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   27-MAR-2024, entry version 187.
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   GlyGen; Q9Y5W3; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9Y5W3; -.
DR   PhosphoSitePlus; Q9Y5W3; -.
DR   BioMuta; KLF2; -.
DR   DMDM; 20141620; -.
DR   jPOST; Q9Y5W3; -.
DR   MassIVE; Q9Y5W3; -.
DR   MaxQB; Q9Y5W3; -.
DR   PaxDb; 9606-ENSP00000248071; -.
DR   PeptideAtlas; Q9Y5W3; -.
DR   ProteomicsDB; 86516; -.
DR   Antibodypedia; 27348; 563 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   AGR; HGNC:6347; -.
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; DCHTQMM; -.
DR   OrthoDB; 5484790at2759; -.
DR   PhylomeDB; Q9Y5W3; -.
DR   TreeFam; TF350556; -.
DR   PathwayCommons; Q9Y5W3; -.
DR   SignaLink; Q9Y5W3; -.
DR   SIGNOR; Q9Y5W3; -.
DR   BioGRID-ORCS; 10365; 27 hits in 1175 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 202 other cell types or tissues.
DR   ExpressionAtlas; Q9Y5W3; baseline and differential.
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:0040029; P:epigenetic regulation of gene expression; IEA:Ensembl.
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:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB.
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: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   Gene3D; 3.30.160.60; Classic Zinc Finger; 3.
DR   InterPro; IPR036236; Znf_C2H2_sf.
DR   InterPro; IPR013087; Znf_C2H2_type.
DR   PANTHER; PTHR23235:SF109; KRUEPPEL-LIKE FACTOR 2; 1.
DR   PANTHER; PTHR23235; KRUEPPEL-LIKE TRANSCRIPTION FACTOR; 1.
DR   Pfam; PF00096; zf-C2H2; 3.
DR   SMART; SM00355; ZnF_C2H2; 3.
DR   SUPFAM; SSF57667; beta-beta-alpha zinc fingers; 2.
DR   PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3.
DR   PROSITE; PS50157; ZINC_FINGER_C2H2_2; 3.
DR   Genevisible; Q9Y5W3; HS.
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
//