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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 313569800 337 RPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVESEKGAVWTVDEFEFRKK 416
Cdd:cd20066    1 RPPFTYASLIRWAILESPEKQLTLNEIYHWFTRMFAFFRNNTATWKNAVRHNLSLHKCFVRVENEKGAVWTVDELEFQRR 80

                 .
gi 313569800 417 R 417
Cdd:cd20066   81 R 81

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 313569800 337 RPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVESEKGAVWTVDEFEFRKK 416
Cdd:cd20066    1 RPPFTYASLIRWAILESPEKQLTLNEIYHWFTRMFAFFRNNTATWKNAVRHNLSLHKCFVRVENEKGAVWTVDELEFQRR 80

                 .
gi 313569800 417 R 417
Cdd:cd20066   81 R 81

Forkhead domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 313569800  337 RPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVESE-----KGAVWTVDE 410
Cdd:pfam00250   1 KPPYSYAALIAMAILSSPEKKLTLSEIYEWISENFPYYRTADKGWQNSIRHNLSLNKCFVKVPRPkdepgKGSYWTIDP 79

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 313569800 335 NMRPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRV-----ESEKGAVWTVD 409
Cdd:COG5025  335 TSKPAFSYANSITQAILSSPSGKMTLSEIYSWISSNLPYYRHKPTAWQNSIRHNLSLNKSFEKVprsasQPGKGCFWKID 414

                         90       100
                 ....*....|....*....|..
gi 313569800 410 E----FEFRKKRSQRPNKCSNP 427
Cdd:COG5025  415 YsyiyEKESKRNPRSPKKSPSA 436

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 313569800 337 RPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVESEKGAVWTVDEFEFRKK 416
Cdd:cd20066    1 RPPFTYASLIRWAILESPEKQLTLNEIYHWFTRMFAFFRNNTATWKNAVRHNLSLHKCFVRVENEKGAVWTVDELEFQRR 80

                 .
gi 313569800 417 R 417
Cdd:cd20066   81 R 81

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 313569800 336 MRPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVESEKGAVWTVDEFEFRK 415
Cdd:cd20065    1 VRPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENVKGAVWTVDEVEYQK 80

                 ..
gi 313569800 416 KR 417
Cdd:cd20065   81 RR 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 313569800 336 MRPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVESEKGAVWTVDEFEFRK 415
Cdd:cd20064    3 VRPPFTYASLIRQAILESPEKQLTLNEIYNWFTRMFAYFRRNAATWKNAVRHNLSLHKCFVRVENVKGAVWTVDEIEFQK 82

                 ....*
gi 313569800 416 KRSQR 420
Cdd:cd20064   83 RRPQK 87

Forkhead domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 313569800  337 RPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVESE-----KGAVWTVDE 410
Cdd:pfam00250   1 KPPYSYAALIAMAILSSPEKKLTLSEIYEWISENFPYYRTADKGWQNSIRHNLSLNKCFVKVPRPkdepgKGSYWTIDP 79

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 313569800 338 PPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVESE-----KGAVWT 407
Cdd:cd00059    1 PPYSYAALIALAILSSPDKRLTLSEIYKWIEDNFPYYRTATKGWKNSIRHNLSLNKCFVKVPREpsdpgKGSYWT 75

Forkhead (FH) domain found in Forkhead box protein Q2 (FOXQ2) and similar proteins; FOXQ2 is the neurogenic ectoderm specification transcription factor that controls aboral development in cnidarians and anterior identity in bilaterians. It plays essential roles in epidermal development and central brain patterning. The foxQ2 gene is absent in placental mammals. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 313569800 337 RPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRV---ESEKGAVWTV----- 408
Cdd:cd20035    1 KPSHSYVALIAKAILSSPEKKLVLSDIYQYIEENYPYFKSRGSSWKNSVRHNLSLNECFVKAgraENGKGNYWTIhpacl 80

                         90
                 ....*....|....*
gi 313569800 409 DEFE---FRKKRSQR 420
Cdd:cd20035   81 EDFEkgdFRRRRARR 95

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 313569800 337 RPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRV-----ESEKGAVWTVD 409
Cdd:cd20023    1 KPPYSYATLICMAMQASKKTKITLSAIYKWITDNFMYYRVADPTWQNSIRHNLSLNKCFIKVprskdEPGKGGFWRID 78

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 313569800 337 RPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRV-----ESEKGAVWTVD 409
Cdd:cd20051    2 KPPYSYATLITYAINSSPAKKMTLSEIYRWICDNFPYYRNAGVGWKNSIRHNLSLNKCFRKVprprdDPGKGSYWMID 79

