Neutral alpha-glucosidase AB precursor

Preferred order of sections

Names and origin

Protein names

Recommended name:
Neutral alpha-glucosidase AB
EC=3.2.1.84

Alternative name(s):
Alpha-glucosidase 2
Glucosidase II subunit alpha

Gene names

Name:	GANAB
Synonyms:	G2AN, KIAA0088

Organism

Homo sapiens (Human) [Reference 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	944 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	Cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc₂Man₉GlcNAc₂ oligosaccharide precursor of immature glycoproteins. Ref.2
Catalytic activity	Hydrolysis of terminal (1->3)-alpha-D-glucosidic links in (1->3)-alpha-D-glucans.
Pathway	Glycan metabolism; N-glycan metabolism.
Subunit structure	Heterodimer of a catalytic alpha subunit (GANAB) and a beta subunit (PRKCSH). Binds glycosylated PTPRC By similarity.
Subcellular location	Endoplasmic reticulum By similarity. Golgi apparatus By similarity. Melanosome. Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Ref.2 Ref.9
Tissue specificity	Detected in placenta. Ref.7
Sequence similarities	Belongs to the glycosyl hydrolase 31 family.
Sequence caution	The sequence AAH65266.1 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Golgi apparatus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Molecular function	Glycosidase Hydrolase
PTM	Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	post-translational protein modification Traceable author statement. Source: Reactome protein N-linked glycosylation via asparagine Traceable author statement. Source: Reactome protein folding Traceable author statement. Source: Reactome
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum lumen Traceable author statement. Source: Reactome glucosidase II complex Inferred from electronic annotation. Source: Compara melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	carbohydrate binding Inferred from electronic annotation. Source: InterPro glucan 1,3-alpha-glucosidase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct
ELF3	P78545	1	EBI-348004,EBI-1057285
PRRC2A	P48634	1	EBI-348004,EBI-347545
TRAF6	Q9Y4K3	1	EBI-348004,EBI-359276

Alternative products

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

Isoform 1 (identifier: Q14697-1) 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 2 (identifier: Q14697-2) The sequence of this isoform differs from the canonical sequence as follows: 187-187: S → SFSDKVNLTLGSIWDKIKNLFSR

Isoform 3 (identifier: Q14697-3) The sequence of this isoform differs from the canonical sequence as follows: 49-52: RQRS → CCWC 53-944: 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

Signal peptide

1 – 28

28

Potential

Chain

29 – 944

916

Neutral alpha-glucosidase AB

PRO_0000018571

Sites

Active site

542

1

Nucleophile

Active site

545

1

By similarity

Active site

618

1

Proton donor By similarity

Amino acid modifications

Glycosylation

97

1

N-linked (GlcNAc...)

Natural variations

Alternative sequence

49 – 52

4

RQRS → CCWC in isoform 3.

VSP_039976

Alternative sequence

53 – 944

892

Missing in isoform 3.

VSP_039977

Alternative sequence

187

1

S → SFSDKVNLTLGSIWDKIKNL FSR in isoform 2.

VSP_010674

Natural variant

154

1

R → W.
Corresponds to variant rs2276296 [ dbSNP | Ensembl ].

VAR_024529

Natural variant

173

1

R → Q.
Corresponds to variant rs2276295 [ dbSNP | Ensembl ].

VAR_022086

Natural variant

309

1

R → C.
Corresponds to variant rs1063445 [ dbSNP | Ensembl ].

