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Q9UK23 (NAGPA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | 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:
N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase

EC=3.1.4.45
Alternative name(s):
Mannose 6-phosphate-uncovering enzyme
Phosphodiester alpha-GlcNAcase
Gene names
Name:NAGPA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length515 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the second step in the formation of the mannose 6-phosphate targeting signal on lysosomal enzyme oligosaccharides by removing GlcNAc residues from GlcNAc-alpha-P-mannose moieties, which are formed in the first step. Also hydrolyzes UDP-GlcNAc, a sugar donor for Golgi N-acetylglucosaminyltransferases. Ref.7

Catalytic activity

Glycoprotein N-acetyl-D-glucosaminyl-phospho-D-mannose + H2O = N-acetyl-D-glucosamine + glycoprotein phospho-D-mannose.

Pathway

Protein modification; protein glycosylation.

Subunit structure

Homotetramer arranged as two disulfide-linked homodimers By similarity. Ref.7

Subcellular location

Golgi apparatusGolgi stack membrane; Single-pass type I membrane protein. Golgi apparatustrans-Golgi network. Note: Cis/medial Golgi. Ref.6

Tissue specificity

Isoform 2 may be brain-specific.

Domain

The tyrosine-based internalization signal may be essential for its retrieval from the plasma membrane to the TGN.

The C-terminal NPFKD sequence is an attractive candidate for either an endocytosis signal acting at the plasma membrane or a retrieval signal acting at the TGN to return the enzyme to the cis/medial-Golgi.

Post-translational modification

The precursor is cleaved and activated in the trans-Golgi network by a furin endopeptidase. Ref.6

Sequence similarities

Contains 1 EGF-like domain.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UK23-1)

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: Q9UK23-2)

The sequence of this isoform differs from the canonical sequence as follows:
     392-425: Missing.
Isoform 3 (identifier: Q9UK23-3)

The sequence of this isoform differs from the canonical sequence as follows:
     307-309: CQD → WQA
     310-515: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Ref.6
Propeptide26 – 4924Removed in mature form
PRO_0000424659
Chain50 – 515466N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase
PRO_0000021788

Regions

Topological domain50 – 448399Lumenal Potential
Transmembrane449 – 46921Helical; Potential
Topological domain470 – 51546Cytoplasmic Potential
Domain358 – 39033EGF-like
Motif488 – 4914Tyrosine-based internalization motif
Motif511 – 5155NPF internalization motif

Amino acid modifications

Glycosylation2081N-linked (GlcNAc...) Potential
Glycosylation2141N-linked (GlcNAc...) Potential
Glycosylation2961N-linked (GlcNAc...) Potential
Glycosylation3661N-linked (GlcNAc...) Potential
Glycosylation3881N-linked (GlcNAc...) Potential
Glycosylation4201N-linked (GlcNAc...) Potential
Disulfide bond115 ↔ 148 Probable
Disulfide bond132 ↔ 323 Ref.7
Disulfide bond307 ↔ 314 Probable
Disulfide bond362 ↔ 373 By similarity
Disulfide bond380 ↔ 389 By similarity

Natural variations

Alternative sequence307 – 3093CQD → WQA in isoform 3.
VSP_012267
Alternative sequence310 – 515206Missing in isoform 3.
VSP_012268
Alternative sequence392 – 42534Missing in isoform 2.
VSP_012269
Natural variant4651T → I. Ref.1
Corresponds to variant rs7188856 [ dbSNP | Ensembl ].
VAR_020609

Experimental info

Mutagenesis511C → M: 65% of wild-type of activity. Ref.7
Mutagenesis1151C → S: 15% of wild-type of activity, and almost no traffic to Golgi. Ref.7
Mutagenesis1321C → V: No traffic to Golgi. Ref.7
Mutagenesis1371N → A: 11% of wild-type of activity. Ref.7
Mutagenesis2211C → L: 10% of wild-type of activity; when associated with M-51. Ref.7
Mutagenesis2251Q → H: 6% of wild-type of activity. Ref.7
Mutagenesis2271T → R: Complete loss of activity. Ref.7
Mutagenesis2471R → A: 87% of wild-type of activity. Ref.7
Mutagenesis2841N → A: 22% of wild-type of activity. Ref.7
Mutagenesis2861D → A: Complete loss of activity. Ref.7
Mutagenesis2871G → A: 16% of wild-type of activity. Ref.7
Mutagenesis2881G → A: Complete loss of activity. Ref.7
Mutagenesis2891G → A: Complete loss of activity. Ref.7
Mutagenesis2901S → A: Complete loss of activity. Ref.7
Mutagenesis3201T → A: 43% of wild-type of activity. Ref.7
Mutagenesis3221V → A: 67% of wild-type of activity. Ref.7
Sequence conflict2591Q → H in AAF08273. Ref.1
Sequence conflict4051P → R in AAF08273. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 18, 2010. Version 2.
Checksum: 9B80335E7F9DBAA9

FASTA51556,073
        10         20         30         40         50         60 
MATSTGRWLL LRLALFGFLW EASGGLDSGA SRDDDLLLPY PRARARLPRD CTRVRAGNRE 

        70         80         90        100        110        120 
HESWPPPPAT PGAGGLAVRT FVSHFRDRAV AGHLTRAVEP LRTFSVLEPG GPGGCAARRR 

       130        140        150        160        170        180 
ATVEETARAA DCRVAQNGGF FRMNSGECLG NVVSDERRVS SSGGLQNAQF GIRRDGTLVT 

       190        200        210        220        230        240 
GYLSEEEVLD TENPFVQLLS GVVWLIRNGS IYINESQATE CDETQETGSF SKFVNVISAR 

