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Symbol PICALM contributors: mct - updated : 23-05-2014
HGNC name phosphatidylinositol binding clathrin assembly protein
HGNC id 15514
Location 11q14.2      Physical location : 85.668.485 - 85.780.108
Synonym name clathrin assembly lymphoid myeloid leukemia gene
Synonym symbol(s) CALM, CLTH, AP180, LAP
TYPE functioning gene
STRUCTURE 111.71 kb     20 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Physical map
MGC33846 11q13.5 hypothetical protein MGC33846 LOC143543 11q13.5 similar to Heterogeneous nuclear ribonucleoprotein G (hnRNP G) (RNA binding motif protein, X chromosome) (Glycoprotein p43) PRCP 11q14 prolylcarboxypeptidase (angiotensinase C) FLJ25416 11q13.5 hypothetical protein FLJ25416 LOC390228 11 hypothetical gene supported by AK058145 RAB30 11q12-q14 RAB30, member RAS oncogene family PCF11 11q13 pre-mRNA cleavage complex II protein Pcf11 DKFZp547G183 11q13.5 hypothetical protein DKFZp547G183 FLJ37874 11q13.5-q14.1 hypothetical protein FLJ37874 MDS025 11q14.1 hypothetical protein MDS025 HCP28 11q14.1 cytochrome c, somatic pseudogene FLJ37266 11q14.1 hypothetical protein FLJ37266 DLG2 11q21 discs, large homolog 2, chapsyn-110 (Drosophila) LOC390229 11 similar to HNRPC protein LOC143548 11q14.1 similar to REST corepressor HT007 11q14.1 uncharacterized hypothalamus protein HT007 DKFZp586C1924 11q14.1 hypothetical protein DKFZp586C1924 ZF 11q14 HCF-binding transcription factor Zhangfei FLJ38159 11q14.1 hypothetical protein FLJ38159 SYTL2 11q14 synaptotagmin-like 2 MGC34732 11q14.1 hypothetical protein MGC34732 PICALM 11q14 phosphatidylinositol binding clathrin assembly protein LOC283226 11q14.1 similar to Protein farnesyltransferase/geranylgeranyltransferase type I alpha subunit (CAAX farnesyltransferase alpha subunit) (Ras proteins prenyltransferase alpha) (FTase-alpha) (Type I protein geranyl-geranyltransferase alpha sub EED 11q14.2-q22.3 embryonic ectoderm development HSPC138 11q14.1 hypothetical protein HSPC138 LOC387796 11 LOC387796 FLJ23514 11q14.1 hypothetical protein FLJ23514 ME3 11q21 malic enzyme 3, NADP(+)-dependent, mitochondrial LOC387797 11 LOC387797 SPUVE 11q14.1 protease, serine, 23 OR7E13P 11q13-q14.3 olfactory receptor, family 7, subfamily E, member 13 pseudogene OR7E2P 11q13-q14 olfactory receptor, family 7, subfamily E, member 2 pseudogene FZD4 11q14.2 frizzled homolog 4 (Drosophila) FLJ22104 11q14.1 hypothetical protein FLJ22104 RAB38 11q14 RAB38, member RAS oncogene family CTSC 11q21 cathepsin C LOC390230 11 similar to Glyceraldehyde 3-phosphate dehydrogenase, liver (GAPDH) GRM5 11q13-q13.4 glutamate receptor, metabotropic 5 TYR 11q14.3 tyrosinase (oculocutaneous albinism IA)
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
20 - 3860 - 652 - 2008 18182011
20 - 4043 - 610 - 2008 18182011
19 - 3734 - 551 - 2008 18182011
20 - 4148 - 645 - 2008 18182011
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularvesselcapillary    Homo sapiens
Nervousbrain     Homo sapiens
SystemCellPubmedSpeciesStageRna symbol
Cardiovascularendothelial cell Homo sapiens
Nervousneuron Homo sapiens
cell lineage
cell lines
  • AP180 N-terminal homology (ANTH) domain required for its effect on VAMP2 trafficking, and the ANTH domain itself acts as a dominant-negative mutant
  • a NAP domain
  • two DLL motifs within the clathrin-binding domain exclusively involved in clathrin binding
  • a CATS interaction domain mapped to AA 221-335, contained in the CALM/MLLT10 fusion protein
  • C-terminal PICALM AAs are critical for its association with clathrin and for the inhibitory effect of PICALM overexpression on TFRC internalization
    interspecies homolog to murine clathrin assembly protein Ap3
    homolog to C.elegans UNC11
    intraspecies homolog to SNAP91
    CATEGORY structural protein
    SUBCELLULAR LOCALIZATION     intracellular
  • coated pits
  • robustly expressed in brain microvessels
  • basic FUNCTION
  • SNAP91 and PICALM function as endocytic accessory proteins at synapses, but each may regulate distinct clathrin pathways
  • involved in the coated pits internalization machinery and in the regulation of clathrin recruitment to the membrane and/or formation of the coated pit
  • regulates the formation of clathrin-coated vesicles
  • playing a role in directing VAMP2 trafficking during endocytosis
  • PICALM/MLLT10 might interfere with normal Ikaros (IKZF1)function, and thereby block lymphoid differentiation in PICALM/MLLT10 positive leukemias
  • SNAP91 and PICALM play critical roles in establishing the polarity and controlling the growth of axons and dendrites in embryonic hippocampal neurons
  • having functions in intracellular trafficking that are essential in the growth of neurons
  • SNAP91 and PICALM, while similar in their domain structures and biochemical properties, are in fact dedicated to separate trafficking pathways in neurons
  • PICALM-mediated trafficking could function as a component of a dedicated system for controlling postsynaptic abundance of GRIA2
  • SNAP91 and PICALM are cargo-specific adaptors for synaptobrevin endocytosis, in the central nervous system
  • SNAP91 and PICALM not only regulate the assembly of the endocytic machinery but also act as sorters for a subset of SNAREs, the vesicle-associated membrane proteins (VAMPs), most notably VAMP/synaptobrevin 2 at synapses
  • SNAP91 and PICALM regulate the assembly of clathrin-coated vesicles (CCVs), which mediate diverse intracellular trafficking processes, including synaptic vesicle (SV) recycling at the synapse
  • SNAP91 and PICALM in the presynaptic terminals of hippocampal neurons, have a similar role in regulating synaptic vesicles
  • plays a critical role in iron homeostasis
  • cytoplasmic adaptor protein that also plays a critical role in clathrin-mediated endocytosis (PMISD: 24067654)
  • crucial role of PICALM in APP metabolism (PMISD: 24067654)
    a component
  • binding to clathrin heavy chain
  • component of coated pits and Golgi
    small molecule
  • clathrin heavy chain binding
  • interacting with auxilin to compete for binding to the alpha-ear domain of AP-2
  • controls the level of the synaptic vesicle protein VAMP2 at the plasma membrane by regulating VAMP2 endocytosis
  • link between SMAP2 and PICALM/STX2 in clathrin-coated vesicle formation from the TGN and subsequent acrosome formation
  • although AP2 and PICALM bind to MAP1LC3A, they do not seem to be direct substrates of autophagy
  • interaction between MAP1LC3A and AP2M1 as well as PICALM showed a significant increase triggered by starvation
  • is able to sort VAMP4 and VAMP7, even though they have sorting signals for other clathrin adaptors
  • cell & other
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    with MLLT10 in acute lymphoblastic,myeloblastic leukemia with translocation t(10;11)(p13;q14) and t(10;11) (p13;q21) and in megakaryoblastic leukemia
    Susceptibility to Alzheimer disease
    Variant & Polymorphism other
  • polymorphisms increasing the risk of Alzheimer disease
  • SNPs in PICALM, in association with APOE epsilon4 homozygotes associated to familial late-onset Alzheimer disease
  • Candidate gene
    Therapy target