Q9UK23 (NAGPA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	515 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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.
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.
Subcellular location	Golgi apparatus › Golgi stack membrane; Single-pass type I membrane protein. Note: Cis/medial Golgi.
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.
Sequence similarities	Contains 1 EGF-like domain.

Ontologies

Keywords
Cellular component	Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	EGF-like domain Signal Transmembrane Transmembrane helix
Molecular function	Hydrolase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	carbohydrate metabolic process Traceable author statement. Source: ProtInc lysosome organization Traceable author statement. Source: ProtInc protein modification process Traceable author statement. Source: ProtInc protein targeting to lysosome Traceable author statement. Source: ProtInc
Cellular component	Golgi cisterna membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Traceable author statement. Source: ProtInc
Molecular function	N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	Potential
	Chain	25 – 515	491	N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase		PRO_0000021788
Regions
	Topological domain	25 – 448	424	Lumenal Potential
	Transmembrane	449 – 469	21	Helical; Potential
	Topological domain	470 – 515	46	Cytoplasmic Potential
	Domain	358 – 390	33	EGF-like
	Motif	488 – 491	4	Tyrosine-based internalization motif
	Motif	511 – 515	5	NPF internalization motif
Amino acid modifications
	Glycosylation	208	1	N-linked (GlcNAc...) Potential
	Glycosylation	214	1	N-linked (GlcNAc...) Potential
	Glycosylation	296	1	N-linked (GlcNAc...) Potential
	Glycosylation	366	1	N-linked (GlcNAc...) Potential
	Glycosylation	388	1	N-linked (GlcNAc...) Potential
	Glycosylation	420	1	N-linked (GlcNAc...) Potential
	Disulfide bond	362 ↔ 373		By similarity
	Disulfide bond	380 ↔ 389		By similarity
Natural variations
	Alternative sequence	307 – 309	3	CQD → WQA in isoform 3.		VSP_012267
	Alternative sequence	310 – 515	206	Missing in isoform 3.		VSP_012268
	Alternative sequence	392 – 425	34	Missing in isoform 2.		VSP_012269
	Natural variant	465	1	T → I. Ref.1 Corresponds to variant rs7188856 [ dbSNP | Ensembl ].		VAR_020609
Experimental info
	Sequence conflict	259	1	Q → H in AAF08273. Ref.1
	Sequence conflict	405	1	P → R in AAF08273. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 18, 2010. Version 2. Checksum: 9B80335E7F9DBAA9	FASTA	515	56,073
	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
	Isoform 2 [UniParc]. Checksum: 2FC910C7DB777505	FASTA	481	52,368
	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 EVKQCLQPPE ATLRAGELSF FTRTAWLALT 430 440 450 460 470 480 LALAFLLLIS TAANLSLLLS RAERNRRLHG DYAYHPLQEM NGEPLAAEKE QPGGAHNPFK D
	Isoform 3 [UniParc]. Checksum: 270763749113C946	FASTA	309	33,577
	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 SYPSDHWQA

References

	« Hide 'large scale' referencesShow '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: 10551838] [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. , 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: 14702039] [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. , 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: 15616553] [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. , 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Colon.
+	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.
IPI	IPI00008303. IPI00513704. IPI00513953.
RefSeq	NP_057340.2. NM_016256.3.
UniGene	Hs.21334.
3D structure databases
ProteinModelPortal	Q9UK23.
SMR	Q9UK23. Positions 333-424.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UK23. 2 interactions.
STRING	Q9UK23.
Polymorphism databases
DMDM	296439239.
Proteomic databases
PRIDE	Q9UK23.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000312251; ENSP00000310998; ENSG00000103174.
GeneID	51172.
KEGG	hsa:51172.
UCSC	uc002cyf.1. human.
Organism-specific databases
CTD	51172.
GeneCards	GC16M005014.
H-InvDB	HIX0013112.
HGNC	HGNC:17378. NAGPA.
MIM	607985. gene.
neXtProt	NX_Q9UK23.
PharmGKB	PA134940049.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG10448.
GeneTree	ENSGT00600000084544.
HOGENOM	HBG716666.
HOVERGEN	HBG052571.
InParanoid	Q9UK23.
OMA	EPLRTFS.
OrthoDB	EOG4STS4S.
PhylomeDB	Q9UK23.
Gene expression databases
ArrayExpress	Q9UK23.
Bgee	Q9UK23.
CleanEx	HS_NAGPA.
Genevestigator	Q9UK23.
GermOnline	ENSG00000103174. Homo sapiens.
Family and domain databases
InterPro	IPR006210. EGF-like. IPR013032. EGF-like_reg_CS. IPR000742. EGF_3. IPR018711. Pdiester_a-GlcNAcase. [Graphical view]
KO	K01125.
Pfam	PF09992. DUF2233. 1 hit. [Graphical view]
SMART	SM00181. EGF. 1 hit. [Graphical view]
PROSITE	PS00022. EGF_1. 1 hit. PS01186. EGF_2. 1 hit. PS50026. EGF_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00141. N-Acetyl-D-glucosamine.
SOURCE	Search...

Entry information

Entry name

NAGPA_HUMAN

Accession

Primary (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:	December 14, 2011
This is version 93 of the entry and version 2 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.