Nck-associated protein 1-like (NCKAP1L)
The protein contains 1127 amino acids for an estimated molecular weight of 128153 Da.
Essential hematopoietic-specific regulator of the actin cytoskeleton (Probable). Controls lymphocyte development, activation, proliferation and homeostasis, erythrocyte membrane stability, as well as phagocytosis and migration by neutrophils and macrophages (PubMed:16417406, PubMed:17696648). Component of the WAVE2 complex which signals downstream of RAC to stimulate F-actin polymerization. Required for stabilization and/or translation of the WAVE2 complex proteins in hematopoietic cells (By similarity). Within the WAVE2 complex, enables the cortical actin network to restrain excessive degranulation and granule release by T-cells (PubMed:32647003). Required for efficient T-lymphocyte and neutrophil migration (PubMed:32647003). Exhibits complex cycles of activation and inhibition to generate waves of propagating the assembly with actin (PubMed:16417406). Also involved in mechanisms WAVE-independent to regulate myosin and actin polymerization during neutrophil chemotaxis (PubMed:17696648). In T-cells, required for proper mechanistic target of rapamycin complex 2 (mTORC2)-dependent AKT phosphorylation, cell proliferation and cytokine secretion, including that of IL2 and TNF (PubMed:32647003). (updated: June 2, 2021)
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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.
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Biological Process
Actin polymerization-dependent cell motility
B cell homeostasis
B cell receptor signaling pathway
Cell migration
Cell morphogenesis
Cell projection assembly
Chemotaxis
Cortical actin cytoskeleton organization
Erythrocyte development
Erythrocyte homeostasis
Fc-gamma receptor signaling pathway involved in phagocytosis
Maintenance of cell polarity
Myeloid cell homeostasis
Negative regulation of apoptotic process
Negative regulation of interleukin-17 production
Negative regulation of interleukin-6 production
Negative regulation of myosin-light-chain-phosphatase activity
Neuron projection morphogenesis
Neutrophil chemotaxis
Neutrophil degranulation
Positive regulation of actin filament polymerization
Positive regulation of B cell differentiation
Positive regulation of B cell proliferation
Positive regulation of CD4-positive, alpha-beta T cell differentiation
Positive regulation of CD8-positive, alpha-beta T cell differentiation
Positive regulation of cell adhesion mediated by integrin
Positive regulation of erythrocyte differentiation
Positive regulation of gamma-delta T cell differentiation
Positive regulation of lymphocyte differentiation
Positive regulation of neutrophil chemotaxis
Positive regulation of phagocytosis, engulfment
Positive regulation of phosphorylation
Positive regulation of protein kinase activity
Positive regulation of T cell proliferation
Protein complex assembly
Protein-containing complex assembly
Response to drug
T cell homeostasis
Vascular endothelial growth factor receptor signaling pathway
The reference OMIM entry for this protein is 141180
Hematopoietic protein hem-1; hem1
CLONING
Hromas et al. (1991) obtained cDNAs 3.8 kb in length containing a long open reading frame and showing hybridization exclusively to transcripts from hematopoietic cells. The protein, which they called HEM1, contains 8 potential membrane domains and 2 possible cAMP/cGMP phosphorylation sites.MAPPING
By hybridization to flow-sorted chromosomes, Hromas et al. (1991) mapped the HEM1 gene to chromosome 12. Using in situ hybridization, they localized it to chromosome 12q13.1, a region of occasional translocations in hematopoietic neoplasia and the site of a rare folic acid fragile site.ANIMAL MODEL
Using chemical mutagenesis and positional cloning, Park et al. (2008) obtained mice with a mutation in exon 13 of the Hem1 gene, resulting in a gln445-to-ter substitution. Mice lacking Hem1 had defective F-actin (see 102610) polymerization and actin capping in lymphocytes and neutrophils due to loss of the Rac (see 602048)-controlled actin regulatory WAVE (WASF1; 605035) protein complex. T-cell development was disrupted at the Cd4 (186940)/Cd8 (see 186910) double-negative to Cd4/Cd8 double-positive stage, and T-cell activation and adhesion were impaired. Hem1-deficient neutrophils failed to migrate in response to chemotactic signals and were deficient in phagocytosing bacteria. Other Rac-dependent functions, such as Th1 differentiation and Nfkb (see 164011)-dependent proinflammatory cytokine transcription, were unimpaired, whereas production of Th17 cells (see 603149) was enhanced. Park et al. (2008) concluded that HEM1 is essential for hematopoietic cell development, function, and homeostasis by controlling a pathway leading to cytoskeletal reorganization. ... More on the omim web site
July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
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 141180 was added.