UniProt functional annotation for P11171



	UniProt functional annotation for P11171

UniProt code: P11171.

Organism: Homo sapiens (Human).

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

Function: Protein 4.1 is a major structural element of the erythrocyte membrane skeleton. It plays a key role in regulating membrane physical properties of mechanical stability and deformability by stabilizing spectrin-actin interaction. Recruits DLG1 to membranes. Required for dynein-dynactin complex and NUMA1 recruitment at the mitotic cell cortex during anaphase (PubMed:23870127). {ECO:0000269|PubMed:23870127}.

Subunit: Binds with a high affinity to glycophorin and with lower affinity to band III protein. Associates with the nuclear mitotic apparatus. Interacts with calmodulin (PubMed:10692436). Interacts with CENPJ (PubMed:11003675). Interacts with DLG1 (PubMed:7937897). Also found to associate with contractile apparatus and tight junctions. Interacts with NUMA1; this interaction is negatively regulated by CDK1 during metaphase and promotes anaphase-specific localization of NUMA1 in symmetrically dividing cells (PubMed:23870127). Interacts with ATP2B1; regulates small intestinal calcium absorption through regulation of membrane expression of ATP2B1 (By similarity). {ECO:0000250|UniProtKB:P48193, ECO:0000269|PubMed:10692436, ECO:0000269|PubMed:11003675, ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:7937897}.

Subcellular location: Cytoplasm, cytoskeleton {ECO:0000269|PubMed:12427749}. Cytoplasm, cell cortex {ECO:0000269|PubMed:12427749, ECO:0000269|PubMed:23870127}. Nucleus {ECO:0000269|PubMed:12427749}.

Ptm: Phosphorylated at multiple sites by different protein kinases and each phosphorylation event selectively modulates the protein's functions.

Ptm: Phosphorylation on Tyr-660 reduces the ability of 4.1 to promote the assembly of the spectrin/actin/4.1 ternary complex. {ECO:0000269|PubMed:1647028}.

Ptm: O-glycosylated; contains N-acetylglucosamine side chains in the C- terminal domain.

Disease: Elliptocytosis 1 (EL1) [MIM:611804]: A Rhesus-linked form of hereditary elliptocytosis, a genetically heterogeneous, autosomal dominant hematologic disorder. It is characterized by variable hemolytic anemia and elliptical or oval red cell shape. {ECO:0000269|PubMed:3467321}. 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:		Protein 4.1 is a major structural element of the erythrocyte membrane skeleton. It plays a key role in regulating membrane physical properties of mechanical stability and deformability by stabilizing spectrin-actin interaction. Recruits DLG1 to membranes. Required for dynein-dynactin complex and NUMA1 recruitment at the mitotic cell cortex during anaphase (PubMed:23870127). {ECO:0000269\|PubMed:23870127}.


Subunit:		Binds with a high affinity to glycophorin and with lower affinity to band III protein. Associates with the nuclear mitotic apparatus. Interacts with calmodulin (PubMed:10692436). Interacts with CENPJ (PubMed:11003675). Interacts with DLG1 (PubMed:7937897). Also found to associate with contractile apparatus and tight junctions. Interacts with NUMA1; this interaction is negatively regulated by CDK1 during metaphase and promotes anaphase-specific localization of NUMA1 in symmetrically dividing cells (PubMed:23870127). Interacts with ATP2B1; regulates small intestinal calcium absorption through regulation of membrane expression of ATP2B1 (By similarity). {ECO:0000250\|UniProtKB:P48193, ECO:0000269\|PubMed:10692436, ECO:0000269\|PubMed:11003675, ECO:0000269\|PubMed:23870127, ECO:0000269\|PubMed:7937897}.
Subcellular location:		Cytoplasm, cytoskeleton {ECO:0000269\|PubMed:12427749}. Cytoplasm, cell cortex {ECO:0000269\|PubMed:12427749, ECO:0000269\|PubMed:23870127}. Nucleus {ECO:0000269\|PubMed:12427749}.
Ptm:		Phosphorylated at multiple sites by different protein kinases and each phosphorylation event selectively modulates the protein's functions.
Ptm:		Phosphorylation on Tyr-660 reduces the ability of 4.1 to promote the assembly of the spectrin/actin/4.1 ternary complex. {ECO:0000269\|PubMed:1647028}.
Ptm:		O-glycosylated; contains N-acetylglucosamine side chains in the C- terminal domain.
Disease:		Elliptocytosis 1 (EL1) [MIM:611804]: A Rhesus-linked form of hereditary elliptocytosis, a genetically heterogeneous, autosomal dominant hematologic disorder. It is characterized by variable hemolytic anemia and elliptical or oval red cell shape. {ECO:0000269\|PubMed:3467321}. Note=The disease is caused by variants affecting the gene represented in this entry.