UniProt functional annotation for P26038



	UniProt functional annotation for P26038

UniProt code: P26038.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Ezrin-radixin-moesin (ERM) family protein that connects the actin cytoskeleton to the plasma membrane and thereby regulates the structure and function of specific domains of the cell cortex. Tethers actin filaments by oscillating between a resting and an activated state providing transient interactions between moesin and the actin cytoskeleton (PubMed:10212266). Once phosphorylated on its C-terminal threonine, moesin is activated leading to interaction with F-actin and cytoskeletal rearrangement (PubMed:10212266). These rearrangements regulate many cellular processes, including cell shape determination, membrane transport, and signal transduction (PubMed:12387735, PubMed:15039356). The role of moesin is particularly important in immunity acting on both T and B-cells homeostasis and self-tolerance, regulating lymphocyte egress from lymphoid organs (PubMed:9298994, PubMed:9616160). Modulates phagolysosomal biogenesis in macrophages (By similarity). Participates also in immunologic synapse formation (PubMed:27405666). {ECO:0000250|UniProtKB:P26041, ECO:0000269|PubMed:10212266, ECO:0000269|PubMed:12387735, ECO:0000269|PubMed:15039356, ECO:0000269|PubMed:27405666, ECO:0000269|PubMed:9298994, ECO:0000269|PubMed:9616160}.

Activity regulation: A head-to-tail association, of the N-terminal and C-terminal halves results in a closed conformation (inactive form) which is incapable of actin or membrane-binding. {ECO:0000269|PubMed:10212266}.

Subunit: In resting T-cells, part of a PAG1-SLC9A3R1-MSN complex which is disrupted upon TCR activation. Interacts with SLC9A3R1 (PubMed:9314537, PubMed:15020681). Interacts with PPP1R16B (PubMed:18586956). Interacts with PDZD8. Interacts with SELPLG and SYK; these interaction mediate the activation of SYK by SELPLG (PubMed:12387735). Interacts with PDPN (via cytoplasmic domain); this interaction activates RHOA and promotes epithelial-mesenchymal transition (PubMed:17046996). Interacts with SPN/CD43 (PubMed:9616160, PubMed:11728332). Interacts with CD44 (PubMed:9298994). Interacts with ICAM2 (By similarity). Interacts with ICAM3 (via C-terminus) (PubMed:9298994). Interacts with PDZD8 (PubMed:21549406). Interacts with F-actin (PubMed:10212266). Interacts with CD46 (PubMed:7884872). Interacts with PTPN6 (By similarity). {ECO:0000250|UniProtKB:P26041, ECO:0000269|PubMed:10212266, ECO:0000269|PubMed:11728332, ECO:0000269|PubMed:12387735, ECO:0000269|PubMed:15020681, ECO:0000269|PubMed:17046996, ECO:0000269|PubMed:18586956, ECO:0000269|PubMed:21549406, ECO:0000269|PubMed:7884872, ECO:0000269|PubMed:9298994, ECO:0000269|PubMed:9314537, ECO:0000269|PubMed:9616160}.

Subunit: (Microbial infection) Interacts with HIV-1 envelope protein gp120. {ECO:0000269|PubMed:9213396}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:11728332, ECO:0000269|PubMed:15039356, ECO:0000269|PubMed:18586956, ECO:0000269|PubMed:7884872, ECO:0000269|PubMed:9298994}; Peripheral membrane protein {ECO:0000250|UniProtKB:P26041}; Cytoplasmic side {ECO:0000250|UniProtKB:P26041}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:P26041}. Apical cell membrane {ECO:0000250|UniProtKB:P26041}; Peripheral membrane protein {ECO:0000250|UniProtKB:P26041}; Cytoplasmic side {ECO:0000250|UniProtKB:P26041}. Cell projection, microvillus membrane {ECO:0000250|UniProtKB:P26041}; Peripheral membrane protein {ECO:0000250|UniProtKB:P26041}; Cytoplasmic side {ECO:0000250|UniProtKB:P26041}. Cell projection, microvillus {ECO:0000250|UniProtKB:P26041}. Note=Phosphorylated form is enriched in microvilli-like structures at apical membrane. Increased cell membrane localization of both phosphorylated and non-phosphorylated forms seen after thrombin treatment (By similarity). Localizes at the uropods of T lymphoblasts. {ECO:0000250|UniProtKB:P26041, ECO:0000269|PubMed:18586956, ECO:0000269|PubMed:9298994}.

