Protein kinase C and casein kinase substrate in neurons protein 2 (PACSIN2)
The protein contains 486 amino acids for an estimated molecular weight of 55739 Da.
Regulates the morphogenesis and endocytosis of caveolae (By similarity). Lipid-binding protein that is able to promote the tubulation of the phosphatidic acid-containing membranes it preferentially binds. Plays a role in intracellular vesicle-mediated transport. Involved in the endocytosis of cell-surface receptors like the EGF receptor, contributing to its internalization in the absence of EGF stimulus.', '(Microbial infection) Specifically enhances the efficiency of HIV-1 virion spread by cell-to-cell transfer (PubMed:29891700). Also promotes the protrusion engulfment during cell-to-cell spread of bacterial pathogens like Listeria monocytogenes (PubMed:31242077). Involved in lipid droplet formation, which is important for HCV virion assembly (PubMed:31801866). (updated: Oct. 7, 2020)
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.
- 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:rs35383004 | |
| dbSNP:rs2746984 | |
| dbSNP:rs1062913 |
Biological Process
Actin cytoskeleton organization
Caveola assembly
Caveolin-mediated endocytosis
Cell projection morphogenesis
Cytoskeleton organization
Membrane organization
Modulation of chemical synaptic transmission
Negative regulation of endocytosis
Plasma membrane tubulation
Protein localization to endosome
Regulation of endocytosis
Cellular Component
Caveola
Cell-cell junction
Cytoplasm
Cytoplasmic vesicle membrane
Cytoskeleton
Cytosol
Early endosome
Endosome
Extracellular exosome
Extrinsic component of membrane
Focal adhesion
Glutamatergic synapse
Intracellular membrane-bounded organelle
Membrane-bounded vesicle
Nuclear speck
Nucleoplasm
Plasma membrane
Recycling endosome membrane
Ruffle membrane
The reference OMIM entry for this protein is 604960
Protein kinase c and casein kinase substrate in neurons 2; pacsin2
DESCRIPTION
Proteins containing a BIN (see 601248)/amphiphysin (AMPH; 600418)/Rvs167 (BAR) domain, such as PACSIN2, regulate membrane curvature. The positively charged surface of the BAR domain binds to the negatively charged inner surface of the plasma membrane, thereby bending the membrane according to the protein structure (Senju et al., 2011).CLONING
PACSIN family members, such as mouse Pacsin1 and chicken FAP52, are cytoplasmic adaptor proteins with a common arrangement of domains and conserved regions, including a CDC15 N-terminal domain, which contains a RAEYL motif and a coiled-coil region, and a C-terminal SH3 domain. By searching an EST database for novel members of the PACSIN family, Ritter et al. (1999) identified ESTs encoding human and mouse PACSIN2. The complete human PACSIN2 coding sequence, obtained from 2 overlapping retina ESTs, encodes a deduced 486-amino acid protein that shares 93.6% sequence identity with mouse Pacsin2. The PACSIN2 proteins contain a CDC15 N-terminal domain, a C-terminal SRC (190090) homology-3 (SH3) domain, 3 conserved regions specific to the PACSIN family, and 3 asn-pro-phe (NPF) motifs, which potentially bind to EH domains. The PACSIN2 proteins share high sequence similarity with chicken FAP52 and mouse Pacsin1 (606512). However, compared to these proteins, PACSIN2 proteins have a 41-amino acid insertion, which contains 1 NPF motif. In contrast to the restricted neural expression of mouse Pacsin1 (Plomann et al., 1998), Northern blot analysis detected mouse Pacsin2 expression in all tissues examined, with the highest levels in brain, heart, skeletal muscle, and ovary. Immunofluorescence microscopy of recombinant Pacsin2 expressed in fibroblasts showed a broad, vesicle-like cytoplasmic distribution that appeared to partially overlap with the distributions of both the actin filament and microtubule networks. Unlike FAP52, Pacsin2 was not detected at focal contacts. Ritter et al. (1999) suggested that PACSIN2 may participate in the organization of the actin cytoskeleton and the regulation of vesicular traffic. By Northern blot analysis, Sumoy et al. (2001) detected ubiquitous distribution of a 3.4-kb PACSIN2 transcript, with marked expression in heart, and a predominant 2.4-kb alternate transcript in pancreas. Senju et al. (2011) reported that the PACSIN2 protein contains an N-terminal extended FES (190030)-CIP4 (TRIP10; 604504) homology BAR (F-BAR) domain, in addition to the C-terminal SH3 domain and NPF motifs. Immunogold electron microscopy localized endogenous PACSIN2 to the neck region of caveolae in HeLa cells. PACSIN2 also localized to the plasma membrane and cytosol. De Kruek et al. (2012) stated that PACSIN2 localized to RAB5 (see 179512)-positive endosomes.GENE FUNCTION
Senju et al. (2011) found that overexpression of the PACSIN2 F-BAR domain in HeLa cells altered the localization of caveolin-1 (CAV1; 601047) and caused mesh-like plasma membrane invaginations. The isolated F-BAR domain of PACSIN2 bound the N terminus of CAV1 more strongly than full-length PACSIN2. Senju et al. (2011) determined that an intramolecular interaction between the SH3 and F-BAR domains of PACSIN2 was autoinhibitory and that CAV1 interrupted this interaction. In addition to binding CAV1, the F-BAR domain of PACSIN2 simultaneously bound the plasma membrane and induced membrane tubulation. Knockdown of PACSIN2 in HeLa cells via small interfering RNA reduced the number of CAV1-pos ... More on the omim web site
Oct. 20, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Dec. 2, 2019: 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604960 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed