PPAL_HUMAN
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 03-AUG-2022, entry version 194.
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}.
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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; 123.
DR ELM; P11117; -.
DR IntAct; P11117; 39.
DR STRING; 9606.ENSP00000256997; -.
DR DEPOD; ACP2; -.
DR GlyConnect; 1476; 13 N-Linked glycans (5 sites), 1 O-Linked glycan (1 site).
DR GlyGen; P11117; 9 sites, 13 N-linked glycans (5 sites), 1 O-linked glycan (1 site).
DR iPTMnet; P11117; -.
DR PhosphoSitePlus; 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; P11117; -.
DR PeptideAtlas; P11117; -.
DR PRIDE; P11117; -.
DR ProteomicsDB; 19451; -.
DR ProteomicsDB; 52693; -. [P11117-1]
DR TopDownProteomics; P11117-1; -. [P11117-1]
DR Antibodypedia; 26620; 111 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 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; 1221585at2759; -.
DR PhylomeDB; P11117; -.
DR TreeFam; TF312893; -.
DR PathwayCommons; P11117; -.
DR SignaLink; P11117; -.
DR BioGRID-ORCS; 53; 12 hits in 1076 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 195 other tissues.
DR ExpressionAtlas; P11117; baseline and differential.
DR Genevisible; P11117; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
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:0016791; F: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; -; 1.
DR InterPro; IPR033379; Acid_Pase_AS.
DR InterPro; IPR000560; His_Pase_clade-2.
DR InterPro; IPR029033; His_PPase_superfam.
DR Pfam; PF00328; His_Phos_2; 1.
DR SUPFAM; SSF53254; SSF53254; 1.
DR PROSITE; PS00616; HIS_ACID_PHOSPHAT_1; 1.
DR PROSITE; PS00778; HIS_ACID_PHOSPHAT_2; 1.
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
