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Q13351 (KLF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Krueppel-like factor 1
Alternative name(s):
Erythroid krueppel-like transcription factor
Short name=EKLF
Gene names
Name:KLF1
Synonyms:EKLF
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length362 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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 By similarity. Ref.6 Ref.7 Ref.8

Subunit structure

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. Ref.5 Ref.8

Subcellular location

Nucleus. Note: Colocalizes with SUMO1 in nuclear speckles By similarity. Ref.6

Tissue specificity

Expression restricted to adult bone marrow and fetal liver. Not expressed in myeloid nor lymphoid cell lines. Ref.1 Ref.2

Post-translational modification

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. Ref.5

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.

Phosphorylated primarily on serine residues in the transactivation domain. Phosphorylation on Thr-23 is critical for the transactivation activity By similarity.

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.

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-).

Involvement in 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6

Sequence similarities

Belongs to the krueppel C2H2-type zinc-finger protein family.

Contains 3 C2H2-type zinc fingers.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   DiseaseCongenital dyserythropoietic anemia
Disease mutation
Hereditary hemolytic anemia
   DomainRepeat
Zinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionActivator
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to peptide

Inferred from electronic annotation. Source: Ensembl

chromatin remodeling

Inferred from electronic annotation. Source: Ensembl

embryonic hemopoiesis

Inferred from electronic annotation. Source: Ensembl

erythrocyte differentiation

Inferred from mutant phenotype Ref.6. Source: UniProtKB

erythrocyte maturation

Inferred from electronic annotation. Source: Ensembl

in utero embryonic development

Inferred from electronic annotation. Source: Ensembl

liver development

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Inferred from direct assay Ref.7Ref.6. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentnuclear chromatin

Inferred from direct assay PubMed 21539536. Source: BHF-UCL

nucleus

Inferred from direct assay Ref.6. Source: UniProtKB

   Molecular_functioncore promoter proximal region sequence-specific DNA binding

Inferred from direct assay PubMed 21539536. Source: BHF-UCL

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

sequence-specific DNA binding transcription factor activity

Traceable author statement Ref.1PubMed 9778250. Source: ProtInc

transcription regulatory region DNA binding

Inferred from direct assay Ref.7. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 362362Krueppel-like factor 1
PRO_0000047160

Regions

Zinc finger279 – 30325C2H2-type 1
Zinc finger309 – 33325C2H2-type 2
Zinc finger339 – 36123C2H2-type 3
Compositional bias1 – 263263Pro-rich
Compositional bias61 – 7616Asp/Glu-rich (acidic)

Amino acid modifications

Modified residue231Phosphothreonine; by CK2 Probable
Modified residue2741N6-acetyllysine By similarity
Modified residue2881N6-acetyllysine By similarity
Cross-link54Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Natural variations

Natural variant1021S → P. Ref.4 Ref.6
Corresponds to variant rs2072597 [ dbSNP | Ensembl ].
VAR_043981
Natural variant1821F → L.
Corresponds to variant rs2072596 [ dbSNP | Ensembl ].
VAR_043982
Natural variant2991H → Y in blood group-In(Lu). Ref.9
VAR_058108
Natural variant3251E → K in CDAN4; has a dominant-negative effect on the transcriptional activation of CD44 and AQP1 promoters. Ref.6
VAR_064901
Natural variant3281R → H in blood group-In(Lu). Ref.9
VAR_058109
Natural variant3281R → L in blood group-In(Lu). Ref.9
VAR_058110
Natural variant3311R → G in blood group-In(Lu). Ref.9
VAR_058111

Experimental info

Sequence conflict1631A → G in AAC51108. Ref.2
Sequence conflict1731P → A in AAC51108. Ref.2
Sequence conflict1841R → G in AAC51108. Ref.2
Sequence conflict1921A → E in AAC51108. Ref.2

Secondary structure

....... 362
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q13351 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 6E9A48A2B6A37C76

FASTA36238,221
        10         20         30         40         50         60 
MATAETALPS ISTLTALGPF PDTQDDFLKW WRSEEAQDMG PGPPDPTEPP LHVKSEDQPG 

        70         80         90        100        110        120 
EEEDDERGAD ATWDLDLLLT NFSGPEPGGA PQTCALAPSE ASGAQYPPPP ETLGAYAGGP 

       130        140        150        160        170        180 
GLVAGLLGSE DHSGWVRPAL RARAPDAFVG PALAPAPAPE PKALALQPVY PGPGAGSSGG 

       190        200        210        220        230        240 
YFPRTGLSVP AASGAPYGLL SGYPAMYPAP QYQGHFQLFR GLQGPAPGPA TSPSFLSCLG 

       250        260        270        280        290        300 
PGTVGTGLGG TAEDPGVIAE TAPSKRGRRS WARKRQAAHT CAHPGCGKSY TKSSHLKAHL 

       310        320        330        340        350        360 
RTHTGEKPYA CTWEGCGWRF ARSDELTRHY RKHTGQRPFR CQLCPRAFSR SDHLALHMKR 


HL 

« Hide

References

« Hide 'large scale' references
[1]"Isolation, genomic structure, and expression of human erythroid Kruppel-like factor (EKLF)."
Bieker J.J.
DNA Cell Biol. 15:347-352(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY.
[2]"The human erythroid-specific transcription factor EKLF localizes to chromosome 19p13.12-p13.13."
van Ree J.H., Roskrow M.A., Becher A.M., McNall R., Valentine V.A., Jane S.M., Cunningham J.M.
Genomics 39:393-395(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[3]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT PRO-102.
Tissue: Lung.
[5]"Acetylation and modulation of erythroid Krueppel-like factor (EKLF) activity by interaction with histone acetyltransferases."
Zhang W., Bieker J.J.
Proc. Natl. Acad. Sci. U.S.A. 95:9855-9860(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION, INTERACTION WITH CBP; EP300 AND PCAF.
[6]"A dominant mutation in the gene encoding the erythroid transcription factor KLF1 causes a congenital dyserythropoietic anemia."
Arnaud L., Saison C., Helias V., Lucien N., Steschenko D., Giarratana M.C., Prehu C., Foliguet B., Montout L., de Brevern A.G., Francina A., Ripoche P., Fenneteau O., Da Costa L., Peyrard T., Coghlan G., Illum N., Birgens H. expand/collapse author list , Tamary H., Iolascon A., Delaunay J., Tchernia G., Cartron J.P.
Am. J. Hum. Genet. 87:721-727(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ROLE IN ERYTHROPOIESIS, FUNCTION AS TRANSCRIPTIONAL ACTIVATOR OF CD44 AND AQP1, SUBCELLULAR LOCATION, VARIANT PRO-102, VARIANT CDAN4 LYS-325, CHARACTERIZATION OF VARIANT CDAN4 LYS-325.
[7]"Haploinsufficiency for the erythroid transcription factor KLF1 causes hereditary persistence of fetal hemoglobin."
Borg J., Papadopoulos P., Georgitsi M., Gutierrez L., Grech G., Fanis P., Phylactides M., Verkerk A.J., van der Spek P.J., Scerri C.A., Cassar W., Galdies R., van Ijcken W., Ozgur Z., Gillemans N., Hou J., Bugeja M., Grosveld F.G. expand/collapse author list , von Lindern M., Felice A.E., Patrinos G.P., Philipsen S.
Nat. Genet. 42:801-805(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS REGULATOR OF FETAL-TO-ADULT GLOBIN SWITCHING, INVOLVEMENT IN HBFQTL6.
[8]"Structural and functional characterization of an atypical activation domain in erythroid Kruppel-like factor (EKLF)."
Mas C., Lussier-Price M., Soni S., Morse T., Arseneault G., Di Lello P., Lafrance-Vanasse J., Bieker J.J., Omichinski J.G.
Proc. Natl. Acad. Sci. U.S.A. 108:10484-10489(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 51-90 IN COMPLEX WITH YEAST TFB1, FUNCTION, INTERACTION WITH TFB1; CREBBP AND EP300.
[9]"Mutations in EKLF/KLF1 form the molecular basis of the rare blood group In(Lu) phenotype."
Singleton B.K., Burton N.M., Green C., Brady R.L., Anstee D.J.
Blood 112:2081-2088(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS BLOOD GROUP-IN(LU) TYR-299; LEU-328; HIS-328 AND GLY-331.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U37106 Genomic DNA. Translation: AAC50562.1.
U65404 mRNA. Translation: AAC51108.1.
AD000092 Genomic DNA. Translation: AAB51173.1.
BC033580 mRNA. Translation: AAH33580.1.
CCDSCCDS12285.1.
PIRT45072.
RefSeqNP_006554.1. NM_006563.3.
UniGeneHs.37860.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2L2INMR-B51-90[»]
2MBHNMR-B2-40[»]
ProteinModelPortalQ13351.
SMRQ13351. Positions 59-85, 279-362.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115904. 18 interactions.
DIPDIP-43776N.
IntActQ13351. 1 interaction.
MINTMINT-1891495.
STRING9606.ENSP00000264834.

PTM databases

PhosphoSiteQ13351.

Polymorphism databases

DMDM2501699.

Proteomic databases

PaxDbQ13351.
PRIDEQ13351.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264834; ENSP00000264834; ENSG00000105610.
GeneID10661.
KEGGhsa:10661.
UCSCuc002mvo.3. human.

Organism-specific databases

CTD10661.
GeneCardsGC19M012995.
HGNCHGNC:6345. KLF1.
HPAHPA051850.
MIM111150. phenotype.
600599. gene.
613566. phenotype.
613673. phenotype.
neXtProtNX_Q13351.
Orphanet293825. Congenital dyserythropoietic anemia type IV.
46532. Hereditary persistence of fetal hemoglobin - beta-thalassemia.
251380. Hereditary persistence of fetal hemoglobin - sickle cell disease.
PharmGKBPA30131.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5048.
HOGENOMHOG000060173.
HOVERGENHBG006220.
InParanoidQ13351.
KOK09204.
OMAGGAPQTC.
OrthoDBEOG747PJ4.
PhylomeDBQ13351.
TreeFamTF350556.

Gene expression databases

ArrayExpressQ13351.
BgeeQ13351.
CleanExHS_KLF1.
GenevestigatorQ13351.

Family and domain databases

Gene3D3.30.160.60. 3 hits.
InterProIPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
SMARTSM00355. ZnF_C2H2. 3 hits.
[Graphical view]
PROSITEPS00028. ZINC_FINGER_C2H2_1. 3 hits.
PS50157. ZINC_FINGER_C2H2_2. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ13351.
GenomeRNAi10661.
NextBio40543.
PROQ13351.
SOURCESearch...

Entry information

Entry nameKLF1_HUMAN
AccessionPrimary (citable) accession number: Q13351
Secondary accession number(s): Q6PIJ5, Q92899
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM