Q8WY54 (PPM1E_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein phosphatase 1E
EC=3.1.3.16

Alternative name(s):
Ca(2+)/calmodulin-dependent protein kinase phosphatase N
Short name=CaMKP-N
CaMKP-nucleus
Short name=CaMKN
Partner of PIX 1
Partner of PIX-alpha
Short name=Partner of PIXA

Gene names

Name:	PPM1E
Synonyms:	CAMKN, KIAA1072, POPX1

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

General annotation (Comments)

Function	Protein phosphatase that inactivates multifunctional CaM kinases such as CAMK4 and CAMK2 By similarity. Dephosphorylates and inactivates PAK. May play a role in the inhibition of actin fiber stress breakdown and in morphological changes driven by TNK2/CDC42. Ref.1
Catalytic activity	A phosphoprotein + H2O = a protein + phosphate.
Cofactor	Binds 2 magnesium or manganese ions per subunit By similarity.
Subunit structure	Heterotrimer. Interacts with PAX1 and ARHGEF6 (or ARHGEF7). Ref.1
Subcellular location	Nucleus. Cytoplasm. Note: A truncated form, major form, with the C-terminal part missing, is mostly found in the cytoplasm and a little in the nucleus. The full length, minor form, is found in the nucleus. Ref.7 Ref.8
Polymorphism	The poly-Pro-Glu stretch is polymorphic.
Sequence similarities	Belongs to the PP2C family. Contains 1 PP2C-like domain.
Sequence caution	The sequence BAA83024.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
Ligand	Magnesium Manganese Metal-binding
Molecular function	Hydrolase Protein phosphatase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to drug Inferred from direct assay PubMed 20801214. Source: UniProtKB negative regulation of protein kinase activity Inferred from direct assay Ref.1. Source: UniProtKB peptidyl-threonine dephosphorylation Inferred from direct assay PubMed 20801214. Source: UniProtKB positive regulation of stress fiber assembly Inferred from direct assay Ref.1. Source: UniProtKB
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleolus Inferred from direct assay. Source: HPA protein complex Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine phosphatase activity Inferred from direct assay PubMed 20801214. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8WY54-1)

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: Q8WY54-2)

The sequence of this isoform differs from the canonical sequence as follows:
     133-141: Missing.

Isoform 3 (identifier: Q8WY54-3)

The sequence of this isoform differs from the canonical sequence as follows:
     247-270: KNMRRKMEDKHVCIPDFNMLFNLE → MKSFRVIFLHIISQRKRMAQKGLW

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 764	764	Protein phosphatase 1E		PRO_0000286820
Regions
	Repeat	31 – 32	2	1
	Repeat	33 – 34	2	2
	Repeat	35 – 36	2	3
	Repeat	37 – 38	2	4
	Repeat	39 – 40	2	5
	Repeat	41 – 42	2	6
	Repeat	43 – 44	2	7
	Repeat	45 – 46	2	8; approximate
	Repeat	47 – 48	2	9
	Repeat	49 – 50	2	10
	Repeat	51 – 52	2	11
	Domain	255 – 497	243	PP2C-like
	Region	31 – 52	22	11 X 2 AA tandem repeats of P-E
	Compositional bias	7 – 100	94	Glu-rich
	Compositional bias	31 – 139	109	Pro-rich
Sites
	Metal binding	282	1	Manganese 1 By similarity
	Metal binding	282	1	Manganese 2 By similarity
	Metal binding	283	1	Manganese 1; via carbonyl oxygen By similarity
	Metal binding	444	1	Manganese 2 By similarity
	Metal binding	488	1	Manganese 2 By similarity
Natural variations
	Alternative sequence	133 – 141	9	Missing in isoform 2.		VSP_025197
	Alternative sequence	247 – 270	24	KNMRR…LFNLE → MKSFRVIFLHIISQRKRMAQ KGLW in isoform 3.		VSP_025198
	Natural variant	44	1	E → EPE.		VAR_063769
	Natural variant	231	1	L → S in a breast cancer sample; somatic mutation. Ref.9		VAR_036518
	Natural variant	320	1	R → G in a breast cancer sample; somatic mutation. Ref.9		VAR_036519
Experimental info
	Sequence conflict	53	1	L → P in DA497512. Ref.6
	Sequence conflict	394	1	V → I in AAF70325. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 2, 2010. Version 2. Checksum: 16F79EB84ED0E295	FASTA	764	85,002
	10 20 30 40 50 60 MAGCIPEEKT YRRFLELFLG EFRGPCGGGE PEPEPEPEPE PEPESEPEPE PELVEAEAAE 70 80 90 100 110 120 ASVEEPGEEA ATVAATEEGD QEQDPEPEEE AAVEGEEEEE GAATAAAAPG HSAVPPPPPQ 130 140 150 160 170 180 LPPLPPLPRP LSERITPRPL SERITREEVE GESLDLCLQQ LYKYNCPSFL AAALARATSD 190 200 210 220 230 240 EVLQSDLSAH YIPKETDGTE GTVEIETVKL ARSVFSKLHE ICCSWVKDFP LRRRPQLYYE 250 260 270 280 290 300 TSIHAIKNMR RKMEDKHVCI PDFNMLFNLE DQEEQAYFAV FDGHGGVDAA IYASIHLHVN 310 320 330 340 350 360 LVRQEMFPHD PAEALCRAFR VTDERFVQKA ARESLRCGTT GVVTFIRGNM LHVAWVGDSQ 370 380 390 400 410 420 VMLVRKGQAV ELMKPHKPDR EDEKQRIEAL GGCVVWFGAW RVNGSLSVSR AIGDAEHKPY 430 440 450 460 470 480 ICGDADSAST VLDGTEDYLI LACDGFYDTV NPDEAVKVVS DHLKENNGDS SMVAHKLVAS 490 500 510 520 530 540 ARDAGSSDNI TVIVVFLRDM NKAVNVSEES DWTENSFQGG QEDGGDDKEN HGECKRPWPQ 550 560 570 580 590 600 HQCSAPADLG YDGRVDSFTD RTSLSPGSQI NVLEDPGYLD LTQIEASKPH SAQFLLPVEM 610 620 630 640 650 660 FGPGAPKKAN LINELMMEKK SVQSSLPEWS GAGEFPTAFN LGSTGEQIYR MQSLSPVCSG 670 680 690 700 710 720 LENEQFKSPG NRVSRLSHLR HHYSKKWHRF RFNPKFYSFL SAQEPSHKIG TSLSSLTGSG 730 740 750 760 KRNRIRSSLP WRQNSWKGYS ENMRKLRKTH DIPCPDLPWS YKIE
	Isoform 2 [UniParc]. Checksum: C24C64A0A1BC1091	FASTA	755	83,952
	10 20 30 40 50 60 MAGCIPEEKT YRRFLELFLG EFRGPCGGGE PEPEPEPEPE PEPESEPEPE PELVEAEAAE 70 80 90 100 110 120 ASVEEPGEEA ATVAATEEGD QEQDPEPEEE AAVEGEEEEE GAATAAAAPG HSAVPPPPPQ 130 140 150 160 170 180 LPPLPPLPRP LSERITREEV EGESLDLCLQ QLYKYNCPSF LAAALARATS DEVLQSDLSA 190 200 210 220 230 240 HYIPKETDGT EGTVEIETVK LARSVFSKLH EICCSWVKDF PLRRRPQLYY ETSIHAIKNM 250 260 270 280 290 300 RRKMEDKHVC IPDFNMLFNL EDQEEQAYFA VFDGHGGVDA AIYASIHLHV NLVRQEMFPH 310 320 330 340 350 360 DPAEALCRAF RVTDERFVQK AARESLRCGT TGVVTFIRGN MLHVAWVGDS QVMLVRKGQA 370 380 390 400 410 420 VELMKPHKPD REDEKQRIEA LGGCVVWFGA WRVNGSLSVS RAIGDAEHKP YICGDADSAS 430 440 450 460 470 480 TVLDGTEDYL ILACDGFYDT VNPDEAVKVV SDHLKENNGD SSMVAHKLVA SARDAGSSDN 490 500 510 520 530 540 ITVIVVFLRD MNKAVNVSEE SDWTENSFQG GQEDGGDDKE NHGECKRPWP QHQCSAPADL 550 560 570 580 590 600 GYDGRVDSFT DRTSLSPGSQ INVLEDPGYL DLTQIEASKP HSAQFLLPVE MFGPGAPKKA 610 620 630 640 650 660 NLINELMMEK KSVQSSLPEW SGAGEFPTAF NLGSTGEQIY RMQSLSPVCS GLENEQFKSP 670 680 690 700 710 720 GNRVSRLSHL RHHYSKKWHR FRFNPKFYSF LSAQEPSHKI GTSLSSLTGS GKRNRIRSSL 730 740 750 PWRQNSWKGY SENMRKLRKT HDIPCPDLPW SYKIE
	Isoform 3 [UniParc]. Checksum: 5B29325645AD2C48	FASTA	764	84,967
	10 20 30 40 50 60 MAGCIPEEKT YRRFLELFLG EFRGPCGGGE PEPEPEPEPE PEPESEPEPE PELVEAEAAE 70 80 90 100 110 120 ASVEEPGEEA ATVAATEEGD QEQDPEPEEE AAVEGEEEEE GAATAAAAPG HSAVPPPPPQ 130 140 150 160 170 180 LPPLPPLPRP LSERITPRPL SERITREEVE GESLDLCLQQ LYKYNCPSFL AAALARATSD 190 200 210 220 230 240 EVLQSDLSAH YIPKETDGTE GTVEIETVKL ARSVFSKLHE ICCSWVKDFP LRRRPQLYYE 250 260 270 280 290 300 TSIHAIMKSF RVIFLHIISQ RKRMAQKGLW DQEEQAYFAV FDGHGGVDAA IYASIHLHVN 310 320 330 340 350 360 LVRQEMFPHD PAEALCRAFR VTDERFVQKA ARESLRCGTT GVVTFIRGNM LHVAWVGDSQ 370 380 390 400 410 420 VMLVRKGQAV ELMKPHKPDR EDEKQRIEAL GGCVVWFGAW RVNGSLSVSR AIGDAEHKPY 430 440 450 460 470 480 ICGDADSAST VLDGTEDYLI LACDGFYDTV NPDEAVKVVS DHLKENNGDS SMVAHKLVAS 490 500 510 520 530 540 ARDAGSSDNI TVIVVFLRDM NKAVNVSEES DWTENSFQGG QEDGGDDKEN HGECKRPWPQ 550 560 570 580 590 600 HQCSAPADLG YDGRVDSFTD RTSLSPGSQI NVLEDPGYLD LTQIEASKPH SAQFLLPVEM 610 620 630 640 650 660 FGPGAPKKAN LINELMMEKK SVQSSLPEWS GAGEFPTAFN LGSTGEQIYR MQSLSPVCSG 670 680 690 700 710 720 LENEQFKSPG NRVSRLSHLR HHYSKKWHRF RFNPKFYSFL SAQEPSHKIG TSLSSLTGSG 730 740 750 760 KRNRIRSSLP WRQNSWKGYS ENMRKLRKTH DIPCPDLPWS YKIE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The p21-activated kinase PAK is negatively regulated by POPX1 and POPX2, a pair of serine/threonine phosphatases of the PP2C family." Koh C.-G., Tan E.-J., Manser E., Lim L. Curr. Biol. 12:317-321(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH ARHGEF, VARIANT PRO-GLU-44 INS.
[2]	"Five novel genes from 17q23 amplicon have different amplification and overexpression frequency in breast cancer." Wu G., Couch F.J. Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT PRO-GLU-44 INS.
[3]	"Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 6:197-205(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT PRO-GLU-44 INS. Tissue: Brain.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Testis.
[5]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes." Kimura K., Wakamatsu A., Suzuki Y., Ota T., Nishikawa T., Yamashita R., Yamamoto J., Sekine M., Tsuritani K., Wakaguri H., Ishii S., Sugiyama T., Saito K., Isono Y., Irie R., Kushida N., Yoneyama T., Otsuka R. , Kanda K., Yokoi T., Kondo H., Wagatsuma M., Murakawa K., Ishida S., Ishibashi T., Takahashi-Fujii A., Tanase T., Nagai K., Kikuchi H., Nakai K., Isogai T., Sugano S. Genome Res. 16:55-65(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-112.
[7]	"Identification and characterization of nuclear localization signals of CaMKP-N." Takeuchi M., Taniguchi T., Fujisawa H. J. Biochem. 136:183-188(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[8]	"Post-translational excision of the carboxyl-terminal segment of CaM kinase phosphatase N and its cytosolic occurrence in the brain." Kitani T., Okuno S., Nakamura Y., Tokuno H., Takeuchi M., Fujisawa H. J. Neurochem. 96:374-384(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[9]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-231 AND GLY-320.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF520614 mRNA. Translation: AAM76058.1. AF260269 mRNA. Translation: AAF70325.1. AB028995 mRNA. Translation: BAA83024.2. Different initiation. CR749253 mRNA. Translation: CAH18109.1. AC025521 Genomic DNA. No translation available. AC100832 Genomic DNA. No translation available. DA497512 mRNA. No translation available. DA791319 mRNA. No translation available.
IPI	IPI00103630. IPI00845240. IPI00845435.
UniGene	Hs.245044.
3D structure databases
HSSP	HSSP built from PDB template 1A6Q based on UniProtKB P35813.
ProteinModelPortal	Q8WY54.
SMR	Q8WY54. Positions 245-498.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8WY54. 1 interaction.
STRING	9606.ENSP00000312411.
PTM databases
PhosphoSite	Q8WY54.
Polymorphism databases
DMDM	311033412.
Proteomic databases
PaxDb	Q8WY54.
PRIDE	Q8WY54.
Protocols and materials databases
DNASU	22843.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000308249; ENSP00000312411; ENSG00000175175.
UCSC	uc002iwx.3. human. uc010ddd.3. human.
Organism-specific databases
GeneCards	GC17P056833.
H-InvDB	HIX0014038.
HGNC	HGNC:19322. PPM1E.
HPA	HPA018462. HPA019263.
neXtProt	NX_Q8WY54.
PharmGKB	PA134943567.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0631.
HOGENOM	HOG000059266.
HOVERGEN	HBG098260.
InParanoid	Q8WY54.
OMA	PVEMFGP.
OrthoDB	EOG48SGSJ.
Gene expression databases
ArrayExpress	Q8WY54.
Bgee	Q8WY54.
CleanEx	HS_PPM1E.
Genevestigator	Q8WY54.
Family and domain databases
Gene3D	3.60.40.10. 1 hit.
InterPro	IPR001932. PP2C-like. IPR000222. PP2C_Mn2_Asp60_BS. IPR015655. Protein_Pase_2C. [Graphical view]
PANTHER	PTHR13832. PTHR13832. 1 hit.
Pfam	PF00481. PP2C. 1 hit. [Graphical view]
SMART	SM00331. PP2C_SIG. 1 hit. SM00332. PP2Cc. 1 hit. [Graphical view]
SUPFAM	SSF81606. PP2C-related. 1 hit.
PROSITE	PS01032. PP2C. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	PPM1E. human.
NextBio	13643771.

Entry information

Entry name

PPM1E_HUMAN

Accession

Primary (citable) accession number: Q8WY54
Secondary accession number(s): Q68DW1, Q7LAF3, Q9UPT0

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 15, 2007
Last sequence update:	November 2, 2010
Last modified:	May 1, 2013
This is version 84 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.