KLF2_HUMAN
ID KLF2_HUMAN Reviewed; 355 AA.
AC Q9Y5W3; Q6IPC4; Q9UJS5; Q9UKR6;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2002, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Krueppel-like factor 2;
DE AltName: Full=Lung krueppel-like factor;
GN Name=KLF2; Synonyms=LKLF;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT PRO-104.
RC TISSUE=Lung;
RX PubMed=10217429; DOI=10.1016/s0014-5793(99)00348-8;
RA Kozyrev S.V., Hansen L.L., Poltaraus A.B., Domninsky D.A., Kisselev L.L.;
RT "Structure of the human CpG-island-containing lung Kruppel-like factor
RT (LKLF) gene and its location in chromosome 19p13.11-13 locus.";
RL FEBS Lett. 448:149-152(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung;
RX PubMed=10458913; DOI=10.1006/geno.1999.5888;
RA Wani M.A., Conkright M.D., Jeffries S., Hughes M.J., Lingrel J.B.;
RT "cDNA isolation, genomic structure, regulation, and chromosomal
RT localization of human lung kruppel-like factor.";
RL Genomics 60:78-86(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hair follicle dermal papilla;
RA Lee H.J., Kim M.K., Kim Y.H., Seo J.M., Lee H.M., Chung H.J., Sohn M.Y.,
RA Hwang S.Y., Im S.U., Jung E.J., Kim J.C.;
RT "A catalogue of genes in the human dermal papilla cells as identified by
RT expressed sequence tags.";
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS PRO-104 AND PRO-145.
RG SeattleSNPs variation discovery resource;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-104.
RC TISSUE=Spleen;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INTERACTION WITH WWP1.
RX PubMed=11375995; DOI=10.1074/jbc.m103670200;
RA Conkright M.D., Wani M.A., Lingrel J.B.;
RT "Lung Krueppel-like factor contains an autoinhibitory domain that regulates
RT its transcriptional activation by binding WWP1, an E3 ubiquitin ligase.";
RL J. Biol. Chem. 276:29299-29306(2001).
RN [7]
RP FUNCTION.
RX PubMed=21063504; DOI=10.1007/s12079-010-0095-x;
RA Lin Z., Natesan V., Shi H., Hamik A., Kawanami D., Hao C.,
RA Mahabaleshwar G.H., Wang W., Jin Z.G., Atkins G.B., Firth S.M., Rittie L.,
RA Perbal B., Jain M.K.;
RT "A novel role of CCN3 in regulating endothelial inflammation.";
RL J. Cell Commun. Signal. 4:141-153(2010).
RN [8]
RP FUNCTION.
RX PubMed=28167758; DOI=10.1073/pnas.1621425114;
RA Lee D.Y., Lin T.E., Lee C.I., Zhou J., Huang Y.H., Lee P.L., Shih Y.T.,
RA Chien S., Chiu J.J.;
RT "MicroRNA-10a is crucial for endothelial response to different flow
RT patterns via interaction of retinoid acid receptors and histone
RT deacetylases.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:2072-2077(2017).
RN [9]
RP 9AATAD MOTIF.
RX PubMed=31375868; DOI=10.1007/s00018-019-03251-w;
RA Piskacek M., Havelka M., Jendruchova K., Knight A., Keegan L.P.;
RT "The evolution of the 9aaTAD domain in Sp2 proteins: inactivation with
RT valines and intron reservoirs.";
RL Cell. Mol. Life Sci. 77:1793-1810(2020).
CC -!- FUNCTION: Transcription factor that binds to the CACCC box in the
CC promoter of target genes such as HBB/beta globin or NOV and activates
CC their transcription (PubMed:21063504). Might be involved in
CC transcriptional regulation by modulating the binding of the RARA
CC nuclear receptor to RARE DNA elements (PubMed:28167758).
CC {ECO:0000269|PubMed:21063504, ECO:0000269|PubMed:28167758}.
CC -!- SUBUNIT: Interacts with WWP1. {ECO:0000269|PubMed:11375995}.
