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 34610227   499 RFPADLDLDMFSGSLECDVESIILNDFMDSDEMDFNFDS 537
Cdd:pfam16676   1 RLPSDLDLDMFQGSLECDVDSIIRNDLMDGDGLDFNFDS 39

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34610227     88 WGNLSYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKDKGDsnssaGWKNSIRHNLSLHTRFIRVQNEGT--GKSSWW 165
Cdd:smart00339   1 KPPYSYIALIAMAILSSPDKRLTLSEIYKWIEDNFPYYRENRA-----GWQNSIRHNLSLNDCFVKVPREGDrpGKGSYW 75

                   ....*
gi 34610227    166 MLNPE 170
Cdd:smart00339  76 TLDPA 80

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 34610227   499 RFPADLDLDMFSGSLECDVESIILNDFMDSDEMDFNFDS 537
Cdd:pfam16676   1 RLPSDLDLDMFQGSLECDVDSIIRNDLMDGDGLDFNFDS 39

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 34610227   358 PPALGSLRRLPMQTIQENKQASF 380
Cdd:pfam16675   6 QPSMNSLRQMPMQTIQENKQSSF 28

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        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34610227  79 KAKSSRRNAWGNLSYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKDKGDSNSSAGWKNSIRHNLSLHTRFIRVQNEG 158
Cdd:cd20060   1 KSSSSRRNAWGNLSYADLITKAIESSAEKRLTLSQIYEWMVKSVPYFKDKGDSNSSAGWKNSIRHNLSLHSKFIRVQNEG 80

                        90
                ....*....|....*....
gi 34610227 159 TGKSSWWMLNPEGGKTGKT 177
Cdd:cd20060  81 TGKSSWWMLNPEGGKSGKS 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        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34610227  88 WGNLSYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKDKGDSNSSAGWKNSIRHNLSLHTRFIRVQNEGTGKSSWWML 167
Cdd:cd20061   1 WGNLSYADLITRAIESSPDKRLTLSQIYDWMVRCVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFIRVQNEGTGKSSWWMI 80

                ...
gi 34610227 168 NPE 170
Cdd:cd20061  81 NPD 83

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        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34610227  89 GNLSYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKDKGDsnssaGWKNSIRHNLSLHTRFIRVQNEGT--GKSSWWM 166
Cdd:cd00059   1 PPYSYAALIALAILSSPDKRLTLSEIYKWIEDNFPYYRTATK-----GWKNSIRHNLSLNKCFVKVPREPSdpGKGSYWT 75

Forkhead domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34610227    90 NLSYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKdkgdsNSSAGWKNSIRHNLSLHTRFIRV--QNEGTGKSSWWML 167
Cdd:pfam00250   3 PYSYAALIAMAILSSPEKKLTLSEIYEWISENFPYYR-----TADKGWQNSIRHNLSLNKCFVKVprPKDEPGKGSYWTI 77

                  ...
gi 34610227   168 NPE 170
Cdd:pfam00250  78 DPE 80

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        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 34610227  91 LSYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKDkgdsnSSAGWKNSIRHNLSLHTRFIRV--QNEGTGKSSWWML 167
Cdd:cd20024   4 YSYATLITFAINSSPKKKMTLSEIYTWICENFPYYRE-----AGTGWKNSIRHNLSLNKCFKKVprSKDDPGKGSYWTL 77

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        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34610227  92 SYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFK--DKgdsnssaGWKNSIRHNLSLHTRFIRVQ--NEGTGKSSWWML 167
Cdd:cd20026   5 SYAQLIVQAISSAPDKQLTLSGIYAYITKNYPYYRtaDK-------GWQNSIRHNLSLNRYFIKVPrsQEEPGKGSFWRI 77

                .
gi 34610227 168 N 168
Cdd:cd20026  78 D 78

Forkhead (FH) domain found in the Forkhead box protein G (FOXG) subfamily; The FOXG subfamily includes a winged helix transcription factor FOXG1, which is also called brain factor 1 (BF-1), brain factor 2 (BF-2), Forkhead box protein G1A, Forkhead box protein G1B, Forkhead box protein G1C, Forkhead-related protein FKHL1, Forkhead-related protein FKHL2, or Forkhead-related protein FKHL3. FOXG1 acts as a transcription repression factor which plays an important role in the establishment of the regional subdivision of the developing brain and in the development of the telencephalon. It is repetitively used in the sequential events of telencephalic development to control multi-steps of brain circuit formation ranging from cell cycle control to neuronal differentiation in a clade- and species-specific manner. Individuals with mutations in FOXG1 harbor "FOXG1-related encephalopathy", characterized by two clinical phenotypes/syndromes including microcephaly, developmental delay, severe cognitive disabilities, early-onset dyskinesia and hyperkinetic movements, stereotypies, epilepsy, and cerebral malformation for those with deletions or intragenic mutations of FOXG1. 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 34610227  92 SYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKDkgdsnSSAGWKNSIRHNLSLHTRFIRVQN--EGTGKSSWWMLNP 169
Cdd:cd20021   5 SYNALIMMAIRQSPEKRLTLNGIYEFIMKNFPYYRE-----NKQGWQNSIRHNLSLNKCFVKVPRhyDDPGKGNYWMLDP 79

Forkhead (FH) domain found in Forkhead box protein N2 (FOXN2) and similar proteins; The FOXN2-like group includes two FOXN subfamily winged helix transcription factors, FOXN2 and FOXN3. FOXN2, also called human T-cell leukemia virus enhancer factor (HTLF), is a potential tumor suppressor that can facilitate replication fork reversal. It acts as a transcription factor that binds to the purine-rich region in human T-cell leukemia virus long terminal repeat (HTLV-I LTR). It may be a potential therapeutic and radiosensitization target for lung cancer. FOXN3, also called checkpoint suppressor 1, acts as a transcriptional repressor that may be involved in DNA damage-inducible cell cycle arrests (checkpoints). 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 34610227  92 SYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKdkgdsNSSAGWKNSIRHNLSLHTRFIRVQNEGT-GKSSWWM 166
Cdd:cd20031   5 SFSCLIFMAIESSPEKALPVKDIYSWIEKHFPYYR-----NAPSGWKNSIRHNLSLNKCFKKVEKEKNkGKGSLWC 75

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 34610227   499 RFPADLDLDMFSGSLECDVESIILNDFMDSDEMDFNFDS 537
Cdd:pfam16676   1 RLPSDLDLDMFQGSLECDVDSIIRNDLMDGDGLDFNFDS 39

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        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 34610227  92 SYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKDKgdsnsSAGWKNSIRHNLSLHTRFIRVQNegtGKSSWWMLN 168
Cdd:cd20033   5 TYASLIRQAILESPNKQLTLNEIYNWFQKTFAYFRRN-----AATWKNAVRHNLSLHKCFVRVEN---VKGAVWTVD 73

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        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34610227  92 SYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKDkgdsnSSAGWKNSIRHNLSLHTRFIRVQNEGT--GKSSWWMLNP 169
Cdd:cd20027   7 SYIALIAMAIKSAPDQKVTLNGIYQFIMDRFPYYHD-----NKQGWQNSIRHNLSLNDCFVKVPREKGrpGKGNYWTLDP 81