Tissue specificity: In all tissues and cultured cells studied.

Domain: The [IL]-x-C-x-x-[DE] motif is a proposed target motif for cysteine S-nitrosylation mediated by the iNOS-S100A8/A9 transnitrosylase complex. {ECO:0000305|PubMed:25417112}.

Ptm: Phosphorylation on Thr-558 is crucial for the formation of microvilli-like structures. Phosphorylation by ROCK2 suppresses the head-to-tail association of the N-terminal and C-terminal halves resulting in an opened conformation which is capable of actin and membrane-binding (By similarity). Phosphorylation on Thr-558 by STK10 negatively regulates lymphocyte migration and polarization. {ECO:0000250, ECO:0000269|PubMed:19255442}.

Ptm: S-nitrosylation of Cys-117 is induced by interferon-gamma and oxidatively-modified low-densitity lipoprotein (LDL(ox)) implicating the iNOS-S100A8/9 transnitrosylase complex. {ECO:0000269|PubMed:25417112}.

Disease: Immunodeficiency 50 (IMD50) [MIM:300988]: A primary immunodeficiency disorder characterized by onset of recurrent bacterial or varicella zoster virus infections in early childhood, profound lymphopenia, hypogammaglobulinemia, fluctuating monocytopenia and neutropenia, and a poor immune response to vaccine antigens. {ECO:0000269|PubMed:27405666}. Note=The disease is caused by variants affecting the gene represented in this entry.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Ezrin-radixin-moesin (ERM) family protein that connects the actin cytoskeleton to the plasma membrane and thereby regulates the structure and function of specific domains of the cell cortex. Tethers actin filaments by oscillating between a resting and an activated state providing transient interactions between moesin and the actin cytoskeleton (PubMed:10212266). Once phosphorylated on its C-terminal threonine, moesin is activated leading to interaction with F-actin and cytoskeletal rearrangement (PubMed:10212266). These rearrangements regulate many cellular processes, including cell shape determination, membrane transport, and signal transduction (PubMed:12387735, PubMed:15039356). The role of moesin is particularly important in immunity acting on both T and B-cells homeostasis and self-tolerance, regulating lymphocyte egress from lymphoid organs (PubMed:9298994, PubMed:9616160). Modulates phagolysosomal biogenesis in macrophages (By similarity). Participates also in immunologic synapse formation (PubMed:27405666). {ECO:0000250\|UniProtKB:P26041, ECO:0000269\|PubMed:10212266, ECO:0000269\|PubMed:12387735, ECO:0000269\|PubMed:15039356, ECO:0000269\|PubMed:27405666, ECO:0000269\|PubMed:9298994, ECO:0000269\|PubMed:9616160}.


Activity regulation:		A head-to-tail association, of the N-terminal and C-terminal halves results in a closed conformation (inactive form) which is incapable of actin or membrane-binding. {ECO:0000269\|PubMed:10212266}.
Subunit:		In resting T-cells, part of a PAG1-SLC9A3R1-MSN complex which is disrupted upon TCR activation. Interacts with SLC9A3R1 (PubMed:9314537, PubMed:15020681). Interacts with PPP1R16B (PubMed:18586956). Interacts with PDZD8. Interacts with SELPLG and SYK; these interaction mediate the activation of SYK by SELPLG (PubMed:12387735). Interacts with PDPN (via cytoplasmic domain); this interaction activates RHOA and promotes epithelial-mesenchymal transition (PubMed:17046996). Interacts with SPN/CD43 (PubMed:9616160, PubMed:11728332). Interacts with CD44 (PubMed:9298994). Interacts with ICAM2 (By similarity). Interacts with ICAM3 (via C-terminus) (PubMed:9298994). Interacts with PDZD8 (PubMed:21549406). Interacts with F-actin (PubMed:10212266). Interacts with CD46 (PubMed:7884872). Interacts with PTPN6 (By similarity). {ECO:0000250\|UniProtKB:P26041, ECO:0000269\|PubMed:10212266, ECO:0000269\|PubMed:11728332, ECO:0000269\|PubMed:12387735, ECO:0000269\|PubMed:15020681, ECO:0000269\|PubMed:17046996, ECO:0000269\|PubMed:18586956, ECO:0000269\|PubMed:21549406, ECO:0000269\|PubMed:7884872, ECO:0000269\|PubMed:9298994, ECO:0000269\|PubMed:9314537, ECO:0000269\|PubMed:9616160}.
Subunit:		(Microbial infection) Interacts with HIV-1 envelope protein gp120. {ECO:0000269\|PubMed:9213396}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:11728332, ECO:0000269\|PubMed:15039356, ECO:0000269\|PubMed:18586956, ECO:0000269\|PubMed:7884872, ECO:0000269\|PubMed:9298994}; Peripheral membrane protein {ECO:0000250\|UniProtKB:P26041}; Cytoplasmic side {ECO:0000250\|UniProtKB:P26041}. Cytoplasm, cytoskeleton {ECO:0000250\|UniProtKB:P26041}. Apical cell membrane {ECO:0000250\|UniProtKB:P26041}; Peripheral membrane protein {ECO:0000250\|UniProtKB:P26041}; Cytoplasmic side {ECO:0000250\|UniProtKB:P26041}. Cell projection, microvillus membrane {ECO:0000250\|UniProtKB:P26041}; Peripheral membrane protein {ECO:0000250\|UniProtKB:P26041}; Cytoplasmic side {ECO:0000250\|UniProtKB:P26041}. Cell projection, microvillus {ECO:0000250\|UniProtKB:P26041}. Note=Phosphorylated form is enriched in microvilli-like structures at apical membrane. Increased cell membrane localization of both phosphorylated and non-phosphorylated forms seen after thrombin treatment (By similarity). Localizes at the uropods of T lymphoblasts. {ECO:0000250\|UniProtKB:P26041, ECO:0000269\|PubMed:18586956, ECO:0000269\|PubMed:9298994}.
Tissue specificity:		In all tissues and cultured cells studied.
Domain:		The [IL]-x-C-x-x-[DE] motif is a proposed target motif for cysteine S-nitrosylation mediated by the iNOS-S100A8/A9 transnitrosylase complex. {ECO:0000305\|PubMed:25417112}.
Ptm:		Phosphorylation on Thr-558 is crucial for the formation of microvilli-like structures. Phosphorylation by ROCK2 suppresses the head-to-tail association of the N-terminal and C-terminal halves resulting in an opened conformation which is capable of actin and membrane-binding (By similarity). Phosphorylation on Thr-558 by STK10 negatively regulates lymphocyte migration and polarization. {ECO:0000250, ECO:0000269\|PubMed:19255442}.
Ptm:		S-nitrosylation of Cys-117 is induced by interferon-gamma and oxidatively-modified low-densitity lipoprotein (LDL(ox)) implicating the iNOS-S100A8/9 transnitrosylase complex. {ECO:0000269\|PubMed:25417112}.
Disease:		Immunodeficiency 50 (IMD50) [MIM:300988]: A primary immunodeficiency disorder characterized by onset of recurrent bacterial or varicella zoster virus infections in early childhood, profound lymphopenia, hypogammaglobulinemia, fluctuating monocytopenia and neutropenia, and a poor immune response to vaccine antigens. {ECO:0000269\|PubMed:27405666}. Note=The disease is caused by variants affecting the gene represented in this entry.