RBCC

Full text data of PDXP

PDXP (CIN, PLP, PLPP) [Confidence: low (only semi-automatic identification from reviews)]
Pyridoxal phosphate phosphatase; PLP phosphatase; 3.1.3.3; 3.1.3.74 (Chronophin)

UniProt Q96GD0
ID PLPP_HUMAN Reviewed; 296 AA.
AC Q96GD0; Q9UGY2;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2004, sequence version 2.
DT 22-JAN-2014, entry version 109.
DE RecName: Full=Pyridoxal phosphate phosphatase;
DE Short=PLP phosphatase;
DE EC=3.1.3.3;
DE EC=3.1.3.74;
DE AltName: Full=Chronophin;
GN Name=PDXP; Synonyms=CIN, PLP, PLPP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, HOMODIMERIZATION, COFACTOR,
RP SUBUNIT, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=14522954; DOI=10.1074/jbc.M309619200;
RA Jang Y.M., Kim D.W., Kang T.-C., Won M.H., Baek N.-I., Moon B.J.,
RA Choi S.Y., Kwon O.-S.;
RT "Human pyridoxal phosphatase. Molecular cloning, functional
RT expression, and tissue distribution.";
RL J. Biol. Chem. 278:50040-50046(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye, Lung, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 19-35; 100-119 AND 145-158, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [5]
RP PROTEIN SEQUENCE OF 19-30 AND 145-158, AND ENZYME ACTIVITY.
RX PubMed=8132548;
RA Gao G.-J., Fonda M.L.;
RT "Identification of an essential cysteine residue in pyridoxal
RT phosphatase from human erythrocytes.";
RL J. Biol. Chem. 269:8234-8239(1994).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, COFACTOR, ACTIVE
RP SITE, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-25, AND TISSUE
RP SPECIFICITY.
RX PubMed=15580268; DOI=10.1038/ncb1201;
RA Gohla A., Birkenfeld J., Bokoch G.M.;
RT "Chronophin, a novel HAD-type serine protein phosphatase, regulates
RT cofilin-dependent actin dynamics.";
RL Nat. Cell Biol. 7:21-29(2005).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 2-296 IN COMPLEXES WITH
RP PYRODOXAL PHOSPHATE; CALCIUM AND MAGNESIUM IONS.
RX PubMed=18058037; DOI=10.1007/s10969-007-9036-1;
RA Almo S.C., Bonanno J.B., Sauder J.M., Emtage S., Dilorenzo T.P.,
RA Malashkevich V., Wasserman S.R., Swaminathan S., Eswaramoorthy S.,
RA Agarwal R., Kumaran D., Madegowda M., Ragumani S., Patskovsky Y.,
RA Alvarado J., Ramagopal U.A., Faber-Barata J., Chance M.R., Sali A.,
RA Fiser A., Zhang Z.Y., Lawrence D.S., Burley S.K.;
RT "Structural genomics of protein phosphatases.";
RL J. Struct. Funct. Genomics 8:121-140(2007).
CC -!- FUNCTION: Protein serine phosphatase that dephosphorylates 'Ser-3'
CC in cofilin and probably also dephosphorylates phospho-serine
CC residues in DSTN. Regulates cofilin-dependent actin cytoskeleton
CC reorganization. Required for normal progress through mitosis and
CC normal cytokinesis. Does not dephosphorylate phospho-threonines in
CC LIMK1. Does not dephosphorylate peptides containing phospho-
CC tyrosine. Pyridoxal phosphate phosphatase. Has some activity
CC towards pyridoxal 5'-phosphate (PLP), pyridoxine 5'-phosphate
CC (PMP) and pyridoxine 5'-phosphate (PNP), with a highest activity
CC with PLP followed by PNP.
CC -!- CATALYTIC ACTIVITY: Pyridoxal 5'-phosphate + H(2)O = pyridoxal +
CC phosphate.
CC -!- CATALYTIC ACTIVITY: O-phospho-L(or D)-serine + H(2)O = L(or D)-
CC serine + phosphate.
CC -!- COFACTOR: Divalent ions. Magnesium is the most effective.
CC -!- ENZYME REGULATION: Inhibited by NaF, Zn(2+), Ca(2+), Mn(2+) and
CC EDTA.
CC -!- SUBUNIT: Homodimer.
CC -!- INTERACTION:
CC P29066:Arrb1 (xeno); NbExp=2; IntAct=EBI-4303060, EBI-4303019;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Cytoplasm, cytoskeleton.
CC Cell projection, ruffle membrane; Peripheral membrane protein;
CC Cytoplasmic side. Cell projection, lamellipodium membrane;
CC Peripheral membrane protein; Cytoplasmic side. Cell membrane;
CC Peripheral membrane protein; Cytoplasmic side. Note=Colocalizes
CC with the actin cytoskeleton in membrane ruffles and lamellipodia.
CC Diffusely distributed throughout the cytosol during pro-metaphase
CC and metaphase. Detected at the dynamic cell poles during
CC telophase. Detected at the cleavage furrow and contractile ring
CC during cytokinesis. Transiently detected at the plasma membrane in
CC late stages of cytokinesis. Detected at the midbody.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed in all the
CC regions of central nerve system except the spinal cord. Also
CC expressed at high level in liver and testis. In fetus, it is
CC weakly expressed in all organs except brain.
CC -!- SIMILARITY: Belongs to the HAD-like hydrolase superfamily.
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DR EMBL; AY125047; AAM94358.1; -; mRNA.
DR EMBL; Z83844; CAB63038.1; -; Genomic_DNA.
DR EMBL; BC000320; AAH00320.1; -; mRNA.
DR EMBL; BC009756; AAH09756.2; -; mRNA.
DR EMBL; BC064922; AAH64922.1; -; mRNA.
DR RefSeq; NP_064711.1; NM_020315.4.
DR UniGene; Hs.632762; -.
DR PDB; 2CFR; X-ray; 2.40 A; A=1-296.
DR PDB; 2CFS; X-ray; 2.40 A; A=1-296.
DR PDB; 2CFT; X-ray; 1.80 A; A=1-296.
DR PDB; 2OYC; X-ray; 1.72 A; A=2-296.
DR PDB; 2P27; X-ray; 1.90 A; A=2-296.
DR PDB; 2P69; X-ray; 2.25 A; A=2-296.
DR PDBsum; 2CFR; -.
DR PDBsum; 2CFS; -.
DR PDBsum; 2CFT; -.
DR PDBsum; 2OYC; -.
DR PDBsum; 2P27; -.
DR PDBsum; 2P69; -.
DR ProteinModelPortal; Q96GD0; -.
DR SMR; Q96GD0; 1-294.
DR IntAct; Q96GD0; 1.
DR STRING; 9606.ENSP00000215904; -.
DR DrugBank; DB00147; Pyridoxal.
DR DrugBank; DB00114; Pyridoxal Phosphate.
DR DrugBank; DB00165; Pyridoxine.
DR PhosphoSite; Q96GD0; -.
DR DMDM; 44888310; -.
DR REPRODUCTION-2DPAGE; IPI00025340; -.
DR UCD-2DPAGE; Q96GD0; -.
DR PaxDb; Q96GD0; -.
DR PeptideAtlas; Q96GD0; -.
DR PRIDE; Q96GD0; -.
DR Ensembl; ENST00000215904; ENSP00000215904; ENSG00000241360.
DR GeneID; 57026; -.
DR KEGG; hsa:57026; -.
DR UCSC; uc003atm.1; human.
DR CTD; 57026; -.
DR GeneCards; GC22P038054; -.
DR HGNC; HGNC:30259; PDXP.
DR HPA; HPA001099; -.
DR MIM; 609246; gene.
DR neXtProt; NX_Q96GD0; -.
DR PharmGKB; PA134882132; -.
DR eggNOG; COG0647; -.
DR HOGENOM; HOG000068104; -.
DR HOVERGEN; HBG049429; -.
DR InParanoid; Q96GD0; -.
