LHPP_HUMAN
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 03-AUG-2022, entry version 150.
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; 36.
DR IntAct; Q9H008; 1.
DR STRING; 9606.ENSP00000357835; -.
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; Q9H008; -.
DR PeptideAtlas; Q9H008; -.
DR PRIDE; Q9H008; -.
DR ProteomicsDB; 80192; -. [Q9H008-1]
DR ProteomicsDB; 80193; -. [Q9H008-2]
DR Antibodypedia; 1952; 131 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 CTD; 64077; -.
DR DisGeNET; 64077; -.
DR GeneCards; LHPP; -.
DR HGNC; HGNC:30042; LHPP.
DR HPA; ENSG00000107902; Tissue enhanced (brain, choroid plexus).
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; 982374at2759; -.
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; 4 hits in 1084 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 136 other tissues.
DR ExpressionAtlas; Q9H008; baseline and differential.
DR Genevisible; Q9H008; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0004427; F:inorganic diphosphatase 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; -; 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 Pfam; PF13344; Hydrolase_6; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR TIGRFAMs; TIGR01460; HAD-SF-IIA; 1.
DR TIGRFAMs; TIGR01458; HAD-SF-IIA-hyp3; 1.
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