CC -!- INTERACTION:
CC Q9Y5W3; Q92831: KAT2B; NbExp=2; IntAct=EBI-9846663, EBI-477430;
CC Q9Y5W3; Q9HCE7: SMURF1; NbExp=2; IntAct=EBI-9846663, EBI-976466;
CC Q9Y5W3; Q9HCE7-2: SMURF1; NbExp=4; IntAct=EBI-9846663, EBI-9845742;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large
CC number of yeast and animal transcription factors.
CC {ECO:0000269|PubMed:31375868}.
CC -!- PTM: Ubiquitinated. Polyubiquitination involves WWP1 and leads to
CC proteasomal degradation of this protein (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein
CC family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/klf2/";
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DR EMBL; AF123344; AAD25076.1; -; Genomic_DNA.
DR EMBL; AF134053; AAD55891.1; -; mRNA.
DR EMBL; AF205849; AAF13295.1; -; mRNA.
DR EMBL; EF078888; ABK41959.1; -; Genomic_DNA.
DR EMBL; BC071983; AAH71983.1; -; mRNA.
DR CCDS; CCDS12343.1; -.
DR RefSeq; NP_057354.1; NM_016270.3.
DR AlphaFoldDB; Q9Y5W3; -.
DR SMR; Q9Y5W3; -.
DR BioGRID; 115645; 13.
DR DIP; DIP-41973N; -.
DR ELM; Q9Y5W3; -.
DR IntAct; Q9Y5W3; 2.
DR STRING; 9606.ENSP00000248071; -.
DR iPTMnet; Q9Y5W3; -.
DR PhosphoSitePlus; Q9Y5W3; -.
DR BioMuta; KLF2; -.
DR DMDM; 20141620; -.
DR jPOST; Q9Y5W3; -.
DR MassIVE; Q9Y5W3; -.
DR MaxQB; Q9Y5W3; -.
DR PaxDb; Q9Y5W3; -.
DR PeptideAtlas; Q9Y5W3; -.
DR PRIDE; Q9Y5W3; -.
DR ProteomicsDB; 86516; -.
DR Antibodypedia; 27348; 459 antibodies from 32 providers.
DR DNASU; 10365; -.
DR Ensembl; ENST00000248071.6; ENSP00000248071.5; ENSG00000127528.6.
DR GeneID; 10365; -.
DR KEGG; hsa:10365; -.
DR MANE-Select; ENST00000248071.6; ENSP00000248071.5; NM_016270.4; NP_057354.1.
DR UCSC; uc002ndw.4; human.
DR CTD; 10365; -.
DR DisGeNET; 10365; -.
DR GeneCards; KLF2; -.
DR HGNC; HGNC:6347; KLF2.
DR HPA; ENSG00000127528; Low tissue specificity.
DR MIM; 602016; gene.
DR neXtProt; NX_Q9Y5W3; -.
DR OpenTargets; ENSG00000127528; -.
DR PharmGKB; PA30136; -.
DR VEuPathDB; HostDB:ENSG00000127528; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000163163; -.
DR HOGENOM; CLU_002678_33_1_1; -.
DR InParanoid; Q9Y5W3; -.
DR OMA; LHERWKC; -.
DR OrthoDB; 1273088at2759; -.
DR PhylomeDB; Q9Y5W3; -.
DR TreeFam; TF350556; -.
DR PathwayCommons; Q9Y5W3; -.
DR SignaLink; Q9Y5W3; -.
DR SIGNOR; Q9Y5W3; -.
DR BioGRID-ORCS; 10365; 22 hits in 1096 CRISPR screens.
DR ChiTaRS; KLF2; human.
DR GeneWiki; KLF2; -.
DR GenomeRNAi; 10365; -.
DR Pharos; Q9Y5W3; Tbio.
DR PRO; PR:Q9Y5W3; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9Y5W3; protein.
DR Bgee; ENSG00000127528; Expressed in urethra and 200 other tissues.
