Q01167 (FOXK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Forkhead box protein K2

Alternative name(s):
Cellular transcription factor ILF-1
FOXK1
Interleukin enhancer-binding factor 1

Gene names

Name:	FOXK2
Synonyms:	ILF, ILF1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	660 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Recognizes the core sequence 5'-TAAACA-3'. Binds to NFAT-like motifs (purine-rich) in the IL2 promoter. Also binds to HIV-1 long terminal repeat. May be involved in both positive and negative regulation of important viral and cellular promoter elements. Ref.1 Ref.2
Cofactor	Binds 1 magnesium ion per subunit. Ref.12
Subcellular location	Nucleus Probable.
Tissue specificity	Expressed in both lymphoid and non-lymphoid cells. Ref.2
Domain	The C-terminal part of the DNA-binding domain may contribute to DNA recognition specificity. Ref.12
Sequence similarities	Contains 1 FHA domain. Contains 1 fork-head DNA-binding domain.
Sequence caution	The sequence AAB02820.1 differs from that shown. Reason: The N-terminal sequence differs due to frameshifts and sequencing errors. The sequence AAB02821.1 differs from that shown. Reason: The N-terminal sequence differs due to frameshifts and sequencing errors. The sequence AAB02822.1 differs from that shown. Reason: The N-terminal sequence differs due to frameshifts and sequencing errors.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	DNA-binding Magnesium Metal-binding
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	embryo development Inferred from Biological aspect of Ancestor. Source: RefGenome pattern specification process Inferred from Biological aspect of Ancestor. Source: RefGenome regulation of sequence-specific DNA binding transcription factor activity Inferred from Biological aspect of Ancestor. Source: RefGenome tissue development Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular_component	transcription factor complex Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	DNA binding, bending Inferred from Biological aspect of Ancestor. Source: RefGenome RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Inferred from Biological aspect of Ancestor. Source: RefGenome double-stranded DNA binding Inferred from Biological aspect of Ancestor. Source: RefGenome magnesium ion binding Inferred from direct assay Ref.12. Source: UniProtKB sequence-specific DNA binding Inferred from direct assay Ref.11Ref.2Ref.12Ref.1. Source: UniProtKB transcription factor binding Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IRF2	P14316	2	EBI-2509991,EBI-2866589

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q01167-1)

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.

Isoform 2 (identifier: Q01167-2)

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

Isoform 3 (identifier: Q01167-3)

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.9

Chain

2 – 660

659

Forkhead box protein K2

PRO_0000091858

Regions

Domain

54 – 128

75

FHA

DNA binding

258 – 353

96

Fork-head Ref.11 Ref.12

Region

300 – 318

19

DNA-binding; major groove

Region

328 – 332

5

DNA-binding; minor groove

Region

348 – 353

6

DNA-binding; minor groove

Compositional bias

10 – 93

84

Gly-rich

Sites

Metal binding

310

1

Magnesium; via carbonyl oxygen

Metal binding

311

1

Magnesium; via carbonyl oxygen

Metal binding

313

1

Magnesium; via carbonyl oxygen

Metal binding

316

1

Magnesium; via carbonyl oxygen

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.9

Modified residue

30

1

Phosphoserine Ref.9

Modified residue

239

1

Phosphoserine Ref.5

Modified residue

398

1

Phosphoserine Ref.8 Ref.9 Ref.10

Modified residue

424

1

Phosphoserine Ref.9

Modified residue

428

1

Phosphoserine Ref.6 Ref.8 Ref.9

Natural variations

Alternative sequence

304 – 328

25

NSIRH…EEPGK → RGESFAHVGNTRIRIGLPAH KAPQR in isoform 3.

VSP_001560

Alternative sequence

329 – 660

332

Missing in isoform 3.

VSP_001561

Alternative sequence

596 – 660

65

AAASP…KGVQN → GPLGLRRPPCASSDWSCLS in isoform 2.

VSP_001559

Experimental info

Mutagenesis

258

1

K → A: Decreases DNA-binding to 40%. Ref.12

Mutagenesis

300

1

K → A: Decreases DNA-binding to 20%. Ref.12

Mutagenesis

305

1

S → A: Decreases DNA-binding to 70%. Ref.12

Mutagenesis

307

1

R → A: Abolishes DNA-binding. Ref.12

Mutagenesis

328

1

K → A: Decreases DNA-binding to 25%. Ref.12

Sequence conflict

3 – 120

118

AAAAA…LGKNG → Q in CAA43200. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

660

Helix Strand Turn

Details...

Helix

263 – 272

10

Beta strand

277 – 279

3

Helix

281 – 291

11

Beta strand

295 – 298

4

Helix

300 – 312

13

Beta strand

316 – 319

4

Beta strand

324 – 329

6

Beta strand

331 – 334

4

Helix

336 – 346

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 28, 2006. Version 3. Checksum: E11C0B24370F1260	FASTA	660	69,062
	10 20 30 40 50 60 MAAAAAALSG AGTPPAGGGA GGGGAGGGGS PPGGWAVARL EGREFEYLMK KRSVTIGRNS 70 80 90 100 110 120 SQGSVDVSMG HSSFISRRHL EIFTPPGGGG HGGAAPELPP AQPRPDAGGD FYLRCLGKNG 130 140 150 160 170 180 VFVDGVFQRR GAPPLQLPRV CTFRFPSTNI KITFTALSSE KREKQEASES PVKAVQPHIS 190 200 210 220 230 240 PLTINIPDTM AHLISPLPSP TGTISAANSC PSSPRGAGSS GYKVGRVMPS DLNLMADNSQ 250 260 270 280 290 300 PENEKEASGG DSPKDDSKPP YSYAQLIVQA ITMAPDKQLT LNGIYTHITK NYPYYRTADK 310 320 330 340 350 360 GWQNSIRHNL SLNRYFIKVP RSQEEPGKGS FWRIDPASES KLIEQAFRKR RPRGVPCFRT 370 380 390 400 410 420 PLGPLSSRSA PASPNHAGVL SAHSSGAQTP ESLSREGSPA PLEPEPGAAQ PKLAVIQEAR 430 440 450 460 470 480 FAQSAPGSPL SSQPVLITVQ RQLPQAIKPV TYTVATPVTT STSQPPVVQT VHVVHQIPAV 490 500 510 520 530 540 SVTSVAGLAP ANTYTVSGQA VVTPAAVLAP PKAEAQENGD HREVKVKVEP IPAIGHATLG 550 560 570 580 590 600 TASRIIQTAQ TTPVQTVTIV QQAPLGQHQL PIKTVTQNGT HVASVPTAVH GQVNNAAASP 610 620 630 640 650 660 LHMLATHASA SASLPTKRHN GDQPEQPELK RIKTEDGEGI VIALSVDTPP AAVREKGVQN
	Isoform 2 [UniParc]. Checksum: F5BE52BA84587655	FASTA	614	64,256
	10 20 30 40 50 60 MAAAAAALSG AGTPPAGGGA GGGGAGGGGS PPGGWAVARL EGREFEYLMK KRSVTIGRNS 70 80 90 100 110 120 SQGSVDVSMG HSSFISRRHL EIFTPPGGGG HGGAAPELPP AQPRPDAGGD FYLRCLGKNG 130 140 150 160 170 180 VFVDGVFQRR GAPPLQLPRV CTFRFPSTNI KITFTALSSE KREKQEASES PVKAVQPHIS 190 200 210 220 230 240 PLTINIPDTM AHLISPLPSP TGTISAANSC PSSPRGAGSS GYKVGRVMPS DLNLMADNSQ 250 260 270 280 290 300 PENEKEASGG DSPKDDSKPP YSYAQLIVQA ITMAPDKQLT LNGIYTHITK NYPYYRTADK 310 320 330 340 350 360 GWQNSIRHNL SLNRYFIKVP RSQEEPGKGS FWRIDPASES KLIEQAFRKR RPRGVPCFRT 370 380 390 400 410 420 PLGPLSSRSA PASPNHAGVL SAHSSGAQTP ESLSREGSPA PLEPEPGAAQ PKLAVIQEAR 430 440 450 460 470 480 FAQSAPGSPL SSQPVLITVQ RQLPQAIKPV TYTVATPVTT STSQPPVVQT VHVVHQIPAV 490 500 510 520 530 540 SVTSVAGLAP ANTYTVSGQA VVTPAAVLAP PKAEAQENGD HREVKVKVEP IPAIGHATLG 550 560 570 580 590 600 TASRIIQTAQ TTPVQTVTIV QQAPLGQHQL PIKTVTQNGT HVASVPTAVH GQVNNGPLGL 610 RRPPCASSDW SCLS
	Isoform 3 [UniParc]. Checksum: 4FCFB7F9FA67C9CA	FASTA	328	34,325
	10 20 30 40 50 60 MAAAAAALSG AGTPPAGGGA GGGGAGGGGS PPGGWAVARL EGREFEYLMK KRSVTIGRNS 70 80 90 100 110 120 SQGSVDVSMG HSSFISRRHL EIFTPPGGGG HGGAAPELPP AQPRPDAGGD FYLRCLGKNG 130 140 150 160 170 180 VFVDGVFQRR GAPPLQLPRV CTFRFPSTNI KITFTALSSE KREKQEASES PVKAVQPHIS 190 200 210 220 230 240 PLTINIPDTM AHLISPLPSP TGTISAANSC PSSPRGAGSS GYKVGRVMPS DLNLMADNSQ 250 260 270 280 290 300 PENEKEASGG DSPKDDSKPP YSYAQLIVQA ITMAPDKQLT LNGIYTHITK NYPYYRTADK 310 320 GWQRGESFAH VGNTRIRIGL PAHKAPQR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of a cellular factor, interleukin binding factor, that binds to NFAT-like motifs in the human immunodeficiency virus long terminal repeat." Li C., Lai C., Sigman D.S., Gaynor R.B. Proc. Natl. Acad. Sci. U.S.A. 88:7739-7743(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION. Tissue: Cervix carcinoma.
[2]	"Characterization and chromosomal mapping of the gene encoding the cellular DNA binding protein ILF." Li C., Lusis A.J., Sparkes R., Nirula A., Gaynor R.B. Genomics 13:665-671(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE SPECIFICITY. Tissue: Cervix carcinoma and Lymphoid tissue.
[3]	Nirula A., Moore D.J., Li C., Gaynor R.B. Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION (ISOFORMS 1; 2 AND 3).
[4]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[6]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[8]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-398 AND SER-428, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[9]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-30; SER-398; SER-424 AND SER-428, MASS SPECTROMETRY, CLEAVAGE OF INITIATOR METHIONINE. Tissue: Cervix carcinoma.
[10]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-398, MASS SPECTROMETRY.
[11]	"Solution structure of the DNA-binding domain of interleukin enhancer binding factor 1 (FOXK1a)." Liu P.-P., Chen Y.-C., Li C., Hsieh Y.-H., Chen S.-W., Chen S.-H., Jeng W.-Y., Chuang W.-J. Proteins 49:543-553(2002) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 256-353 (ISOFORM 1), DNA-BINDING.
[12]	"Crystal structure of the human FOXK1a-DNA complex and its implications on the diverse binding specificity of winged helix/forkhead proteins." Tsai K.-L., Huang C.-Y., Chang C.-H., Sun Y.-J., Chuang W.-J., Hsiao C.-D. J. Biol. Chem. 281:17400-17409(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 256-353 (ISOFORM 1) IN COMPLEX WITH MAGNESIUM AND DUPLEX DNA, DNA-BINDING, COFACTOR, DOMAIN, MUTAGENESIS OF LYS-258; LYS-300; SER-305; ARG-307 AND LYS-328.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00006029.
IPI00220426.
IPI00479612.

PIR

A41285.

RefSeq

NP_004505.2. NM_004514.3.

UniGene

Hs.591140.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JXS	NMR	-	A	256-353	[»]
2C6Y	X-ray	2.40	A/B	256-353	[»]

ProteinModelPortal

Q01167.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q01167. 9 interactions.

STRING

9606.ENSP00000335677.

PTM databases

PhosphoSite

Q01167.

Polymorphism databases

DMDM

118572648.

Proteomic databases

PaxDb

Q01167.

PRIDE

Q01167.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000335255; ENSP00000335677; ENSG00000141568.
ENST00000473637; ENSP00000436108; ENSG00000141568.

GeneID

3607.

KEGG

hsa:3607.

UCSC

uc002kfm.1. human.
uc002kfn.3. human.
uc010diu.3. human.

Organism-specific databases

CTD

3607.

GeneCards

GC17P080477.

H-InvDB

HIX0014279.

HGNC

HGNC:6036. FOXK2.

HPA

HPA027523.

MIM

147685. gene.

neXtProt

NX_Q01167.

PharmGKB

PA29851.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5025.

HOGENOM

HOG000072588.

HOVERGEN

HBG051649.

InParanoid

Q01167.

KO

K09404.

OMA

HGQVNNA.

OrthoDB

EOG4XD3QX.

PhylomeDB

Q01167.

Gene expression databases

ArrayExpress

Q01167.

Bgee

Q01167.

CleanEx

HS_FOXK2.

Genevestigator

Q01167.

GermOnline

ENSG00000141568. Homo sapiens.

Family and domain databases

Gene3D

1.10.10.10. 1 hit.
2.60.200.20. 1 hit.

InterPro

IPR000253. FHA_dom.
IPR008984. SMAD_FHA_domain.
IPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]

Pfam

PF00498. FHA. 1 hit.
PF00250. Fork_head. 1 hit.
[Graphical view]

PRINTS

PR00053. FORKHEAD.

SMART

SM00339. FH. 1 hit.
SM00240. FHA. 1 hit.
[Graphical view]

SUPFAM

SSF49879. SMAD_FHA. 1 hit.

PROSITE

PS50006. FHA_DOMAIN. 1 hit.
PS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

FOXK2. human.

EvolutionaryTrace

Q01167.

GenomeRNAi

3607.

NextBio

14097.

SOURCE

Search...

Entry information

Entry name

FOXK2_HUMAN

Accession

Primary (citable) accession number: Q01167
Secondary accession number(s): A6NEP5 , Q13622, Q13623, Q13624

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	November 28, 2006
Last modified:	May 1, 2013
This is version 144 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.