                .
gi 34610227 170 E 170
Cdd:cd20027  82 D 82

Forkhead (FH) domain found in Forkhead box protein P1 (FOXP1); FOXP1, also called Mac-1-regulated Forkhead (MFH), is a transcription factor that is widely expressed and has a broad range of functions. It has been shown to have a role in cardiac, lung, and lymphocyte development. Deregulation of FOXP1 is an important contributor to the pathogenesis of diffuse large B-cell lymphoma (DLBCL), suggesting it may function as an oncogene. Loss of FOXP1 expression in breast cancer is associated with a worse outcome, suggesting that FOXP1 may function as a tumor suppressor in some tissues. Haploinsufficiency of the FOXP1 gene leads to a neurodevelopmental disorder termed FOXP1 syndrome, characterized by developmental delay, intellectual disability, autism spectrum disorder, speech delay, and dysmorphic features. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 34610227  91 LSYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKdkgdsNSSAGWKNSIRHNLSLHTRFIRVQN 156
Cdd:cd20064   7 FTYASLIRQAILESPEKQLTLNEIYNWFTRMFAYFR-----RNAATWKNAVRHNLSLHKCFVRVEN 67

Forkhead (FH) domain found in Forkhead box protein P2 (FOXP2); 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. An arginine-to-histidine missense mutation (R553H) in the FOXP2 Forkhead domain has been linked to a severe speech and language disorder. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 34610227  92 SYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKdkgdsNSSAGWKNSIRHNLSLHTRFIRVQN 156
Cdd:cd20065   6 TYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFR-----RNAATWKNAVRHNLSLHKCFVRVEN 65

Forkhead (FH) domain found in the Forkhead box protein C (FOXC) subfamily; The FOXC subfamily includes two winged helix transcription factors, FOXC1 (also called Forkhead-related protein FKHL7, or Forkhead-related transcription factor 3) and FOXC2 (also called Forkhead-related protein FKHL14, or Mesenchyme fork head protein 1). FOXC1 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. FOXC2 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        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 34610227  92 SYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKDkgdsnSSAGWKNSIRHNLSLHTRFIRV--QNEGTGKSSWWML 167
Cdd:cd20017   5 SYIALIAMAIQNAPDKKITLNGIYQFIMDRFPFYRE-----NKQGWQNSIRHNLSLNECFVKVprDDKKPGKGSYWTL 77

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 34610227  92 SYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKDkgdsnSSAGWKNSIRHNLSLHTRFIRVQNE--GTGKSSWWMLNP 169
Cdd:cd20019   5 SYIALIAMAIANSPERKLTLGGIYKFIMERFPFYRD-----NSKKWQNSIRHNLTLNDCFVKIPREpgRPGKGNYWTLDP 79

                        90       100
                ....*....|....*....|....
gi 34610227 170 EggktgktprrrAVSMDNGAKFLR 193
Cdd:cd20019  80 A-----------AEDMFDNGSFLR 92

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        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34610227  92 SYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKDkgdsnSSAGWKNSIRHNLSLHTRFIRV--QNEGTGKSSWWMLNP 169
Cdd:cd20044  10 SYIALITMAIQNAPDKKITLNGIYQFIMERFPFYRD-----NKQGWQNSIRHNLSLNECFVKVprDDKKPGKGSYWTLDP 84

                .
gi 34610227 170 E 170
Cdd:cd20044  85 D 85

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        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34610227  92 SYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKdkgdsNSSAGWKNSIRHNLSLHTRFIRV--QNEGTGKSSWWMLNP 169
Cdd:cd20055   7 SYAQLIVQAITMAPDKQLTLNGIYTHITKNYPYYR-----TADKGWQNSIRHNLSLNRYFIKVprSQEEPGKGSFWRIDP 81

Forkhead (FH) domain found in Forkhead box protein N2 (FOXN2); FOXN2, also called human T-cell leukemia virus enhancer factor (HTLF), is a potential tumor suppressor that can facilitate replication fork reversal. It acts as a transcription factor that binds to the purine-rich region in human T-cell leukemia virus long terminal repeat (HTLV-I LTR). It may be a potential therapeutic and radiosensitization target for lung cancer. FOXN2 has also been found to be down-regulated in breast cancer, where it regulates migration, invasion, and epithelial-mesenchymal transition. 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 34610227  92 SYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFkdkgdSNSSAGWKNSIRHNLSLHTRFIRVQ---NEGTGKSSWWMLN 168
Cdd:cd20058   6 SFSLLIYMAIEHSPNKCLPVKEIYSWILEHFPYF-----STAPTGWKNSVRHNLSLNKCFRKVErshGKVNGKGSLWCVD 80

                ..
gi 34610227 169 PE 170
Cdd:cd20058  81 PE 82

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        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34610227  92 SYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKDkgdsnSSAGWKNSIRHNLSLHTRFIRV--QNEGTGKSSWWMLNP 169
Cdd:cd20045   7 SYIALITMAIQNAPDKKITLNGIYQFIMDRFPFYRE-----NKQGWQNSIRHNLSLNECFVKVprDDKKPGKGSYWTLDP 81

                .
gi 34610227 170 E 170
Cdd:cd20045  82 D 82

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        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34610227  92 SYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKDKgdsnsSAGWKNSIRHNLSLHTRFIRVQNE--GTGKSSWWMLNP 169
Cdd:cd20048   5 SYIALITMAILQSPHKRLTLSGICAFISGRFPYYRRK-----FPAWQNSIRHNLSLNDCFVKIPREpgHPGKGNYWSLDP 79

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        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34610227  92 SYADLITKAIESAPDKRLTLSQIYDW-MVRYVPYFKDKgdsnssAGWKNSIRHNLSLHTRFIRV--QNEGTGKSSWWMLN 168
Cdd:cd20037   6 SYIALIAMAIQSSPGQRATLSGIYRYiMGRFAFYRHNR------PGWQNSIRHNLSLNECFVKVprDDRKPGKGSYWTLD 79

                ..
gi 34610227 169 PE 170
Cdd:cd20037  80 PD 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        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34610227  92 SYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKdkgdsNSSAGWKNSIRHNLSLHTRFIRVQN--EGTGKSSWWMLNP 169
Cdd:cd20041   5 SYISLITMAIQNSPNKMVTLSEIYQFIMDLFPFYR-----QNQQRWQNSIRHSLSFNDCFVKVPRtpDKPGKGSFWTLHP 79

                ...
gi 34610227 170 EGG 172
Cdd:cd20041  80 DSG 82

Forkhead (FH) domain found in the Forkhead box protein R (FOXR) subfamily; The FOXR subfamily includes two winged helix transcription factors, FOXR1-2. FOXR1, also called Forkhead box protein N5 (FOXN5), is required for proper cell division and survival possibly via the p21 and mTOR pathways. FOXR2, also called Forkhead box protein N6 (FOXN6), is an important player in a wide range of cellular processes such as proliferation, migration, differentiation, and apoptosis. 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 34610227  91 LSYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKDkgdsnSSAGWKNSIRHNLSLHTRF----IRVQNEGTGKSSWWM 166
Cdd:cd20036   6 LSYPNLIALALRNSETGSLNVQEIYDFIRFHFPFFRT-----APDGWKNSVRHNLSFSDSFekvpTSVSGYGGRRSCLWK 80

                ....*
gi 34610227 167 LNPEG 171
Cdd:cd20036  81 LTPEG 85

Forkhead (FH) domain found in Forkhead box proteins FOXD1, FOXD2 and similar proteins; 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. It has been found that long noncoding RNA FOXD2 adjacent opposite strand RNA1 (lncRNA FOXD2-AS1) expression is upregulated in various human malignancies, including gastric, lung, bladder, colorectal, nasopharyngeal, esophageal, hepatocellular, thyroid and skin cancer. It is a promising candidate as a new biomarker and therapeutic target for cancer diagnosis/prognostication due to high tissue specificity and elevated efficiency. 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 34610227  92 SYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKDKgdsnsSAGWKNSIRHNLSLHTRFIRVQNE--GTGKSSWWMLNP 169
Cdd:cd20046   5 SYIALITMAILQSPKKRLTLSEICEFISNRFPYYREK-----FPAWQNSIRHNLSLNDCFVKIPREpgNPGKGNYWTLDP 79

