ID PICAL_HUMAN Reviewed; 652 AA. AC Q13492; B4DTM3; E9PN05; F8VPG7; O60700; Q4LE54; Q6GMQ6; Q86XZ9; DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 2. DT 27-MAR-2024, entry version 208. DE RecName: Full=Phosphatidylinositol-binding clathrin assembly protein; DE AltName: Full=Clathrin assembly lymphoid myeloid leukemia protein; GN Name=PICALM; Synonyms=CALM; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHROMOSOMAL TRANSLOCATION, TISSUE RP SPECIFICITY, AND VARIANTS CYS-578 AND GLU-579. RX PubMed=8643484; DOI=10.1073/pnas.93.10.4804; RA Dreyling M.H., Martinez-Climent J.A., Zheng M., Mao J., Rowley J.D., RA Bohlander S.K.; RT "The t(10;11)(p13;q14) in the U937 cell line results in the fusion of the RT AF10 gene and CALM, encoding a new member of the AP-3 clathrin assembly RT protein family."; RL Proc. Natl. Acad. Sci. U.S.A. 93:4804-4809(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). RC TISSUE=Brain; RA Nakajima D., Saito K., Yamakawa H., Kikuno R.F., Nakayama M., Ohara R., RA Okazaki N., Koga H., Nagase T., Ohara O.; RT "Preparation of a set of expression-ready clones of mammalian long cDNAs RT encoding large proteins by the ORF trap cloning method."; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=PNS; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 575-652 (ISOFORMS 1 AND 2), AND VARIANTS RP CYS-578 AND GLU-579. RC TISSUE=Bone marrow; RX PubMed=9737689; DOI=10.1038/sj.leu.2401109; RA Silliman C.C., McGavran L., Wei Q., Miller L.A., Li S., Hunger S.P.; RT "Alternative splicing in wild-type AF10 and CALM cDNAs and in AF10-CALM and RT CALM-AF10 fusion cDNAs produced by the t(10;11)(p13-14;q14-q21) suggests a RT potential role for truncated AF10 polypeptides."; RL Leukemia 12:1404-1410(1998). RN [8] RP FUNCTION, INTERACTION WITH CLATHRIN, AND SUBCELLULAR LOCATION. RX PubMed=10436022; DOI=10.1091/mbc.10.8.2687; RA Tebar F., Bohlander S.K., Sorkin A.; RT "Clathrin assembly lymphoid myeloid leukemia (CALM) protein: localization RT in endocytic-coated pits, interactions with clathrin, and the impact of RT overexpression on clathrin-mediated traffic."; RL Mol. Biol. Cell 10:2687-2702(1999). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH AP2A1 AND CLATHRIN. RX PubMed=16262731; DOI=10.1111/j.1600-0854.2005.00355.x; RA Meyerholz A., Hinrichsen L., Groos S., Esk P.C., Brandes G., RA Ungewickell E.J.; RT "Effect of clathrin assembly lymphoid myeloid leukemia protein depletion on RT clathrin coat formation."; RL Traffic 6:1225-1234(2005). RN [10] RP SUBCELLULAR LOCATION, AND INTERACTION WITH PIMREG. RX PubMed=16491119; DOI=10.1038/sj.onc.1209438; RA Archangelo L.F., Glaesner J., Krause A., Bohlander S.K.; RT "The novel CALM interactor CATS influences the subcellular localization of RT the leukemogenic fusion protein CALM/AF10."; RL Oncogene 25:4099-4109(2006). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [12] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [15] RP FUNCTION, AND INTERACTION WITH VAMP2; VAMP3 AND VAMP8. RX PubMed=22118466; DOI=10.1016/j.cell.2011.10.038; RA Miller S.E., Sahlender D.A., Graham S.C., Honing S., Robinson M.S., RA Peden A.A., Owen D.J.; RT "The molecular basis for the endocytosis of small R-SNAREs by the clathrin RT adaptor CALM."; RL Cell 147:1118-1131(2011). RN [16] RP FUNCTION, AND INTERACTION WITH VAMP2. RX PubMed=21808019; DOI=10.1073/pnas.1107067108; RA Koo S.J., Markovic S., Puchkov D., Mahrenholz C.C., Beceren-Braun F., RA Maritzen T., Dernedde J., Volkmer R., Oschkinat H., Haucke V.; RT "SNARE motif-mediated sorting of synaptobrevin by the endocytic adaptors RT clathrin assembly lymphoid myeloid leukemia (CALM) and AP180 at synapses."; RL Proc. Natl. Acad. Sci. U.S.A. 108:13540-13545(2011). RN [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [18] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [19] RP FUNCTION, AND INTERACTION WITH VAMP7. RX PubMed=23741335; DOI=10.1371/journal.pone.0064514; RA Sahlender D.A., Kozik P., Miller S.E., Peden A.A., Robinson M.S.; RT "Uncoupling the functions of CALM in VAMP sorting and clathrin-coated pit RT formation."; RL PLoS ONE 8:E64514-E64514(2013). RN [20] RP FUNCTION, AND INTERACTION WITH LC3/MAP1LC3A. RX PubMed=24067654; DOI=10.1073/pnas.1315110110; RA Tian Y., Chang J.C., Fan E.Y., Flajolet M., Greengard P.; RT "Adaptor complex AP2/PICALM, through interaction with LC3, targets RT Alzheimer's APP-CTF for terminal degradation via autophagy."; RL Proc. Natl. Acad. Sci. U.S.A. 110:17071-17076(2013). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16; SER-20; SER-303 AND RP SER-315, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [23] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-238, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [24] RP FUNCTION. RX PubMed=25241929; DOI=10.1038/ncomms5998; RA Moreau K., Fleming A., Imarisio S., Lopez Ramirez A., Mercer J.L., RA Jimenez-Sanchez M., Bento C.F., Puri C., Zavodszky E., Siddiqi F., RA Lavau C.P., Betton M., O'Kane C.J., Wechsler D.S., Rubinsztein D.C.; RT "PICALM modulates autophagy activity and tau accumulation."; RL Nat. Commun. 5:4998-4998(2014). RN [25] RP FUNCTION. RX PubMed=25898166; DOI=10.1016/j.devcel.2015.03.002; RA Miller S.E., Mathiasen S., Bright N.A., Pierre F., Kelly B.T., Kladt N., RA Schauss A., Merrifield C.J., Stamou D., Hoening S., Owen D.J.; RT "CALM regulates clathrin-coated vesicle size and maturation by directly RT sensing and driving membrane curvature."; RL Dev. Cell 33:163-175(2015). RN [26] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [27] RP FUNCTION. RX PubMed=27574975; DOI=10.1371/journal.pone.0162050; RA Moshkanbaryans L., Xue J., Wark J.R., Robinson P.J., Graham M.E.; RT "A Novel Sequence in AP180 and CALM Promotes Efficient Clathrin Binding and RT Assembly."; RL PLoS ONE 11:E0162050-E0162050(2016). CC -!- FUNCTION: Cytoplasmic adapter protein that plays a critical role in CC clathrin-mediated endocytosis which is important in processes such as CC internalization of cell receptors, synaptic transmission or removal of CC apoptotic cells. Recruits AP-2 and attaches clathrin triskelions to the CC cytoplasmic side of plasma membrane leading to clathrin-coated vesicles CC (CCVs) assembly (PubMed:10436022, PubMed:16262731, PubMed:27574975). CC Furthermore, regulates clathrin-coated vesicle size and maturation by CC directly sensing and driving membrane curvature (PubMed:25898166). In CC addition to binding to clathrin, mediates the endocytosis of small R- CC SNARES (Soluble NSF Attachment Protein REceptors) between plasma CC membranes and endosomes including VAMP2, VAMP3, VAMP4, VAMP7 or VAMP8 CC (PubMed:22118466, PubMed:21808019, PubMed:23741335). In turn, PICALM- CC dependent SNARE endocytosis is required for the formation and CC maturation of autophagic precursors (PubMed:25241929). Modulates CC thereby autophagy and the turnover of autophagy substrates such as CC MAPT/TAU or amyloid precursor protein cleaved C-terminal fragment (APP- CC CTF) (PubMed:25241929, PubMed:24067654). {ECO:0000269|PubMed:10436022, CC ECO:0000269|PubMed:16262731, ECO:0000269|PubMed:21808019, CC ECO:0000269|PubMed:22118466, ECO:0000269|PubMed:23741335, CC ECO:0000269|PubMed:24067654, ECO:0000269|PubMed:25241929, CC ECO:0000269|PubMed:25898166, ECO:0000269|PubMed:27574975}. CC -!- SUBUNIT: Binds to clathrin; involves primarily the C-terminal CC sequences, but the full-length protein is required for full binding CC capacity. Binds phosphatidylinositol 4,5- bisphosphate. Interacts with CC PIMREG; this interaction may change the subcellular location into the CC nucleus (PubMed:16491119). Interacts with AP2A1 (via its alpha- CC appendage domain) (PubMed:16262731). Interacts (via N-terminus) with CC VAMP2; VAMP3; VAMP7 and VAMP8 (Via N-terminus) (PubMed:22118466, CC PubMed:21808019, PubMed:23741335). Interacts with LC3/MAP1LC3A CC (PubMed:24067654). {ECO:0000269|PubMed:16262731, CC ECO:0000269|PubMed:16491119, ECO:0000269|PubMed:21808019, CC ECO:0000269|PubMed:22118466, ECO:0000269|PubMed:23741335, CC ECO:0000269|PubMed:24067654}. CC -!- INTERACTION: CC Q13492; P42566: EPS15; NbExp=2; IntAct=EBI-2803688, EBI-396684; CC Q13492; Q14192: FHL2; NbExp=8; IntAct=EBI-2803688, EBI-701903; CC Q13492-3; P54253: ATXN1; NbExp=3; IntAct=EBI-11031437, EBI-930964; CC Q13492-3; P0C7T5: ATXN1L; NbExp=3; IntAct=EBI-11031437, EBI-8624731; CC Q13492-3; Q96K80: ZC3H10; NbExp=3; IntAct=EBI-11031437, EBI-742550; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16262731}. CC Membrane, clathrin-coated pit {ECO:0000269|PubMed:10436022}. Golgi CC apparatus {ECO:0000269|PubMed:10436022}. Cytoplasmic vesicle, clathrin- CC coated vesicle {ECO:0000269|PubMed:10436022}. Nucleus CC {ECO:0000269|PubMed:16491119}. Note=Colocalized with clathrin in the CC Golgi area (PubMed:10436022). Interaction with PIMREG may target PICALM CC to the nucleus in some cells (PubMed:16491119). CC {ECO:0000269|PubMed:10436022, ECO:0000269|PubMed:16491119}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; Synonyms=Type I; CC IsoId=Q13492-1; Sequence=Displayed; CC Name=2; Synonyms=Type II; CC IsoId=Q13492-2; Sequence=VSP_004067; CC Name=3; CC IsoId=Q13492-3; Sequence=VSP_009607, VSP_009608; CC Name=4; CC IsoId=Q13492-4; Sequence=VSP_044567, VSP_009607; CC Name=5; CC IsoId=Q13492-5; Sequence=VSP_044568; CC -!- TISSUE SPECIFICITY: Expressed in all tissues examined. CC {ECO:0000269|PubMed:8643484}. CC -!- DISEASE: Note=A chromosomal aberration involving PICALM is found in CC diffuse histiocytic lymphomas. Translocation t(10;11)(p13;q14) with CC MLLT10. {ECO:0000269|PubMed:8643484}. CC -!- SIMILARITY: Belongs to the PICALM/SNAP91 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAE06099.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/64/CALM"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U45976; AAB07762.1; -; mRNA. DR EMBL; AK300275; BAG62035.1; -; mRNA. DR EMBL; AB210017; BAE06099.1; ALT_INIT; mRNA. DR EMBL; AP000767; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471076; EAW75120.1; -; Genomic_DNA. DR EMBL; BC048259; AAH48259.2; -; mRNA. DR EMBL; BC064357; AAH64357.1; -; mRNA. DR EMBL; BC073961; AAH73961.1; -; mRNA. DR EMBL; AF060939; AAC16711.1; -; mRNA. DR EMBL; AF060940; AAC16712.1; -; mRNA. DR CCDS; CCDS31653.1; -. [Q13492-3] DR CCDS; CCDS55783.1; -. [Q13492-4] DR CCDS; CCDS55784.1; -. [Q13492-5] DR CCDS; CCDS8272.1; -. [Q13492-1] DR CCDS; CCDS91570.1; -. [Q13492-2] DR RefSeq; NP_001008660.1; NM_001008660.2. [Q13492-3] DR RefSeq; NP_001193875.1; NM_001206946.1. [Q13492-5] DR RefSeq; NP_001193876.1; NM_001206947.1. [Q13492-4] DR RefSeq; NP_009097.2; NM_007166.3. [Q13492-1] DR RefSeq; XP_005274388.1; XM_005274331.2. DR AlphaFoldDB; Q13492; -. DR SMR; Q13492; -. DR BioGRID; 113902; 261. DR ELM; Q13492; -. DR IntAct; Q13492; 94. DR MINT; Q13492; -. DR STRING; 9606.ENSP00000377015; -. DR MoonDB; Q13492; Curated. DR MoonProt; Q13492; -. DR GlyCosmos; Q13492; 16 sites, 2 glycans. DR GlyGen; Q13492; 28 sites, 2 O-linked glycans (28 sites). DR iPTMnet; Q13492; -. DR MetOSite; Q13492; -. DR PhosphoSitePlus; Q13492; -. DR SwissPalm; Q13492; -. DR BioMuta; PICALM; -. DR DMDM; 116242714; -. DR EPD; Q13492; -. DR jPOST; Q13492; -. DR MassIVE; Q13492; -. DR MaxQB; Q13492; -. DR PaxDb; 9606-ENSP00000377015; -. DR PeptideAtlas; Q13492; -. DR ProteomicsDB; 22268; -. DR ProteomicsDB; 28286; -. DR ProteomicsDB; 59489; -. [Q13492-1] DR ProteomicsDB; 59490; -. [Q13492-2] DR ProteomicsDB; 59491; -. [Q13492-3] DR Pumba; Q13492; -. DR Antibodypedia; 17636; 239 antibodies from 34 providers. DR DNASU; 8301; -. DR Ensembl; ENST00000356360.9; ENSP00000348718.5; ENSG00000073921.18. [Q13492-2] DR Ensembl; ENST00000393346.8; ENSP00000377015.3; ENSG00000073921.18. [Q13492-1] DR Ensembl; ENST00000526033.5; ENSP00000433846.1; ENSG00000073921.18. [Q13492-5] DR Ensembl; ENST00000528398.5; ENSP00000434884.1; ENSG00000073921.18. [Q13492-4] DR Ensembl; ENST00000532317.5; ENSP00000436958.1; ENSG00000073921.18. [Q13492-3] DR GeneID; 8301; -. DR KEGG; hsa:8301; -. DR MANE-Select; ENST00000393346.8; ENSP00000377015.3; NM_007166.4; NP_009097.2. DR UCSC; uc001pbl.4; human. [Q13492-1] DR AGR; HGNC:15514; -. DR CTD; 8301; -. DR DisGeNET; 8301; -. DR GeneCards; PICALM; -. DR HGNC; HGNC:15514; PICALM. DR HPA; ENSG00000073921; Low tissue specificity. DR MalaCards; PICALM; -. DR MIM; 