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 74747718   1 MPRPGKSSYSDQKPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQ 80
Cdd:cd20043   1 MPRPGKNSYSDQKPPYSYISLTAMAIQSSQEKMLPLSDIYKFIMDRFPYYRENTQRWQNSLRHNLSFNDCFIKIPRRPDQ 80

                        90       100       110
                ....*....|....*....|....*....|
gi 74747718  81 PGKGSFWALHPDCGDMFENGSFLRRRKRFK 110
Cdd:cd20043  81 PGKGSFWALHPDCGDMFENGSFLRRRKRFK 110

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 74747718   1 MPRPGKSSYSDQKPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQ 80
Cdd:cd20043   1 MPRPGKNSYSDQKPPYSYISLTAMAIQSSQEKMLPLSDIYKFIMDRFPYYRENTQRWQNSLRHNLSFNDCFIKIPRRPDQ 80

                        90       100       110
                ....*....|....*....|....*....|
gi 74747718  81 PGKGSFWALHPDCGDMFENGSFLRRRKRFK 110
Cdd:cd20043  81 PGKGSFWALHPDCGDMFENGSFLRRRKRFK 110

Forkhead domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74747718    13 KPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQPGKGSFWALHPD 92
Cdd:pfam00250   1 KPPYSYAALIAMAILSSPEKKLTLSEIYEWISENFPYYRTADKGWQNSIRHNLSLNKCFVKVPRPKDEPGKGSYWTIDPE 80

                  ....*.
gi 74747718    93 CGDMFE 98
Cdd:pfam00250  81 YEEMFE 86

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 74747718   1 MPRPGKSSYSDQKPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQ 80
Cdd:cd20043   1 MPRPGKNSYSDQKPPYSYISLTAMAIQSSQEKMLPLSDIYKFIMDRFPYYRENTQRWQNSLRHNLSFNDCFIKIPRRPDQ 80

                        90       100       110
                ....*....|....*....|....*....|
gi 74747718  81 PGKGSFWALHPDCGDMFENGSFLRRRKRFK 110
Cdd:cd20043  81 PGKGSFWALHPDCGDMFENGSFLRRRKRFK 110

Forkhead (FH) domain found in the Forkhead box protein B (FOXB) subfamily; The FOXB subfamily includes two winged helix transcription factors, FOXB1 (also called transcription factor FKH-5) and FOXB2 (also called transcription factor FKH-4). FOXB1 controls development of mammary glands and regions of the central nervous system (CNS) that regulate the milk-ejection reflex. It is essential for access of mammillothalamic axons to the thalamus. FOXB2 may act as a tumor suppressor; it has been found to inhibit the malignant characteristics of the pancreatic cancer cell line Panc-1 in vitro. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 74747718  13 KPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQPGKGSFWALHP 91
Cdd:cd20016   1 KPPYSYISLTAMAIQSSPEKMLPLSDIYKFIMDRFPYYRKNTQRWQNSLRHNLSFNDCFIKIPRRPDRPGKGSYWALHP 79

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74747718     13 KPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQPGKGSFWALHPD 92
Cdd:smart00339   1 KPPYSYIALIAMAILSSPDKRLTLSEIYKWIEDNFPYYRENRAGWQNSIRHNLSLNDCFVKVPREGDRPGKGSYWTLDPA 80

                   ....*....
gi 74747718     93 CGDMFENGS 101
Cdd:smart00339  81 AENMFENGN 89

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 74747718  13 KPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQPGKGSFWALHPD 92
Cdd:cd20019   1 KPPYSYIALIAMAIANSPERKLTLGGIYKFIMERFPFYRDNSKKWQNSIRHNLTLNDCFVKIPREPGRPGKGNYWTLDPA 80

                        90
                ....*....|....
gi 74747718  93 CGDMFENGSFLRRR 106
Cdd:cd20019  81 AEDMFDNGSFLRRR 94

Forkhead domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74747718    13 KPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQPGKGSFWALHPD 92
Cdd:pfam00250   1 KPPYSYAALIAMAILSSPEKKLTLSEIYEWISENFPYYRTADKGWQNSIRHNLSLNKCFVKVPRPKDEPGKGSYWTIDPE 80

                  ....*.
gi 74747718    93 CGDMFE 98
Cdd:pfam00250  81 YEEMFE 86

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 74747718  13 KPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQPGKGSFWALHPD 92
Cdd:cd20039   5 KPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTLHPD 84

                        90
                ....*....|....*...
gi 74747718  93 CGDMFENGSFLRRRKRFK 110
Cdd:cd20039  85 SGNMFENGCYLRRQKRFK 102

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 74747718  13 KPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQPGKGSFWALHPD 92
Cdd:cd20037   2 KPPYSYIALIAMAIQSSPGQRATLSGIYRYIMGRFAFYRHNRPGWQNSIRHNLSLNECFVKVPRDDRKPGKGSYWTLDPD 81

