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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17136486  11 NFSIDAILAKKPINTATQPIKTEPVHHHHQYVHP---YSNSDGELS-----ASEDFDSPSRtSTPMSSAAESLSsqnndk 82
Cdd:COG5025 223 DIIKSSALIRIPADSSSNLDVSLGHHISQPSTHTpvlDNHSSGEENisrinNSSQIDSPTP-NYRMSSIDSSVN------ 295

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17136486  83 ldvefDDELEDQLDEDQESEDGNPSKKQKMTA---------GSDTKKPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINR 153
Cdd:COG5025 296 -----PSRLANNKDEGRKGSKSSPVPKDAAPPstlsdlsadVNRTSKPAFSYANSITQAILSSPSGKMTLSEIYSWISSN 370

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 17136486 154 FPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDDPGKGNYWILDPSaeevFIGETTGKLRRKNPGASRTRLAAYRQA 230
Cdd:COG5025 371 LPYYRHKPTAWQNSIRHNLSLNKSFEKVPRSASQPGKGCFWKIDYS----YIYEKESKRNPRSPKKSPSAHSVHQKL 443

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 17136486 120 KPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDDPGKGNYWILDP 198
Cdd:cd20021   1 KPPFSYNALIMMAIRQSPEKRLTLNGIYEFIMKNFPYYRENKQGWQNSIRHNLSLNKCFVKVPRHYDDPGKGNYWMLDP 79

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17136486  11 NFSIDAILAKKPINTATQPIKTEPVHHHHQYVHP---YSNSDGELS-----ASEDFDSPSRtSTPMSSAAESLSsqnndk 82
Cdd:COG5025 223 DIIKSSALIRIPADSSSNLDVSLGHHISQPSTHTpvlDNHSSGEENisrinNSSQIDSPTP-NYRMSSIDSSVN------ 295

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17136486  83 ldvefDDELEDQLDEDQESEDGNPSKKQKMTA---------GSDTKKPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINR 153
Cdd:COG5025 296 -----PSRLANNKDEGRKGSKSSPVPKDAAPPstlsdlsadVNRTSKPAFSYANSITQAILSSPSGKMTLSEIYSWISSN 370

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 17136486 154 FPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDDPGKGNYWILDPSaeevFIGETTGKLRRKNPGASRTRLAAYRQA 230
Cdd:COG5025 371 LPYYRHKPTAWQNSIRHNLSLNKSFEKVPRSASQPGKGCFWKIDYS----YIYEKESKRNPRSPKKSPSAHSVHQKL 443

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 17136486 120 KPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDDPGKGNYWILDP 198
Cdd:cd20021   1 KPPFSYNALIMMAIRQSPEKRLTLNGIYEFIMKNFPYYRENKQGWQNSIRHNLSLNKCFVKVPRHYDDPGKGNYWMLDP 79

Forkhead (FH) domain found in Forkhead box protein L1 (FOXL1) and similar proteins; FOXL1, also called Forkhead-related protein FKHL11 or Forkhead-related transcription factor 7 (FREAC-7), acts as a transcription factor required for proper proliferation and differentiation in the gastrointestinal epithelium. It may play a critical role in suppressing tumorigenesis. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17136486 119 KKPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDDPGKGNYWILDP 198
Cdd:cd20027   2 QKPPYSYIALIAMAIKSAPDQKVTLNGIYQFIMDRFPYYHDNKQGWQNSIRHNLSLNDCFVKVPREKGRPGKGNYWTLDP 81

                        90
                ....*....|....*..
gi 17136486 199 SAEEVFigETTGKLRRK 215
Cdd:cd20027  82 DCEEMF--ENGNYRRRK 96

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 17136486 121 PPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDDPGKGNYW 194
Cdd:cd00059   1 PPYSYAALIALAILSSPDKRLTLSEIYKWIEDNFPYYRTATKGWKNSIRHNLSLNKCFVKVPREPSDPGKGSYW 74

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 17136486 121 PPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDDPGKGNYWILD 197
Cdd:cd20025   1 PPYSYSALIAMAIQSAPEKKLTLSQIYQYVAENFPFYKRSKAGWQNSIRHNLSLNDCFKKVPRDEDDPGKGNYWTLD 77

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 17136486 120 KPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDDPGKGNYWIL 196
Cdd:cd20017   1 KPPYSYIALIAMAIQNAPDKKITLNGIYQFIMDRFPFYRENKQGWQNSIRHNLSLNECFVKVPRDDKKPGKGSYWTL 77

