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Q13351

- KLF1_HUMAN

UniProt

Q13351 - KLF1_HUMAN

Protein

Krueppel-like factor 1

Gene

KLF1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 123 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    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

    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

    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

    ArrayExpressiQ13351.
    BgeeiQ13351.
    CleanExiHS_KLF1.
    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.
    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

    MATAETALPS ISTLTALGPF PDTQDDFLKW WRSEEAQDMG PGPPDPTEPP    50
    LHVKSEDQPG EEEDDERGAD ATWDLDLLLT NFSGPEPGGA PQTCALAPSE 100
    ASGAQYPPPP ETLGAYAGGP GLVAGLLGSE DHSGWVRPAL RARAPDAFVG 150
    PALAPAPAPE PKALALQPVY PGPGAGSSGG YFPRTGLSVP AASGAPYGLL 200
    SGYPAMYPAP QYQGHFQLFR GLQGPAPGPA TSPSFLSCLG PGTVGTGLGG 250
    TAEDPGVIAE TAPSKRGRRS WARKRQAAHT CAHPGCGKSY TKSSHLKAHL 300
    RTHTGEKPYA CTWEGCGWRF ARSDELTRHY RKHTGQRPFR CQLCPRAFSR 350
    SDHLALHMKR HL 362
    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.
    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

    ArrayExpressi Q13351.
    Bgeei Q13351.
    CleanExi HS_KLF1.
    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

    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 1, 2014
    This is version 123 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