PPAT_HUMAN
ID PPAT_HUMAN Reviewed; 426 AA.
AC Q9BZG2; C0H3P7; Q9BZG3; Q9BZG4;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Testicular acid phosphatase {ECO:0000305};
DE EC=3.1.3.2;
DE AltName: Full=Acid phosphatase 4 {ECO:0000312|HGNC:HGNC:14376};
DE Flags: Precursor;
GN Name=ACP4 {ECO:0000312|HGNC:HGNC:14376};
GN Synonyms=ACPT {ECO:0000303|PubMed:11414767, ECO:0000312|HGNC:HGNC:14376};
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 [GENOMIC DNA] (ISOFORMS 1; 2 AND 3), INDUCTION, AND
RP TISSUE SPECIFICITY.
RX PubMed=11414767; DOI=10.1006/geno.2001.6556;
RA Yousef G.M., Diamandis M., Jung K., Diamandis E.P.;
RT "Molecular cloning of a novel human acid phosphatase gene (ACPT) that is
RT highly expressed in the testis.";
RL Genomics 74:385-395(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, AND GLYCOSYLATION.
RC TISSUE=Testis;
RX PubMed=15219672; DOI=10.1016/j.neuroscience.2004.04.060;
RA Fleisig H., El-Din El-Husseini A., Vincent S.R.;
RT "Regulation of ErbB4 phosphorylation and cleavage by a novel histidine acid
RT phosphatase.";
RL Neuroscience 127:91-100(2004).
RN [3]
RP INVOLVEMENT IN AI1J, VARIANTS AI1J CYS-76; CYS-111; PRO-128; LYS-133 AND
RP LEU-238, AND FUNCTION.
RX PubMed=27843125; DOI=10.1016/j.ajhg.2016.09.018;
RA Seymen F., Kim Y.J., Lee Y.J., Kang J., Kim T.H., Choi H., Koruyucu M.,
RA Kasimoglu Y., Tuna E.B., Gencay K., Shin T.J., Hyun H.K., Kim Y.J.,
RA Lee S.H., Lee Z.H., Zhang H., Hu J.C., Simmer J.P., Cho E.S., Kim J.W.;
RT "Recessive mutations in ACPT, encoding testicular acid phosphatase, cause
RT hypoplastic amelogenesis imperfecta.";
RL Am. J. Hum. Genet. 99:1199-1205(2016).
CC -!- FUNCTION: May dephosphorylate receptor tyrosine-protein kinase ERBB4
CC and inhibits its ligand-induced proteolytic cleavage (PubMed:15219672).
CC May play a role in odontogenesis (PubMed:27843125).
CC {ECO:0000269|PubMed:15219672, ECO:0000269|PubMed:27843125}.
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 -!- SUBUNIT: Homodimer. {ECO:0000305|PubMed:15219672}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass type I
CC membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9BZG2-1; Sequence=Displayed;
CC Name=2; Synonyms=Variant 3;
CC IsoId=Q9BZG2-2; Sequence=VSP_021494;
CC Name=3; Synonyms=Truncated variant 1, Truncated variant 2;
CC IsoId=Q9BZG2-3; Sequence=VSP_021493, VSP_021495;
CC -!- TISSUE SPECIFICITY: Expressed mainly in the testis. Also expressed in
CC the brain where they are enriched at the postsynaptic sites. Expressed
CC at lower levels in the trachea, prostate, bone marrow, spinal cord,
CC colon, fetal brain, heart, thymus, fetal liver, spleen, leukocytes,
CC ovary, small intestine, pancreas and skeletal muscle. Expression is
CC significantly lower in testicular cancer tissues than in normal
CC testicular tissues. Isoform 3 is expressed in the testis, trachea,
CC prostate and bone marrow. {ECO:0000269|PubMed:11414767}.
CC -!- INDUCTION: Up-regulated by mibolerone (a synthetic androgen) and
CC dihydrotestosterone (DHT) and is down-regulated by estrogen and
CC progestin. {ECO:0000269|PubMed:11414767}.
CC -!- PTM: Glycosylated. {ECO:0000305|PubMed:15219672}.
