Q9WUA5 (EPM2A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Laforin
EC=3.1.3.16
EC=3.1.3.48

Alternative name(s):
Lafora PTPase
Short name=LAFPTPase

Gene names

Name:

Epm2a

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	330 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Dual specificity protein phosphatase. May be involved in the control of glycogen metabolism, particularly in monitoring for and preventing the formation of poorly branched glycogen molecules (polyglucosans). Acts as a scaffold protein to facilitate PPP1R3C/PTG ubiquitination by NHLRC1/malin By similarity. Forms a complex with NHLRC1/malin and HSP70 and this complex suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system (UPS). Ref.7
Catalytic activity	Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. A phosphoprotein + H2O = a protein + phosphate.
Subunit structure	Interacts with itself; interacts also with PPP1R3C, HIRIP5 and EPM2AIP1. Interacts with NHLRC1/malin (via the NHL repeats) By similarity. Forms a complex with NHLRC1/malin and HSP70. Binds polyglucosans and glycogen. Ref.6
Subcellular location	Cytoplasm. Endoplasmic reticulum. Note: Under glycogenolytic conditions localizes to the nucleus By similarity. Ref.6
Tissue specificity	Widely expressed. Higher levels of expression are found in heart, brain, liver, skeletal muscle and kidney. Found in neuronal dendrites and perikarya, but not in axons. Ref.1 Ref.6
Developmental stage	In the embryo, highly expressed at 17 dpc. Detected in all postnatal stages, but highest expression is found at day 160 after birth. Ref.5
Post-translational modification	Polyubiquitinated by NHLRC1/malin By similarity. Phosphorylation on Ser-25 by AMPK affects the phosphatase activity of the enzyme and its ability to homodimerize and interact with NHLRC1, PPP1R3C or PRKAA2 By similarity.
Sequence similarities	Belongs to the protein-tyrosine phosphatase family. Contains 1 CBM20 (carbohydrate binding type-20) domain. Contains 1 tyrosine-protein phosphatase domain.

Ontologies

Keywords
Biological process	Carbohydrate metabolism Glycogen metabolism
Cellular component	Cytoplasm Endoplasmic reticulum
Molecular function	Hydrolase Protein phosphatase
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	behavior Inferred from mutant phenotype PubMed 12019206. Source: MGI glycogen metabolic process Inferred from electronic annotation. Source: UniProtKB-KW nervous system development Inferred from mutant phenotype PubMed 12019206. Source: MGI protein dephosphorylation Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular_component	cytosol Inferred from sequence alignment PubMed 12915448. Source: MGI endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay PubMed 17908927. Source: MGI polysome Inferred from electronic annotation. Source: Compara
Molecular_function	protein tyrosine phosphatase activity Inferred from electronic annotation. Source: EC protein tyrosine/serine/threonine phosphatase activity Inferred from Biological aspect of Ancestor. Source: RefGenome starch binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Gsk3b	Q9WV60	2	EBI-1040928,EBI-400793

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 330	330	Laforin		PRO_0000094839
Regions
	Domain	1 – 123	123	CBM20
	Domain	242 – 310	69	Tyrosine-protein phosphatase
Amino acid modifications
	Modified residue	25	1	Phosphoserine; by AMPK By similarity
Experimental info
	Sequence conflict	140	1	H → R in AAD26336. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9WUA5 [UniParc]. Last modified October 3, 2012. Version 2. Checksum: 89B18C64BBBAB02A	FASTA	330	36,958
	10 20 30 40 50 60 MLFRFGVVVP PAVAGARQEL LLAGSRPELG RWEPHGAVRL RPAGTAAGAA ALALQEPGLW 70 80 90 100 110 120 LAEVELEAYE EAGGAEPGRV DTFWYKFLQR EPGGELHWEG NGPHHDRCCT YNEDNLVDGV 130 140 150 160 170 180 YCLPVGHWIE ATGHTNEMKH TTDFYFNIAG HQAMHYSRIL PNIWLGSCPR QLEHVTIKLK 190 200 210 220 230 240 HELGVTAVMN FQTEWDIIQN SSGCNRYPEP MTPDTMMKLY KEEGLSYIWM PTPDMSTEGR 250 260 270 280 290 300 VQMLPQAVCL LHALLENGHT VYVHCNAGVG RSTAAVCGWL HYVIGWNLRK VQYFIMAKRP 310 320 330 AVYIDEDALA QAQQDFSQKF GKVHSSICAL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of mouse homologue for the human epilepsy gene, EPM2A." Ganesh S., Amano K., Delgado-Escueta A.V., Yamakawa K. Biochem. Biophys. Res. Commun. 257:24-28(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Strain: ICR. Tissue: Brain.
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[3]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 10-137. Strain: C57BL/6J. Tissue: Thymus.
[5]	"Regional and developmental expression of Epm2a gene and its evolutionary conservation." Ganesh S., Agarwala K.L., Amano K., Suzuki T., Delgado-Escueta A.V., Yamakawa K. Biochem. Biophys. Res. Commun. 283:1046-1053(2001) [PubMed] [Europe PMC] [Abstract] Cited for: DEVELOPMENTAL STAGE.
[6]	"Laforin preferentially binds the neurotoxic starch-like polyglucosans, which form in its absence in progressive myoclonus epilepsy." Chan E.M., Ackerley C.A., Lohi H., Ianzano L., Cortez M.A., Shannon P., Scherer S.W., Minassian B.A. Hum. Mol. Genet. 13:1117-1129(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH POLYGLUCOSANS AND GLYCOGEN.
[7]	"The malin-laforin complex suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system." Garyali P., Siwach P., Singh P.K., Puri R., Mittal S., Sengupta S., Parihar R., Ganesh S. Hum. Mol. Genet. 18:688-700(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, COMPLEX FORMATION WITH NHLRC1 AND HSP70.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF124044 mRNA. Translation: AAD26336.1. AC101984 Genomic DNA. No translation available. AC157018 Genomic DNA. No translation available. CH466562 Genomic DNA. Translation: EDL03516.1. AK041609 mRNA. Translation: BAC31004.1.
IPI	IPI00124446.
RefSeq	NP_034276.2. NM_010146.2.
UniGene	Mm.89946.
3D structure databases
ProteinModelPortal	Q9WUA5.
SMR	Q9WUA5. Positions 153-315.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9WUA5. 1 interaction.
MINT	MINT-8374088.
Protein family/group databases
CAZy	CBM20. Carbohydrate-Binding Module Family 20.
PTM databases
PhosphoSite	Q9WUA5.
Proteomic databases
PRIDE	Q9WUA5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000069106; ENSMUSP00000066050; ENSMUSG00000055493.
GeneID	13853.
KEGG	mmu:13853.
UCSC	uc007ejv.1. mouse.
Organism-specific databases
CTD	7957.
MGI	MGI:1341085. Epm2a.
Phylogenomic databases
eggNOG	NOG243912.
GeneTree	ENSGT00390000010101.
HOGENOM	HOG000285975.
HOVERGEN	HBG051493.
InParanoid	Q9WUA5.
KO	K14165.
OMA	RKVQYFV.
OrthoDB	EOG4PZJ72.
Gene expression databases
Genevestigator	Q9WUA5.
GermOnline	ENSMUSG00000055493. Mus musculus.
Family and domain databases
Gene3D	2.60.40.10. 1 hit.
InterPro	IPR013784. Carb-bd-like_fold. IPR002044. CBM_fam20. IPR000340. Dual-sp_phosphatase_cat-dom. IPR020422. Dual-sp_phosphatase_subgr_cat. IPR024950. DUSP. IPR013783. Ig-like_fold. IPR000387. Tyr/Dual-sp_Pase. IPR016130. Tyr_Pase_AS. [Graphical view]
PANTHER	PTHR10159. PTHR10159. 1 hit.
Pfam	PF00686. CBM_20. 1 hit. PF00782. DSPc. 1 hit. [Graphical view]
SMART	SM01065. CBM_2. 1 hit. [Graphical view]
SUPFAM	SSF49452. CBD_4. 1 hit.
PROSITE	PS51166. CBM20. 1 hit. PS00383. TYR_PHOSPHATASE_1. 1 hit. PS50056. TYR_PHOSPHATASE_2. 1 hit. PS50054. TYR_PHOSPHATASE_DUAL. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	284714.
SOURCE	Search...

Entry information

Entry name

EPM2A_MOUSE

Accession

Primary (citable) accession number: Q9WUA5
Secondary accession number(s): G5E8E2, Q8BY80

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	October 3, 2012
Last modified:	May 29, 2013
This is version 95 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program