Q8TCT1 (PHOP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phosphoethanolamine/phosphocholine phosphatase
EC=3.1.3.75

Gene names

Name:

PHOSPHO1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	267 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Phosphatase that has a high activity toward phosphoethanolamine (PEA) and phosphocholine (PCho). Involved in the generation of inorganic phosphate for bone mineralization.
Catalytic activity	O-phosphoethanolamine + H2O = ethanolamine + phosphate. Ref.4 Phosphocholine + H2O = choline + phosphate. Ref.4
Cofactor	Magnesium. Ref.4
Tissue specificity	Expressed at sites of mineralization in bone and cartilage. Highly expressed in osteoblast cell line SaOS-2 which produces a mineralized matrix, but not in MG-63 cell line, which do not mineralize. Ref.5
Sequence similarities	Belongs to the HAD-like hydrolase superfamily. PHOSPHO family.
Biophysicochemical properties	Kinetic parameters: KM=3 µM for PEA Ref.4 KM=11.4 µM for PCho pH dependence: Optimum pH is 6.7.

Ontologies

Keywords
Biological process	Mineral balance
Coding sequence diversity	Alternative splicing
Ligand	Magnesium Metal-binding
Molecular function	Hydrolase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	regulation of bone mineralization Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW phosphocholine phosphatase activity Inferred from electronic annotation. Source: EC phosphoethanolamine phosphatase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q8TCT1-1)

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: Q8TCT1-2)

Also known as: PHOSPHO1-3a;

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: MSGCFPVSGLRCLSR → MCQRLWPANQPLPGGLLPRPLSLAPSSSSSCCSPPCSQ

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 267	267	Phosphoethanolamine/phosphocholine phosphatase		PRO_0000068829
Sites
	Active site	32	1	Nucleophile Probable
	Active site	34	1	Proton donor By similarity
	Metal binding	32	1	Magnesium Probable
	Metal binding	34	1	Magnesium By similarity
	Metal binding	203	1	Magnesium Probable
	Binding site	43	1	Substrate Probable
	Binding site	123	1	Substrate Probable
Natural variations
	Alternative sequence	1 – 15	15	MSGCF…RCLSR → MCQRLWPANQPLPGGLLPRP LSLAPSSSSSCCSPPCSQ in isoform 2.		VSP_040624
Experimental info
	Mutagenesis	32	1	D → N: Abolishes phosphatase activity. Ref.7
	Mutagenesis	43	1	D → N: Strongly reduces reactivity toward PEA and PCho substrates. Abolishes phosphatase activity; when associated with N-123. Ref.7
	Mutagenesis	123	1	D → N: Strongly reduces reactivity toward PEA and PCho substrates. Abolishes phosphatase activity; when associated with N-43. Ref.7
	Mutagenesis	203	1	D → S: Abolishes phosphatase activity. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2002. Version 1. Checksum: 539F65C749D39E81	FASTA	267	29,713
	10 20 30 40 50 60 MSGCFPVSGL RCLSRDGRMA AQGAPRFLLT FDFDETIVDE NSDDSIVRAA PGQRLPESLR 70 80 90 100 110 120 ATYREGFYNE YMQRVFKYLG EQGVRPRDLS AIYEAIPLSP GMSDLLQFVA KQGACFEVIL 130 140 150 160 170 180 ISDANTFGVE SSLRAAGHHS LFRRILSNPS GPDARGLLAL RPFHTHSCAR CPANMCKHKV 190 200 210 220 230 240 LSDYLRERAH DGVHFERLFY VGDGANDFCP MGLLAGGDVA FPRRGYPMHR LIQEAQKAEP 250 260 SSFRASVVPW ETAADVRLHL QQVLKSC
	Isoform 2 (PHOSPHO1-3a) [UniParc]. Checksum: E7E5C497A540C458	FASTA	290	32,068
	10 20 30 40 50 60 MCQRLWPANQ PLPGGLLPRP LSLAPSSSSS CCSPPCSQDG RMAAQGAPRF LLTFDFDETI 70 80 90 100 110 120 VDENSDDSIV RAAPGQRLPE SLRATYREGF YNEYMQRVFK YLGEQGVRPR DLSAIYEAIP 130 140 150 160 170 180 LSPGMSDLLQ FVAKQGACFE VILISDANTF GVESSLRAAG HHSLFRRILS NPSGPDARGL 190 200 210 220 230 240 LALRPFHTHS CARCPANMCK HKVLSDYLRE RAHDGVHFER LFYVGDGAND FCPMGLLAGG 250 260 270 280 290 DVAFPRRGYP MHRLIQEAQK AEPSSFRASV VPWETAADVR LHLQQVLKSC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Chromosomal localization of the chicken and mammalian orthologues of the orphan phosphatase PHOSPHO1 gene." Houston B., Paton I.R., Burt D.W., Farquharson C. Anim. Genet. 33:451-454(2002) [PubMed: 12464021] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Identification of a novel splice variant of the haloacid dehalogenase: PHOSPHO1." Roberts S.J., Owen H.C., Farquharson C. Biochem. Biophys. Res. Commun. 371:872-876(2008) [PubMed: 18471996] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING.
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Colon.
[4]	"Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities." Roberts S.J., Stewart A.J., Sadler P.J., Farquharson C. Biochem. J. 382:59-65(2004) [PubMed: 15175005] [Abstract] Cited for: ENZYME ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES.
[5]	"PHOSPHO1 -- a novel phosphatase specifically expressed at sites of mineralisation in bone and cartilage." Houston B., Stewart A.J., Farquharson C. Bone 34:629-637(2004) [PubMed: 15050893] [Abstract] Cited for: TISSUE SPECIFICITY.
[6]	"Comparative modelling of human PHOSPHO1 reveals a new group of phosphatases within the haloacid dehalogenase superfamily." Stewart A.J., Schmid R., Blindauer C.A., Paisey S.J., Farquharson C. Protein Eng. 16:889-895(2003) [PubMed: 14983068] [Abstract] Cited for: SIMILARITY TO HAD-LIKE HYDROLASE SUPERFAMILY.
[7]	"Probing the substrate specificities of human PHOSPHO1 and PHOSPHO2." Roberts S.J., Stewart A.J., Schmid R., Blindauer C.A., Bond S.R., Sadler P.J., Farquharson C. Biochim. Biophys. Acta 1752:73-82(2005) [PubMed: 16054448] [Abstract] Cited for: MUTAGENESIS OF ASP-32; ASP-43; ASP-123 AND ASP-203.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ457189 mRNA. Translation: CAD29803.1. BC117187 mRNA. Translation: AAI17188.1.
IPI	IPI00152434. IPI00916923.
RefSeq	NP_001137276.1. NM_001143804.1. NP_848595.1. NM_178500.3.
UniGene	Hs.405607.
3D structure databases
ProteinModelPortal	Q8TCT1.
SMR	Q8TCT1. Positions 167-267.
ModBase	Search...
Protein-protein interaction databases
STRING	Q8TCT1.
PTM databases
PhosphoSite	Q8TCT1.
Polymorphism databases
DMDM	74715842.
Proteomic databases
PRIDE	Q8TCT1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000310544; ENSP00000311925; ENSG00000173868.
GeneID	162466.
KEGG	hsa:162466.
UCSC	uc002ior.1. human.
Organism-specific databases
CTD	162466.
GeneCards	GC17M047300.
H-InvDB	HIX0039112.
HGNC	HGNC:16815. PHOSPHO1.
neXtProt	NX_Q8TCT1.
PharmGKB	PA33276.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG13707.
GeneTree	ENSGT00390000007741.
HOVERGEN	HBG080058.
InParanoid	Q8TCT1.
OrthoDB	EOG4S4PH0.
PhylomeDB	Q8TCT1.
Enzyme and pathway databases
BRENDA	3.1.3.75. 2681.
Gene expression databases
ArrayExpress	Q8TCT1.
Bgee	Q8TCT1.
CleanEx	HS_PHOSPHO1.
Genevestigator	Q8TCT1.
GermOnline	ENSG00000173868. Homo sapiens.
Family and domain databases
InterPro	IPR023214. HAD-like_dom. IPR006383. HAD-SF_hydro_IB_PSP-like. IPR016965. Pase_PHOSPHO-typ. IPR006384. PyrdxlP_Pase-rel. [Graphical view]
Gene3D	G3DSA:3.40.50.1000. HAD-like_dom. 2 hits.
KO	K06124.
Pfam	PF06888. Put_Phosphatase. 1 hit. [Graphical view]
PIRSF	PIRSF031051. PyrdxlP_Pase_PHOSPHO2. 1 hit.
SUPFAM	SSF56784. HAD-like_dom. 1 hit.
TIGRFAMs	TIGR01489. DKMTPPase-SF. 1 hit. TIGR01488. HAD-SF-IB. 1 hit.
ProtoNet	Search...
Other
DrugBank	DB00122. Choline.
NextBio	88177.

Entry information

Entry name

PHOP1_HUMAN

Accession

Primary (citable) accession number: Q8TCT1
Secondary accession number(s): Q17RU6

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 10, 2006
Last sequence update:	June 1, 2002
Last modified:	January 25, 2012
This is version 67 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.