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Q9NPH0 (PPA6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 110. 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·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Lysophosphatidic acid phosphatase type 6

EC=3.1.3.2
Alternative name(s):
Acid phosphatase 6, lysophosphatidic
Acid phosphatase-like protein 1
PACPL1
Gene names
Name:ACP6
Synonyms:ACPL1, LPAP
ORF Names:UNQ205/PRO231
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length428 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Hydrolyzes lysophosphatidic acid (LPA) containing a medium length fatty acid chain to the corresponding monoacylglycerol. Has highest activity with lysophosphatidic acid containing myristate (C14:0), monounsaturated oleate (C18:1) or palmitate (C16:0), and lower activity with C18:0 and C6:0 lysophosphatidic acid. Ref.1 Ref.10

Catalytic activity

A phosphate monoester + H2O = an alcohol + phosphate. Ref.10

Subunit structure

Monomer. Ref.10

Subcellular location

Mitochondrion Ref.1.

Tissue specificity

Highly expressed in kidney, heart, small intestine, muscle, liver, prostate, testis, ovary and weakly expressed in thymus and colon. Ref.1 Ref.2

Induction

Induced with the differentiation from myoblast to myotube. Ref.1

Sequence similarities

Belongs to the histidine acid phosphatase family.

Caution

It is uncertain whether Met-1 or Met-8 is the initiator.

Was originally (Ref.1) reported to be located in the mitochondrion, but the evidence seems to be weak and contradictory with the presence of a cleaved signal sequence.

Sequence caution

The sequence BAA89311.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAD92485.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processLipid metabolism
Phospholipid metabolism
   Cellular componentMitochondrion
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransit peptide
   Molecular functionHydrolase
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processlysobisphosphatidic acid metabolic process

Inferred from direct assay Ref.10. Source: UniProtKB

   Cellular_componentmitochondrion

Inferred from direct assay Ref.1. Source: UniProtKB

   Molecular_functionacid phosphatase activity

Inferred from electronic annotation. Source: UniProtKB-EC

lysophosphatidic acid phosphatase activity

Inferred from direct assay Ref.1Ref.10. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NPH0-1)

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.
Isoform 2 (identifier: Q9NPH0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     261-271: AHNLPSCPMLK → EKMGSCRFHGS
     272-428: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3232Mitochondrion Ref.9
Chain33 – 428396Lysophosphatidic acid phosphatase type 6
PRO_0000023965

Regions

Region58 – 168111Substrate binding By similarity

Sites

Active site591Nucleophile Ref.10
Active site3351Proton donor Probable

Natural variations

Alternative sequence261 – 27111AHNLPSCPMLK → EKMGSCRFHGS in isoform 2.
VSP_014121
Alternative sequence272 – 428157Missing in isoform 2.
VSP_014122
Natural variant3161V → M. Ref.1 Ref.2 Ref.3 Ref.4 Ref.7 Ref.8
Corresponds to variant rs6593795 [ dbSNP | Ensembl ].
VAR_022678

Experimental info

Mutagenesis581R → A: Abolishes enzyme activity. Ref.10
Mutagenesis591H → A: Abolishes enzyme activity. Ref.1 Ref.10
Mutagenesis621R → A: Abolishes enzyme activity. Ref.10
Mutagenesis1061Y → F: Decreases enzyme activity. Ref.10
Mutagenesis1101Y → F: Decreases enzyme activity.
Mutagenesis1681R → A: Abolishes enzyme activity. Ref.10
Mutagenesis2571A → F or L: Decreases enzyme activity by interfering with water access to the active site cavity. Ref.10
Mutagenesis2571A → W: Abolishes enzyme activity by interfering with water access to the active site cavity. Ref.10
Mutagenesis2851S → W: Decreases activity toward substrates with medium and long aliphatic chains, but not toward substrates with short aliphatic chains. Ref.10
Mutagenesis2891L → W: Decreases activity toward substrates with medium and long aliphatic chains, but not toward substrates with short aliphatic chains. Ref.10
Mutagenesis3341H → A: Abolishes enzyme activity. Ref.10
Mutagenesis3351D → A: Abolishes enzyme activity. Ref.10
Sequence conflict4281E → D in CAG33382. Ref.8

Secondary structure

.................................................................... 428
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 11, 2011. Version 2.
Checksum: 37A09CFD1BB45BFA

FASTA42848,854
        10         20         30         40         50         60 
MITGVFSMRL WTPVGVLTSL AYCLHQRRVA LAELQEADGQ CPVDRSLLKL KMVQVVFRHG 

        70         80         90        100        110        120 
ARSPLKPLPL EEQVEWNPQL LEVPPQTQFD YTVTNLAGGP KPYSPYDSQY HETTLKGGMF 

       130        140        150        160        170        180 
AGQLTKVGMQ QMFALGERLR KNYVEDIPFL SPTFNPQEVF IRSTNIFRNL ESTRCLLAGL 

       190        200        210        220        230        240 
FQCQKEGPII IHTDEADSEV LYPNYQSCWS LRQRTRGRRQ TASLQPGISE DLKKVKDRMG 

       250        260        270        280        290        300 
IDSSDKVDFF ILLDNVAAEQ AHNLPSCPML KRFARMIEQR AVDTSLYILP KEDRESLQMA 

       310        320        330        340        350        360 
VGPFLHILES NLLKAVDSAT APDKIRKLYL YAAHDVTFIP LLMTLGIFDH KWPPFAVDLT 

       370        380        390        400        410        420 
MELYQHLESK EWFVQLYYHG KEQVPRGCPD GLCPLDMFLN AMSVYTLSPE KYHALCSQTQ 


VMEVGNEE 

« Hide

Isoform 2 [UniParc].

Checksum: FF6FF0AFF8D01144
Show »

FASTA27130,790

References

« Hide 'large scale' references
[1]"Isolation of a cDNA encoding human lysophosphatidic acid phosphatase that is involved in the regulation of mitochondrial lipid biosynthesis."
Hiroyama M., Takenawa T.
J. Biol. Chem. 274:29172-29180(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, MUTAGENESIS OF HIS-59, INDUCTION, VARIANT MET-316.
Tissue: Brain.
[2]"Novel human and mouse genes encoding an acid phosphatase family member and its downregulation in W/W(V) mouse jejunum."
Takayama I., Daigo Y., Ward S.M., Sanders K.M., Walker R.L., Horowitz B., Yamanaka T., Fujino M.A.
Gut 50:790-796(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANT MET-316.
[3]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT MET-316.
[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] (ISOFORM 1), VARIANT MET-316.
[5]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Brain.
[6]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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] (ISOFORM 1), VARIANT MET-316.
Tissue: Cervix and Pancreas.
[8]"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] OF 8-428 (ISOFORM 1), VARIANT MET-316.
[9]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 33-47.
[10]"Crystal structures and biochemical studies of human lysophosphatidic acid phosphatase type 6."
Li J., Dong Y., Lu X., Wang L., Peng W., Zhang X.C., Rao Z.
Protein Cell 4:548-561(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.17 ANGSTROMS) OF 33-428 IN COMPLEXES WITH MALONATE AND TARTRATE, ACTIVE SITE, PROBABLE SUBSTRATE-BINDING SITES, CATALYTIC ACTIVITY, FUNCTION, SUBUNIT, MUTAGENESIS OF ARG-58; HIS-59; ARG-62; TYR-106; ARG-168; ALA-257; SER-285; LEU-289; HIS-334 AND ASP-335.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB031478 mRNA. Translation: BAA89311.1. Different initiation.
AB030039 mRNA. Translation: BAA94309.2.
AY358552 mRNA. Translation: AAQ88916.1.
AK000657 mRNA. Translation: BAA91310.1.
AB209248 mRNA. Translation: BAD92485.1. Different initiation.
AL359207 Genomic DNA. Translation: CAI15199.1.
BC009965 mRNA. Translation: AAH09965.1.
BC034686 mRNA. Translation: AAH34686.1.
CR457101 mRNA. Translation: CAG33382.1.
RefSeqNP_057445.4. NM_016361.4.
XP_005273020.1. XM_005272963.1.
XP_005277457.1. XM_005277400.1.
UniGeneHs.562154.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4JOBX-ray2.17A33-428[»]
4JOCX-ray2.21A33-428[»]
4JODX-ray2.21A33-428[»]
ProteinModelPortalQ9NPH0.
SMRQ9NPH0. Positions 42-419.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119378. 9 interactions.
IntActQ9NPH0. 2 interactions.
MINTMINT-1387194.
STRING9606.ENSP00000358241.

PTM databases

PhosphoSiteQ9NPH0.

Polymorphism databases

DMDM68052821.

Proteomic databases

PaxDbQ9NPH0.
PRIDEQ9NPH0.

Protocols and materials databases

DNASU51205.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000369238; ENSP00000358241; ENSG00000162836. [Q9NPH0-1]
ENST00000392988; ENSP00000376714; ENSG00000162836. [Q9NPH0-2]
GeneID51205.
KEGGhsa:51205.
UCSCuc001epr.2. human. [Q9NPH0-1]
uc009wjj.1. human. [Q9NPH0-2]

Organism-specific databases

CTD51205.
GeneCardsGC01M147119.
H-InvDBHIX0000989.
HGNCHGNC:29609. ACP6.
HPAHPA028560.
MIM611471. gene.
neXtProtNX_Q9NPH0.
PharmGKBPA134930830.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG235758.
HOGENOMHOG000290692.
HOVERGENHBG079458.
InParanoidQ9NPH0.
KOK14395.
OMAHDVTLMP.
OrthoDBEOG747PJ2.
PhylomeDBQ9NPH0.
TreeFamTF318821.

Gene expression databases

BgeeQ9NPH0.
CleanExHS_ACP6.
GenevestigatorQ9NPH0.

Family and domain databases

InterProIPR000560. His_Pase_superF_clade-2.
[Graphical view]
PfamPF00328. His_Phos_2. 1 hit.
[Graphical view]
PROSITEPS00616. HIS_ACID_PHOSPHAT_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiACP6.
NextBio54254.
PROQ9NPH0.
SOURCESearch...

Entry information

Entry namePPA6_HUMAN
AccessionPrimary (citable) accession number: Q9NPH0
Secondary accession number(s): Q59G61 expand/collapse secondary AC list , Q5T490, Q6IAQ3, Q7LG81, Q9UIG6
Entry history
Integrated into UniProtKB/Swiss-Prot: June 21, 2005
Last sequence update: January 11, 2011
Last modified: March 19, 2014
This is version 110 of the entry and version 2 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 1

Human chromosome 1: entries, gene names and cross-references to MIM