603025; gene. DR neXtProt; NX_Q13492; -. DR NIAGADS; ENSG00000073921; -. DR OpenTargets; ENSG00000073921; -. DR Orphanet; 99861; Precursor T-cell acute lymphoblastic leukemia. DR PharmGKB; PA33287; -. DR VEuPathDB; HostDB:ENSG00000073921; -. DR eggNOG; KOG0251; Eukaryota. DR GeneTree; ENSGT00950000183068; -. DR HOGENOM; CLU_014080_0_0_1; -. DR InParanoid; Q13492; -. DR OMA; XPFSATV; -. DR OrthoDB; 3667239at2759; -. DR PhylomeDB; Q13492; -. DR TreeFam; TF314861; -. DR PathwayCommons; Q13492; -. DR Reactome; R-HSA-432722; Golgi Associated Vesicle Biogenesis. DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis. DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis. DR Reactome; R-HSA-9696264; RND3 GTPase cycle. DR SignaLink; Q13492; -. DR SIGNOR; Q13492; -. DR BioGRID-ORCS; 8301; 50 hits in 1166 CRISPR screens. DR ChiTaRS; PICALM; human. DR GeneWiki; PICALM; -. DR GenomeRNAi; 8301; -. DR Pharos; Q13492; Tbio. DR PRO; PR:Q13492; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q13492; Protein. DR Bgee; ENSG00000073921; Expressed in calcaneal tendon and 203 other cell types or tissues. DR ExpressionAtlas; Q13492; baseline and differential. DR GO; GO:0009986; C:cell surface; IDA:ARUK-UCL. DR GO; GO:0030132; C:clathrin coat of coated pit; IDA:BHF-UCL. DR GO; GO:0045334; C:clathrin-coated endocytic vesicle; NAS:ARUK-UCL. DR GO; GO:0005905; C:clathrin-coated pit; IDA:UniProtKB. DR GO; GO:0030136; C:clathrin-coated vesicle; IMP:ARUK-UCL. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005769; C:early endosome; IDA:ARUK-UCL. DR GO; GO:0070381; C:endosome to plasma membrane transport vesicle; IDA:ARUK-UCL. DR GO; GO:0098894; C:extrinsic component of presynaptic endocytic zone membrane; IBA:GO_Central. DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0097418; C:neurofibrillary tangle; IMP:Alzheimers_University_of_Toronto. DR GO; GO:0043025; C:neuronal cell body; IDA:Alzheimers_University_of_Toronto. DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0045211; C:postsynaptic membrane; ISS:BHF-UCL. DR GO; GO:0042734; C:presynaptic membrane; ISS:BHF-UCL. DR GO; GO:0008021; C:synaptic vesicle; IBA:GO_Central. DR GO; GO:0031982; C:vesicle; ISS:Alzheimers_University_of_Toronto. DR GO; GO:0005545; F:1-phosphatidylinositol binding; ISS:UniProtKB. DR GO; GO:0001540; F:amyloid-beta binding; IC:ARUK-UCL. DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL. DR GO; GO:0030276; F:clathrin binding; IDA:UniProtKB. DR GO; GO:0032050; F:clathrin heavy chain binding; IDA:BHF-UCL. DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; IPI:ARUK-UCL. DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; ISS:ARUK-UCL. DR GO; GO:0031267; F:small GTPase binding; IPI:ARUK-UCL. DR GO; GO:0000149; F:SNARE binding; IDA:UniProtKB. DR GO; GO:0048156; F:tau protein binding; IPI:Alzheimers_University_of_Toronto. DR GO; GO:0150093; P:amyloid-beta clearance by transcytosis; IGI:ARUK-UCL. DR GO; GO:0007409; P:axonogenesis; IEA:Ensembl. DR GO; GO:0048268; P:clathrin coat assembly; IDA:UniProtKB. DR GO; GO:0072583; P:clathrin-dependent endocytosis; IMP:Alzheimers_University_of_Toronto. DR GO; GO:0048813; P:dendrite morphogenesis; IEA:Ensembl. DR GO; GO:0006897; P:endocytosis; IDA:UniProtKB. DR GO; GO:0016197; P:endosomal transport; IMP:BHF-UCL. DR GO; GO:0030097; P:hemopoiesis; IEA:Ensembl. DR GO; GO:0006879; P:intracellular iron ion homeostasis; IMP:ARUK-UCL. DR GO; GO:0007611; P:learning or memory; ISS:ARUK-UCL. DR GO; GO:0097753; P:membrane bending; IMP:ARUK-UCL. DR GO; GO:0060586; P:multicellular organismal-level iron ion homeostasis; IMP:Alzheimers_University_of_Toronto. DR GO; GO:0010629; P:negative regulation of gene expression; IMP:Alzheimers_University_of_Toronto. DR GO; GO:1902963; P:negative regulation of metalloendopeptidase activity involved in amyloid precursor protein catabolic process; ISS:Alzheimers_University_of_Toronto. DR GO; GO:2000009; P:negative regulation of protein localization to cell surface; IMP:ARUK-UCL. DR GO; GO:1903077; P:negative regulation of protein localization to plasma membrane; IMP:ARUK-UCL. DR GO; GO:0048261; P:negative regulation of receptor-mediated endocytosis; IDA:BHF-UCL. DR GO; GO:1902004; P:positive regulation of amyloid-beta formation; IMP:Alzheimers_University_of_Toronto. DR GO; GO:1902961; P:positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process; ISS:Alzheimers_University_of_Toronto. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:BHF-UCL. DR GO; GO:0043547; P:positive regulation of GTPase activity; IMP:ARUK-UCL. DR GO; GO:0065003; P:protein-containing complex assembly; TAS:ProtInc. DR GO; GO:0031623; P:receptor internalization; IMP:BHF-UCL. DR GO; GO:0006898; P:receptor-mediated endocytosis; IDA:UniProtKB. DR GO; GO:1902959; P:regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process; IMP:Alzheimers_University_of_Toronto. DR GO; GO:0030100; P:regulation of endocytosis; IMP:BHF-UCL. DR GO; GO:0032880; P:regulation of protein localization; IDA:BHF-UCL. DR GO; GO:0097494; P:regulation of vesicle size; IMP:ARUK-UCL. DR GO; GO:0016185; P:synaptic vesicle budding from presynaptic endocytic zone membrane; IBA:GO_Central. DR GO; GO:0016188; P:synaptic vesicle maturation; ISS:Alzheimers_University_of_Toronto. DR GO; GO:0006900; P:vesicle budding from membrane; IMP:ARUK-UCL. DR GO; GO:0035459; P:vesicle cargo loading; IMP:Alzheimers_University_of_Toronto. DR GO; GO:0016192; P:vesicle-mediated transport; TAS:ProtInc. DR CDD; cd16985; ANTH_N_AP180; 1. DR Gene3D; 1.25.40.90; -; 1. DR Gene3D; 1.20.58.150; ANTH domain; 1. DR InterPro; IPR011417; ANTH_dom. DR InterPro; IPR014712; ANTH_dom_sf. DR InterPro; IPR045192; AP180-like. DR InterPro; IPR013809; ENTH. DR InterPro; IPR008942; ENTH_VHS. DR PANTHER; PTHR22951; CLATHRIN ASSEMBLY PROTEIN; 1. DR PANTHER; PTHR22951:SF16; PHOSPHATIDYLINOSITOL-BINDING CLATHRIN ASSEMBLY PROTEIN; 1. DR Pfam; PF07651; ANTH; 1. DR SMART; SM00273; ENTH; 1. DR SUPFAM; SSF48464; ENTH/VHS domain; 1. DR SUPFAM; SSF89009; GAT-like domain; 1. DR PROSITE; PS50942; ENTH; 1. DR Genevisible; Q13492; HS. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Cell membrane; KW Chromosomal rearrangement; Coated pit; Cytoplasmic vesicle; Endocytosis; KW Golgi apparatus; Isopeptide bond; Membrane; Nucleus; Phosphoprotein; KW Proto-oncogene; Reference proteome; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:22814378" FT CHAIN 2..652 FT /note="Phosphatidylinositol-binding clathrin assembly FT protein" FT /id="PRO_0000187062" FT DOMAIN 14..145 FT /note="ENTH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00243" FT REGION 221..294 FT /note="Interaction with PIMREG" FT /evidence="ECO:0000269|PubMed:16491119" FT REGION 559..580 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 648..649 FT /note="Breakpoint for translocation to form CALM/MLLT10 FT fusion protein" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:22814378" FT MOD_RES 16 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 20 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 303 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 315 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CROSSLNK 238 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25218447" FT VAR_SEQ 1..51 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_044567" FT VAR_SEQ 420..469 FT /note="Missing (in isoform 3 and isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_009607" FT VAR_SEQ 420..426 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_044568" FT VAR_SEQ 593 FT /note="M -> MNGMHFPQY (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_009608" FT VAR_SEQ 594..613 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:9737689" FT /id="VSP_004067" FT VARIANT 158 FT /note="T -> P (in dbSNP:rs12800974)" FT /id="VAR_028191" FT VARIANT 383 FT /note="S -> F (in dbSNP:rs12222608)" FT /id="VAR_028192" FT VARIANT 578 FT /note="W -> C (in dbSNP:rs1043858)" FT /evidence="ECO:0000269|PubMed:8643484, FT ECO:0000269|PubMed:9737689" FT /id="VAR_028193" FT VARIANT 579 FT /note="Q -> E (in dbSNP:rs1043859)" FT /evidence="ECO:0000269|PubMed:8643484, FT ECO:0000269|PubMed:9737689" FT /id="VAR_028194" FT VARIANT 641 FT /note="F -> L (in dbSNP:rs556337)" FT /id="VAR_028195" FT CONFLICT 132 FT /note="N -> D (in Ref. 2; BAG62035)" FT /evidence="ECO:0000305" FT CONFLICT 212 FT /note="N -> H (in Ref. 1; AAB07762)" FT /evidence="ECO:0000305" FT CONFLICT 331 FT /note="E -> G (in Ref. 2; BAG62035)" FT /evidence="ECO:0000305" SQ SEQUENCE 652 AA; 70755 MW; AC3227E9D32AFEDA CRC64; MSGQSLTDRI TAAQHSVTGS AVSKTVCKAT THEIMGPKKK HLDYLIQCTN EMNVNIPQLA DSLFERTTNS SWVVVFKSLI TTHHLMVYGN ERFIQYLASR NTLFNLSNFL DKSGLQGYDM STFIRRYSRY LNEKAVSYRQ VAFDFTKVKR GADGVMRTMN TEKLLKTVPI IQNQMDALLD FNVNSNELTN GVINAAFMLL FKDAIRLFAA YNEGIINLLE KYFDMKKNQC KEGLDIYKKF LTRMTRISEF LKVAEQVGID RGDIPDLSQA PSSLLDALEQ HLASLEGKKI KDSTAASRAT TLSNAVSSLA STGLSLTKVD EREKQAALEE EQARLKALKE QRLKELAKKP HTSLTTAASP VSTSAGGIMT APAIDIFSTP SSSNSTSKLP NDLLDLQQPT FHPSVHPMST ASQVASTWGD PFSATVDAVD DAIPSLNPFL TKSSGDVHLS ISSDVSTFTT RTPTHEMFVG FTPSPVAQPH PSAGLNVDFE SVFGNKSTNV IVDSGGFDEL GGLLKPTVAS QNQNLPVAKL PPSKLVSDDL DSSLANLVGN LGIGNGTTKN DVNWSQPGEK KLTGGSNWQP KVAPTTAWNA ATMAPPVMAY PATTPTGMIG YGIPPQMGSV PVMTQPTLIY SQPVMRPPNP FGPVSGAQIQ FM //