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Protein

Krueppel-like factor 1

Gene

KLF1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 similarity1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri279 – 303C2H2-type 1PROSITE-ProRule annotationAdd BLAST25
Zinc fingeri309 – 333C2H2-type 2PROSITE-ProRule annotationAdd BLAST25
Zinc fingeri339 – 361C2H2-type 3PROSITE-ProRule annotationAdd BLAST23

GO - Molecular functioni

  • DNA binding transcription factor activity Source: ProtInc
  • metal ion binding Source: UniProtKB-KW
  • proximal promoter sequence-specific DNA binding Source: BHF-UCL
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: NTNU_SB
  • transcription regulatory region DNA binding Source: UniProtKB

GO - Biological processi

  • cellular response to peptide Source: Ensembl
  • erythrocyte differentiation Source: UniProtKB
  • maternal process involved in female pregnancy Source: Ensembl
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionActivator, DNA-binding
Biological processTranscription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

SIGNORiQ13351

Names & Taxonomyi

Protein namesi
Recommended name:
Krueppel-like factor 1
Alternative name(s):
Erythroid krueppel-like transcription factor
Short name:
EKLF
Gene namesi
Name:KLF1
Synonyms:EKLF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000105610.4
HGNCiHGNC:6345 KLF1
MIMi600599 gene
neXtProtiNX_Q13351

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Anemia, congenital dyserythropoietic, 4 (CDAN4)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:613673
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_064901325E → K in CDAN4; has a dominant-negative effect on the transcriptional activation of CD44 and AQP1 promoters. 1 PublicationCorresponds to variant dbSNP:rs267607201EnsemblClinVar.1

Keywords - Diseasei

Congenital dyserythropoietic anemia, Disease mutation, Hereditary hemolytic anemia

Organism-specific databases

DisGeNETi10661
MalaCardsiKLF1
MIMi111150 phenotype
613566 phenotype
613673 phenotype
OpenTargetsiENSG00000105610
Orphaneti293825 Congenital dyserythropoietic anemia type IV
46532 Hereditary persistence of fetal hemoglobin - beta-thalassemia
251380 Hereditary persistence of fetal hemoglobin - sickle cell disease
PharmGKBiPA30131

Chemistry databases

ChEMBLiCHEMBL3407313

Polymorphism and mutation databases

BioMutaiKLF1
DMDMi2501699

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000471601 – 362Krueppel-like factor 1Add BLAST362

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei23Phosphothreonine; by CK2By similarityCurated1
Cross-linki54Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei184Omega-N-methylarginineBy similarity1
Modified residuei274N6-acetyllysineBy similarity1
Modified residuei288N6-acetyllysineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ13351
PaxDbiQ13351
PeptideAtlasiQ13351
PRIDEiQ13351
ProteomicsDBi59335

PTM databases

iPTMnetiQ13351
PhosphoSitePlusiQ13351

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000105610
CleanExiHS_KLF1
GenevisibleiQ13351 HS

Organism-specific databases

HPAiHPA051850

Interactioni

Subunit structurei

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.By similarity2 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi115904, 17 interactors
DIPiDIP-43776N
IntActiQ13351, 23 interactors
MINTiQ13351
STRINGi9606.ENSP00000264834

Structurei

Secondary structure

1362
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi24 – 35Combined sources12
Beta strandi64 – 67Combined sources4
Beta strandi70 – 75Combined sources6

3D structure databases

ProteinModelPortaliQ13351
SMRiQ13351
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13351

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1 – 263Pro-richAdd BLAST263
Compositional biasi61 – 76Asp/Glu-rich (acidic)Add BLAST16

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri279 – 303C2H2-type 1PROSITE-ProRule annotationAdd BLAST25
Zinc fingeri309 – 333C2H2-type 2PROSITE-ProRule annotationAdd BLAST25
Zinc fingeri339 – 361C2H2-type 3PROSITE-ProRule annotationAdd BLAST23

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1721 Eukaryota
COG5048 LUCA
GeneTreeiENSGT00760000118998
HOGENOMiHOG000060173
HOVERGENiHBG006220
InParanoidiQ13351
KOiK09204
OMAiQYQGHFQ
OrthoDBiEOG091G1BN0
PhylomeDBiQ13351
TreeFamiTF350556

Family and domain databases

InterProiView protein in InterPro
IPR031786 EKLF_TAD1
IPR031784 EKLF_TAD2
IPR036236 Znf_C2H2_sf
IPR013087 Znf_C2H2_type
PfamiView protein in Pfam
PF16832 EKLF_TAD1, 1 hit
PF16833 EKLF_TAD2, 1 hit
SMARTiView protein in SMART
SM00355 ZnF_C2H2, 3 hits
SUPFAMiSSF57667 SSF57667, 2 hits
PROSITEiView protein in PROSITE
PS00028 ZINC_FINGER_C2H2_1, 3 hits
PS50157 ZINC_FINGER_C2H2_2, 3 hits

Sequencei

Sequence statusi: Complete.

Q13351-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATAETALPS ISTLTALGPF PDTQDDFLKW WRSEEAQDMG PGPPDPTEPP
60 70 80 90 100
LHVKSEDQPG EEEDDERGAD ATWDLDLLLT NFSGPEPGGA PQTCALAPSE
110 120 130 140 150
ASGAQYPPPP ETLGAYAGGP GLVAGLLGSE DHSGWVRPAL RARAPDAFVG
160 170 180 190 200
PALAPAPAPE PKALALQPVY PGPGAGSSGG YFPRTGLSVP AASGAPYGLL
210 220 230 240 250
SGYPAMYPAP QYQGHFQLFR GLQGPAPGPA TSPSFLSCLG PGTVGTGLGG
260 270 280 290 300
TAEDPGVIAE TAPSKRGRRS WARKRQAAHT CAHPGCGKSY TKSSHLKAHL
310 320 330 340 350
RTHTGEKPYA CTWEGCGWRF ARSDELTRHY RKHTGQRPFR CQLCPRAFSR
360
SDHLALHMKR HL
Length:362
Mass (Da):38,221
Last modified:November 1, 1996 - v1
Checksum:i6E9A48A2B6A37C76
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti163A → G in AAC51108 (PubMed:9119377).Curated1
Sequence conflicti173P → A in AAC51108 (PubMed:9119377).Curated1
Sequence conflicti184R → G in AAC51108 (PubMed:9119377).Curated1
Sequence conflicti192A → E in AAC51108 (PubMed:9119377).Curated1

Polymorphismi

Genetic variations in KLF1 underlie the fetal hemoglobin quantitative trait locus 6 (HBFQTL6) [MIMi: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.1 Publication
Genetic variations in KLF1 underlie the blood group-Lutheran inhibitor (In(Lu)) phenotype [MIMi: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-).1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0742725E → K1 PublicationCorresponds to variant dbSNP:rs483352842EnsemblClinVar.1
Natural variantiVAR_043981102S → P2 PublicationsCorresponds to variant dbSNP:rs2072597EnsemblClinVar.1
Natural variantiVAR_043982182F → L. Corresponds to variant dbSNP:rs2072596EnsemblClinVar.1
Natural variantiVAR_072737298A → P Found in a patient with autosomal recessive microcytic hypochromic anemia and increased fetal hemoglobin; compound heterozygous with a frameshift mutation of the same gene; unknown pathological significance; no effect on protein abundance; no effect on protein localization; decreased transcriptional activity. 2 PublicationsCorresponds to variant dbSNP:rs387907598EnsemblClinVar.1
Natural variantiVAR_074273299H → D1 PublicationCorresponds to variant dbSNP:rs137852688EnsemblClinVar.1
Natural variantiVAR_058108299H → Y in blood group-In(Lu). 1 PublicationCorresponds to variant dbSNP:rs137852688EnsemblClinVar.1
Natural variantiVAR_074274316C → W1 Publication1
Natural variantiVAR_064901325E → K in CDAN4; has a dominant-negative effect on the transcriptional activation of CD44 and AQP1 promoters. 1 PublicationCorresponds to variant dbSNP:rs267607201EnsemblClinVar.1
Natural variantiVAR_058109328R → H in blood group-In(Lu). 1 PublicationCorresponds to variant dbSNP:rs140252918Ensembl.1
Natural variantiVAR_058110328R → L in blood group-In(Lu). 1 Publication1
Natural variantiVAR_058111331R → G in blood group-In(Lu). 1 Publication1
Natural variantiVAR_074275334T → R1 PublicationCorresponds to variant dbSNP:rs483352841EnsemblClinVar.1
Natural variantiVAR_072738338P → S Found in a patient with autosomal recessive microcytic hypochromic anemia and increased fetal hemoglobin; with microcytic hypochromic anemia; compound heterozygous with a frameshift mutation of the same gene; no effect on protein abundance; no effect on protein localization; decreased transcriptional activity. 1 PublicationCorresponds to variant dbSNP:rs387907599EnsemblClinVar.1
Natural variantiVAR_074276341C → Y1 PublicationCorresponds to variant dbSNP:rs483352839EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U37106 Genomic DNA Translation: AAC50562.1
U65404 mRNA Translation: AAC51108.1
AD000092 Genomic DNA Translation: AAB51173.1
BC033580 mRNA Translation: AAH33580.1
CCDSiCCDS12285.1
PIRiT45072
RefSeqiNP_006554.1, NM_006563.4
UniGeneiHs.37860

Genome annotation databases

EnsembliENST00000264834; ENSP00000264834; ENSG00000105610
GeneIDi10661
KEGGihsa:10661
UCSCiuc002mvo.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiKLF1_HUMAN
AccessioniPrimary (citable) accession number: Q13351
Secondary accession number(s): Q6PIJ5, Q92899
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: July 18, 2018
This is version 157 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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