P11117 (PPAL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Lysosomal acid phosphatase
Short name=LAP
EC=3.1.3.2

Gene names

Name:

ACP2

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	423 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)

Catalytic activity	A phosphate monoester + H2O = an alcohol + phosphate.
Subcellular location	Lysosome membrane; Single-pass membrane protein; Lumenal side. Lysosome lumen. Note: The soluble form arises by proteolytic processing of the membrane-bound form. Ref.6 Ref.8
Post-translational modification	The membrane-bound form is converted to the soluble form by sequential proteolytic processing. First, the C-terminal cytoplasmic tail is removed. Cleavage by a lysosomal protease releases the soluble form in the lysosome lumen. N-glycosylated. The intermediates formed during enzymatic deglycosylation suggest that all eight predicted N-glycosylation sites are used. Ref.8
Involvement in disease	Acid phosphatase deficiency (ACPHD) [MIM:200950]: A disorder characterized by intermittent vomiting, hypotonia, lethargy, opisthotonos, terminal bleedingand death in early infancy. Lysosomal acid phosphatase is deficient in cultured fibroblasts and multiple tissues. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7
Sequence similarities	Belongs to the histidine acid phosphatase family.

Ontologies

Keywords
Cellular component	Lysosome Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Hydrolase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	lysosome organization Inferred from electronic annotation. Source: Compara skeletal system development Inferred from electronic annotation. Source: Compara
Cellular_component	integral to membrane Traceable author statement Ref.2. Source: ProtInc lysosomal lumen Inferred from electronic annotation. Source: UniProtKB-SubCell lysosomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell lysosome Inferred from direct assay PubMed 3160696. Source: MGI
Molecular_function	acid phosphatase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P11117-1)

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: P11117-2)

The sequence of this isoform differs from the canonical sequence as follows:
     151-160: LLKFPLGPCP → VRVASPSLGW
     161-423: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 30	30
	Chain	31 – 423	393	Lysosomal acid phosphatase		PRO_0000023960
Regions
	Topological domain	31 – 380	350	Lumenal Potential
	Transmembrane	381 – 401	21	Helical; Potential
	Topological domain	402 – 423	22	Cytoplasmic Potential
Sites
	Active site	42	1	Nucleophile By similarity
	Active site	287	1	Proton donor By similarity
Amino acid modifications
	Glycosylation	92	1	N-linked (GlcNAc...) Ref.9
	Glycosylation	133	1	N-linked (GlcNAc...) Ref.9
	Glycosylation	167	1	N-linked (GlcNAc...) Ref.9
	Glycosylation	177	1	N-linked (GlcNAc...) Ref.9
	Glycosylation	191	1	N-linked (GlcNAc...) Probable
	Glycosylation	267	1	N-linked (GlcNAc...) Ref.9
	Glycosylation	322	1	N-linked (GlcNAc...) Probable
	Glycosylation	331	1	N-linked (GlcNAc...) Ref.9
	Disulfide bond	159 ↔ 370		By similarity
	Disulfide bond	212 ↔ 310		By similarity
	Disulfide bond	345 ↔ 349		By similarity
Natural variations
	Alternative sequence	151 – 160	10	LLKFPLGPCP → VRVASPSLGW in isoform 2.		VSP_045629
	Alternative sequence	161 – 423	263	Missing in isoform 2.		VSP_045630
	Natural variant	29	1	R → Q. Ref.3 Ref.5 Corresponds to variant rs2167079 [ dbSNP | Ensembl ].		VAR_027801
	Natural variant	320	1	S → F. Corresponds to variant rs34425282 [ dbSNP | Ensembl ].		VAR_034394
	Natural variant	402	1	V → I. Corresponds to variant rs4647764 [ dbSNP | Ensembl ].		VAR_050519

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 3, 2006. Version 3. Checksum: 3431A30B83A1E2B4	FASTA	423	48,344
	10 20 30 40 50 60 MAGKRSGWSR AALLQLLLGV NLVVMPPTRA RSLRFVTLLY RHGDRSPVKT YPKDPYQEEE 70 80 90 100 110 120 WPQGFGQLTK EGMLQHWELG QALRQRYHGF LNTSYHRQEV YVRSTDFDRT LMSAEANLAG 130 140 150 160 170 180 LFPPNGMQRF NPNISWQPIP VHTVPITEDR LLKFPLGPCP RYEQLQNETR QTPEYQNESS 190 200 210 220 230 240 RNAQFLDMVA NETGLTDLTL ETVWNVYDTL FCEQTHGLRL PPWASPQTMQ RLSRLKDFSF 250 260 270 280 290 300 RFLFGIYQQA EKARLQGGVL LAQIRKNLTL MATTSQLPKL LVYSAHDTTL VALQMALDVY 310 320 330 340 350 360 NGEQAPYASC HIFELYQEDS GNFSVEMYFR NESDKAPWPL SLPGCPHRCP LQDFLRLTEP 370 380 390 400 410 420 VVPKDWQQEC QLASGPADTE VIVALAVCGS ILFLLIVLLL TVLFRMQAQP PGYRHVADGE DHA
	Isoform 2 [UniParc]. Checksum: 18EA6F3F31278714	FASTA	160	18,417
	10 20 30 40 50 60 MAGKRSGWSR AALLQLLLGV NLVVMPPTRA RSLRFVTLLY RHGDRSPVKT YPKDPYQEEE 70 80 90 100 110 120 WPQGFGQLTK EGMLQHWELG QALRQRYHGF LNTSYHRQEV YVRSTDFDRT LMSAEANLAG 130 140 150 160 LFPPNGMQRF NPNISWQPIP VHTVPITEDR VRVASPSLGW

