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Q9H008

- LHPP_HUMAN

UniProt

Q9H008 - LHPP_HUMAN

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Protein
Phospholysine phosphohistidine inorganic pyrophosphate phosphatase
Gene
LHPP
Organism
Homo sapiens (Human)
Status
Reviewed - 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.

Catalytic activityi

Diphosphate + H2O = 2 phosphate.1 Publication

Cofactori

Binds 1 magnesium 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. Nucleus 1 Publication

GO - Cellular componenti

  1. cytoplasm Source: HPA
  2. cytosol Source: UniProtKB
  3. 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 phosphatase
PRO_0000305074Add
BLAST

Proteomic databases

MaxQBiQ9H008.
PaxDbiQ9H008.
PRIDEiQ9H008.

PTM databases

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

ArrayExpressiQ9H008.
BgeeiQ9H008.
GenevestigatoriQ9H008.

Organism-specific databases

HPAiHPA009163.
HPA009269.

Interactioni

Subunit structurei

Homodimer.1 Publication

Protein-protein interaction databases

STRINGi9606.ENSP00000357835.

Structurei

Secondary structure

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

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2X4DX-ray1.92A/B1-270[»]
ProteinModelPortaliQ9H008.
SMRiQ9H008. Positions 1-269.

Family & Domainsi

Region

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

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0647.
HOGENOMiHOG000068106.
HOVERGENiHBG075146.
InParanoidiQ9H008.
KOiK11725.
OMAiEAHQAVM.
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. Align

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

MAPWGKRLAG VRGVLLDISG VLYDSGAGGG TAIAGSVEAV ARLKRSRLKV    50
RFCTNESQKS RAELVGQLQR LGFDISEQEV TAPAPAACQI LKEQGLRPYL 100
LIHDGVRSEF DQIDTSNPNC VVIADAGESF SYQNMNNAFQ VLMELEKPVL 150
ISLGKGRYYK ETSGLMLDVG PYMKALEYAC GIKAEVVGKP SPEFFKSALQ 200
AIGVEAHQAV MIGDDIVGDV GGAQRCGMRA LQVRTGKFRP SDEHHPEVKA 250
DGYVDNLAEA VDLLLQHADK 270
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

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.
VSP_041685
Alternative sequencei211 – 27060Missing in isoform 2.
VSP_041686Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti155 – 1551K → R in BAG51532. 1 Publication
Sequence conflicti170 – 1701G → C in AAI10345. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS53587.1. [Q9H008-2 ]
CCDS7640.1. [Q9H008-1 ]
RefSeqi NP_001161352.1. NM_001167880.1. [Q9H008-2 ]
NP_071409.3. NM_022126.3. [Q9H008-1 ]
UniGenei Hs.527748.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2X4D X-ray 1.92 A/B 1-270 [» ]
ProteinModelPortali Q9H008.
SMRi Q9H008. Positions 1-269.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9606.ENSP00000357835.

PTM databases

PhosphoSitei Q9H008.

Polymorphism databases

DMDMi 158705883.

Proteomic databases

MaxQBi Q9H008.
PaxDbi Q9H008.
PRIDEi Q9H008.

Protocols and materials databases

DNASUi 64077.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000368839 ; ENSP00000357832 ; ENSG00000107902 . [Q9H008-2 ]
ENST00000368842 ; ENSP00000357835 ; ENSG00000107902 . [Q9H008-1 ]
GeneIDi 64077.
KEGGi hsa:64077.
UCSCi uc001lhs.2. human. [Q9H008-1 ]
uc001lht.2. human. [Q9H008-2 ]

Organism-specific databases

CTDi 64077.
GeneCardsi GC10P126140.
HGNCi HGNC:30042. LHPP.
HPAi HPA009163.
HPA009269.
neXtProti NX_Q9H008.
PharmGKBi PA165548763.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0647.
HOGENOMi HOG000068106.
HOVERGENi HBG075146.
InParanoidi Q9H008.
KOi K11725.
OMAi EAHQAVM.
PhylomeDBi Q9H008.
TreeFami TF314344.

Miscellaneous databases

GenomeRNAii 64077.
NextBioi 65859.
PROi Q9H008.

Gene expression databases

ArrayExpressi Q9H008.
Bgeei Q9H008.
Genevestigatori Q9H008.

Family and domain databases

Gene3Di 3.40.50.1000. 2 hits.
3.40.50.10410. 1 hit.
InterProi IPR023214. HAD-like_dom.
IPR006357. HAD-SF_hydro_IIA.
IPR006355. HAD-SF_hydro_IIA_hyp2.
IPR023215. NPhePase-like_dom.
[Graphical view ]
Pfami PF13344. Hydrolase_6. 1 hit.
[Graphical view ]
SUPFAMi SSF56784. SSF56784. 1 hit.
TIGRFAMsi TIGR01460. HAD-SF-IIA. 1 hit.
TIGR01458. HAD-SF-IIA-hyp3. 1 hit.
ProtoNeti Search...

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. "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: July 9, 2014
This is version 95 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

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