UniProt functional annotation for Q13351



	UniProt functional annotation for Q13351

UniProt code: Q13351.

Organism: Homo sapiens (Human).

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

Function: Transcription regulator of erythrocyte development that probably serves as a general switch factor during erythropoiesis. Is a dual regulator of fetal-to-adult globin switching. Binds to the CACCC box in the beta-globin gene promoter and acts as a preferential activator of this gene. Furthermore, it binds to the BCL11A promoter and activates expression of BCL11A, which in turn represses the HBG1 and HBG2 genes. This dual activity ensures that, in most adults, fetal hemoglobin levels are low. Able to activate CD44 and AQP1 promoters. When sumoylated, acts as a transcriptional repressor by promoting interaction with CDH2/MI2beta and also represses megakaryocytic differentiation. {ECO:0000250|UniProtKB:P46099, ECO:0000269|PubMed:25585695}.

Subunit: Interacts with PCAF; the interaction does not acetylate EKLF and inhibits its transactivation activity (By similarity). Interacts with CREBBP/CBP and EP300; the interactions enhance the transactivation activity. Interacts with TFB1. {ECO:0000250, ECO:0000269|PubMed:21670263, ECO:0000269|PubMed:9707565}.

Subcellular location: Nucleus {ECO:0000269|PubMed:21055716, ECO:0000269|PubMed:25585695}. Note=Colocalizes with SUMO1 in nuclear speckles. {ECO:0000250}.

Tissue specificity: Expression restricted to adult bone marrow and fetal liver. Not expressed in myeloid nor lymphoid cell lines. {ECO:0000269|PubMed:8924208, ECO:0000269|PubMed:9119377}.

Domain: The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. {ECO:0000269|PubMed:31375868}.

Ptm: Acetylated; can be acetylated on both Lys-274 and Lys-288. Acetylation on Lys-274 (by CBP) appears to be the major site affecting EKLF transactivation activity (By similarity). {ECO:0000250}.

Ptm: Sumoylated; sumoylation, promoted by PIAS1, leads to repression of megakaryocyte differentiation. Also promotes the interaction with the CDH4 subunit of the NuRD repression complex (By similarity). {ECO:0000250}.

Ptm: Phosphorylated primarily on serine residues in the transactivation domain. Phosphorylation on Thr-23 is critical for the transactivation activity (By similarity). {ECO:0000250}.

Polymorphism: Genetic variations in KLF1 underlie the fetal hemoglobin quantitative trait locus 6 (HBFQTL6) [MIM:613566]. Classic hereditary persistence of fetal hemoglobin (HPFH) is characterized by a substantial elevation of fetal hemoglobin (HbF) in adult red blood cells. There are no other phenotypic or hematologic manifestations. In healthy adults, fetal hemoglobin (HbF) is present at residual levels (less than 0.06% of total hemoglobin) with over 20-fold variation. Ten to fifteen percent of adults fall within the upper tail of the distribution. {ECO:0000269|PubMed:20676099}.

Polymorphism: Genetic variations in KLF1 underlie the blood group- Lutheran inhibitor (In(Lu)) phenotype [MIM:111150]; also known as dominant Lu (a-b-) phenotype. In(Lu) is characterized phenotypically by the apparent absence of the Lu antigen (BCAM) on red blood cells during serologic tests: Lu(a-b-). {ECO:0000269|PubMed:18487511}.

Disease: Anemia, congenital dyserythropoietic, 4 (CDAN4) [MIM:613673]: A blood disorder characterized by ineffective erythropoiesis and hemolysis resulting in anemia. Circulating erythroblasts and erythroblasts in the bone marrow show various morphologic abnormalities. Affected individuals with CDA4 also have increased levels of fetal hemoglobin. {ECO:0000269|PubMed:21055716, ECO:0000269|PubMed:25585695}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the krueppel C2H2-type zinc-finger protein family. {ECO:0000305}.

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:		Transcription regulator of erythrocyte development that probably serves as a general switch factor during erythropoiesis. Is a dual regulator of fetal-to-adult globin switching. Binds to the CACCC box in the beta-globin gene promoter and acts as a preferential activator of this gene. Furthermore, it binds to the BCL11A promoter and activates expression of BCL11A, which in turn represses the HBG1 and HBG2 genes. This dual activity ensures that, in most adults, fetal hemoglobin levels are low. Able to activate CD44 and AQP1 promoters. When sumoylated, acts as a transcriptional repressor by promoting interaction with CDH2/MI2beta and also represses megakaryocytic differentiation. {ECO:0000250\|UniProtKB:P46099, ECO:0000269\|PubMed:25585695}.


Subunit:		Interacts with PCAF; the interaction does not acetylate EKLF and inhibits its transactivation activity (By similarity). Interacts with CREBBP/CBP and EP300; the interactions enhance the transactivation activity. Interacts with TFB1. {ECO:0000250, ECO:0000269\|PubMed:21670263, ECO:0000269\|PubMed:9707565}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:21055716, ECO:0000269\|PubMed:25585695}. Note=Colocalizes with SUMO1 in nuclear speckles. {ECO:0000250}.
Tissue specificity:		Expression restricted to adult bone marrow and fetal liver. Not expressed in myeloid nor lymphoid cell lines. {ECO:0000269\|PubMed:8924208, ECO:0000269\|PubMed:9119377}.
Domain:		The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. {ECO:0000269\|PubMed:31375868}.
Ptm:		Acetylated; can be acetylated on both Lys-274 and Lys-288. Acetylation on Lys-274 (by CBP) appears to be the major site affecting EKLF transactivation activity (By similarity). {ECO:0000250}.
Ptm:		Sumoylated; sumoylation, promoted by PIAS1, leads to repression of megakaryocyte differentiation. Also promotes the interaction with the CDH4 subunit of the NuRD repression complex (By similarity). {ECO:0000250}.
Ptm:		Phosphorylated primarily on serine residues in the transactivation domain. Phosphorylation on Thr-23 is critical for the transactivation activity (By similarity). {ECO:0000250}.
Polymorphism:		Genetic variations in KLF1 underlie the fetal hemoglobin quantitative trait locus 6 (HBFQTL6) [MIM:613566]. Classic hereditary persistence of fetal hemoglobin (HPFH) is characterized by a substantial elevation of fetal hemoglobin (HbF) in adult red blood cells. There are no other phenotypic or hematologic manifestations. In healthy adults, fetal hemoglobin (HbF) is present at residual levels (less than 0.06% of total hemoglobin) with over 20-fold variation. Ten to fifteen percent of adults fall within the upper tail of the distribution. {ECO:0000269\|PubMed:20676099}.
Polymorphism:		Genetic variations in KLF1 underlie the blood group- Lutheran inhibitor (In(Lu)) phenotype [MIM:111150]; also known as dominant Lu (a-b-) phenotype. In(Lu) is characterized phenotypically by the apparent absence of the Lu antigen (BCAM) on red blood cells during serologic tests: Lu(a-b-). {ECO:0000269\|PubMed:18487511}.
Disease:		Anemia, congenital dyserythropoietic, 4 (CDAN4) [MIM:613673]: A blood disorder characterized by ineffective erythropoiesis and hemolysis resulting in anemia. Circulating erythroblasts and erythroblasts in the bone marrow show various morphologic abnormalities. Affected individuals with CDA4 also have increased levels of fetal hemoglobin. {ECO:0000269\|PubMed:21055716, ECO:0000269\|PubMed:25585695}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the krueppel C2H2-type zinc-finger protein family. {ECO:0000305}.