Q9NRX4 (PHP14_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
14 kDa phosphohistidine phosphatase
EC=3.1.3.-

Alternative name(s):
Phosphohistidine phosphatase 1
Protein janus-A homolog

Gene names

Name:	PHPT1
Synonyms:	PHP14
ORF Names:	CGI-202, HSPC141

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	125 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Exhibits phosphohistidine phosphatase activity.
Subunit structure	Monomer.
Subcellular location	Cytoplasm By similarity.
Tissue specificity	Expressed abundantly in heart and skeletal muscle.
Sequence similarities	Belongs to the janus family.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Molecular function	Hydrolase Protein phosphatase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of ATP citrate synthase activity Inferred from direct assay PubMed 18656514. Source: BHF-UCL negative regulation of T cell receptor signaling pathway Inferred from mutant phenotype PubMed 18796614. Source: BHF-UCL negative regulation of lyase activity Inferred from direct assay PubMed 20110805PubMed 20501872. Source: BHF-UCL peptidyl-histidine dephosphorylation Inferred from direct assay Ref.8PubMed 19138678. Source: BHF-UCL positive regulation of cell motility Inferred from mutant phenotype PubMed 19344975. Source: BHF-UCL positive regulation of insulin secretion involved in cellular response to glucose stimulus Inferred from electronic annotation. Source: Compara regulation of actin cytoskeleton reorganization Inferred from mutant phenotype PubMed 19344975. Source: BHF-UCL
Cellular_component	cytosol Inferred from direct assay PubMed 20501872. Source: BHF-UCL
Molecular_function	calcium channel inhibitor activity Inferred from direct assay PubMed 18796614. Source: BHF-UCL phosphohistidine phosphatase activity Inferred from direct assay Ref.8PubMed 19138678PubMed 20501872. Source: BHF-UCL phosphoprotein phosphatase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q9NRX4-1)

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: Q9NRX4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     96-125: AYGPAQHAISTEKIKAKYPDYEVTWANDGY → MRPTCVPLGASGPRIHHQGLWSCPARHFN

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 125

125

14 kDa phosphohistidine phosphatase

PRO_0000206152

Regions

Region

94 – 96

3

Substrate binding

Sites

Active site

53

1

Proton acceptor Ref.11

Binding site

21

1

Substrate

Amino acid modifications

Modified residue

93

1

Phosphotyrosine By similarity

Natural variations

Alternative sequence

96 – 125

30

AYGPA…ANDGY → MRPTCVPLGASGPRIHHQGL WSCPARHFN in isoform 2.

VSP_041159

Experimental info

Mutagenesis

21

1

K → A: Decreased affinity for substrate and strongly reduced catalytic activity. Ref.11

Mutagenesis

45

1

R → A: Slightly decreased affinity for substrate, but no effect on catalytic activity. Ref.8 Ref.11

Mutagenesis

53

1

H → A: Loss of activity. Ref.8 Ref.11

Mutagenesis

78

1

R → A: Decreased affinity for substrate and reduced catalytic activity. Ref.8 Ref.11

Mutagenesis

94

1

S → A: Decreased affinity for substrate and strongly reduced catalytic activity.

Mutagenesis

102

1

H → A: Decreased affinity for substrate and slightly reduced catalytic activity. Ref.8 Ref.11

Sequence conflict

14

1

I → T in CAB66579. Ref.4

Sequence conflict

27

1

V → I in CAB66579. Ref.4

Sequence conflict

79

1

I → T in CAB66579. Ref.4

Secondary structure

1

.

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125

Helix Strand Turn

Details...

Helix

6 – 8

3

Beta strand

11 – 14

4

Beta strand

17 – 28

12

Helix

31 – 33

3

Beta strand

40 – 46

7

Helix

53 – 66

14

Beta strand

70 – 82

13

Turn

83 – 86

4

Beta strand

87 – 91

5

Turn

95 – 97

3

Helix

102 – 112

11

Beta strand

116 – 120

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 24F0CA2BADB78478	FASTA	125	13,833
	10 20 30 40 50 60 MAVADLALIP DVDIDSDGVF KYVLIRVHSA PRSGAPAAES KEIVRGYKWA EYHADIYDKV 70 80 90 100 110 120 SGDMQKQGCD CECLGGGRIS HQSQDKKIHV YGYSMAYGPA QHAISTEKIK AKYPDYEVTW ANDGY
	Isoform 2 [UniParc]. Checksum: B504A355D275D9C6	FASTA	124	13,672
	10 20 30 40 50 60 MAVADLALIP DVDIDSDGVF KYVLIRVHSA PRSGAPAAES KEIVRGYKWA EYHADIYDKV 70 80 90 100 110 120 SGDMQKQGCD CECLGGGRIS HQSQDKKIHV YGYSMMRPTC VPLGASGPRI HHQGLWSCPA RHFN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and characterization of a mammalian 14-kDa phosphohistidine phosphatase." Ek P., Pettersson G., Ek B., Gong F., Li J.-P., Zetterqvist O. Eur. J. Biochem. 269:5016-5023(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 2-21; 49-59; 88-108 AND 111-125, CHARACTERIZATION. Tissue: Embryonic kidney.
[2]	"Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning." Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M. , Zhou J., Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L. Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Adrenal gland.
[3]	"Identification of the human crooked neck gene by comparative gene identification." Lai C.-H., Chiu J.-Y., Lin W.-C. Biochim. Biophys. Acta 1517:449-454(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Fetal brain.
[5]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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). Tissue: Brain and Lung.
[8]	"Mutational study of human phosphohistidine phosphatase: effect on enzymatic activity." Ma R., Kanders E., Sundh U.B., Geng M., Ek P., Zetterqvist O., Li J.-P. Biochem. Biophys. Res. Commun. 337:887-891(2005) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ARG-45; HIS-53; ARG-78 AND HIS-102.
[9]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]	"First structure of a eukaryotic phosphohistidine phosphatase." Busam R.D., Thorsell A.-G., Flores A., Hammarstroem M., Persson C., Hallberg B.M. J. Biol. Chem. 281:33830-33834(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 5-125.
[11]	"Solution structure and catalytic mechanism of human protein histidine phosphatase 1." Gong W., Li Y., Cui G., Hu J., Fang H., Jin C., Xia B. Biochem. J. 418:337-344(2009) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR IN COMPLEXES WITH PHOSPHATE, ACTIVE SITE, ENZYME ACTIVITY, MUTAGENESIS OF LYS-21; ARG-45; HIS-53; ARG-78 AND HIS-102.
[12]	"Crystal structure of human phosphohistidine phosphatase. Northeast structural genomics consortium target HR1409." Northeast structural genomics consortium (NESG) Submitted (JAN-2007) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF393504 mRNA. Translation: AAN52504.1.
AF164795 mRNA. Translation: AAF80759.1.
AF285119 mRNA. Translation: AAG01156.1.
AL136644 mRNA. Translation: CAB66579.1.
AL355987 Genomic DNA. Translation: CAI12692.1.
AL355987 Genomic DNA. Translation: CAI12693.1.
CH471090 Genomic DNA. Translation: EAW88289.1.
BC024648 mRNA. Translation: AAH24648.1.
BQ922335 mRNA. No translation available.

IPI

IPI00299977.
IPI00513775.

RefSeq

NP_001129333.1. NM_001135861.1.
NP_054891.2. NM_014172.4.

UniGene

Hs.409834.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2AI6	NMR	-	A	1-125	[»]
2HW4	X-ray	1.90	A	5-125	[»]
2NMM	X-ray	2.70	A/B/C	1-125	[»]
2OZW	NMR	-	A	1-125	[»]
2OZX	NMR	-	A	1-125	[»]

ProteinModelPortal

Q9NRX4.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48597N.

IntAct

Q9NRX4. 2 interactions.

MINT

MINT-1394164.

STRING

9606.ENSP00000247665.

PTM databases

PhosphoSite

Q9NRX4.

Polymorphism databases

DMDM

25008934.

Proteomic databases

PaxDb

Q9NRX4.

PeptideAtlas

Q9NRX4.

PRIDE

Q9NRX4.

Protocols and materials databases

DNASU

29085.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000247665; ENSP00000247665; ENSG00000054148.
ENST00000371661; ENSP00000360724; ENSG00000054148.
ENST00000545326; ENSP00000444757; ENSG00000054148.

GeneID

29085.

KEGG

hsa:29085.

UCSC

uc004cjq.4. human.
uc011mei.2. human.

Organism-specific databases

CTD

29085.

GeneCards

GC09P139743.

HGNC

HGNC:30033. PHPT1.

HPA

CAB013584.
HPA020952.

MIM

610167. gene.

neXtProt

NX_Q9NRX4.

PharmGKB

PA134948141.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG73026.

HOGENOM

HOG000231559.

HOVERGEN

HBG053589.

KO

K01112.

OMA

EVTWADD.

OrthoDB

EOG418BPT.

PhylomeDB

Q9NRX4.

Gene expression databases

Bgee

Q9NRX4.

CleanEx

HS_PHPT1.

Genevestigator

Q9NRX4.

GermOnline

ENSG00000054148. Homo sapiens.

Family and domain databases

InterPro

IPR007702. Ocnus.
[Graphical view]

Pfam

PF05005. Ocnus. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

PHPT1. human.

EvolutionaryTrace

Q9NRX4.

GenomeRNAi

29085.

NextBio

52068.

SOURCE

Search...

Entry information

Entry name

PHP14_HUMAN

Accession

Primary (citable) accession number: Q9NRX4
Secondary accession number(s): B1AMX0, B1AMX1, Q9H0Y3

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 8, 2002
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 105 of the entry and version 1 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.