Details of the Target

General Information of Target

Target ID LDTP05895
Target Name Phosphatidylinositol-binding clathrin assembly protein (PICALM)
Gene Name PICALM
Gene ID 8301
Synonyms
CALM; Phosphatidylinositol-binding clathrin assembly protein; Clathrin assembly lymphoid myeloid leukemia protein
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MSGQSLTDRITAAQHSVTGSAVSKTVCKATTHEIMGPKKKHLDYLIQCTNEMNVNIPQLA
DSLFERTTNSSWVVVFKSLITTHHLMVYGNERFIQYLASRNTLFNLSNFLDKSGLQGYDM
STFIRRYSRYLNEKAVSYRQVAFDFTKVKRGADGVMRTMNTEKLLKTVPIIQNQMDALLD
FNVNSNELTNGVINAAFMLLFKDAIRLFAAYNEGIINLLEKYFDMKKNQCKEGLDIYKKF
LTRMTRISEFLKVAEQVGIDRGDIPDLSQAPSSLLDALEQHLASLEGKKIKDSTAASRAT
TLSNAVSSLASTGLSLTKVDEREKQAALEEEQARLKALKEQRLKELAKKPHTSLTTAASP
VSTSAGGIMTAPAIDIFSTPSSSNSTSKLPNDLLDLQQPTFHPSVHPMSTASQVASTWGD
PFSATVDAVDDAIPSLNPFLTKSSGDVHLSISSDVSTFTTRTPTHEMFVGFTPSPVAQPH
PSAGLNVDFESVFGNKSTNVIVDSGGFDELGGLLKPTVASQNQNLPVAKLPPSKLVSDDL
DSSLANLVGNLGIGNGTTKNDVNWSQPGEKKLTGGSNWQPKVAPTTAWNAATMAPPVMAY
PATTPTGMIGYGIPPQMGSVPVMTQPTLIYSQPVMRPPNPFGPVSGAQIQFM
Target Bioclass
Other
Family
PICALM/SNAP91 family
Subcellular location
Cell membrane
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. Furthermore, regulates clathrin-coated vesicle size and maturation by directly sensing and driving membrane curvature. 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. In turn, PICALM-dependent SNARE endocytosis is required for the formation and maturation of autophagic precursors. Modulates thereby autophagy and the turnover of autophagy substrates such as MAPT/TAU or amyloid precursor protein cleaved C-terminal fragment (APP-CTF).
Uniprot ID
Q13492
Ensemble ID
ENST00000356360.9
HGNC ID
HGNC:15514

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
HCT116 SNV: p.R126W .
HCT15 SNV: p.D454Y .
KMRC1 SNV: p.N50S .
KYSE180 SNV: p.L485P .
RKO SNV: p.S645P .
SUPT1 Deletion: p.P596LfsTer2 .
SW948 SNV: p.L106V .
THP1 SNV: p.P434A .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 16 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
m-APA
 Probe Info  		15.00  LDD0402  [1]
A-EBA
 Probe Info  		3.34  LDD0215  [2]
STPyne
 Probe Info  		K163(5.35); K24(6.47); K28(4.09); K291(10.00)  LDD0277  [3]
OPA-S-S-alkyne
 Probe Info  		K324(1.36)  LDD3494  [4]
DBIA
 Probe Info  		C48(1.60)  LDD3337  [5]
HHS-475
 Probe Info  		Y118(0.22)  LDD0264  [6]
5E-2FA
 Probe Info  		N.A.  LDD2235  [7]
ATP probe
 Probe Info  		K24(0.00); K28(0.00)  LDD0199  [8]
4-Iodoacetamidophenylacetylene
 Probe Info  		N.A.  LDD0038  [9]
IA-alkyne
 Probe Info  		N.A.  LDD0036  [9]
Lodoacetamide azide
 Probe Info  		N.A.  LDD0037  [9]
NAIA_4
 Probe Info  		N.A.  LDD2226  [10]
Phosphinate-6
 Probe Info  		N.A.  LDD0018  [11]
Acrolein
 Probe Info  		N.A.  LDD0217  [12]
Crotonaldehyde
 Probe Info  		H32(0.00); H15(0.00)  LDD0219  [12]
NAIA_5
 Probe Info  		C48(0.00); C27(0.00)  LDD2223  [10]
