Clathrin interactor 1 (CLINT1)
The protein contains 625 amino acids for an estimated molecular weight of 68259 Da.
Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). May have a role in transport via clathrin-coated vesicles from the trans-Golgi network to endosomes. Stimulates clathrin assembly. (updated: April 1, 2015)
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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Biological Process
Clathrin coat assembly
Endocytosis
Membrane organization
Post-Golgi vesicle-mediated transport
The reference OMIM entry for this protein is 607265
Clathrin interactor 1; clint1
Epsin 4; epn4
Epsin-related protein; epnr
Enthoprotin
Kiaa0171
For background information on epsins, see EPN1 (607262).
CLONING
Nagase et al. (1996) isolated a cDNA encoding EPN4, which they designated KIAA0171, from the immature myeloid cell line KG-1. The deduced protein contains 625 amino acids. Northern blot analysis revealed moderate expression in all tissues tested, with highest expression in skeletal muscle. Wasiak et al. (2002) identified rat Epn4, which they called enthoprotin, by subcellular proteomics of clathrin-coated vesicles (CCVs). Epn4 was highly enriched on CCVs isolated from rat brain and liver extracts. By sequence analysis of tryptic peptides, they identified an epsin N-terminal homology (ENTH) domain and a consensus type-2 clathrin box in the C-terminal domain. The predicted molecular mass is about 68 kD, and Epn4 expressed by transfected COS-7 cells showed an apparent molecular mass of about 80 kD. Endogenous Epn4 localized in COS-7 cells in a punctate pattern that was enriched in a perinuclear pool that colocalized with clathrin (118955) and with the clathrin adaptor protein complex AP1 (see 607291).GENE FUNCTION
Using pull-down assays, Wasiak et al. (2002) found that rat Epn4 interacts with AP1, AP2, clathrin, and GGA2 (606005). They determined that, through its C-terminal domain, Epn4 binds to the terminal domain of the clathrin heavy chain and stimulates clathrin assembly. Saint-Pol et al. (2004) found that HeLa cell EPN4 was involved in retrograde transport of endogenous cargo proteins and bacterial Shiga toxin from early and recycling endosomes to the trans-Golgi network.MAPPING
By radiation hybrid analysis, Nagase et al. (1996) mapped the EPN4 gene to chromosome 5.MOLECULAR GENETICS
Pimm et al. (2005) investigated 450 unrelated white English, Irish, Welsh, and Scottish research subjects with schizophrenia and 450 ancestrally matched supernormal controls. Four adjacent markers at the 5-prime end of the EPN4 gene showed significant evidence of linkage disequilibrium with schizophrenia. These included included 2 microsatellite markers and 2 SNPs within the EPN4 gene. A series of different 2- and 3-marker haplotypes were also significantly associated with schizophrenia. Since the EPN4 gene encodes enthoprotin, which has a role in transport and stability of neurotransmitter vesicles at the synapses and within neurons, they considered it likely that a genetically determined abnormality in the structure, function, or expression of this protein is responsible for genetic susceptibility to a subtype of schizophrenia on 5q33.3 (SCZD1; 181510).BIOCHEMICAL FEATURES
- Crystal Structure Miller et al. (2007) characterized the molecular details governing the sorting of a SNARE into clathrin-coated vesicles, namely, the direct recognition of the 3-helical bundle H(abc) domain of the mouse SNARE Vti1b (603207) by the human clathrin adaptor epsinR (EPNR, also known as CLINT1). Structures of each domain and of their complex showed that this interaction (dissociation constant 22 microM) is mediated by surface patches composed of approximately 15 residues each, the topographies of which are dependent on each domain's overall fold. Disruption of the interface with point mutations abolished the interaction in vitro and caused Vti1b to become relocalized to late endosomes and lysosomes. Miller et al. (2007) stated that this new class of highly specific, surface-surface interaction between the clathrin coat component and the cargo is di ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
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
Oct. 26, 2017: Protein entry updated
Automatic update: model status changed
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 607265 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed