KLF3_HUMAN
ID KLF3_HUMAN Reviewed; 345 AA.
AC P57682; Q6PIR1; Q86TN0; Q9P2X6;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 1.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Krueppel-like factor 3;
DE AltName: Full=Basic krueppel-like factor;
DE AltName: Full=CACCC-box-binding protein BKLF;
DE AltName: Full=TEF-2;
GN Name=KLF3; Synonyms=BKLF;
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 [MRNA] (ISOFORM 1).
RA Matsumoto N., Yoshida T., Terada M.;
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=12812068;
RA Wang M.J., Qu X.H., Wang L.S., Zhai Y., Wu S.L., He F.C.;
RT "cDNA cloning, subcellular localization and tissue expression of a new
RT human Kruppel-like transcription factor: human basic Kruppel-like factor
RT (hBKLF).";
RL Yi Chuan Xue Bao 30:1-9(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Hippocampus;
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-250, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-92 AND SER-101, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-92 AND SER-111, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-71; SER-92; SER-101 AND
RP SER-250, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [9]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-198, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [10]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-68; LYS-196 AND LYS-198, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [11]
RP INACTIVATION OF 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: Binds to the CACCC box of erythroid cell-expressed genes. May
CC play a role in hematopoiesis (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- INTERACTION:
CC P57682; Q86V38: ATN1; NbExp=3; IntAct=EBI-8472267, EBI-11954292;
CC P57682; P54253: ATXN1; NbExp=4; IntAct=EBI-8472267, EBI-930964;
CC P57682; Q9Y5Z0: BACE2; NbExp=3; IntAct=EBI-8472267, EBI-11282723;
CC P57682; P46379-2: BAG6; NbExp=3; IntAct=EBI-8472267, EBI-10988864;
CC P57682; P02489: CRYAA; NbExp=3; IntAct=EBI-8472267, EBI-6875961;
CC P57682; Q13363-2: CTBP1; NbExp=3; IntAct=EBI-8472267, EBI-10171858;
CC P57682; P56545-3: CTBP2; NbExp=3; IntAct=EBI-8472267, EBI-10171902;
CC P57682; Q9NX09: DDIT4; NbExp=3; IntAct=EBI-8472267, EBI-715104;
CC P57682; Q92997: DVL3; NbExp=3; IntAct=EBI-8472267, EBI-739789;
CC P57682; A2ABF9: EHMT2; NbExp=3; IntAct=EBI-8472267, EBI-10174566;
CC P57682; Q96KQ7: EHMT2; NbExp=4; IntAct=EBI-8472267, EBI-744366;
CC P57682; P22607: FGFR3; NbExp=3; IntAct=EBI-8472267, EBI-348399;
CC P57682; Q13643: FHL3; NbExp=11; IntAct=EBI-8472267, EBI-741101;
CC P57682; O14908-2: GIPC1; NbExp=3; IntAct=EBI-8472267, EBI-25913156;
CC P57682; P28799: GRN; NbExp=4; IntAct=EBI-8472267, EBI-747754;
CC P57682; P01112: HRAS; NbExp=3; IntAct=EBI-8472267, EBI-350145;
CC P57682; P04792: HSPB1; NbExp=3; IntAct=EBI-8472267, EBI-352682;
CC P57682; O43464: HTRA2; NbExp=3; IntAct=EBI-8472267, EBI-517086;
CC P57682; P42858: HTT; NbExp=6; IntAct=EBI-8472267, EBI-466029;
CC P57682; Q9Y2W7: KCNIP3; NbExp=3; IntAct=EBI-8472267, EBI-751501;
CC P57682; O60333-2: KIF1B; NbExp=3; IntAct=EBI-8472267, EBI-10975473;
CC P57682; O14901: KLF11; NbExp=3; IntAct=EBI-8472267, EBI-948266;
CC P57682; Q92876: KLK6; NbExp=3; IntAct=EBI-8472267, EBI-2432309;
CC P57682; Q9UPM6: LHX6; NbExp=3; IntAct=EBI-8472267, EBI-10258746;
CC P57682; Q68G74: LHX8; NbExp=3; IntAct=EBI-8472267, EBI-8474075;
CC P57682; Q5T3J3: LRIF1; NbExp=3; IntAct=EBI-8472267, EBI-473196;
CC P57682; Q9BVL2: NUP58; NbExp=3; IntAct=EBI-8472267, EBI-2811583;
CC P57682; P32243-2: OTX2; NbExp=3; IntAct=EBI-8472267, EBI-9087860;
CC P57682; O43933: PEX1; NbExp=3; IntAct=EBI-8472267, EBI-988601;
CC P57682; P60891: PRPS1; NbExp=3; IntAct=EBI-8472267, EBI-749195;
CC P57682; Q12933: TRAF2; NbExp=6; IntAct=EBI-8472267, EBI-355744;
CC P57682; O76024: WFS1; NbExp=3; IntAct=EBI-8472267, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P57682-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P57682-2; Sequence=VSP_014532;
CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large
CC number of yeast and animal transcription factors. In KLF3, the motif is
CC inactive. {ECO:0000269|PubMed:31375868}.
CC -!- PTM: Sumoylated with SUMO1. Sumoylation is enhanced by PIAS1,
CC PIAS2alpha and PIAS2beta, and PIAS4, but not by Pc2. Enhances
CC transcriptional repression, but has no effect on DNA binding.
CC Sumoylation on Lys-198 is the major site (By similarity).
CC {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be due to intron retention.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein
CC family. {ECO:0000305}.
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DR EMBL; AB024523; BAA92271.1; -; mRNA.
DR EMBL; AF285837; AAK27329.1; -; mRNA.
DR EMBL; BC030662; AAH30662.1; -; mRNA.
DR EMBL; BC051687; AAH51687.1; -; mRNA.
DR CCDS; CCDS3444.1; -. [P57682-1]
DR RefSeq; NP_057615.3; NM_016531.5. [P57682-1]
DR AlphaFoldDB; P57682; -.
DR SMR; P57682; -.
DR BioGRID; 119426; 159.
DR IntAct; P57682; 175.
DR MINT; P57682; -.
DR STRING; 9606.ENSP00000261438; -.
DR GlyGen; P57682; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P57682; -.
DR PhosphoSitePlus; P57682; -.
DR BioMuta; KLF3; -.
DR DMDM; 12644533; -.
DR EPD; P57682; -.
DR jPOST; P57682; -.
DR MassIVE; P57682; -.
DR MaxQB; P57682; -.
DR PaxDb; P57682; -.
DR PeptideAtlas; P57682; -.
DR PRIDE; P57682; -.
DR ProteomicsDB; 57007; -. [P57682-1]
DR ProteomicsDB; 57008; -. [P57682-2]
DR Antibodypedia; 10444; 185 antibodies from 29 providers.
DR DNASU; 51274; -.
DR Ensembl; ENST00000261438.10; ENSP00000261438.5; ENSG00000109787.13. [P57682-1]
DR Ensembl; ENST00000514033.1; ENSP00000421252.1; ENSG00000109787.13. [P57682-2]
DR GeneID; 51274; -.
DR KEGG; hsa:51274; -.
DR MANE-Select; ENST00000261438.10; ENSP00000261438.5; NM_016531.6; NP_057615.3.
DR UCSC; uc003gtg.3; human. [P57682-1]
DR CTD; 51274; -.
DR DisGeNET; 51274; -.
DR GeneCards; KLF3; -.
DR HGNC; HGNC:16516; KLF3.
DR HPA; ENSG00000109787; Low tissue specificity.
DR MIM; 609392; gene.
DR neXtProt; NX_P57682; -.
DR OpenTargets; ENSG00000109787; -.
DR PharmGKB; PA30137; -.
DR VEuPathDB; HostDB:ENSG00000109787; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000157456; -.
DR HOGENOM; CLU_002678_33_0_1; -.
DR InParanoid; P57682; -.
DR OMA; QEAMEPV; -.
DR PhylomeDB; P57682; -.
DR TreeFam; TF350556; -.
DR PathwayCommons; P57682; -.
DR SignaLink; P57682; -.
DR SIGNOR; P57682; -.
DR BioGRID-ORCS; 51274; 26 hits in 1097 CRISPR screens.
DR ChiTaRS; KLF3; human.
DR GeneWiki; KLF3; -.
DR GenomeRNAi; 51274; -.
DR Pharos; P57682; Tbio.
DR PRO; PR:P57682; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P57682; protein.
DR Bgee; ENSG00000109787; Expressed in upper leg skin and 195 other tissues.
DR Genevisible; P57682; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; NAS:ProtInc.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
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:1901653; P:cellular response to peptide; IEA:Ensembl.
DR GO; GO:0030097; P:hemopoiesis; TAS:ProtInc.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
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; Alternative splicing; DNA-binding; Isopeptide bond;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Repressor; Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..345
FT /note="Krueppel-like factor 3"
FT /id="PRO_0000047165"
FT ZN_FING 260..284
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 290..314
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 320..342
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 1..74
FT /note="Repressor domain"
FT REGION 66..112
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 60..68
FT /note="9aaTAD; inactive"
FT /evidence="ECO:0000269|PubMed:31375868"
FT MOTIF 61..65
FT /note="CTBP-binding motif"
FT COMPBIAS 66..102
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 71
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 92
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 101
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 108
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60980"
FT MOD_RES 111
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 216
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60980"
FT MOD_RES 224
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60980"
FT MOD_RES 250
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:23186163"
FT CROSSLNK 10
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 68
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 196
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 198
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:28112733"
FT VAR_SEQ 233..345
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_014532"
FT VARIANT 207
FT /note="R -> S (in dbSNP:rs17616226)"
FT /id="VAR_052715"
FT CONFLICT 85
FT /note="P -> R (in Ref. 3; AAH51687)"
FT /evidence="ECO:0000305"
FT CONFLICT 116
FT /note="P -> H (in Ref. 3; AAH51687)"
FT /evidence="ECO:0000305"
FT CONFLICT 305
FT /note="D -> G (in Ref. 3; AAH30662)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 345 AA; 38829 MW; A490D642AB8F1FDC CRC64;
MLMFDPVPVK QEAMDPVSVS YPSNYMESMK PNKYGVIYST PLPEKFFQTP EGLSHGIQME
PVDLTVNKRS SPPSAGNSPS SLKFPSSHRR ASPGLSMPSS SPPIKKYSPP SPGVQPFGVP
LSMPPVMAAA LSRHGIRSPG ILPVIQPVVV QPVPFMYTSH LQQPLMVSLS EEMENSSSSM
QVPVIESYEK PISQKKIKIE PGIEPQRTDY YPEEMSPPLM NSVSPPQALL QENHPSVIVQ
PGKRPLPVES PDTQRKRRIH RCDYDGCNKV YTKSSHLKAH RRTHTGEKPY KCTWEGCTWK
FARSDELTRH FRKHTGIKPF QCPDCDRSFS RSDHLALHRK RHMLV
