIQTSTAR in isoform 1.
VSP_041734
Natural variant4121Q → R.
Corresponds to variant rs2106673 [ dbSNP | Ensembl ].
VAR_047912
Natural variant6651S → F.
Corresponds to variant rs1266494 [ dbSNP | Ensembl ].
VAR_047913

Sequences

Sequence LengthMass (Da)Tools
Isoform 3 [UniParc].

Last modified September 21, 2011. Version 3.
Checksum: BFB3D763A6A55444

FASTA1,150130,539
        10         20         30         40         50         60 
MKLKKQVTVC GAAIFCVAVF SLYLMLDRVQ HDPTRHQNGG NFPRSQISVL QNRIEQLEQL 

        70         80         90        100        110        120 
LEENHEIISH IKDSVLELTA NAEGPPAMLP YYTVNGSWVV PPEPRPSFFS ISPQDCQFAL 

       130        140        150        160        170        180 
GGRGQKPELQ MLTVSEELPF DNVDGGVWRQ GFDISYDPHD WDAEDLQVFV VPHSHNDPGW 

       190        200        210        220        230        240 
IKTFDKYYTE QTQHILNSMV SKLQEDPRRR FLWAEVSFFA KWWDNINVQK RAAVRRLVGN 

       250        260        270        280        290        300 
GQLEIATGGW VMPDEANSHY FALIDQLIEG HQWLERNLGA TPRSGWAVDP FGYSSTMPYL 

       310        320        330        340        350        360 
LRRANLTSML IQRVHYAIKK HFAATHSLEF MWRQTWDSDS STDIFCHMMP FYSYDVPHTC 

       370        380        390        400        410        420 
GPDPKICCQF DFKRLPGGRI NCPWKVPPRA ITEANVAERA ALLLDQYRKK SQLFRSNVLL 

       430        440        450        460        470        480 
VPLGDDFRYD KPQEWDAQFF NYQRLFDFFN SRPNLHVQAQ FGTLSDYFDA LYKRTGVEPG 

       490        500        510        520        530        540 
ARPPGFPVLS GDFFSYADRE DHYWTGYYTS RPFYKSLDRV LEAHLRGAEV LYSLAAAHAR 

       550        560        570        580        590        600 
RSGLAGRYPL SDFTLLTEAR RTLGLFQHHD AITGTAKEAV VVDYGVRLLR SLVNLKQVII 

       610        620        630        640        650        660 
HAAHYLVLGD KETYHFDPEA PFLQVDDTRL SHDALPERTV IQLDSSPRFV VLFNPLEQER 

       670        680        690        700        710        720 
FSMVSLLVNS PRVRVLSEEG QPLAVQISAH WSSATEAVPD VYQVSVPVRL PALGLGVLQL 

       730        740        750        760        770        780 
QLGLDGHRTL PSSVRIYLHG RQLSVSRHEA FPLRVIDSGT SDFALSNRYM QVWFSGLTGL 

       790        800        810        820        830        840 
LKSIRRVDEE HEQQVDMQVL VYGTRTSKDK SGAYLFLPDG EAKPYVPKEP PVLRVTEGPF 

       850        860        870        880        890        900 
FSEVVAYYEH IHQAVRLYNL PGVEGLSLDI SSLVDIRDYV NKELALHIHT DIDSQGIFFT 

       910        920        930        940        950        960 
DLNGFQVQPR RYLKKLPLQA NFYPMPVMAY IQDAQKRLTL HTAQALGVSS LKDGQLEVIL 

       970        980        990       1000       1010       1020 
DRRLMQDDNR GLGQGLKDNK RTCNRFRLLL ERRTVGSEVQ DSHSTSYPSL LSHLTSMYLN 

      1030       1040       1050       1060       1070       1080 
APALALPVAR MQLPGPGLRS FHPLASSLPC DFHLLNLRTL QAEEDTLPSA ETALILHRKG 

      1090       1100       1110       1120       1130       1140 
FDCGLEAKNL GFNCTTSQGK VALGSLFHGL DVVFLQPTSL TLLYPLASPS NSTDVYLEPM 

      1150 
EIATFRLRLG 

« Hide

Isoform 1 (Long) [UniParc].

Checksum: C16551A585F7F7FA
Show »

FASTA1,139128,915
Isoform 2 (Short) [UniParc].

Checksum: FDAC30CA17B00E6E
Show »

FASTA79691,059

References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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]"An unappreciated role for RNA surveillance."
Hillman R.T., Green R.E., Brenner S.E.
Genome Biol. 5:R8.1-R8.16(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_006113.2. NM_006122.2.
UniGeneHs.116459.

3D structure databases

ProteinModelPortalP49641.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110295. 7 interactions.
IntActP49641. 6 interactions.
MINTMINT-1369139.
STRING9606.ENSP00000353655.

Chemistry

BindingDBP49641.

Protein family/group databases

CAZyGH38. Glycoside Hydrolase Family 38.

PTM databases

PhosphoSiteP49641.

Polymorphism databases

DMDM347595795.

Proteomic databases

PaxDbP49641.
PRIDEP49641.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000360468; ENSP00000353655; ENSG00000196547. [P49641-3]
ENST00000558161; ENSP00000452631; ENSG00000196547.
ENST00000559717; ENSP00000452948; ENSG00000196547. [P49641-3]
GeneID4122.
KEGGhsa:4122.
UCSCuc002bqc.3. human. [P49641-3]

Organism-specific databases

CTD4122.
GeneCardsGC15P091447.
H-InvDBHIX0202164.
HGNCHGNC:6825. MAN2A2.
HPAHPA017226.
MIM600988. gene.
neXtProtNX_P49641.
PharmGKBPA30574.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0383.
HOGENOMHOG000293253.
HOVERGENHBG052390.
KOK01231.
OMATEQTQHI.
TreeFamTF313152.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.
UniPathwayUPA00378.

Gene expression databases

ArrayExpressP49641.
BgeeP49641.
CleanExHS_MAN2A2.
GenevestigatorP49641.

Family and domain databases

Gene3D1.20.1270.50. 1 hit.
2.60.40.1180. 1 hit.
3.20.110.10. 1 hit.
InterProIPR011013. 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.
[Graphical view]
PfamPF09261. Alpha-mann_mid. 1 hit.
PF01074. Glyco_hydro_38. 1 hit.
PF07748. Glyco_hydro_38C. 1 hit.
[Graphical view]
SMARTSM00872. Alpha-mann_mid. 1 hit.
[Graphical view]
SUPFAMSSF74650. SSF74650. 1 hit.
SSF88713. SSF88713. 1 hit.
ProtoNetSearch...

Other

ChiTaRSMAN2A2. human.
GenomeRNAi4122.
NextBio16184.
PROP49641.
SOURCESearch...

Entry information

Entry nameMA2A2_HUMAN
AccessionPrimary (citable) accession number: P49641
Secondary accession number(s): A6NH12, A8K1E8, Q13754
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: September 21, 2011
Last modified: April 16, 2014
This is version 130 of the entry and version 3 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

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 15

Human chromosome 15: entries, gene names and cross-references to MIM

Glycosyl hydrolases

Classification of glycosyl hydrolase families and list of entries