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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328708966  92 GNQSYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFEKIQNEGTGKSSWWQIN 171
Cdd:cd20032    1 GNMSYADLITKAIESSPDKRLTLQQIYDWMVRNVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFVRVQNEGTGKSSWWTLN 80

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328708966  92 GNQSYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFEKIQNEGTGKSSWWQIN 171
Cdd:cd20032    1 GNMSYADLITKAIESSPDKRLTLQQIYDWMVRNVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFVRVQNEGTGKSSWWTLN 80

Forkhead domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328708966   93 NQSYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFEKI--QNEGTGKSSWWQI 170
Cdd:pfam00250   3 PYSYAALIAMAILSSPEKKLTLSEIYEWISENFPYYR-----TADKGWQNSIRHNLSLNKCFVKVprPKDEPGKGSYWTI 77

                  .
gi 328708966  171 N 171
Cdd:pfam00250  78 D 78

Transactivation domain of FOXO protein family; TAD is a promiscuous binding domain that mediates the association of the transcription factor FOXO with the coactivator CBP/p300. Both this domain and the FOXO-KIX_bd family pfam16675 bind simultaneously the KIX domain of CBP/p300. Coactivator CBP/p300 is recruited by FOXO3 though binding to these two regions. The promiscuity of the TAD is further evidenced by that the finding that they also bind the TAZ1 and TAZ2 domains of CBP/p300.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 328708966  379 SHLSFDELNINLdkfppvECNVDEVISHEVSLGGCLDFnNFNP 421
Cdd:pfam16676   4 SDLDLDMFQGSL------ECDVDSIIRNDLMDGDGLDF-NFDS 39

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328708966  92 GNQSYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFEKIQNEGTGKSSWWQIN 171
Cdd:cd20032    1 GNMSYADLITKAIESSPDKRLTLQQIYDWMVRNVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFVRVQNEGTGKSSWWTLN 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328708966  82 KKTSSRRNAWGNQSYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFEKIQNEG 161
Cdd:cd20060    1 KSSSSRRNAWGNLSYADLITKAIESSAEKRLTLSQIYEWMVKSVPYFKDKGDSNSSAGWKNSIRHNLSLHSKFIRVQNEG 80

                         90       100
                 ....*....|....*....|
gi 328708966 162 TGKSSWWQINHNASRtTGKS 181
Cdd:cd20060   81 TGKSSWWMLNPEGGK-SGKS 99

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 328708966  92 GNQSYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFEKIQNEGTGKSSWWQIN 171
Cdd:cd20063    1 GNLSYADLITKAIESSPDKRLTLSQIYDWMVRYVPYFKDKGDSNSSAGWKNSIRHNLSLHTRFIRVQNEGTGKSSWWMLN 80

                 ....*.
gi 328708966 172 HNASRT 177
Cdd:cd20063   81 PEGGKT 86

FORKHEAD; FORKHEAD, also known as a "winged helix"

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328708966    91 WGNQSYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKDKGDsnssaGWKNSIRHNLSLHSRFEKIQNEGT--GKSSWW 168
Cdd:smart00339   1 KPPYSYIALIAMAILSSPDKRLTLSEIYKWIEDNFPYYRENRA-----GWQNSIRHNLSLNDCFVKVPREGDrpGKGSYW 75

                   ....*..
gi 328708966   169 QINHNAS 175
Cdd:smart00339  76 TLDPAAE 82

Forkhead (FH) domain found in Forkhead box proteins, FOXJ2, FOXJ3 and similar proteins; The FOXJ2-like subfamily includes two winged helix transcription factors, FOXJ2 and FOXJ3. FOXJ2, also called Forkhead homologous X (FHX), plays an important role in tumorigenesis, progression, and metastasis of certain cancers. It acts as a transcriptional activator that can bind to two different type of DNA binding sites. FOXJ3 is a transcription factor which regulates sperm function. It transcriptionally activates Mef2c and regulates adult skeletal muscle fiber type identity. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 328708966  94 QSYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKDkgdsnSSAGWKNSIRHNLSLHSRFEKI--QNEGTGKSSWWQI 170
Cdd:cd20024    4 YSYATLITFAINSSPKKKMTLSEIYTWICENFPYYRE-----AGTGWKNSIRHNLSLNKCFKKVprSKDDPGKGSYWTL 77

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328708966  95 SYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFK--DKgdsnssaGWKNSIRHNLSLHSRFEKIQ--NEGTGKSSWWQI 170
Cdd:cd20026    5 SYAQLIVQAISSAPDKQLTLSGIYAYITKNYPYYRtaDK-------GWQNSIRHNLSLNRYFIKVPrsQEEPGKGSFWRI 77

                 .
gi 328708966 171 N 171
Cdd:cd20026   78 D 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 328708966  95 SYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFEKI--QNEGTGKSSWWQIN 171
Cdd:cd20051    6 SYATLITYAINSSPAKKMTLSEIYRWICDNFPYYR-----NAGVGWKNSIRHNLSLNKCFRKVprPRDDPGKGSYWMID 79

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 328708966  95 SYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKDKgdsnsSAGWKNSIRHNLSLHSRFEKIQNEGTG--KSSWWQIN 171
Cdd:cd20028    5 SYVALIAMAIRESPEKRLTLSGIYQYIIAKFPYYEKN-----KKGWQNSIRHNLSLNECFVKVPREGGGerKGNYWTLD 78

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 328708966  95 SYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKDkgdsnSSAGWKNSIRHNLSLHSRFEKIQN--EGTGKSSWWQIN 171
Cdd:cd20021    5 SYNALIMMAIRQSPEKRLTLNGIYEFIMKNFPYYRE-----NKQGWQNSIRHNLSLNKCFVKVPRhyDDPGKGNYWMLD 78

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 328708966  95 SYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKDKgdsnsSAGWKNSIRHNLSLHSRFEKIQNegtGKSSWWQIN 171
Cdd:cd20033    5 TYASLIRQAILESPNKQLTLNEIYNWFQKTFAYFRRN-----AATWKNAVRHNLSLHKCFVRVEN---VKGAVWTVD 73

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 328708966  95 SYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFEKI--QNEGTGKSSWWQIN 171
Cdd:cd20023    5 SYATLICMAMQASKKTKITLSAIYKWITDNFMYYR-----VADPTWQNSIRHNLSLNKCFIKVprSKDEPGKGGFWRID 78

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 328708966  95 SYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFkdkgdSNSSAGWKNSIRHNLSLHSRFEKI--QNEGTGKSSWWQINH 172
Cdd:cd20053    8 SYSALIAMAIHGAPDKRLTLSQIYQYVADNFPFY-----NKSKAGWQNSIRHNLSLNDCFKKVprDEDDPGKGNYWTLDP 82

                         90
                 ....*....|....
gi 328708966 173 NASRT--TGKSRRR 184
Cdd:cd20053   83 NCEKMfdNGNFRRK 96

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 328708966  95 SYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFEKIQNEGTG----KSSWWQI 170
Cdd:cd20030    5 SYSCLIAMALKNSRTGCLPVSEIYSFMCENFPYFK-----TAPDGWKNSVRHNLSLNKCFEKIERPDGNgssrKGCLWAL 79

                 .
gi 328708966 171 N 171
Cdd:cd20030   80 N 80

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 328708966  95 SYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFEKIQNEgtgKSSWWQIN 171
Cdd:cd20064    8 TYASLIRQAILESPEKQLTLNEIYNWFTRMFAYFR-----RNAATWKNAVRHNLSLHKCFVRVENV---KGAVWTVD 76

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 328708966  95 SYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFEKIQNE---GTGKSSWWQIN 171
Cdd:cd20059    5 SFSCLIFMAIEDSPTKRLPVKDIYNWILEHFPYFA-----NAPTGWKNSVRHNLSLNKCFKKVDKEkgqSIGKGSLWCID 79

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 328708966  95 SYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFEKIQNEgtgKSSWWQIN 171
Cdd:cd20065    6 TYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFR-----RNAATWKNAVRHNLSLHKCFVRVENV---KGAVWTVD 74

Forkhead (FH) domain found in Forkhead box protein P3 (FOXP3) and similar proteins; FOXP3, also called Scurfin, is a transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg), which are required for maintaining self-tolerance. It may also have intrinsic regulatory function in conventional T (Tconv) cells. A deletion of the Forkhead domain arising from a frame-shift mutation in mouse FOXP3 is linked to the autoimmune disorder scurfy, and a similar congenital disease in humans is known as IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome). The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 328708966  95 SYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFEKIQNEgtgKSSWWQIN 171
Cdd:cd20066    5 TYASLIRWAILESPEKQLTLNEIYHWFTRMFAFFR-----NNTATWKNAVRHNLSLHKCFVRVENE---KGAVWTVD 73

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328708966  95 SYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKDKgdsnsSAGWKNSIRHNLSLHSRFEKIQNE--GTGKSSWWQINH 172
Cdd:cd20048    5 SYIALITMAILQSPHKRLTLSGICAFISGRFPYYRRK-----FPAWQNSIRHNLSLNDCFVKIPREpgHPGKGNYWSLDP 79

                 ..
gi 328708966 173 NA 174
Cdd:cd20048   80 AS 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 328708966  95 SYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKDKgdsnsSAGWKNSIRHNLSLHSRFEKIQNE--GTGKSSWWQIN 171
Cdd:cd20018    5 SYIALITMAILQSPQKKLTLSGICEFIMNRFPYYREK-----FPAWQNSIRHNLSLNDCFVKIPREpgNPGKGNYWTLD 78

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 328708966  95 SYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKDkgdsnSSAGWKNSIRHNLSLHSRFEKI--QNEGTGKSSWWQINH 172
Cdd:cd20045    7 SYIALITMAIQNAPDKKITLNGIYQFIMDRFPFYRE-----NKQGWQNSIRHNLSLNECFVKVprDDKKPGKGSYWTLDP 81