DR KO; K07758; -.
DR OMA; CITEDFS; -.
DR OrthoDB; EOG7XDBG1; -.
DR PhylomeDB; Q96GD0; -.
DR BRENDA; 3.1.3.74; 2681.
DR SABIO-RK; Q96GD0; -.
DR EvolutionaryTrace; Q96GD0; -.
DR GenomeRNAi; 57026; -.
DR NextBio; 62777; -.
DR PRO; PR:Q96GD0; -.
DR ArrayExpress; Q96GD0; -.
DR Bgee; Q96GD0; -.
DR CleanEx; HS_PDXP; -.
DR Genevestigator; Q96GD0; -.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0031258; C:lamellipodium membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031072; F:heat shock protein binding; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IDA:UniProtKB.
DR GO; GO:0004647; F:phosphoserine phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0033883; F:pyridoxal phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0031247; P:actin rod assembly; IDA:MGI.
DR GO; GO:0071318; P:cellular response to ATP; IDA:MGI.
DR GO; GO:0030836; P:positive regulation of actin filament depolymerization; IMP:UniProtKB.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:UniProtKB.
DR GO; GO:0032465; P:regulation of cytokinesis; IMP:UniProtKB.
DR GO; GO:0007088; P:regulation of mitosis; IMP:UniProtKB.
DR Gene3D; 3.40.50.1000; -; 2.
DR Gene3D; 3.40.50.10410; -; 1.
DR InterPro; IPR023214; HAD-like_dom.
DR InterPro; IPR006357; HAD-SF_hydro_IIA.
DR InterPro; IPR023215; NPhePase-like_dom.
DR InterPro; IPR006349; PGP_euk.
DR Pfam; PF13344; Hydrolase_6; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR TIGRFAMs; TIGR01460; HAD-SF-IIA; 1.
DR TIGRFAMs; TIGR01452; PGP_euk; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cell projection; Complete proteome;
KW Cytoplasm; Cytoskeleton; Direct protein sequencing; Hydrolase;
KW Magnesium; Membrane; Metal-binding; Pyridoxal phosphate;
KW Reference proteome.
FT CHAIN 1 296 Pyridoxal phosphate phosphatase.
FT /FTId=PRO_0000068837.
FT REGION 58 62 Substrate binding.
FT ACT_SITE 25 25 Nucleophile.
FT ACT_SITE 27 27 Proton donor (Probable).
FT METAL 25 25 Magnesium.
FT METAL 27 27 Magnesium; via carbonyl oxygen.
FT METAL 238 238 Magnesium.
FT BINDING 182 182 Substrate.
FT BINDING 213 213 Substrate.
FT MUTAGEN 25 25 D->N: Abolishes phosphatase activity.
FT HELIX 9 18
FT STRAND 20 24
FT TURN 27 29
FT STRAND 30 32
FT HELIX 40 49
FT STRAND 53 58
FT HELIX 65 74
FT HELIX 82 84
FT STRAND 85 87
FT HELIX 88 99
FT STRAND 104 106
FT STRAND 109 114
FT HELIX 116 124
FT STRAND 143 148
FT HELIX 156 166
FT STRAND 171 176
FT STRAND 181 183
FT STRAND 189 191
FT HELIX 193 204
FT HELIX 217 225
FT HELIX 230 232
FT STRAND 233 238
FT TURN 240 242
FT HELIX 243 250
FT STRAND 253 261
FT HELIX 264 272
FT HELIX 276 278
FT STRAND 281 286
FT HELIX 287 293
SQ SEQUENCE 296 AA; 31698 MW; 33466C35A76B458C CRC64;
MARCERLRGA ALRDVLGRAQ GVLFDCDGVL WNGERAVPGA PELLERLARA GKAALFVSNN
SRRARPELAL RFARLGFGGL RAEQLFSSAL CAARLLRQRL PGPPDAPGAV FVLGGEGLRA
ELRAAGLRLA GDPSAGDGAA PRVRAVLVGY DEHFSFAKLR EACAHLRDPE CLLVATDRDP
WHPLSDGSRT PGTGSLAAAV ETASGRQALV VGKPSPYMFE CITENFSIDP ARTLMVGDRL
ETDILFGHRC GMTTVLTLTG VSRLEEAQAY LAAGQHDLVP HYYVESIADL TEGLED
//

