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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386765427 327 VRPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFVRYEDDFGSFWMVDDNEFVK 406
Cdd:cd20065    1 VRPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENVKGAVWTVDEVEYQK 80

                 ..
gi 386765427 407 RR 408
Cdd:cd20065   81 RR 82

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 386765427 327 VRPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFVRYEDDFGSFWMVDDNEFVK 406
Cdd:cd20065    1 VRPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENVKGAVWTVDEVEYQK 80

                 ..
gi 386765427 407 RR 408
Cdd:cd20065   81 RR 82

Forkhead domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386765427  328 RPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFV---RYEDDF--GSFWMVDD 401
Cdd:pfam00250   1 KPPYSYAALIAMAILSSPEKKLTLSEIYEWISENFPYYRTADKGWQNSIRHNLSLNKCFVkvpRPKDEPgkGSYWTIDP 79

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386765427 324 NADVRPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFVR-----YEDDFGSFWM 398
Cdd:COG5025  333 NRTSKPAFSYANSITQAILSSPSGKMTLSEIYSWISSNLPYYRHKPTAWQNSIRHNLSLNKSFEKvprsaSQPGKGCFWK 412

                         90       100
                 ....*....|....*....|....*...
gi 386765427 399 VD-DNEFVKRRHLSRGRPRKYEPSSSPN 425
Cdd:COG5025  413 IDySYIYEKESKRNPRSPKKSPSAHSVH 440

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 386765427 327 VRPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFVRYEDDFGSFWMVDDNEFVK 406
Cdd:cd20065    1 VRPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENVKGAVWTVDEVEYQK 80

                 ..
gi 386765427 407 RR 408
Cdd:cd20065   81 RR 82

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 386765427 328 RPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFVRYEDDFGSFWMVDDNEFVKR 407
Cdd:cd20066    1 RPPFTYASLIRWAILESPEKQLTLNEIYHWFTRMFAFFRNNTATWKNAVRHNLSLHKCFVRVENEKGAVWTVDELEFQRR 80

                 .
gi 386765427 408 R 408
Cdd:cd20066   81 R 81

Forkhead (FH) domain found in Forkhead box protein P4 (FOXP4) and similar proteins; FOXP4, also called Forkhead-related protein-like A, is a transcriptional repressor that represses lung-specific expression. It is not required for T cell development, but is necessary for normal T cell cytokine recall responses to antigen following pathogenic infection. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386765427 328 RPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFVRYEDDFGSFWMVDDNEFVKR 407
Cdd:cd20067    1 RPPFTYASLIRQAILETPDRQLTLNEIYNWFTRMFAYFRRNTATWKNAVRHNLSLHKCFVRVENVKGAVWTVDELEYQKR 80

                 .
gi 386765427 408 R 408
Cdd:cd20067   81 R 81

Forkhead domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386765427  328 RPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFV---RYEDDF--GSFWMVDD 401
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 386765427 329 PPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFVR-----YEDDFGSFWM 398
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 386765427 328 RPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFV---RYEDDFGSFWMVDD--- 401
Cdd:cd20035    1 KPSHSYVALIAKAILSSPEKKLVLSDIYQYIEENYPYFKSRGSSWKNSVRHNLSLNECFVkagRAENGKGNYWTIHPacl 80

                         90
                 ....*....|...
gi 386765427 402 -----NEFVKRRH 409
Cdd:cd20035   81 edfekGDFRRRRA 93

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 386765427 328 RPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAAT-WKNAIRTNLSLHKCFVR--YEDDFGSFW 397
Cdd:cd20029    1 RPPYSYMALIQFAINSTEDKRMTLKEIYTWIEDHFPYFKHTAKPgWKNSIRHNLSLHDIFVRetSANGKGSFW 73

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 386765427 328 RPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFV---RYEDD--FGSFWMVD 400
Cdd:cd20021    1 KPPFSYNALIMMAIRQSPEKRLTLNGIYEFIMKNFPYYRENKQGWQNSIRHNLSLNKCFVkvpRHYDDpgKGNYWMLD 78

Forkhead (FH) domain found in the Forkhead box protein K (FOXK) subfamily; The FOXK subfamily includes two winged helix transcription factors, FOXK1 and FOXK2. FOXK1, also called myocyte nuclear factor (MNF), acts as a transcriptional regulator that binds to the upstream enhancer region (CCAC box) of myoglobin genes. It positively regulates Wnt/beta-catenin signaling by translocating dishevelled (DVL) proteins into the nucleus. It also reduces virus replication, probably by binding the interferon stimulated response element (ISRE) to promote antiviral gene expression. In addition, FOXK1 plays important roles in multiple human cancers. FOXK2, also called cellular transcription factor ILF-1 or interleukin enhancer-binding factor 1, is a transcriptional regulator that recognizes the core sequence 5'-TAAACA-3'. It binds to NFAT-like motifs (purine-rich) in the IL2 promoter. It also binds to the HIV-1 long terminal repeat. FOXK2 may be involved in both, positive and negative regulation of important viral and cellular promoter elements. In addition, FOXK2 plays a critical role in suppressing tumorigenesis. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386765427 328 RPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFV---RYEDDF--GSFWMVD 400
Cdd:cd20026    1 KPPYSYAQLIVQAISSAPDKQLTLSGIYAYITKNYPYYRTADKGWQNSIRHNLSLNRYFIkvpRSQEEPgkGSFWRID 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 386765427 328 RPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCF---VRYEDD--FGSFWMVD 400
Cdd:cd20051    2 KPPYSYATLITYAINSSPAKKMTLSEIYRWICDNFPYYRNAGVGWKNSIRHNLSLNKCFrkvPRPRDDpgKGSYWMID 79