                 ..
gi 328708966 173 NA 174
Cdd:cd20045   82 DS 83

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 328708966  95 SYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFEKIQNE--GTGKSSWWQIN 171
Cdd:cd20050    4 SYIALIVMAIQSSPSKKLTLSEIYQFLQARFPFFR-----GAYQGWKNSVRHNLSLNECFIKLPKGlgRPGKGHYWTID 77

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 328708966  95 SYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFEKIQN--EGTGKSSWWQINH 172
Cdd:cd20049    4 SYIALIVMAIQSSPTKRLTLSEIYQFLQSRFPFFR-----GSYQGWKNSVRHNLSLNECFIKLPKglGRPGKGHYWTIDP 78

                         90
                 ....*....|....
gi 328708966 173 NASRT--TGKSRRR 184
Cdd:cd20049   79 ASEFMfeEGSFRRR 92

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 328708966  95 SYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKDKgdsnsSAGWKNSIRHNLSLHSRFEKIQNE--GTGKSSWWQINH 172
Cdd:cd20046    5 SYIALITMAILQSPKKRLTLSEICEFISNRFPYYREK-----FPAWQNSIRHNLSLNDCFVKIPREpgNPGKGNYWTLDP 79

                         90       100       110
                 ....*....|....*....|....*....|
gi 328708966 173 NAsrttgksrrrAVSMETPKFEKKRGRVKK 202
Cdd:cd20046   80 ES----------ADMFDNGSFLRRRKRFKR 99

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 328708966  95 SYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKDKgdsnsSAGWKNSIRHNLSLHSRFEKIQNE--GTGKSSWWQIN 171
Cdd:cd20047    6 SYIALITMAILQSPQKKLTLSGICEFISNRFPYYREK-----FPAWQNSIRHNLSLNDCFVKIPREpgNPGKGNYWTLD 79

Forkhead (FH) domain found in Forkhead box protein N4 (FOXN4); FOXN4 acts as a transcription factor essential for neural and some non-neural tissue development, such as retina and lung, respectively. During development of the central nervous system, FOXN4 is required in specifying the amacrine and horizontal cell fates from multipotent retinal progenitors, while suppressing alternative photoreceptor cell fates. In non-neural tissues, it plays an essential role in specifying the atrioventricular canal and is indirectly required for patterning the distal airway during lung development. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328708966  95 SYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKDKGDsnssaGWKNSIRHNLSLHSRFEKIQNEGTG---KSSWWQIN 171
Cdd:cd20057   10 SYSCLIAMALKNSKTGSLPVSEIYSFMKEHFPYFKTAPD-----GWKNSVRHNLSLNKCFEKVENKMSGssrKGCLWALN 84

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 328708966  95 SYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFEKIQN--EGTGKSSWWQINH 172
Cdd:cd20038   18 SYISLITMAIQQAPSKMLTLSEIYQWIMDLFPYYR-----QNQQRWQNSIRHSLSFNDCFVKVARspDKPGKGSYWTLHP 92

                 ..
gi 328708966 173 NA 174
Cdd:cd20038   93 DS 94

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328708966  95 SYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFEKIQNE---GTGKSSWWQIN 171
Cdd:cd20022    5 SYLAMIALAIQNSPEKRLTLSEIIKALSTMFPFFK-----GEYKGWKDSVRHNLSSNDCFVKVLKDpgkPQAKGNYWTVD 79

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328708966  95 SYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFEKIQN--EGTGKSSWWQINH 172
Cdd:cd20039    9 SYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYR-----QNQQRWQNSIRHSLSFNDCFLKVPRspDKPGKGSFWTLHP 83

                 ..
gi 328708966 173 NA 174
Cdd:cd20039   84 DS 85

Forkhead (FH) domain found in Forkhead box protein B2 (FOXB2) and similar proteins; FOXB2, also called transcription factor FKH-4, may act as a transcription factor. It may also act as a tumor suppressor; it has been found to inhibit the malignant characteristics of the pancreatic cancer cell line Panc-1 in vitro. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328708966  88 RNAWGNQ----SYADLITQAISSVPEQRLTLSQIYEWMVQNVPYFKDkgdsnSSAGWKNSIRHNLSLHSRFEKI--QNEG 161
Cdd:cd20043    6 KNSYSDQkppySYISLTAMAIQSSQEKMLPLSDIYKFIMDRFPYYRE-----NTQRWQNSLRHNLSFNDCFIKIprRPDQ 80

                         90
                 ....*....|
gi 328708966 162 TGKSSWWQIN 171
Cdd:cd20043   81 PGKGSFWALH 90

Transactivation domain of FOXO protein family; TAD is a promiscuous binding domain that mediates the association of the transcription factor FOXO with the coactivator CBP/p300. Both this domain and the FOXO-KIX_bd family pfam16675 bind simultaneously the KIX domain of CBP/p300. Coactivator CBP/p300 is recruited by FOXO3 though binding to these two regions. The promiscuity of the TAD is further evidenced by that the finding that they also bind the TAZ1 and TAZ2 domains of CBP/p300.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 328708966  379 SHLSFDELNINLdkfppvECNVDEVISHEVSLGGCLDFnNFNP 421
Cdd:pfam16676   4 SDLDLDMFQGSL------ECDVDSIIRNDLMDGDGLDF-NFDS 39