MIM 609246
*RECORD*
*FIELD* NO
609246
*FIELD* TI
*609246 PYRIDOXAL PHOSPHATASE; PDXP
;;PLP PHOSPHATASE;;
CHRONOPHIN; CIN
*FIELD* TX
read more
DESCRIPTION

Pyridoxal 5-prime-phosphate (PLP) is the active form of vitamin B6 that
acts as a coenzyme in maintaining biochemical homeostasis. The preferred
degradation route from PLP to 4-pyridoxic acid involves the
dephosphorylation of PLP by PDXP (Jang et al., 2003).

CLONING

By searching an EST database for sequences similar to tryptic fragments
of purified erythrocyte PDXP, followed by PCR of a brain cDNA library,
Jang et al. (2003) cloned PDXP, which they called PLP phosphatase. The
deduced 296-amino acid protein has a calculated molecular mass of 31.7
kD. PDXP contains 2 N-glycosylation sites, 7 phosphorylation sites, and
4 N-myristoylation sites. Gel filtration analysis showed that
recombinant PDXP expressed in E. coli formed dimers of about 60 kD.
Northern blot analysis detected a 2.1-kb transcript expressed at
variable levels in all adult tissues examined. RNA dot blot analysis
detected ubiquitous expression, with highest levels in fetal brain and
all adult brain regions examined. High expression was also detected in
liver and testis. Jang et al. (2003) also cloned mouse Pdxp, which
encodes a deduced 292-amino acid protein that shares 94% identity with
human PDXP.

Gohla et al. (2005) cloned human PDXP, which they called chronophin, by
searching databases using the bovine sequence and RT-PCR of HeLa cell
RNA. They derived the name chronophin from 'chronos,' the Greek word for
time, because the protein seemed to regulate cofilin (see
601442)-dependent actin dynamics in a temporal and spatial manner. The
deduced protein contains motifs characteristic of haloacid
dehalogenases. Endogenous PDXP partially colocalized with F-actin and
cofilin in membrane ruffles and lamellipodia. It showed a dynamic
localization during the cell cycle, with strong colocalization with
cofilin at constricting cleavage furrows during cytokinesis.

GENE FUNCTION

By expression in E. coli, Jang et al. (2003) obtained catalytically
active PDXP that showed highest phosphatase activity toward PLP and
required a divalent ion, preferably Mg(2+). PDXP had lower catalytic
activity against pyridoxine 5-prime-phosphate and pyridoxamine
5-prime-phosphate, and very low activity against p-nitrophenyl
phosphate.

Gohla et al. (2005) demonstrated that recombinant PDXP hydrolyzed
p-nitrophenyl phosphate in a concentration-dependent manner. Mutation of
a conserved catalytic residue, asp25, inactivated the enzyme. PDXP
dephosphorylated ser3 of cofilin in a concentration-dependent manner,
but it was inactive against several other phosphorylated protein and
peptide substrates. Overexpression of PDXP in HeLa cells decreased the
steady-state levels of phosphorylated cofilin. Overexpression also
caused dissolution of cortical actin cytoskeletons and reduced stress
fiber content. Catalytically inactive PDXP functioned as a
dominant-negative phosphatase when overexpressed, increasing
phosphorylated cofilin levels and actin polymerization. Depletion of
endogenous PDXP levels with RNA interference increased phosphorylated
cofilin levels, elevated total cellular F-actin content, and stabilized
membrane protrusions and stress fibers. Gohla et al. (2005) concluded
that PDXP has a role in cofilin-mediated actin reorganization.

GENE STRUCTURE

Jang et al. (2003) determined that the coding region of the PDXP gene is
contained within 2 exons.

MAPPING

By genomic sequence analysis, Jang et al. (2003) mapped the PDXP gene to
chromosome 22q12.3. They mapped the mouse Pdxp gene to chromosome 15E1.

*FIELD* RF
1. Gohla, A.; Birkenfeld, J.; Bokoch, G. M.: Chronophin, a novel
HAD-type serine protein phosphatase, regulates cofilin-dependent actin
dynamics. Nature Cell Biol. 7: 21-29, 2005.

2. Jang, Y. M.; Kim, D. W.; Kang, T.-C.; Won, M. H.; Baek, N.-I.;
Moon, B. J.; Choi, S. Y.; Kwon, O.-S.: Human pyridoxal phosphatase:
molecular cloning, functional expression, and tissue distribution. J.
Biol. Chem. 278: 50040-50046, 2003.

*FIELD* CD
Patricia A. Hartz: 3/9/2005

*FIELD* ED
mgross: 03/09/2005

RBCC Red Blood Cell Collection

Full text data of PDXP