P49641 (MA2A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	MAN2A2
Synonyms:	MANA2X

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1150 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
Ligand	Metal-binding Zinc
Molecular function	Glycosidase Hydrolase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	mannose metabolic process Inferred from electronic annotation. Source: InterPro post-translational protein modification Traceable author statement. Source: Reactome protein N-linked glycosylation via asparagine Traceable author statement. Source: Reactome
Cellular_component	Golgi membrane Non-traceable author statement. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	carbohydrate binding Inferred from electronic annotation. Source: InterPro hydrolase activity, hydrolyzing N-glycosyl compounds Inferred from electronic annotation. Source: Compara mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase activity Non-traceable author statement. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1150	1150	Alpha-mannosidase 2x		PRO_0000206905
Regions
	Topological domain	1 – 5	5	Cytoplasmic Potential
	Transmembrane	6 – 26	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	27 – 796	770	Lumenal Potential
Sites
	Active site	289	1	Nucleophile By similarity
	Metal binding	175	1	Zinc By similarity
	Metal binding	177	1	Zinc By similarity
	Metal binding	289	1	Zinc By similarity
	Metal binding	569	1	Zinc By similarity
Amino acid modifications
	Glycosylation	95	1	N-linked (GlcNAc...) Potential
	Glycosylation	305	1	N-linked (GlcNAc...) Potential
	Glycosylation	1093	1	N-linked (GlcNAc...) Potential
	Glycosylation	1131	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	783 – 796	14	SIRRV…EQQVD → GSGLCFLAEHPKGG in isoform 1.		VSP_041732
	Alternative sequence	797 – 1150	354	Missing in isoform 2.		VSP_041733
	Alternative sequence	823 – 906	84	KPYVP…LNGFQ → SPTSPRSPPCCVSLKALSSQ RWLRTMSTFTRRSGFTICQG WRGCLWTYHPWWTSGTTSTR SWPCTSIQTSTAR in isoform 1.		VSP_041734
	Natural variant	412	1	Q → R. Corresponds to variant rs2106673 [ dbSNP | Ensembl ].		VAR_047912
	Natural variant	665	1	S → F. Corresponds to variant rs1266494 [ dbSNP | Ensembl ].		VAR_047913

Sequences

	Sequence		Length	Mass (Da)
	Isoform 3 [UniParc]. Last modified September 21, 2011. Version 3. Checksum: BFB3D763A6A55444	FASTA	1,150	130,539
	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
	Isoform 1 (Long) [UniParc]. Checksum: C16551A585F7F7FA	FASTA	1,139	128,915
	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 LKGSGLCFLA EHPKGGMQVL VYGTRTSKDK SGAYLFLPDG EASPTSPRSP PCCVSLKALS 850 860 870 880 890 900 SQRWLRTMST FTRRSGFTIC QGWRGCLWTY HPWWTSGTTS TRSWPCTSIQ TSTARVQPRR 910 920 930 940 950 960 YLKKLPLQAN FYPMPVMAYI QDAQKRLTLH TAQALGVSSL KDGQLEVILD RRLMQDDNRG 970 980 990 1000 1010 1020 LGQGLKDNKR TCNRFRLLLE RRTVGSEVQD SHSTSYPSLL SHLTSMYLNA PALALPVARM 1030 1040 1050 1060 1070 1080 QLPGPGLRSF HPLASSLPCD FHLLNLRTLQ AEEDTLPSAE TALILHRKGF DCGLEAKNLG 1090 1100 1110 1120 1130 FNCTTSQGKV ALGSLFHGLD VVFLQPTSLT LLYPLASPSN STDVYLEPME IATFRLRLG
	Isoform 2 (Short) [UniParc]. Checksum: FDAC30CA17B00E6E	FASTA	796	91,059
	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 LKSIRRVDEE HEQQVD

References

	« Hide 'large scale' referencesShow '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. , 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]	"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.
IPI	IPI00027703. IPI00220303. IPI00943037.
RefSeq	NP_006113.2. NM_006122.2.
UniGene	Hs.116459.
3D structure databases
ProteinModelPortal	P49641.
SMR	P49641. Positions 128-1022, 1038-1149.
ModBase	Search...
Protein-protein interaction databases
IntAct	P49641. 6 interactions.
MINT	MINT-1369139.
STRING	9606.ENSP00000353655.
Protein family/group databases
CAZy	GH38. Glycoside Hydrolase Family 38.
PTM databases
PhosphoSite	P49641.
Polymorphism databases
DMDM	3123244.
Proteomic databases
PaxDb	P49641.
PRIDE	P49641.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000360468; ENSP00000353655; ENSG00000196547. ENST00000558161; ENSP00000452631; ENSG00000196547. ENST00000559717; ENSP00000452948; ENSG00000196547.
GeneID	4122.
KEGG	hsa:4122.
UCSC	uc002bqc.3. human.
Organism-specific databases
CTD	4122.
GeneCards	GC15P091447.
H-InvDB	HIX0202164.
HGNC	HGNC:6825. MAN2A2.
HPA	HPA017226.
MIM	600988. gene.
neXtProt	NX_P49641.
PharmGKB	PA30574.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0383.
HOGENOM	HOG000293253.
HOVERGEN	HBG052390.
KO	K01231.
OMA	FYPMPVM.
OrthoDB	EOG4CRKZ7.
Enzyme and pathway databases
Reactome	REACT_17015. Metabolism of proteins.
UniPathway	UPA00378.
Gene expression databases
ArrayExpress	P49641.
Bgee	P49641.
CleanEx	HS_MAN2A2.
Genevestigator	P49641.
Family and domain databases
Gene3D	2.60.40.1180. 1 hit. 3.20.110.10. 1 hit.
InterPro	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_dom. IPR000602. Glyco_hydro_38_N. [Graphical view]
Pfam	PF09261. Alpha-mann_mid. 1 hit. PF01074. Glyco_hydro_38. 1 hit. PF07748. Glyco_hydro_38C. 1 hit. [Graphical view]
SMART	SM00872. Alpha-mann_mid. 1 hit. [Graphical view]
SUPFAM	SSF74650. Gal_mut_like. 1 hit. SSF88713. Glyco_hydro/deAcase_b/a-brl. 1 hit.
ProtoNet	Search...
Other
BindingDB	P49641.
ChEMBL	CHEMBL2825.
ChiTaRS	MAN2A2. human.
GenomeRNAi	4122.
NextBio	16184.
SOURCE	Search...

Entry information

Entry name

MA2A2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 122 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.