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Q13351

- KLF1_HUMAN

UniProt

Q13351 - KLF1_HUMAN

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Protein

Krueppel-like factor 1

Gene

KLF1

Organism
Homo sapiens (Human)
Status
Reviewed - 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 similarity.By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri279 – 30325C2H2-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri309 – 33325C2H2-type 2PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri339 – 36123C2H2-type 3PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. core promoter proximal region sequence-specific DNA binding Source: BHF-UCL
  2. metal ion binding Source: UniProtKB-KW
  3. sequence-specific DNA binding transcription factor activity Source: ProtInc
  4. transcription regulatory region DNA binding Source: UniProtKB

GO - Biological processi

  1. cellular response to peptide Source: Ensembl
  2. chromatin remodeling Source: Ensembl
  3. embryonic hemopoiesis Source: Ensembl
  4. erythrocyte differentiation Source: UniProtKB
  5. erythrocyte maturation Source: Ensembl
  6. in utero embryonic development Source: Ensembl
  7. liver development Source: Ensembl
  8. positive regulation of transcription, DNA-templated Source: UniProtKB
  9. 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

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
ProteomesiUP000005640: Chromosome 19

Organism-specific databases

HGNCiHGNC:6345. KLF1.

Subcellular locationi

Nucleus 1 Publication
Note: Colocalizes with SUMO1 in nuclear speckles.By similarity

GO - Cellular componenti

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

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti325 – 3251E → K in CDAN4; has a dominant-negative effect on the transcriptional activation of CD44 and AQP1 promoters. 1 Publication
VAR_064901

Keywords - Diseasei

Congenital dyserythropoietic anemia, Disease mutation, Hereditary hemolytic anemia

Organism-specific databases

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 362362Krueppel-like factor 1PRO_0000047160Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei23 – 231Phosphothreonine; by CK2Curated
Cross-linki54 – 54Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei274 – 2741N6-acetyllysineBy similarity
Modified residuei288 – 2881N6-acetyllysineBy similarity

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, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ13351.
PRIDEiQ13351.

PTM databases

PhosphoSiteiQ13351.

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

BgeeiQ13351.
CleanExiHS_KLF1.
ExpressionAtlasiQ13351. baseline and differential.
GenevestigatoriQ13351.

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. 18 interactions.
DIPiDIP-43776N.
IntActiQ13351. 1 interaction.
MINTiMINT-1891495.
STRINGi9606.ENSP00000264834.

Structurei

Secondary structure

1
362
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi24 – 3512
Beta strandi64 – 674
Beta strandi70 – 756

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2L2INMR-B51-90[»]
2MBHNMR-B2-40[»]
ProteinModelPortaliQ13351.
SMRiQ13351. Positions 59-85, 279-362.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13351.

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi1 – 263263Pro-richAdd
BLAST
Compositional biasi61 – 7616Asp/Glu-rich (acidic)Add
BLAST

Sequence similaritiesi

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

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri279 – 30325C2H2-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri309 – 33325C2H2-type 2PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri339 – 36123C2H2-type 3PROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiCOG5048.
GeneTreeiENSGT00760000118998.
HOGENOMiHOG000060173.
HOVERGENiHBG006220.
InParanoidiQ13351.
KOiK09204.
OMAiGGAPQTC.
OrthoDBiEOG747PJ4.
PhylomeDBiQ13351.
TreeFamiTF350556.

Family and domain databases

Gene3Di3.30.160.60. 3 hits.
InterProiIPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti163 – 1631A → G in AAC51108. (PubMed:9119377)Curated
Sequence conflicti173 – 1731P → A in AAC51108. (PubMed:9119377)Curated
Sequence conflicti184 – 1841R → G in AAC51108. (PubMed:9119377)Curated
Sequence conflicti192 – 1921A → E in AAC51108. (PubMed:9119377)Curated

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.
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-).

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti102 – 1021S → P.2 Publications
Corresponds to variant rs2072597 [ dbSNP | Ensembl ].
VAR_043981
Natural varianti182 – 1821F → L.
Corresponds to variant rs2072596 [ dbSNP | Ensembl ].
VAR_043982
Natural varianti299 – 2991H → Y in blood group-In(Lu). 1 Publication
VAR_058108
Natural varianti325 – 3251E → K in CDAN4; has a dominant-negative effect on the transcriptional activation of CD44 and AQP1 promoters. 1 Publication
VAR_064901
Natural varianti328 – 3281R → H in blood group-In(Lu). 1 Publication
VAR_058109
Natural varianti328 – 3281R → L in blood group-In(Lu). 1 Publication
VAR_058110
Natural varianti331 – 3311R → G in blood group-In(Lu). 1 Publication
VAR_058111

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_006563.3.
UniGeneiHs.37860.

Genome annotation databases

EnsembliENST00000264834; ENSP00000264834; ENSG00000105610.
GeneIDi10661.
KEGGihsa:10661.
UCSCiuc002mvo.3. human.

Polymorphism databases

DMDMi2501699.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U37106 Genomic DNA. Translation: AAC50562.1 .
U65404 mRNA. Translation: AAC51108.1 .
AD000092 Genomic DNA. Translation: AAB51173.1 .
BC033580 mRNA. Translation: AAH33580.1 .
CCDSi CCDS12285.1.
PIRi T45072.
RefSeqi NP_006554.1. NM_006563.3.
UniGenei Hs.37860.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2L2I NMR - B 51-90 [» ]
2MBH NMR - B 2-40 [» ]
ProteinModelPortali Q13351.
SMRi Q13351. Positions 59-85, 279-362.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 115904. 18 interactions.
DIPi DIP-43776N.
IntActi Q13351. 1 interaction.
MINTi MINT-1891495.
STRINGi 9606.ENSP00000264834.

PTM databases

PhosphoSitei Q13351.

Polymorphism databases

DMDMi 2501699.

Proteomic databases

PaxDbi Q13351.
PRIDEi Q13351.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000264834 ; ENSP00000264834 ; ENSG00000105610 .
GeneIDi 10661.
KEGGi hsa:10661.
UCSCi uc002mvo.3. human.

Organism-specific databases

CTDi 10661.
GeneCardsi GC19M012995.
HGNCi HGNC:6345. KLF1.
HPAi HPA051850.
MIMi 111150. phenotype.
600599. gene.
613566. phenotype.
613673. phenotype.
neXtProti NX_Q13351.
Orphaneti 293825. Congenital dyserythropoietic anemia type IV.
46532. Hereditary persistence of fetal hemoglobin - beta-thalassemia.
251380. Hereditary persistence of fetal hemoglobin - sickle cell disease.
PharmGKBi PA30131.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG5048.
GeneTreei ENSGT00760000118998.
HOGENOMi HOG000060173.
HOVERGENi HBG006220.
InParanoidi Q13351.
KOi K09204.
OMAi GGAPQTC.
OrthoDBi EOG747PJ4.
PhylomeDBi Q13351.
TreeFami TF350556.

Miscellaneous databases

EvolutionaryTracei Q13351.
GenomeRNAii 10661.
NextBioi 40543.
PROi Q13351.
SOURCEi Search...

Gene expression databases

Bgeei Q13351.
CleanExi HS_KLF1.
ExpressionAtlasi Q13351. baseline and differential.
Genevestigatori Q13351.

Family and domain databases

Gene3Di 3.30.160.60. 3 hits.
InterProi IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view ]
SMARTi SM00355. ZnF_C2H2. 3 hits.
[Graphical view ]
PROSITEi PS00028. ZINC_FINGER_C2H2_1. 3 hits.
PS50157. ZINC_FINGER_C2H2_2. 3 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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. 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.

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: October 29, 2014
This is version 124 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

External Data

Dasty 3