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Protein

Alpha-mannosidase 2x

Gene

MAN2A2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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 activityi

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

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Pathwayi: protein glycosylation

This protein is involved in the pathway protein glycosylation, which is part of Protein modification.
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
Metal bindingi175ZincBy similarity1
Metal bindingi177ZincBy similarity1
Active sitei289NucleophileBy similarity1
Metal bindingi289ZincBy similarity1
Metal bindingi569ZincBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Glycosidase, Hydrolase

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciMetaCyc:HS11961-MONOMER.
ZFISH:HS11961-MONOMER.
ReactomeiR-HSA-6811438. Intra-Golgi traffic.
R-HSA-975578. Reactions specific to the complex N-glycan synthesis pathway.
UniPathwayiUPA00378.

Protein family/group databases

CAZyiGH38. Glycoside Hydrolase Family 38.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:MAN2A2
Synonyms:MANA2X
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:6825. MAN2A2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 5CytoplasmicSequence analysis5
Transmembranei6 – 26Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini27 – 796LumenalSequence analysisAdd BLAST770

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Golgi apparatus, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi4122.
OpenTargetsiENSG00000196547.
PharmGKBiPA30574.

Polymorphism and mutation databases

BioMutaiMAN2A2.
DMDMi347595795.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002069051 – 1150Alpha-mannosidase 2xAdd BLAST1150

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi95N-linked (GlcNAc...)Sequence analysis1
Glycosylationi305N-linked (GlcNAc...)Sequence analysis1
Glycosylationi1093N-linked (GlcNAc...)Sequence analysis1
Glycosylationi1131N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiP49641.
PaxDbiP49641.
PeptideAtlasiP49641.
PRIDEiP49641.

PTM databases

iPTMnetiP49641.
PhosphoSitePlusiP49641.
SwissPalmiP49641.

Expressioni

Gene expression databases

BgeeiENSG00000196547.
CleanExiHS_MAN2A2.
ExpressionAtlasiP49641. baseline and differential.
GenevisibleiP49641. HS.

Organism-specific databases

HPAiHPA017226.

Interactioni

Subunit structurei

Homodimer; disulfide-linked.By similarity

Protein-protein interaction databases

BioGridi110295. 26 interactors.
IntActiP49641. 6 interactors.
MINTiMINT-1369139.
STRINGi9606.ENSP00000353655.

Structurei

3D structure databases

ProteinModelPortaliP49641.
SMRiP49641.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the glycosyl hydrolase 38 family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1958. Eukaryota.
KOG1959. Eukaryota.
ENOG410XQMZ. LUCA.
GeneTreeiENSGT00510000046304.
HOGENOMiHOG000293253.
HOVERGENiHBG052390.
InParanoidiP49641.
KOiK01231.
OMAiQIQPRRF.
OrthoDBiEOG091G00YH.
PhylomeDBiP49641.
TreeFamiTF313152.

