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UniProtKB - P15309 (PPAP_HUMAN)

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Protein

Prostatic acid phosphatase

Gene

ACPP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

A non-specific tyrosine phosphatase that dephosphorylates a diverse number of substrates under acidic conditions (pH 4-6) including alkyl, aryl, and acyl orthophosphate monoesters and phosphorylated proteins. Has lipid phosphatase activity and inactivates lysophosphatidic acid in seminal plasma.
Isoform 2: the cellular form also has ecto-5'-nucleotidase activity in dorsal root ganglion (DRG) neurons. Generates adenosine from AMP which acts as a pain suppressor. Acts as a tumor suppressor of prostate cancer through dephosphorylation of ERBB2 and deactivation of MAPK-mediated signaling.

Miscellaneous

Used as a diagnostic tool for staging metastatic prostatic cancer.

Catalytic activityi

A phosphate monoester + H2O = an alcohol + phosphate.1 Publication
A 5'-ribonucleotide + H2O = a ribonucleoside + phosphate.1 Publication

Enzyme regulationi

Phosphatase activity inhibited by L+-tartrate, and by its derivative, alpha-benzylaminobenzylphosphonic acid.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei43Substrate1
Active sitei44Nucleophile1 Publication1
Binding sitei47Substrate1
Sitei49Important for substrate specificity1
Binding sitei111Substrate1
Sitei138Required for homodimerizationBy similarity1
Sitei144Required for homodimerizationBy similarity1
Sitei206Required for structural stability1
Binding sitei289Substrate1
Active sitei290Proton donor1 Publication1

GO - Molecular functioni

  • 5'-nucleotidase activity Source: UniProtKB
  • acid phosphatase activity Source: UniProtKB
  • identical protein binding Source: IntAct
  • lysophosphatidic acid phosphatase activity Source: UniProtKB
  • phosphatase activity Source: UniProtKB
  • protein homodimerization activity Source: CAFA
  • thiamine phosphate phosphatase activity Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • adenosine metabolic process Source: UniProtKB
  • dephosphorylation Source: UniProtKB
  • neutrophil degranulation Source: Reactome
  • nucleotide metabolic process Source: Ensembl
  • positive regulation of adenosine receptor signaling pathway Source: UniProtKB
  • protein homotetramerization Source: CAFA
  • purine nucleobase metabolic process Source: Ensembl
  • regulation of sensory perception of pain Source: UniProtKB
  • thiamine metabolic process Source: UniProtKB
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionHydrolase

Enzyme and pathway databases

BRENDAi3.1.3.2 2681
ReactomeiR-HSA-6798695 Neutrophil degranulation
SABIO-RKiP15309

Chemistry databases

SwissLipidsiSLP:000001295 [P15309-1]

Names & Taxonomyi

Protein namesi
Recommended name:
Prostatic acid phosphatase (EC:3.1.3.2)
Short name:
PAP
Alternative name(s):
5'-nucleotidase (EC:3.1.3.5)
Short name:
5'-NT
Ecto-5'-nucleotidase
Thiamine monophosphatase
Short name:
TMPase
Cleaved into the following chain:
PAPf39
Gene namesi
Name:ACPP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000014257.15
HGNCiHGNC:125 ACPP
MIMi171790 gene
neXtProtiNX_P15309

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Amyloid, Cell membrane, Lysosome, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi206W → F: Greatly reduced enzyme activity, marked decrease in structural stability, and increased binding of the inhibitor, L(+)-tartrate. 1 Publication1
Mutagenesisi206W → L: Reduced enzyme activity, marked decrease in structural stability, and increased binding of the inhibitor, L(+)-tartrate. 1 Publication1

Organism-specific databases

DisGeNETi55
OpenTargetsiENSG00000014257
PharmGKBiPA24449

Chemistry databases

ChEMBLiCHEMBL2633
DrugBankiDB03577 Alpha-Benzyl-Aminobenzyl-Phosphonic Acid
DB03390 N-Propyl-Tartramic Acid
DB06688 Sipuleucel-T

Polymorphism and mutation databases

BioMutaiACPP
DMDMi130730

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 32Add BLAST32
ChainiPRO_000002396333 – 386Prostatic acid phosphataseAdd BLAST354
PeptideiPRO_0000411250248 – 286PAPf39Add BLAST39

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi94N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi161 ↔ 372
Disulfide bondi215 ↔ 313
Glycosylationi220N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi333N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi347 ↔ 351

Post-translational modificationi

N-glycosylated. High mannose content, partially sialylated and fucosylated biantennary complex. Also fucosylated with partially sialylated triantennary complex oligosaccharides.2 Publications
Proteolytically cleaved in seminal fluid to produce several peptides. Peptide PAPf39, the most prominent, forms amyloid beta-sheet fibrils, SEVI (semen-derived enhancer of viral infection) which entrap HIV virions, attach them to target cells and enhance infection. SEVI amyloid fibrils are degraded by polyphenol epigallocatechin-3-gallate (EGCG), a constituent of green tea. Target cell attachment and enhancement of HIV infection is inhibited by surfen. Also similarly boosts XMRV (xenotropic murine leukemia virus-related virus) infection.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiP15309
MaxQBiP15309
PaxDbiP15309
PeptideAtlasiP15309
PRIDEiP15309
ProteomicsDBi53126
53127 [P15309-2]

PTM databases

DEPODiP15309
iPTMnetiP15309
PhosphoSitePlusiP15309

Miscellaneous databases

PMAP-CutDBiP15309

Expressioni

Tissue specificityi

Highly expressed in the prostate, restricted to glandular and ductal epithelial cells. Also expressed in bladder, kidney, pancreas, lung, cervix, testis and ovary. Weak expression in a subset of pancreatic islet cells, squamous epithelia, the pilosebaceous unit, colonic neuroendocrine cells and skin adnexal structures. Isoform 2 also expressed in the sarcolemma of skeletal muscle. Levels of this cellular isoform decreased in prostate cancer.2 Publications

Gene expression databases

BgeeiENSG00000014257
CleanExiHS_ACPP
ExpressionAtlasiP15309 baseline and differential
GenevisibleiP15309 HS

Organism-specific databases

HPAiCAB000071
HPA004335
HPA063916

Interactioni

Subunit structurei

Homodimer; dimer formation is required for phosphatase activity.By similarity

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • protein homodimerization activity Source: CAFA
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi106571, 26 interactors
ComplexPortaliCPX-120 Prostatic acid phosphatase complex
IntActiP15309, 3 interactors
MINTiP15309
STRINGi9606.ENSP00000323036

Chemistry databases

BindingDBiP15309

Structurei

Secondary structure

1386
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi34 – 43Combined sources10
Helixi60 – 62Combined sources3
Helixi72 – 88Combined sources17
Turni89 – 93Combined sources5
Helixi99 – 101Combined sources3
Beta strandi102 – 108Combined sources7
Helixi110 – 123Combined sources14
Helixi128 – 130Combined sources3
Beta strandi134 – 136Combined sources3
Beta strandi144 – 146Combined sources3
Helixi148 – 150Combined sources3
Beta strandi152 – 155Combined sources4
Helixi162 – 173Combined sources12
Helixi175 – 181Combined sources7
Helixi182 – 184Combined sources3
Helixi185 – 195Combined sources11
Helixi202 – 208Combined sources7
Helixi210 – 218Combined sources9
Helixi229 – 247Combined sources19
Beta strandi248 – 251Combined sources4
Helixi252 – 258Combined sources7
Helixi261 – 276Combined sources16
Beta strandi277 – 279Combined sources3
Beta strandi282 – 288Combined sources7
Helixi290 – 299Combined sources10
Beta strandi313 – 321Combined sources9
Beta strandi324 – 332Combined sources9
Beta strandi335 – 337Combined sources3
Beta strandi340 – 342Combined sources3
Beta strandi349 – 352Combined sources4
Helixi353 – 360Combined sources8
Helixi361 – 363Combined sources3
Helixi368 – 371Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CVIX-ray3.20A/B/C/D33-374[»]
1ND5X-ray2.90A/B/C/D33-386[»]
1ND6X-ray2.40A/B/C/D33-386[»]
2HPAX-ray2.90A/B/C/D33-374[»]
2L3HNMR-A248-286[»]
2L77NMR-A248-286[»]
2L79NMR-A248-286[»]
2MG0NMR-A262-270[»]
3PPDX-ray1.50A260-265[»]
DisProtiDP00628
ProteinModelPortaliP15309
SMRiP15309
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP15309

