Q96GD0 (PLPP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pyridoxal phosphate phosphatase
Short name=PLP phosphatase

Alternative name(s):
Chronophin
EC=3.1.3.3
EC=3.1.3.74

Gene names

Name:	PDXP
Synonyms:	CIN, PLP, PLPP

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

General annotation (Comments)

Function	Protein serine phosphatase that dephosphorylates 'Ser-3' in cofilin and probably also dephosphorylates phospho-serine residues in DSTN. Regulates cofilin-dependent actin cytoskeleton reorganization. Required for normal progress through mitosis and normal cytokinesis. Does not dephosphorylate phospho-threonines in LIMK1. Does not dephosphorylate peptides containing phospho-tyrosine. Pyridoxal phosphate phosphatase. Has some activity towards pyridoxal 5'-phosphate (PLP), pyridoxine 5'-phosphate (PMP) and pyridoxine 5'-phosphate (PNP), with a highest activity with PLP followed by PNP. Ref.1 Ref.7
Catalytic activity	Pyridoxal 5'-phosphate + H2O = pyridoxal + phosphate. Ref.5 Ref.7 O-phospho-L(or D)-serine + H2O = L(or D)-serine + phosphate. Ref.5 Ref.7
Cofactor	Divalent ions. Magnesium is the most effective. Ref.1 Ref.7
Enzyme regulation	Inhibited by NaF, Zn2+, Ca2+, Mn2+ and EDTA. Ref.7
Subunit structure	Homodimer. Ref.1
Subcellular location	Cytoplasm › cytosol. Cytoplasm › cytoskeleton. Cell projection › ruffle membrane; Peripheral membrane protein; Cytoplasmic side. Cell projection › lamellipodium membrane; Peripheral membrane protein; Cytoplasmic side. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Note: Colocalizes with the actin cytoskeleton in membrane ruffles and lamellipodia. Diffusely distributed throughout the cytosol during pro-metaphase and metaphase. Detected at the dynamic cell poles during telophase. Detected at the cleavage furrow and contractile ring during cytokinesis. Transiently detected at the plasma membrane in late stages of cytokinesis. Detected at the midbody. Ref.7
Tissue specificity	Ubiquitous. Highly expressed in all the regions of central nerve system except the spinal cord. Also expressed at high level in liver and testis. In fetus, it is weakly expressed in all organs except brain. Ref.1 Ref.7
Sequence similarities	Belongs to the HAD-like hydrolase superfamily.

Ontologies

Keywords
Cellular component	Cell membrane Cell projection Cytoplasm Cytoskeleton Membrane
Ligand	Magnesium Metal-binding Pyridoxal phosphate
Molecular function	Hydrolase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	actin rod assembly Inferred from direct assay. Source: MGI cellular response to ATP Inferred from direct assay. Source: MGI positive regulation of actin filament depolymerization Inferred from mutant phenotype Ref.7. Source: UniProtKB protein dephosphorylation Inferred from direct assay Ref.7. Source: UniProtKB regulation of cytokinesis Inferred from mutant phenotype Ref.7. Source: UniProtKB regulation of mitosis Inferred from mutant phenotype Ref.7. Source: UniProtKB
Cellular component	cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Inferred from direct assay Ref.7. Source: UniProtKB lamellipodium membrane Inferred from electronic annotation. Source: UniProtKB-SubCell ruffle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	heat shock protein binding Inferred from direct assay. Source: MGI metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW phosphoprotein phosphatase activity Inferred from direct assay Ref.7. Source: UniProtKB phosphoserine phosphatase activity Inferred from electronic annotation. Source: EC pyridoxal phosphatase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Arrb1	P29066	2	EBI-4303060,EBI-4303019	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 296

296

Pyridoxal phosphate phosphatase

PRO_0000068837

Regions

Region

58 – 62

5

Substrate binding

Sites

Active site

25

1

Nucleophile Ref.7

Active site

27

1

Proton donor Probable

Metal binding

25

1

Magnesium

Metal binding

27

1

Magnesium; via carbonyl oxygen

Metal binding

238

1

Magnesium

Binding site

182

1

Substrate

Binding site

213

1

Substrate

Experimental info

Mutagenesis

25

1

D → N: Abolishes phosphatase activity. Ref.7

Secondary structure

1

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296

Helix Strand Turn

Details...

Helix

9 – 18

10

Beta strand

20 – 24

5

Turn

27 – 29

3

Beta strand

30 – 32

3

Helix

40 – 49

10

Beta strand

53 – 58

6

Helix

65 – 74

10

Helix

82 – 84

3

Beta strand

85 – 87

3

Helix

88 – 99

12

Beta strand

109 – 114

6

Helix

116 – 124

9

Beta strand

143 – 148

6

Helix

156 – 165

10

Beta strand

171 – 176

6

Beta strand

181 – 183

3

Beta strand

189 – 191

3

Helix

193 – 204

12

Helix

217 – 222

6

Turn

223 – 225

3

Helix

230 – 232

3

Beta strand

233 – 238

6

Turn

240 – 242

3

Helix

243 – 250

8

Beta strand

253 – 257

5

Helix

264 – 272

9

Helix

276 – 278

3

Beta strand

281 – 286

6

Helix

287 – 289

3

Helix

291 – 294

4

Sequences

	Sequence		Length	Mass (Da)
	Q96GD0 [UniParc]. Last modified March 1, 2004. Version 2. Checksum: 33466C35A76B458C	FASTA	296	31,698
	10 20 30 40 50 60 MARCERLRGA ALRDVLGRAQ GVLFDCDGVL WNGERAVPGA PELLERLARA GKAALFVSNN 70 80 90 100 110 120 SRRARPELAL RFARLGFGGL RAEQLFSSAL CAARLLRQRL PGPPDAPGAV FVLGGEGLRA 130 140 150 160 170 180 ELRAAGLRLA GDPSAGDGAA PRVRAVLVGY DEHFSFAKLR EACAHLRDPE CLLVATDRDP 190 200 210 220 230 240 WHPLSDGSRT PGTGSLAAAV ETASGRQALV VGKPSPYMFE CITENFSIDP ARTLMVGDRL 250 260 270 280 290 ETDILFGHRC GMTTVLTLTG VSRLEEAQAY LAAGQHDLVP HYYVESIADL TEGLED

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human pyridoxal phosphatase. Molecular cloning, functional expression, and tissue distribution." Jang Y.M., Kim D.W., Kang T.-C., Won M.H., Baek N.-I., Moon B.J., Choi S.Y., Kwon O.-S. J. Biol. Chem. 278:50040-50046(2003) [PubMed: 14522954] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, HOMODIMERIZATION, COFACTOR, SUBUNIT, TISSUE SPECIFICITY. Tissue: Brain.
[2]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed: 10591208] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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]. Tissue: Eye, Lung and Placenta.
[4]	Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 19-35; 100-119 AND 145-158, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[5]	"Identification of an essential cysteine residue in pyridoxal phosphatase from human erythrocytes." Gao G.-J., Fonda M.L. J. Biol. Chem. 269:8234-8239(1994) [PubMed: 8132548] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-30 AND 145-158, ENZYME ACTIVITY.
[6]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]	"Chronophin, a novel HAD-type serine protein phosphatase, regulates cofilin-dependent actin dynamics." Gohla A., Birkenfeld J., Bokoch G.M. Nat. Cell Biol. 7:21-29(2005) [PubMed: 15580268] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, COFACTOR, ACTIVE SITE, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-25, TISSUE SPECIFICITY.
[8]	"Structural genomics of protein phosphatases." Almo S.C., Bonanno J.B., Sauder J.M., Emtage S., Dilorenzo T.P., Malashkevich V., Wasserman S.R., Swaminathan S., Eswaramoorthy S., Agarwal R., Kumaran D., Madegowda M., Ragumani S., Patskovsky Y., Alvarado J., Ramagopal U.A., Faber-Barata J., Chance M.R. , Sali A., Fiser A., Zhang Z.Y., Lawrence D.S., Burley S.K. J. Struct. Funct. Genomics 8:121-140(2007) [PubMed: 18058037] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 2-296 IN COMPLEXES WITH PYRODOXAL PHOSPHATE; CALCIUM AND MAGNESIUM IONS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY125047 mRNA. Translation: AAM94358.1.
Z83844 Genomic DNA. Translation: CAB63038.1.
BC000320 mRNA. Translation: AAH00320.1.
BC009756 mRNA. Translation: AAH09756.2.
BC064922 mRNA. Translation: AAH64922.1.

