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Protein

Phospholysine phosphohistidine inorganic pyrophosphate phosphatase

Gene

LHPP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Phosphatase that hydrolyzes imidodiphosphate, 3-phosphohistidine and 6-phospholysine. Has broad substrate specificity and can also hydrolyze inorganic diphosphate, but with lower efficiency (By similarity).By similarity

Catalytic activityi

Diphosphate + H2O = 2 phosphate.1 Publication

Cofactori

Mg2+2 PublicationsNote: Binds 1 Mg2+ ion per subunit.2 Publications

pH dependencei

Optimum pH is 7.0 for PNP, and 5.5 for PPi.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi17 – 171Magnesium
Metal bindingi19 – 191Magnesium; via carbonyl oxygen
Binding sitei189 – 1891Substrate
Metal bindingi214 – 2141Magnesium

GO - Molecular functioni

  1. inorganic diphosphatase activity Source: UniProtKB
  2. magnesium ion binding Source: UniProtKB
  3. phosphohistidine phosphatase activity Source: UniProtKB
  4. protein homodimerization activity Source: UniProtKB

GO - Biological processi

  1. phosphate-containing compound metabolic process Source: UniProtKB
  2. protein dephosphorylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Magnesium, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (EC:3.1.3.-, EC:3.6.1.1)
Short name:
hLHPP
Gene namesi
Name:LHPP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 10

Organism-specific databases

HGNCiHGNC:30042. LHPP.

Subcellular locationi

Cytoplasm 1 Publication. Nucleus 1 Publication

GO - Cellular componenti

  1. cytoplasm Source: HPA
  2. cytosol Source: UniProtKB
  3. nucleoplasm Source: HPA
  4. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA165548763.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 270270Phospholysine phosphohistidine inorganic pyrophosphate phosphatasePRO_0000305074Add
BLAST

Proteomic databases

MaxQBiQ9H008.
PaxDbiQ9H008.
PRIDEiQ9H008.

PTM databases

DEPODiQ9H008.
PhosphoSiteiQ9H008.

Expressioni

Tissue specificityi

Expressed in brain, and at lower levels in liver and kidney. Detected in thyroid (at protein level). Expressed in liver, kidney and moderately in brain.2 Publications

Gene expression databases

BgeeiQ9H008.
ExpressionAtlasiQ9H008. baseline and differential.
GenevestigatoriQ9H008.

Organism-specific databases

HPAiHPA009163.
HPA009269.

Interactioni

Subunit structurei

Homodimer.2 Publications

Protein-protein interaction databases

BioGridi122044. 1 interaction.
STRINGi9606.ENSP00000357835.

Structurei

Secondary structure

1
270
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi4 – 74Combined sources
Turni8 – 103Combined sources
Beta strandi13 – 164Combined sources
Turni19 – 213Combined sources
Beta strandi22 – 243Combined sources
Turni27 – 293Combined sources
Helixi36 – 4510Combined sources
Beta strandi46 – 538Combined sources
Helixi61 – 7010Combined sources
Helixi77 – 793Combined sources
Helixi83 – 9412Combined sources
Beta strandi98 – 1014Combined sources
Helixi104 – 1107Combined sources
Beta strandi119 – 1235Combined sources
Helixi127 – 1293Combined sources
Helixi132 – 14413Combined sources
Beta strandi150 – 1534Combined sources
Beta strandi157 – 1615Combined sources
Beta strandi164 – 1674Combined sources
Helixi169 – 18012Combined sources
Beta strandi185 – 1884Combined sources
Helixi192 – 20211Combined sources
Helixi206 – 2083Combined sources
Beta strandi209 – 2146Combined sources
Turni216 – 2194Combined sources
Helixi220 – 2256Combined sources
Beta strandi229 – 2357Combined sources
Helixi240 – 2445Combined sources
Beta strandi251 – 2566Combined sources
Helixi257 – 26711Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2X4DX-ray1.92A/B1-270[»]
ProteinModelPortaliQ9H008.
SMRiQ9H008. Positions 1-269.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni17 – 193Substrate binding
Regioni54 – 552Substrate binding

Sequence similaritiesi

Belongs to the HAD-like hydrolase superfamily.Curated

Phylogenomic databases

eggNOGiCOG0647.
GeneTreeiENSGT00510000046678.
HOGENOMiHOG000068106.
HOVERGENiHBG075146.
InParanoidiQ9H008.
KOiK11725.
OMAiLQLRFCT.
PhylomeDBiQ9H008.
TreeFamiTF314344.

