PICAL_RAT
ID PICAL_RAT Reviewed; 640 AA.
AC O55012; O55011;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Phosphatidylinositol-binding clathrin assembly protein;
DE AltName: Full=Clathrin assembly lymphoid myeloid leukemia protein;
DE Short=rCALM;
GN Name=Picalm; Synonyms=Calm;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116 {ECO:0000312|EMBL:AAB97079.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley {ECO:0000312|EMBL:AAB97079.1};
RC TISSUE=Brain {ECO:0000312|EMBL:AAB97079.1};
RX PubMed=10630373; DOI=10.1038/emm.1999.31;
RA Kim H.-L., Lee S.C.;
RT "Molecular cloning of clathrin assembly protein gene (rCALM) and its
RT differential expression to AP180 in rat brain.";
RL Exp. Mol. Med. 31:191-196(1999).
RN [2]
RP FUNCTION, AND INTERACTION WITH CLATHRIN.
RX PubMed=11190274; DOI=10.1038/emm.2000.36;
RA Kim H.L., Kim J.A.;
RT "Purification of clathrin assembly protein from rat liver.";
RL Exp. Mol. Med. 32:222-226(2000).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 19-281.
RX PubMed=11161218; DOI=10.1126/science.291.5506.1051;
RA Ford M.G., Pearse B.M., Higgins M.K., Vallis Y., Owen D.J., Gibson A.,
RA Hopkins C.R., Evans P.R., McMahon H.T.;
RT "Simultaneous binding of PtdIns(4,5)P2 and clathrin by AP180 in the
RT nucleation of clathrin lattices on membranes.";
RL Science 291:1051-1055(2001).
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. Furthermore, regulates clathrin-coated vesicle size
CC and maturation by directly sensing and driving membrane curvature. 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 In turn, PICALM-dependent SNARE endocytosis is required for the
CC formation and maturation of autophagic precursors. Modulates thereby
CC autophagy and the turnover of autophagy substrates such as MAPT/TAU or
CC amyloid precursor protein cleaved C-terminal fragment (APP-CTF).
CC {ECO:0000250|UniProtKB:Q13492, ECO:0000269|PubMed:11190274}.
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. Interacts with AP2A1 (via its alpha-appendage domain).
CC Interacts (via N-terminus) with VAMP2; VAMP3; VAMP7 and VAMP8 (Via N-
CC terminus). Interacts with LC3/MAP1LC3A. {ECO:0000250|UniProtKB:Q13492,
CC ECO:0000269|PubMed:11190274}.
CC -!- INTERACTION:
CC O55012; O55012: Picalm; NbExp=3; IntAct=EBI-915601, EBI-915601;
CC O55012; P63027: VAMP2; Xeno; NbExp=2; IntAct=EBI-915601, EBI-520113;
CC O55012; Q15836: VAMP3; Xeno; NbExp=2; IntAct=EBI-915601, EBI-722343;
CC O55012; O70404: Vamp8; Xeno; NbExp=4; IntAct=EBI-915601, EBI-1812572;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q13492}.
CC Membrane, clathrin-coated pit {ECO:0000250|UniProtKB:Q13492}. Golgi
CC apparatus {ECO:0000250|UniProtKB:Q13492}. Cytoplasmic vesicle,
CC clathrin-coated vesicle {ECO:0000250|UniProtKB:Q13492}. Nucleus
CC {ECO:0000250|UniProtKB:Q13492}. Note=Colocalized with clathrin in the
CC Golgi area. Interaction with PIMREG may target PICALM to the nucleus in
CC some cells. {ECO:0000250|UniProtKB:Q13492}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:10630373}; Synonyms=Long
CC {ECO:0000269|PubMed:10630373};
CC IsoId=O55012-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:10630373}; Synonyms=Short
CC {ECO:0000269|PubMed:10630373};
CC IsoId=O55012-2; Sequence=VSP_050687;
CC -!- TISSUE SPECIFICITY: Isoform 2 was found in most tissues examined.
CC Isoform 1 has an overlapping expression pattern but is absent from
CC lung, heart and pancreas. Both isoforms are widely expressed in the
CC brain, higher levels are seen in hippocampus, dentate gyrus, medial
CC habenula nucleus and cerebellar granule cells.
CC {ECO:0000269|PubMed:10630373}.
CC -!- SIMILARITY: Belongs to the PICALM/SNAP91 family. {ECO:0000305}.
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DR EMBL; AF041373; AAB97078.1; -; mRNA.
DR EMBL; AF041374; AAB97079.1; -; mRNA.
DR RefSeq; NP_446006.1; NM_053554.2. [O55012-1]
DR PDB; 1HF8; X-ray; 2.00 A; A=1-289.
DR PDB; 1HFA; X-ray; 2.00 A; A=1-289.
DR PDB; 1HG2; X-ray; 2.00 A; A=1-289.
DR PDB; 1HG5; X-ray; 2.00 A; A=1-289.
DR PDB; 3ZYK; X-ray; 1.80 A; A/B=1-289.
DR PDB; 3ZYL; X-ray; 1.70 A; A/B=1-264.