Forkhead (FH) domain found in Forkhead box protein J3 (FOXJ3) and similar proteins; FOXJ3 is a transcription factor which regulates sperm function. It transcriptionally activates Mef2c and regulates adult skeletal muscle fiber type identity. Polymorphisms in the FOXJ3 gene may be associated with the development of rheumatoid arthritis. 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 313569800 337 RPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRV-----ESEKGAVWTVD 409
Cdd:cd20052    2 KPPYSYANLITFAINSSPKKKMTLSEIYQWICDNFPYYREAGNGWKNSIRHNLSLNKCFLKVprskdDPGKGSYWAID 79

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 313569800 337 RPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVESE-----KGAVWTVD-- 409
Cdd:cd20028    1 KPPYSYVALIAMAIRESPEKRLTLSGIYQYIIAKFPYYEKNKKGWQNSIRHNLSLNECFVKVPREgggerKGNYWTLDpa 80

                 ....*..
gi 313569800 410 -EFEFRK 415
Cdd:cd20028   81 cEDMFEK 87

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 313569800 337 RPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVESE-----KGAVWTVD 409
Cdd:cd20019    1 KPPYSYIALIAMAIANSPERKLTLGGIYKFIMERFPFYRDNSKKWQNSIRHNLTLNDCFVKIPREpgrpgKGNYWTLD 78

Forkhead (FH) domain found in Forkhead box protein N3 (FOXN3); FOXN3, also called checkpoint suppressor 1 (CHES1), acts as a transcriptional repressor that may be involved in DNA damage-inducible cell cycle arrests (checkpoints). It displays transcriptional inhibitory activity, and is involved in cell cycle regulation and tumorigenesis. Alterations in FOXN3 are found in of a variety of cancers including melanoma, osteosarcoma, and hepatocellular carcinoma. FOXN3 also regulates hepatic glucose utilization/metabolism by regulating gluconeogenic substrate selection. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 313569800 337 RPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVESE------KGAVWTVDE 410
Cdd:cd20059    1 KPPYSFSCLIFMAIEDSPTKRLPVKDIYNWILEHFPYFANAPTGWKNSVRHNLSLNKCFKKVDKEkgqsigKGSLWCIDP 80

                 ....
gi 313569800 411 fEFR 414
Cdd:cd20059   81 -EYR 83

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 313569800 337 RPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVESE------KGAVWTVD 409
Cdd:cd20022    1 KPPYSYLAMIALAIQNSPEKRLTLSEIIKALSTMFPFFKGEYKGWKDSVRHNLSSNDCFVKVLKDpgkpqaKGNYWTVD 79

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 313569800 337 RPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRV 398
Cdd:cd20034    1 KPPYSYIALIAMAIRDSPSGRLTLAEINEYLMKKFPFFRGSYTGWRNSVRHNLSLNDCFVKV 62

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 313569800 336 MRPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVESE-----KGAVWTVD 409
Cdd:cd20045    2 VKPPYSYIALITMAIQNAPDKKITLNGIYQFIMDRFPFYRENKQGWQNSIRHNLSLNECFVKVPRDdkkpgKGSYWTLD 80

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 313569800 337 RPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVESE------KGAVWTVD 409
Cdd:cd20058    2 KPPYSFSLLIYMAIEHSPNKCLPVKEIYSWILEHFPYFSTAPTGWKNSVRHNLSLNKCFRKVERShgkvngKGSLWCVD 80

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 313569800 337 RPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRV-----ESEKGAVWTVD-- 409
Cdd:cd20055    3 KPPYSYAQLIVQAITMAPDKQLTLNGIYTHITKNYPYYRTADKGWQNSIRHNLSLNRYFIKVprsqeEPGKGSFWRIDpa 82

                         90
                 ....*....|....*.
gi 313569800 410 ------EFEFRKKRSQ 419
Cdd:cd20055   83 seskliEQAFRKRRPR 98

Forkhead (FH) domain found in Forkhead box protein A1 (FOXA1) and similar proteins; FOXA1, also called hepatocyte nuclear factor 3-alpha (HNF-3-alpha or HNF-3A) or transcription factor 3A (TCF-3A), acts as a transcription factor that is essential for epithelial lineage differentiation. It has been found to be upregulated in numerous 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 313569800 333 YHNMRPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVESE-----KGAVWT 407
Cdd:cd20038   10 YPHAKPPYSYISLITMAIQQAPSKMLTLSEIYQWIMDLFPYYRQNQQRWQNSIRHSLSFNDCFVKVARSpdkpgKGSYWT 89

