CLTC (clathrin heavy polypeptide)

2005-04-01   Pedram Argani , Marc Ladanyi 

Identity

HGNC
LOCATION
17q23.1
LOCUSID
ALIAS
CHC,CHC17,CLH-17,CLTCL2,Hc,MRD56
FUSION GENES

DNA/RNA

Transcription

32 exons, 6111 bp mRNA

Proteins

Description

Clathrin is the major protein constituent of the coat that surrounds organelles (cytoplasmic vesicles) to mediate selective protein transport. Clathrin coats are involved in receptor-mediated endocytosis and intracellular trafficking and recycling of receptors, which accounts for its characteristic punctate cytoplasmic and perinuclear cellular distribution. Structurally, clathrin is a triskelion (three-legged) shaped protein complex that is composed of a trimer of heavy chains (CLTC) each bound to a single light chain. CLTC is a 1675 amino acid residue protein encoded by a gene consisting of 32 exons. Its known domains include a N-terminal globular domain (residues 1-494) that interacts with adaptor proteins (AP-1, AP-2, b-arrestin), a light chain-binding region (residues 1074-1552), and a trimerization domain (residues 1550-1600) near the C-terminus.

Localisation

Cytoplasmic vesicles

Function

mediate endocytosis of transmembrane receptors.

Implicated in

Disease
ALCL are high grade non Hodgkin lymphomas; ALK+ ALCL are ALCL where ALK is involved in a fusion gene; ALK+ ALCL represent 50 to 60 % of ALCL cases (they are CD30+, ALK+;); belong to the "cytoplasmic ALK+" subset.
Prognosis
Although presenting as a high grade tumour, a 80% five yr survival is associated with this anomaly
Hybrid gene
5 CLTC - 3 ALK
Fusion protein
NH2 CLTC - COOH ALK
Entity name
Inflammatory myofibroblastic tumors with t(2;17)(p23;q23)
Note
In these tumors, the fusion point in CLTC is identical, being at amino acid 1634 (corresponding to the 3 end of exon 31 of CLTC), such that almost all of CLTC is included in the fusion protein, including its trimerization domain . As a fusion partner, CLTC has been postulated to provide CLTC-ALK with deregulated expression driven by its constitutively activated promoter and constitutive oligomerization of the chimeric protein via the CLTC multimerization domains normally used for clathrin coat assembly. Since ALK is a tyrosine kinase that is activated by cross-phosphorylation following ligand binding, CLTC-ALK-induced oligomerization may result in a constitutively activated ALK tyrosine kinase domain. In this sense, CLTC is likely to function in CLTC-ALK as other prototypical "dimerizing translocation partners" in fusions involving tyrosine kinase genes.
Disease
rare soft tissue tumour found in children and young adults
Prognosis
good prognosis
Hybrid gene
5 CLTC - 3 ALK
Entity name
Xp11 renal translocation carcinoma with t(X;17)(p11;q23)
Note
In the CLTC-TFE3 fusion, the fusion point on CLTC is at amino acid 932 (corresponding to the end of exon 17), thereby excluding the CLTC trimerization domain from the predicted fusion protein. As in other TFE3 gene fusions, the nuclear localization and DNA binding domains of TFE3 are retained in CLTC-TFE3. Based on these features and existing data on other TFE3 fusion proteins, CLTC-TFE3 may act as an aberrant transcription factor, with the CLTC promoter driving constitutive expression.
Disease
rare renal carcinoma (single case report)
Prognosis
Unknown prognosis
Hybrid gene
5 CLTC 3TFE3

Breakpoints

Atlas Image

Bibliography

Pubmed IDLast YearTitleAuthors
129176402003A novel CLTC-TFE3 gene fusion in pediatric renal adenocarcinoma with t(X;17)(p11.2;q23).Argani P et al
114858982001Fusion of the ALK gene to the clathrin heavy chain gene, CLTC, in inflammatory myofibroblastic tumor.Bridge JA et al
121125242002Identification of novel fusion partners of ALK, the anaplastic lymphoma kinase, in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor.Cools J et al
17653751991Human clathrin heavy chain (CLTC): partial molecular cloning, expression, and mapping of the gene to human chromosome 17q11-qter.Dodge GR et al
109664732000Clathrin.Kirchhausen T et al
92429161997Clathrin-coated vesicle formation and protein sorting: an integrated process.Schmid SL et al
103605761999Clathrin self-assembly is mediated by a tandemly repeated superhelix.Ybe JA et al

Other Information

Locus ID:

NCBI: 1213
MIM: 118955
HGNC: 2092
Ensembl: ENSG00000141367

Variants:

dbSNP: 1213
ClinVar: 1213
TCGA: ENSG00000141367
COSMIC: CLTC

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000141367ENST00000269122Q00610
ENSG00000141367ENST00000393043Q00610
ENSG00000141367ENST00000472651K7EJJ5
ENSG00000141367ENST00000475458J3KRF5
ENSG00000141367ENST00000483176J3KTN1
ENSG00000141367ENST00000579456J3KS13
ENSG00000141367ENST00000580081J3KSQ2
ENSG00000141367ENST00000584313J3QL20
ENSG00000141367ENST00000621829A0A087WVQ6

Expression (GTEx)

0
50
100
150
200

Pathways

PathwaySourceExternal ID
Huntington's diseaseKEGGko05016
Huntington's diseaseKEGGhsa05016
LysosomeKEGGko04142
LysosomeKEGGhsa04142
EndocytosisKEGGko04144
EndocytosisKEGGhsa04144
Bacterial invasion of epithelial cellsKEGGko05100
Bacterial invasion of epithelial cellsKEGGhsa05100
Endocrine and other factor-regulated calcium reabsorptionKEGGko04961
Endocrine and other factor-regulated calcium reabsorptionKEGGhsa04961
Synaptic vesicle cycleKEGGko04721
Synaptic vesicle cycleKEGGhsa04721
DiseaseREACTOMER-HSA-1643685
Infectious diseaseREACTOMER-HSA-5663205
Influenza InfectionREACTOMER-HSA-168254
Influenza Life CycleREACTOMER-HSA-168255
Entry of Influenza Virion into Host Cell via EndocytosisREACTOMER-HSA-168275
Immune SystemREACTOMER-HSA-168256
Adaptive Immune SystemREACTOMER-HSA-1280218
MHC class II antigen presentationREACTOMER-HSA-2132295
Signal TransductionREACTOMER-HSA-162582
Signalling by NGFREACTOMER-HSA-166520
NGF signalling via TRKA from the plasma membraneREACTOMER-HSA-187037
Retrograde neurotrophin signallingREACTOMER-HSA-177504
Signaling by WntREACTOMER-HSA-195721
Beta-catenin independent WNT signalingREACTOMER-HSA-3858494
PCP/CE pathwayREACTOMER-HSA-4086400
WNT5A-dependent internalization of FZD4REACTOMER-HSA-5099900
WNT5A-dependent internalization of FZD2, FZD5 and ROR2REACTOMER-HSA-5140745
Vesicle-mediated transportREACTOMER-HSA-5653656
Membrane TraffickingREACTOMER-HSA-199991
trans-Golgi Network Vesicle BuddingREACTOMER-HSA-199992
Clathrin derived vesicle buddingREACTOMER-HSA-421837
Golgi Associated Vesicle BiogenesisREACTOMER-HSA-432722
Lysosome Vesicle BiogenesisREACTOMER-HSA-432720
Gap junction trafficking and regulationREACTOMER-HSA-157858
Gap junction traffickingREACTOMER-HSA-190828
Gap junction degradationREACTOMER-HSA-190873
Formation of annular gap junctionsREACTOMER-HSA-196025
MetabolismREACTOMER-HSA-1430728
Metabolism of lipids and lipoproteinsREACTOMER-HSA-556833
Lipid digestion, mobilization, and transportREACTOMER-HSA-73923
Lipoprotein metabolismREACTOMER-HSA-174824
LDL-mediated lipid transportREACTOMER-HSA-171052
Developmental BiologyREACTOMER-HSA-1266738
Axon guidanceREACTOMER-HSA-422475
L1CAM interactionsREACTOMER-HSA-373760
Recycling pathway of L1REACTOMER-HSA-437239
EPH-Ephrin signalingREACTOMER-HSA-2682334
EPH-ephrin mediated repulsion of cellsREACTOMER-HSA-3928665
VLDL interactionsREACTOMER-HSA-8855121
VLDLR internalisation and degradationREACTOMER-HSA-8866427
Clathrin-mediated endocytosisREACTOMER-HSA-8856828
Cargo recognition for clathrin-mediated endocytosisREACTOMER-HSA-8856825

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
206398722010Plasma membrane contributes to the formation of pre-autophagosomal structures.330
129529412003Clathrin-mediated endocytosis in AP-2-depleted cells.272
129601472003Effect of clathrin heavy chain- and alpha-adaptin-specific small inhibitory RNAs on endocytic accessory proteins and receptor trafficking in HeLa cells.104
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
175509712007The retromer complex and clathrin define an early endosomal retrograde exit site.73
212975822011A TACC3/ch-TOG/clathrin complex stabilises kinetochore fibres by inter-microtubule bridging.64
204988562010Clostridial glucosylating toxins enter cells via clathrin-mediated endocytosis.56
205666842010Clathrin heavy chain mediates TACC3 targeting to mitotic spindles to ensure spindle stability.41
186564762008Double-membrane gap junction internalization requires the clathrin-mediated endocytic machinery.35
196542082009GAK, a regulator of clathrin-mediated membrane traffic, also controls centrosome integrity and chromosome congression.33

Citation

Pedram Argani ; Marc Ladanyi

CLTC (clathrin heavy polypeptide)

Atlas Genet Cytogenet Oncol Haematol. 2005-04-01

Online version: http://atlasgeneticsoncology.org/gene/360/cltc

Historical Card

2003-08-01 CLTC (clathrin heavy polypeptide) by  Jean-Loup Huret,Sylvie Senon 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

2001-08-01 CLTC (clathrin heavy polypeptide) by  Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France