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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392890244  30 ENPNIVGSVNVSPLVLSPTVPAET----------SKPVAPAHEGKRRRIF-DGADKPPYSYSQLIRLAIEDTPDKKCTLA 98
Cdd:COG5025   31 EVVINGKSHNVSSVLSSPKAPTRVsldysnslnrSVGSEEIQAYAKLAGSnWTYYVPPYSYATGRGLAILNSPDKPLTLS 110

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392890244  99 EIYSFIaHNFQFYRENRNSSWKNSIRHNLSLNKQFSRIEKTDG-DRRGWWVCVDPPAKKPRILKGSpvrvnPIYEHLYHN 177
Cdd:COG5025  111 KIYTWI-HNTFFYYAKVVSRWQNSIRHNLSLNDAFIKIEGRNGaKVKGHFWSIGPGHETQFLKSGL-----RLDGGGKQM 184

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 392890244 178 KQDMPNFTP---PPEDPFLSEINGNVHELTEHEIRDLNLFESY 217
Cdd:COG5025  185 MFTLPSSTEikiTYSSTHSMPLLESNDSLNSNNERELLDIIKS 227

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 392890244  75 PPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYRENrNSSWKNSIRHNLSLNKQFSRIEKTDGD--RRGWWV 148
Cdd:cd00059    1 PPYSYAALIALAILSSPDKRLTLSEIYKWIEDNFPYYRTA-TKGWKNSIRHNLSLNKCFVKVPREPSDpgKGSYWT 75

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392890244  46 SPTVPAETSKPVAPAHEGKRRRifdgadKPPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYREnRNSSWKNSIRH 125
Cdd:COG5025  315 VPKDAAPPSTLSDLSADVNRTS------KPAFSYANSITQAILSSPSGKMTLSEIYSWISSNLPYYRH-KPTAWQNSIRH 387

                         90
                 ....*....|....
gi 392890244 126 NLSLNKQFSRIEKT 139
Cdd:COG5025  388 NLSLNKSFEKVPRS 401

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 392890244  75 PPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYRENrNSSWKNSIRHNLSLNKQFSRIEKTDGD--RRGWWV 148
Cdd:cd00059    1 PPYSYAALIALAILSSPDKRLTLSEIYKWIEDNFPYYRTA-TKGWKNSIRHNLSLNKCFVKVPREPSDpgKGSYWT 75

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 392890244  74 KPPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYRENrNSSWKNSIRHNLSLNKQFSRIEKTDGD 142
Cdd:cd20024    1 KPPYSYATLITFAINSSPKKKMTLSEIYTWICENFPYYREA-GTGWKNSIRHNLSLNKCFKKVPRSKDD 68

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 392890244  74 KPPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYRENrNSSWKNSIRHNLSLNKQFSRIEKT 139
Cdd:cd20031    1 KPPYSFSCLIFMAIESSPEKALPVKDIYSWIEKHFPYYRNA-PSGWKNSIRHNLSLNKCFKKVEKE 65

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 392890244  74 KPPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYReNRNSSWKNSIRHNLSLNKQFSRIEKTDGDRRGWW 147
Cdd:cd20035    1 KPSHSYVALIAKAILSSPEKKLVLSDIYQYIEENYPYFK-SRGSSWKNSVRHNLSLNECFVKAGRAENGKGNYW 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392890244  74 KPPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYRENRNsSWKNSIRHNLSLNKQFSRIEKT--DGDRRGWWVcVD 151
Cdd:cd20021    1 KPPFSYNALIMMAIRQSPEKRLTLNGIYEFIMKNFPYYRENKQ-GWQNSIRHNLSLNKCFVKVPRHydDPGKGNYWM-LD 78

                 .
gi 392890244 152 P 152
Cdd:cd20021   79 P 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 392890244  75 PPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYRENRnSSWKNSIRHNLSLNKQFSRIEKTDGD-RRGWWVCVDP 152
Cdd:cd20020    1 PPYSYIALIVMAIQASPTKRLTLSEIYQFLQQRFPFFRGPY-QGWKNSVRHNLSLNECFIKLPKGLGRpGKGHYWTIDP 78

Forkhead (FH) domain found in Forkhead box protein J3 (FOXJ3) and similar proteins; FOXJ3 is a transcription factor which regulates sperm function. It transcriptionally activates Mef2c and regulates adult skeletal muscle fiber type identity. Polymorphisms in the FOXJ3 gene may be associated with the development of rheumatoid arthritis. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 392890244  74 KPPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYRENRNsSWKNSIRHNLSLNKQFSRIEKTDGD 142
Cdd:cd20052    2 KPPYSYANLITFAINSSPKKKMTLSEIYQWICDNFPYYREAGN-GWKNSIRHNLSLNKCFLKVPRSKDD 69

