IST1 homolog (IST1)
The protein contains 364 amino acids for an estimated molecular weight of 39751 Da.
ESCRT-III-like protein involved in specific functions of the ESCRT machinery. Is required for efficient abscission during cytokinesis, but not for HIV-1 budding. The involvement in the MVB pathway is not established. Involved in recruiting VPS4A and/or VPS4B to the midbody of dividing cells (PubMed:19129479, PubMed:19129480). During late anaphase, involved in nuclear envelope reassembly and mitotic spindle disassembly together with the ESCRT-III complex: IST1 acts by mediating the recruitment of SPAST to the nuclear membrane, leading to microtubule severing (PubMed:26040712). Regulates early endosomal tubulation together with the ESCRT-III complex by mediating the recruitment of SPAST (PubMed:23897888). (updated: Oct. 25, 2017)
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.
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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Biological Process
Abscission
Cell division
Cytokinesis
Cytoskeleton-dependent cytokinesis
ESCRT III complex disassembly
Establishment of protein localization
Mitotic nuclear membrane reassembly
Multivesicular body assembly
Neutrophil degranulation
Positive regulation of collateral sprouting
Positive regulation of proteolysis
Protein localization
Protein transport
Viral capsid secondary envelopment
Viral release from host cell
The reference OMIM entry for this protein is 616434
Increased sodium tolerance 1, yeast, homolog of; ist1
Kiaa0174
DESCRIPTION
Endosomal sorting complexes required for transport (ESCRT) function in the terminal stages of cytokinesis, enveloped virus budding, and intraluminal vesicle formation at the multivesicular body. All 3 of these processes terminate with the severing of thin, cytoplasm-filled membrane 'necks' and require the ATPase activity of VPS4 (see VPS4A, 609982). IST1 functions with ESCRT and is a critical element in cytokinesis (Bajorek et al., 2009).CLONING
By sequencing clones obtained from a size-fractionated KG-1 human myeloid leukemia cell line cDNA library, Nagase et al. (1996) cloned IST1, which they designated KIAA0174. The deduced protein contains 364 amino acids. Northern blot analysis detected KIAA0174 in all tissues examined, with highest expression in kidney and lowest in lung. Bajorek et al. (2009) reported that the N-terminal half of the deduced 366-amino acid IST1 protein constitutes a helical region called the ELYC domain, followed by a central proline-rich linker and 2 C-terminal microtubule-interacting and transport (MIT)-interacting motifs (MIMs). Immunohistochemical analysis revealed that IST1 localized both diffusely and in small cytoplasmic puncta in nondividing HeLa cells, but it concentrated at microtubule organizing centers and at the emerging midbody with progression of mitosis. At late telophase, IST1 concentrated at both ends of the Flemming body in a double-ring pattern after midbody thinning, but immediately before abscission. By sequencing ESTs, Agromayor et al. (2009) identified 4 protein isoforms of IST1.GENE FUNCTION
Using yeast 2-hybrid screens, followed by coimmunoprecipitation and protein-binding assays, Bajorek et al. (2009) found that human IST1 interacted with the ESCRT proteins CHMP1A (164010), CHMP1B (606486), and LIP5 (C6ORF55; 610902), as well as with VPS4A and VPS4B (609983). Mutation and nuclear magnetic resonance (NMR) spectroscopic studies revealed that 2 C-terminal MIM motifs of IST1 wrapped around and bound in different grooves of the MIT helical bundle of VPS4. IST1 also bound CHMP1 directly; like IST1, CHMP1 has a C-terminal MIM element that bound VPS4 MIT domains. Depletion of either IST1 or CHMP1 in HeLa cells blocked VPS4 recruitment to the midbody during cytokinesis and blocked cell division. Time-lapse imaging revealed that IST1 depletion caused dividing cells to arrest during the abscission stage. Cells remained tethered together through their midbodies before eventually recoalescing into a single cell with multiple nuclei. IST1 depletion did not inhibit budding of human immunodeficiency virus (HIV)-1 (see 609423). Bajorek et al. (2009) concluded that IST1 is specifically required for the cytokinesis function of ESCRT and that IST1 and CHMP1 recruit VPS4 to the midbody for abscission. Independently, Agromayor et al. (2009) found that human IST1 bound MIT domain-containing proteins and played a critical role in cytokinesis, but not in endosomal sorting or HIV-1 budding. Renvoise et al. (2010) observed that IST1 bound with high affinity to spartin (SPG20; 607111) and that the 2 proteins colocalized to the ends of Flemming bodies during cytokinesis. Deletion analysis revealed that the N-terminal MIT domain of spartin interacted with the MIM1 domain of IST1. Depletion of IST1 in HeLa cells reduced the localization of both spartin and IST1 at midbodies, but depletion of spartin had little effect on IST1 localization. Depletion of either IST1 or spart ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: OMIM entry 616434 was added.
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
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed