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Protein

Phosphatidylinositol-binding clathrin assembly protein

Gene

PICALM

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Assembly protein recruiting clathrin and adapter protein complex 2 (AP2) to cell membranes at sites of coated-pit formation and clathrin-vesicle assembly. May be required to determine the amount of membrane to be recycled, possibly by regulating the size of the clathrin cage. Involved in AP2-dependent clathrin-mediated endocytosis at the neuromuscular junction.1 Publication

GO - Molecular functioni

  • 1-phosphatidylinositol binding Source: UniProtKB
  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • clathrin adaptor activity Source: Alzheimers_University_of_Toronto
  • clathrin binding Source: UniProtKB
  • clathrin heavy chain binding Source: BHF-UCL

GO - Biological processi

  • axonogenesis Source: Ensembl
  • cargo loading into vesicle Source: Alzheimers_University_of_Toronto
  • cell proliferation Source: Alzheimers_University_of_Toronto
  • clathrin coat assembly Source: BHF-UCL
  • clathrin-dependent endocytosis Source: Alzheimers_University_of_Toronto
  • dendrite morphogenesis Source: Ensembl
  • endosomal transport Source: BHF-UCL
  • hemopoiesis Source: Ensembl
  • iron ion homeostasis Source: Alzheimers_University_of_Toronto
  • iron ion import into cell Source: Alzheimers_University_of_Toronto
  • negative regulation of gene expression Source: Alzheimers_University_of_Toronto
  • negative regulation of metalloendopeptidase activity involved in amyloid precursor protein catabolic process Source: Alzheimers_University_of_Toronto
  • negative regulation of receptor-mediated endocytosis Source: BHF-UCL
  • positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process Source: Alzheimers_University_of_Toronto
  • positive regulation of beta-amyloid formation Source: Alzheimers_University_of_Toronto
  • positive regulation of neuron death Source: Alzheimers_University_of_Toronto
  • positive regulation of transcription, DNA-templated Source: BHF-UCL
  • protein complex assembly Source: ProtInc
  • receptor internalization Source: BHF-UCL
  • receptor-mediated endocytosis Source: UniProtKB
  • regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process Source: Alzheimers_University_of_Toronto
  • regulation of endocytosis Source: BHF-UCL
  • regulation of protein localization Source: BHF-UCL
  • synaptic vesicle maturation Source: Alzheimers_University_of_Toronto
  • vesicle-mediated transport Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Endocytosis

Enzyme and pathway databases

BioCyciZFISH:ENSG00000073921-MONOMER.
ReactomeiR-HSA-432722. Golgi Associated Vesicle Biogenesis.
R-HSA-8856825. Cargo recognition for clathrin-mediated endocytosis.
R-HSA-8856828. Clathrin-mediated endocytosis.
SIGNORiQ13492.

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphatidylinositol-binding clathrin assembly protein
Alternative name(s):
Clathrin assembly lymphoid myeloid leukemia protein
Gene namesi
Name:PICALM
Synonyms:CALM
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:15514. PICALM.

Subcellular locationi

  • Membraneclathrin-coated pit 1 Publication
  • Golgi apparatus 1 Publication
  • Cytoplasmic vesicleclathrin-coated vesicle 1 Publication
  • Nucleus 1 Publication

  • Note: Colocalized with clathrin in the Golgi area (PubMed:10436022). Interaction with FAM64A may target PICALM to the nucleus in some cells (PubMed:16491119).2 Publications

GO - Cellular componenti

  • cell-cell adherens junction Source: BHF-UCL
  • clathrin-coated pit Source: UniProtKB
  • clathrin-coated vesicle Source: UniProtKB-SubCell
  • Golgi apparatus Source: UniProtKB-SubCell
  • membrane Source: UniProtKB
  • neurofibrillary tangle Source: Alzheimers_University_of_Toronto
  • neuronal cell body Source: Alzheimers_University_of_Toronto
  • nucleus Source: BHF-UCL
  • perinuclear region of cytoplasm Source: Ensembl
  • postsynaptic membrane Source: BHF-UCL
  • presynaptic membrane Source: BHF-UCL
  • vesicle Source: Alzheimers_University_of_Toronto
Complete GO annotation...