PAL-AfBPP Probe
Click To Hide/Show 5 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
FFF probe14
 Probe Info  		20.00  LDD0477  [13]
FFF probe2
 Probe Info  		15.57  LDD0463  [13]
FFF probe3
 Probe Info  		5.29  LDD0465  [13]
STS-2
 Probe Info  		N.A.  LDD0138  [14]
DA-2
 Probe Info  		N.A.  LDD0073  [15]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0214  AC1 HEK-293T C48(0.92)  LDD1507  [16]
 LDCM0226  AC11 HEK-293T C48(1.00)  LDD1509  [16]
 LDCM0270  AC15 HEK-293T C48(1.03)  LDD1513  [16]
 LDCM0276  AC17 HEK-293T C48(1.04)  LDD1515  [16]
 LDCM0278  AC19 HEK-293T C48(1.10)  LDD1517  [16]
 LDCM0281  AC21 HEK-293T C48(1.05)  LDD1520  [16]
 LDCM0283  AC23 HEK-293T C48(0.98)  LDD1522  [16]
 LDCM0284  AC24 HEK-293T C48(0.93)  LDD1523  [16]
 LDCM0285  AC25 HEK-293T C48(1.08)  LDD1524  [16]
 LDCM0287  AC27 HEK-293T C48(1.20)  LDD1526  [16]
 LDCM0289  AC29 HEK-293T C48(1.04)  LDD1528  [16]
 LDCM0290  AC3 HEK-293T C48(0.92)  LDD1529  [16]
 LDCM0292  AC31 HEK-293T C48(1.07)  LDD1531  [16]
 LDCM0293  AC32 HEK-293T C48(0.85)  LDD1532  [16]
 LDCM0294  AC33 HEK-293T C48(1.00)  LDD1533  [16]
 LDCM0296  AC35 HEK-293T C48(0.99)  LDD1535  [16]
 LDCM0298  AC37 HEK-293T C48(0.95)  LDD1537  [16]
 LDCM0300  AC39 HEK-293T C48(1.07)  LDD1539  [16]
 LDCM0302  AC40 HEK-293T C48(0.74)  LDD1541  [16]
 LDCM0303  AC41 HEK-293T C48(0.92)  LDD1542  [16]
 LDCM0305  AC43 HEK-293T C48(0.99)  LDD1544  [16]
 LDCM0307  AC45 HEK-293T C48(1.00)  LDD1546  [16]
 LDCM0309  AC47 HEK-293T C48(1.21)  LDD1548  [16]
 LDCM0310  AC48 HEK-293T C48(0.74)  LDD1549  [16]
 LDCM0311  AC49 HEK-293T C48(0.97)  LDD1550  [16]
 LDCM0312  AC5 HEK-293T C48(1.06)  LDD1551  [16]
 LDCM0314  AC51 HEK-293T C48(1.03)  LDD1553  [16]
 LDCM0316  AC53 HEK-293T C48(1.09)  LDD1555  [16]
 LDCM0318  AC55 HEK-293T C48(1.06)  LDD1557  [16]
 LDCM0319  AC56 HEK-293T C48(0.82)  LDD1558  [16]
 LDCM0320  AC57 HEK-293T C48(0.97)  LDD1559  [16]
 LDCM0322  AC59 HEK-293T C48(1.09)  LDD1561  [16]
 LDCM0325  AC61 HEK-293T C48(1.00)  LDD1564  [16]
 LDCM0327  AC63 HEK-293T C48(0.99)  LDD1566  [16]
 LDCM0328  AC64 HEK-293T C48(0.92)  LDD1567  [16]
 LDCM0334  AC7 HEK-293T C48(1.17)  LDD1568  [16]
 LDCM0345  AC8 HEK-293T C48(0.87)  LDD1569  [16]
 LDCM0248  AKOS034007472 HEK-293T C48(0.99)  LDD1511  [16]
 LDCM0356  AKOS034007680 HEK-293T C48(1.00)  LDD1570  [16]
 LDCM0275  AKOS034007705 HEK-293T C48(0.85)  LDD1514  [16]
 LDCM0156  Aniline NCI-H1299 11.58  LDD0403  [1]
 LDCM0108  Chloroacetamide HeLa N.A.  LDD0222  [12]
 LDCM0367  CL1 HEK-293T C48(1.07)  LDD1571  [16]
 LDCM0369  CL100 HEK-293T C48(1.23)  LDD1573  [16]
 LDCM0370  CL101 HEK-293T C48(0.91)  LDD1574  [16]
 LDCM0371  CL102 HEK-293T C48(1.11)  LDD1575  [16]
 LDCM0372  CL103 HEK-293T C48(0.88)  LDD1576  [16]
 LDCM0373  CL104 HEK-293T C48(0.98)  LDD1577  [16]
 LDCM0374  CL105 HEK-293T C48(0.91)  LDD1578  [16]
 LDCM0375  CL106 HEK-293T C48(1.16)  LDD1579  [16]
 LDCM0376  CL107 HEK-293T C48(1.08)  LDD1580  [16]
 LDCM0377  CL108 HEK-293T C48(0.77)  LDD1581  [16]
 LDCM0378  CL109 HEK-293T C48(0.89)  LDD1582  [16]
 LDCM0379  CL11 HEK-293T C48(1.19)  LDD1583  [16]
 LDCM0380  CL110 HEK-293T C48(0.98)  LDD1584  [16]
 LDCM0381  CL111 HEK-293T C48(0.84)  LDD1585  [16]
 LDCM0382  CL112 HEK-293T C48(1.00)  LDD1586  [16]
 LDCM0383  CL113 HEK-293T C48(0.93)  LDD1587  [16]
 LDCM0384  CL114 HEK-293T C48(1.02)  LDD1588  [16]
 LDCM0385  CL115 HEK-293T C48(0.94)  LDD1589  [16]
 LDCM0386  CL116 HEK-293T C48(1.12)  LDD1590  [16]
 LDCM0387  CL117 HEK-293T C48(0.93)  LDD1591  [16]
 LDCM0388  CL118 HEK-293T C48(1.06)  LDD1592  [16]
 LDCM0389  CL119 HEK-293T C48(0.96)  LDD1593  [16]
 LDCM0390  CL12 HEK-293T C48(0.74)  LDD1594  [16]
 LDCM0391  CL120 HEK-293T C48(1.03)  LDD1595  [16]
 LDCM0392  CL121 HEK-293T C48(0.91)  LDD1596  [16]
 LDCM0393  CL122 HEK-293T C48(1.06)  LDD1597  [16]
 LDCM0394  CL123 HEK-293T C48(0.83)  LDD1598  [16]
 LDCM0395  CL124 HEK-293T C48(1.15)  LDD1599  [16]
 LDCM0396  CL125 HEK-293T C48(1.03)  LDD1600  [16]
 LDCM0397  CL126 HEK-293T C48(0.73)  LDD1601  [16]
 LDCM0398  CL127 HEK-293T C48(0.90)  LDD1602  [16]
 LDCM0399  CL128 HEK-293T C48(0.98)  LDD1603  [16]
 LDCM0400  CL13 HEK-293T C48(0.91)  LDD1604  [16]
 LDCM0401  CL14 HEK-293T C48(1.31)  LDD1605  [16]
 LDCM0402  CL15 HEK-293T C48(0.96)  LDD1606  [16]
 LDCM0403  CL16 HEK-293T C48(1.18)  LDD1607  [16]
 LDCM0404  CL17 HEK-293T C48(0.97)  LDD1608  [16]
 LDCM0406  CL19 HEK-293T C48(1.00)  LDD1610  [16]
 LDCM0407  CL2 HEK-293T C48(1.15)  LDD1611  [16]
 LDCM0409  CL21 HEK-293T C48(0.87)  LDD1613  [16]
 LDCM0411  CL23 HEK-293T C48(1.04)  LDD1615  [16]
 LDCM0412  CL24 HEK-293T C48(0.88)  LDD1616  [16]
 LDCM0413  CL25 HEK-293T C48(0.41)  LDD1617  [16]
 LDCM0414  CL26 HEK-293T C48(1.04)  LDD1618  [16]
 LDCM0415  CL27 HEK-293T C48(1.04)  LDD1619  [16]
 LDCM0416  CL28 HEK-293T C48(1.08)  LDD1620  [16]
 LDCM0417  CL29 HEK-293T C48(0.98)  LDD1621  [16]
 LDCM0418  CL3 HEK-293T C48(0.93)  LDD1622  [16]
 LDCM0420  CL31 HEK-293T C48(1.08)  LDD1624  [16]
 LDCM0422  CL33 HEK-293T C48(0.77)  LDD1626  [16]
 LDCM0424  CL35 HEK-293T C48(0.95)  LDD1628  [16]
 LDCM0425  CL36 HEK-293T C48(0.88)  LDD1629  [16]
 LDCM0426  CL37 HEK-293T C48(0.88)  LDD1630  [16]
 LDCM0428  CL39 HEK-293T C48(0.87)  LDD1632  [16]
 LDCM0429  CL4 HEK-293T C48(0.99)  LDD1633  [16]
 LDCM0430  CL40 HEK-293T C48(1.01)  LDD1634  [16]
 LDCM0431  CL41 HEK-293T C48(0.87)  LDD1635  [16]
 LDCM0433  CL43 HEK-293T C48(0.97)  LDD1637  [16]
 LDCM0435  CL45 HEK-293T C48(0.91)  LDD1639  [16]
 LDCM0437  CL47 HEK-293T C48(0.85)  LDD1641  [16]
 LDCM0438  CL48 HEK-293T C48(0.77)  LDD1642  [16]
 LDCM0439  CL49 HEK-293T C48(0.90)  LDD1643  [16]
 LDCM0440  CL5 HEK-293T C48(1.05)  LDD1644  [16]
 LDCM0441  CL50 HEK-293T C48(1.26)  LDD1645  [16]
 LDCM0443  CL52 HEK-293T C48(1.02)  LDD1646  [16]
 LDCM0444  CL53 HEK-293T C48(1.03)  LDD1647  [16]
 LDCM0446  CL55 HEK-293T C48(1.12)  LDD1649  [16]
 LDCM0448  CL57 HEK-293T C48(0.85)  LDD1651  [16]
 LDCM0450  CL59 HEK-293T C48(1.12)  LDD1653  [16]
 LDCM0452  CL60 HEK-293T C48(0.73)  LDD1655  [16]
 LDCM0453  CL61 HEK-293T C48(0.93)  LDD1656  [16]
 LDCM0454  CL62 HEK-293T C48(1.16)  LDD1657  [16]
 LDCM0455  CL63 HEK-293T C48(0.98)  LDD1658  [16]
 LDCM0456  CL64 HEK-293T C48(0.92)  LDD1659  [16]
 LDCM0457  CL65 HEK-293T C48(1.07)  LDD1660  [16]
 LDCM0459  CL67 HEK-293T C48(0.87)  LDD1662  [16]
 LDCM0461  CL69 HEK-293T C48(0.88)  LDD1664  [16]
 LDCM0462  CL7 HEK-293T C48(0.79)  LDD1665  [16]
 LDCM0464  CL71 HEK-293T C48(1.04)  LDD1667  [16]
 LDCM0465  CL72 HEK-293T C48(0.86)  LDD1668  [16]
 LDCM0466  CL73 HEK-293T C48(1.02)  LDD1669  [16]
 LDCM0467  CL74 HEK-293T C48(1.14)  LDD1670  [16]
 LDCM0469  CL76 HEK-293T C48(1.27)  LDD1672  [16]
 LDCM0470  CL77 HEK-293T C48(0.90)  LDD1673  [16]
 LDCM0472  CL79 HEK-293T C48(0.98)  LDD1675  [16]
 LDCM0475  CL81 HEK-293T C48(0.96)  LDD1678  [16]
 LDCM0477  CL83 HEK-293T C48(0.93)  LDD1680  [16]
 LDCM0478  CL84 HEK-293T C48(0.58)  LDD1681  [16]
 LDCM0479  CL85 HEK-293T C48(0.85)  LDD1682  [16]
 LDCM0480  CL86 HEK-293T C48(1.09)  LDD1683  [16]
 LDCM0481  CL87 HEK-293T C48(0.95)  LDD1684  [16]
 LDCM0482  CL88 HEK-293T C48(0.96)  LDD1685  [16]
 LDCM0483  CL89 HEK-293T C48(0.90)  LDD1686  [16]
 LDCM0484  CL9 HEK-293T C48(0.96)  LDD1687  [16]
 LDCM0486  CL91 HEK-293T C48(1.04)  LDD1689  [16]
 LDCM0488  CL93 HEK-293T C48(0.78)  LDD1691  [16]
 LDCM0490  CL95 HEK-293T C48(0.83)  LDD1693  [16]
 LDCM0491  CL96 HEK-293T C48(0.72)  LDD1694  [16]
 LDCM0492  CL97 HEK-293T C48(0.78)  LDD1695  [16]
 LDCM0493  CL98 HEK-293T C48(1.06)  LDD1696  [16]
 LDCM0494  CL99 HEK-293T C48(0.94)  LDD1697  [16]
 LDCM0495  E2913 HEK-293T C48(1.01)  LDD1698  [16]
 LDCM0468  Fragment33 HEK-293T C48(0.89)  LDD1671  [16]
 LDCM0427  Fragment51 HEK-293T C48(0.94)  LDD1631  [16]
 LDCM0116  HHS-0101 DM93 Y118(0.22)  LDD0264  [6]
 LDCM0117  HHS-0201 DM93 Y118(0.34)  LDD0265  [6]
 LDCM0118  HHS-0301 DM93 Y118(0.16)  LDD0266  [6]
 LDCM0119  HHS-0401 DM93 Y118(0.44)  LDD0267  [6]
 LDCM0120  HHS-0701 DM93 Y118(0.39)  LDD0268  [6]
 LDCM0107  IAA HeLa H15(0.00); H32(0.00)  LDD0221  [12]
 LDCM0022  KB02 HEK-293T C48(1.07)  LDD1492  [16]
 LDCM0023  KB03 HEK-293T C48(1.14)  LDD1497  [16]
 LDCM0024  KB05 MSTO-211H C48(1.60)  LDD3337  [5]
 LDCM0109  NEM HeLa H15(0.00); H32(0.00)  LDD0223  [12]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Other
Click To Hide/Show 5 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Ataxin-1 (ATXN1) ATXN1 family P54253
Ataxin-1-like (ATXN1L) ATXN1 family P0C7T5