Forkhead (FH) domain found in the Forkhead box protein E (FOXE) subfamily; The FOXE subfamily includes two winged helix transcription factors, FOXE1 (also known as FOXE2) and FOXE3. FOXE1, also called Forkhead-related protein FKHL15, HFKH4, HNF-3/fork head-like protein 5 (HFKL5), or thyroid transcription factor 2 (TTF-2), is a transcription factor that binds consensus sites on a variety of gene promoters and activate their transcription. FOXE3, also called Forkhead-related protein FKHL12 or Forkhead-related transcription factor 8 (FREAC-8), is a transcription factor that controls lens epithelial cell growth through regulation of proliferation, apoptosis, and the cell cycle. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392890244  74 KPPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYRENRnSSWKNSIRHNLSLNKQFSRIEKTDGDR-RGWWVCVDP 152
Cdd:cd20019    1 KPPYSYIALIAMAIANSPERKLTLGGIYKFIMERFPFYRDNS-KKWQNSIRHNLTLNDCFVKIPREPGRPgKGNYWTLDP 79

                 ...
gi 392890244 153 PAK 155
Cdd:cd20019   80 AAE 82

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 392890244  74 KPPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYReNRNSSWKNSIRHNLSLNKQFSRIEKTDGDRRG----WwvC 149
Cdd:cd20059    1 KPPYSFSCLIFMAIEDSPTKRLPVKDIYNWILEHFPYFA-NAPTGWKNSVRHNLSLNKCFKKVDKEKGQSIGkgslW--C 77

                         90
                 ....*....|..
gi 392890244 150 VDpPAKKPRILK 161
Cdd:cd20059   78 ID-PEYRPNLLQ 88

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 392890244  78 SYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYRE----NRNSSWKNSIRHNLSLNKQFSRIEKTDGDRRGWWV 148
Cdd:cd20032    4 SYADLITKAIESSPDKRLTLQQIYDWMVRNVPYFKDkgdsNSSAGWKNSIRHNLSLHSRFVRVQNEGTGKSSWWT 78

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 392890244  74 KPPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYRENRnSSWKNSIRHNLSLNKQFSRIEKTDG 141
Cdd:cd20065    2 RPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNA-ATWKNAVRHNLSLHKCFVRVENVKG 68

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392890244  74 KPPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYrENRNSSWKNSIRHNLSLNKQFSRIEKTDGDRRG---WWvCV 150
Cdd:cd20058    2 KPPYSFSLLIYMAIEHSPNKCLPVKEIYSWILEHFPYF-STAPTGWKNSVRHNLSLNKCFRKVERSHGKVNGkgsLW-CV 79

                 ..
gi 392890244 151 DP 152
Cdd:cd20058   80 DP 81

Forkhead (FH) domain found in Drosophila melanogaster protein fork head (dFKH) and similar proteins; 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 392890244  74 KPPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYRENRNsSWKNSIRHNLSLNKQFSRIEKTDgDRRG 145
Cdd:cd20041    1 KPPYSYISLITMAIQNSPNKMVTLSEIYQFIMDLFPFYRQNQQ-RWQNSIRHSLSFNDCFVKVPRTP-DKPG 70

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 392890244  74 KPPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYRENRNsSWKNSIRHNLSLNKQFSRIEKTDGDR-RGWWVCVDP 152
Cdd:cd20045    3 KPPYSYIALITMAIQNAPDKKITLNGIYQFIMDRFPFYRENKQ-GWQNSIRHNLSLNECFVKVPRDDKKPgKGSYWTLDP 81

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 392890244  74 KPPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYRENrNSSWKNSIRHNLSLNKQFSRIEKTDG 141
Cdd:cd20066    1 RPPFTYASLIRWAILESPEKQLTLNEIYHWFTRMFAFFRNN-TATWKNAVRHNLSLHKCFVRVENEKG 67

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 392890244  74 KPPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYRENRnSSWKNSIRHNLSLNKQFSRIEKTDGDR-RGWWVCVDP 152
Cdd:cd20053    4 RPPYSYSALIAMAIHGAPDKRLTLSQIYQYVADNFPFYNKSK-AGWQNSIRHNLSLNDCFKKVPRDEDDPgKGNYWTLDP 82

                 ....
gi 392890244 153 PAKK 156
Cdd:cd20053   83 NCEK 86

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 392890244  74 KPPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYREnRNSSWKNSIRHNLSLNKQFSRIEKTDGD 142
Cdd:cd20018    1 KPPYSYIALITMAILQSPQKKLTLSGICEFIMNRFPYYRE-KFPAWQNSIRHNLSLNDCFVKIPREPGN 68

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 392890244  75 PPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYReNRNSSWKNSIRHNLSLNKQFSRIEKTDGDR-RGWWVCVDPP 153
Cdd:cd20050    1 PPYSYIALIVMAIQSSPSKKLTLSEIYQFLQARFPFFR-GAYQGWKNSVRHNLSLNECFIKLPKGLGRPgKGHYWTIDPA 79

