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Overview

Uniprot IDQ13492
Protein NamePhosphatidylinositol-binding clathrin assembly protein
Gene NamePICALM
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
291 SLEGKKIKDSTAASR

Function

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:21808019, PubMed:22118466, 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:24067654, PubMed:25241929)

Protein Sequence

10 MSGQSLTDRI 20 TAAQHSVTGS 30 AVSKTVCKAT 40 THEIMGPKKK 50 HLDYLIQCTN 60 EMNVNIPQLA 70 DSLFERTTNS 80 SWVVVFKSLI 90 TTHHLMVYGN 100 ERFIQYLASR 110 NTLFNLSNFL 120 DKSGLQGYDM 130 STFIRRYSRY 140 LNEKAVSYRQ 150 VAFDFTKVKR 160 GADGVMRTMN 170 TEKLLKTVPI 180 IQNQMDALLD 190 FNVNSNELTN 200 GVINAAFMLL 210 FKDAIRLFAA 220 YNEGIINLLE 230 KYFDMKKNQC 240 KEGLDIYKKF 250 LTRMTRISEF 260 LKVAEQVGID 270 RGDIPDLSQA 280 PSSLLDALEQ 290 HLASLEGKKI 300 KDSTAASRAT 310 TLSNAVSSLA 320 STGLSLTKVD 330 EREKQAALEE 340 EQARLKALKE 350 QRLKELAKKP 360 HTSLTTAASP 370 VSTSAGGIMT 380 APAIDIFSTP 390 SSSNSTSKLP 400 NDLLDLQQPT 410 FHPSVHPMST 420 ASQVASTWGD 430 PFSATVDAVD 440 DAIPSLNPFL 450 TKSSGDVHLS 460 ISSDVSTFTT 470 RTPTHEMFVG 480 FTPSPVAQPH 490 PSAGLNVDFE 500 SVFGNKSTNV 510 IVDSGGFDEL 520 GGLLKPTVAS 530 QNQNLPVAKL 540 PPSKLVSDDL 550 DSSLANLVGN 560 LGIGNGTTKN 570 DVNWSQPGEK 580 KLTGGSNWQP 590 KVAPTTAWNA 600 ATMAPPVMAY 610 PATTPTGMIG 620 YGIPPQMGSV 630 PVMTQPTLIY 640 SQPVMRPPNP 650 FGPVSGAQIQ FM

Gene Ontology

Classification GO ID Description
Cellular Component GO:0009986 cell surface
Cellular Component GO:0030132 clathrin coat of coated pit
Cellular Component GO:0045334 clathrin-coated endocytic vesicle
Cellular Component GO:0005905 clathrin-coated pit
Cellular Component GO:0030136 clathrin-coated vesicle
Cellular Component GO:0005829 cytosol
Cellular Component GO:0005769 early endosome
Cellular Component GO:0070381 endosome to plasma membrane transport vesicle
Cellular Component GO:0098894 extrinsic component of presynaptic endocytic zone membrane
Cellular Component GO:0005794 Golgi apparatus
Cellular Component GO:0016020 membrane
Cellular Component GO:0097418 neurofibrillary tangle
Cellular Component GO:0043025 neuronal cell body
Cellular Component GO:0005634 nucleus
Cellular Component GO:0048471 perinuclear region of cytoplasm
Cellular Component GO:0005886 plasma membrane
Cellular Component GO:0045211 postsynaptic membrane
Cellular Component GO:0042734 presynaptic membrane
Cellular Component GO:0008021 synaptic vesicle
Cellular Component GO:0031982 vesicle
Molecular Function GO:0005545 1-phosphatidylinositol binding
Molecular Function GO:0001540 amyloid-beta binding
Molecular Function GO:0045296 cadherin binding
Molecular Function GO:0030276 clathrin binding
Molecular Function GO:0032050 clathrin heavy chain binding
Molecular Function GO:0050750 low-density lipoprotein particle receptor binding
Molecular Function GO:0005546 phosphatidylinositol-4,5-bisphosphate binding
Molecular Function GO:0031267 small GTPase binding
Molecular Function GO:0000149 SNARE binding
Molecular Function GO:0048156 tau protein binding
Biological Process GO:0150093 amyloid-beta clearance by transcytosis
Biological Process GO:0007409 axonogenesis
Biological Process GO:0048268 clathrin coat assembly
Biological Process GO:0072583 clathrin-dependent endocytosis
Biological Process GO:0048813 dendrite morphogenesis
Biological Process GO:0006897 endocytosis
Biological Process GO:0016197 endosomal transport
Biological Process GO:0030097 hemopoiesis
Biological Process GO:0006879 intracellular iron ion homeostasis
Biological Process GO:0007611 learning or memory
Biological Process GO:0097753 membrane bending
Biological Process GO:0060586 multicellular organismal-level iron ion homeostasis
Biological Process GO:0010629 negative regulation of gene expression
Biological Process GO:2000009 negative regulation of protein localization to cell surface
Biological Process GO:1903077 negative regulation of protein localization to plasma membrane
Biological Process GO:0048261 negative regulation of receptor-mediated endocytosis
Biological Process GO:1902993 positive regulation of amyloid precursor protein catabolic process
Biological Process GO:1902004 positive regulation of amyloid-beta formation
Biological Process GO:0045893 positive regulation of DNA-templated transcription
Biological Process GO:0046579 positive regulation of Ras protein signal transduction
Biological Process GO:0065003 protein-containing complex assembly
Biological Process GO:0031623 receptor internalization
Biological Process GO:0006898 receptor-mediated endocytosis
Biological Process GO:1902991 regulation of amyloid precursor protein catabolic process
Biological Process GO:0030100 regulation of endocytosis
Biological Process GO:0032880 regulation of protein localization
Biological Process GO:0097494 regulation of vesicle size
Biological Process GO:0016188 synaptic vesicle maturation
Biological Process GO:0006900 vesicle budding from membrane
Biological Process GO:0035459 vesicle cargo loading
Biological Process GO:0016192 vesicle-mediated transport

Reference

[1] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.