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human lysosomal acid phosphatase: cloning, expression and chromosomal assignment." Pohlmann R., Krentler C., Schmidt B., Schroeder W., Lorkowski G., Culley J., Mersmann G., Geier C., Waheed A., Gottschalk S., Grzeschik K.H., Hasikik A., von Figura K. EMBO J. 7:2343-2350(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE. Tissue: Placenta.
[2]	"Structure of the human lysosomal acid phosphatase gene." Geier C., von Figura K., Pohlmann R. Eur. J. Biochem. 183:611-616(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Leukocyte.
[3]	"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 2), VARIANT GLN-29. Tissue: Thalamus.
[4]	"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. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] 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 1), VARIANT GLN-29. Tissue: Kidney and Placenta.
[6]	"Sequential processing of lysosomal acid phosphatase by a cytoplasmic thiol proteinase and a lysosomal aspartyl proteinase." Gottschalk S., Waheed A., Schmidt B., Laidler P., von Figura K. EMBO J. 8:3215-3219(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, PROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION.
[7]	"Deficiency of lysosomal acid phosphatase. A new familial metabolic disorder." Nadler H.L., Egan T.J. N. Engl. J. Med. 282:302-307(1970) [PubMed] [Europe PMC] [Abstract] Cited for: DISEASE.
[8]	"Human lysosomal acid phosphatase is transported as a transmembrane protein to lysosomes in transfected baby hamster kidney cells." Waheed A., Gottschalk S., Hille A., Krentler C., Pohlmann R., Braulke T., Hauser H., Geuze H., von Figura K. EMBO J. 7:2351-2358(1988) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, GLYCOSYLATION, MEMBRANE TOPOLOGY, PROTEOLYTIC PROCESSING.
[9]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-92; ASN-133; ASN-167; ASN-177; ASN-267 AND ASN-331, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X12548 mRNA. Translation: CAA31064.1. X15525 , X15526, X15527, X15528, X15529, X15530, X15531, X15532, X15533, X15534, X15535 Genomic DNA. Translation: CAA33542.1. DA382854 mRNA. No translation available. AC018410 Genomic DNA. No translation available. BC003160 mRNA. Translation: AAH03160.1. BC093010 mRNA. Translation: AAH93010.1.
IPI	IPI00003807. IPI00909518.
PIR	S06167.
RefSeq	NP_001124536.1. NM_001131064.1. NP_001601.1. NM_001610.2.
UniGene	Hs.532492.
3D structure databases
ProteinModelPortal	P11117.
ModBase	Search...
Protein-protein interaction databases
IntAct	P11117. 2 interactions.
STRING	9606.ENSP00000256997.
PTM databases
PhosphoSite	P11117.
Polymorphism databases
DMDM	115502439.
Proteomic databases
PaxDb	P11117.
PeptideAtlas	P11117.
PRIDE	P11117.
Protocols and materials databases
DNASU	53.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000256997; ENSP00000256997; ENSG00000134575. ENST00000444355; ENSP00000414911; ENSG00000134575.
GeneID	53.
KEGG	hsa:53.
UCSC	uc001nei.3. human.
Organism-specific databases
CTD	53.
GeneCards	GC11M047260.
HGNC	HGNC:123. ACP2.
MIM	171650. gene. 200950. phenotype.
neXtProt	NX_P11117.
Orphanet	35121. Acid phosphatase deficiency.
PharmGKB	PA24447.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG85977.
HOGENOM	HOG000231439.
HOVERGEN	HBG002203.
InParanoid	P11117.
KO	K14410.
OMA	CHMFELY.
OrthoDB	EOG4JQ3XM.
PhylomeDB	P11117.
Gene expression databases
ArrayExpress	P11117.
Bgee	P11117.
CleanEx	HS_ACP2.
Genevestigator	P11117.
GermOnline	ENSG00000134575. Homo sapiens.
Family and domain databases
InterPro	IPR000560. His_Pase_superF_clade-2. [Graphical view]
Pfam	PF00328. His_Phos_2. 1 hit. [Graphical view]
PROSITE	PS00616. HIS_ACID_PHOSPHAT_1. 1 hit. PS00778. HIS_ACID_PHOSPHAT_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	53.
NextBio	213.
SOURCE	Search...

Entry information

Entry name

PPAL_HUMAN

Accession

Primary (citable) accession number: P11117
Secondary accession number(s): E9PCI1, Q561W5, Q9BTU7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	October 3, 2006
Last modified:	May 1, 2013
This is version 128 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.