ID   LHPP_HUMAN              Reviewed;         270 AA.
AC   Q9H008; B3KP20; Q2TBE9; Q5VUV9; Q5VUW0;
DT   02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT   02-OCT-2007, sequence version 2.
DT   24-JAN-2024, entry version 157.
DE   RecName: Full=Phospholysine phosphohistidine inorganic pyrophosphate phosphatase;
DE            Short=hLHPP;
DE            EC=3.1.3.-;
DE            EC=3.6.1.1;
GN   Name=LHPP;
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 [MRNA] (ISOFORM 1), SUBUNIT, CATALYTIC ACTIVITY,
RP   COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, AND VARIANT
RP   ARG-94.
RC   TISSUE=Cervix carcinoma;
RX   PubMed=12801912; DOI=10.1093/jb/mvg078;
RA   Yokoi F., Hiraishi H., Izuhara K.;
RT   "Molecular cloning of a cDNA for the human phospholysine phosphohistidine
RT   inorganic pyrophosphate phosphatase.";
RL   J. Biochem. 133:607-614(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-94.
RC   TISSUE=Heart;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164054; DOI=10.1038/nature02462;
RA   Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA   Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA   Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA   Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA   Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA   Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA   Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA   Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA   Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA   Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA   Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA   Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA   McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA   Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA   Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA   Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA   Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA   Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA   Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA   Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA   Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 10.";
RL   Nature 429:375-381(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP   ARG-94.
RC   TISSUE=Brain;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=16430861; DOI=10.1016/j.bbrc.2006.01.016;
RA   Koike E., Toda S., Yokoi F., Izuhara K., Koike N., Itoh K., Miyazaki K.,
RA   Sugihara H.;
RT   "Expression of new human inorganic pyrophosphatase in thyroid diseases: its
RT   intimate association with hyperthyroidism.";
RL   Biochem. Biophys. Res. Commun. 341:691-696(2006).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG AND
RP   MAGNESIUM IONS, AND COFACTOR.
RG   Structural genomics consortium (SGC);
RT   "Crystal structure of human phospholysine phosphohistidine inorganic
RT   pyrophosphate phosphatase LHPP.";
RL   Submitted (MAR-2010) to the PDB data bank.
CC   -!- FUNCTION: Phosphatase that hydrolyzes imidodiphosphate, 3-
CC       phosphohistidine and 6-phospholysine. Has broad substrate specificity
CC       and can also hydrolyze inorganic diphosphate, but with lower efficiency
CC       (By similarity). {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=diphosphate + H2O = H(+) + 2 phosphate; Xref=Rhea:RHEA:24576,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC         ChEBI:CHEBI:43474; EC=3.6.1.1;
CC         Evidence={ECO:0000269|PubMed:12801912};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:12801912, ECO:0000269|Ref.7};
CC       Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000269|PubMed:12801912,
CC       ECO:0000269|Ref.7};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 7.0 for PNP, and 5.5 for PPi.
CC         {ECO:0000269|PubMed:12801912};
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:12801912, ECO:0000269|Ref.7}.
CC   -!- INTERACTION:
CC       Q9H008; Q3MJ62: ZSCAN23; NbExp=3; IntAct=EBI-1059330, EBI-5667532;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16430861}. Nucleus
CC       {ECO:0000269|PubMed:16430861}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9H008-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9H008-2; Sequence=VSP_041685, VSP_041686;
CC   -!- TISSUE SPECIFICITY: Expressed in brain, and at lower levels in liver
CC       and kidney. Detected in thyroid (at protein level). Expressed in liver,
CC       kidney and moderately in brain. {ECO:0000269|PubMed:12801912,
CC       ECO:0000269|PubMed:16430861}.
CC   -!- SIMILARITY: Belongs to the HAD-like hydrolase superfamily.
CC       {ECO:0000305}.
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DR   EMBL; AB049629; BAB16411.1; -; mRNA.
DR   EMBL; AK055532; BAG51532.1; -; mRNA.
DR   EMBL; AL513190; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL391708; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL445237; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC110344; AAI10345.1; -; mRNA.
DR   EMBL; BC113629; AAI13630.1; -; mRNA.
DR   EMBL; BC113631; AAI13632.1; -; mRNA.
DR   CCDS; CCDS53587.1; -. [Q9H008-2]
DR   CCDS; CCDS7640.1; -. [Q9H008-1]
DR   RefSeq; NP_001161352.1; NM_001167880.1. [Q9H008-2]
DR   RefSeq; NP_001305260.1; NM_001318331.1.
DR   RefSeq; NP_001305261.1; NM_001318332.1.
DR   RefSeq; NP_071409.3; NM_022126.3. [Q9H008-1]
DR   PDB; 2X4D; X-ray; 1.92 A; A/B=1-270.
DR   PDBsum; 2X4D; -.
DR   AlphaFoldDB; Q9H008; -.
DR   SMR; Q9H008; -.
DR   BioGRID; 122044; 37.
DR   IntAct; Q9H008; 1.
DR   STRING; 9606.ENSP00000357835; -.
DR   ChEMBL; CHEMBL5169196; -.
DR   DEPOD; LHPP; -.
DR   iPTMnet; Q9H008; -.
DR   PhosphoSitePlus; Q9H008; -.
DR   BioMuta; LHPP; -.
DR   DMDM; 158705883; -.
DR   EPD; Q9H008; -.
DR   jPOST; Q9H008; -.
DR   MassIVE; Q9H008; -.
DR   MaxQB; Q9H008; -.
DR   PaxDb; 9606-ENSP00000357835; -.
DR   PeptideAtlas; Q9H008; -.
DR   ProteomicsDB; 80192; -. [Q9H008-1]
DR   ProteomicsDB; 80193; -. [Q9H008-2]
DR   Pumba; Q9H008; -.
DR   Antibodypedia; 1952; 149 antibodies from 23 providers.
DR   DNASU; 64077; -.
DR   Ensembl; ENST00000368839.1; ENSP00000357832.1; ENSG00000107902.14. [Q9H008-2]
DR   Ensembl; ENST00000368842.10; ENSP00000357835.5; ENSG00000107902.14. [Q9H008-1]
DR   GeneID; 64077; -.
DR   KEGG; hsa:64077; -.
DR   MANE-Select; ENST00000368842.10; ENSP00000357835.5; NM_022126.4; NP_071409.3.
DR   UCSC; uc001lhs.3; human. [Q9H008-1]
DR   AGR; HGNC:30042; -.
DR   CTD; 64077; -.
DR   DisGeNET; 64077; -.
DR   GeneCards; LHPP; -.
DR   HGNC; HGNC:30042; LHPP.
DR   HPA; ENSG00000107902; Tissue enriched (brain).
DR   MIM; 617231; gene.
DR   neXtProt; NX_Q9H008; -.
DR   OpenTargets; ENSG00000107902; -.
DR   PharmGKB; PA165548763; -.
DR   VEuPathDB; HostDB:ENSG00000107902; -.
DR   eggNOG; KOG3040; Eukaryota.
DR   GeneTree; ENSGT00940000159002; -.
DR   HOGENOM; CLU_043473_4_1_1; -.
DR   InParanoid; Q9H008; -.
DR   OMA; GPCIDVG; -.
DR   OrthoDB; 2876640at2759; -.
DR   PhylomeDB; Q9H008; -.
DR   TreeFam; TF314344; -.
DR   BRENDA; 3.9.1.3; 2681.
DR   PathwayCommons; Q9H008; -.
DR   Reactome; R-HSA-71737; Pyrophosphate hydrolysis.
DR   SignaLink; Q9H008; -.
DR   BioGRID-ORCS; 64077; 5 hits in 1174 CRISPR screens.
DR   ChiTaRS; LHPP; human.
DR   GenomeRNAi; 64077; -.
DR   Pharos; Q9H008; Tbio.
DR   PRO; PR:Q9H008; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   RNAct; Q9H008; Protein.
DR   Bgee; ENSG00000107902; Expressed in C1 segment of cervical spinal cord and 138 other cell types or tissues.
DR   ExpressionAtlas; Q9H008; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0004427; F:inorganic diphosphate phosphatase activity; IDA:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0016791; F:phosphatase activity; IBA:GO_Central.
DR   GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR   GO; GO:0016311; P:dephosphorylation; IEA:InterPro.
DR   GO; GO:0006796; P:phosphate-containing compound metabolic process; IDA:UniProtKB.
DR   CDD; cd07509; HAD_PPase; 1.
