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 157822733 156 WGNLSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFMRVQNEGTGKSSWWII 235
Cdd:cd20061    1 WGNLSYADLITRAIESSPDKRLTLSQIYDWMVRCVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFIRVQNEGTGKSSWWMI 80

                 ...
gi 157822733 236 NPD 238
Cdd:cd20061   81 NPD 83

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 157822733  605 KFPSDLDLDMFNGSLECDMESIIRSELMDADGLDFNFDS 643
Cdd:pfam16676   1 RLPSDLDLDMFQGSLECDVDSIIRNDLMDGDGLDFNFDS 39

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 157822733 156 WGNLSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFMRVQNEGTGKSSWWII 235
Cdd:cd20061    1 WGNLSYADLITRAIESSPDKRLTLSQIYDWMVRCVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFIRVQNEGTGKSSWWMI 80

                 ...
gi 157822733 236 NPD 238
Cdd:cd20061   81 NPD 83

Forkhead domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157822733  158 NLSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRV--QNEGTGKSSWWII 235
Cdd:pfam00250   3 PYSYAALIAMAILSSPEKKLTLSEIYEWISENFPYYR-----TADKGWQNSIRHNLSLNKCFVKVprPKDEPGKGSYWTI 77

                  ...
gi 157822733  236 NPD 238
Cdd:pfam00250  78 DPE 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 157822733  605 KFPSDLDLDMFNGSLECDMESIIRSELMDADGLDFNFDS 643
Cdd:pfam16676   1 RLPSDLDLDMFQGSLECDVDSIIRNDLMDGDGLDFNFDS 39

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 157822733 156 WGNLSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFMRVQNEGTGKSSWWII 235
Cdd:cd20061    1 WGNLSYADLITRAIESSPDKRLTLSQIYDWMVRCVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFIRVQNEGTGKSSWWMI 80

                 ...
gi 157822733 236 NPD 238
Cdd:cd20061   81 NPD 83

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 157822733 147 RKCSSRRNAWGNLSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFMRVQNEG 226
Cdd:cd20060    1 KSSSSRRNAWGNLSYADLITKAIESSAEKRLTLSQIYEWMVKSVPYFKDKGDSNSSAGWKNSIRHNLSLHSKFIRVQNEG 80

                         90
                 ....*....|....*....
gi 157822733 227 TGKSSWWIINPDGGKSGKA 245
Cdd:cd20060   81 TGKSSWWMLNPEGGKSGKS 99

Forkhead (FH) domain found in Forkhead box protein O4 (FOXO4) and similar proteins; 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. 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 157822733 153 RNAWGNLSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFMRVQNEGTGKSSW 232
Cdd:cd20062    1 RNAWGNQSYAELISQAIESSPEKRLTLAQIYEWMVKSVPYFKDKGDSNSSAGWKNSIRHNLSLHSKFIKVHNEATGKSSW 80

                 ....*.
gi 157822733 233 WIINPD 238
Cdd:cd20062   81 WMLNPE 86

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 157822733 157 GNLSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKGDsnssaGWKNSIRHNLSLHSRFMRVQNEGT--GKSSWW 233
Cdd:cd00059    1 PPYSYAALIALAILSSPDKRLTLSEIYKWIEDNFPYYRTATK-----GWKNSIRHNLSLNKCFVKVPREPSdpGKGSYW 74

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        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157822733  431 STVFGPASLNSLRQSPMQTIQENRPATFSSVSHYGN-QTLQDLLTSDSLSHSDVmMTQSDPLMSQASTAVSAQNARRNVM 509
Cdd:pfam16675   1 KSIYGQPSMNSLRQMPMQTIQENKQSSFGSMSQYGPaGLLQELLTSDSYPHSDI-LTQVDPLMSQASGRVLSQNHRQNSV 79

                  .
gi 157822733  510 L 510
Cdd:pfam16675  80 M 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 157822733 159 LSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDkgdsnSSAGWKNSIRHNLSLHSRFMRV--QNEGTGKSSWWII 235
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 157822733 160 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFK--DKgdsnssaGWKNSIRHNLSLHSRFMRVQ--NEGTGKSSWWII 235
Cdd:cd20026    5 SYAQLIVQAISSAPDKQLTLSGIYAYITKNYPYYRtaDK-------GWQNSIRHNLSLNRYFIKVPrsQEEPGKGSFWRI 77

                 .
gi 157822733 236 N 236
Cdd:cd20026   78 D 78

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        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157822733 160 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKgdsnsSAGWKNSIRHNLSLHSRFMRVQNEGTG--KSSWWIINP 237
Cdd:cd20028    5 SYVALIAMAIRESPEKRLTLSGIYQYIIAKFPYYEKN-----KKGWQNSIRHNLSLNECFVKVPREGGGerKGNYWTLDP 79

                 .
gi 157822733 238 D 238
Cdd:cd20028   80 A 80

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 157822733 160 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRVQNEGT-GKSSWWII 235
Cdd:cd20031    5 SFSCLIFMAIESSPEKALPVKDIYSWIEKHFPYYR-----NAPSGWKNSIRHNLSLNKCFKKVEKEKNkGKGSLWCV 76

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 157822733 160 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDkgdsnSSAGWKNSIRHNLSLHSRFMRVQN--EGTGKSSWWIINP 237
Cdd:cd20021    5 SYNALIMMAIRQSPEKRLTLNGIYEFIMKNFPYYRE-----NKQGWQNSIRHNLSLNKCFVKVPRhyDDPGKGNYWMLDP 79

Forkhead (FH) domain found in the Forkhead box protein I (FOXI) subfamily; The FOXI subfamily includes three human winged helix transcription factors, FOXI1-3, Xenopus laevis FoxI1c, and similar proteins. FOXI1 acts as a transcriptional activator required for the development of normal hearing, sense of balance, and kidney function. FOXI2 may act as a transcriptional activator that plays a possible role in controlling cellular identity. Loss of function mutations in the FOXI2 gene may contribute to ectodermal dysplasia. FOXI3 plays a critical role in the development of the inner ear and jaw. It is a regulator of ectodermal development. 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 157822733 160 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRV--QNEGTGKSSWWIIN 236
Cdd:cd20025    4 SYSALIAMAIQSAPEKKLTLSQIYQYVAENFPFYK-----RSKAGWQNSIRHNLSLNDCFKKVprDEDDPGKGNYWTLD 77

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 157822733 160 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDkgdsnSSAGWKNSIRHNLSLHSRFMRVQNEGT--GKSSWWIINP 237
Cdd:cd20027    7 SYIALIAMAIKSAPDQKVTLNGIYQFIMDRFPYYHD-----NKQGWQNSIRHNLSLNDCFVKVPREKGrpGKGNYWTLDP 81

                 .
gi 157822733 238 D 238
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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 157822733 159 LSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRVQNEgtgKSSWWIIN 236
Cdd:cd20064    7 FTYASLIRQAILESPEKQLTLNEIYNWFTRMFAYFR-----RNAATWKNAVRHNLSLHKCFVRVENV---KGAVWTVD 76

Forkhead (FH) domain found in Forkhead box protein P3 (FOXP3) and similar proteins; FOXP3, also called Scurfin, is a transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg), which are required for maintaining self-tolerance. It may also have intrinsic regulatory function in conventional T (Tconv) cells. A deletion of the Forkhead domain arising from a frame-shift mutation in mouse FOXP3 is linked to the autoimmune disorder scurfy, and a similar congenital disease in humans is known as IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome). 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 157822733 159 LSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRVQNEgtgKSSWWIIN 236
Cdd:cd20066    4 FTYASLIRWAILESPEKQLTLNEIYHWFTRMFAFFR-----NNTATWKNAVRHNLSLHKCFVRVENE---KGAVWTVD 73

