Hematopoietic lineage cell-specific protein (HCLS1)
The protein contains 486 amino acids for an estimated molecular weight of 54014 Da.
Substrate of the antigen receptor-coupled tyrosine kinase. Plays a role in antigen receptor signaling for both clonal expansion and deletion in lymphoid cells. May also be involved in the regulation of gene expression. (updated: March 4, 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.
This protein is annotated as membranous in Gene Ontology.
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| Variant | Description |
|---|---|
| dbSNP:rs2070179 | |
| dbSNP:rs2070180 | |
| dbSNP:rs9869984 |
Biological Process
Actin filament polymerization
Cellular response to cytokine stimulus
Erythrocyte differentiation
Intracellular signal transduction
Negative regulation of leukocyte apoptotic process
Negative regulation of transcription by RNA polymerase II
Neuron projection morphogenesis
Obsolete positive regulation of transcription factor import into nucleus
Positive regulation of actin cytoskeleton reorganization
Positive regulation of axon extension
Positive regulation of cell population proliferation
Positive regulation of dendritic spine morphogenesis
Positive regulation of DNA-binding transcription factor activity
Positive regulation of granulocyte differentiation
Positive regulation of macrophage differentiation
Positive regulation of peptidyl-serine phosphorylation
Positive regulation of peptidyl-tyrosine phosphorylation
Positive regulation of phosphatidylinositol 3-kinase signaling
Positive regulation of protein import into nucleus
Positive regulation of protein kinase B signaling
Positive regulation of transcription by RNA polymerase II
Positive regulation of tyrosine phosphorylation of STAT protein
Postsynaptic actin cytoskeleton organization
Regulation of actin filament polymerization
Regulation of transcription, DNA-templated
Response to hormone
The reference OMIM entry for this protein is 601306
Hematopoietic cell-specific lyn substrate 1; hcls1
Hs1
CLONING
By screening a hybridoma cDNA library with a probe to the transactivating region of adenovirus-2 E1A, Kitamura et al. (1989) obtained a cDNA encoding HCLS1, which they called HS1. Sequence analysis predicted that the 486-amino acid hydrophilic protein lacks a signal peptide, N-glycosylation sites, and a transmembrane region, but contains several potential phosphorylation sites. HCLS1 has an N-terminal series of at least three 37-amino acid repeats, each of which includes 2 alpha helices, that are called HS1 repeats and are also found in contactin (CNTN1; 600016). In addition, HCLS1 has a central region homologous to the adenovirus E1A probe and a C-terminal SH3 domain. Northern blot analysis revealed expression of a 2.0-kb HCLS1 transcript restricted to hemopoietic tissues and cell lines. Western blot analysis showed expression of a 75-kD protein, considerably larger than the predicted 54 kD. Kitamura et al. (1989) concluded that HCLS1 should be a good marker for cells of hematopoietic origin.GENE FUNCTION
The human HCLS1 gene encodes a 75-kD intracellular protein whose expression is limited to hematopoietic cell lineages. Egashira et al. (1996) noted that the protein is a major substrate of protein-tyrosine kinases. It is an intracellular protein involved in the signal transduction pathways that initiate at the antigen receptors of both B and T lymphocytes. The protein is associated with LYN kinase (165120), and is rapidly tyrosine-phosphorylated after crosslinking of surface IgM on B cells. Scielzo et al. (2005) analyzed 40 patients with chronic lymphocytic leukemia (CLL; 151400) and found that those with predominantly phosphorylated HS1 had a significantly shorter median survival time. Scielzo et al. (2005) studied the expression pattern of HS1 after B-cell receptor engagement and found that normal mature B cells stimulated by anti-IgM shifted the non- or less-phosphorylated form of HS1 toward the more-phosphorylated form, naive B cells showed both HS1 forms, and memory B cells expressed mainly the phosphorylated fraction. Scielzo et al. (2005) concluded that antigen stimulation plays a central role in CLL.MAPPING
Using fluorescence in situ hybridization, Egashira et al. (1996) mapped HCLS1 to chromosome 3q13. ... 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
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601306 was added.