Laforin (EC 3.1.3.-) (EC 3.1.3.16) (EC 3.1.3.48) (Glucan phosphatase) (Glycogen phosphatase) (Lafora PTPase) (LAFPTPase)
1_MRFRF 6_ GVVVP 11_ PAVAG 16_ ARPEL 21_ LVVGS 26_ RPELG 31_ RWEPR 36_ GAVRL 41_ RPAGT 46_ AAGDG 51_ ALALQ 56_ EPGLW 61_ LGEVE 66_ LAAEE 71_ AAQDG 76_ AEPGR 81_ VDTFW 86_ YKFLK 91_ REPGG 96_ ELSWE 101_ GNGPH 106_ HDRCC 111_ TYNEN 116_ NLVDG 121_ VYCLP 126_ IGHWI 131_ EATGH 136_ TNEMK 141_ HTTDF 146_ YFNIA 151_ GHQAM 156_ HYSRI 161_ LPNIW 166_ LGSCP 171_ RQVEH 176_ VTIKL 181_ KHELG 186_ ITAVM 191_ NFQTE 196_ WDIVQ 201_ NSSGC 206_ NRYPE 211_ PMTPD 216_ TMIKL 221_ YREEG 226_ LAYIW 231_ MPTPD 236_ MSTEG 241_ RVQML 246_ PQAVC 251_ LLHAL 256_ LEKGH 261_ IVYVH 266_ CNAGV 271_ GRSTA 276_ AVCGW 281_ LQYVM 286_ GWNLR 291_ KVQYF 296_ LMAKR 301_ PAVYI 306_ DEEAL 311_ ARAQE 316_ DFFQK 321_ FGKVR 326_SSVCS
1: Plays an important role in preventing glycogen hyperphosphorylation and the formation of insoluble aggregates, via its activity as glycogen phosphatase, and by promoting the ubiquitination of proteins involved in glycogen metabolism via its interaction with the E3 ubiquitin ligase NHLRC1/malin. Shows strong phosphatase activity towards complex carbohydrates in vitro, avoiding glycogen hyperphosphorylation which is associated with reduced branching and formation of insoluble aggregates (PubMed:16901901, PubMed:23922729, PubMed:25538239, PubMed:25544560, PubMed:26231210). Dephosphorylates phosphotyrosine and synthetic substrates, such as para-nitrophenylphosphate (pNPP), and has low activity with phosphoserine and phosphothreonine substrates (in vitro) (PubMed:11001928, PubMed:11220751, PubMed:11739371, PubMed:14532330, PubMed:14722920, PubMed:16971387, PubMed:18617530, PubMed:22036712, PubMed:23922729). Has been shown to dephosphorylate MAPT (By similarity). Forms a complex with NHLRC1/malin and HSP70, which suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system (UPS). Acts as a scaffold protein to facilitate PPP1R3C/PTG ubiquitination by NHLRC1/malin (PubMed:23922729). Also promotes proteasome-independent protein degradation through the macroautophagy pathway (PubMed:20453062)
2: Does not bind to glycogen (PubMed:18617530). Lacks phosphatase activity and might function as a dominant-negative regulator for the phosphatase activity of isoform 1 and isoform 7 (PubMed:18617530, PubMed:22036712)
3: Has phosphatase activity (in vitro)