VAR_050272

Experimental info

Mutagenesis

542

1

D → N: Loss of activity. Ref.2

Sequence conflict

400

1

R → C in AAH65266. Ref.5

Sequence conflict

461

1

R → W in AAH65266. Ref.5

Sequence conflict

850

1

H → Y in CAA04006. Ref.1

Sequence conflict

850

1

H → Y in BAA07642. Ref.4

Sequences

Sequence		Length	Mass (Da)
Isoform 1 [UniParc]. Last modified July 5, 2004. Version 3. Checksum: 9E3426FE9A016BF1 Show »	FASTA	944	106,874
10 20 30 40 50 60 MAAVAAVAAR RRRSWASLVL AFLGVCLGIT LAVDRSNFKT CEESSFCKRQ RSIRPGLSPY 70 80 90 100 110 120 RALLDSLQLG PDSLTVHLIH EVTKVLLVLE LQGLQKNMTR FRIDELEPRR PRYRVPDVLV 130 140 150 160 170 180 ADPPIARLSV SGRDENSVEL TMAEGPYKII LTARPFRLDL LEDRSLLLSV NARGLLEFEH 190 200 210 220 230 240 QRAPRVSQGS KDPAEGDGAQ PEETPRDGDK PEETQGKAEK DEPGAWEETF KTHSDSKPYG 250 260 270 280 290 300 PMSVGLDFSL PGMEHVYGIP EHADNLRLKV TEGGEPYRLY NLDVFQYELY NPMALYGSVP 310 320 330 340 350 360 VLLAHNPHRD LGIFWLNAAE TWVDISSNTA GKTLFGKMMD YLQGSGETPQ TDVRWMSETG 370 380 390 400 410 420 IIDVFLLLGP SISDVFRQYA SLTGTQALPP LFSLGYHQSR WNYRDEADVL EVDQGFDDHN 430 440 450 460 470 480 LPCDVIWLDI EHADGKRYFT WDPSRFPQPR TMLERLASKR RKLVAIVDPH IKVDSGYRVH 490 500 510 520 530 540 EELRNLGLYV KTRDGSDYEG WCWPGSAGYP DFTNPTMRAW WANMFSYDNY EGSAPNLFVW 550 560 570 580 590 600 NDMNEPSVFN GPEVTMLKDA QHYGGWEHRD VHNIYGLYVH MATADGLRQR SGGMERPFVL 610 620 630 640 650 660 ARAFFAGSQR FGAVWTGDNT AEWDHLKISI PMCLSLGLVG LSFCGADVGG FFKNPEPELL 670 680 690 700 710 720 VRWYQMGAYQ PFFRAHAHLD TGRREPWLLP SQHNDIIRDA LGQRYSLLPF WYTLLYQAHR 730 740 750 760 770 780 EGIPVMRPLW VQYPQDVTTF NIDDQYLLGD ALLVHPVSDS GAHGVQVYLP GQGEVWYDIQ 790 800 810 820 830 840 SYQKHHGPQT LYLPVTLSSI PVFQRGGTIV PRWMRVRRSS ECMKDDPITL FVALSPQGTA 850 860 870 880 890 900 QGELFLDDGH TFNYQTRQEF LLRRFSFSGN TLVSSSADPE GHFETPIWIE RVVIIGAGKP 910 920 930 940 AAVVLQTKGS PESRLSFQHD PETSVLVLRK PGINVASDWS IHLR « Hide
Isoform 2 [UniParc]. Checksum: D0CD9E47C8E88FB5 Show »	FASTA	966	109,438
10 20 30 40 50 60 MAAVAAVAAR RRRSWASLVL AFLGVCLGIT LAVDRSNFKT CEESSFCKRQ RSIRPGLSPY 70 80 90 100 110 120 RALLDSLQLG PDSLTVHLIH EVTKVLLVLE LQGLQKNMTR FRIDELEPRR PRYRVPDVLV 130 140 150 160 170 180 ADPPIARLSV SGRDENSVEL TMAEGPYKII LTARPFRLDL LEDRSLLLSV NARGLLEFEH 190 200 210 220 230 240 QRAPRVSFSD KVNLTLGSIW DKIKNLFSRQ GSKDPAEGDG AQPEETPRDG DKPEETQGKA 250 260 270 280 290 300 EKDEPGAWEE TFKTHSDSKP YGPMSVGLDF SLPGMEHVYG IPEHADNLRL KVTEGGEPYR 310 320 330 340 350 360 LYNLDVFQYE LYNPMALYGS VPVLLAHNPH RDLGIFWLNA AETWVDISSN TAGKTLFGKM 370 380 390 400 410 420 MDYLQGSGET PQTDVRWMSE TGIIDVFLLL GPSISDVFRQ YASLTGTQAL PPLFSLGYHQ 430 440 450 460 470 480 SRWNYRDEAD VLEVDQGFDD HNLPCDVIWL DIEHADGKRY FTWDPSRFPQ PRTMLERLAS 490 500 510 520 530 540 KRRKLVAIVD PHIKVDSGYR VHEELRNLGL YVKTRDGSDY EGWCWPGSAG YPDFTNPTMR 550 560 570 580 590 600 AWWANMFSYD NYEGSAPNLF VWNDMNEPSV FNGPEVTMLK DAQHYGGWEH RDVHNIYGLY 610 620 630 640 650 660 VHMATADGLR QRSGGMERPF VLARAFFAGS QRFGAVWTGD NTAEWDHLKI SIPMCLSLGL 670 680 