ID   PPAL_HUMAN              Reviewed;         423 AA.
AC   P11117; E9PCI1; Q561W5; Q9BTU7;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   03-OCT-2006, sequence version 3.
DT   24-JAN-2024, entry version 202.
DE   RecName: Full=Lysosomal acid phosphatase;
DE            Short=LAP;
DE            EC=3.1.3.2;
DE   Flags: Precursor;
GN   Name=ACP2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE.
RC   TISSUE=Placenta;
RX   PubMed=3191910; DOI=10.1002/j.1460-2075.1988.tb03078.x;
RA   Pohlmann R., Krentler C., Schmidt B., Schroeder W., Lorkowski G.,
RA   Culley J., Mersmann G., Geier C., Waheed A., Gottschalk S., Grzeschik K.H.,
RA   Hasikik A., von Figura K.;
RT   "Human lysosomal acid phosphatase: cloning, expression and chromosomal
RT   assignment.";
RL   EMBO J. 7:2343-2350(1988).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Leukocyte;
RX   PubMed=2776754; DOI=10.1111/j.1432-1033.1989.tb21090.x;
RA   Geier C., von Figura K., Pohlmann R.;
RT   "Structure of the human lysosomal acid phosphatase gene.";
RL   Eur. J. Biochem. 183:611-616(1989).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT GLN-29.
RC   TISSUE=Thalamus;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16554811; DOI=10.1038/nature04632;
RA   Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA   Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA   Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA   Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA   Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA   Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT   "Human chromosome 11 DNA sequence and analysis including novel gene
RT   identification.";
RL   Nature 440:497-500(2006).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLN-29.
RC   TISSUE=Kidney, and Placenta;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   PARTIAL PROTEIN SEQUENCE, PROTEOLYTIC PROCESSING, AND SUBCELLULAR LOCATION.
RX   PubMed=2684640; DOI=10.1002/j.1460-2075.1989.tb08480.x;
RA   Gottschalk S., Waheed A., Schmidt B., Laidler P., von Figura K.;
RT   "Sequential processing of lysosomal acid phosphatase by a cytoplasmic thiol
RT   proteinase and a lysosomal aspartyl proteinase.";
RL   EMBO J. 8:3215-3219(1989).
RN   [7]
RP   DISEASE.
RX   PubMed=5410815; DOI=10.1056/nejm197002052820604;
RA   Nadler H.L., Egan T.J.;
RT   "Deficiency of lysosomal acid phosphatase. A new familial metabolic
RT   disorder.";
RL   N. Engl. J. Med. 282:302-307(1970).
RN   [8]
RP   SUBCELLULAR LOCATION, GLYCOSYLATION, MEMBRANE TOPOLOGY, AND PROTEOLYTIC
RP   PROCESSING.
RX   PubMed=3056714; DOI=10.1002/j.1460-2075.1988.tb03079.x;
RA   Waheed A., Gottschalk S., Hille A., Krentler C., Pohlmann R., Braulke T.,
RA   Hauser H., Geuze H., von Figura K.;
RT   "Human lysosomal acid phosphatase is transported as a transmembrane protein
RT   to lysosomes in transfected baby hamster kidney cells.";
RL   EMBO J. 7:2351-2358(1988).
RN   [9]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-92; ASN-133; ASN-167; ASN-177;
RP   ASN-267 AND ASN-331.
RC   TISSUE=Liver;
RX   PubMed=19159218; DOI=10.1021/pr8008012;
RA   Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT   "Glycoproteomics analysis of human liver tissue by combination of multiple
RT   enzyme digestion and hydrazide chemistry.";
RL   J. Proteome Res. 8:651-661(2009).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a phosphate monoester + H2O = an alcohol + phosphate;
CC         Xref=Rhea:RHEA:15017, ChEBI:CHEBI:15377, ChEBI:CHEBI:30879,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:67140; EC=3.1.3.2;
CC   -!- INTERACTION:
CC       P11117; Q86V38: ATN1; NbExp=3; IntAct=EBI-2907070, EBI-11954292;
CC       P11117; Q9UQC2: GAB2; NbExp=3; IntAct=EBI-2907070, EBI-975200;
CC       P11117; Q92876: KLK6; NbExp=3; IntAct=EBI-2907070, EBI-2432309;
CC       P11117; Q13153: PAK1; NbExp=3; IntAct=EBI-2907070, EBI-1307;
CC   -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:2684640,
CC       ECO:0000269|PubMed:3056714}; Single-pass membrane protein
CC       {ECO:0000255}; Lumenal side {ECO:0000305|PubMed:2684640,
CC       ECO:0000305|PubMed:3056714}. Lysosome lumen. Note=The soluble form
CC       arises by proteolytic processing of the membrane-bound form.
CC       {ECO:0000269|PubMed:2684640, ECO:0000269|PubMed:3056714}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P11117-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P11117-2; Sequence=VSP_045629, VSP_045630;
CC   -!- PTM: The membrane-bound form is converted to the soluble form by
CC       sequential proteolytic processing. First, the C-terminal cytoplasmic
CC       tail is removed. Cleavage by a lysosomal protease releases the soluble
CC       form in the lysosome lumen. {ECO:0000269|PubMed:2684640,
CC       ECO:0000269|PubMed:3056714}.
