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P13686 (PPA5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tartrate-resistant acid phosphatase type 5

Short name=TR-AP
EC=3.1.3.2
Alternative name(s):
Tartrate-resistant acid ATPase
Short name=TrATPase
Type 5 acid phosphatase
Gene names
Name:ACP5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length325 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in osteopontin/bone sialoprotein dephosphorylation. Its expression seems to increase in certain pathological states such as Gaucher and Hodgkin diseases, the hairy cell, the B-cell, and the T-cell leukemias.

Catalytic activity

A phosphate monoester + H2O = an alcohol + phosphate.

Cofactor

Binds 2 iron ions per subunit.

Subunit structure

Exists either as monomer or, after proteolytic processing, as a dimer of two chains linked by disulfide bond(s). Ref.8 Ref.11

Subcellular location

Lysosome.

Involvement in disease

Spondyloenchondrodysplasia with immune dysregulation (SPENCDI) [MIM:607944]: A disease characterized by vertebral and metaphyseal dysplasia, spasticity with cerebral calcifications, and strong predisposition to autoimmune diseases. The skeletal dysplasia is characterized by radiolucent and irregular spondylar and metaphyseal lesions that represent islands of chondroid tissue within bone.
Note: The disease is caused by mutations affecting the gene represented in this entry. ACP5 inactivating mutations result in a functional excess of phosphorylated osteopontin causing deregulation of osteopontin signaling and consequential autoimmune disease. Ref.13 Ref.14

Sequence similarities

Belongs to the metallophosphoesterase superfamily. Purple acid phosphatase family.

Ontologies

Keywords
   Cellular componentLysosome
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainSignal
   LigandIron
Metal-binding
   Molecular functionHydrolase
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processbone morphogenesis

Inferred from electronic annotation. Source: Ensembl

bone resorption

Inferred from electronic annotation. Source: Ensembl

defense response to Gram-positive bacterium

Inferred from electronic annotation. Source: Ensembl

negative regulation of inflammatory response

Inferred from electronic annotation. Source: Ensembl

negative regulation of interleukin-1 beta production

Inferred from electronic annotation. Source: Ensembl

negative regulation of interleukin-12 production

Inferred from electronic annotation. Source: Ensembl

negative regulation of nitric oxide biosynthetic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of superoxide anion generation

Inferred from electronic annotation. Source: Ensembl

negative regulation of tumor necrosis factor production

Inferred from electronic annotation. Source: Ensembl

response to cytokine

Inferred from electronic annotation. Source: Ensembl

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

riboflavin metabolic process

Traceable author statement. Source: Reactome

small molecule metabolic process

Traceable author statement. Source: Reactome

vitamin metabolic process

Traceable author statement. Source: Reactome

water-soluble vitamin metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

integral component of membrane

Traceable author statement Ref.2. Source: ProtInc

lysosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionacid phosphatase activity

Traceable author statement. Source: Reactome

ferric iron binding

Inferred from direct assay Ref.12. Source: UniProtKB

ferrous iron binding

Inferred from direct assay Ref.12. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Ref.7 Ref.8 Ref.9 Ref.10
Chain22 – 325304Tartrate-resistant acid phosphatase type 5
PRO_0000023981

Sites

Metal binding331Iron 1
Metal binding711Iron 1
Metal binding711Iron 2
Metal binding741Iron 1
Metal binding1101Iron 2
Metal binding2051Iron 2
Metal binding2401Iron 2
Metal binding2421Iron 1

Amino acid modifications

Glycosylation1161N-linked (GlcNAc...) Ref.12
Glycosylation1471N-linked (GlcNAc...) Potential
Disulfide bond161 ↔ 219 By similarity

Natural variations

Natural variant521K → M in SPENCDI. Ref.14
VAR_065920
Natural variant891T → I in SPENCDI. Ref.13
VAR_065921
Natural variant1091G → R in SPENCDI. Ref.14
VAR_065922
Natural variant1481V → M. Ref.3
Corresponds to variant rs2305799 [ dbSNP | Ensembl ].
VAR_020602
Natural variant2001V → M. Ref.3
Corresponds to variant rs2229531 [ dbSNP | Ensembl ].
VAR_020603
Natural variant2011L → P in SPENCDI. Ref.14
VAR_065923
Natural variant2151G → R in SPENCDI. Ref.13 Ref.14
VAR_065924
Natural variant2211V → I.
Corresponds to variant rs2229532 [ dbSNP | Ensembl ].
VAR_029288
Natural variant2411D → N in SPENCDI. Ref.13
VAR_065925
Natural variant2621N → H in SPENCDI. Ref.14
VAR_065926
Natural variant2641M → K in SPENCDI. Ref.13 Ref.14
VAR_065927
Natural variant2781Missing in SPENCDI. Ref.14
VAR_065928

Experimental info

Sequence conflict45 – 462AR → GP in AAA76849. Ref.1
Sequence conflict471E → G AA sequence Ref.8
Sequence conflict471E → Q AA sequence Ref.7
Sequence conflict501N → W AA sequence Ref.7
Sequence conflict177 – 1804DVKL → LT in AAA76849. Ref.1

Secondary structure

......................................................... 325
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P13686 [UniParc].

