Erbin (ERBB2IP)
The protein contains 1412 amino acids for an estimated molecular weight of 158298 Da.
Acts as an adapter for the receptor ERBB2, in epithelia. By binding the unphosphorylated 'Tyr-1248' of receptor ERBB2, it may contribute to stabilize this unphosphorylated state (PubMed:16203728). Inhibits NOD2-dependent NF-kappa-B signaling and proinflammatory cytokine secretion (PubMed:16203728). (updated: Jan. 31, 2018)
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.
- 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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| dbSNP:rs3213837 | |
| dbSNP:rs191137999 | |
| dbSNP:rs16894812 | |
| dbSNP:rs34521887 | |
| dbSNP:rs35601230 | |
| dbSNP:rs3805466 | |
| empty |
Biological Process
Basal protein localization
Cell adhesion
Cell cycle
Cell growth
Cellular response to tumor necrosis factor
Epidermal growth factor receptor signaling pathway
ERBB2 signaling pathway
Establishment or maintenance of epithelial cell apical/basal polarity
Integrin-mediated signaling pathway
Intermediate filament cytoskeleton organization
Negative regulation of monocyte chemotactic protein-1 production
Negative regulation of NF-kappaB transcription factor activity
Negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway
Positive regulation of Ras protein signal transduction
Protein targeting
Regulation of postsynaptic membrane neurotransmitter receptor levels
Response to lipopolysaccharide
Response to muramyl dipeptide
Signal transduction
The reference OMIM entry for this protein is 606944
Erbb2 interacting protein; erbb2ip
Densin-180-like protein; erbin
CLONING
In a yeast 2-hybrid screen of a mouse kidney cDNA library with the 9 C-terminal residues of Erbb2 (164870) as bait, Borg et al. (2000) cloned Erbb2ip, which they called Erbin. They cloned human ERBB2IP by RT-PCR of a human B-lymphocyte cell line. The deduced 1,371-amino acid protein contains 16 canonical LRR (leucine-rich repeat) motifs at the N terminus, followed by an LRR-like domain, proline-rich stretches that may represent binding sites for SH3 and WW domains, and a C-terminal PDZ domain. Northern blot analysis revealed a 7.2-kb transcript in most human and mouse tissues. Western blot analysis indicated a 180-kD doublet in all tissues tested. Favre et al. (2001) cloned ERBB2IP in a yeast 2-hybrid screen of a human keratinocyte cDNA library with the N terminus of bullous pemphigoid antigen-1 (BPAG1; 113810) as bait. They observed several splice variants. ERBB2IP was expressed as a doublet of about 6.9 to 7.4 kb in human keratinocytes and in a keratinocyte cell line. Semiquantitative RT-PCR indicated numerous transcripts expressed in most tissues. Western blot analysis showed a 200-kD in differentiated cells but not in undifferentiated keratinocytes. Huang et al. (2001) cloned Erbb2ip from mouse muscle, brain, and heart cDNA libraries in a yeast 2-hybrid screen using Erbb2 as bait. Erbb2ip was expressed as a 180-kD protein in brain, skeletal muscle, primary muscle cultures, and muscle cell lines. Erbb2ip expression was found at a similar level in myoblasts and myotubes, suggesting that expression is not differentially regulated in muscle. By immunolocalization studies, they colocalized Erbb2ip with the acetylcholine receptor at the neuromuscular junction. Both Erbb2 and Erbb2ip were also found in synaptosomes from adult mouse brain and copurified with postsynaptic densities.GENE FUNCTION
Using coimmunoprecipitation, mutation analysis, and GST pull-down experiments, Borg et al. (2000) determined that ERBB2IP interacts with nonactivated ERBB2 and that the interaction requires the PDZ domain of ERBB2IP. They further showed by immunolocalization studies that the 2 proteins colocalize to the basolateral surface of polarized human colon carcinoma cells and that mutation of the PDZ domain of ERBB2IP causes mislocalization of ERBB2 in stably transfected canine kidney cells. By mutation analysis and in vitro binding assays, Favre et al. (2001) determined that ERBB2IP interacts specifically with BPAG1 and integrin beta-4 (147557). Huang et al. (2001) found that mouse Erbb2ip associates with Psd95 (602887). Mutation analysis indicated that the interaction is dependent upon the PDZ domain of Psd95.GENE STRUCTURE
Favre et al. (2001) determined that the ERBB2IP gene contains at least 26 exons. Sequence comparison of ERBB2IP variants indicated that the variants are likely caused by alternate splicing between exons 21 and 26.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the ERBB2IP gene to chromosome 5 (TMAP WI-31186). Favre et al. (2001) stated that sequence analysis places the ERBB2IP gene on the long arm of chromosome 5 between D5S427 and D5S647.MOLECULAR GENETICS
Tran et al. (2014) used whole-exome sequencing to demonstrate that tumor-infiltrating lymphocytes (TILs) from a patient with metastatic cholangiocarcinoma contained CD4 (186940)+ T-helper-1 (TH1) cells that recognized a mutation in ERBB2IP expressed by the cancer. After adoptive transfer of TILs co ... More on the omim web site
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
Sept. 16, 2016: Protein entry updated
Automatic update: OMIM entry 606944 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed