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Protein

Forkhead box protein K2

Gene

FOXK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcriptional regulator that recognizes the core sequence 5'-TAAACA-3'. Binds to NFAT-like motifs (purine-rich) in the IL2 promoter (PubMed:1339390). Positively regulates WNT/beta-catenin signaling by translocating DVL proteins into the nucleus (PubMed:25805136). Also binds to HIV-1 long terminal repeat. May be involved in both positive and negative regulation of important viral and cellular promoter elements (PubMed:1909027).3 Publications

Cofactori

Mg2+1 PublicationNote: Binds 1 Mg2+ ion per subunit.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi310Magnesium; via carbonyl oxygen1
Metal bindingi311Magnesium; via carbonyl oxygen1
Metal bindingi313Magnesium; via carbonyl oxygen1
Metal bindingi316Magnesium; via carbonyl oxygen1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi258 – 353Fork-headPROSITE-ProRule annotationAdd BLAST96

GO - Molecular functioni

  • magnesium ion binding Source: UniProtKB
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  • sequence-specific DNA binding Source: UniProtKB
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: NTNU_SB
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB

GO - Biological processi

  • anatomical structure morphogenesis Source: GO_Central
  • cell differentiation Source: GO_Central
  • positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  • protein deubiquitination Source: Reactome
  • regulation of transcription, DNA-templated Source: UniProtKB
  • regulation of transcription from RNA polymerase II promoter Source: ProtInc

Keywordsi

Molecular functionDNA-binding
Biological processTranscription, Transcription regulation
LigandMagnesium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-5689603. UCH proteinases.
SIGNORiQ01167.

Names & Taxonomyi

Protein namesi
Recommended name:
Forkhead box protein K2
Alternative name(s):
Cellular transcription factor ILF-1
FOXK1
Interleukin enhancer-binding factor 1
Gene namesi
Name:FOXK2
Synonyms:ILF, ILF1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000141568.19.
HGNCiHGNC:6036. FOXK2.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi129R → A: No effect on interaction with DVL2. 1 Publication1
Mutagenesisi130R → A: No effect on interaction with DVL2. 1 Publication1
Mutagenesisi131G → A: No effect on interaction with DVL2. 1 Publication1
Mutagenesisi133P → A: No effect on interaction with DVL2. 1 Publication1
Mutagenesisi136Q → A: No effect on interaction with DVL2. 1 Publication1
Mutagenesisi137L → A: Abolishes interaction with DVL2 and SUDS3 as well as DVL2 nuclear translocation. 1 Publication1
Mutagenesisi138P → A: No effect on interaction with DVL2. 1 Publication1
Mutagenesisi141C → A: No effect on interaction with DVL2. 1 Publication1
Mutagenesisi142T → A: No effect on interaction with DVL2. 1 Publication1
Mutagenesisi145F → A: Abolishes interaction with DVL2 and SUDS3 as well as DVL2 nuclear translocation. 1 Publication1
Mutagenesisi146P → A: Highly reduces interaction with DVL2. 1 Publication1
Mutagenesisi147S → A: No effect on interaction with DVL2. 1 Publication1
Mutagenesisi148T → A: No effect on interaction with DVL2. 1 Publication1
Mutagenesisi150I → A: No effect on interaction with DVL2. 1 Publication1
Mutagenesisi151K → A: No effect on interaction with DVL2. 1 Publication1
Mutagenesisi152I → A: No effect on interaction with DVL2. 1 Publication1
Mutagenesisi154F → A: Abolishes interaction with DVL2 and SUDS3 as well as DVL2 nuclear translocation. 1 Publication1
Mutagenesisi155T → A: No effect on interaction with DVL2. 1 Publication1
Mutagenesisi157L → A: No effect on interaction with DVL2. 1 Publication1
Mutagenesisi258K → A: Decreases DNA-binding to 40%. 1 Publication1
Mutagenesisi300K → A: Decreases DNA-binding to 20%. 1 Publication1
Mutagenesisi305S → A: Decreases DNA-binding to 70%. 1 Publication1
Mutagenesisi307R → A: Abolishes DNA-binding. 1 Publication1
Mutagenesisi308H → A: No effect on interaction with DVL2. 1 Publication1
Mutagenesisi328K → A: Decreases DNA-binding to 25%. 1 Publication1

Organism-specific databases

DisGeNETi3607.
OpenTargetsiENSG00000141568.
PharmGKBiPA29851.

Polymorphism and mutation databases

BioMutaiFOXK2.
DMDMi118572648.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000918582 – 660Forkhead box protein K2Add BLAST659

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei30PhosphoserineCombined sources1
Modified residuei144Omega-N-methylarginineCombined sources1
Cross-linki161Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki164Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei239PhosphoserineCombined sources1
Modified residuei373PhosphoserineBy similarity1
Modified residuei398PhosphoserineCombined sources1
Modified residuei424PhosphoserineCombined sources1
Modified residuei428PhosphoserineCombined sources1
Cross-linki527Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei599PhosphoserineBy similarity1
Cross-linki633Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ01167.
MaxQBiQ01167.
PaxDbiQ01167.
PeptideAtlasiQ01167.
PRIDEiQ01167.

PTM databases

iPTMnetiQ01167.
PhosphoSitePlusiQ01167.

Expressioni

Tissue specificityi

Expressed in both lymphoid and non-lymphoid cells.1 Publication

Gene expression databases

BgeeiENSG00000141568.
CleanExiHS_FOXK2.
ExpressionAtlasiQ01167. baseline and differential.
GenevisibleiQ01167. HS.

Organism-specific databases

HPAiHPA027523.

Interactioni

Subunit structurei

Interacts with DVL1, DVL2 (when phosphorylated) and DVL3; the interaction induces DVL2 nuclear translocation (PubMed:25805136). Interacts with SUDS3 (PubMed:25805136).1 Publication

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi109820. 127 interactors.
IntActiQ01167. 108 interactors.
MINTiMINT-1522265.
STRINGi9606.ENSP00000335677.

Structurei

Secondary structure

1660
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi263 – 272Combined sources10
Beta strandi277 – 279Combined sources3
Helixi281 – 291Combined sources11
Beta strandi295 – 298Combined sources4
Helixi300 – 312Combined sources13
Beta strandi316 – 319Combined sources4
Beta strandi324 – 329Combined sources6
Beta strandi331 – 334Combined sources4
Helixi336 – 346Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JXSNMR-A256-353[»]
2C6YX-ray2.40A/B256-353[»]
ProteinModelPortaliQ01167.
SMRiQ01167.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ01167.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini54 – 128FHAPROSITE-ProRule annotationAdd BLAST75

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni129 – 171Required for interaction with DVL2 and SUDS31 PublicationAdd BLAST43
Regioni300 – 318DNA-binding; major grooveAdd BLAST19
Regioni328 – 332DNA-binding; minor groove5
Regioni348 – 353DNA-binding; minor groove6

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi10 – 93Gly-richAdd BLAST84

Domaini

The C-terminal part of the DNA-binding domain may contribute to DNA recognition specificity.1 Publication

Phylogenomic databases

eggNOGiKOG2294. Eukaryota.
COG5025. LUCA.
GeneTreeiENSGT00800000124014.
HOGENOMiHOG000072588.
HOVERGENiHBG051649.
InParanoidiQ01167.
KOiK09404.
OMAiYKMGRVI.
OrthoDBiEOG091G099F.
PhylomeDBiQ01167.
TreeFamiTF325718.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiView protein in InterPro
IPR000253. FHA_dom.
IPR001766. Fork_head_dom.
IPR008984. SMAD_FHA_domain.
IPR018122. TF_fork_head_CS_1.
IPR030456. TF_fork_head_CS_2.
IPR011991. WHTH_DNA-bd_dom.
PfamiView protein in Pfam
PF00498. FHA. 1 hit.
PF00250. Forkhead. 1 hit.
PRINTSiPR00053. FORKHEAD.
SMARTiView protein in SMART
SM00339. FH. 1 hit.
SM00240. FHA. 1 hit.
SUPFAMiSSF46785. SSF46785. 1 hit.
SSF49879. SSF49879. 1 hit.
PROSITEiView protein in PROSITE
PS50006. FHA_DOMAIN. 1 hit.
PS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q01167-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAAAAAALSG AGTPPAGGGA GGGGAGGGGS PPGGWAVARL EGREFEYLMK
60 70 80 90 100
KRSVTIGRNS SQGSVDVSMG HSSFISRRHL EIFTPPGGGG HGGAAPELPP
110 120 130 140 150
AQPRPDAGGD FYLRCLGKNG VFVDGVFQRR GAPPLQLPRV CTFRFPSTNI
160 170 180 190 200
KITFTALSSE KREKQEASES PVKAVQPHIS PLTINIPDTM AHLISPLPSP
210 220 230 240 250
TGTISAANSC PSSPRGAGSS GYKVGRVMPS DLNLMADNSQ PENEKEASGG
260 270 280 290 300
DSPKDDSKPP YSYAQLIVQA ITMAPDKQLT LNGIYTHITK NYPYYRTADK
310 320 330 340 350
GWQNSIRHNL SLNRYFIKVP RSQEEPGKGS FWRIDPASES KLIEQAFRKR
360 370 380 390 400
RPRGVPCFRT PLGPLSSRSA PASPNHAGVL SAHSSGAQTP ESLSREGSPA
410 420 430 440 450
PLEPEPGAAQ PKLAVIQEAR FAQSAPGSPL SSQPVLITVQ RQLPQAIKPV
460 470 480 490 500
TYTVATPVTT STSQPPVVQT VHVVHQIPAV SVTSVAGLAP ANTYTVSGQA
510 520 530 540 550
VVTPAAVLAP PKAEAQENGD HREVKVKVEP IPAIGHATLG TASRIIQTAQ
560 570 580 590 600
TTPVQTVTIV QQAPLGQHQL PIKTVTQNGT HVASVPTAVH GQVNNAAASP
610 620 630 640 650
LHMLATHASA SASLPTKRHN GDQPEQPELK RIKTEDGEGI VIALSVDTPP
660
AAVREKGVQN
Length:660
Mass (Da):69,062
Last modified:November 28, 2006 - v3
Checksum:iE11C0B24370F1260
GO
Isoform 2 (identifier: Q01167-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     596-660: AAASPLHMLA...AAVREKGVQN → GPLGLRRPPCASSDWSCLS

Show »
Length:614
Mass (Da):64,256
Checksum:iF5BE52BA84587655
GO
Isoform 3 (identifier: Q01167-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     304-328: NSIRHNLSLNRYFIKVPRSQEEPGK → RGESFAHVGNTRIRIGLPAHKAPQR
     329-660: Missing.

Show »
Length:328
Mass (Da):34,325
Checksum:i4FCFB7F9FA67C9CA
GO

Sequence cautioni

The sequence AAB02820 differs from that shown. The N-terminal sequence differs due to frameshifts and sequencing errors.Curated
The sequence AAB02821 differs from that shown. The N-terminal sequence differs due to frameshifts and sequencing errors.Curated
The sequence AAB02822 differs from that shown. The N-terminal sequence differs due to frameshifts and sequencing errors.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti3 – 120AAAAA…LGKNG → Q in CAA43200 (PubMed:1909027).CuratedAdd BLAST118

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001560304 – 328NSIRH…EEPGK → RGESFAHVGNTRIRIGLPAH KAPQR in isoform 3. CuratedAdd BLAST25
Alternative sequenceiVSP_001561329 – 660Missing in isoform 3. CuratedAdd BLAST332
Alternative sequenceiVSP_001559596 – 660AAASP…KGVQN → GPLGLRRPPCASSDWSCLS in isoform 2. 1 PublicationAdd BLAST65

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X60787 mRNA. Translation: CAA43200.1.
U58196 mRNA. Translation: AAB02820.1. Sequence problems.
U58197 mRNA. Translation: AAB02821.1. Sequence problems.
U58198 mRNA. Translation: AAB02822.1. Sequence problems.
AC124287 Genomic DNA. No translation available.
CCDSiCCDS11813.1. [Q01167-1]
PIRiA41285.
RefSeqiNP_004505.2. NM_004514.3. [Q01167-1]
UniGeneiHs.591140.

Genome annotation databases

EnsembliENST00000335255; ENSP00000335677; ENSG00000141568. [Q01167-1]
ENST00000473637; ENSP00000436108; ENSG00000141568. [Q01167-2]
GeneIDi3607.
KEGGihsa:3607.
UCSCiuc002kfm.2. human. [Q01167-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiFOXK2_HUMAN
AccessioniPrimary (citable) accession number: Q01167
Secondary accession number(s): A6NEP5
, Q13622, Q13623, Q13624
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: November 28, 2006
Last modified: September 27, 2017
This is version 188 of the entry and version 3 of the sequence. See 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 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references