Forkhead (FH) domain found in Forkhead box (FOX) family of transcription factors and similar proteins; The FOX family comprises diverse tissue- and cell type-specific transcription factors with an evolutionary conserved "Forkhead (FH)" or "winged helix" DNA-binding domain. FH is named for the Drosophila fork head protein, a transcription factor which promotes terminal rather than segmental development. The structure of the FH domain contains 2 flexible loops or "wings" in the C-terminal region, hence the term winged helix. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'. They participate in a variety of cellular processes, such as cell cycle progression, proliferation, differentiation, migration, metabolism, and DNA damage response. Their expression can be regulated by multiple factors, and they can act as co-activators and/or transcriptional repressors. Fifty FOX-encoding genes in humans have been categorized into 19 subfamilies based on protein sequence homology (FOXA to FOXS).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1938808397 428 TSPRWThNSIRHNLSLHTRFIRVQNEGTGKSSWWMLNPEGGKTGK 472
Cdd:cd20063    45 SSAGWK-NSIRHNLSLHTRFIRVQNEGTGKSSWWMLNPEGGKTGK 88

KIX-binding domain of forkhead box O, CR2; FOXO_KIX_bd is the first part of the region of transcription factor forkhead box O family proteins that binds to the CREB-binding proteins via the KIX domain. Coactivator CBP/p300 is recruited by FOXO3 via the binding of this domain as well as the simultaneous binding of the more C-terminal TAD domain.

                          10        20
                  ....*....|....*....|
gi 1938808397 654 PPAMGALRRLPMQTIQENKQ 673
Cdd:pfam16675   6 QPSMNSLRQMPMQTIQENKQ 25

Forkhead (FH) domain found in Forkhead box protein O6 (FOXO6) and similar proteins; FOXO6 acts as a transcriptional activator that may play an important role on tumor invasion, metastasis and prognosis. The FH domain is a winged helix DNA-binding domain. All FOXOs bind to the consensus sequence 5'-GTAAACAA-3', known as the DAF-16 family member-binding element, which includes the core sequence 5'-(A/C)AA(C/T)A-3' recognized by all FOX family members.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1938808397 428 TSPRWThNSIRHNLSLHTRFIRVQNEGTGKSSWWMLNPEGGKTGK 472
Cdd:cd20063    45 SSAGWK-NSIRHNLSLHTRFIRVQNEGTGKSSWWMLNPEGGKTGK 88

FORKHEAD; FORKHEAD, also known as a "winged helix"

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1938808397  429 SPRWtHNSIRHNLSLHTRFIRVQNEGT--GKSSWWMLNPE 466
Cdd:smart00339  42 RAGW-QNSIRHNLSLNDCFVKVPREGDrpGKGSYWTLDPA 80

KIX-binding domain of forkhead box O, CR2; FOXO_KIX_bd is the first part of the region of transcription factor forkhead box O family proteins that binds to the CREB-binding proteins via the KIX domain. Coactivator CBP/p300 is recruited by FOXO3 via the binding of this domain as well as the simultaneous binding of the more C-terminal TAD domain.

                          10        20
                  ....*....|....*....|
gi 1938808397 654 PPAMGALRRLPMQTIQENKQ 673
Cdd:pfam16675   6 QPSMNSLRQMPMQTIQENKQ 25

Forkhead (FH) domain found in Forkhead box protein O6 (FOXO6) and similar proteins; FOXO6 acts as a transcriptional activator that may play an important role on tumor invasion, metastasis and prognosis. The FH domain is a winged helix DNA-binding domain. All FOXOs bind to the consensus sequence 5'-GTAAACAA-3', known as the DAF-16 family member-binding element, which includes the core sequence 5'-(A/C)AA(C/T)A-3' recognized by all FOX family members.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1938808397 428 TSPRWThNSIRHNLSLHTRFIRVQNEGTGKSSWWMLNPEGGKTGK 472
Cdd:cd20063    45 SSAGWK-NSIRHNLSLHTRFIRVQNEGTGKSSWWMLNPEGGKTGK 88

Forkhead (FH) domain found in Forkhead box protein O1 (FOXO1); FOXO1, also called Forkhead box protein O1A or Forkhead in rhabdomyosarcoma (FKHR), is a transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress. It binds to the insulin response element (IRE) with the consensus sequence 5'-TT[G/A]TTTTG-3' and the related Daf-16 family binding element (DBE) with the consensus sequence 5'-TT[G/A]TTTAC-3'. The FH domain is a winged helix DNA-binding domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1938808397 428 TSPRWThNSIRHNLSLHTRFIRVQNEGTGKSSWWMLNPEGGKTGKT 473
Cdd:cd20060    55 SSAGWK-NSIRHNLSLHSKFIRVQNEGTGKSSWWMLNPEGGKSGKS 99

Forkhead (FH) domain found in Forkhead box protein O3 (FOXO3); FOXO3, also called AF6q21 protein or Forkhead in rhabdomyosarcoma-like 1 (FKHRL1), is a transcriptional activator which triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress. It recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3'. The FH domain is a winged helix DNA-binding domain. All FOXOs bind to the consensus sequence 5'-GTAAACAA-3', known as the DAF-16 family member-binding element, which includes the core sequence 5'-(A/C)AA(C/T)A-3' recognized by all FOX family members.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1938808397 428 TSPRWThNSIRHNLSLHTRFIRVQNEGTGKSSWWMLNPE 466
Cdd:cd20061    46 SSAGWK-NSIRHNLSLHSRFIRVQNEGTGKSSWWMINPD 83

FORKHEAD; FORKHEAD, also known as a "winged helix"

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1938808397  429 SPRWtHNSIRHNLSLHTRFIRVQNEGT--GKSSWWMLNPE 466
Cdd:smart00339  42 RAGW-QNSIRHNLSLNDCFVKVPREGDrpGKGSYWTLDPA 80

Forkhead domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1938808397 427 RTSPR-WtHNSIRHNLSLHTRFIRV--QNEGTGKSSWWMLNPE 466
Cdd:pfam00250  39 RTADKgW-QNSIRHNLSLNKCFVKVprPKDEPGKGSYWTIDPE 80

Forkhead (FH) domain found in Forkhead box protein J1 (FOXJ1) and similar proteins; FOXJ1, also called Forkhead-related protein FKHL13 or hepatocyte nuclear factor 3 Forkhead homolog 4 (HFH-4), acts as a transcription factor specifically required for the formation of motile cilia. It acts by activating transcription of genes that mediate assembly of motile cilia, such as CFAP157. FOXJ1 binds the DNA consensus sequences 5'-HWDTGTTTGTTTA-3' or 5'-KTTTGTTGTTKTW-3' (where H is not G, W is A or T, D is not C, and K is G or T). It activates the transcription of a variety of ciliary proteins in the developing brain and lung. The FH domain is a winged helix DNA-binding domain.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1938808397 430 PRWtHNSIRHNLSLHTRFIRV--QNEGTGKSSWWMLNP 465
Cdd:cd20023    43 PTW-QNSIRHNLSLNKCFIKVprSKDEPGKGGFWRIDP 79

Forkhead (FH) domain found in Forkhead box protein L2 (FOXL2) and similar proteins; FOXL2 is a transcriptional regulator that is essential for ovary differentiation and maintenance, and repression of the genetic program for somatic testis determination. Mutations in the FOXL2 gene cause blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) types I and II, a rare genetic disorder. In BPES type I, a complex eyelid malformation is associated with premature ovarian failure (POF), whereas in BPES type II, the eyelid defect occurs as an isolated entity. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30
                  ....*....|....*....|....*....|...
gi 1938808397 435 NSIRHNLSLHTRFIRVQNEGTG--KSSWWMLNP 465
Cdd:cd20028    47 NSIRHNLSLNECFVKVPREGGGerKGNYWTLDP 79

Forkhead (FH) domain found in the Forkhead box protein K (FOXK) subfamily; The FOXK subfamily includes two winged helix transcription factors, FOXK1 and FOXK2. FOXK1, also called myocyte nuclear factor (MNF), acts as a transcriptional regulator that binds to the upstream enhancer region (CCAC box) of myoglobin genes. It positively regulates Wnt/beta-catenin signaling by translocating dishevelled (DVL) proteins into the nucleus. It also reduces virus replication, probably by binding the interferon stimulated response element (ISRE) to promote antiviral gene expression. In addition, FOXK1 plays important roles in multiple human cancers. FOXK2, also called cellular transcription factor ILF-1 or interleukin enhancer-binding factor 1, is a transcriptional regulator that recognizes the core sequence 5'-TAAACA-3'. It binds to NFAT-like motifs (purine-rich) in the IL2 promoter. It also binds to the HIV-1 long terminal repeat. FOXK2 may be involved in both, positive and negative regulation of important viral and cellular promoter elements. In addition, FOXK2 plays a critical role in suppressing tumorigenesis. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1938808397 427 RTSPRWTHNSIRHNLSLHTRFIRVQ--NEGTGKSSWWMLN 464
Cdd:cd20026    39 RTADKGWQNSIRHNLSLNRYFIKVPrsQEEPGKGSFWRID 78

Forkhead (FH) domain found in the Forkhead box protein E (FOXE) subfamily; The FOXE subfamily includes two winged helix transcription factors, FOXE1 (also known as FOXE2) and FOXE3. FOXE1, also called Forkhead-related protein FKHL15, HFKH4, HNF-3/fork head-like protein 5 (HFKL5), or thyroid transcription factor 2 (TTF-2), is a transcription factor that binds consensus sites on a variety of gene promoters and activate their transcription. FOXE3, also called Forkhead-related protein FKHL12 or Forkhead-related transcription factor 8 (FREAC-8), is a transcription factor that controls lens epithelial cell growth through regulation of proliferation, apoptosis, and the cell cycle. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938808397 387 PTSRIKATATArpAGSAVTYKLTGSWSHEgFIGQRaHSTERTSPRWTHNSIRHNLSLHTRFIRVQNE--GTGKSSWWMLN 464
Cdd:cd20019     3 PYSYIALIAMA--IANSPERKLTLGGIYK-FIMER-FPFYRDNSKKWQNSIRHNLTLNDCFVKIPREpgRPGKGNYWTLD 78

                          90       100
                  ....*....|....*....|....*
gi 1938808397 465 PEggktgktprrrAVSMDNGAKFLR 489
Cdd:cd20019    79 PA-----------AEDMFDNGSFLR 92

Forkhead (FH) domain found in Forkhead box protein D4 (FOXD4) and similar proteins; FOXD4, also called Forkhead-related protein FKHL9, Forkhead-related transcription factor 5 (FREAC-5), or myeloid factor-alpha, is essential for establishing neural cell fate and for neuronal differentiation. The family also includes Forkhead box protein D4-like proteins, FOXD4L1-6. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1938808397 417 FIGQRAHSTERTSPRWtHNSIRHNLSLHTRFIRVQNE--GTGKSSWWMLNP 465
Cdd:cd20048    30 FISGRFPYYRRKFPAW-QNSIRHNLSLNDCFVKIPREpgHPGKGNYWSLDP 79

Forkhead (FH) domain found in Forkhead box proteins, FOXJ2, FOXJ3 and similar proteins; The FOXJ2-like subfamily includes two winged helix transcription factors, FOXJ2 and FOXJ3. FOXJ2, also called Forkhead homologous X (FHX), plays an important role in tumorigenesis, progression, and metastasis of certain cancers. It acts as a transcriptional activator that can bind to two different type of DNA binding sites. FOXJ3 is a transcription factor which regulates sperm function. It transcriptionally activates Mef2c and regulates adult skeletal muscle fiber type identity. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 1938808397 435 NSIRHNLSLHTRFIRV--QNEGTGKSSWWML 463
Cdd:cd20024    47 NSIRHNLSLNKCFKKVprSKDDPGKGSYWTL 77

Forkhead (FH) domain found in Forkhead box protein N1 (FOXN1) and similar proteins; The FOXN1-like group includes two FOXN subfamily winged helix transcription factors, FOXN1 and FOXN4. FOXN1, also called winged helix transcription factor nude, acts as a transcriptional regulator which regulates the development, differentiation, and function of thymic epithelial cells (TECs), both in the prenatal and postnatal thymus. FOXN4 acts as a transcription factor essential for neural and some non-neural tissue development, such as retina and lung, respectively. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1938808397 427 RTSPRWTHNSIRHNLSLHTRFIRVQNEGTG----KSSWWMLNP 465
Cdd:cd20030    39 KTAPDGWKNSVRHNLSLNKCFEKIERPDGNgssrKGCLWALNP 81

Forkhead (FH) domain found in Forkhead box protein L1 (FOXL1) and similar proteins; FOXL1, also called Forkhead-related protein FKHL11 or Forkhead-related transcription factor 7 (FREAC-7), acts as a transcription factor required for proper proliferation and differentiation in the gastrointestinal epithelium. It may play a critical role in suppressing tumorigenesis. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 1938808397 435 NSIRHNLSLHTRFIRVQNEGT--GKSSWWMLNPE 466
Cdd:cd20027    49 NSIRHNLSLNDCFVKVPREKGrpGKGNYWTLDPD 82

Forkhead (FH) domain found in Forkhead box protein K2 (FOXK2) and similar proteins; FOXK2, also called cellular transcription factor ILF-1 or interleukin enhancer-binding factor 1, is a transcriptional regulator that recognizes the core sequence 5'-TAAACA-3'. It binds to NFAT-like motifs (purine-rich) in the IL2 promoter. It also binds to the HIV-1 long terminal repeat. FOXK2 may be involved in both, positive and negative regulation of important viral and cellular promoter elements. In addition, FOXK2 plays a critical role in suppressing tumorigenesis. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1938808397 427 RTSPRWTHNSIRHNLSLHTRFIRV--QNEGTGKSSWWMLNP 465
Cdd:cd20055    41 RTADKGWQNSIRHNLSLNRYFIKVprSQEEPGKGSFWRIDP 81

Forkhead (FH) domain found in Forkhead box protein C2 (FOXC2) and similar proteins; FOXC2, also called Forkhead-related protein FKHL14, Mesenchyme fork head protein 1 (MFH-1 protein), or transcription factor FKH-14, acts as a transcriptional activator that might be involved in the formation of special mesenchymal tissues. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1938808397 427 RTSPRWTHNSIRHNLSLHTRFIRV--QNEGTGKSSWWMLNPE 466
Cdd:cd20045    41 RENKQGWQNSIRHNLSLNECFVKVprDDKKPGKGSYWTLDPD 82

Forkhead (FH) domain found in Forkhead box protein C1 (FOXC1) and similar proteins; FOXC1, also called Forkhead-related protein FKHL7, or Forkhead-related transcription factor 3 (FREAC-3), is a DNA-binding transcriptional factor that plays a role in a broad range of cellular and developmental processes such as the development of the eyes, bones, cardiovascular system, kidneys, and skin. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1938808397 427 RTSPRWTHNSIRHNLSLHTRFIRV--QNEGTGKSSWWMLNPE 466
Cdd:cd20044    44 RDNKQGWQNSIRHNLSLNECFVKVprDDKKPGKGSYWTLDPD 85

Forkhead (FH) domain found in the Forkhead box protein A (FOXA) subfamily; The FOXA subfamily includes three winged helix transcription factors, FOXA1 (also called hepatocyte nuclear factor 3-alpha or transcription factor 3A), FOXA2 (also called hepatocyte nuclear factor 3-beta or transcription factor 3B), and FOXA3 (also called hepatocyte nuclear factor 3-gamma or transcription factor 3G). FOXA1 is essential for epithelial lineage differentiation and has been found to be upregulated in numerous cancers. FOXA2 controls cell differentiation. It is a key transcriptional regulator that maintains airway mucus homeostasis and may also have an important role in bone metabolism. FOXA3 acts as an essential transcriptional regulator engaged in adipogenesis and energy metabolism. This subfamily also includes Xenopus tropicalis FOXA4, Drosophila melanogaster protein fork head (dFKH), and similar proteins. FOXA4 is only present in amphibians, where it is required for the correct regionalization and maintenance of the central nervous system. dFKH promotes terminal as opposed to segmental development. In the absence of dFKH, this developmental switch does not occur. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1938808397 431 RWtHNSIRHNLSLHTRFIRVQN--EGTGKSSWWMLNPEGG 468
Cdd:cd20015    44 RW-QNSIRHSLSFNDCFVKVPRspDKPGKGSYWTLHPDSG 82