                 .
gi 313569800 408 V 408
Cdd:cd20038   90 L 90

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 313569800 340 FTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFR-----NHPATWKNAIRHNLSLHKCFVRVESE---KGAVWTVD 409
Cdd:cd20061    4 LSYADLITRAIESSPDKRLTLSQIYDWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFIRVQNEgtgKSSWWMIN 81

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 313569800 341 TYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFR-----NHPATWKNAIRHNLSLHKCFVRVESE---KGAVWTVD 409
Cdd:cd20062    8 SYAELISQAIESSPEKRLTLAQIYEWMVKSVPYFKdkgdsNSSAGWKNSIRHNLSLHSKFIKVHNEatgKSSWWMLN 84

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 313569800 341 TYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFR-----NHPATWKNAIRHNLSLHKCFVRVESE---KGAVWTVD 409
Cdd:cd20063    4 SYADLITKAIESSPDKRLTLSQIYDWMVRYVPYFKdkgdsNSSAGWKNSIRHNLSLHTRFIRVQNEgtgKSSWWMLN 80

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 313569800 337 RPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVESE-----KGAVWTVD 409
Cdd:cd20018    1 KPPYSYIALITMAILQSPQKKLTLSGICEFIMNRFPYYREKFPAWQNSIRHNLSLNDCFVKIPREpgnpgKGNYWTLD 78

Forkhead (FH) domain found in Forkhead box protein A3 (FOXA3) and similar proteins; FOXA3, also called hepatocyte nuclear factor 3-gamma (HNF-3-gamma or HNF-3G), fork head-related protein FKH H3, or transcription factor 3G (TCF-3G), acts as an essential transcriptional regulator engaged in adipogenesis and energy 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 313569800 337 RPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVESE-----KGAVWTV 408
Cdd:cd20040    3 KPPYSYISLITMAIQQAPSKMLTLNEIYQWIMDLFPYYRENQQRWQNSIRHSLSFNDCFVKVARSpdkpgKGSYWAL 79

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 313569800 337 RPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRV-----ESEKGAVWTV 408
Cdd:cd20016    1 KPPYSYISLTAMAIQSSPEKMLPLSDIYKFIMDRFPYYRKNTQRWQNSLRHNLSFNDCFIKIprrpdRPGKGSYWAL 77

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 313569800 337 RPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVESE-----KGAVWTV 408
Cdd:cd20039    5 KPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSpdkpgKGSFWTL 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 313569800 338 PPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVESE-----KGAVWTVD--- 409
Cdd:cd20050    1 PPYSYIALIVMAIQSSPSKKLTLSEIYQFLQARFPFFRGAYQGWKNSVRHNLSLNECFIKLPKGlgrpgKGHYWTIDpas 80

                         90
                 ....*....|.
gi 313569800 410 EFEFRKKRSQR 420
Cdd:cd20050   81 EFMFEEGSFRR 91

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 313569800 333 YHNMRPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRV-----ESEKGAVWT 407
Cdd:cd20042    2 YSDQKPPYSYISLTAMAIQSSPEKMLPLSEIYKFIMDRFPYYRENTQRWQNSLRHNLSFNDCFIKIprrpdQPGKGSFWA 81

                 .
gi 313569800 408 V 408
Cdd:cd20042   82 L 82

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 313569800 337 RPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVE------SEKGAVWTVDE 410
Cdd:cd20056    2 KPIYSYSILIFMALKNSKTGSLPVSEIYNFMTEHFPYFKTAPDGWKNSVRHNLSLNKCFEKVEnksgssSRKGCLWALNP 81

                 ....*....
gi 313569800 411 FEFRKKRSQ 419
Cdd:cd20056   82 AKIDKMQEE 90

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 313569800 334 HNMRPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVE------SEKGAVWT 407
Cdd:cd20057    3 HYPKPIYSYSCLIAMALKNSKTGSLPVSEIYSFMKEHFPYFKTAPDGWKNSVRHNLSLNKCFEKVEnkmsgsSRKGCLWA 82

                 ..
gi 313569800 408 VD 409
Cdd:cd20057   83 LN 84

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 313569800 335 NMRPPFTYATLIRWAILEAPERQRTLNEIYHWFTRMFAYFRNHPATWKNAIRHNLSLHKCFVRVESEK 402
Cdd:cd20036    1 WPKPPLSYPNLIALALRNSETGSLNVQEIYDFIRFHFPFFRTAPDGWKNSVRHNLSFSDSFEKVPTSV 68