DR PDB; 3ZYM; X-ray; 2.03 A; A/B/C=1-264.
DR PDB; 7JXV; X-ray; 2.35 A; A=1-281.
DR PDBsum; 1HF8; -.
DR PDBsum; 1HFA; -.
DR PDBsum; 1HG2; -.
DR PDBsum; 1HG5; -.
DR PDBsum; 3ZYK; -.
DR PDBsum; 3ZYL; -.
DR PDBsum; 3ZYM; -.
DR PDBsum; 7JXV; -.
DR AlphaFoldDB; O55012; -.
DR SMR; O55012; -.
DR BioGRID; 250139; 2.
DR ELM; O55012; -.
DR IntAct; O55012; 4.
DR STRING; 10116.ENSRNOP00000025415; -.
DR iPTMnet; O55012; -.
DR PhosphoSitePlus; O55012; -.
DR jPOST; O55012; -.
DR PeptideAtlas; O55012; -.
DR PRIDE; O55012; -.
DR GeneID; 89816; -.
DR KEGG; rno:89816; -.
DR UCSC; RGD:621054; rat. [O55012-1]
DR CTD; 8301; -.
DR RGD; 621054; Picalm.
DR eggNOG; KOG0251; Eukaryota.
DR InParanoid; O55012; -.
DR OrthoDB; 1592722at2759; -.
DR PhylomeDB; O55012; -.
DR Reactome; R-RNO-432722; Golgi Associated Vesicle Biogenesis.
DR Reactome; R-RNO-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-RNO-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-RNO-9696264; RND3 GTPase cycle.
DR EvolutionaryTrace; O55012; -.
DR PRO; PR:O55012; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0030132; C:clathrin coat of coated pit; ISO:RGD.
DR GO; GO:0005905; C:clathrin-coated pit; ISS:UniProtKB.
DR GO; GO:0030136; C:clathrin-coated vesicle; IDA:BHF-UCL.
DR GO; GO:0005769; C:early endosome; ISO:RGD.
DR GO; GO:0005768; C:endosome; IDA:BHF-UCL.
DR GO; GO:0070381; C:endosome to plasma membrane transport vesicle; ISO:RGD.
DR GO; GO:0098894; C:extrinsic component of presynaptic endocytic zone membrane; IDA:SynGO.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0031224; C:intrinsic component of membrane; IMP:ARUK-UCL.
DR GO; GO:0097418; C:neurofibrillary tangle; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; IDA:SynGO.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0098794; C:postsynapse; IDA:SynGO.
DR GO; GO:0014069; C:postsynaptic density; IDA:BHF-UCL.
DR GO; GO:0045211; C:postsynaptic membrane; IDA:BHF-UCL.
DR GO; GO:0042734; C:presynaptic membrane; IDA:BHF-UCL.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA:SynGO.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0008021; C:synaptic vesicle; IDA:BHF-UCL.
DR GO; GO:0031982; C:vesicle; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0005545; F:1-phosphatidylinositol binding; IDA:UniProtKB.
DR GO; GO:0030276; F:clathrin binding; IDA:UniProtKB.
DR GO; GO:0032050; F:clathrin heavy chain binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; ISO:RGD.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IMP:ARUK-UCL.
DR GO; GO:0017124; F:SH3 domain binding; IDA:RGD.
DR GO; GO:0031267; F:small GTPase binding; ISO:RGD.
DR GO; GO:0000149; F:SNARE binding; IPI:RGD.
DR GO; GO:0048156; F:tau protein binding; ISO:RGD.
DR GO; GO:0150093; P:amyloid-beta clearance by transcytosis; ISO:RGD.
DR GO; GO:0007409; P:axonogenesis; IMP:BHF-UCL.
DR GO; GO:0048268; P:clathrin coat assembly; IDA:RGD.
DR GO; GO:1905224; P:clathrin-coated pit assembly; ISO:RGD.
DR GO; GO:0072583; P:clathrin-dependent endocytosis; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0048813; P:dendrite morphogenesis; IMP:BHF-UCL.
DR GO; GO:0006897; P:endocytosis; ISO:RGD.
DR GO; GO:0016197; P:endosomal transport; ISO:RGD.
DR GO; GO:0030097; P:hemopoiesis; ISO:RGD.
DR GO; GO:0055072; P:iron ion homeostasis; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0007611; P:learning or memory; ISO:RGD.
DR GO; GO:0097753; P:membrane bending; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISS: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; ISO:RGD.
DR GO; GO:1903077; P:negative regulation of protein localization to plasma membrane; ISO:RGD.
DR GO; GO:0048261; P:negative regulation of receptor-mediated endocytosis; ISO:RGD.
DR GO; GO:1902004; P:positive regulation of amyloid-beta formation; ISS: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:0050772; P:positive regulation of axonogenesis; IMP:RGD.
DR GO; GO:1903861; P:positive regulation of dendrite extension; IMP:RGD.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISO:RGD.
DR GO; GO:1901216; P:positive regulation of neuron death; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:2000809; P:positive regulation of synaptic vesicle clustering; IMP:RGD.
DR GO; GO:1900244; P:positive regulation of synaptic vesicle endocytosis; IMP:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0031623; P:receptor internalization; ISO:RGD.
DR GO; GO:0006898; P:receptor-mediated endocytosis; ISS:UniProtKB.
DR GO; GO:1902959; P:regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:2000369; P:regulation of clathrin-dependent endocytosis; IEA:InterPro.
DR GO; GO:0030100; P:regulation of endocytosis; IMP:BHF-UCL.
DR GO; GO:0032880; P:regulation of protein localization; ISO:RGD.
DR GO; GO:0051223; P:regulation of protein transport; IMP:BHF-UCL.
DR GO; GO:1900242; P:regulation of synaptic vesicle endocytosis; IMP:RGD.
DR GO; GO:1902803; P:regulation of synaptic vesicle transport; IMP:RGD.
DR GO; GO:2000331; P:regulation of terminal button organization; IMP:RGD.
DR GO; GO:0097494; P:regulation of vesicle size; ISO:RGD.
DR GO; GO:0016185; P:synaptic vesicle budding from presynaptic endocytic zone membrane; IBA:GO_Central.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; IDA:SynGO.
DR GO; GO:0016188; P:synaptic vesicle maturation; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0006900; P:vesicle budding from membrane; ISO:RGD.
DR GO; GO:0035459; P:vesicle cargo loading; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0016192; P:vesicle-mediated transport; IMP:BHF-UCL.
DR Gene3D; 1.20.58.150; -; 1.
DR Gene3D; 1.25.40.90; -; 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 InterPro; IPR030412; PICALM.
DR PANTHER; PTHR22951; PTHR22951; 2.
DR PANTHER; PTHR22951:SF16; PTHR22951:SF16; 2.
DR Pfam; PF07651; ANTH; 1.
DR SMART; SM00273; ENTH; 1.
DR SUPFAM; SSF48464; SSF48464; 1.
DR PROSITE; PS50942; ENTH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell membrane; Coated pit;
KW Cytoplasmic vesicle; Endocytosis; Golgi apparatus; Isopeptide bond;
KW Membrane; Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q13492"
FT CHAIN 2..640
FT /note="Phosphatidylinositol-binding clathrin assembly
FT protein"
FT /id="PRO_0000187064"
FT DOMAIN 14..145
FT /note="ENTH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00243,
FT ECO:0000305"
FT REGION 221..294
FT /note="Interaction with PIMREG"
FT /evidence="ECO:0000250"
FT REGION 543..568
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q13492"
FT MOD_RES 16
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13492"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13492"
FT MOD_RES 303
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13492"
FT MOD_RES 315
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13492"
FT CROSSLNK 238
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q13492"
FT VAR_SEQ 420..462
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10630373"
FT /id="VSP_050687"
FT HELIX 6..29
FT /evidence="ECO:0007829|PDB:3ZYL"
FT STRAND 32..35
FT /evidence="ECO:0007829|PDB:3ZYL"
FT HELIX 39..50
FT /evidence="ECO:0007829|PDB:3ZYL"
FT HELIX 56..66
FT /evidence="ECO:0007829|PDB:3ZYL"
FT HELIX 72..88
FT /evidence="ECO:0007829|PDB:3ZYL"
FT HELIX 91..99
FT /evidence="ECO:0007829|PDB:3ZYL"
FT HELIX 115..141
FT /evidence="ECO:0007829|PDB:3ZYL"
FT TURN 145..147
FT /evidence="ECO:0007829|PDB:3ZYL"
FT STRAND 151..154
FT /evidence="ECO:0007829|PDB:1HF8"
FT HELIX 155..158
FT /evidence="ECO:0007829|PDB:3ZYL"
FT HELIX 161..179
FT /evidence="ECO:0007829|PDB:3ZYL"
FT HELIX 185..187
FT /evidence="ECO:0007829|PDB:3ZYL"
FT HELIX 191..220
FT /evidence="ECO:0007829|PDB:3ZYL"
FT HELIX 222..224
FT /evidence="ECO:0007829|PDB:3ZYL"
FT HELIX 227..256
FT /evidence="ECO:0007829|PDB:3ZYL"
FT HELIX 261..263
FT /evidence="ECO:0007829|PDB:3ZYL"
FT HELIX 267..269
FT /evidence="ECO:0007829|PDB:3ZYK"
FT HELIX 275..285
FT /evidence="ECO:0007829|PDB:3ZYK"
SQ SEQUENCE 640 AA; 69286 MW; 7395A92C285FA10A 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 FHPSVHAMSA APQVASTWGD
AVDDAIPSLN PFLTKSSGDV HLPISSDVST FTTRTPTHEM FVGFSPSPVT QPHPSAGLNV
DFESVFGNKS TNVAVDSGGG LLKPTVASQN QSLPVAKLPP NKLVSDDLDS SLANLVGNLG
IGNGTTKNDV SCSQPGEKKL TGGSNWQPKV APTTAWSAAT MAPPVMAYPA TTPTGMIGYG
IPPQMGSVPV MTQPTLIYSQ PVMRPPNPFG PVPGAQIQFM