Family & Domainsi

Sequence similaritiesi

Belongs to the histidine acid phosphatase family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3720 Eukaryota
ENOG410ZVBQ LUCA
GeneTreeiENSGT00530000062956
HOGENOMiHOG000231439
HOVERGENiHBG002203
InParanoidiP15309
KOiK19283
OMAiYGIHKQK
OrthoDBiEOG091G09FA
PhylomeDBiP15309
TreeFamiTF312893

Family and domain databases

CDDicd07061 HP_HAP_like, 1 hit
Gene3Di3.40.50.1240, 1 hit
InterProiView protein in InterPro
IPR033379 Acid_Pase_AS
IPR000560 His_Pase_clade-2
IPR029033 His_PPase_superfam
PfamiView protein in Pfam
PF00328 His_Phos_2, 1 hit
SUPFAMiSSF53254 SSF53254, 1 hit
PROSITEiView protein in PROSITE
PS00616 HIS_ACID_PHOSPHAT_1, 1 hit
PS00778 HIS_ACID_PHOSPHAT_2, 1 hit

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P15309-1) [UniParc]FASTAAdd to basket
Also known as: Secreted PAP, sPAP

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.

« Hide

        10         20         30         40         50
MRAAPLLLAR AASLSLGFLF LLFFWLDRSV LAKELKFVTL VFRHGDRSPI 
        60         70         80         90        100
DTFPTDPIKE SSWPQGFGQL TQLGMEQHYE LGEYIRKRYR KFLNESYKHE 
       110        120        130        140        150
QVYIRSTDVD RTLMSAMTNL AALFPPEGVS IWNPILLWQP IPVHTVPLSE 
       160        170        180        190        200
DQLLYLPFRN CPRFQELESE TLKSEEFQKR LHPYKDFIAT LGKLSGLHGQ 
       210        220        230        240        250
DLFGIWSKVY DPLYCESVHN FTLPSWATED TMTKLRELSE LSLLSLYGIH 
       260        270        280        290        300
KQKEKSRLQG GVLVNEILNH MKRATQIPSY KKLIMYSAHD TTVSGLQMAL 
       310        320        330        340        350
DVYNGLLPPY ASCHLTELYF EKGEYFVEMY YRNETQHEPY PLMLPGCSPS 
       360        370        380 
CPLERFAELV GPVIPQDWST ECMTTNSHQG TEDSTD
Length:386
Mass (Da):44,566
Last modified:March 1, 1992 - v3
Checksum:iEF81E11DFAECADEA
GO
Isoform 2 (identifier: P15309-2) [UniParc]FASTAAdd to basket
Also known as: TMPase, TM-PAP, cellular PAP, cPAP

The sequence of this isoform differs from the canonical sequence as follows:
     380-386: GTEDSTD → VLKVIFAVAFCLISAVLMVLLFIHIRRGLCWQRESYGNI

Show »
Length:418
Mass (Da):48,336
Checksum:i68E1131197595362
GO
Isoform 3 (identifier: P15309-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     153-185: Missing.

Show »
Length:353
Mass (Da):40,443
Checksum:iC3E376122B63DA82
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti15 – 24SLGFLFLLFF → AFASCFCFFC in CAA37673 (PubMed:2395659).Curated10
Sequence conflicti15 – 24SLGFLFLLFF → ALASCFCFFC in AAA60022 (PubMed:2712834).Curated10
Sequence conflicti15 – 24SLGFLFLLFF → ALASCFCFFC in CAA36422 (PubMed:2842184).Curated10
Sequence conflicti46D → H in CAA37673 (PubMed:2395659).Curated1
Sequence conflicti66 – 73GFGQLTQL → RIWPTHPA in CAA37673 (PubMed:2395659).Curated8
Sequence conflicti66 – 73GFGQLTQL → WIWPTHPA in CAA36422 (PubMed:2842184).Curated8
Sequence conflicti95E → D in AAA60022 (PubMed:2712834).Curated1
Sequence conflicti116A → R in AAA60022 (PubMed:2712834).Curated1
Sequence conflicti139Q → E in CAA37673 (PubMed:2395659).Curated1
Sequence conflicti157P → R in CAA37673 (PubMed:2395659).Curated1
Sequence conflicti212P → A in CAA36422 (PubMed:2842184).Curated1
Sequence conflicti215C → S in AAA60022 (PubMed:2712834).Curated1
Sequence conflicti294S → T in AAA60022 (PubMed:2712834).Curated1
Sequence conflicti372C → V in AAA60022 (PubMed:2712834).Curated1
Sequence conflicti383D → N in CAA37673 (PubMed:2395659).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04796015S → N1 PublicationCorresponds to variant dbSNP:rs17850347Ensembl.1
Natural variantiVAR_047961124F → V1 PublicationCorresponds to variant dbSNP:rs17856254Ensembl.1
Natural variantiVAR_047962226W → R1 PublicationCorresponds to variant dbSNP:rs17856253Ensembl.1
Natural variantiVAR_047963330Y → H1 PublicationCorresponds to variant dbSNP:rs17851392Ensembl.1
Natural variantiVAR_047964360V → A1 PublicationCorresponds to variant dbSNP:rs17850198Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_053360153 – 185Missing in isoform 3. 2 PublicationsAdd BLAST33
Alternative sequenceiVSP_036023380 – 386GTEDSTD → VLKVIFAVAFCLISAVLMVL LFIHIRRGLCWQRESYGNI in isoform 2. 1 Publication7

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M97589
, M97580, M97581, M97582, M97583, M97584, M97585, M97586, M97587, M97588 Genomic DNA Translation: AAA60021.1
M34840 mRNA Translation: AAA69694.1
M24902 mRNA Translation: AAA60022.1
X52174 mRNA Translation: CAA36422.1
X53605 mRNA Translation: CAA37673.1
U07097
, U07083, U07085, U07086, U07088, U07091, U07092, U07093, U07095 Genomic DNA Translation: AAB60640.1
AB102888 mRNA Translation: BAD89417.1
AK300540 mRNA Translation: BAG62248.1
AC020633 Genomic DNA No translation available.
CH471052 Genomic DNA Translation: EAW79203.1
CH471052 Genomic DNA Translation: EAW79205.1
BC007460 mRNA Translation: AAH07460.1
BC008493 mRNA Translation: AAH08493.1
BC016344 mRNA Translation: AAH16344.1
CCDSiCCDS3073.1 [P15309-1]
CCDS46916.1 [P15309-2]
CCDS77818.1 [P15309-3]
PIRiJH0610
RefSeqiNP_001090.2, NM_001099.4 [P15309-1]
NP_001127666.1, NM_001134194.1 [P15309-2]
NP_001278966.1, NM_001292037.1 [P15309-3]
UniGeneiHs.433060

Genome annotation databases

EnsembliENST00000336375; ENSP00000337471; ENSG00000014257 [P15309-1]
ENST00000351273; ENSP00000323036; ENSG00000014257 [P15309-2]
ENST00000475741; ENSP00000417744; ENSG00000014257 [P15309-3]
GeneIDi55
KEGGihsa:55
UCSCiuc003eon.4 human [P15309-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPPAP_HUMAN
AccessioniPrimary (citable) accession number: P15309
Secondary accession number(s): D3DNC6
, Q5FBY0, Q96KY0, Q96QK9, Q96QM0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: March 1, 1992
Last modified: June 20, 2018
This is version 175 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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