Keywords - Cellular componenti

Coated pit, Cytoplasmic vesicle, Golgi apparatus, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

A chromosomal aberration involving PICALM is found in diffuse histiocytic lymphomas. Translocation t(10;11)(p13;q14) with MLLT10.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei648 – 649Breakpoint for translocation to form CALM/MLLT10 fusion protein2

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi8301.
MalaCardsiPICALM.
OpenTargetsiENSG00000073921.
Orphaneti99861. Precursor T-cell acute lymphoblastic leukemia.
PharmGKBiPA33287.

Polymorphism and mutation databases

BioMutaiPICALM.
DMDMi116242714.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001870622 – 652Phosphatidylinositol-binding clathrin assembly proteinAdd BLAST651

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei16PhosphoserineCombined sources1
Modified residuei20PhosphoserineCombined sources1
Cross-linki238Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei303PhosphoserineCombined sources1
Modified residuei315PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ13492.
MaxQBiQ13492.
PaxDbiQ13492.
PeptideAtlasiQ13492.
PRIDEiQ13492.

PTM databases

iPTMnetiQ13492.
PhosphoSitePlusiQ13492.
SwissPalmiQ13492.

Miscellaneous databases

PMAP-CutDBQ13492.

Expressioni

Tissue specificityi

Expressed in all tissues examined.1 Publication

Gene expression databases

BgeeiENSG00000073921.
CleanExiHS_PICALM.
ExpressionAtlasiQ13492. baseline and differential.
GenevisibleiQ13492. HS.

Organism-specific databases

HPAiHPA019053.
HPA019061.

Interactioni

Subunit structurei

Binds clathrin; involves primarily the C-terminal sequences, but the full-length protein is required for full binding capacity. Binds phosphatidylinositol 4,5- bisphosphate. Interacts with FAM64A; this interaction may change the subcellular location into the nucleus.2 Publications

GO - Molecular functioni

  • cadherin binding involved in cell-cell adhesion Source: BHF-UCL
  • clathrin adaptor activity Source: Alzheimers_University_of_Toronto
  • clathrin binding Source: UniProtKB
  • clathrin heavy chain binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi113902. 99 interactors.
IntActiQ13492. 53 interactors.
MINTiMINT-1636298.
STRINGi9606.ENSP00000377015.

Structurei

3D structure databases

ProteinModelPortaliQ13492.
SMRiQ13492.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini14 – 145ENTHPROSITE-ProRule annotationAdd BLAST132

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni221 – 294Interaction with FAM64A1 PublicationAdd BLAST74

Sequence similaritiesi

Belongs to the PICALM/SNAP91 family.Curated
Contains 1 ENTH (epsin N-terminal homology) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0251. Eukaryota.
ENOG410XQ90. LUCA.
GeneTreeiENSGT00390000008805.
HOGENOMiHOG000015764.
HOVERGENiHBG049391.
InParanoidiQ13492.
KOiK20044.
OMAiWNAATMA.
OrthoDBiEOG091G0810.
PhylomeDBiQ13492.
TreeFamiTF314861.

Family and domain databases

Gene3Di1.20.58.150. 1 hit.
1.25.40.90. 1 hit.
InterProiIPR011417. ANTH_dom.
IPR014712. Clathrin_AP_2.
IPR013809. ENTH.
IPR008942. ENTH_VHS.
IPR030412. PICALM.
[Graphical view]
PANTHERiPTHR22951:SF16. PTHR22951:SF16. 2 hits.
PfamiPF07651. ANTH. 1 hit.
[Graphical view]
SMARTiSM00273. ENTH. 1 hit.
[Graphical view]
SUPFAMiSSF48464. SSF48464. 1 hit.
PROSITEiPS50942. ENTH. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q13492-1) [UniParc]FASTAAdd to basket
Also known as: Type I

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

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

FM
Length:652
Mass (Da):70,755
Last modified:October 17, 2006 - v2
Checksum:iAC3227E9D32AFEDA
GO
Isoform 2 (identifier: Q13492-2) [UniParc]FASTAAdd to basket
Also known as: Type II

The sequence of this isoform differs from the canonical sequence as follows:
     594-613: Missing.