Forkhead (FH) domain found in the Forkhead box protein F (FOXF) subfamily; The FOXF subfamily includes two winged helix transcription factors, FOXF1 and FOXF2, both of which are probable transcription activators for a number of lung-specific genes. FOXF1 mutations in sporadic and familial cases of alveolar capillary dysplasia with misaligned pulmonary veins (ACD/MPV) suggest its involvement in ACD/MPV and lung organogenesis. FOXF2 is involved in programming organogenesis and regulating epithelial-to-mesenchymal transition (EMT) and cell proliferation. 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 157822733 159 LSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRV-QNEG-TGKSSWWIIN 236
Cdd:cd20020    3 YSYIALIVMAIQASPTKRLTLSEIYQFLQQRFPFFR-----GPYQGWKNSVRHNLSLNECFIKLpKGLGrPGKGHYWTID 77

                 .
gi 157822733 237 P 237
Cdd:cd20020   78 P 78

Forkhead (FH) domain found in Forkhead box protein P4 (FOXP4) and similar proteins; FOXP4, also called Forkhead-related protein-like A, is a transcriptional repressor that represses lung-specific expression. It is not required for T cell development, but 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157822733 159 LSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRVQNEgtgKSSWWIINPD 238
Cdd:cd20067    4 FTYASLIRQAILETPDRQLTLNEIYNWFTRMFAYFR-----RNTATWKNAVRHNLSLHKCFVRVENV---KGAVWTVDEL 75

                 ....*....
gi 157822733 239 GGKSGKAPR 247
Cdd:cd20067   76 EYQKRRPPK 84

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        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157822733 160 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRV--QNEGTGKSSWWIINP 237
Cdd:cd20023    5 SYATLICMAMQASKKTKITLSAIYKWITDNFMYYR-----VADPTWQNSIRHNLSLNKCFIKVprSKDEPGKGGFWRIDP 79

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 157822733 160 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFkdkgdSNSSAGWKNSIRHNLSLHSRFMRVQ---NEGTGKSSWWIIN 236
Cdd:cd20058    6 SFSLLIYMAIEHSPNKCLPVKEIYSWILEHFPYF-----STAPTGWKNSVRHNLSLNKCFRKVErshGKVNGKGSLWCVD 80

                 ..
gi 157822733 237 PD 238
Cdd:cd20058   81 PE 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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157822733 160 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRV--QNEGTGKSSWWIINP 237
Cdd:cd20055    7 SYAQLIVQAITMAPDKQLTLNGIYTHITKNYPYYR-----TADKGWQNSIRHNLSLNRYFIKVprSQEEPGKGSFWRIDP 81

Forkhead (FH) domain found in Forkhead box protein A2 (FOXA2) and similar proteins; FOXA2, also called hepatocyte nuclear factor 3-beta (HNF-3-beta or HNF-3B) or transcription factor 3B (TCF-3B), acts as a core transcription factor that controls cell differentiation. It is a key transcriptional regulator that maintains airway mucus homeostasis. It may also have an important role in bone metabolism. 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 157822733 160 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRVQN--EGTGKSSWWIINP 237
Cdd:cd20039    9 SYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYR-----QNQQRWQNSIRHSLSFNDCFLKVPRspDKPGKGSFWTLHP 83

                 ...
gi 157822733 238 DGG 240
Cdd:cd20039   84 DSG 86

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        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157822733 159 LSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRV--QNEGTGKSSWWIIN 236
Cdd:cd20054    6 YSYAQLIVQAISSAQDRQLTLSGIYAHITKHYPYYR-----TADKGWQNSIRHNLSLNRYFIKVprSQEEPGKGSFWRID 80

                 .
gi 157822733 237 P 237
Cdd:cd20054   81 P 81

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 157822733 160 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKgdsnsSAGWKNSIRHNLSLHSRFMRVQNE--GTGKSSWWIINP 237
Cdd:cd20048    5 SYIALITMAILQSPHKRLTLSGICAFISGRFPYYRRK-----FPAWQNSIRHNLSLNDCFVKIPREpgHPGKGNYWSLDP 79

                         90
                 ....*....|....*
gi 157822733 238 ---DGGKSGKAPRRR 249
Cdd:cd20048   80 asqDMFDNGSFLRRR 94