DR   Gene3D; 3.40.50.1000; HAD superfamily/HAD-like; 2.
DR   InterPro; IPR036412; HAD-like_sf.
DR   InterPro; IPR006357; HAD-SF_hydro_IIA.
DR   InterPro; IPR023214; HAD_sf.
DR   InterPro; IPR006355; LHPP/HDHD2.
DR   NCBIfam; TIGR01460; HAD-SF-IIA; 1.
DR   NCBIfam; TIGR01458; HAD-SF-IIA-hyp3; 1.
DR   PANTHER; PTHR19288; 4-NITROPHENYLPHOSPHATASE-RELATED; 1.
DR   PANTHER; PTHR19288:SF44; PHOSPHOLYSINE PHOSPHOHISTIDINE INORGANIC PYROPHOSPHATE PHOSPHATASE; 1.
DR   Pfam; PF13344; Hydrolase_6; 1.
DR   Pfam; PF13242; Hydrolase_like; 1.
DR   SFLD; SFLDG01129; C1.5:_HAD__Beta-PGM__Phosphata; 1.
DR   SFLD; SFLDG01139; C2.A:_Pyridoxal_Phosphate_Phos; 1.
DR   SFLD; SFLDS00003; Haloacid_Dehalogenase; 2.
DR   SUPFAM; SSF56784; HAD-like; 1.
DR   Genevisible; Q9H008; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cytoplasm; Hydrolase; Magnesium;
KW   Metal-binding; Nucleus; Reference proteome.
FT   CHAIN           1..270
FT                   /note="Phospholysine phosphohistidine inorganic
FT                   pyrophosphate phosphatase"
FT                   /id="PRO_0000305074"
FT   BINDING         17..19
FT                   /ligand="substrate"
FT   BINDING         17
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT   BINDING         19
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT   BINDING         54..55
FT                   /ligand="substrate"
FT   BINDING         189
FT                   /ligand="substrate"
FT   BINDING         214
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT   VAR_SEQ         210
FT                   /note="V -> Q (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_041685"
FT   VAR_SEQ         211..270
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_041686"
FT   VARIANT         94
FT                   /note="Q -> R (in dbSNP:rs6597801)"
FT                   /evidence="ECO:0000269|PubMed:12801912,
FT                   ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334"
FT                   /id="VAR_035163"
FT   CONFLICT        155
FT                   /note="K -> R (in Ref. 2; BAG51532)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        170
FT                   /note="G -> C (in Ref. 4; AAI10345)"
FT                   /evidence="ECO:0000305"
FT   HELIX           4..7
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   TURN            8..10
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   STRAND          13..16
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   TURN            19..21
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   STRAND          22..24
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   TURN            27..29
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   HELIX           36..45
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   STRAND          46..53
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   HELIX           61..70
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   HELIX           77..79
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   HELIX           83..94
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   STRAND          98..101
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   HELIX           104..110
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   STRAND          119..123
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   HELIX           127..129
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   HELIX           132..144
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   STRAND          150..153
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   STRAND          157..161
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   STRAND          164..167
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   HELIX           169..180
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   STRAND          185..188
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   HELIX           192..202
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   HELIX           206..208
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   STRAND          209..214
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   TURN            216..219
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   HELIX           220..225
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   STRAND          229..235
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   HELIX           240..244
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   STRAND          251..256
FT                   /evidence="ECO:0007829|PDB:2X4D"
FT   HELIX           257..267
FT                   /evidence="ECO:0007829|PDB:2X4D"
SQ   SEQUENCE   270 AA;  29165 MW;  09C301584453E79D CRC64;
     MAPWGKRLAG VRGVLLDISG VLYDSGAGGG TAIAGSVEAV ARLKRSRLKV RFCTNESQKS
     RAELVGQLQR LGFDISEQEV TAPAPAACQI LKEQGLRPYL LIHDGVRSEF DQIDTSNPNC
     VVIADAGESF SYQNMNNAFQ VLMELEKPVL ISLGKGRYYK ETSGLMLDVG PYMKALEYAC
     GIKAEVVGKP SPEFFKSALQ AIGVEAHQAV MIGDDIVGDV GGAQRCGMRA LQVRTGKFRP
     SDEHHPEVKA DGYVDNLAEA VDLLLQHADK
//