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P49641

- MA2A2_HUMAN

UniProt

P49641 - MA2A2_HUMAN

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Protein

Alpha-mannosidase 2x

Gene

MAN2A2

Organism
Homo sapiens (Human)
Status
Reviewed - 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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi175 – 1751ZincBy similarity
Metal bindingi177 – 1771ZincBy similarity
Active sitei289 – 2891NucleophileBy similarity
Metal bindingi289 – 2891ZincBy similarity
Metal bindingi569 – 5691ZincBy similarity

GO - Molecular functioni

  1. carbohydrate binding Source: InterPro
  2. hydrolase activity, hydrolyzing N-glycosyl compounds Source: Ensembl
  3. mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase activity Source: UniProtKB-EC
  4. zinc ion binding Source: InterPro

GO - Biological processi

  1. cellular protein metabolic process Source: Reactome
  2. mannose metabolic process Source: InterPro
  3. post-translational protein modification Source: Reactome
  4. protein N-linked glycosylation via asparagine Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Glycosidase, Hydrolase

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciMetaCyc:HS11961-MONOMER.
ReactomeiREACT_25302. 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
ProteomesiUP000005640: Chromosome 15

Organism-specific databases

HGNCiHGNC:6825. MAN2A2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 55CytoplasmicSequence Analysis
Transmembranei6 – 2621Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST
Topological domaini27 – 796770LumenalSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. Golgi membrane Source: Reactome
  2. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Golgi apparatus, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA30574.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11501150Alpha-mannosidase 2xPRO_0000206905Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi95 – 951N-linked (GlcNAc...)Sequence Analysis
Glycosylationi305 – 3051N-linked (GlcNAc...)Sequence Analysis
Glycosylationi1093 – 10931N-linked (GlcNAc...)Sequence Analysis
Glycosylationi1131 – 11311N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP49641.
PaxDbiP49641.
PRIDEiP49641.

PTM databases

PhosphoSiteiP49641.

Expressioni

Gene expression databases

BgeeiP49641.
CleanExiHS_MAN2A2.
ExpressionAtlasiP49641. baseline and differential.
GenevestigatoriP49641.

Organism-specific databases

HPAiHPA017226.

Interactioni

Subunit structurei

Homodimer; disulfide-linked.By similarity

Protein-protein interaction databases

BioGridi110295. 15 interactions.
IntActiP49641. 6 interactions.
MINTiMINT-1369139.
STRINGi9606.ENSP00000353655.

Structurei

3D structure databases

ProteinModelPortaliP49641.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the glycosyl hydrolase 38 family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0383.
GeneTreeiENSGT00510000046304.
HOGENOMiHOG000293253.
HOVERGENiHBG052390.
InParanoidiP49641.
KOiK01231.
OMAiYLEPMEI.
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.
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.
IPR028995. Glyco_hydro_57/38_cen.
[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. Align

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti412 – 4121Q → R.
Corresponds to variant rs2106673 [ dbSNP | Ensembl ].
VAR_047912
Natural varianti665 – 6651S → F.
Corresponds to variant rs1266494 [ dbSNP | Ensembl ].
VAR_047913

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei783 – 79614SIRRV…EQQVD → GSGLCFLAEHPKGG in isoform 1. 1 PublicationVSP_041732Add
BLAST
Alternative sequencei797 – 1150354Missing in isoform 2. 1 PublicationVSP_041733Add
BLAST
Alternative sequencei823 – 90684KPYVP…LNGFQ → SPTSPRSPPCCVSLKALSSQ RWLRTMSTFTRRSGFTICQG WRGCLWTYHPWWTSGTTSTR SWPCTSIQTSTAR in isoform 1. 1 PublicationVSP_041734Add
BLAST

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_006122.2. [P49641-3]
UniGeneiHs.116459.

Genome annotation databases

EnsembliENST00000360468; ENSP00000353655; ENSG00000196547. [P49641-3]
ENST00000558161; ENSP00000452631; ENSG00000196547.
ENST00000559717; ENSP00000452948; ENSG00000196547. [P49641-3]
GeneIDi4122.
KEGGihsa:4122.
UCSCiuc002bqc.3. human. [P49641-3]

Polymorphism databases

DMDMi347595795.

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 .
CCDSi CCDS32332.1. [P49641-3 ]
RefSeqi NP_006113.2. NM_006122.2. [P49641-3 ]
UniGenei Hs.116459.

3D structure databases

ProteinModelPortali P49641.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 110295. 15 interactions.
IntActi P49641. 6 interactions.
MINTi MINT-1369139.
STRINGi 9606.ENSP00000353655.

Protein family/group databases

CAZyi GH38. Glycoside Hydrolase Family 38.

PTM databases

PhosphoSitei P49641.

Polymorphism databases

DMDMi 347595795.

Proteomic databases

MaxQBi P49641.
PaxDbi P49641.
PRIDEi P49641.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000360468 ; ENSP00000353655 ; ENSG00000196547 . [P49641-3 ]
ENST00000558161 ; ENSP00000452631 ; ENSG00000196547 .
ENST00000559717 ; ENSP00000452948 ; ENSG00000196547 . [P49641-3 ]
GeneIDi 4122.
KEGGi hsa:4122.
UCSCi uc002bqc.3. human. [P49641-3 ]

Organism-specific databases

CTDi 4122.
GeneCardsi GC15P091447.
H-InvDB HIX0202164.
HGNCi HGNC:6825. MAN2A2.
HPAi HPA017226.
MIMi 600988. gene.
neXtProti NX_P49641.
PharmGKBi PA30574.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0383.
GeneTreei ENSGT00510000046304.
HOGENOMi HOG000293253.
HOVERGENi HBG052390.
InParanoidi P49641.
KOi K01231.
OMAi YLEPMEI.
PhylomeDBi P49641.
TreeFami TF313152.

Enzyme and pathway databases

UniPathwayi UPA00378 .
BioCyci MetaCyc:HS11961-MONOMER.
Reactomei REACT_25302. Reactions specific to the complex N-glycan synthesis pathway.

Miscellaneous databases

ChiTaRSi MAN2A2. human.
GenomeRNAii 4122.
NextBioi 16184.
PROi P49641.
SOURCEi Search...

Gene expression databases

Bgeei P49641.
CleanExi HS_MAN2A2.
ExpressionAtlasi P49641. baseline and differential.
Genevestigatori P49641.

Family and domain databases

Gene3Di 1.20.1270.50. 1 hit.
2.60.40.1180. 1 hit.
3.20.110.10. 1 hit.
InterProi IPR011013. 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.
IPR028995. Glyco_hydro_57/38_cen.
[Graphical view ]
Pfami PF09261. Alpha-mann_mid. 1 hit.
PF01074. Glyco_hydro_38. 1 hit.
PF07748. Glyco_hydro_38C. 1 hit.
[Graphical view ]
SMARTi SM00872. Alpha-mann_mid. 1 hit.
[Graphical view ]
SUPFAMi SSF74650. SSF74650. 1 hit.
SSF88688. SSF88688. 1 hit.
SSF88713. SSF88713. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.
    , 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. Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).

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 26, 2014
This is version 137 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

External Data

Dasty 3