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 4503739  157 WGNLSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFMRVQNEGTGKSSWWII 236
Cdd:cd20061   1 WGNLSYADLITRAIESSPDKRLTLSQIYDWMVRCVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFIRVQNEGTGKSSWWMI 80

                ...
gi 4503739  237 NPD 239
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 4503739    606 KFPSDLDLDMFNGSLECDMESIIRSELMDADGLDFNFDS 644
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 4503739  157 WGNLSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFMRVQNEGTGKSSWWII 236
Cdd:cd20061   1 WGNLSYADLITRAIESSPDKRLTLSQIYDWMVRCVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFIRVQNEGTGKSSWWMI 80

                ...
gi 4503739  237 NPD 239
Cdd:cd20061  81 NPD 83

Forkhead domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503739    159 NLSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRV--QNEGTGKSSWWII 236
Cdd:pfam00250   3 PYSYAALIAMAILSSPEKKLTLSEIYEWISENFPYYR-----TADKGWQNSIRHNLSLNKCFVKVprPKDEPGKGSYWTI 77

                  ...
gi 4503739    237 NPD 239
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 4503739    606 KFPSDLDLDMFNGSLECDMESIIRSELMDADGLDFNFDS 644
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 4503739  157 WGNLSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFMRVQNEGTGKSSWWII 236
Cdd:cd20061   1 WGNLSYADLITRAIESSPDKRLTLSQIYDWMVRCVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFIRVQNEGTGKSSWWMI 80

                ...
gi 4503739  237 NPD 239
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 4503739  148 RKCSSRRNAWGNLSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFMRVQNEG 227
Cdd:cd20060   1 KSSSSRRNAWGNLSYADLITKAIESSAEKRLTLSQIYEWMVKSVPYFKDKGDSNSSAGWKNSIRHNLSLHSKFIRVQNEG 80

                        90
                ....*....|....*....
gi 4503739  228 TGKSSWWIINPDGGKSGKA 246
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 4503739  154 RNAWGNLSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFMRVQNEGTGKSSW 233
Cdd:cd20062   1 RNAWGNQSYAELISQAIESSPEKRLTLAQIYEWMVKSVPYFKDKGDSNSSAGWKNSIRHNLSLHSKFIKVHNEATGKSSW 80

                ....*.
gi 4503739  234 WIINPD 239
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 4503739  158 GNLSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKGDsnssaGWKNSIRHNLSLHSRFMRVQNEGT--GKSSWW 234
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 4503739    432 STVFGPSSLNSLRQSPMQTIQENKPATFSSMSHYGN-QTLQDLLTSDSLSHSDVmMTQSDPLMSQASTAVSAQNSRRNVM 510
Cdd:pfam16675   1 KSIYGQPSMNSLRQMPMQTIQENKQSSFGSMSQYGPaGLLQELLTSDSYPHSDI-LTQVDPLMSQASGRVLSQNHRQNSV 79

                  .
gi 4503739    511 L 511
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 4503739  160 LSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDkgdsnSSAGWKNSIRHNLSLHSRFMRV--QNEGTGKSSWWII 236
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 4503739  161 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFK--DKgdsnssaGWKNSIRHNLSLHSRFMRVQ--NEGTGKSSWWII 236
Cdd:cd20026   5 SYAQLIVQAISSAPDKQLTLSGIYAYITKNYPYYRtaDK-------GWQNSIRHNLSLNRYFIKVPrsQEEPGKGSFWRI 77

                .
gi 4503739  237 N 237
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 4503739  161 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKgdsnsSAGWKNSIRHNLSLHSRFMRVQNEGTG--KSSWWIINP 238
Cdd:cd20028   5 SYVALIAMAIRESPEKRLTLSGIYQYIIAKFPYYEKN-----KKGWQNSIRHNLSLNECFVKVPREGGGerKGNYWTLDP 79

                .
gi 4503739  239 D 239
Cdd:cd20028  80 A 80

Forkhead (FH) domain found in Forkhead box protein J2 (FOXJ2) and similar proteins; FOXJ2, also called Fork head 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. It is specifically expressed in meiotic spermatocytes in adult mouse testes and appears to promote meiotic progression during spermatogenesis. 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 4503739  161 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRV--QNEGTGKSSWWIIN 237
Cdd:cd20051   6 SYATLITYAINSSPAKKMTLSEIYRWICDNFPYYR-----NAGVGWKNSIRHNLSLNKCFRKVprPRDDPGKGSYWMID 79

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 4503739    606 KFPSDLDLDMFNGSLECDMESIIRSELMDADGLDFNFDS 644
Cdd:pfam16676   1 RLPSDLDLDMFQGSLECDVDSIIRNDLMDGDGLDFNFDS 39

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 4503739  161 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRV--QNEGTGKSSWWIIN 237
Cdd:cd20025   4 SYSALIAMAIQSAPEKKLTLSQIYQYVAENFPFYK-----RSKAGWQNSIRHNLSLNDCFKKVprDEDDPGKGNYWTLD 77

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        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503739  160 LSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRVQNEGT---GKSSWWII 236
Cdd:cd20034   4 YSYIALIAMAIRDSPSGRLTLAEINEYLMKKFPFFR-----GSYTGWRNSVRHNLSLNDCFVKVLRDPSrpwGKDNYWTI 78

                .
gi 4503739  237 N 237
Cdd:cd20034  79 N 79

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 4503739  160 LSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRVQNEgtgKSSWWIIN 237
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 4503739  160 LSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRVQNEgtgKSSWWIIN 237
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 4503739  160 LSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRV-QNEG-TGKSSWWIIN 237
Cdd:cd20020   3 YSYIALIVMAIQASPTKRLTLSEIYQFLQQRFPFFR-----GPYQGWKNSVRHNLSLNECFIKLpKGLGrPGKGHYWTID 77

                .
gi 4503739  238 P 238
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 4503739  160 LSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRVQNEgtgKSSWWIINPD 239
Cdd:cd20067   4 FTYASLIRQAILETPDRQLTLNEIYNWFTRMFAYFR-----RNTATWKNAVRHNLSLHKCFVRVENV---KGAVWTVDEL 75

                ....*....
gi 4503739  240 GGKSGKAPR 248
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 4503739  161 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRV--QNEGTGKSSWWIINP 238
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 4503739  161 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFkdkgdSNSSAGWKNSIRHNLSLHSRFMRVQ---NEGTGKSSWWIIN 237
Cdd:cd20058   6 SFSLLIYMAIEHSPNKCLPVKEIYSWILEHFPYF-----STAPTGWKNSVRHNLSLNKCFRKVErshGKVNGKGSLWCVD 80

                ..
gi 4503739  238 PD 239
Cdd:cd20058  81 PE 82

Forkhead (FH) domain found in Forkhead box protein I1 (FOXI1) and similar proteins; FOXI1 is also called Forkhead-related protein FKHL10, Forkhead-related transcription factor 6 (FREAC-6), Hepatocyte nuclear factor 3 Forkhead homolog 3 (HFH-3), or HNF-3/fork-head homolog 3. It is a master regulator of vacuolar H-ATPase proton pump subunits in the inner ear, kidney, and epididymis, and is required for the development of normal hearing, sense of balance, and kidney function. Its epididymal expression is required for male fertility. 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 4503739  161 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFkdkgdSNSSAGWKNSIRHNLSLHSRFMRV--QNEGTGKSSWWIINP 238
Cdd:cd20053   8 SYSALIAMAIHGAPDKRLTLSQIYQYVADNFPFY-----NKSKAGWQNSIRHNLSLNDCFKKVprDEDDPGKGNYWTLDP 82

                        90
                ....*....|....*
gi 4503739  239 DGGK---SGKAPRRR 250
Cdd:cd20053  83 NCEKmfdNGNFRRKR 97

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 4503739  161 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRV--QNEGTGKSSWWIINP 238
Cdd:cd20055   7 SYAQLIVQAITMAPDKQLTLNGIYTHITKNYPYYR-----TADKGWQNSIRHNLSLNRYFIKVprSQEEPGKGSFWRIDP 81

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 4503739  161 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDkgdsnSSAGWKNSIRHNLSLHSRFMRV--QNEGTGKSSWWIINP 238
Cdd:cd20037   6 SYIALIAMAIQSSPGQRATLSGIYRYIMGRFAFYRH-----NRPGWQNSIRHNLSLNECFVKVprDDRKPGKGSYWTLDP 80

                .
gi 4503739  239 D 239
Cdd:cd20037  81 D 81

Forkhead (FH) domain found in Forkhead box protein F1 (FOXF1) and similar proteins; FOXF1, also called Forkhead-related activator 1 (FREAC-1), Forkhead-related protein FKHL5, or Forkhead-related transcription factor 1, is a probable transcription activator 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. The role of FOXF1 in cancer is conflicting; its loss in some cancers suggests a tumor suppressive function, but its abundance in others is associated with protumorigenic and metastatic traits. 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 4503739  161 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRVQN--EGTGKSSWWIINP 238
Cdd:cd20049   4 SYIALIVMAIQSSPTKRLTLSEIYQFLQSRFPFFR-----GSYQGWKNSVRHNLSLNECFIKLPKglGRPGKGHYWTIDP 78

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 4503739  161 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRVQNEGTG----KSSWWII 236
Cdd:cd20030   5 SYSCLIAMALKNSRTGCLPVSEIYSFMCENFPYFK-----TAPDGWKNSVRHNLSLNKCFEKIERPDGNgssrKGCLWAL 79

                ..
gi 4503739  237 NP 238
Cdd:cd20030  80 NP 81

Forkhead (FH) domain found in Forkhead box protein F2 (FOXF2) and similar proteins; FOXF2, also called Forkhead-related activator 2 (FREAC-2), Forkhead-related protein FKHL6, or Forkhead-related transcription factor 2, is a probable transcription activator for a number of lung-specific genes. It is involved in programming organogenesis and regulating epithelial-to-mesenchymal transition (EMT) and cell proliferation. FOXF2 dysregulation is critical for tumorigenesis of various tissue types. Its expression correlates with good prognosis in patients with early non-invasive stages of breast cancer, but with poor prognosis in advanced breast cancer. 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 4503739  161 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFMRVQNE--GTGKSSWWIINP 238
Cdd:cd20050   4 SYIALIVMAIQSSPSKKLTLSEIYQFLQARFPFFR-----GAYQGWKNSVRHNLSLNECFIKLPKGlgRPGKGHYWTIDP 78

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 4503739  161 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKgdsnsSAGWKNSIRHNLSLHSRFMRVQNE--GTGKSSWWIINP 238
Cdd:cd20046   5 SYIALITMAILQSPKKRLTLSEICEFISNRFPYYREK-----FPAWQNSIRHNLSLNDCFVKIPREpgNPGKGNYWTLDP 79

                        90
                ....*....|....*
gi 4503739  239 DGG---KSGKAPRRR 250
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 4503739  161 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKgdsnsSAGWKNSIRHNLSLHSRFMRVQNE--GTGKSSWWIINP 238
Cdd:cd20047   6 SYIALITMAILQSPQKKLTLSGICEFISNRFPYYREK-----FPAWQNSIRHNLSLNDCFVKIPREpgNPGKGNYWTLDP 80

                        90
                ....*....|....*
gi 4503739  239 ---DGGKSGKAPRRR 250
Cdd:cd20047  81 qseDMFDNGSFLRRR 95

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        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503739  161 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDkgdsnSSAGWKNSIRHNLSLHSRFMRVQNEGT--GKSSWWIINP 238
Cdd:cd20016   5 SYISLTAMAIQSSPEKMLPLSDIYKFIMDRFPYYRK-----NTQRWQNSLRHNLSFNDCFIKIPRRPDrpGKGSYWALHP 79

Forkhead (FH) domain found in Forkhead box protein B1 (FOXB1) and similar proteins; FOXB1, also called transcription factor FKH-5, is a winged helix transcription factor that 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. 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 4503739  161 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDkgdsnSSAGWKNSIRHNLSLHSRFMRV--QNEGTGKSSWWIINP 238
Cdd:cd20042  10 SYISLTAMAIQSSPEKMLPLSEIYKFIMDRFPYYRE-----NTQRWQNSLRHNLSFNDCFIKIprRPDQPGKGSFWALHP 84

                ...
gi 4503739  239 DGG 241
Cdd:cd20042  85 SCG 87

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 4503739  161 SYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKGDsnssaGWKNSIRHNLSLHSRFMRVQNEGTG---KSSWWIIN 237
Cdd:cd20057  10 SYSCLIAMALKNSKTGSLPVSEIYSFMKEHFPYFKTAPD-----GWKNSVRHNLSLNKCFEKVENKMSGssrKGCLWALN 84

                .
gi 4503739  238 P 238
Cdd:cd20057  85 P 85

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503739  151 SSRRNAWGNLSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKGDsnssaGWKNSIRHNLSLHSRFMRVQNE--GT 228
Cdd:COG5025 331 DVNRTSKPAFSYANSITQAILSSPSGKMTLSEIYSWISSNLPYYRHKPT-----AWQNSIRHNLSLNKSFEKVPRSasQP 405

                        90       100
                ....*....|....*....|....
gi 4503739  229 GKSSWWIINPDGG--KSGKAPRRR 250
Cdd:COG5025 406 GKGCFWKIDYSYIyeKESKRNPRS 429