Forkhead (FH) domain found in Forkhead box protein S1 (FOXS1); FOXS1, also called Forkhead-like 18 protein or Forkhead-related transcription factor 10 (FREAC-10), is a transcriptional repressor that suppresses transcription from the FASLG, FOXO3, and FOXO4 promoters. It may have a role in the organization of the testicular vasculature. It has also been implicated in energy turnover, motor function, and body weight. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1938808397 430 PRWtHNSIRHNLSLHTRFIRV--QNEGTGKSSWWMLNPE 466
Cdd:cd20037    44 PGW-QNSIRHNLSLNECFVKVprDDRKPGKGSYWTLDPD 81

Forkhead (FH) domain found in the Forkhead box protein P (FOXP) subfamily; The FOXP subfamily includes four winged helix transcription factors, FOXP1-4. They are involved in the development of the central nervous system. Mutations in FOXP1, also called Mac-1-regulated Forkhead (MFH), leads to developmental delay, intellectual disability, autism spectrum disorder, speech delay, and dysmorphic features. FOXP2, also called CAG repeat protein 44 or Trinucleotide repeat-containing gene 10 protein, is a transcriptional repressor that may play a role in the specification and differentiation of lung epithelium. It may also play a role in developing neural, gastrointestinal and cardiovascular tissues. FOXP3, also called Scurfin, is a transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg). FOXP4, also called Forkhead-related protein-like A, is a transcriptional repressor that represses lung-specific expression. It is necessary for normal T cell cytokine recall responses to antigen following pathogenic infection. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1938808397 427 RTSPRWThNSIRHNLSLHTRFIRVQNegtGKSSWWMLN 464
Cdd:cd20033    40 RNAATWK-NAVRHNLSLHKCFVRVEN---VKGAVWTVD 73

Forkhead (FH) domain found in the Forkhead box protein D (FOXD) subfamily; The FOXD subfamily includes four winged helix transcription factors, FOXD1-4. FOXD1, also called Forkhead-related protein FKHL8 or Forkhead-related transcription factor 4 (FREAC-4), is involved in transcriptional activation of Placental Growth Factor (PGF) and the complement component (C3) genes. It plays an important role in early embryonic development and organogenesis, and functions as an oncogene in several cancers. FOXD2, also called Forkhead-related protein FKHL17 or Forkhead-related transcription factor 9 (FREAC-9), is a probable transcription factor involved in embryogenesis and somatogenesis. FOXD3, also called HNF3/FH transcription factor genesis, acts as a transcriptional repressor that binds to the consensus sequence 5'-A[AT]T[AG]TTTGTTT-3'. It also acts as a transcriptional activator. It promotes development of neural crest cells from neural tube progenitors and restricts neural progenitor cells to the neural crest lineage while suppressing interneuron differentiation. FOXD3 is required for maintenance of pluripotent cells in the pre-implantation and peri-implantation stages of embryogenesis. FOXD4, also called Forkhead-related protein FKHL9 or Forkhead-related transcription factor 5 (FREAC-5), is essential for establishing neural cell fate and for neuronal differentiation. The family also includes Forkhead box protein D4-like proteins, FOXD4L1-6. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1938808397 417 FIGQRAHSTERTSPRWtHNSIRHNLSLHTRFIRVQNE--GTGKSSWWMLN 464
Cdd:cd20018    30 FIMNRFPYYREKFPAW-QNSIRHNLSLNDCFVKIPREpgNPGKGNYWTLD 78