P13686 (PPA5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	325 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)

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 component	Lysosome
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal
Ligand	Iron Metal-binding
Molecular function	Hydrolase
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	riboflavin metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome integral to membrane Traceable author statement Ref.2. Source: ProtInc lysosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	acid 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 21

21

Ref.7 Ref.8 Ref.9 Ref.10

Chain

22 – 325

304

Tartrate-resistant acid phosphatase type 5

PRO_0000023981

Sites

Metal binding

33

1

Iron 1

Metal binding

71

1

Iron 1

Metal binding

71

1

Iron 2

Metal binding

74

1

Iron 1

Metal binding

110

1

Iron 2

Metal binding

205

1

Iron 2

Metal binding

240

1

Iron 2

Metal binding

242

1

Iron 1

Amino acid modifications

Glycosylation

116

1

N-linked (GlcNAc...) Ref.12

Glycosylation

147

1

N-linked (GlcNAc...) Potential

Disulfide bond

161 ↔ 219

By similarity

Natural variations

Natural variant

52

1

K → M in SPENCDI. Ref.14

VAR_065920

Natural variant

89

1

T → I in SPENCDI. Ref.13

VAR_065921

Natural variant

109

1

G → R in SPENCDI. Ref.14

VAR_065922

Natural variant

148

1

V → M. Ref.3
Corresponds to variant rs2305799 [ dbSNP | Ensembl ].

VAR_020602

Natural variant

200

1

V → M. Ref.3
Corresponds to variant rs2229531 [ dbSNP | Ensembl ].

VAR_020603

Natural variant

201

1

L → P in SPENCDI. Ref.14

VAR_065923

Natural variant

215

1

G → R in SPENCDI. Ref.13 Ref.14

VAR_065924

Natural variant

221

1

V → I.
Corresponds to variant rs2229532 [ dbSNP | Ensembl ].

VAR_029288

Natural variant

241

1

D → N in SPENCDI. Ref.13

VAR_065925

Natural variant

262

1

N → H in SPENCDI. Ref.14

VAR_065926

Natural variant

264

1

M → K in SPENCDI. Ref.13 Ref.14

VAR_065927

Natural variant

278

1

Missing in SPENCDI. Ref.14

VAR_065928

Experimental info

Sequence conflict

45 – 46

2

AR → GP in AAA76849. Ref.1

Sequence conflict

47

1

E → G AA sequence Ref.8

Sequence conflict

47

1

E → Q AA sequence Ref.7

Sequence conflict

50

1

N → W AA sequence Ref.7

Sequence conflict

177 – 180

4

DVKL → LT in AAA76849. Ref.1

Secondary structure

1

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325

Helix Strand Turn

Details...

Beta strand

26 – 31

6

Helix

45 – 61

17

Beta strand

64 – 68

5

Turn

74 – 76

3

Helix

85 – 89

5

Turn

90 – 93

4

Helix

97 – 100

4

Beta strand

104 – 106

3

Helix

110 – 113

4

Helix

117 – 122

6

Helix

123 – 125

3

Beta strand

128 – 131

4

Beta strand

134 – 142

9

Beta strand

149 – 154

6

Helix

157 – 161

5

Helix

164 – 166

3

Helix

178 – 194

17

Beta strand

198 – 203

6

Beta strand

211 – 214

4

Helix

218 – 223

6

Helix

225 – 230

6

Beta strand

235 – 238

4

Beta strand

240 – 248

9

Beta strand

254 – 258

5

Helix

271 – 273

3

Beta strand

279 – 283

5

Beta strand

291 – 297

7

Beta strand

299 – 308

10

Beta strand

313 – 320

8

Sequences

	Sequence		Length	Mass (Da)
	P13686 [UniParc]. Last modified December 21, 2004. Version 3. Checksum: 079174A71A5BA264	FASTA	325	36,599
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.

IPI

IPI00419240.

PIR

S15752.

RefSeq

NP_001104504.1. NM_001111034.1.
NP_001104505.1. NM_001111035.1.
NP_001104506.1. NM_001111036.1.
NP_001602.1. NM_001611.3.

UniGene

Hs.1211.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WAR	X-ray	2.22	A	22-325	[»]
2BQ8	X-ray	2.20	X	22-325	[»]

ProteinModelPortal

P13686.

ModBase

Search...

Protein-protein interaction databases

IntAct

P13686. 8 interactions.

MINT

MINT-1387442.

STRING

9606.ENSP00000218758.

PTM databases

PhosphoSite

P13686.

Polymorphism databases

DMDM

56757583.

Proteomic databases

PaxDb

P13686.

PRIDE

P13686.

Protocols and materials databases

DNASU

54.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000218758; ENSP00000218758; ENSG00000102575.
ENST00000412435; ENSP00000392374; ENSG00000102575.
ENST00000433365; ENSP00000413456; ENSG00000102575.
ENST00000592828; ENSP00000468767; ENSG00000102575.

GeneID

54.

KEGG

hsa:54.

UCSC

uc002msg.4. human.

Organism-specific databases

CTD

54.

GeneCards

GC19M011685.

HGNC

HGNC:124. ACP5.

HPA

CAB002584.

MIM

171640. gene.
607944. phenotype.

neXtProt

NX_P13686.

Orphanet

1855. Spondyloenchondrodysplasia.

PharmGKB

PA24448.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1409.

HOVERGEN

HBG000433.

InParanoid

P13686.

KO

K14379.

OMA

GEEMDIN.

OrthoDB

EOG4Z36FB.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

SABIO-RK

P13686.

Gene expression databases

Bgee

P13686.

CleanEx

HS_ACP5.

Genevestigator

P13686.

GermOnline

ENSG00000102575. Homo sapiens.

Family and domain databases

InterPro

IPR024927. Acid_Pase_5.
IPR004843. Metallo_PEstase_dom.
[Graphical view]

Pfam

PF00149. Metallophos. 1 hit.
[Graphical view]

PIRSF

PIRSF000898. Acid_Ptase_5. 1 hit.

ProtoNet

Search...

Other

ChiTaRS

ACP5. human.

EvolutionaryTrace

P13686.

GenomeRNAi

54.

NextBio

217.

PMAP-CutDB

P13686.

SOURCE

Search...

Entry information

Entry name

PPA5_HUMAN

Accession

Primary (citable) accession number: P13686
Secondary accession number(s): A8K3V2 , Q2TAB1, Q6IAS6, Q9UCJ5, Q9UCJ6, Q9UCJ7

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	December 21, 2004
Last modified:	May 1, 2013
This is version 137 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.