                        90
                ....*....|....*..
gi 74747718  93 CGDMFENGSFLRRRKRF 109
Cdd:cd20037  82 CHDMFEHGSFLRRRRRF 98

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74747718  13 KPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQPGKGSFWALHPD 92
Cdd:cd20028   1 KPPYSYVALIAMAIRESPEKRLTLSGIYQYIIAKFPYYEKNKKGWQNSIRHNLSLNECFVKVPREGGGERKGNYWTLDPA 80

                ....*...
gi 74747718  93 CGDMFENG 100
Cdd:cd20028  81 CEDMFEKG 88

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74747718  13 KPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQPGKGSFWALHPD 92
Cdd:cd20047   2 KPPYSYIALITMAILQSPQKKLTLSGICEFISNRFPYYREKFPAWQNSIRHNLSLNDCFVKIPREPGNPGKGNYWTLDPQ 81

                        90
                ....*....|....*.
gi 74747718  93 CGDMFENGSFLRRRKR 108
Cdd:cd20047  82 SEDMFDNGSFLRRRKR 97

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 74747718  14 PPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQPGKGSFWA 88
Cdd:cd00059   1 PPYSYAALIALAILSSPDKRLTLSEIYKWIEDNFPYYRTATKGWKNSIRHNLSLNKCFVKVPREPSDPGKGSYWT 75

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 74747718  13 KPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQPGKGSFWAL 89
Cdd:cd20017   1 KPPYSYIALIAMAIQNAPDKKITLNGIYQFIMDRFPFYRENKQGWQNSIRHNLSLNECFVKVPRDDKKPGKGSYWTL 77

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 74747718  13 KPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQPGKGSFWALHPD 92
Cdd:cd20053   4 RPPYSYSALIAMAIHGAPDKRLTLSQIYQYVADNFPFYNKSKAGWQNSIRHNLSLNDCFKKVPRDEDDPGKGNYWTLDPN 83

                        90
                ....*....|....*.
gi 74747718  93 CGDMFENGSFLRRRKR 108
Cdd:cd20053  84 CEKMFDNGNFRRKRKR 99

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 74747718  13 KPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQPGKGSFWALHP 91
Cdd:cd20021   1 KPPFSYNALIMMAIRQSPEKRLTLNGIYEFIMKNFPYYRENKQGWQNSIRHNLSLNKCFVKVPRHYDDPGKGNYWMLDP 79

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 74747718  13 KPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQPGKGSFWAL 89
Cdd:cd20018   1 KPPYSYIALITMAILQSPQKKLTLSGICEFIMNRFPYYREKFPAWQNSIRHNLSLNDCFVKIPREPGNPGKGNYWTL 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 74747718  13 KPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQPGKGSFWALH 90
Cdd:cd20026   1 KPPYSYAQLIVQAISSAPDKQLTLSGIYAYITKNYPYYRTADKGWQNSIRHNLSLNRYFIKVPRSQEEPGKGSFWRID 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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 74747718  13 KPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQPGKGSFWAL 89
Cdd:cd20052   2 KPPYSYANLITFAINSSPKKKMTLSEIYQWICDNFPYYREAGNGWKNSIRHNLSLNKCFLKVPRSKDDPGKGSYWAI 78

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 74747718  14 PPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQPGKGSFWALHPDC 93
Cdd:cd20050   1 PPYSYIALIVMAIQSSPSKKLTLSEIYQFLQARFPFFRGAYQGWKNSVRHNLSLNECFIKLPKGLGRPGKGHYWTIDPAS 80

                        90
                ....*....|..
gi 74747718  94 GDMFENGSFLRR 105
Cdd:cd20050  81 EFMFEEGSFRRR 92

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 74747718  11 DQKPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQPGKGSFWALH 90
Cdd:cd20055   1 DSKPPYSYAQLIVQAITMAPDKQLTLNGIYTHITKNYPYYRTADKGWQNSIRHNLSLNRYFIKVPRSQEEPGKGSFWRID 80

                        90
                ....*....|....*...
gi 74747718  91 PDCGDMFENGSFLRRRKR 108
Cdd:cd20055  81 PASESKLIEQAFRKRRPR 98

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 74747718  13 KPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQPGKGSFWAL 89
Cdd:cd20051   2 KPPYSYATLITYAINSSPAKKMTLSEIYRWICDNFPYYRNAGVGWKNSIRHNLSLNKCFRKVPRPRDDPGKGSYWMI 78

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 74747718  13 KPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQpGKGSFW 87
Cdd:cd20031   1 KPPYSFSCLIFMAIESSPEKALPVKDIYSWIEKHFPYYRNAPSGWKNSIRHNLSLNKCFKKVEKEKNK-GKGSLW 74

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 74747718  13 KPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQP-GKGSFWALHP 91
Cdd:cd20059   1 KPPYSFSCLIFMAIEDSPTKRLPVKDIYNWILEHFPYFANAPTGWKNSVRHNLSLNKCFKKVDKEKGQSiGKGSLWCIDP 80

                .
gi 74747718  92 D 92
Cdd:cd20059  81 E 81

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74747718  12 QKPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQPGKGSFWALHP 91
Cdd:COG5025 336 SKPAFSYANSITQAILSSPSGKMTLSEIYSWISSNLPYYRHKPTAWQNSIRHNLSLNKSFEKVPRSASQPGKGCFWKIDY 415

                        90       100
                ....*....|....*....|...
gi 74747718  92 DcgDMFENGSFLRRRKRFKVLRA 114
Cdd:COG5025 416 S--YIYEKESKRNPRSPKKSPSA 436

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 74747718  13 KPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIprrpdQPGKGSFW 87
Cdd:cd20033   1 RPPFTYASLIRQAILESPNKQLTLNEIYNWFQKTFAYFRRNAATWKNAVRHNLSLHKCFVRV-----ENVKGAVW 70

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74747718  12 QKPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRPDQPG--KGSFWAL 89
Cdd:cd20036   2 PKPPLSYPNLIALALRNSETGSLNVQEIYDFIRFHFPFFRTAPDGWKNSVRHNLSFSDSFEKVPTSVSGYGgrRSCLWKL 81

                ...
gi 74747718  90 HPD 92
Cdd:cd20036  82 TPE 84

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 74747718  13 KPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIPRRpdqpgKGSFWalhpd 92
Cdd:cd20066   1 RPPFTYASLIRWAILESPEKQLTLNEIYHWFTRMFAFFRNNTATWKNAVRHNLSLHKCFVRVENE-----KGAVW----- 70

                        90
                ....*....|....
gi 74747718  93 cgdMFENGSFLRRR 106
Cdd:cd20066  71 ---TVDELEFQRRR 81

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 74747718  17 SYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQR-----WQNSLRHNLSFNDCFIKIPrrPDQPGKGSFWAL 89
Cdd:cd20032   4 SYADLITKAIESSPDKRLTLQQIYDWMVRNVPYFKDKGDSnssagWKNSIRHNLSLHSRFVRVQ--NEGTGKSSWWTL 79

Forkhead (FH) domain found in Forkhead box protein P1 (FOXP1); FOXP1, also called Mac-1-regulated Forkhead (MFH), is a transcription factor that is widely expressed and has a broad range of functions. It has been shown to have a role in cardiac, lung, and lymphocyte development. Deregulation of FOXP1 is an important contributor to the pathogenesis of diffuse large B-cell lymphoma (DLBCL), suggesting it may function as an oncogene. Loss of FOXP1 expression in breast cancer is associated with a worse outcome, suggesting that FOXP1 may function as a tumor suppressor in some tissues. Haploinsufficiency of the FOXP1 gene leads to a neurodevelopmental disorder termed FOXP1 syndrome, characterized by developmental delay, intellectual disability, autism spectrum disorder, speech delay, and dysmorphic features. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74747718  10 SDQKPPYSYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREHTQRWQNSLRHNLSFNDCFIKIprrpdQPGKGSFWAL 89
Cdd:cd20064   1 AEVRPPFTYASLIRQAILESPEKQLTLNEIYNWFTRMFAYFRRNAATWKNAVRHNLSLHKCFVRV-----ENVKGAVWTV 75

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74747718  17 SYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREH-----TQRWQNSLRHNLSFNDCFIKIprRPDQPGKGSFWALHP 91
Cdd:cd20062   8 SYAELISQAIESSPEKRLTLAQIYEWMVKSVPYFKDKgdsnsSAGWKNSIRHNLSLHSKFIKV--HNEATGKSSWWMLNP 85

                .
gi 74747718  92 D 92
Cdd:cd20062  86 E 86

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 74747718  17 SYISLTAMAIQHSAEKMLPLSDIYKFIMERFPYYREH-----TQRWQNSLRHNLSFNDCFIKIprRPDQPGKGSFWALHP 91
Cdd:cd20063   4 SYADLITKAIESSPDKRLTLSQIYDWMVRYVPYFKDKgdsnsSAGWKNSIRHNLSLHTRFIRV--QNEGTGKSSWWMLNP 81

                ....*
gi 74747718  92 DCGDM 96
Cdd:cd20063  82 EGGKT 86