       250        260        270        280        290        300 
TAIGHDRKGQ LVLFHADGQT EQRGINLWEM AEFLLKQDVV NAINLDGGGS ATFVLNGTLA 

       310        320        330        340        350        360 
SYPSDHCQDN MWRCPRQVST VVCVHEPRCQ PPDCHGHGTC VDGHCQCTGH FWRGPGCDEL 

       370        380        390        400        410        420 
DCGPSNCSQH GLCTETGCRC DAGWTGSNCS EECPLGWHGP GCQRPCKCEH HCPCDPKTGN 

       430        440        450        460        470        480 
CSVSRVKQCL QPPEATLRAG ELSFFTRTAW LALTLALAFL LLISTAANLS LLLSRAERNR 

       490        500        510 
RLHGDYAYHP LQEMNGEPLA AEKEQPGGAH NPFKD 

« Hide

Isoform 2 [UniParc].

Checksum: 2FC910C7DB777505
Show »

FASTA48152,368
Isoform 3 [UniParc].

Checksum: 270763749113C946
Show »

FASTA30933,577

References

« Hide 'large scale' references
[1]"Molecular cloning and functional expression of two splice forms of human N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase."
Kornfeld R.H., Bao M., Brewer K., Noll C., Canfield W.M.
J. Biol. Chem. 274:32778-32785(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT ILE-465.
[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 1).
Tissue: Mammary gland and Tongue.
[3]"The sequence and analysis of duplication-rich human chromosome 16."
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. expand/collapse author list , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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).
Tissue: Colon.
[6]"Human mannose 6-phosphate-uncovering enzyme is synthesized as a proenzyme that is activated by the endoprotease furin."
Do H., Lee W.S., Ghosh P., Hollowell T., Canfield W., Kornfeld S.
J. Biol. Chem. 277:29737-29744(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 26-36, SIGNAL SEQUENCE CLEAVAGE SITE, PROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION.
[7]"Structure and function of the DUF2233 domain in bacteria and in the human mannose 6-phosphate uncovering enzyme."
Das D., Lee W.S., Grant J.C., Chiu H.J., Farr C.L., Vance J., Klock H.E., Knuth M.W., Miller M.D., Elsliger M.A., Deacon A.M., Godzik A., Lesley S.A., Kornfeld S., Wilson I.A.
J. Biol. Chem. 288:16789-16799(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF CYS-51; CYS-115; CYS-132; ASN-137; CYS-221; GLN-225; THR-227; ARG-247; ASN-284; ASP-286; GLY-287; GLY-288; GLY-289; SER-290; THR-320 AND VAL-322, 3D-STRUCTURE MODELING, DISULFIDE BONDS, FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF187072 mRNA. Translation: AAF08273.1.
AK127952 mRNA. Translation: BAG54605.1.
AK314320 mRNA. Translation: BAG36968.1.
AC026458 Genomic DNA. No translation available.
CH471112 Genomic DNA. Translation: EAW85245.1.
BC012194 mRNA. Translation: AAH12194.1.
CCDSCCDS10527.1. [Q9UK23-1]
RefSeqNP_057340.2. NM_016256.3. [Q9UK23-1]
UniGeneHs.21334.

3D structure databases

ProteinModelPortalQ9UK23.
SMRQ9UK23. Positions 314-434.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119351. 4 interactions.
IntActQ9UK23. 2 interactions.
STRING9606.ENSP00000310998.

Chemistry

ChEMBLCHEMBL5920.
DrugBankDB00141. N-Acetyl-D-glucosamine.

PTM databases

PhosphoSiteQ9UK23.

Polymorphism databases

DMDM296439239.

Proteomic databases

MaxQBQ9UK23.
PaxDbQ9UK23.
PRIDEQ9UK23.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000312251; ENSP00000310998; ENSG00000103174. [Q9UK23-1]
ENST00000381955; ENSP00000371381; ENSG00000103174. [Q9UK23-2]
ENST00000562746; ENSP00000455900; ENSG00000103174. [Q9UK23-3]
GeneID51172.
KEGGhsa:51172.
UCSCuc002cyg.3. human. [Q9UK23-1]

Organism-specific databases

CTD51172.
GeneCardsGC16M005014.
H-InvDBHIX0013112.
HGNCHGNC:17378. NAGPA.
MIM607985. gene.
neXtProtNX_Q9UK23.
PharmGKBPA134940049.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG126864.
HOGENOMHOG000059612.
HOVERGENHBG052571.
InParanoidQ9UK23.
KOK01125.
OMAPSDHCQD.
OrthoDBEOG7R2BJP.
PhylomeDBQ9UK23.
TreeFamTF331920.

Enzyme and pathway databases

UniPathwayUPA00378.

Gene expression databases

ArrayExpressQ9UK23.
BgeeQ9UK23.
CleanExHS_NAGPA.
GenevestigatorQ9UK23.

Family and domain databases

InterProIPR018711. DUF2233.
IPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
[Graphical view]
PfamPF09992. DUF2233. 1 hit.
[Graphical view]
SMARTSM00181. EGF. 1 hit.
[Graphical view]
PROSITEPS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiNAGPA.
GenomeRNAi51172.
NextBio54121.
PROQ9UK23.
SOURCESearch...

Entry information

Entry nameNAGPA_HUMAN
AccessionPrimary (citable) accession number: Q9UK23
Secondary accession number(s): B2RAS1, Q96EJ8
Entry history
Integrated into UniProtKB/Swiss-Prot: December 21, 2004
Last sequence update: May 18, 2010
Last modified: July 9, 2014
This is version 117 of the entry and version 2 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 16

Human chromosome 16: entries, gene names and cross-references to MIM