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
                 ....*....|....*....|....*....|....*...
gi 755508331  25 NSIRHNLSLHTRFIRVQNEGTGKSSWWMLNPEGGKTGK 62
Cdd:cd20063   51 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 755508331  244 PPALGSLRRLPMQTIQENKQASF 266
Cdd:pfam16675   6 QPSMNSLRQMPMQTIQENKQSSF 28

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
                 ....*....|....*....|....*....|....*...
gi 755508331  25 NSIRHNLSLHTRFIRVQNEGTGKSSWWMLNPEGGKTGK 62
Cdd:cd20063   51 NSIRHNLSLHTRFIRVQNEGTGKSSWWMLNPEGGKTGK 88

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

                           10        20        30
                   ....*....|....*....|....*....|....
gi 755508331    25 NSIRHNLSLHTRFIRVQNEGT--GKSSWWMLNPE 56
Cdd:smart00339  47 NSIRHNLSLNDCFVKVPREGDrpGKGSYWTLDPA 80

Forkhead domain;

                          10        20        30
                  ....*....|....*....|....*....|....
gi 755508331   25 NSIRHNLSLHTRFIRV--QNEGTGKSSWWMLNPE 56
Cdd:pfam00250  47 NSIRHNLSLNKCFVKVprPKDEPGKGSYWTIDPE 80

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
                 ....*....|....*....|....*....|....*...
gi 755508331  25 NSIRHNLSLHTRFIRVQNEGTGKSSWWMLNPEGGKTGK 62
Cdd:cd20063   51 NSIRHNLSLHTRFIRVQNEGTGKSSWWMLNPEGGKTGK 88

Transactivation domain of FOXO protein family; TAD is a promiscuous binding domain that mediates the association of the transcription factor FOXO with the coactivator CBP/p300. Both this domain and the FOXO-KIX_bd family pfam16675 bind simultaneously the KIX domain of CBP/p300. Coactivator CBP/p300 is recruited by FOXO3 though binding to these two regions. The promiscuity of the TAD is further evidenced by that the finding that they also bind the TAZ1 and TAZ2 domains of CBP/p300.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 755508331  385 RFPADLDLDMFSGSLECDVESIILNDFMDSDEMDFNFDS 423
Cdd:pfam16676   1 RLPSDLDLDMFQGSLECDVDSIIRNDLMDGDGLDFNFDS 39

Forkhead (FH) domain found in the Forkhead box protein O (FOXO) subfamily; The FOXO subfamily includes several winged helix transcription factors: FOXO1, FOXO3, FOXO4 and FOXO6. FOXO transcription factors are involved in the regulation of longevity phenomenon via insulin and insulin-like growth factor signaling. 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. 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. 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'. FOXO4, also called Fork head domain transcription factor AFX1, is a transcription factor involved in the regulation of the insulin signaling pathway. It binds to insulin-response elements (IREs) and can activate transcription of IGFBP1. 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.

                         10        20        30
                 ....*....|....*....|....*....|
gi 755508331  25 NSIRHNLSLHTRFIRVQNEGTGKSSWWMLN 54
Cdd:cd20032   51 NSIRHNLSLHSRFVRVQNEGTGKSSWWTLN 80

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

                           10        20        30
                   ....*....|....*....|....*....|....
gi 755508331    25 NSIRHNLSLHTRFIRVQNEGT--GKSSWWMLNPE 56
Cdd:smart00339  47 NSIRHNLSLNDCFVKVPREGDrpGKGSYWTLDPA 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 755508331  244 PPALGSLRRLPMQTIQENKQASF 266
Cdd:pfam16675   6 QPSMNSLRQMPMQTIQENKQSSF 28

Forkhead (FH) domain found in Forkhead box protein Q2 (FOXQ2) and similar proteins; FOXQ2 is the neurogenic ectoderm specification transcription factor that controls aboral development in cnidarians and anterior identity in bilaterians. It plays essential roles in epidermal development and central brain patterning. The foxQ2 gene is absent in placental mammals. 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 755508331  25 NSIRHNLSLHTRFIRVQNEGTGKSSWWMLNPEGGKT---GKTPRRRA 68
Cdd:cd20035   47 NSVRHNLSLNECFVKAGRAENGKGNYWTIHPACLEDfekGDFRRRRA 93

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 755508331  25 NSIRHNLSLHTRFIRVQNEGTG--KSSWWMLNP 55
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
                 ....*....|....*....|....*....|..
gi 755508331  25 NSIRHNLSLHTRFIRVQ--NEGTGKSSWWMLN 54
Cdd:cd20026   47 NSIRHNLSLNRYFIKVPrsQEEPGKGSFWRID 78

Forkhead (FH) domain found in Forkhead box protein Q1 (FOXQ1) and similar proteins; FOXQ1, also called HNF-3/Forkhead-like protein 1 (HFH-1), or hepatocyte nuclear factor 3 Forkhead homolog 1, plays a role in hair follicle differentiation. It has also been reported to promote epithelial differentiation, inhibit smooth muscle differentiation, activate T cells and autoimmunity, and control mucin gene expression and granule content in stomach surface mucous cells. FOXQ1 is significantly associated with the pathogenesis of various tumor types including gastric, breast, colorectal, pancreatic, bladder and ovarian cancer, and glioma. 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 755508331  25 NSIRHNLSLHTRFIRVQNEGT---GKSSWWMLN 54
Cdd:cd20034   47 NSVRHNLSLNDCFVKVLRDPSrpwGKDNYWTIN 79

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 755508331  25 NSIRHNLSLHTRFIRVQNEGT--GKSSWWMLNPE 56
Cdd:cd20027   49 NSIRHNLSLNDCFVKVPREKGrpGKGNYWTLDPD 82

Forkhead (FH) domain found in Forkhead box protein N3 (FOXN3); FOXN3, also called checkpoint suppressor 1 (CHES1), acts as a transcriptional repressor that may be involved in DNA damage-inducible cell cycle arrests (checkpoints). It displays transcriptional inhibitory activity, and is involved in cell cycle regulation and tumorigenesis. Alterations in FOXN3 are found in of a variety of cancers including melanoma, osteosarcoma, and hepatocellular carcinoma. FOXN3 also regulates hepatic glucose utilization/metabolism by regulating gluconeogenic substrate selection. 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 755508331  25 NSIRHNLSLHTRFIRVQNE---GTGKSSWWMLNPE 56
Cdd:cd20059   47 NSVRHNLSLNKCFKKVDKEkgqSIGKGSLWCIDPE 81

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
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 755508331  25 NSIRHNLSLHTRFIRVQNE--GTGKSSWWMLNPEggktgktprrrAVSMDNGAKFLR 79
Cdd:cd20019   47 NSIRHNLTLNDCFVKIPREpgRPGKGNYWTLDPA-----------AEDMFDNGSFLR 92

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 755508331  25 NSIRHNLSLHTRFIRV--QNEGTGKSSWWMLNPE 56
Cdd:cd20037   48 NSIRHNLSLNECFVKVprDDRKPGKGSYWTLDPD 81

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
                 ....*....|....*....|....*....|...
gi 755508331  25 NSIRHNLSLHTRFIRV--QNEGTGKSSWWMLNP 55
Cdd:cd20055   49 NSIRHNLSLNRYFIKVprSQEEPGKGSFWRIDP 81

Forkhead (FH) domain found in Forkhead box protein K1 (FOXK1) and similar proteins; 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. 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 755508331  25 NSIRHNLSLHTRFIRV--QNEGTGKSSWWMLNP 55
Cdd:cd20054   49 NSIRHNLSLNRYFIKVprSQEEPGKGSFWRIDP 81

Forkhead (FH) domain found in Drosophila melanogaster protein fork head (dFKH) and similar proteins; 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
                 ....*....|....*....|....*....|....*.
gi 755508331  25 NSIRHNLSLHTRFIRVQN--EGTGKSSWWMLNPEGG 58
Cdd:cd20041   47 NSIRHSLSFNDCFVKVPRtpDKPGKGSFWTLHPDSG 82

Forkhead (FH) domain found in the Forkhead box protein B (FOXB) subfamily; The FOXB subfamily includes two winged helix transcription factors, FOXB1 (also called transcription factor FKH-5) and FOXB2 (also called transcription factor FKH-4). FOXB1 controls development of mammary glands and regions of the central nervous system (CNS) that regulate the milk-ejection reflex. It is essential for access of mammillothalamic axons to the thalamus. FOXB2 may act as a tumor suppressor; it has been found to inhibit the malignant characteristics of the pancreatic cancer cell line Panc-1 in vitro. 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 755508331  25 NSIRHNLSLHTRFIRVQNEGT--GKSSWWMLNP 55
Cdd:cd20016   47 NSLRHNLSFNDCFIKIPRRPDrpGKGSYWALHP 79

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
                 ....*....|....*....|....*....|....*.
gi 755508331  25 NSIRHNLSLHTRFIRVQN--EGTGKSSWWMLNPEGG 58
Cdd:cd20015   47 NSIRHSLSFNDCFVKVPRspDKPGKGSYWTLHPDSG 82

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 755508331  25 NSIRHNLSLHTRFIRVQNegtGKSSWWMLN 54
Cdd:cd20033   47 NAVRHNLSLHKCFVRVEN---VKGAVWTVD 73