Forkhead (FH) domain found in the Forkhead box protein F (FOXF) subfamily; The FOXF subfamily includes two winged helix transcription factors, FOXF1 and FOXF2, both of which are probable transcription activators for a number of lung-specific genes. FOXF1 mutations in sporadic and familial cases of alveolar capillary dysplasia with misaligned pulmonary veins (ACD/MPV) suggest its involvement in ACD/MPV and lung organogenesis. FOXF2 is involved in programming organogenesis and regulating epithelial-to-mesenchymal transition (EMT) and cell proliferation. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386765427 329 PPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFVRYEDDF-----GSFWMVDD 401
Cdd:cd20020    1 PPYSYIALIVMAIQASPTKRLTLSEIYQFLQQRFPFFRGPYQGWKNSVRHNLSLNECFIKLPKGLgrpgkGHYWTIDP 78

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 386765427 328 RPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFVRYEDD----FG--SFWMVD 400
Cdd:cd20034    1 KPPYSYIALIAMAIRDSPSGRLTLAEINEYLMKKFPFFRGSYTGWRNSVRHNLSLNDCFVKVLRDpsrpWGkdNYWTIN 79

Forkhead (FH) domain found in Forkhead box protein F1 (FOXF1) and similar proteins; FOXF1, also called Forkhead-related activator 1 (FREAC-1), Forkhead-related protein FKHL5, or Forkhead-related transcription factor 1, is a probable transcription activator for a number of lung-specific genes. FOXF1 mutations in sporadic and familial cases of alveolar capillary dysplasia with misaligned pulmonary veins (ACD/MPV) suggest its involvement in ACD/MPV and lung organogenesis. The role of FOXF1 in cancer is conflicting; its loss in some cancers suggests a tumor suppressive function, but its abundance in others is associated with protumorigenic and metastatic traits. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386765427 329 PPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFVRYEDDFGS-----FWMVDD-N 402
Cdd:cd20049    1 PPYSYIALIVMAIQSSPTKRLTLSEIYQFLQSRFPFFRGSYQGWKNSVRHNLSLNECFIKLPKGLGRpgkghYWTIDPaS 80

                         90
                 ....*....|....*.
gi 386765427 403 EFVKRRHLSRGRPRKY 418
Cdd:cd20049   81 EFMFEEGSFRRRPRGF 96

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 386765427 329 PPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFV---RYEDD--FGSFWMVD 400
Cdd:cd20025    1 PPYSYSALIAMAIQSAPEKKLTLSQIYQYVAENFPFYKRSKAGWQNSIRHNLSLNDCFKkvpRDEDDpgKGNYWTLD 77

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 386765427 327 VRPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFVRYEDD-----FGSFWMVDD 401
Cdd:cd20044    5 VKPPYSYIALITMAIQNAPDKKITLNGIYQFIMERFPFYRDNKQGWQNSIRHNLSLNECFVKVPRDdkkpgKGSYWTLDP 84

                 ...
gi 386765427 402 NEF 404
Cdd:cd20044   85 DSY 87

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386765427 328 RPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFVRY-----EDDFGSFW 397
Cdd:cd20015    1 KPPYSYISLITMAIQQSPSKMLTLSEIYQWIMDLFPYYRQNQQRWQNSIRHSLSFNDCFVKVprspdKPGKGSYW 75

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 386765427 329 PPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFVRYEDDFGS-----FWMVDD-N 402
Cdd:cd20050    1 PPYSYIALIVMAIQSSPSKKLTLSEIYQFLQARFPFFRGAYQGWKNSVRHNLSLNECFIKLPKGLGRpgkghYWTIDPaS 80

                         90
                 ....*....|...
gi 386765427 403 EFVKRRHLSRGRP 415
Cdd:cd20050   81 EFMFEEGSFRRRP 93

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 386765427 328 RPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFVRYEDDF------GSFWMVD 400
Cdd:cd20058    2 KPPYSFSLLIYMAIEHSPNKCLPVKEIYSWILEHFPYFSTAPTGWKNSVRHNLSLNKCFRKVERSHgkvngkGSLWCVD 80

