PICALM

This gene encodes a clathrin assembly protein, which recruits clathrin and adaptor protein complex 2 (AP2) to cell membranes at sites of coated-pit formation and clathrin-vesicle assembly. The protein may be required to determine the amount of membrane to be recycled, possibly by regulating the size of the clathrin cage. The protein is involved in AP2-dependent clathrin-mediated endocytosis at the neuromuscular junction. A chromosomal translocation t(10;11)(p13;q14) leading to the fusion of this gene and the MLLT10 gene is found in acute lymphoblastic leukemia, acute myeloid leukemia and malignant lymphomas. The polymorphisms of this gene are associated with the risk of Alzheimer disease. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

Phosphatidylinositol Binding Clathrin Assembly Protein

Cytoplasmic adapter protein that plays a critical role in clathrin-mediated endocytosis which is important in processes such as internalization of cell receptors, synaptic transmission or removal of apoptotic cells. Recruits AP-2 and attaches clathrin triskelions to the cytoplasmic side of plasma membrane leading to clathrin-coated vesicles (CCVs) assembly (PubMed:10436022, PubMed:16262731, PubMed:27574975).
Furthermore, regulates clathrin-coated vesicle size and maturation by directly sensing and driving membrane curvature (PubMed:25898166).
In addition to binding to clathrin, mediates the endocytosis of small R-SNARES (Soluble NSF Attachment Protein REceptors) between plasma membranes and endosomes including VAMP2, VAMP3, VAMP4, VAMP7 or VAMP8 (PubMed:22118466, PubMed:21808019, PubMed:23741335).
In turn, PICALM-dependent SNARE endocytosis is required for the formation and maturation of autophagic precursors (PubMed:25241929).
Modulates thereby autophagy and the turnover of autophagy substrates such as MAPT/TAU or amyloid precursor protein cleaved C-terminal fragment (APP-CTF) (PubMed:25241929, PubMed:24067654).

Amyloid-beta clearance by transcytosisManual Assertion Based On ExperimentIGI:ARUK-UCL
AxonogenesisIEA:Ensembl
Clathrin coat assemblyManual Assertion Based On ExperimentIMP:BHF-UCL
Clathrin-coated pit assemblyManual Assertion Based On ExperimentIDA:UniProtKB
Clathrin-dependent endocytosisManual Assertion Based On ExperimentIMP:Alzheimers_University_of_Toronto
Dendrite morphogenesisIEA:Ensembl
EndocytosisManual Assertion Based On ExperimentIDA:UniProtKB
Endosomal transportManual Assertion Based On ExperimentIMP:BHF-UCL
HemopoiesisIEA:Ensembl
Iron ion homeostasisManual Assertion Based On ExperimentIMP:Alzheimers_University_of_Toronto
Learning or memoryBy SimilarityISS:ARUK-UCL
Membrane bendingManual Assertion Based On ExperimentIMP:ARUK-UCL
Modulation of age-related behavioral declineBy SimilarityISS:ARUK-UCL
Negative regulation of gene expressionManual Assertion Based On ExperimentIMP:Alzheimers_University_of_Toronto
Negative regulation of metalloendopeptidase activity involved in amyloid precursor protein catabolic processISS:Alzheimers_University_of_Toronto
Negative regulation of protein localization to cell surfaceManual Assertion Based On ExperimentIMP:ARUK-UCL
Negative regulation of protein localization to plasma membraneManual Assertion Based On ExperimentIMP:ARUK-UCL
Negative regulation of receptor-mediated endocytosisManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of amyloid-beta formationManual Assertion Based On ExperimentIMP:Alzheimers_University_of_Toronto
Positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic processISS:Alzheimers_University_of_Toronto
Positive regulation of GTPase activityManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of neuron deathManual Assertion Based On ExperimentIMP:Alzheimers_University_of_Toronto
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:BHF-UCL
Protein-containing complex assemblyManual Assertion Based On ExperimentTAS:ProtInc
Receptor internalizationManual Assertion Based On ExperimentIMP:BHF-UCL
Receptor-mediated endocytosisManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic processManual Assertion Based On ExperimentIMP:Alzheimers_University_of_Toronto
Regulation of clathrin-dependent endocytosisIEA:InterPro
Regulation of endocytosisManual Assertion Based On ExperimentIMP:BHF-UCL
Regulation of protein localizationManual Assertion Based On ExperimentIDA:BHF-UCL
Regulation of vesicle sizeManual Assertion Based On ExperimentIMP:ARUK-UCL
Biological Process synaptic vesicle budding from presynaptic endocytic zone membraneManual Assertion Based On ExperimentIBA:GO_Central
Synaptic vesicle maturationISS:Alzheimers_University_of_Toronto
Vesicle budding from membraneManual Assertion Based On ExperimentIMP:ARUK-UCL
Vesicle cargo loadingManual Assertion Based On ExperimentIMP:Alzheimers_University_of_Toronto
Vesicle-mediated transportManual Assertion Based On ExperimentTAS:ProtInc

Cell membrane
Membrane, clathrin-coated pit
Golgi apparatus
Cytoplasmic vesicle, clathrin-coated vesicle
Nucleus
Colocalized with clathrin in the Golgi area (PubMed:10436022).
Interaction with PIMREG may target PICALM to the nucleus in some cells (PubMed:16491119).

A chromosomal aberration involving PICALM is found in diffuse histiocytic lymphomas. Translocation t(10;11)(p13;q14) with MLLT10.