690 700 710 720 VGLSFCGADV GGFFKNPEPE LLVRWYQMGA YQPFFRAHAH LDTGRREPWL LPSQHNDIIR 730 740 750 760 770 780 DALGQRYSLL PFWYTLLYQA HREGIPVMRP LWVQYPQDVT TFNIDDQYLL GDALLVHPVS 790 800 810 820 830 840 DSGAHGVQVY LPGQGEVWYD IQSYQKHHGP QTLYLPVTLS SIPVFQRGGT IVPRWMRVRR 850 860 870 880 890 900 SSECMKDDPI TLFVALSPQG TAQGELFLDD GHTFNYQTRQ EFLLRRFSFS GNTLVSSSAD 910 920 930 940 950 960 PEGHFETPIW IERVVIIGAG KPAAVVLQTK GSPESRLSFQ HDPETSVLVL RKPGINVASD WSIHLR « Hide
Isoform 3 [UniParc]. Checksum: 012B4BAD808BCD74 Show »	FASTA	52	5,673
10 20 30 40 50 MAAVAAVAAR RRRSWASLVL AFLGVCLGIT LAVDRSNFKT CEESSFCKCC WC « Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence and analysis of the endoplasmic reticulum protein glucosidase II." Stuerzenhofecker B., Nguyenvan P., Soeling H.D. Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"The heterodimeric structure of glucosidase II is required for its activity, solubility, and localization in vivo." Pelletier M.F., Marcil A., Sevigny G., Jakob C.A., Tessier D.C., Chevet E., Menard R., Bergeron J.J.M., Thomas D.Y. Glycobiology 10:815-827(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, MUTAGENESIS OF ASP-542, INTERACTION WITH PRKCSH, SUBCELLULAR LOCATION, ALTERNATIVE SPLICING.
[3]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1." Nagase T., Miyajima N., Tanaka A., Sazuka T., Seki N., Sato S., Tabata S., Ishikawa K., Kawarabayasi Y., Kotani H., Nomura N. DNA Res. 2:37-43(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-944 (ISOFORM 1). Tissue: Bone marrow.
[5]	"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), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 457-944 (ISOFORMS 1/2). Tissue: Lymph and Uterus.
[6]	Lubec G., Afjehi-Sadat L. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 915-929, MASS SPECTROMETRY. Tissue: Brain and Cajal-Retzius cell.
[7]	"Identity of neutral alpha-glucosidase AB and the glycoprotein processing enzyme glucosidase II. Biochemical and genetic studies." Martiniuk F., Ellenbogen A., Hirschhorn R. J. Biol. Chem. 260:1238-1242(1985) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION, TISSUE SPECIFICITY.
[8]	"Endoplasmic reticulum glucosidase II is composed of a catalytic subunit, conserved from yeast to mammals, and a tightly bound noncatalytic HDEL-containing subunit." Trombetta E.S., Simons J.F., Helenius A. J. Biol. Chem. 271:27509-27516(1996) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PRKCSH.
[9]	"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes." Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F. J. Proteome Res. 5:3135-3144(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Tissue: Melanoma.
[10]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ000332 mRNA. Translation: CAA04006.1. AF144074 mRNA. Translation: AAF66685.1. AP001458 Genomic DNA. No translation available. D42041 mRNA. Translation: BAA07642.1. BC017433 mRNA. Translation: AAH17433.2. BC017435 mRNA. Translation: AAH17435.2. BC065266 mRNA. Translation: AAH65266.1. Sequence problems.
