Clathrin heavy chain 1 (CLTC)
The protein contains 1675 amino acids for an estimated molecular weight of 191615 Da.
Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans-Golgi network. Acts as component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge (PubMed:15858577, PubMed:16968737, PubMed:21297582). The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:23532825). Plays a role in early autophagosome formation (PubMed:20639872). (updated: Jan. 31, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
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| Variant | Description |
|---|---|
| MRD56 | |
| MRD56 | |
| MRD56; unknown pathological significance |
Biological Process
Amyloid-beta clearance by transcytosis
Antigen processing and presentation of exogenous peptide antigen via MHC class II
Autophagy
Cell division
Clathrin coat assembly
Clathrin-dependent endocytosis
Intracellular protein transport
Low-density lipoprotein particle clearance
Low-density lipoprotein particle receptor catabolic process
Membrane organization
Microtubule-based movement
Mitotic cell cycle
Mitotic nuclear division
Negative regulation of hyaluronan biosynthetic process
Negative regulation of protein localization to plasma membrane
Osteoblast differentiation
Post-Golgi vesicle-mediated transport
Receptor internalization
Receptor-mediated endocytosis
Regulation of mitotic spindle organization
Retrograde transport, endosome to Golgi
Transcytosis
Transferrin transport
Wnt signaling pathway, planar cell polarity pathway
Cellular Component
Clathrin coat
Clathrin coat of coated pit
Clathrin coat of trans-Golgi network vesicle
Clathrin complex
Clathrin-coated endocytic vesicle
Clathrin-coated endocytic vesicle membrane
Clathrin-coated vesicle
Cytoplasm
Cytosol
Endolysosome membrane
Endosome
Extracellular exosome
Extracellular matrix
Extracellular vesicle
Focal adhesion
Intracellular membrane-bounded organelle
Lysosome
Melanosome
Membrane
Mitotic spindle
Mitotic spindle microtubule
Plasma membrane
Protein complex
Protein-containing complex
Spindle
T-tubule
Trans-Golgi network membrane
Vesicle
Molecular Function
Ankyrin binding
Arrestin family protein binding
Clathrin light chain binding
Disordered domain specific binding
Double-stranded RNA binding
Heat shock protein binding
Identical protein binding
Low-density lipoprotein particle receptor binding
Peptide binding
Poly(A) RNA binding
Protein kinase binding
RNA binding
Structural molecule activity
Ubiquitin-specific protease binding
The reference OMIM entry for this protein is 118955
Clathrin, heavy polypeptide; cltc
Clathrin heavy chain; chc cltc/tfe3 fusion gene, included
Cltc/alk fusion gene, included
DESCRIPTION
Clathrin is a major protein component of the cytoplasmic face of intracellular organelles, called coated vesicles and coated pits. These specialized organelles are involved in the intracellular trafficking of receptors and endocytosis of a variety of macromolecules. Clathrin molecules have a triskelion structure composed of 3 noncovalently bound heavy chains (CLTC) and 3 light chains (e.g., CLTA; 118960) (Dodge et al., 1991).CLONING
Dodge et al. (1991) isolated a 916-bp cDNA for the heavy chain of clathrin.GENE FUNCTION
Huntingtin-interacting protein 1 (HIP1; 601767) is enriched in membrane-containing cell fractions and has been implicated in vesicle trafficking. It is a multidomain protein containing an epsin (607262) N-terminal homology (ENTH) domain, a central coiled-coil-forming region, and a C-terminal actin-binding domain. Waelter et al. (2001) identified 3 HIP1-associated proteins, clathrin heavy chain and alpha-adaptin A and C (AP2A1; 601026). In vitro binding studies revealed that the central coiled-coil domain of HIP1 is required for the interaction with clathrin, whereas DPF-like motifs located upstream to this domain are important for HIP1 binding to the C-terminal 'appendage' domain of alpha-adaptin A and C. Expression of full-length HIP1 in mammalian cells resulted in a punctate cytoplasmic immunostaining characteristic of clathrin-coated vesicles. In contrast, when a truncated HIP1 protein containing both the DPF-like motifs and the coiled-coil domain was overexpressed, large perinuclear vesicle-like structures containing HIP1, huntingtin (613004), clathrin, and endocytosed transferrin were observed, suggesting that HIP1 is an endocytic protein, the structural integrity of which may be crucial for maintenance of normal vesicle size in vivo. Royle et al. (2005) showed that clathrin stabilizes fibers of the mitotic spindle to aid congression of chromosomes. Clathrin bound to the spindle directly by the N-terminal domain of clathrin heavy chain. Depletion of clathrin heavy chain using RNA interference prolonged mitosis; kinetochore fibers were destabilized, leading to defective congression of chromosomes to the metaphase plate and persistent activation of the spindle checkpoint. Normal mitosis was rescued by clathrin triskelia but not the N-terminal domain of clathrin heavy chain, indicating that stabilization of kinetochore fibers was dependent on the unique structure of clathrin. Enari et al. (2006) found that CHC localized to both cytosol and nuclei in several human cell lines. Immunoprecipitation analysis showed that CHC interacted directly with p53 (TP53; 191170). CHC overexpression enhanced p53-dependent transactivation, whereas reduction of CHC expression by RNA interference attenuated p53 transcriptional activity. CHC bound to a p53-responsive promoter in vivo and stabilized the interaction between p53 and p300 (EP300; 602700) to promote p53-mediated transcription. Binding of p300 and p53 increased in a CHC dose-dependent manner, and CHC formed a complex with p53 and p300 in response to DNA damage. Clathrin light chains were absent from nuclear CHC-p53 complexes, and CLTA or CLTB (118970) blocked p53-CHC associations in vitro by sequestering CHC. Enari et al. (2006) hypothesized that CHC recruits p300 and p53 to p53-responsive promoters and may function as a scaffold protein bridging p53 and p300. Deborde et al. (2008) showed that clathrin is required for polarity of the ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 118955 was added.