IPI

IPI00025340.

RefSeq

NP_064711.1. NM_020315.4.

UniGene

Hs.632762.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CFR	X-ray	2.40	A	1-296	[»]
2CFS	X-ray	2.40	A	1-296	[»]
2CFT	X-ray	1.80	A	1-296	[»]
2OYC	X-ray	1.72	A	2-296	[»]
2P27	X-ray	1.90	A	2-296	[»]
2P69	X-ray	2.25	A	2-296	[»]

ProteinModelPortal

Q96GD0.

SMR

Q96GD0. Positions 1-294.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q96GD0. 1 interaction.

STRING

Q96GD0.

PTM databases

PhosphoSite

Q96GD0.

Polymorphism databases

DMDM

44888310.

2D gel databases

REPRODUCTION-2DPAGE

IPI00025340.

UCD-2DPAGE

Q96GD0.

Proteomic databases

PeptideAtlas

Q96GD0.

PRIDE

Q96GD0.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000215904; ENSP00000215904; ENSG00000241360.

GeneID

57026.

KEGG

hsa:57026.

UCSC

uc003atm.1. human.

Organism-specific databases

CTD

57026.

GeneCards

GC22P038054.

HGNC

HGNC:30259. PDXP.

HPA

HPA001099.

MIM

609246. gene.

neXtProt

NX_Q96GD0.

PharmGKB

PA134882132.

GenAtlas

Search...

Phylogenomic databases

eggNOG

maNOG18850.

GeneTree

ENSGT00510000047020.

HOVERGEN

HBG049429.

InParanoid

Q96GD0.

OMA

WNGERAV.

OrthoDB

EOG44F69M.

PhylomeDB

Q96GD0.

Enzyme and pathway databases

BRENDA

3.1.3.74. 2681.

Gene expression databases

ArrayExpress

Q96GD0.

Bgee

Q96GD0.

CleanEx

HS_PDXP.

Genevestigator

Q96GD0.

Family and domain databases

InterPro

IPR005834. Dehalogen-like_hydro.
IPR023214. HAD-like_dom.
IPR006357. HAD-SF_hydro_IIA.
IPR023215. NPhePase-like_dom.
IPR006349. PGP_euk.
[Graphical view]

Gene3D

G3DSA:3.40.50.1000. HAD-like_dom. 2 hits.
G3DSA:3.40.50.10410. NPhePase-like_dom. 1 hit.

KO

K07758.

Pfam

PF00702. Hydrolase. 1 hit.
[Graphical view]

SUPFAM

SSF56784. HAD-like_dom. 1 hit.

TIGRFAMs

TIGR01460. HAD-SF-IIA. 1 hit.
TIGR01452. PGP_euk. 1 hit.

ProtoNet

Search...

Other

DrugBank

DB00147. Pyridoxal.
DB00114. Pyridoxal Phosphate.
DB00165. Pyridoxine.

NextBio

62777.

SOURCE

Search...

Entry information

Entry name

PLPP_HUMAN

Accession

Primary (citable) accession number: Q96GD0
Secondary accession number(s): Q9UGY2

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 2004
Last sequence update:	March 1, 2004
Last modified:	January 25, 2012
This is version 92 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.