Show »
Length:632
Mass (Da):68,764
Checksum:iD13D4427A30EE4FD
GO
Isoform 3 (identifier: Q13492-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     420-469: Missing.
     593-593: M → MNGMHFPQY

Note: No experimental confirmation available.
Show »
Length:610
Mass (Da):66,393
Checksum:i3B0D0AEB901CF85D
GO
Isoform 4 (identifier: Q13492-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-51: Missing.
     420-469: Missing.

Note: No experimental confirmation available.
Show »
Length:551
Mass (Da):59,918
Checksum:iA39E7E594F66D57F
GO
Isoform 5 (identifier: Q13492-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     420-426: Missing.

Note: No experimental confirmation available.
Show »
Length:645
Mass (Da):70,037
Checksum:iE4F76B25065B499A
GO

Sequence cautioni

The sequence BAE06099 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti132N → D in BAG62035 (PubMed:14702039).Curated1
Sequence conflicti212N → H in AAB07762 (PubMed:8643484).Curated1
Sequence conflicti331E → G in BAG62035 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_028191158T → P.Corresponds to variant rs12800974dbSNPEnsembl.1
Natural variantiVAR_028192383S → F.Corresponds to variant rs12222608dbSNPEnsembl.1
Natural variantiVAR_028193578W → C.2 PublicationsCorresponds to variant rs1043858dbSNPEnsembl.1
Natural variantiVAR_028194579Q → E.2 PublicationsCorresponds to variant rs1043859dbSNPEnsembl.1
Natural variantiVAR_028195641F → L.Corresponds to variant rs556337dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0445671 – 51Missing in isoform 4. 1 PublicationAdd BLAST51
Alternative sequenceiVSP_009607420 – 469Missing in isoform 3 and isoform 4. 2 PublicationsAdd BLAST50
Alternative sequenceiVSP_044568420 – 426Missing in isoform 5. 1 Publication7
Alternative sequenceiVSP_009608593M → MNGMHFPQY in isoform 3. 1 Publication1
Alternative sequenceiVSP_004067594 – 613Missing in isoform 2. 1 PublicationAdd BLAST20

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U45976 mRNA. Translation: AAB07762.1.
AK300275 mRNA. Translation: BAG62035.1.
AB210017 mRNA. Translation: BAE06099.1. Different initiation.
AP000767 Genomic DNA. No translation available.
CH471076 Genomic DNA. Translation: EAW75120.1.
BC048259 mRNA. Translation: AAH48259.2.
BC064357 mRNA. Translation: AAH64357.1.
BC073961 mRNA. Translation: AAH73961.1.
AF060939 mRNA. Translation: AAC16711.1.
AF060940 mRNA. Translation: AAC16712.1.
CCDSiCCDS31653.1. [Q13492-3]
CCDS55783.1. [Q13492-4]
CCDS55784.1. [Q13492-5]
CCDS8272.1. [Q13492-1]
RefSeqiNP_001008660.1. NM_001008660.2. [Q13492-3]
NP_001193875.1. NM_001206946.1. [Q13492-5]
NP_001193876.1. NM_001206947.1. [Q13492-4]
NP_009097.2. NM_007166.3. [Q13492-1]
XP_005274388.1. XM_005274331.2. [Q13492-2]
UniGeneiHs.163893.

Genome annotation databases

EnsembliENST00000356360; ENSP00000348718; ENSG00000073921. [Q13492-2]
ENST00000393346; ENSP00000377015; ENSG00000073921. [Q13492-1]
ENST00000526033; ENSP00000433846; ENSG00000073921. [Q13492-5]
ENST00000528398; ENSP00000434884; ENSG00000073921. [Q13492-4]
ENST00000532317; ENSP00000436958; ENSG00000073921. [Q13492-3]
GeneIDi8301.
KEGGihsa:8301.
UCSCiuc001pbl.4. human. [Q13492-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U45976 mRNA. Translation: AAB07762.1.
AK300275 mRNA. Translation: BAG62035.1.
AB210017 mRNA. Translation: BAE06099.1. Different initiation.
AP000767 Genomic DNA. No translation available.
CH471076 Genomic DNA. Translation: EAW75120.1.
BC048259 mRNA. Translation: AAH48259.2.
BC064357 mRNA. Translation: AAH64357.1.
BC073961 mRNA. Translation: AAH73961.1.
AF060939 mRNA. Translation: AAC16711.1.
AF060940 mRNA. Translation: AAC16712.1.
CCDSiCCDS31653.1. [Q13492-3]
CCDS55783.1. [Q13492-4]
CCDS55784.1. [Q13492-5]
CCDS8272.1. [Q13492-1]
RefSeqiNP_001008660.1. NM_001008660.2. [Q13492-3]
NP_001193875.1. NM_001206946.1. [Q13492-5]
NP_001193876.1. NM_001206947.1. [Q13492-4]
NP_009097.2. NM_007166.3. [Q13492-1]
XP_005274388.1. XM_005274331.2. [Q13492-2]
UniGeneiHs.163893.