Epidermal growth factor receptor substrate 15 (EPS15) . P42566
Four and a half LIM domains protein 2 (FHL2) . Q14192
Zinc finger CCCH domain-containing protein 10 (ZC3H10) . Q96K80

References

1 Quantitative and Site-Specific Chemoproteomic Profiling of Targets of Acrolein. Chem Res Toxicol. 2019 Mar 18;32(3):467-473. doi: 10.1021/acs.chemrestox.8b00343. Epub 2019 Jan 15.
2 2-Ethynylbenzaldehyde-Based, Lysine-Targeting Irreversible Covalent Inhibitors for Protein Kinases and Nonkinases. J Am Chem Soc. 2023 Feb 12. doi: 10.1021/jacs.2c11595. Online ahead of print.
Mass spectrometry data entry: PXD037665
3 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
4 A chemical proteomics approach for global mapping of functional lysines on cell surface of living cell. Nat Commun. 2024 Apr 8;15(1):2997. doi: 10.1038/s41467-024-47033-w.
Mass spectrometry data entry: PXD042888
5 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
6 Discovery of a Cell-Active SuTEx Ligand of Prostaglandin Reductase 2. Chembiochem. 2021 Jun 15;22(12):2134-2139. doi: 10.1002/cbic.202000879. Epub 2021 Apr 29.
7 Global profiling of functional histidines in live cells using small-molecule photosensitizer and chemical probe relay labelling. Nat Chem. 2024 Jun 4. doi: 10.1038/s41557-024-01545-6. Online ahead of print.
Mass spectrometry data entry: PXD042377
8 Targeted Proteomic Approaches for Proteome-Wide Characterizations of the AMP-Binding Capacities of Kinases. J Proteome Res. 2022 Aug 5;21(8):2063-2070. doi: 10.1021/acs.jproteome.2c00225. Epub 2022 Jul 12.
9 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
10 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264
11 DFT-Guided Discovery of Ethynyl-Triazolyl-Phosphinates as Modular Electrophiles for Chemoselective Cysteine Bioconjugation and Profiling. Angew Chem Int Ed Engl. 2022 Oct 10;61(41):e202205348. doi: 10.1002/anie.202205348. Epub 2022 Aug 22.
Mass spectrometry data entry: PXD033004
12 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
13 Ligand and Target Discovery by Fragment-Based Screening in Human Cells. Cell. 2017 Jan 26;168(3):527-541.e29. doi: 10.1016/j.cell.2016.12.029. Epub 2017 Jan 19.
14 Design and synthesis of minimalist terminal alkyne-containing diazirine photo-crosslinkers and their incorporation into kinase inhibitors for cell- and tissue-based proteome profiling. Angew Chem Int Ed Engl. 2013 Aug 12;52(33):8551-6. doi: 10.1002/anie.201300683. Epub 2013 Jun 10.
15 Cell-based proteome profiling of potential dasatinib targets by use of affinity-based probes. J Am Chem Soc. 2012 Feb 15;134(6):3001-14. doi: 10.1021/ja208518u. Epub 2012 Feb 1.
16 Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input. Cell Chem Biol. 2024 Mar 21;31(3):565-576.e4. doi: 10.1016/j.chembiol.2023.11.015. Epub 2023 Dec 19.
Mass spectrometry data entry: PXD044402