                        90
                ....*....|....*
gi 34610227 170 EGG---KTGKTPRRR 181
Cdd:cd20046  80 ESAdmfDNGSFLRRR 94

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        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 34610227  92 SYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKDKgdsnsSAGWKNSIRHNLSLHTRFIRVQNE--GTGKSSWWMLN 168
Cdd:cd20018   5 SYIALITMAILQSPQKKLTLSGICEFIMNRFPYYREK-----FPAWQNSIRHNLSLNDCFVKIPREpgNPGKGNYWTLD 78

Forkhead (FH) domain found in Forkhead box protein D3 (FOXD3) and similar proteins; 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. The FH domain is a winged helix DNA-binding domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34610227  92 SYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKDKgdsnsSAGWKNSIRHNLSLHTRFIRVQNE--GTGKSSWWMLNP 169
Cdd:cd20047   6 SYIALITMAILQSPQKKLTLSGICEFISNRFPYYREK-----FPAWQNSIRHNLSLNDCFVKIPREpgNPGKGNYWTLDP 80

                        90
                ....*....|....*
gi 34610227 170 EGG---KTGKTPRRR 181
Cdd:cd20047  81 QSEdmfDNGSFLRRR 95

Forkhead (FH) domain found in Forkhead box protein N1 (FOXN1); 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. It is also an important factor in controlling the skin wound healing process, as it actively participates in re-epithelialization and is responsible for scar formation. 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 34610227  92 SYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKDKGDsnssaGWKNSIRHNLSLHTRFIRVQNE---GTGKSSWWMLN 168
Cdd:cd20056   6 SYSILIFMALKNSKTGSLPVSEIYNFMTEHFPYFKTAPD-----GWKNSVRHNLSLNKCFEKVENKsgsSSRKGCLWALN 80

                .
gi 34610227 169 P 169
Cdd:cd20056  81 P 81

Forkhead (FH) domain found in the Forkhead box protein H (FOXH) subfamily; The FOXH subfamily includes a winged helix transcription factor, FOXH1, which is also called Forkhead activin signal transducer 1 (Fast-1), or Forkhead activin signal transducer 2 (Fast-2). FOXH1 acts as a transcriptional activator that recognizes and binds to the DNA sequence 5'-TGT[GT][GT]ATT-3'. It is required for induction of the goosecoid (GSC) promoter by TGF-beta or activin signaling. FOXH1 forms a transcriptionally active complex containing FOXH1/SMAD2/SMAD4 on a site on the GSC promoter called TARE (TGF-beta/activin response element). 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 34610227  92 SYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKdkgdsNSSAGWKNSIRHNLSLHTRFIRVQNE---GTGKSSWW 165
Cdd:cd20022   5 SYLAMIALAIQNSPEKRLTLSEIIKALSTMFPFFK-----GEYKGWKDSVRHNLSSNDCFVKVLKDpgkPQAKGNYW 76

Forkhead (FH) domain found in Forkhead box protein B2 (FOXB2) and similar proteins; FOXB2, also called transcription factor FKH-4, may act as a transcription factor. It may also 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        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34610227  78 RKAKSSRRNAWGNLSYADLITKAIESAPDKRLTLSQIYDWMVRYVPYFKDkgdsnSSAGWKNSIRHNLSLHTRFIRV--Q 155
Cdd:cd20043   3 RPGKNSYSDQKPPYSYISLTAMAIQSSQEKMLPLSDIYKFIMDRFPYYRE-----NTQRWQNSLRHNLSFNDCFIKIprR 77

                        90       100
                ....*....|....*....|....*....
gi 34610227 156 NEGTGKSSWWMLNPEGG---KTGKTPRRR 181
Cdd:cd20043  78 PDQPGKGSFWALHPDCGdmfENGSFLRRR 106

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 34610227   358 PPALGSLRRLPMQTIQENKQASF 380
Cdd:pfam16675   6 QPSMNSLRQMPMQTIQENKQSSF 28