Last modified December 21, 2004. Version 3.
Checksum: 079174A71A5BA264

FASTA32536,599
        10         20         30         40         50         60 
MDMWTALLIL QALLLPSLAD GATPALRFVA VGDWGGVPNA PFHTAREMAN AKEIARTVQI 

        70         80         90        100        110        120 
LGADFILSLG DNFYFTGVQD INDKRFQETF EDVFSDRSLR KVPWYVLAGN HDHLGNVSAQ 

       130        140        150        160        170        180 
IAYSKISKRW NFPSPFYRLH FKIPQTNVSV AIFMLDTVTL CGNSDDFLSQ QPERPRDVKL 

       190        200        210        220        230        240 
ARTQLSWLKK QLAAAREDYV LVAGHYPVWS IAEHGPTHCL VKQLRPLLAT YGVTAYLCGH 

       250        260        270        280        290        300 
DHNLQYLQDE NGVGYVLSGA GNFMDPSKRH QRKVPNGYLR FHYGTEDSLG GFAYVEISSK 

       310        320 
EMTVTYIEAS GKSLFKTRLP RRARP 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of the type 5, iron-containing, tartrate-resistant acid phosphatase from human placenta."
Ketcham C.M., Roberts R.M., Simmen R.C.M., Nick H.S.
J. Biol. Chem. 264:557-563(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Placenta.
[2]"Type 5 acid phosphatase. Sequence, expression and chromosomal localization of a differentiation-associated protein of the human macrophage."
Lord D.K., Cross N.C.P., Bevilacqua M.A., Roder S.H., Gorman P.A., Groves A.V., Moss D.W., Sheer D., Cox T.M.
Eur. J. Biochem. 189:287-293(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Placenta.
[3]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS MET-148 AND MET-200.
[4]"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. expand/collapse author list , 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].
Tissue: Lung.
[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].
Tissue: Brain and Skin.
[6]"Isolation and characterization of the genes encoding mouse and human type-5 acid phosphatase."
Cassady A.I., King A.G., Cross N.C.P., Hume D.A.
Gene 130:201-207(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-245.
[7]"Purification and characterization of a tartrate-resistant acid phosphatase from human osteoclastomas."
Hayman A.R., Warburton M.J., Pringle J.A.S., Coles B., Chambers T.J.
Biochem. J. 261:601-609(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 22-64 AND 183-202.
Tissue: Osteoclastoma.
[8]"Heterogeneity of hairy cell tartrate-resistant acid phosphatase."
Janckila A.J., Latham M.D., Lam K.-W., Chow K.-C., Li C.-Y., Yam L.T.
Clin. Biochem. 25:437-443(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 22-55 AND 183-203, SUBUNIT.
Tissue: Spleen.
[9]"Purification and N-terminal sequence of two tartrate-resistant acid phosphatases type-5 from the hairy cell leukemia spleen."
Stepan J.J., Lau K.H.W., Mohan S., Kraenzlin M., Baylink D.J.
Biochem. Biophys. Res. Commun. 165:1027-1034(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 22-37.
Tissue: Osteoclastoma.
[10]"Purification and N-terminal amino acid sequence of the tartrate-resistant acid phosphatase from human osteoclastoma: evidence for a single structure."
Stepan J.J., Lau K.H.W., Mohan S., Singer F.R., Baylink D.J.
Biochem. Biophys. Res. Commun. 168:792-800(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 22-31.
Tissue: Osteoclastoma.
[11]"Tartrate-resistant acid phosphatase from human osteoclastomas is translated as a single polypeptide."
Hayman A.R., Dryden A.J., Chambers T.J., Warburton M.J.
Biochem. J. 277:631-634(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[12]"Crystal structures of recombinant human purple acid phosphatase with and without an inhibitory conformation of the repression loop."
Straeter N., Jasper B., Scholte M., Krebs B., Duff A.P., Langley D.B., Han R., Averill B.A., Freeman H.C., Guss J.M.
J. Mol. Biol. 351:233-246(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 22-325 IN COMPLEX WITH IRON IONS, GLYCOSYLATION AT ASN-116.
[13]"Tartrate-resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature."
Briggs T.A., Rice G.I., Daly S., Urquhart J., Gornall H., Bader-Meunier B., Baskar K., Baskar S., Baudouin V., Beresford M.W., Black G.C., Dearman R.J., de Zegher F., Foster E.S., Frances C., Hayman A.R., Hilton E., Job-Deslandre C. expand/collapse author list , Kulkarni M.L., Le Merrer M., Linglart A., Lovell S.C., Maurer K., Musset L., Navarro V., Picard C., Puel A., Rieux-Laucat F., Roifman C.M., Scholl-Burgi S., Smith N., Szynkiewicz M., Wiedeman A., Wouters C., Zeef L.A., Casanova J.L., Elkon K.B., Janckila A., Lebon P., Crow Y.J.
Nat. Genet. 43:127-131(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SPENCDI ILE-89; ARG-215; ASN-241 AND LYS-264.
[14]"Genetic deficiency of tartrate-resistant acid phosphatase associated with skeletal dysplasia, cerebral calcifications and autoimmunity."
Lausch E., Janecke A., Bros M., Trojandt S., Alanay Y., De Laet C., Hubner C.A., Meinecke P., Nishimura G., Matsuo M., Hirano Y., Tenoutasse S., Kiss A., Rosa R.F., Unger S.L., Renella R., Bonafe L., Spranger J. expand/collapse author list , Unger S., Zabel B., Superti-Furga A.
Nat. Genet. 43:132-137(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SPENCDI MET-52; ARG-109; PRO-201; ARG-215; HIS-262; LYS-264 AND TYR-278 DEL.
+Additional computationally mapped references.