IPI	IPI00011454. IPI00383581. IPI00441414.
RefSeq	NP_938148.1. NM_198334.1. NP_938149.2. NM_198335.2.
UniGene	Hs.595071.
3D structure databases
ProteinModelPortal	Q14697.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q14697. 17 interactions.
STRING	9606.ENSP00000340466.
Protein family/group databases
CAZy	GH31. Glycoside Hydrolase Family 31.
PTM databases
PhosphoSite	Q14697.
Polymorphism databases
DMDM	54037162.
2D gel databases
REPRODUCTION-2DPAGE	IPI00383581.
Proteomic databases
PaxDb	Q14697.
PRIDE	Q14697.
Protocols and materials databases
DNASU	23193.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000346178; ENSP00000340466; ENSG00000089597. ENST00000356638; ENSP00000349053; ENSG00000089597. ENST00000526210; ENSP00000433799; ENSG00000089597. ENST00000532402; ENSP00000432181; ENSG00000089597. ENST00000534613; ENSP00000434921; ENSG00000089597.
GeneID	23193.
KEGG	hsa:23193.
UCSC	uc001nua.3. human. uc001nub.3. human.
Organism-specific databases
CTD	23193.
GeneCards	GC11M062430.
HGNC	HGNC:4138. GANAB.
HPA	HPA026874.
MIM	104160. gene.
neXtProt	NX_Q14697.
PharmGKB	PA28551.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1501.
HOVERGEN	HBG051683.
KO	K05546.
OMA	DNETGWY.
Enzyme and pathway databases
BRENDA	3.2.1.84. 2681.
Reactome	REACT_17015. Metabolism of proteins.
UniPathway	UPA00957.
Gene expression databases
ArrayExpress	Q14697.
Bgee	Q14697.
CleanEx	HS_GANAB.
Genevestigator	Q14697.
GermOnline	ENSG00000089597. Homo sapiens.
Family and domain databases
InterPro	IPR011013. Gal_mutarotase_SF_dom. IPR000322. Glyco_hydro_31. IPR025887. Glyco_hydro_31_N_dom. IPR017853. Glycoside_hydrolase_SF. [Graphical view]
PANTHER	PTHR22762. PTHR22762. 1 hit.
Pfam	PF13802. Gal_mutarotas_2. 1 hit. PF01055. Glyco_hydro_31. 1 hit. [Graphical view]
SUPFAM	SSF74650. Gal_mut_like. 1 hit. SSF51445. Glyco_hydro_cat. 1 hit.
PROSITE	PS00129. GLYCOSYL_HYDROL_F31_1. 1 hit. PS00707. GLYCOSYL_HYDROL_F31_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q14697.
ChEMBL	CHEMBL2519.
ChiTaRS	GANAB. human.
GenomeRNAi	23193.
NextBio	44685.
SOURCE	Search...

Entry information

Entry name

GANAB_HUMAN

Accession

Primary (citable) accession number: Q14697
Secondary accession number(s): A6NC20, Q8WTS9, Q9P0X0

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 5, 2004
Last sequence update:	July 5, 2004
Last modified:	May 1, 2013
This is version 115 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.

Relevant documents

Glycosyl hydrolases

Classification of glycosyl hydrolase families and list of entries

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Alternative products

Sequence annotation (Features)

Molecule processing

Sites

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

PTM databases

Polymorphism databases

2D gel databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents