G2Cdb::Gene report

Gene id
G00002402
Gene symbol
PPFIA2 (HGNC)
Species
Homo sapiens
Description
protein tyrosine phosphatase, receptor type, f polypeptide (PTPRF), interacting protein (liprin), alpha 2
Orthologue
G00001153 (Mus musculus)

Databases (7)

Gene
ENSG00000139220 (Ensembl human gene)
8499 (Entrez Gene)
1034 (G2Cdb plasticity & disease)
PPFIA2 (GeneCards)
Literature
603143 (OMIM)
Marker Symbol
HGNC:9246 (HGNC)
Protein Sequence
O75334 (UniProt)

Literature (7)

Pubmed - other

  • A PP2A phosphatase high density interaction network identifies a novel striatin-interacting phosphatase and kinase complex linked to the cerebral cavernous malformation 3 (CCM3) protein.

    Goudreault M, D'Ambrosio LM, Kean MJ, Mullin MJ, Larsen BG, Sanchez A, Chaudhry S, Chen GI, Sicheri F, Nesvizhskii AI, Aebersold R, Raught B and Gingras AC

    Samuel Lunenfeld Research Institute at Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.

    The serine/threonine protein phosphatases are targeted to specific subcellular locations and substrates in part via interactions with a wide variety of regulatory proteins. Understanding these interactions is thus critical to understanding phosphatase function. Using an iterative affinity purification/mass spectrometry approach, we generated a high density interaction map surrounding the protein phosphatase 2A catalytic subunit. This approach recapitulated the assembly of the PP2A catalytic subunit into many different trimeric complexes but also revealed several new protein-protein interactions. Here we define a novel large multiprotein assembly, referred to as the striatin-interacting phosphatase and kinase (STRIPAK) complex. STRIPAK contains the PP2A catalytic (PP2Ac) and scaffolding (PP2A A) subunits, the striatins (PP2A regulatory B''' subunits), the striatin-associated protein Mob3, the novel proteins STRIP1 and STRIP2 (formerly FAM40A and FAM40B), the cerebral cavernous malformation 3 (CCM3) protein, and members of the germinal center kinase III family of Ste20 kinases. Although the function of the CCM3 protein is unknown, the CCM3 gene is mutated in familial cerebral cavernous malformations, a condition associated with seizures and strokes. Our proteomics survey indicates that a large portion of the CCM3 protein resides within the STRIPAK complex, opening the way for further studies of CCM3 biology. The STRIPAK assembly establishes mutually exclusive interactions with either the CTTNBP2 proteins (which interact with the cytoskeletal protein cortactin) or a second subcomplex consisting of the sarcolemmal membrane-associated protein (SLMAP) and the related coiled-coil proteins suppressor of IKKepsilon (SIKE) and FGFR1OP2. We have thus identified several novel PP2A-containing protein complexes, including a large assembly linking kinases and phosphatases to a gene mutated in human disease.

    Funded by: NHLBI NIH HHS: N01-HV-28179, N01HV28179

    Molecular & cellular proteomics : MCP 2009;8;1;157-71

  • Interaction of the ERC family of RIM-binding proteins with the liprin-alpha family of multidomain proteins.

    Ko J, Na M, Kim S, Lee JR and Kim E

    National Creative Research Initiative Center for Synaptogenesis and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.

    Liprin-alpha/SYD-2 is a family of multidomain proteins with four known isoforms. One of the reported functions of liprin-alpha is to regulate the development of presynaptic active zones, but the underlying mechanism is poorly understood. Here we report that liprin-alpha directly interacts with the ERC (ELKS-Rab6-interacting protein-CAST) family of proteins, members of which are known to bind RIMs, the active zone proteins that regulate neurotransmitter release. In vitro results indicate that ERC2/CAST, an active zone-specific isoform, interacts with all of the known isoforms of liprin-alpha and that liprin-alpha1 associates with both ERC2 and ERC1b, a splice variant of ERC1 that distributes to both cytosolic and active zone regions. ERC2 colocalizes with liprin-alpha1 in cultured neurons and forms a complex with liprin-alpha1 in brain. Liprin-alpha1, when expressed alone in cultured neurons, shows a partial synaptic localization. When coexpressed with ERC2, however, liprin-alpha1 is redistributed to synaptic sites. Moreover, roughly the first half of ERC2, which contains the liprin-alpha-binding region, is sufficient for the synaptic localization of liprin-alpha1 while the second half is not. These results suggest that the interaction between ERC2 and liprin-alpha may be involved in the presynaptic localization of liprin-alpha and the molecular organization of presynaptic active zones.

    The Journal of biological chemistry 2003;278;43;42377-85

  • Interaction between liprin-alpha and GIT1 is required for AMPA receptor targeting.

    Ko J, Kim S, Valtschanoff JG, Shin H, Lee JR, Sheng M, Premont RT, Weinberg RJ and Kim E

    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.

    Liprin-alpha is a multidomain protein that interacts with the LAR family of receptor protein tyrosine phosphatases and the GRIP/ABP family of AMPA receptor-interacting proteins. Previous studies have indicated that liprin-alpha regulates the development of presynaptic active zones and that the association of liprin-alpha with GRIP is required for postsynaptic targeting of AMPA receptors. However, the underlying molecular mechanisms are not well understood. Here we report that liprin-alpha directly interacts with GIT1, a multidomain protein with GTPase-activating protein activity for the ADP-ribosylation factor family of small GTPases known to regulate protein trafficking and the actin cytoskeleton. Electron microscopic analysis indicates that GIT1 distributes to the region of postsynaptic density (PSD) as well as presynaptic active zones. GIT1 is enriched in PSD fractions and forms a complex with liprin-alpha, GRIP, and AMPA receptors in brain. Expression of dominant-negative constructs interfering with the GIT1-liprin-alpha interaction leads to a selective and marked reduction in the dendritic and surface clustering of AMPA receptors in cultured neurons. These results suggest that the GIT1-liprin-alpha interaction is required for AMPA receptor targeting and that GIT1 may play an important role in the organization of presynaptic and postsynaptic multiprotein complexes.