Web resources

Wikipedia

Tartrate-resistant acid phosphatase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J04430 mRNA. Translation: AAA76849.1.
X14618 mRNA. Translation: CAA32771.1.
CR457078 mRNA. Translation: CAG33359.1.
AK290717 mRNA. Translation: BAF83406.1.
BC025414 mRNA. Translation: AAH25414.1.
BC111014 mRNA. Translation: AAI11015.1.
X67123 Genomic DNA. No translation available.
CCDSCCDS12265.1.
PIRS15752.
RefSeqNP_001104504.1. NM_001111034.1.
NP_001104505.1. NM_001111035.1.
NP_001104506.1. NM_001111036.1.
NP_001602.1. NM_001611.3.
XP_005259995.1. XM_005259938.1.
XP_005259996.1. XM_005259939.2.
UniGeneHs.1211.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1WARX-ray2.22A22-325[»]
2BQ8X-ray2.20X22-325[»]
ProteinModelPortalP13686.
SMRP13686. Positions 22-325.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106570. 8 interactions.
IntActP13686. 9 interactions.
MINTMINT-1387442.
STRING9606.ENSP00000218758.

PTM databases

PhosphoSiteP13686.

Polymorphism databases

DMDM56757583.

Proteomic databases

PaxDbP13686.
PRIDEP13686.

Protocols and materials databases

DNASU54.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000218758; ENSP00000218758; ENSG00000102575.
ENST00000412435; ENSP00000392374; ENSG00000102575.
ENST00000433365; ENSP00000413456; ENSG00000102575.
ENST00000592828; ENSP00000468767; ENSG00000102575.
GeneID54.
KEGGhsa:54.
UCSCuc002msg.4. human.

Organism-specific databases

CTD54.
GeneCardsGC19M011685.
HGNCHGNC:124. ACP5.
HPACAB002584.
MIM171640. gene.
607944. phenotype.
neXtProtNX_P13686.
Orphanet1855. Spondyloenchondrodysplasia.
PharmGKBPA24448.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1409.
HOVERGENHBG000433.
InParanoidP13686.
KOK14379.
OMAGEEMDIN.
OrthoDBEOG7WHH9R.
PhylomeDBP13686.
TreeFamTF313175.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
SABIO-RKP13686.

Gene expression databases

ArrayExpressP13686.
BgeeP13686.
CleanExHS_ACP5.
GenevestigatorP13686.

Family and domain databases

Gene3D3.60.21.10. 1 hit.
InterProIPR024927. Acid_Pase_5.
IPR004843. Calcineurin-like_PHP_apaH.
IPR029052. Metallo-depent_PP-like.
[Graphical view]
PfamPF00149. Metallophos. 1 hit.
[Graphical view]
PIRSFPIRSF000898. Acid_Ptase_5. 1 hit.
SUPFAMSSF56300. SSF56300. 1 hit.
ProtoNetSearch...

Other

ChiTaRSACP5. human.
EvolutionaryTraceP13686.
GeneWikiTartrate-resistant_acid_phosphatase.
GenomeRNAi54.
NextBio217.
PMAP-CutDBP13686.
PROP13686.
SOURCESearch...

Entry information

Entry namePPA5_HUMAN
AccessionPrimary (citable) accession number: P13686
Secondary accession number(s): A8K3V2 expand/collapse secondary AC list , Q2TAB1, Q6IAS6, Q9UCJ5, Q9UCJ6, Q9UCJ7
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: December 21, 2004
Last modified: July 9, 2014
This is version 147 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM