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 672048900 499 VRPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENVKGAVWTVDEVEYQK 578
Cdd:cd20065    1 VRPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENVKGAVWTVDEVEYQK 80

                 ..
gi 672048900 579 RR 580
Cdd:cd20065   81 RR 82

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672048900 473 RRHSDKYNIPMSSEIAPNYE--------FYKnadvrPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATW 544
Cdd:COG5025   56 LDYSNSLNRSVGSEEIQAYAklagsnwtYYV-----PPYSYATGRGLAILNSPDKPLTLSKIYTWIHNTFFYYAKVVSRW 130

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672048900 545 KNAVRHNLSLHKCFVRVEN-----VKGAVWTVDEVEYQKR---------------------RSQKITGSPT----LVKNI 594
Cdd:COG5025  131 QNSIRHNLSLNDAFIKIEGrngakVKGHFWSIGPGHETQFlksglrldgggkqmmftlpssTEIKITYSSThsmpLLESN 210

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672048900 595 PTSLGYGAALNASLQAALAESSLPLLSNPGLINNASSGLLQA-VHEDLNGSLDHIDSN----GNSSPGCSPQPHIHSIHV 669
Cdd:COG5025  211 DSLNSNNERELLDIIKSSALIRIPADSSSNLDVSLGHHISQPsTHTPVLDNHSSGEENisriNNSSQIDSPTPNYRMSSI 290

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|...
gi 672048900 670 KEE---PVIAEDEDCPM-----SLVTTANHSPELEDDREIEEE 704
Cdd:COG5025  291 DSSvnpSRLANNKDEGRkgsksSPVPKDAAPPSTLSDLSADVN 333

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 672048900 499 VRPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENVKGAVWTVDEVEYQK 578
Cdd:cd20065    1 VRPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENVKGAVWTVDEVEYQK 80

                 ..
gi 672048900 579 RR 580
Cdd:cd20065   81 RR 82

Forkhead domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 672048900  500 RPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENV-----KGAVWTVDE 573
Cdd:pfam00250   1 KPPYSYAALIAMAILSSPEKKLTLSEIYEWISENFPYYRTADKGWQNSIRHNLSLNKCFVKVPRPkdepgKGSYWTIDP 79

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672048900 496 NADVRPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENV-----KGAVWT 570
Cdd:COG5025  333 NRTSKPAFSYANSITQAILSSPSGKMTLSEIYSWISSNLPYYRHKPTAWQNSIRHNLSLNKSFEKVPRSasqpgKGCFWK 412

                         90       100
                 ....*....|....*....|....
gi 672048900 571 VDEVEYQKRRSQKITGSPTLVKNI 594
Cdd:COG5025  413 IDYSYIYEKESKRNPRSPKKSPSA 436

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 672048900 499 VRPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENVKGAVWTVDEVEYQK 578
Cdd:cd20065    1 VRPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENVKGAVWTVDEVEYQK 80

                 ..
gi 672048900 579 RR 580
Cdd:cd20065   81 RR 82

Forkhead (FH) domain found in the Forkhead box protein P (FOXP) subfamily; The FOXP subfamily includes four winged helix transcription factors, FOXP1-4. They are involved in the development of the central nervous system. Mutations in FOXP1, also called Mac-1-regulated Forkhead (MFH), leads to developmental delay, intellectual disability, autism spectrum disorder, speech delay, and dysmorphic features. FOXP2, also called CAG repeat protein 44 or Trinucleotide repeat-containing gene 10 protein, is a transcriptional repressor that may play a role in the specification and differentiation of lung epithelium. It may also play a role in developing neural, gastrointestinal and cardiovascular tissues. FOXP3, also called Scurfin, is a transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg). FOXP4, also called Forkhead-related protein-like A, is a transcriptional repressor that represses lung-specific expression. It is necessary for normal T cell cytokine recall responses to antigen following pathogenic infection. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 672048900 500 RPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENVKGAVWTVD 572
Cdd:cd20033    1 RPPFTYASLIRQAILESPNKQLTLNEIYNWFQKTFAYFRRNAATWKNAVRHNLSLHKCFVRVENVKGAVWTVD 73

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 672048900 497 ADVRPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENVKGAVWTVDEVEY 576
Cdd:cd20064    1 AEVRPPFTYASLIRQAILESPEKQLTLNEIYNWFTRMFAYFRRNAATWKNAVRHNLSLHKCFVRVENVKGAVWTVDEIEF 80

                 ....*..
gi 672048900 577 QKRRSQK 583
Cdd:cd20064   81 QKRRPQK 87

Forkhead domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 672048900  500 RPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENV-----KGAVWTVDE 573
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 672048900 501 PPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENV-----KGAVWT 570
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 672048900 500 RPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRV---ENVKGAVWTVDEV-- 574
Cdd:cd20035    1 KPSHSYVALIAKAILSSPEKKLVLSDIYQYIEENYPYFKSRGSSWKNSVRHNLSLNECFVKAgraENGKGNYWTIHPAcl 80

                         90
                 ....*....|....*
gi 672048900 575 ------EYQKRRSQK 583
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 672048900 500 RPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRV-----ENVKGAVWTVD 572
Cdd:cd20023    1 KPPYSYATLICMAMQASKKTKITLSAIYKWITDNFMYYRVADPTWQNSIRHNLSLNKCFIKVprskdEPGKGGFWRID 78

Forkhead (FH) domain found in the Forkhead box protein O (FOXO) subfamily; The FOXO subfamily includes several winged helix transcription factors: FOXO1, FOXO3, FOXO4 and FOXO6. FOXO transcription factors are involved in the regulation of longevity phenomenon via insulin and insulin-like growth factor signaling. All FOXOs bind to the consensus sequence 5'-GTAAACAA-3', known as the DAF-16 family member-binding element, which includes the core sequence 5'-(A/C)AA(C/T)A-3' recognized by all FOX family members. FOXO1, also called Forkhead box protein O1A or Forkhead in rhabdomyosarcoma (FKHR), is a transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress. FOXO3, also called AF6q21 protein or Forkhead in rhabdomyosarcoma-like 1 (FKHRL1), is a transcriptional activator which triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress. It recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3'. FOXO4, also called Fork head domain transcription factor AFX1, is a transcription factor involved in the regulation of the insulin signaling pathway. It binds to insulin-response elements (IREs) and can activate transcription of IGFBP1. FOXO6 acts as a transcriptional activator that may play an important role on tumor invasion, metastasis, and prognosis. The FH domain is a winged helix DNA-binding domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 672048900 502 PFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNA-----ATWKNAVRHNLSLHKCFVRVENV---KGAVWTVD 572
Cdd:cd20032    2 NMSYADLITKAIESSPDKRLTLQQIYDWMVRNVPYFKDKGdsnssAGWKNSIRHNLSLHSRFVRVQNEgtgKSSWWTLN 80

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 672048900 500 RPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRV-----ENVKGAVWTVD 572
Cdd:cd20021    1 KPPFSYNALIMMAIRQSPEKRLTLNGIYEFIMKNFPYYRENKQGWQNSIRHNLSLNKCFVKVprhydDPGKGNYWMLD 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 672048900 500 RPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRV-----ENVKGAVWTVD 572
Cdd:cd20051    2 KPPYSYATLITYAINSSPAKKMTLSEIYRWICDNFPYYRNAGVGWKNSIRHNLSLNKCFRKVprprdDPGKGSYWMID 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 672048900 500 RPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRV 561
Cdd:cd20034    1 KPPYSYIALIAMAIRDSPSGRLTLAEINEYLMKKFPFFRGSYTGWRNSVRHNLSLNDCFVKV 62

Forkhead (FH) domain found in the Forkhead box protein C (FOXC) subfamily; The FOXC subfamily includes two winged helix transcription factors, FOXC1 (also called Forkhead-related protein FKHL7, or Forkhead-related transcription factor 3) and FOXC2 (also called Forkhead-related protein FKHL14, or Mesenchyme fork head protein 1). FOXC1 is a DNA-binding transcriptional factor that plays a role in a broad range of cellular and developmental processes such as the development of the eyes, bones, cardiovascular system, kidneys, and skin. FOXC2 acts as a transcriptional activator that might be involved in the formation of special mesenchymal tissues. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 672048900 500 RPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRV-----ENVKGAVWTV 571
Cdd:cd20017    1 KPPYSYIALIAMAIQNAPDKKITLNGIYQFIMDRFPFYRENKQGWQNSIRHNLSLNECFVKVprddkKPGKGSYWTL 77

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 672048900 500 RPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVE------NVKGAVWTVD 572
Cdd:cd20058    2 KPPYSFSLLIYMAIEHSPNKCLPVKEIYSWILEHFPYFSTAPTGWKNSVRHNLSLNKCFRKVErshgkvNGKGSLWCVD 80

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 672048900 500 RPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENV-----KGAVWTVD 572
Cdd:cd20019    1 KPPYSYIALIAMAIANSPERKLTLGGIYKFIMERFPFYRDNSKKWQNSIRHNLTLNDCFVKIPREpgrpgKGNYWTLD 78

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 672048900 501 PPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRV---ENV--KGAVWTVD 572
Cdd:cd20025    1 PPYSYSALIAMAIQSAPEKKLTLSQIYQYVAENFPFYKRSKAGWQNSIRHNLSLNDCFKKVprdEDDpgKGNYWTLD 77

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 672048900 500 RPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRV-----ENVKGAVWTVD-- 572
Cdd:cd20054    3 KPPYSYAQLIVQAISSAQDRQLTLSGIYAHITKHYPYYRTADKGWQNSIRHNLSLNRYFIKVprsqeEPGKGSFWRIDpa 82

                         90
                 ....*....|....*....
gi 672048900 573 ------EVEYQKRRSQKIT 585
Cdd:cd20054   83 seaklvEQAFRKRRQRGVS 101

Forkhead (FH) domain found in Forkhead box protein C2 (FOXC2) and similar proteins; FOXC2, also called Forkhead-related protein FKHL14, Mesenchyme fork head protein 1 (MFH-1 protein), or transcription factor FKH-14, acts as a transcriptional activator that might be involved in the formation of special mesenchymal tissues. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672048900 499 VRPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRV-----ENVKGAVWTVDE 573
Cdd:cd20045    2 VKPPYSYIALITMAIQNAPDKKITLNGIYQFIMDRFPFYRENKQGWQNSIRHNLSLNECFVKVprddkKPGKGSYWTLDP 81

                 ...
gi 672048900 574 VEY 576
Cdd:cd20045   82 DSY 84

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 672048900 500 RPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVEN------VKGAVWTVD 572
Cdd:cd20022    1 KPPYSYLAMIALAIQNSPEKRLTLSEIIKALSTMFPFFKGEYKGWKDSVRHNLSSNDCFVKVLKdpgkpqAKGNYWTVD 79

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 672048900 500 RPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENV-----KGAVWTV 571
Cdd:cd20038   14 KPPYSYISLITMAIQQAPSKMLTLSEIYQWIMDLFPYYRQNQQRWQNSIRHSLSFNDCFVKVARSpdkpgKGSYWTL 90

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 672048900 500 RPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENV-----KGAVWTV 571
Cdd:cd20039    5 KPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSpdkpgKGSFWTL 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 672048900 504 TYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFR-----RNAATWKNAVRHNLSLHKCFVRVEN 563
Cdd:cd20062    8 SYAELISQAIESSPEKRLTLAQIYEWMVKSVPYFKdkgdsNSSAGWKNSIRHNLSLHSKFIKVHN 72

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 672048900 500 RPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENV-----KGAVWTVD 572
Cdd:cd20048    1 KPPYSYIALITMAILQSPHKRLTLSGICAFISGRFPYYRRKFPAWQNSIRHNLSLNDCFVKIPREpghpgKGNYWSLD 78

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 672048900 500 RPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENV-----KGAVWTVD 572
Cdd:cd20018    1 KPPYSYIALITMAILQSPQKKLTLSGICEFIMNRFPYYREKFPAWQNSIRHNLSLNDCFVKIPREpgnpgKGNYWTLD 78

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 672048900 503 FTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFR-----RNAATWKNAVRHNLSLHKCFVRVENV---KGAVWTVD 572
Cdd:cd20061    4 LSYADLITRAIESSPDKRLTLSQIYDWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFIRVQNEgtgKSSWWMIN 81

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 672048900 500 RPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENV-----KGAVWTVD 572
Cdd:cd20046    1 KPPYSYIALITMAILQSPKKRLTLSEICEFISNRFPYYREKFPAWQNSIRHNLSLNDCFVKIPREpgnpgKGNYWTLD 78

Forkhead (FH) domain found in Forkhead box protein D3 (FOXD3) and similar proteins; FOXD3, also called HNF3/FH transcription factor genesis, acts as a transcriptional repressor that binds to the consensus sequence 5'-A[AT]T[AG]TTTGTTT-3'. It also acts as a transcriptional activator. It promotes development of neural crest cells from neural tube progenitors and restricts neural progenitor cells to the neural crest lineage while suppressing interneuron differentiation. FOXD3 is required for maintenance of pluripotent cells in the pre-implantation and peri-implantation stages of embryogenesis. The FH domain is a winged helix DNA-binding domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 672048900 499 VRPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENV-----KGAVWTVD 572
Cdd:cd20047    1 VKPPYSYIALITMAILQSPQKKLTLSGICEFISNRFPYYREKFPAWQNSIRHNLSLNDCFVKIPREpgnpgKGNYWTLD 79

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 672048900 500 RPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENV------KGAVWTVDE 573
Cdd:cd20056    2 KPIYSYSILIFMALKNSKTGSLPVSEIYNFMTEHFPYFKTAPDGWKNSVRHNLSLNKCFEKVENKsgsssrKGCLWALNP 81

                 ....*....
gi 672048900 574 VEYQKRRSQ 582
Cdd:cd20056   82 AKIDKMQEE 90

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 672048900 503 FTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFR-----RNAATWKNAVRHNLSLHKCFVRVEN 563
Cdd:cd20060   13 LSYADLITKAIESSAEKRLTLSQIYEWMVKSVPYFKdkgdsNSSAGWKNSIRHNLSLHSKFIRVQN 78

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672048900 496 NADVRPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENV-----KGAVWT 570
Cdd:COG5025  333 NRTSKPAFSYANSITQAILSSPSGKMTLSEIYSWISSNLPYYRHKPTAWQNSIRHNLSLNKSFEKVPRSasqpgKGCFWK 412

                         90       100
                 ....*....|....*....|....
gi 672048900 571 VDEVEYQKRRSQKITGSPTLVKNI 594
Cdd:COG5025  413 IDYSYIYEKESKRNPRSPKKSPSA 436

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 672048900 500 RPPFTYATLIRQAIMESSDRQLTLNEIYSwFTRT-FAYFRRNAATWKNAVRHNLSLHKCFVRVE 562
Cdd:cd20036    3 KPPLSYPNLIALALRNSETGSLNVQEIYD-FIRFhFPFFRTAPDGWKNSVRHNLSFSDSFEKVP 65