Forkhead (FH) domain found in Forkhead box protein I1 (FOXI1) and similar proteins; FOXI1 is also called Forkhead-related protein FKHL10, Forkhead-related transcription factor 6 (FREAC-6), Hepatocyte nuclear factor 3 Forkhead homolog 3 (HFH-3), or HNF-3/fork-head homolog 3. It is a master regulator of vacuolar H-ATPase proton pump subunits in the inner ear, kidney, and epididymis, and is required for the development of normal hearing, sense of balance, and kidney function. Its epididymal expression is required for male fertility. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386765427 327 VRPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFV---RYEDD--FGSFWMVDD 401
Cdd:cd20053    3 VRPPYSYSALIAMAIHGAPDKRLTLSQIYQYVADNFPFYNKSKAGWQNSIRHNLSLNDCFKkvpRDEDDpgKGNYWTLDP 82

                         90
                 ....*....|....*...
gi 386765427 402 N--EFVKRRHLSRGRPRK 417
Cdd:cd20053   83 NceKMFDNGNFRRKRKRK 100

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 386765427 328 RPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFVRYEDD-----FGSFWMVD-- 400
Cdd:cd20037    2 KPPYSYIALIAMAIQSSPGQRATLSGIYRYIMGRFAFYRHNRPGWQNSIRHNLSLNECFVKVPRDdrkpgKGSYWTLDpd 81

                         90
                 ....*....|....
gi 386765427 401 ------DNEFVKRR 408
Cdd:cd20037   82 chdmfeHGSFLRRR 95

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 386765427 328 RPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFVRY-----EDDFGSFWMV 399
Cdd:cd20039    5 KPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVprspdKPGKGSFWTL 81

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 386765427 328 RPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFVRYEDD-----FGSFWMVD 400
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 386765427 331 FTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFR-----RNAATWKNAIRTNLSLHKCFVRYEDDF---GSFWMVD 400
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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386765427 328 RPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFVRYEDD-----FGSFW----- 397
Cdd:cd20046    1 KPPYSYIALITMAILQSPKKRLTLSEICEFISNRFPYYREKFPAWQNSIRHNLSLNDCFVKIPREpgnpgKGNYWtldpe 80

                         90
                 ....*....|....
gi 386765427 398 ---MVDDNEFVKRR 408
Cdd:cd20046   81 sadMFDNGSFLRRR 94

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 386765427 328 RPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFVRY-----EDDFGSFWMVD-- 400
Cdd:cd20054    3 KPPYSYAQLIVQAISSAQDRQLTLSGIYAHITKHYPYYRTADKGWQNSIRHNLSLNRYFIKVprsqeEPGKGSFWRIDpa 82

                         90
                 ....*....|....*
gi 386765427 401 ------DNEFVKRRH 409
Cdd:cd20054   83 seaklvEQAFRKRRQ 97

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 386765427 332 TYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFR-----RNAATWKNAIRTNLSLHKCFVRYEDD---FGSFWMVD 400
Cdd:cd20063    4 SYADLITKAIESSPDKRLTLSQIYDWMVRYVPYFKdkgdsNSSAGWKNSIRHNLSLHTRFIRVQNEgtgKSSWWMLN 80

Forkhead (FH) domain found in Forkhead box protein O1 (FOXO1); FOXO1, also called Forkhead box protein O1A or Forkhead in rhabdomyosarcoma (FKHR), is a transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress. It binds to the insulin response element (IRE) with the consensus sequence 5'-TT[G/A]TTTTG-3' and the related Daf-16 family binding element (DBE) with the consensus sequence 5'-TT[G/A]TTTAC-3'. The FH domain is a winged helix DNA-binding domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386765427 331 FTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFR-----RNAATWKNAIRTNLSLHKCFVRYEDD---FGSFWMVD 400
Cdd:cd20060   13 LSYADLITKAIESSAEKRLTLSQIYEWMVKSVPYFKdkgdsNSSAGWKNSIRHNLSLHSKFIRVQNEgtgKSSWWMLN 90

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386765427 324 NADVRPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFVR-----YEDDFGSFWM 398
Cdd:COG5025  333 NRTSKPAFSYANSITQAILSSPSGKMTLSEIYSWISSNLPYYRHKPTAWQNSIRHNLSLNKSFEKvprsaSQPGKGCFWK 412

                         90       100
                 ....*....|....*....|....*...
gi 386765427 399 VD-DNEFVKRRHLSRGRPRKYEPSSSPN 425
Cdd:COG5025  413 IDySYIYEKESKRNPRSPKKSPSAHSVH 440

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 386765427 328 RPPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCFVRYED 391
Cdd:cd20057    6 KPIYSYSCLIAMALKNSKTGSLPVSEIYSFMKEHFPYFKTAPDGWKNSVRHNLSLNKCFEKVEN 69

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 386765427 329 PPFTYASLIRQAIIDSPDKQLTLNEIYNWFQNTFCYFRRNAATWKNAIRTNLSLHKCF 386
Cdd:COG5025   87 PPYSYATGRGLAILNSPDKPLTLSKIYTWIHNTFFYYAKVVSRWQNSIRHNLSLNDAF 144