DR ExpressionAtlas; Q9Y5W3; baseline and differential.
DR Genevisible; Q9Y5W3; HS.
DR GO; GO:0000785; C:chromatin; IMP:BHF-UCL.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IMP:BHF-UCL.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IMP:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0000902; P:cell morphogenesis; IEA:Ensembl.
DR GO; GO:0071409; P:cellular response to cycloheximide; IEA:Ensembl.
DR GO; GO:0071498; P:cellular response to fluid shear stress; IMP:BHF-UCL.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl.
DR GO; GO:0071347; P:cellular response to interleukin-1; IEA:Ensembl.
DR GO; GO:0071499; P:cellular response to laminar fluid shear stress; IMP:BHF-UCL.
DR GO; GO:1901653; P:cellular response to peptide; IEA:Ensembl.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
DR GO; GO:0097533; P:cellular stress response to acid chemical; IMP:BHF-UCL.
DR GO; GO:0043249; P:erythrocyte maturation; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IEA:Ensembl.
DR GO; GO:1903671; P:negative regulation of sprouting angiogenesis; IMP:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0051247; P:positive regulation of protein metabolic process; IGI:BHF-UCL.
DR GO; GO:0048386; P:positive regulation of retinoic acid receptor signaling pathway; IDA:CACAO.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0036003; P:positive regulation of transcription from RNA polymerase II promoter in response to stress; IMP:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0040029; P:regulation of gene expression, epigenetic; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0060509; P:type I pneumocyte differentiation; IEA:Ensembl.
DR GO; GO:0042311; P:vasodilation; IMP:BHF-UCL.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF00096; zf-C2H2; 3.
DR SMART; SM00355; ZnF_C2H2; 3.
DR SUPFAM; SSF57667; SSF57667; 2.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 3.
PE 1: Evidence at protein level;
KW Activator; DNA-binding; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Transcription; Transcription regulation;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..355
FT /note="Krueppel-like factor 2"
FT /id="PRO_0000047162"
FT ZN_FING 272..296
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 302..326
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 332..354
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 1..42
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 55..90
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 111..268
FT /note="Interaction with WWP1"
FT /evidence="ECO:0000250"
FT REGION 120..209
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 43..51
FT /note="9aaTAD"
FT /evidence="ECO:0000269|PubMed:31375868"
FT COMPBIAS 22..36
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 60..85
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 162..209
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 173
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q60843"
FT MOD_RES 244
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q60843"
FT VARIANT 104
FT /note="L -> P (in dbSNP:rs3745318)"
FT /evidence="ECO:0000269|PubMed:10217429,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.4"
FT /id="VAR_038830"
FT VARIANT 145
FT /note="R -> P (in dbSNP:rs45586032)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_038831"
FT CONFLICT 43
FT /note="S -> N (in Ref. 2; AAD55891)"
FT /evidence="ECO:0000305"
FT CONFLICT 175
FT /note="P -> S (in Ref. 2; AAD55891)"
FT /evidence="ECO:0000305"
FT CONFLICT 184
FT /note="L -> M (in Ref. 2; AAD55891)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 355 AA; 37420 MW; D5849C831D676AE1 CRC64;
MALSEPILPS FSTFASPCRE RGLQERWPRA EPESGGTDDD LNSVLDFILS MGLDGLGAEA
APEPPPPPPP PAFYYPEPGA PPPYSAPAGG LVSELLRPEL DAPLGPALHG RFLLAPPGRL
VKAEPPEADG GGGYGCAPGL TRGPRGLKRE GAPGPAASCM RGPGGRPPPP PDTPPLSPDG
PARLPAPGPR ASFPPPFGGP GFGAPGPGLH YAPPAPPAFG LFDDAAAAAA ALGLAPPAAR
GLLTPPASPL ELLEAKPKRG RRSWPRKRTA THTCSYAGCG KTYTKSSHLK AHLRTHTGEK
PYHCNWDGCG WKFARSDELT RHYRKHTGHR PFQCHLCDRA FSRSDHLALH MKRHM