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 17136486 120 KPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDDPGKGNYWILDPS 199
Cdd:cd20037   2 KPPYSYIALIAMAIQSSPGQRATLSGIYRYIMGRFAFYRHNRPGWQNSIRHNLSLNECFVKVPRDDRKPGKGSYWTLDPD 81

                        90
                ....*....|....*.
gi 17136486 200 AEEVFigETTGKLRRK 215
Cdd:cd20037  82 CHDMF--EHGSFLRRR 95

Forkhead (FH) domain found in Forkhead box protein C1 (FOXC1) and similar proteins; FOXC1, also called Forkhead-related protein FKHL7, or Forkhead-related transcription factor 3 (FREAC-3), is a DNA-binding transcriptional factor that plays a role in a broad range of cellular and developmental processes such as the development of the eyes, bones, cardiovascular system, kidneys, and skin. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17136486 117 DTKKPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDDPGKGNYWIL 196
Cdd:cd20044   3 DMVKPPYSYIALITMAIQNAPDKKITLNGIYQFIMERFPFYRDNKQGWQNSIRHNLSLNECFVKVPRDDKKPGKGSYWTL 82

                ....*...
gi 17136486 197 DPSAEEVF 204
Cdd:cd20044  83 DPDSYNMF 90

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 17136486 120 KPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDDPGKGNYWILDP 198
Cdd:cd20023   1 KPPYSYATLICMAMQASKKTKITLSAIYKWITDNFMYYRVADPTWQNSIRHNLSLNKCFIKVPRSKDEPGKGGFWRIDP 79

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 17136486 120 KPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDdpGKGNYWILDPS 199
Cdd:cd20035   1 KPSHSYVALIAKAILSSPEKKLVLSDIYQYIEENYPYFKSRGSSWKNSVRHNLSLNECFVKAGRAEN--GKGNYWTIHPA 78

                        90
                ....*....|....*.
gi 17136486 200 AEEVFIgetTGKLRRK 215
Cdd:cd20035  79 CLEDFE---KGDFRRR 91

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 17136486 120 KPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDDPGKGNYWILDPS 199
Cdd:cd20047   2 KPPYSYIALITMAILQSPQKKLTLSGICEFISNRFPYYREKFPAWQNSIRHNLSLNDCFVKIPREPGNPGKGNYWTLDPQ 81

                        90
                ....*....|....*.
gi 17136486 200 AEEVFigETTGKLRRK 215
Cdd:cd20047  82 SEDMF--DNGSFLRRR 95

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 17136486 120 KPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDDP-GKGNYWILD 197
Cdd:cd20034   1 KPPYSYIALIAMAIRDSPSGRLTLAEINEYLMKKFPFFRGSYTGWRNSVRHNLSLNDCFVKVLRDPSRPwGKDNYWTIN 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 17136486 120 KPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDDPGKGNYWILDP 198
Cdd:cd20016   1 KPPYSYISLTAMAIQSSPEKMLPLSDIYKFIMDRFPYYRKNTQRWQNSLRHNLSFNDCFIKIPRRPDRPGKGSYWALHP 79

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 17136486 121 PPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDDPGKGNYWILDPSA 200
Cdd:cd20050   1 PPYSYIALIVMAIQSSPSKKLTLSEIYQFLQARFPFFRGAYQGWKNSVRHNLSLNECFIKLPKGLGRPGKGHYWTIDPAS 80

                        90
                ....*....|....*
gi 17136486 201 EEVFigeTTGKLRRK 215
Cdd:cd20050  81 EFMF---EEGSFRRR 92

Forkhead (FH) domain found in the Forkhead box protein A (FOXA) subfamily; The FOXA subfamily includes three winged helix transcription factors, FOXA1 (also called hepatocyte nuclear factor 3-alpha or transcription factor 3A), FOXA2 (also called hepatocyte nuclear factor 3-beta or transcription factor 3B), and FOXA3 (also called hepatocyte nuclear factor 3-gamma or transcription factor 3G). FOXA1 is essential for epithelial lineage differentiation and has been found to be upregulated in numerous cancers. FOXA2 controls cell differentiation. It is a key transcriptional regulator that maintains airway mucus homeostasis and may also have an important role in bone metabolism. FOXA3 acts as an essential transcriptional regulator engaged in adipogenesis and energy metabolism. This subfamily also includes Xenopus tropicalis FOXA4, Drosophila melanogaster protein fork head (dFKH), and similar proteins. FOXA4 is only present in amphibians, where it is required for the correct regionalization and maintenance of the central nervous system. dFKH promotes terminal as opposed to segmental development. In the absence of dFKH, this developmental switch does not occur. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17136486 120 KPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDDPGKGNYWILDPS 199
Cdd:cd20015   1 KPPYSYISLITMAIQQSPSKMLTLSEIYQWIMDLFPYYRQNQQRWQNSIRHSLSFNDCFVKVPRSPDKPGKGSYWTLHPD 80

                        90
                ....*....|....*.
gi 17136486 200 AEEVFigETTGKLRRK 215
Cdd:cd20015  81 SGNMF--ENGCYLRRQ 94

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 17136486 120 KPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDDPGKGNYWILDPS 199
Cdd:cd20046   1 KPPYSYIALITMAILQSPKKRLTLSEICEFISNRFPYYREKFPAWQNSIRHNLSLNDCFVKIPREPGNPGKGNYWTLDPE 80

                        90
                ....*....|....*.
gi 17136486 200 AEEVFigETTGKLRRK 215
Cdd:cd20046  81 SADMF--DNGSFLRRR 94

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 17136486 120 KPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDDPGKGNYWILDPS 199
Cdd:cd20055   3 KPPYSYAQLIVQAITMAPDKQLTLNGIYTHITKNYPYYRTADKGWQNSIRHNLSLNRYFIKVPRSQEEPGKGSFWRIDPA 82

                        90
                ....*....|....
gi 17136486 200 AEEVFIGETTGKLR 213
Cdd:cd20055  83 SESKLIEQAFRKRR 96

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 17136486 119 KKPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDDPGKGNYWILDP 198
Cdd:cd20042   5 QKPPYSYISLTAMAIQSSPEKMLPLSEIYKFIMDRFPYYRENTQRWQNSLRHNLSFNDCFIKIPRRPDQPGKGSFWALHP 84

                ....*.
gi 17136486 199 SAEEVF 204
Cdd:cd20042  85 SCGDMF 90

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 17136486 120 KPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDDPGKGNYWILDPS 199
Cdd:cd20038  14 KPPYSYISLITMAIQQAPSKMLTLSEIYQWIMDLFPYYRQNQQRWQNSIRHSLSFNDCFVKVARSPDKPGKGSYWTLHPD 93

                        90
                ....*....|....*.
gi 17136486 200 AEEVFigETTGKLRRK 215
Cdd:cd20038  94 SGNMF--ENGCYLRRQ 107

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 17136486 120 KPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDDP-GKGNYWILDP 198
Cdd:cd20059   1 KPPYSFSCLIFMAIEDSPTKRLPVKDIYNWILEHFPYFANAPTGWKNSVRHNLSLNKCFKKVDKEKGQSiGKGSLWCIDP 80

Forkhead (FH) domain found in Forkhead box protein N2 (FOXN2) and similar proteins; The FOXN2-like group includes two FOXN subfamily winged helix transcription factors, FOXN2 and FOXN3. FOXN2, also called human T-cell leukemia virus enhancer factor (HTLF), is a potential tumor suppressor that can facilitate replication fork reversal. It acts as a transcription factor that binds to the purine-rich region in human T-cell leukemia virus long terminal repeat (HTLV-I LTR). It may be a potential therapeutic and radiosensitization target for lung cancer. FOXN3, also called checkpoint suppressor 1, acts as a transcriptional repressor that may be involved in DNA damage-inducible cell cycle arrests (checkpoints). The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 17136486 120 KPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDDpGKGNYW 194
Cdd:cd20031   1 KPPYSFSCLIFMAIESSPEKALPVKDIYSWIEKHFPYYRNAPSGWKNSIRHNLSLNKCFKKVEKEKNK-GKGSLW 74

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 17136486 120 KPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKI--PRSYDDPGKGNYWILD 197
Cdd:cd20030   1 KPAYSYSCLIAMALKNSRTGCLPVSEIYSFMCENFPYFKTAPDGWKNSVRHNLSLNKCFEKIerPDGNGSSRKGCLWALN 80

                .
gi 17136486 198 P 198
Cdd:cd20030  81 P 81

Forkhead (FH) domain found in the Forkhead box protein M (FOXM) subfamily; The FOXM subfamily includes a winged helix transcription factor, FOXM1, which is also called Forkhead-related protein FKHL16, Hepatocyte nuclear factor 3 Forkhead homolog 11 (HFH-11), HNF-3/fork-head homolog 11, M-phase phosphoprotein 2, MPM-2 reactive phosphoprotein 2, transcription factor Trident, or Winged-helix factor from INS-1 cells. FOXM1 acts as a transcriptional factor regulating the expression of cell cycle genes essential for DNA replication and mitosis. It plays a role in the control of cell proliferation. It is also involved in DNA break repair, participating in the DNA damage checkpoint response. 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 17136486 120 KPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKAN-KRGWQNSIRHNLSLNKCFTKIPRSyddPGKGNYWILDP 198
Cdd:cd20029   1 RPPYSYMALIQFAINSTEDKRMTLKEIYTWIEDHFPYFKHTaKPGWKNSIRHNLSLHDIFVRETSA---NGKGSFWTLRP 77

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 17136486 120 KPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKIPRSyddpgKGNYWILDPS 199
Cdd:cd20065   2 RPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENV-----KGAVWTVDEV 76

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17136486  11 NFSIDAILAKKPINTATQPIKTEPVHHHHQYVHP---YSNSDGELS-----ASEDFDSPSRtSTPMSSAAESLSsqnndk 82
Cdd:COG5025 223 DIIKSSALIRIPADSSSNLDVSLGHHISQPSTHTpvlDNHSSGEENisrinNSSQIDSPTP-NYRMSSIDSSVN------ 295

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17136486  83 ldvefDDELEDQLDEDQESEDGNPSKKQKMTA---------GSDTKKPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINR 153
Cdd:COG5025 296 -----PSRLANNKDEGRKGSKSSPVPKDAAPPstlsdlsadVNRTSKPAFSYANSITQAILSSPSGKMTLSEIYSWISSN 370

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 17136486 154 FPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDDPGKGNYWILDPSaeevFIGETTGKLRRKNPGASRTRLAAYRQA 230
Cdd:COG5025 371 LPYYRHKPTAWQNSIRHNLSLNKSFEKVPRSASQPGKGCFWKIDYS----YIYEKESKRNPRSPKKSPSAHSVHQKL 443

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 17136486 120 KPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKIPRSyddpgKGNYWILD 197
Cdd:cd20064   4 RPPFTYASLIRQAILESPEKQLTLNEIYNWFTRMFAYFRRNAATWKNAVRHNLSLHKCFVRVENV-----KGAVWTVD 76

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 17136486 124 SYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFK-----ANKRGWQNSIRHNLSLNKCFTKIPRsyDDPGKGNYWILDP 198
Cdd:cd20061   5 SYADLITRAIESSPDKRLTLSQIYDWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFIRVQN--EGTGKSSWWMINP 82

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 17136486 124 SYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFK-----ANKRGWQNSIRHNLSLNKCFTKIPRsyDDPGKGNYWILDP 198
Cdd:cd20062   8 SYAELISQAIESSPEKRLTLAQIYEWMVKSVPYFKdkgdsNSSAGWKNSIRHNLSLHSKFIKVHN--EATGKSSWWMLNP 85

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17136486 124 SYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFK-----ANKRGWQNSIRHNLSLNKCFTKIPRsyDDPGKGNYWILDP 198
Cdd:cd20063   4 SYADLITKAIESSPDKRLTLSQIYDWMVRYVPYFKdkgdsNSSAGWKNSIRHNLSLHTRFIRVQN--EGTGKSSWWMLNP 81

                        90
                ....*....|...
gi 17136486 199 SaeevfiGETTGK 211
Cdd:cd20063  82 E------GGKTGK 88

Forkhead (FH) domain found in the Forkhead box protein R (FOXR) subfamily; The FOXR subfamily includes two winged helix transcription factors, FOXR1-2. FOXR1, also called Forkhead box protein N5 (FOXN5), is required for proper cell division and survival possibly via the p21 and mTOR pathways. FOXR2, also called Forkhead box protein N6 (FOXN6), is an important player in a wide range of cellular processes such as proliferation, migration, differentiation, and apoptosis. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 17136486 120 KPPYSYNALIMMAIQDSPEQRLTLNGIYQYLINRFPYFKANKRGWQNSIRHNLSLNKCFTKIPRSYDDPGK 190
Cdd:cd20036   3 KPPLSYPNLIALALRNSETGSLNVQEIYDFIRFHFPFFRTAPDGWKNSVRHNLSFSDSFEKVPTSVSGYGG 73