                 ..
gi 392890244 154 AK 155
Cdd:cd20050   80 SE 81

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 392890244  74 KPPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYRENRnSSWKNSIRHNLSLNKQFSRIEKTDG 141
Cdd:cd20064    4 RPPFTYASLIRQAILESPEKQLTLNEIYNWFTRMFAYFRRNA-ATWKNAVRHNLSLHKCFVRVENVKG 70

Forkhead (FH) domain found in Forkhead box protein O4 (FOXO4) and similar proteins; FOXO4, also called Fork head domain transcription factor AFX1, is a transcription factor involved in the regulation of the insulin signaling pathway. It binds to insulin-response elements (IREs) and can activate transcription of IGFBP1. The FH domain is a winged helix DNA-binding domain. All FOXOs bind to the consensus sequence 5'-GTAAACAA-3', known as the DAF-16 family member-binding element, which includes the core sequence 5'-(A/C)AA(C/T)A-3' recognized by all FOX family members.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 392890244  78 SYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYRE----NRNSSWKNSIRHNLSLNKQFSRIEKTDGDRRGWWV 148
Cdd:cd20062    8 SYAELISQAIESSPEKRLTLAQIYEWMVKSVPYFKDkgdsNSSAGWKNSIRHNLSLHSKFIKVHNEATGKSSWWM 82

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 392890244  74 KPPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYRENRNsSWKNSIRHNLSLNKQFSRIEKT 139
Cdd:cd20015    1 KPPYSYISLITMAIQQSPSKMLTLSEIYQWIMDLFPYYRQNQQ-RWQNSIRHSLSFNDCFVKVPRS 65

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 392890244  74 KPPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYReNRNSSWKNSIRHNLSLNKQFSRIEKTDGDR-RGWWVCVDP 152
Cdd:cd20055    3 KPPYSYAQLIVQAITMAPDKQLTLNGIYTHITKNYPYYR-TADKGWQNSIRHNLSLNRYFIKVPRSQEEPgKGSFWRIDP 81

                 ...
gi 392890244 153 PAK 155
Cdd:cd20055   82 ASE 84

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 392890244  78 SYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYRE----NRNSSWKNSIRHNLSLNKQFSRIEKTDGDRRGWWV 148
Cdd:cd20061    5 SYADLITRAIESSPDKRLTLSQIYDWMVRCVPYFKDkgdsNSSAGWKNSIRHNLSLHSRFIRVQNEGTGKSSWWM 79

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 392890244  74 KPPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYRENrNSSWKNSIRHNLSLNKQFSRIEK 138
Cdd:cd20042    6 KPPYSYISLTAMAIQSSPEKMLPLSEIYKFIMDRFPYYREN-TQRWQNSLRHNLSFNDCFIKIPR 69

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 392890244  74 KPPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYRENRNsSWKNSIRHNLSLNKQFSRIEKT 139
Cdd:cd20038   14 KPPYSYISLITMAIQQAPSKMLTLSEIYQWIMDLFPYYRQNQQ-RWQNSIRHSLSFNDCFVKVARS 78

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 392890244  78 SYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYRE----NRNSSWKNSIRHNLSLNKQFSRIEKTDGDRRGWWV 148
Cdd:cd20060   14 SYADLITKAIESSAEKRLTLSQIYEWMVKSVPYFKDkgdsNSSAGWKNSIRHNLSLHSKFIRVQNEGTGKSSWWM 88

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 392890244  71 GADKPPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYRENrNSSWKNSIRHNLSLNKQFSRIEK 138
Cdd:cd20043   10 SDQKPPYSYISLTAMAIQSSQEKMLPLSDIYKFIMDRFPYYREN-TQRWQNSLRHNLSFNDCFIKIPR 76

Forkhead (FH) domain found in Forkhead box protein N1 (FOXN1); FOXN1, also called winged helix transcription factor nude, acts as a transcriptional regulator which regulates the development, differentiation, and function of thymic epithelial cells (TECs), both in the prenatal and postnatal thymus. It is also an important factor in controlling the skin wound healing process, as it actively participates in re-epithelialization and is responsible for scar formation. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392890244  74 KPPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYRENRNSsWKNSIRHNLSLNKQFSRIEKTDGD--RRGWWVCVD 151
Cdd:cd20056    2 KPIYSYSILIFMALKNSKTGSLPVSEIYNFMTEHFPYFKTAPDG-WKNSVRHNLSLNKCFEKVENKSGSssRKGCLWALN 80

                 .
gi 392890244 152 P 152
Cdd:cd20056   81 P 81

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 392890244  74 KPPYSYSQLIRLAIEDTPDKKCTLAEIYSFIAHNFQFYRENRNSsWKNSIRHNLSLNKQFSRIE-KTDGDRR 144
Cdd:cd20057    6 KPIYSYSCLIAMALKNSKTGSLPVSEIYSFMKEHFPYFKTAPDG-WKNSVRHNLSLNKCFEKVEnKMSGSSR 76