CC -!- DISEASE: Amelogenesis imperfecta 1J (AI1J) [MIM:617297]: A form of
CC amelogenesis imperfecta, a disorder characterized by defective enamel
CC formation. The enamel may be hypoplastic, hypomineralized or both, and
CC affected teeth may be discoloured, sensitive or prone to
CC disintegration. AI1J is an autosomal recessive form characterized by
CC hypoplastic enamel, enamel discolorization ranging from yellow to
CC black, and normal dentin. {ECO:0000269|PubMed:27843125}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the histidine acid phosphatase family.
CC {ECO:0000305}.
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DR EMBL; AF321918; AAK09393.1; -; Genomic_DNA.
DR EMBL; AF321918; AAK09394.1; -; Genomic_DNA.
DR EMBL; AF321918; AAK09395.1; -; Genomic_DNA.
DR EMBL; AF321918; AAK09396.1; -; Genomic_DNA.
DR CCDS; CCDS12802.1; -. [Q9BZG2-1]
DR RefSeq; NP_149059.1; NM_033068.2. [Q9BZG2-1]
DR AlphaFoldDB; Q9BZG2; -.
DR SMR; Q9BZG2; -.
DR BioGRID; 125045; 124.
DR STRING; 9606.ENSP00000270593; -.
DR DEPOD; ACP4; -.
DR GlyGen; Q9BZG2; 4 sites.
DR iPTMnet; Q9BZG2; -.
DR PhosphoSitePlus; Q9BZG2; -.
DR BioMuta; ACP4; -.
DR DMDM; 74717749; -.
DR MassIVE; Q9BZG2; -.
DR PaxDb; Q9BZG2; -.
DR PeptideAtlas; Q9BZG2; -.
DR PRIDE; Q9BZG2; -.
DR ProteomicsDB; 79839; -. [Q9BZG2-1]
DR TopDownProteomics; Q9BZG2-2; -. [Q9BZG2-2]
DR Antibodypedia; 32366; 81 antibodies from 20 providers.
DR DNASU; 93650; -.
DR Ensembl; ENST00000270593.2; ENSP00000270593.1; ENSG00000142513.6. [Q9BZG2-1]
DR GeneID; 93650; -.
DR KEGG; hsa:93650; -.
DR MANE-Select; ENST00000270593.2; ENSP00000270593.1; NM_033068.3; NP_149059.1.
DR UCSC; uc002pta.1; human. [Q9BZG2-1]
DR CTD; 93650; -.
DR DisGeNET; 93650; -.
DR GeneCards; ACP4; -.
DR HGNC; HGNC:14376; ACP4.
DR HPA; ENSG00000142513; Tissue enhanced (skin, testis).
DR MalaCards; ACP4; -.
DR MIM; 606362; gene.
DR MIM; 617297; phenotype.
DR neXtProt; NX_Q9BZG2; -.
DR OpenTargets; ENSG00000142513; -.
DR Orphanet; 100031; Hypoplastic amelogenesis imperfecta.
DR PharmGKB; PA24450; -.
DR VEuPathDB; HostDB:ENSG00000142513; -.
DR eggNOG; KOG3720; Eukaryota.
DR GeneTree; ENSGT00940000161433; -.
DR HOGENOM; CLU_030431_1_1_1; -.
DR InParanoid; Q9BZG2; -.
DR OMA; PCHGSRE; -.
DR OrthoDB; 1221585at2759; -.
DR PhylomeDB; Q9BZG2; -.
DR TreeFam; TF312893; -.
DR PathwayCommons; Q9BZG2; -.
DR BioGRID-ORCS; 93650; 19 hits in 1071 CRISPR screens.
DR GenomeRNAi; 93650; -.
DR Pharos; Q9BZG2; Tbio.
DR PRO; PR:Q9BZG2; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9BZG2; protein.
DR Bgee; ENSG00000142513; Expressed in tendon of biceps brachii and 75 other tissues.
DR Genevisible; Q9BZG2; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005764; C:lysosome; IBA:GO_Central.
DR GO; GO:0045211; C:postsynaptic membrane; IBA:GO_Central.
DR GO; GO:0003993; F:acid phosphatase activity; IBA:GO_Central.
DR GO; GO:0016791; F:phosphatase activity; IBA:GO_Central.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IDA:UniProtKB.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IDA:UniProtKB.
DR GO; GO:0016311; P:dephosphorylation; IBA:GO_Central.
DR GO; GO:0007040; P:lysosome organization; IBA:GO_Central.
DR GO; GO:0120154; P:negative regulation of ERBB4 signaling pathway; IDA:UniProtKB.
DR GO; GO:0010977; P:negative regulation of neuron projection development; IDA:UniProtKB.
DR GO; GO:0010955; P:negative regulation of protein processing; IMP:UniProtKB.
DR GO; GO:0042476; P:odontogenesis; IMP:UniProtKB.
DR GO; GO:1990264; P:peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity; IDA:UniProtKB.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; IDA:UniProtKB.
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; Amelogenesis imperfecta; Disease variant;
KW Disulfide bond; Glycoprotein; Hydrolase; Membrane; Reference proteome;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..426
FT /note="Testicular acid phosphatase"
FT /id="PRO_0000259643"
FT TOPO_DOM 27..393
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 394..414
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 415..426
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ACT_SITE 41
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P15309"
FT ACT_SITE 289
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P15309"
FT CARBOHYD 191
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 269
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 330
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 339
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 159..378
FT /evidence="ECO:0000250|UniProtKB:P15309"
FT DISULFID 214..312
FT /evidence="ECO:0000250|UniProtKB:P15309"
FT DISULFID 353..357
FT /evidence="ECO:0000250|UniProtKB:P15309"
FT VAR_SEQ 39..92
FT /note="FRHGDRAPLASYPMDPHKEVASTLWPRGLGQLTTEGVRQQLELGRFLRSRYE
FT AF -> RRPHPGLPLAPPGLALTSPVPRYSAMATGPRWPPTPWTHTRRWPPPCGHEAWA
FT S (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_021493"
FT VAR_SEQ 91..183
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_021494"
FT VAR_SEQ 93..426
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_021495"
FT VARIANT 76
FT /note="R -> C (in AI1J; dbSNP:rs1057519277 and
FT dbSNP:rs902112287)"
FT /evidence="ECO:0000269|PubMed:27843125"
FT /id="VAR_078014"
FT VARIANT 111
FT /note="R -> C (in AI1J; dbSNP:rs202073531)"
FT /evidence="ECO:0000269|PubMed:27843125"
FT /id="VAR_078015"
FT VARIANT 128
FT /note="A -> P (in AI1J; unknown pathological significance;
FT dbSNP:rs767907487)"
FT /evidence="ECO:0000269|PubMed:27843125"
FT /id="VAR_078016"
FT VARIANT 133
FT /note="E -> K (in AI1J; unknown pathological significance;
FT dbSNP:rs779823931)"
FT /evidence="ECO:0000269|PubMed:27843125"
FT /id="VAR_078017"
FT VARIANT 238
FT /note="S -> L (in AI1J; dbSNP:rs763573828)"
FT /evidence="ECO:0000269|PubMed:27843125"
FT /id="VAR_078018"
SQ SEQUENCE 426 AA; 46090 MW; BE930398041DB061 CRC64;
MAGLGFWGHP AGPLLLLLLL VLPPRALPEG PLVFVALVFR HGDRAPLASY PMDPHKEVAS
TLWPRGLGQL TTEGVRQQLE LGRFLRSRYE AFLSPEYRRE EVYIRSTDFD RTLESAQANL
AGLFPEAAPG SPEARWRPIP VHTVPVAEDK LLRFPMRSCP RYHELLREAT EAAEYQEALE
GWTGFLSRLE NFTGLSLVGE PLRRAWKVLD TLMCQQAHGL PLPAWASPDV LRTLAQISAL
DIGAHVGPPR AAEKAQLTGG ILLNAILANF SRVQRLGLPL KMVMYSAHDS TLLALQGALG
LYDGHTPPYA ACLGFEFRKH LGNPAKDGGN VTVSLFYRND SAHLPLPLSL PGCPAPCPLG
RFYQLTAPAR PPAHGVSCHG PYEAAIPPAP VVPLLAGAVA VLVALSLGLG LLAWRPGCLR
ALGGPV