Family and domain databases

Gene3Di1.20.1270.50. 1 hit.
2.60.40.1180. 1 hit.
3.20.110.10. 1 hit.
InterProiIPR011013. Gal_mutarotase_SF_dom.
IPR011330. Glyco_hydro/deAcase_b/a-brl.
IPR027291. Glyco_hydro_38/57_N.
IPR011682. Glyco_hydro_38_C.
IPR015341. Glyco_hydro_38_cen.
IPR000602. Glyco_hydro_38_N.
IPR028995. Glyco_hydro_57/38_cen.
IPR013780. Glyco_hydro_b.
[Graphical view]
PfamiPF09261. Alpha-mann_mid. 1 hit.
PF01074. Glyco_hydro_38. 1 hit.
PF07748. Glyco_hydro_38C. 1 hit.
[Graphical view]
SMARTiSM00872. Alpha-mann_mid. 1 hit.
[Graphical view]
SUPFAMiSSF74650. SSF74650. 1 hit.
SSF88688. SSF88688. 1 hit.
SSF88713. SSF88713. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 3 (identifier: P49641-3) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MKLKKQVTVC GAAIFCVAVF SLYLMLDRVQ HDPTRHQNGG NFPRSQISVL
60 70 80 90 100
QNRIEQLEQL LEENHEIISH IKDSVLELTA NAEGPPAMLP YYTVNGSWVV
110 120 130 140 150
PPEPRPSFFS ISPQDCQFAL GGRGQKPELQ MLTVSEELPF DNVDGGVWRQ
160 170 180 190 200
GFDISYDPHD WDAEDLQVFV VPHSHNDPGW IKTFDKYYTE QTQHILNSMV
210 220 230 240 250
SKLQEDPRRR FLWAEVSFFA KWWDNINVQK RAAVRRLVGN GQLEIATGGW
260 270 280 290 300
VMPDEANSHY FALIDQLIEG HQWLERNLGA TPRSGWAVDP FGYSSTMPYL
310 320 330 340 350
LRRANLTSML IQRVHYAIKK HFAATHSLEF MWRQTWDSDS STDIFCHMMP
360 370 380 390 400
FYSYDVPHTC GPDPKICCQF DFKRLPGGRI NCPWKVPPRA ITEANVAERA
410 420 430 440 450
ALLLDQYRKK SQLFRSNVLL VPLGDDFRYD KPQEWDAQFF NYQRLFDFFN
460 470 480 490 500
SRPNLHVQAQ FGTLSDYFDA LYKRTGVEPG ARPPGFPVLS GDFFSYADRE
510 520 530 540 550
DHYWTGYYTS RPFYKSLDRV LEAHLRGAEV LYSLAAAHAR RSGLAGRYPL
560 570 580 590 600
SDFTLLTEAR RTLGLFQHHD AITGTAKEAV VVDYGVRLLR SLVNLKQVII
610 620 630 640 650
HAAHYLVLGD KETYHFDPEA PFLQVDDTRL SHDALPERTV IQLDSSPRFV
660 670 680 690 700
VLFNPLEQER FSMVSLLVNS PRVRVLSEEG QPLAVQISAH WSSATEAVPD
710 720 730 740 750
VYQVSVPVRL PALGLGVLQL QLGLDGHRTL PSSVRIYLHG RQLSVSRHEA
760 770 780 790 800
FPLRVIDSGT SDFALSNRYM QVWFSGLTGL LKSIRRVDEE HEQQVDMQVL
810 820 830 840 850
VYGTRTSKDK SGAYLFLPDG EAKPYVPKEP PVLRVTEGPF FSEVVAYYEH
860 870 880 890 900
IHQAVRLYNL PGVEGLSLDI SSLVDIRDYV NKELALHIHT DIDSQGIFFT
910 920 930 940 950
DLNGFQVQPR RYLKKLPLQA NFYPMPVMAY IQDAQKRLTL HTAQALGVSS
960 970 980 990 1000
LKDGQLEVIL DRRLMQDDNR GLGQGLKDNK RTCNRFRLLL ERRTVGSEVQ
1010 1020 1030 1040 1050
DSHSTSYPSL LSHLTSMYLN APALALPVAR MQLPGPGLRS FHPLASSLPC
1060 1070 1080 1090 1100
DFHLLNLRTL QAEEDTLPSA ETALILHRKG FDCGLEAKNL GFNCTTSQGK
1110 1120 1130 1140 1150
VALGSLFHGL DVVFLQPTSL TLLYPLASPS NSTDVYLEPM EIATFRLRLG
Length:1,150
Mass (Da):130,539
Last modified:September 21, 2011 - v3
Checksum:iBFB3D763A6A55444
GO
Isoform 1 (identifier: P49641-1) [UniParc]FASTAAdd to basket
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

Show »
Length:1,139
Mass (Da):128,915
Checksum:iC16551A585F7F7FA
GO
Isoform 2 (identifier: P49641-2) [UniParc]FASTAAdd to basket
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.
Show »
Length:796
Mass (Da):91,059
Checksum:iFDAC30CA17B00E6E
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_047912412Q → R.Corresponds to variant rs2106673dbSNPEnsembl.1
Natural variantiVAR_047913665S → F.Corresponds to variant rs1266494dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_041732783 – 796SIRRV…EQQVD → GSGLCFLAEHPKGG in isoform 1. 1 PublicationAdd BLAST14
Alternative sequenceiVSP_041733797 – 1150Missing in isoform 2. 1 PublicationAdd BLAST354
Alternative sequenceiVSP_041734823 – 906KPYVP…LNGFQ → SPTSPRSPPCCVSLKALSSQ RWLRTMSTFTRRSGFTICQG WRGCLWTYHPWWTSGTTSTR SWPCTSIQTSTAR in isoform 1. 1 PublicationAdd BLAST84

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS32332.1. [P49641-3]
RefSeqiNP_006113.2. NM_006122.3. [P49641-3]
XP_016877674.1. XM_017022185.1. [P49641-3]
UniGeneiHs.116459.

Genome annotation databases

EnsembliENST00000360468; ENSP00000353655; ENSG00000196547. [P49641-3]
ENST00000559717; ENSP00000452948; ENSG00000196547. [P49641-3]
GeneIDi4122.
KEGGihsa:4122.
UCSCiuc002bqc.4. human. [P49641-3]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS32332.1. [P49641-3]
RefSeqiNP_006113.2. NM_006122.3. [P49641-3]
XP_016877674.1. XM_017022185.1. [P49641-3]
UniGeneiHs.116459.

3D structure databases

ProteinModelPortaliP49641.
SMRiP49641.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110295. 26 interactors.
IntActiP49641. 6 interactors.
MINTiMINT-1369139.
STRINGi9606.ENSP00000353655.

Protein family/group databases

CAZyiGH38. Glycoside Hydrolase Family 38.

PTM databases

iPTMnetiP49641.
PhosphoSitePlusiP49641.
SwissPalmiP49641.

Polymorphism and mutation databases

BioMutaiMAN2A2.
DMDMi347595795.

Proteomic databases

EPDiP49641.
PaxDbiP49641.
PeptideAtlasiP49641.
PRIDEiP49641.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000360468; ENSP00000353655; ENSG00000196547. [P49641-3]
ENST00000559717; ENSP00000452948; ENSG00000196547. [P49641-3]
GeneIDi4122.
KEGGihsa:4122.
UCSCiuc002bqc.4. human. [P49641-3]

Organism-specific databases

CTDi4122.
DisGeNETi4122.
GeneCardsiMAN2A2.
H-InvDBHIX0202164.
HGNCiHGNC:6825. MAN2A2.
HPAiHPA017226.
MIMi600988. gene.
neXtProtiNX_P49641.
OpenTargetsiENSG00000196547.
PharmGKBiPA30574.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1958. Eukaryota.
KOG1959. Eukaryota.
ENOG410XQMZ. LUCA.
GeneTreeiENSGT00510000046304.
HOGENOMiHOG000293253.
HOVERGENiHBG052390.
InParanoidiP49641.
KOiK01231.
OMAiQIQPRRF.
OrthoDBiEOG091G00YH.
PhylomeDBiP49641.
TreeFamiTF313152.

Enzyme and pathway databases

UniPathwayiUPA00378.
BioCyciMetaCyc:HS11961-MONOMER.
ZFISH:HS11961-MONOMER.
ReactomeiR-HSA-6811438. Intra-Golgi traffic.
R-HSA-975578. Reactions specific to the complex N-glycan synthesis pathway.

Miscellaneous databases

ChiTaRSiMAN2A2. human.
GenomeRNAii4122.
PROiP49641.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000196547.
CleanExiHS_MAN2A2.
ExpressionAtlasiP49641. baseline and differential.
GenevisibleiP49641. HS.

Family and domain databases

Gene3Di1.20.1270.50. 1 hit.
2.60.40.1180. 1 hit.
3.20.110.10. 1 hit.
InterProiIPR011013. Gal_mutarotase_SF_dom.
IPR011330. Glyco_hydro/deAcase_b/a-brl.
IPR027291. Glyco_hydro_38/57_N.
IPR011682. Glyco_hydro_38_C.
IPR015341. Glyco_hydro_38_cen.
IPR000602. Glyco_hydro_38_N.
IPR028995. Glyco_hydro_57/38_cen.
IPR013780. Glyco_hydro_b.
[Graphical view]
PfamiPF09261. Alpha-mann_mid. 1 hit.
PF01074. Glyco_hydro_38. 1 hit.
PF07748. Glyco_hydro_38C. 1 hit.
[Graphical view]
SMARTiSM00872. Alpha-mann_mid. 1 hit.
[Graphical view]
SUPFAMiSSF74650. SSF74650. 1 hit.
SSF88688. SSF88688. 1 hit.
SSF88713. SSF88713. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiMA2A2_HUMAN
AccessioniPrimary (citable) accession number: P49641
Secondary accession number(s): A6NH12, A8K1E8, Q13754
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: September 21, 2011
Last modified: November 2, 2016
This is version 156 of the entry and version 3 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Glycosyl hydrolases
    Classification of glycosyl hydrolase families and list of entries
  2. Human chromosome 15
    Human chromosome 15: 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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.