3D structure databases

ProteinModelPortaliQ13492.
SMRiQ13492.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113902. 99 interactors.
IntActiQ13492. 53 interactors.
MINTiMINT-1636298.
STRINGi9606.ENSP00000377015.

PTM databases

iPTMnetiQ13492.
PhosphoSitePlusiQ13492.
SwissPalmiQ13492.

Polymorphism and mutation databases

BioMutaiPICALM.
DMDMi116242714.

Proteomic databases

EPDiQ13492.
MaxQBiQ13492.
PaxDbiQ13492.
PeptideAtlasiQ13492.
PRIDEiQ13492.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000356360; ENSP00000348718; ENSG00000073921. [Q13492-2]
ENST00000393346; ENSP00000377015; ENSG00000073921. [Q13492-1]
ENST00000526033; ENSP00000433846; ENSG00000073921. [Q13492-5]
ENST00000528398; ENSP00000434884; ENSG00000073921. [Q13492-4]
ENST00000532317; ENSP00000436958; ENSG00000073921. [Q13492-3]
GeneIDi8301.
KEGGihsa:8301.
UCSCiuc001pbl.4. human. [Q13492-1]

Organism-specific databases

CTDi8301.
DisGeNETi8301.
GeneCardsiPICALM.
HGNCiHGNC:15514. PICALM.
HPAiHPA019053.
HPA019061.
MalaCardsiPICALM.
MIMi603025. gene.
neXtProtiNX_Q13492.
OpenTargetsiENSG00000073921.
Orphaneti99861. Precursor T-cell acute lymphoblastic leukemia.
PharmGKBiPA33287.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0251. Eukaryota.
ENOG410XQ90. LUCA.
GeneTreeiENSGT00390000008805.
HOGENOMiHOG000015764.
HOVERGENiHBG049391.
InParanoidiQ13492.
KOiK20044.
OMAiWNAATMA.
OrthoDBiEOG091G0810.
PhylomeDBiQ13492.
TreeFamiTF314861.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000073921-MONOMER.
ReactomeiR-HSA-432722. Golgi Associated Vesicle Biogenesis.
R-HSA-8856825. Cargo recognition for clathrin-mediated endocytosis.
R-HSA-8856828. Clathrin-mediated endocytosis.
SIGNORiQ13492.

Miscellaneous databases

ChiTaRSiPICALM. human.
GeneWikiiPICALM.
GenomeRNAii8301.
PMAP-CutDBQ13492.
PROiQ13492.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000073921.
CleanExiHS_PICALM.
ExpressionAtlasiQ13492. baseline and differential.
GenevisibleiQ13492. HS.

Family and domain databases

Gene3Di1.20.58.150. 1 hit.
1.25.40.90. 1 hit.
InterProiIPR011417. ANTH_dom.
IPR014712. Clathrin_AP_2.
IPR013809. ENTH.
IPR008942. ENTH_VHS.
IPR030412. PICALM.
[Graphical view]
PANTHERiPTHR22951:SF16. PTHR22951:SF16. 2 hits.
PfamiPF07651. ANTH. 1 hit.
[Graphical view]
SMARTiSM00273. ENTH. 1 hit.
[Graphical view]
SUPFAMiSSF48464. SSF48464. 1 hit.
PROSITEiPS50942. ENTH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPICAL_HUMAN
AccessioniPrimary (citable) accession number: Q13492
Secondary accession number(s): B4DTM3
, E9PN05, F8VPG7, O60700, Q4LE54, Q6GMQ6, Q86XZ9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 15, 2002
Last sequence update: October 17, 2006
Last modified: November 30, 2016
This is version 158 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.