Family and domain databases

Gene3Di3.40.50.1000. 2 hits.
3.40.50.10410. 1 hit.
InterProiIPR023214. HAD-like_dom.
IPR006357. HAD-SF_hydro_IIA.
IPR006355. HAD-SF_hydro_IIA_hyp2.
IPR023215. NPhePase-like_dom.
[Graphical view]
PfamiPF13344. Hydrolase_6. 1 hit.
[Graphical view]
SUPFAMiSSF56784. SSF56784. 1 hit.
TIGRFAMsiTIGR01460. HAD-SF-IIA. 1 hit.
TIGR01458. HAD-SF-IIA-hyp3. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9H008-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAPWGKRLAG VRGVLLDISG VLYDSGAGGG TAIAGSVEAV ARLKRSRLKV
60 70 80 90 100
RFCTNESQKS RAELVGQLQR LGFDISEQEV TAPAPAACQI LKEQGLRPYL
110 120 130 140 150
LIHDGVRSEF DQIDTSNPNC VVIADAGESF SYQNMNNAFQ VLMELEKPVL
160 170 180 190 200
ISLGKGRYYK ETSGLMLDVG PYMKALEYAC GIKAEVVGKP SPEFFKSALQ
210 220 230 240 250
AIGVEAHQAV MIGDDIVGDV GGAQRCGMRA LQVRTGKFRP SDEHHPEVKA
260 270
DGYVDNLAEA VDLLLQHADK
Length:270
Mass (Da):29,165
Last modified:October 2, 2007 - v2
Checksum:i09C301584453E79D
GO
Isoform 2 (identifier: Q9H008-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     210-210: V → Q
     211-270: Missing.

Note: No experimental confirmation available.

Show »
Length:210
Mass (Da):22,696
Checksum:i93F0D37C2D348195
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti155 – 1551K → R in BAG51532 (PubMed:14702039).Curated
Sequence conflicti170 – 1701G → C in AAI10345 (PubMed:15489334).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti94 – 941Q → R.3 Publications
Corresponds to variant rs6597801 [ dbSNP | Ensembl ].
VAR_035163

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei210 – 2101V → Q in isoform 2. 1 PublicationVSP_041685
Alternative sequencei211 – 27060Missing in isoform 2. 1 PublicationVSP_041686Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB049629 mRNA. Translation: BAB16411.1.
AK055532 mRNA. Translation: BAG51532.1.
AL513190, AL445237 Genomic DNA. Translation: CAH70377.1.
AL513190, AL391708, AL445237 Genomic DNA. Translation: CAH70378.1.
AL391708, AL445237, AL513190 Genomic DNA. Translation: CAH74011.1.
AL445237, AL513190 Genomic DNA. Translation: CAI17295.1.
AL445237, AL391708, AL513190 Genomic DNA. Translation: CAI17296.1.
BC110344 mRNA. Translation: AAI10345.1.
BC113629 mRNA. Translation: AAI13630.1.
BC113631 mRNA. Translation: AAI13632.1.
CCDSiCCDS53587.1. [Q9H008-2]
CCDS7640.1. [Q9H008-1]
RefSeqiNP_001161352.1. NM_001167880.1. [Q9H008-2]
NP_071409.3. NM_022126.3. [Q9H008-1]
UniGeneiHs.527748.

Genome annotation databases

EnsembliENST00000368839; ENSP00000357832; ENSG00000107902. [Q9H008-2]
ENST00000368842; ENSP00000357835; ENSG00000107902. [Q9H008-1]
GeneIDi64077.
KEGGihsa:64077.
UCSCiuc001lhs.2. human. [Q9H008-1]
uc001lht.2. human. [Q9H008-2]

Polymorphism databases

DMDMi158705883.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB049629 mRNA. Translation: BAB16411.1.
AK055532 mRNA. Translation: BAG51532.1.
AL513190, AL445237 Genomic DNA. Translation: CAH70377.1.
AL513190, AL391708, AL445237 Genomic DNA. Translation: CAH70378.1.
AL391708, AL445237, AL513190 Genomic DNA. Translation: CAH74011.1.
AL445237, AL513190 Genomic DNA. Translation: CAI17295.1.
AL445237, AL391708, AL513190 Genomic DNA. Translation: CAI17296.1.
BC110344 mRNA. Translation: AAI10345.1.
BC113629 mRNA. Translation: AAI13630.1.
BC113631 mRNA. Translation: AAI13632.1.
CCDSiCCDS53587.1. [Q9H008-2]
CCDS7640.1. [Q9H008-1]
RefSeqiNP_001161352.1. NM_001167880.1. [Q9H008-2]
NP_071409.3. NM_022126.3. [Q9H008-1]
UniGeneiHs.527748.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2X4DX-ray1.92A/B1-270[»]
ProteinModelPortaliQ9H008.
SMRiQ9H008. Positions 1-269.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122044. 1 interaction.
STRINGi9606.ENSP00000357835.

PTM databases

DEPODiQ9H008.
PhosphoSiteiQ9H008.

Polymorphism databases

DMDMi158705883.

Proteomic databases

MaxQBiQ9H008.
PaxDbiQ9H008.
PRIDEiQ9H008.

Protocols and materials databases

DNASUi64077.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000368839; ENSP00000357832; ENSG00000107902. [Q9H008-2]
ENST00000368842; ENSP00000357835; ENSG00000107902. [Q9H008-1]
GeneIDi64077.
KEGGihsa:64077.
UCSCiuc001lhs.2. human. [Q9H008-1]
uc001lht.2. human. [Q9H008-2]

Organism-specific databases

CTDi64077.
GeneCardsiGC10P126140.
HGNCiHGNC:30042. LHPP.
HPAiHPA009163.
HPA009269.
neXtProtiNX_Q9H008.
PharmGKBiPA165548763.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0647.
GeneTreeiENSGT00510000046678.
HOGENOMiHOG000068106.
HOVERGENiHBG075146.
InParanoidiQ9H008.
KOiK11725.
OMAiLQLRFCT.
PhylomeDBiQ9H008.
TreeFamiTF314344.

Miscellaneous databases

ChiTaRSiLHPP. human.
GenomeRNAii64077.
NextBioi65859.
PROiQ9H008.

Gene expression databases

BgeeiQ9H008.
ExpressionAtlasiQ9H008. baseline and differential.
GenevestigatoriQ9H008.

Family and domain databases

Gene3Di3.40.50.1000. 2 hits.
3.40.50.10410. 1 hit.
InterProiIPR023214. HAD-like_dom.
IPR006357. HAD-SF_hydro_IIA.
IPR006355. HAD-SF_hydro_IIA_hyp2.
IPR023215. NPhePase-like_dom.
[Graphical view]
PfamiPF13344. Hydrolase_6. 1 hit.
[Graphical view]
SUPFAMiSSF56784. SSF56784. 1 hit.
TIGRFAMsiTIGR01460. HAD-SF-IIA. 1 hit.
TIGR01458. HAD-SF-IIA-hyp3. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning of a cDNA for the human phospholysine phosphohistidine inorganic pyrophosphate phosphatase."
    Yokoi F., Hiraishi H., Izuhara K.
    J. Biochem. 133:607-614(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBUNIT, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, VARIANT ARG-94.
    Tissue: Cervix carcinoma.
  2. "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] (ISOFORM 1), VARIANT ARG-94.
    Tissue: Heart.
  3. "The DNA sequence and comparative analysis of human chromosome 10."
    Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J.
    , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
    Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "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] (ISOFORMS 1 AND 2), VARIANT ARG-94.
    Tissue: Brain.
  5. "Expression of new human inorganic pyrophosphatase in thyroid diseases: its intimate association with hyperthyroidism."
    Koike E., Toda S., Yokoi F., Izuhara K., Koike N., Itoh K., Miyazaki K., Sugihara H.
    Biochem. Biophys. Res. Commun. 341:691-696(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  6. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  7. "Crystal structure of human phospholysine phosphohistidine inorganic pyrophosphate phosphatase LHPP."
    Structural genomics consortium (SGC)
    Submitted (MAR-2010) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG AND MAGNESIUM IONS, COFACTOR.

Entry informationi

Entry nameiLHPP_HUMAN
AccessioniPrimary (citable) accession number: Q9H008
Secondary accession number(s): B3KP20
, Q2TBE9, Q5VUV9, Q5VUW0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 2, 2007
Last sequence update: October 2, 2007
Last modified: March 4, 2015
This is version 101 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.