Tectonin beta-propeller repeat-containing protein 1 (TECPR1)
The protein contains 1165 amino acids for an estimated molecular weight of 129696 Da.
Tethering factor involved in autophagy. Involved in autophagosome maturation by promoting the autophagosome fusion with lysosomes: acts by associating with both the ATG5-ATG12 conjugate and phosphatidylinositol-3-phosphate (PtdIns(3)P) present at the surface of autophagosomes. Also involved in selective autophagy against bacterial pathogens, by being required for phagophore/preautophagosomal structure biogenesis and maturation. (updated: Jan. 7, 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.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
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.
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| Variant | Description |
|---|---|
| dbSNP:rs35623371 | |
| dbSNP:rs11762014 |
The reference OMIM entry for this protein is 614781
Tectonin beta-propeller repeat-containing 1; tecpr1
Kiaa1358
DESCRIPTION
TECPR1 has a central role in autophagy and mediates the fusion of autophagosomes with lysosomes for degradation of autophagosome contents (Chen et al., 2012).CLONING
By sequencing clones obtained from a size-fractionated fetal brain cDNA library, Nagase et al. (2000) cloned TECPR1, which they designated KIAA1358. The transcript contains a repetitive element in its 3-prime end and the deduced protein contains 1,123 amino acids. RT-PCR analysis revealed variable TECPR1 expression in all tissues examined. Highest expression was detected in lung, whole adult brain, and in most specific adult brain regions examined, and lowest expression was detected in adult heart, skeletal muscle, pancreas, spleen, and in fetal liver. Chen et al. (2012) reported that the full-length TECPR1 protein contains 1,165 amino acids. It has a dysferlin (603009) domain near the N terminus, followed by 4 TECPR beta-propeller repeats, an ATG5 (604261)-ATG12 (609608) interacting region (AIR), a pleckstrin homology (PH) domain, another beta-propeller repeat, a second dysferlin domain, and 4 additional beta-propeller repeats near the C terminus. Epitope-tagged TECPR1 localized to cellular puncta that proved to be mature autophagic structures, with a subset of TECPR1 colocalizing with the lysosome marker LAMP2 (309060).GENE FUNCTION
Behrends et al. (2010) reported a proteomic analysis of the autophagy interaction network in human cells under conditions of ongoing (basal) autophagy, revealing 751 interactions among 409 candidate-interacting proteins with extensive connectivity among subnetworks. TECPR1 was identified by its interaction with ATG12, ATG3 (609606), and ATG5 and appeared to be part of a ubiquitin-like transfer cascade subnetwork. TECPR1 also associated with components of the TRAPP vesicle-tethering complex, including FLJ12716 (TRAPPC11; 614138), TTC15 (TRAPPC12; 614139), KIAA1012 (TRAPPC8; 614136), TRAPPC2L (610970), TRAPPC3 (610955), TRAPPC4 (610971), and TRAPPC5. Using coimmunoprecipitation experiments with HEK293 cells, Chen et al. (2012) found that full-length TECPR1 precipitated with the ATG12-ATG5 conjugate, free ATG5, and free ATG12, but did not precipitate with ATG12-ATG5 complexes that also included ATG16 (ATG16L1; 610767). Mutation analysis helped define the central AIR domain required for the interaction of TECPR1 with ATG12-ATG5 and showed that an N-terminal dysferlin domain bound free ATG5. Protein-lipid overlay assays revealed that the isolated PH domain of TECPR1, but not full-length TECPR1, specifically interacted with phosphatidylinositol-3-phosphate (PtdIns(3)P). Binding of the AIR domain by ATG12-ATG5 permitted full-length TECPR1 to interact with PtdIns(3)P. Treatment of human cells with an agent that elevated lysosomal pH resulted in formation of large TECPR1- and ATG5-positive autolysosomes. Depletion of TECPR1 in HeLa cells via short hairpin RNA did not alter autophagophore formation or lysosomal activity, but inhibited degradation of autophagosome content and resulted in accumulation of autophagic vacuoles. Both the AIR domain and PH domain of TECPR1 were required for the autophagic function of TECPR1. Chen et al. (2012) concluded that TECPR1 is required for autophagosome maturation. They hypothesized that TECPR1 may function as a tethering factor to join autophagosomes with lysosomes through its association with ATG12-ATG5 and PtdIns(3)P.MAPPING
By radiation hybrid analysis, Nag ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for TECPR1
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 614781 was added.