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Protein

Krueppel-like factor 1

Gene

KLF1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • core promoter proximal region sequence-specific DNA binding Source: BHF-UCL
  • metal ion binding Source: UniProtKB-KW
  • transcription factor activity, sequence-specific DNA binding Source: ProtInc
  • 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
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000105610-MONOMER.
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

HGNCiHGNC:6345. KLF1.

Subcellular locationi

GO - Cellular componenti

  • nuclear chromatin Source: BHF-UCL
  • nucleus Source: UniProtKB
Complete GO annotation...

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 rs267607201dbSNPEnsembl.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 CK2Curated1
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.

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

Protein-protein interaction databases

BioGridi115904. 17 interactors.
DIPiDIP-43776N.
IntActiQ13351. 1 interactor.
MINTiMINT-1891495.
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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2L2INMR-B51-90[»]
2MBHNMR-B2-40[»]
2N23NMR-B22-40[»]
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

Contains 3 C2H2-type zinc fingers.PROSITE-ProRule annotation

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.
OMAiGGAPQTC.
OrthoDBiEOG091G1BN0.
PhylomeDBiQ13351.
TreeFamiTF350556.

Family and domain databases

Gene3Di3.30.160.60. 3 hits.
InterProiIPR031786. EKLF_TAD1.
IPR031784. EKLF_TAD2.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamiPF16832. EKLF_TAD1. 1 hit.
PF16833. EKLF_TAD2. 1 hit.
PF00096. zf-C2H2. 1 hit.
[Graphical view]
SMARTiSM00355. ZnF_C2H2. 3 hits.
[Graphical view]
PROSITEiPS00028. ZINC_FINGER_C2H2_1. 3 hits.
PS50157. ZINC_FINGER_C2H2_2. 3 hits.
[Graphical view]

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 → K.1 PublicationCorresponds to variant rs483352842dbSNPEnsembl.1
Natural variantiVAR_043981102S → P.2 PublicationsCorresponds to variant rs2072597dbSNPEnsembl.1
Natural variantiVAR_043982182F → L.Corresponds to variant rs2072596dbSNPEnsembl.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 rs387907598dbSNPEnsembl.1
Natural variantiVAR_074273299H → D.1 PublicationCorresponds to variant rs137852688dbSNPEnsembl.1
Natural variantiVAR_058108299H → Y in blood group-In(Lu). 1 PublicationCorresponds to variant rs137852688dbSNPEnsembl.1
Natural variantiVAR_074274316C → W.1 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 rs267607201dbSNPEnsembl.1
Natural variantiVAR_058109328R → H in blood group-In(Lu). 1 PublicationCorresponds to variant rs140252918dbSNPEnsembl.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 → R.1 PublicationCorresponds to variant rs483352841dbSNPEnsembl.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 rs387907599dbSNPEnsembl.1
Natural variantiVAR_074276341C → Y.1 PublicationCorresponds to variant rs483352839dbSNPEnsembl.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

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2L2INMR-B51-90[»]
2MBHNMR-B2-40[»]
2N23NMR-B22-40[»]
ProteinModelPortaliQ13351.
SMRiQ13351.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115904. 17 interactors.
DIPiDIP-43776N.
IntActiQ13351. 1 interactor.
MINTiMINT-1891495.
STRINGi9606.ENSP00000264834.

Chemistry databases

ChEMBLiCHEMBL3407313.

PTM databases

iPTMnetiQ13351.
PhosphoSitePlusiQ13351.

Polymorphism and mutation databases

BioMutaiKLF1.
DMDMi2501699.

Proteomic databases

MaxQBiQ13351.
PaxDbiQ13351.
PeptideAtlasiQ13351.
PRIDEiQ13351.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi10661.
DisGeNETi10661.
GeneCardsiKLF1.
HGNCiHGNC:6345. KLF1.
HPAiHPA051850.
MalaCardsiKLF1.
MIMi111150. phenotype.
600599. gene.
613566. phenotype.
613673. phenotype.
neXtProtiNX_Q13351.
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.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000105610-MONOMER.
SIGNORiQ13351.

Miscellaneous databases

EvolutionaryTraceiQ13351.
GenomeRNAii10661.
PROiQ13351.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105610.
CleanExiHS_KLF1.
GenevisibleiQ13351. HS.

Family and domain databases

Gene3Di3.30.160.60. 3 hits.
InterProiIPR031786. EKLF_TAD1.
IPR031784. EKLF_TAD2.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamiPF16832. EKLF_TAD1. 1 hit.
PF16833. EKLF_TAD2. 1 hit.
PF00096. zf-C2H2. 1 hit.
[Graphical view]
SMARTiSM00355. ZnF_C2H2. 3 hits.
[Graphical view]
PROSITEiPS00028. ZINC_FINGER_C2H2_1. 3 hits.
PS50157. ZINC_FINGER_C2H2_2. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKLF1_HUMAN
AccessioniPrimary (citable) accession number: Q13351
Secondary accession number(s): Q6PIJ5, Q92899
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: November 2, 2016
This is version 144 of the entry and version 1 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.