Q9H008 (LHPP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phospholysine phosphohistidine inorganic pyrophosphate phosphatase
Short name=hLHPP
EC=3.1.3.-
EC=3.6.1.1

Gene names

Name:

LHPP

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	270 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 activity	Diphosphate + H2O = 2 phosphate. Ref.1
Cofactor	Binds 1 magnesium ion per subunit. Ref.1 Ref.6
Subunit structure	Homodimer. Ref.1
Subcellular location	Cytoplasm. Nucleus Ref.5.
Tissue specificity	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. Ref.1 Ref.5
Sequence similarities	Belongs to the HAD-like hydrolase superfamily.
Biophysicochemical properties	pH dependence: Optimum pH is 7.0 for PNP, and 5.5 for PPi. Ref.1

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Magnesium Metal-binding
Molecular function	Hydrolase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein dephosphorylation Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytosol Inferred from direct assay Ref.5. Source: UniProtKB nucleus Inferred from direct assay Ref.5. Source: UniProtKB
Molecular_function	inorganic diphosphatase activity Inferred from direct assay Ref.1. Source: UniProtKB magnesium ion binding Inferred from sequence or structural similarity. Source: UniProtKB phosphohistidine phosphatase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9H008-1)

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: Q9H008-2)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 270

270

Phospholysine phosphohistidine inorganic pyrophosphate phosphatase

PRO_0000305074

Regions

Region

17 – 19

3

Substrate binding

Region

54 – 55

2

Substrate binding

Sites

Metal binding

17

1

Magnesium

Metal binding

19

1

Magnesium; via carbonyl oxygen

Metal binding

214

1

Magnesium

Binding site

189

1

Substrate

Natural variations

Alternative sequence

210

1

V → Q in isoform 2.

VSP_041685

Alternative sequence

211 – 270

60

Missing in isoform 2.

VSP_041686

Natural variant

94

1

Q → R. Ref.1 Ref.2 Ref.4
Corresponds to variant rs6597801 [ dbSNP | Ensembl ].

VAR_035163

Experimental info

Sequence conflict

155

1

K → R in BAG51532. Ref.2

Sequence conflict

170

1

G → C in AAI10345. Ref.4

Secondary structure

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270

Helix Strand Turn

Details...

Helix

4 – 7

4

Turn

8 – 10

3

Beta strand

13 – 16

4

Turn

19 – 21

3

Beta strand

22 – 24

3

Turn

27 – 29

3

Helix

36 – 45

10

Beta strand

46 – 53

8

Helix

61 – 70

10

Helix

77 – 79

3

Helix

83 – 94

12

Beta strand

98 – 101

4

Helix

104 – 110

7

Beta strand

119 – 123

5

Helix

127 – 129

3

Helix

132 – 144

13

Beta strand

150 – 153

4

Beta strand

157 – 161

5

Beta strand

164 – 167

4

Helix

169 – 180

12

Beta strand

185 – 188

4

Helix

192 – 202

11

Helix

206 – 208

3

Beta strand

209 – 214

6

Turn

216 – 219

4

Helix

220 – 225

6

Beta strand

229 – 235

7

Helix

240 – 244

5

Beta strand

251 – 256

6

Helix

257 – 267

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 2, 2007. Version 2. Checksum: 09C301584453E79D	FASTA	270	29,165
	10 20 30 40 50 60 MAPWGKRLAG VRGVLLDISG VLYDSGAGGG TAIAGSVEAV ARLKRSRLKV RFCTNESQKS 70 80 90 100 110 120 RAELVGQLQR LGFDISEQEV TAPAPAACQI LKEQGLRPYL LIHDGVRSEF DQIDTSNPNC 130 140 150 160 170 180 VVIADAGESF SYQNMNNAFQ VLMELEKPVL ISLGKGRYYK ETSGLMLDVG PYMKALEYAC 190 200 210 220 230 240 GIKAEVVGKP SPEFFKSALQ AIGVEAHQAV MIGDDIVGDV GGAQRCGMRA LQVRTGKFRP 250 260 270 SDEHHPEVKA DGYVDNLAEA VDLLLQHADK
	Isoform 2 [UniParc]. Checksum: 93F0D37C2D348195	FASTA	210	22,696
	10 20 30 40 50 60 MAPWGKRLAG VRGVLLDISG VLYDSGAGGG TAIAGSVEAV ARLKRSRLKV RFCTNESQKS 70 80 90 100 110 120 RAELVGQLQR LGFDISEQEV TAPAPAACQI LKEQGLRPYL LIHDGVRSEF DQIDTSNPNC 130 140 150 160 170 180 VVIADAGESF SYQNMNNAFQ VLMELEKPVL ISLGKGRYYK ETSGLMLDVG PYMKALEYAC 190 200 210 GIKAEVVGKP SPEFFKSALQ AIGVEAHQAQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00005474.
IPI00642397.

RefSeq

NP_001161352.1. NM_001167880.1.
NP_071409.3. NM_022126.3.

UniGene

Hs.527748.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2X4D	X-ray	1.92	A/B	1-270	[»]

ProteinModelPortal

Q9H008.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000357835.

PTM databases

PhosphoSite

Q9H008.

Polymorphism databases

DMDM

158705883.

Proteomic databases

PaxDb

Q9H008.

PRIDE

Q9H008.

Protocols and materials databases

DNASU

64077.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000368839; ENSP00000357832; ENSG00000107902.
ENST00000368842; ENSP00000357835; ENSG00000107902.

GeneID

64077.

KEGG

hsa:64077.

UCSC

uc001lhs.2. human.
uc001lht.2. human.

Organism-specific databases

CTD

64077.

GeneCards

GC10P126140.

HGNC

HGNC:30042. LHPP.

HPA

HPA009163.
HPA009269.

neXtProt

NX_Q9H008.

PharmGKB

PA165548763.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0647.

HOGENOM

HOG000068106.

HOVERGEN

HBG075146.

InParanoid

Q9H008.

KO

K11725.

OMA

HEGVRSE.

PhylomeDB

Q9H008.

Gene expression databases

ArrayExpress

Q9H008.

Bgee

Q9H008.

Genevestigator

Q9H008.

Family and domain databases

Gene3D

3.40.50.1000. 2 hits.
3.40.50.10410. 1 hit.

InterPro

IPR023214. HAD-like_dom.
IPR006357. HAD-SF_hydro_IIA.
IPR006355. HAD-SF_hydro_IIA_hyp2.
IPR023215. NPhePase-like_dom.
[Graphical view]

Pfam

PF13344. Hydrolase_6. 1 hit.
[Graphical view]

SUPFAM

SSF56784. HAD-like_dom. 1 hit.

TIGRFAMs

TIGR01460. HAD-SF-IIA. 1 hit.
TIGR01458. HAD-SF-IIA-hyp3. 1 hit.

ProtoNet

Search...

Other

GenomeRNAi

64077.

NextBio

65859.

Entry information

Entry name

LHPP_HUMAN

Accession

Primary (citable) accession number: Q9H008
Secondary accession number(s): B3KP20 , Q2TBE9, Q5VUV9, Q5VUW0

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 2, 2007
Last sequence update:	October 2, 2007
Last modified:	May 1, 2013
This is version 86 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.