    The Journal of neuroscience : the official journal of the Society for Neuroscience 2003;23;5;1667-77

  • Liprin-alpha2 gene, protein tyrosine phosphatase LAR interacting protein related gene, is downregulated by androgens in the human prostate cancer cell line LNCaP.

    Fujinami K, Uemura H, Ishiguro H and Kubota Y

    Department of Urology, Yokohama City University, Yokohama, Japan.

    Prostate cancer is one of the most common neoplasms in the USA and Europe. We used differential display PCR (DD-PCR) to identify androgen-regulated genes in prostate cancer. The RNA of LNCaP cells treated with dihydrotestosterone (DHT) was analyzed for differentially expressed genes. Using DD-PCR, we identified a down-regulated cDNA fragment by DHT in LNCaP cells. This fragment was cloned and expressions of this fragment in prostate cancer cell lines were analyzed by RT-PCR. Sequence analysis revealed that a cDNA fragment is identical to protein tyrosine phosphatase LAR related gene, liprin-alpha2. liprin-alpha2 was downregulated by dihydrotestosterone (DHT) in LNCaP cells in a time- and androgen concentration-dependent manner. Downregulation by DHT was not inhibited by the protein synthesis inhibitor cycloheximide. This liprin-alpha2 gene was not expressed in androgen independent prostate cancer cell lines PC-3 and DU-145 at the mRNA level. And also, we first revealed here that liprin-alpha2 mRNA is expressed in LNCaP cells as well as human prostate cancer tissues and normal prostate tissues. These data suggest that liprin-alpha2 might play a role in androgen responsive human prostate cancer cell line as well as human prostate cells, and the loss of this gene expression might be associated with the androgen independent characteristics of prostate cancer.

    International journal of molecular medicine 2002;10;2;173-6

  • Interaction between GRIP and liprin-alpha/SYD2 is required for AMPA receptor targeting.

    Wyszynski M, Kim E, Dunah AW, Passafaro M, Valtschanoff JG, Serra-Pagès C, Streuli M, Weinberg RJ and Sheng M

    Department of Neurobiology and Howard Hughes Medical Institute, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

    Interaction with the multi-PDZ protein GRIP is required for the synaptic targeting of AMPA receptors, but the underlying mechanism is unknown. We show that GRIP binds to the liprin-alpha/SYD2 family of proteins that interact with LAR receptor protein tyrosine phosphatases (LAR-RPTPs) and that are implicated in presynaptic development. In neurons, liprin-alpha and LAR-RPTP are enriched at synapses and coimmunoprecipitate with GRIP and AMPA receptors. Dominant-negative constructs that interfere with the GRIP-liprin interaction disrupt the surface expression and dendritic clustering of AMPA receptors in cultured neurons. Thus, by mediating the targeting of liprin/GRIP-associated proteins, liprin-alpha is important for postsynaptic as well as presynaptic maturation.

    Funded by: NCI NIH HHS: CA 55547; NINDS NIH HHS: NS35050

    Neuron 2002;34;1;39-52

  • Liprins, a family of LAR transmembrane protein-tyrosine phosphatase-interacting proteins.

    Serra-Pagès C, Medley QG, Tang M, Hart A and Streuli M

    Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.

    LAR family transmembrane protein-tyrosine phosphatases function in axon guidance and mammary gland development. In cultured cells, LAR binds to the intracellular, coiled coil LAR-interacting protein at discrete ends of focal adhesions, implicating these proteins in the regulation of cell-matrix interactions. We describe seven LAR-interacting protein-like genes in humans and Caenorhabditis elegans that form the liprin gene family. Based on sequence similarities and binding characteristics, liprins are subdivided into alpha-type and beta-type liprins. The C-terminal, non-coiled coil regions of alpha-liprins bind to the membrane-distal phosphatase domains of LAR family members, as well as to the C-terminal, non-coiled coil region of beta-liprins. Both alpha- and beta-liprins homodimerize via their N-terminal, coiled coil regions. Liprins are thus multivalent proteins that potentially form complex structures. Some liprins have broad mRNA tissue distributions, whereas others are predominately expressed in the brain. Co-expression studies indicate that liprin-alpha2 alters LAR cellular localization and induces LAR clustering. We propose that liprins function to localize LAR family tyrosine phosphatases at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates.

    Funded by: NCI NIH HHS: CA55547

    The Journal of biological chemistry 1998;273;25;15611-20

Gene lists (6)

Gene List Source Species Name Description Gene count
L00000009 G2C Homo sapiens Human PSD Human orthologues of mouse PSD adapted from Collins et al (2006) 1080
L00000016 G2C Homo sapiens Human PSP Human orthologues of mouse PSP adapted from Collins et al (2006) 1121
L00000059 G2C Homo sapiens BAYES-COLLINS-HUMAN-PSD-CONSENSUS Human cortex PSD consensus 748
L00000061 G2C Homo sapiens BAYES-COLLINS-MOUSE-PSD-CONSENSUS Mouse cortex PSD consensus (ortho) 984
L00000069 G2C Homo sapiens BAYES-COLLINS-HUMAN-PSD-FULL Human cortex biopsy PSD full list 1461
L00000071 G2C Homo sapiens BAYES-COLLINS-MOUSE-PSD-FULL Mouse cortex PSD full list (ortho) 1556
© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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