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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157822733 160 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRVQNEGTG----KSSWWII 235
Cdd:cd20030    5 SYSCLIAMALKNSRTGCLPVSEIYSFMCENFPYFK-----TAPDGWKNSVRHNLSLNKCFEKIERPDGNgssrKGCLWAL 79

                 ..
gi 157822733 236 NP 237
Cdd:cd20030   80 NP 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 157822733 160 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRVQN--EGTGKSSWWIINP 237
Cdd:cd20041    5 SYISLITMAIQNSPNKMVTLSEIYQFIMDLFPFYR-----QNQQRWQNSIRHSLSFNDCFVKVPRtpDKPGKGSFWTLHP 79

                 ...
gi 157822733 238 DGG 240
Cdd:cd20041   80 DSG 82

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 157822733 160 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKgdsnsSAGWKNSIRHNLSLHSRFMRVQNE--GTGKSSWWIINP 237
Cdd:cd20046    5 SYIALITMAILQSPKKRLTLSEICEFISNRFPYYREK-----FPAWQNSIRHNLSLNDCFVKIPREpgNPGKGNYWTLDP 79

                         90
                 ....*....|....*
gi 157822733 238 DGG---KSGKAPRRR 249
Cdd:cd20046   80 ESAdmfDNGSFLRRR 94

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 157822733 160 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKgdsnsSAGWKNSIRHNLSLHSRFMRVQNE--GTGKSSWWIINP 237
Cdd:cd20047    6 SYIALITMAILQSPQKKLTLSGICEFISNRFPYYREK-----FPAWQNSIRHNLSLNDCFVKIPREpgNPGKGNYWTLDP 80

                         90
                 ....*....|....*
gi 157822733 238 ---DGGKSGKAPRRR 249
Cdd:cd20047   81 qseDMFDNGSFLRRR 95

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 157822733 159 LSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDkgdsnSSAGWKNSIRHNLSLHSRF----MRVQNEGTGKSSWWI 234
Cdd:cd20036    6 LSYPNLIALALRNSETGSLNVQEIYDFIRFHFPFFRT-----APDGWKNSVRHNLSFSDSFekvpTSVSGYGGRRSCLWK 80

                 ....*
gi 157822733 235 INPDG 239
Cdd:cd20036   81 LTPEG 85

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157822733 160 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRVQNE---GTGKSSWWIIN 236
Cdd:cd20022    5 SYLAMIALAIQNSPEKRLTLSEIIKALSTMFPFFK-----GEYKGWKDSVRHNLSSNDCFVKVLKDpgkPQAKGNYWTVD 79

Forkhead (FH) domain found in Forkhead box protein N4 (FOXN4); FOXN4 acts as a transcription factor essential for neural and some non-neural tissue development, such as retina and lung, respectively. During development of the central nervous system, FOXN4 is required in specifying the amacrine and horizontal cell fates from multipotent retinal progenitors, while suppressing alternative photoreceptor cell fates. In non-neural tissues, it plays an essential role in specifying the atrioventricular canal and is indirectly required for patterning the distal airway during lung development. 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 157822733 160 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKGDsnssaGWKNSIRHNLSLHSRFMRVQNEGTG---KSSWWIIN 236
Cdd:cd20057   10 SYSCLIAMALKNSKTGSLPVSEIYSFMKEHFPYFKTAPD-----GWKNSVRHNLSLNKCFEKVENKMSGssrKGCLWALN 84

                 .
gi 157822733 237 P 237
Cdd:cd20057   85 P 85

Transcription factor of the Forkhead/HNF3 family [Transcription];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157822733 150 SSRRNAWGNLSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKGDsnssaGWKNSIRHNLSLHSRFMRVQNE--GT 227
Cdd:COG5025  331 DVNRTSKPAFSYANSITQAILSSPSGKMTLSEIYSWISSNLPYYRHKPT-----AWQNSIRHNLSLNKSFEKVPRSasQP 405

                         90       100
                 ....*....|....*....|....
gi 157822733 228 GKSSWWIINPDGG--KSGKAPRRR 249
Cdd:COG5025  406 GKGCFWKIDYSYIyeKESKRNPRS 429