CC   -!- PTM: N-glycosylated. The intermediates formed during enzymatic
CC       deglycosylation suggest that all eight predicted N-glycosylation sites
CC       are used. {ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:3056714}.
CC   -!- DISEASE: Note=Lysosomal acid phosphatase has been shown to be deficient
CC       in cultured fibroblasts from patients manifesting intermittent
CC       vomiting, hypotonia, lethargy, opisthotonos, terminal bleeding and
CC       death in early infancy. {ECO:0000269|PubMed:5410815}.
CC   -!- SIMILARITY: Belongs to the histidine acid phosphatase family.
CC       {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; X12548; CAA31064.1; -; mRNA.
DR   EMBL; X15525; CAA33542.1; -; Genomic_DNA.
DR   EMBL; X15526; CAA33542.1; JOINED; Genomic_DNA.
DR   EMBL; X15527; CAA33542.1; JOINED; Genomic_DNA.
DR   EMBL; X15528; CAA33542.1; JOINED; Genomic_DNA.
DR   EMBL; X15529; CAA33542.1; JOINED; Genomic_DNA.
DR   EMBL; X15530; CAA33542.1; JOINED; Genomic_DNA.
DR   EMBL; X15531; CAA33542.1; JOINED; Genomic_DNA.
DR   EMBL; X15532; CAA33542.1; JOINED; Genomic_DNA.
DR   EMBL; X15533; CAA33542.1; JOINED; Genomic_DNA.
DR   EMBL; X15534; CAA33542.1; JOINED; Genomic_DNA.
DR   EMBL; X15535; CAA33542.1; JOINED; Genomic_DNA.
DR   EMBL; DA382854; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; AC018410; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC003160; AAH03160.1; -; mRNA.
DR   EMBL; BC093010; AAH93010.1; -; mRNA.
DR   CCDS; CCDS7928.1; -. [P11117-1]
DR   PIR; S06167; S06167.
DR   RefSeq; NP_001289418.1; NM_001302489.1.
DR   RefSeq; NP_001289419.1; NM_001302490.1.
DR   RefSeq; NP_001289420.1; NM_001302491.1.
DR   RefSeq; NP_001289421.1; NM_001302492.1.
DR   RefSeq; NP_001601.1; NM_001610.3. [P11117-1]
DR   AlphaFoldDB; P11117; -.
DR   BMRB; P11117; -.
DR   SMR; P11117; -.
DR   BioGRID; 106569; 133.
DR   ELM; P11117; -.
DR   IntAct; P11117; 41.
DR   DEPOD; ACP2; -.
DR   GlyConnect; 1476; 13 N-Linked glycans (5 sites), 1 O-Linked glycan (1 site).
DR   GlyCosmos; P11117; 9 sites, 13 glycans.
DR   GlyGen; P11117; 13 sites, 19 N-linked glycans (6 sites), 2 O-linked glycans (5 sites).
DR   iPTMnet; P11117; -.
DR   PhosphoSitePlus; P11117; -.
DR   SwissPalm; P11117; -.
DR   BioMuta; ACP2; -.
DR   DMDM; 115502439; -.
DR   CPTAC; CPTAC-1309; -.
DR   EPD; P11117; -.
DR   jPOST; P11117; -.
DR   MassIVE; P11117; -.
DR   MaxQB; P11117; -.
DR   PaxDb; 9606-ENSP00000256997; -.
DR   PeptideAtlas; P11117; -.
DR   ProteomicsDB; 19451; -.
DR   ProteomicsDB; 52693; -. [P11117-1]
DR   Pumba; P11117; -.
DR   TopDownProteomics; P11117-1; -. [P11117-1]
DR   Antibodypedia; 26620; 120 antibodies from 24 providers.
DR   DNASU; 53; -.
DR   Ensembl; ENST00000256997.9; ENSP00000256997.3; ENSG00000134575.13. [P11117-1]
DR   Ensembl; ENST00000672073.1; ENSP00000500291.1; ENSG00000134575.13. [P11117-1]
DR   GeneID; 53; -.
DR   KEGG; hsa:53; -.
DR   MANE-Select; ENST00000672073.1; ENSP00000500291.1; NM_001610.4; NP_001601.1.
DR   UCSC; uc001nei.3; human. [P11117-1]
DR   AGR; HGNC:123; -.
DR   CTD; 53; -.
DR   DisGeNET; 53; -.
DR   GeneCards; ACP2; -.
DR   HGNC; HGNC:123; ACP2.
DR   HPA; ENSG00000134575; Low tissue specificity.
DR   MalaCards; ACP2; -.
DR   MIM; 171650; gene.
DR   neXtProt; NX_P11117; -.
DR   NIAGADS; ENSG00000134575; -.
DR   OpenTargets; ENSG00000134575; -.
DR   PharmGKB; PA24447; -.
DR   VEuPathDB; HostDB:ENSG00000134575; -.
DR   eggNOG; KOG3720; Eukaryota.
DR   GeneTree; ENSGT00940000158446; -.
DR   InParanoid; P11117; -.
DR   OMA; QESDWPQ; -.
DR   OrthoDB; 5489935at2759; -.
DR   PhylomeDB; P11117; -.
DR   TreeFam; TF312893; -.
DR   PathwayCommons; P11117; -.
DR   SignaLink; P11117; -.
DR   BioGRID-ORCS; 53; 12 hits in 1168 CRISPR screens.
DR   ChiTaRS; ACP2; human.
DR   GeneWiki; ACP2; -.
DR   GenomeRNAi; 53; -.
DR   Pharos; P11117; Tbio.
DR   PRO; PR:P11117; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; P11117; Protein.
DR   Bgee; ENSG00000134575; Expressed in right lobe of liver and 197 other cell types or tissues.
DR   ExpressionAtlas; P11117; baseline and differential.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0043202; C:lysosomal lumen; IEA:UniProtKB-SubCell.
DR   GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005764; C:lysosome; IDA:MGI.
DR   GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR   GO; GO:0003993; F:acid phosphatase activity; IBA:GO_Central.
DR   GO; GO:0016311; P:dephosphorylation; IBA:GO_Central.
DR   GO; GO:0007040; P:lysosome organization; IBA:GO_Central.
DR   CDD; cd07061; HP_HAP_like; 1.
DR   Gene3D; 3.40.50.1240; Phosphoglycerate mutase-like; 1.
DR   InterPro; IPR033379; Acid_Pase_AS.
DR   InterPro; IPR000560; His_Pase_clade-2.
DR   InterPro; IPR029033; His_PPase_superfam.
DR   PANTHER; PTHR11567; ACID PHOSPHATASE-RELATED; 1.
DR   PANTHER; PTHR11567:SF180; LYSOSOMAL ACID PHOSPHATASE; 1.
DR   Pfam; PF00328; His_Phos_2; 1.
DR   SUPFAM; SSF53254; Phosphoglycerate mutase-like; 1.
DR   PROSITE; PS00616; HIS_ACID_PHOSPHAT_1; 1.
DR   PROSITE; PS00778; HIS_ACID_PHOSPHAT_2; 1.
DR   Genevisible; P11117; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Direct protein sequencing; Disulfide bond;
KW   Glycoprotein; Hydrolase; Lysosome; Membrane; Reference proteome; Signal;
KW   Transmembrane; Transmembrane helix.
FT   SIGNAL          1..30
FT   CHAIN           31..423
FT                   /note="Lysosomal acid phosphatase"
FT                   /id="PRO_0000023960"
FT   TOPO_DOM        31..380
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        381..401
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        402..423
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        42
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        287
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        92
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19159218"
FT   CARBOHYD        133
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19159218"
FT   CARBOHYD        167
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19159218"
FT   CARBOHYD        177
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19159218"
FT   CARBOHYD        191
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000305|PubMed:3056714"
FT   CARBOHYD        267
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19159218"
FT   CARBOHYD        322
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000305|PubMed:3056714"
FT   CARBOHYD        331
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19159218"
FT   DISULFID        159..370
FT                   /evidence="ECO:0000250"
FT   DISULFID        212..310
FT                   /evidence="ECO:0000250"
FT   DISULFID        345..349
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         151..160
FT                   /note="LLKFPLGPCP -> VRVASPSLGW (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_045629"
FT   VAR_SEQ         161..423
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_045630"
FT   VARIANT         29
FT                   /note="R -> Q (in dbSNP:rs2167079)"
FT                   /evidence="ECO:0000269|PubMed:14702039,
FT                   ECO:0000269|PubMed:15489334"
FT                   /id="VAR_027801"
FT   VARIANT         320
FT                   /note="S -> F (in dbSNP:rs34425282)"
FT                   /id="VAR_034394"
FT   VARIANT         402
FT                   /note="V -> I (in dbSNP:rs4647764)"
FT                   /id="VAR_050519"
SQ   SEQUENCE   423 AA;  48344 MW;  3431A30B83A1E2B4 CRC64;
     MAGKRSGWSR AALLQLLLGV NLVVMPPTRA RSLRFVTLLY RHGDRSPVKT YPKDPYQEEE
     WPQGFGQLTK EGMLQHWELG QALRQRYHGF LNTSYHRQEV YVRSTDFDRT LMSAEANLAG
     LFPPNGMQRF NPNISWQPIP VHTVPITEDR LLKFPLGPCP RYEQLQNETR QTPEYQNESS
     RNAQFLDMVA NETGLTDLTL ETVWNVYDTL FCEQTHGLRL PPWASPQTMQ RLSRLKDFSF
     RFLFGIYQQA EKARLQGGVL LAQIRKNLTL MATTSQLPKL LVYSAHDTTL VALQMALDVY
     NGEQAPYASC HIFELYQEDS GNFSVEMYFR NESDKAPWPL SLPGCPHRCP LQDFLRLTEP
     VVPKDWQQEC QLASGPADTE VIVALAVCGS ILFLLIVLLL TVLFRMQAQP PGYRHVADGE
     DHA
//