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 1029201558 104 GNQSYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKDKGDSNSSAGWKNSIRHNLSLHTRFIRVQNEGTGKSSWWMLN 183
Cdd:cd20063     1 GNLSYADLITKAIESSPDKRLTLSQIYDWMVRYVPYFKDKGDSNSSAGWKNSIRHNLSLHTRFIRVQNEGTGKSSWWMLN 80

                  ....*...
gi 1029201558 184 PEGGKMGK 191
Cdd:cd20063    81 PEGGKTGK 88

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 1029201558 641 RLQSELEMDVHQSSLDCDVESILLNDFMDStEGMDFNFDGS 681
Cdd:pfam16676   1 RLPSDLDLDMFQGSLECDVDSIIRNDLMDG-DGLDFNFDSM 40

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 1029201558 104 GNQSYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKDKGDSNSSAGWKNSIRHNLSLHTRFIRVQNEGTGKSSWWMLN 183
Cdd:cd20063     1 GNLSYADLITKAIESSPDKRLTLSQIYDWMVRYVPYFKDKGDSNSSAGWKNSIRHNLSLHTRFIRVQNEGTGKSSWWMLN 80

                  ....*...
gi 1029201558 184 PEGGKMGK 191
Cdd:cd20063    81 PEGGKTGK 88

Forkhead domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1029201558 105 NQSYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKdkgdsNSSAGWKNSIRHNLSLHTRFIRV--QNEGTGKSSWWML 182
Cdd:pfam00250   3 PYSYAALIAMAILSSPEKKLTLSEIYEWISENFPYYR-----TADKGWQNSIRHNLSLNKCFVKVprPKDEPGKGSYWTI 77

                  ....*..
gi 1029201558 183 NPEGGKM 189
Cdd:pfam00250  78 DPEYEEM 84

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 1029201558 641 RLQSELEMDVHQSSLDCDVESILLNDFMDStEGMDFNFDGS 681
Cdd:pfam16676   1 RLPSDLDLDMFQGSLECDVDSIIRNDLMDG-DGLDFNFDSM 40

Topoisomerase II-associated protein PAT1; Members of this family are necessary for accurate chromosome transmission during cell division.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1029201558 476 VTHEQNPSHHHNPNQAHNKHHPSLD-YNHHKQHRGHDYVQSHDHklnaspNHMHNHLQHNNSRQPDLSPRVSndmlqpyn 554
Cdd:pfam09770 216 PAPAQPPAAPPAQQAQQQQQFPPQIqQQQQPQQQPQQPQQHPGQ------GHPVTILQRPQSPQPDPAQPSI-------- 281

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1029201558 555 hkspslyGPRAHLPSTALPPNPASVLDVPQDPCRLASAPHPRHQsypgshLHQGMTEPWQGYYHHTSQNANYHGNHQASH 634
Cdd:pfam09770 282 -------QPQAQQFHQQPPPVPVQPTQILQNPNRLSAARVGYPQ------NPQPGVQPAPAHQAHRQQGSFGRQAPIITH 348

                  ..
gi 1029201558 635 HH 636
Cdd:pfam09770 349 PQ 350

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 1029201558 104 GNQSYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKDKGDSNSSAGWKNSIRHNLSLHTRFIRVQNEGTGKSSWWMLN 183
Cdd:cd20063     1 GNLSYADLITKAIESSPDKRLTLSQIYDWMVRYVPYFKDKGDSNSSAGWKNSIRHNLSLHTRFIRVQNEGTGKSSWWMLN 80

                  ....*...
gi 1029201558 184 PEGGKMGK 191
Cdd:cd20063    81 PEGGKTGK 88

Forkhead (FH) domain found in Forkhead box protein O3 (FOXO3); FOXO3, also called AF6q21 protein or Forkhead in rhabdomyosarcoma-like 1 (FKHRL1), is a transcriptional activator which triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress. It recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3'. The FH domain is a winged helix DNA-binding domain. All FOXOs bind to the consensus sequence 5'-GTAAACAA-3', known as the DAF-16 family member-binding element, which includes the core sequence 5'-(A/C)AA(C/T)A-3' recognized by all FOX family members.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1029201558 103 WGNQSYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKDKGDSNSSAGWKNSIRHNLSLHTRFIRVQNEGTGKSSWWML 182
Cdd:cd20061     1 WGNLSYADLITRAIESSPDKRLTLSQIYDWMVRCVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFIRVQNEGTGKSSWWMI 80

                  ...
gi 1029201558 183 NPE 185
Cdd:cd20061    81 NPD 83

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 1029201558 104 GNQSYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKDKGDSNSSAGWKNSIRHNLSLHTRFIRVQNEGTGKSSWWMLN 183
Cdd:cd20032     1 GNMSYADLITKAIESSPDKRLTLQQIYDWMVRNVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFVRVQNEGTGKSSWWTLN 80

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1029201558  103 WGNQSYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKDKGDsnssaGWKNSIRHNLSLHTRFIRVQNEGT--GKSSWW 180
Cdd:smart00339   1 KPPYSYIALIAMAILSSPDKRLTLSEIYKWIEDNFPYYRENRA-----GWQNSIRHNLSLNDCFVKVPREGDrpGKGSYW 75

                   ....*....
gi 1029201558  181 MLNPEGGKM 189
Cdd:smart00339  76 TLDPAAENM 84

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 1029201558 106 QSYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKDkgdsnSSAGWKNSIRHNLSLHTRFIRV--QNEGTGKSSWWML 182
Cdd:cd20024     4 YSYATLITFAINSSPKKKMTLSEIYTWICENFPYYRE-----AGTGWKNSIRHNLSLNKCFKKVprSKDDPGKGSYWTL 77

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 1029201558 107 SYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKDKgdsnsSAGWKNSIRHNLSLHTRFIRVQNEGTG--KSSWWMLNP 184
Cdd:cd20028     5 SYVALIAMAIRESPEKRLTLSGIYQYIIAKFPYYEKN-----KKGWQNSIRHNLSLNECFVKVPREGGGerKGNYWTLDP 79

Forkhead (FH) domain found in the Forkhead box protein M (FOXM) subfamily; The FOXM subfamily includes a winged helix transcription factor, FOXM1, which is also called Forkhead-related protein FKHL16, Hepatocyte nuclear factor 3 Forkhead homolog 11 (HFH-11), HNF-3/fork-head homolog 11, M-phase phosphoprotein 2, MPM-2 reactive phosphoprotein 2, transcription factor Trident, or Winged-helix factor from INS-1 cells. FOXM1 acts as a transcriptional factor regulating the expression of cell cycle genes essential for DNA replication and mitosis. It plays a role in the control of cell proliferation. It is also involved in DNA break repair, participating in the DNA damage checkpoint response. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1029201558 107 SYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKdkgdSNSSAGWKNSIRHNLSLHTRFIRvQNEGTGKSSWWMLNP 184
Cdd:cd20029     5 SYMALIQFAINSTEDKRMTLKEIYTWIEDHFPYFK----HTAKPGWKNSIRHNLSLHDIFVR-ETSANGKGSFWTLRP 77

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 1029201558 107 SYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKDkgdsnSSAGWKNSIRHNLSLHTRFIRVQN--EGTGKSSWWMLNP 184
Cdd:cd20021     5 SYNALIMMAIRQSPEKRLTLNGIYEFIMKNFPYYRE-----NKQGWQNSIRHNLSLNKCFVKVPRhyDDPGKGNYWMLDP 79

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 1029201558 107 SYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKDKGdsnssAGWKNSIRHNLSLHTRFIRV--QNEGTGKSSWWMLN 183
Cdd:cd20051     6 SYATLITYAINSSPAKKMTLSEIYRWICDNFPYYRNAG-----VGWKNSIRHNLSLNKCFRKVprPRDDPGKGSYWMID 79

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 1029201558 107 SYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKDKgdsnsSAGWKNSIRHNLSLHTRFIRVQNegtGKSSWWMLN 183
Cdd:cd20033     5 TYASLIRQAILESPNKQLTLNEIYNWFQKTFAYFRRN-----AATWKNAVRHNLSLHKCFVRVEN---VKGAVWTVD 73

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 1029201558 107 SYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKdkgdsNSSAGWKNSIRHNLSLHTRFIRVQN 171
Cdd:cd20064     8 TYASLIRQAILESPEKQLTLNEIYNWFTRMFAYFR-----RNAATWKNAVRHNLSLHKCFVRVEN 67

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 1029201558 107 SYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKdkgdsNSSAGWKNSIRHNLSLHTRFIRVQNE---GTGKSSWWMLN 183
Cdd:cd20059     5 SFSCLIFMAIEDSPTKRLPVKDIYNWILEHFPYFA-----NAPTGWKNSVRHNLSLNKCFKKVDKEkgqSIGKGSLWCID 79

                  ..
gi 1029201558 184 PE 185
Cdd:cd20059    80 PE 81

KIX-binding domain of forkhead box O, CR2; FOXO_KIX_bd is the first part of the region of transcription factor forkhead box O family proteins that binds to the CREB-binding proteins via the KIX domain. Coactivator CBP/p300 is recruited by FOXO3 via the binding of this domain as well as the simultaneous binding of the more C-terminal TAD domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1029201558 364 GTVYGQPSMGMLRHhTPMQTIQENKPTSFQrALRAYSENNALESLLAGGPqYCGKDMvvgqGGTSHSLMSQSNTAVHSHG 443
Cdd:pfam16675   1 KSIYGQPSMNSLRQ-MPMQTIQENKQSSFG-SMSQYGPAGLLQELLTSDS-YPHSDI----LTQVDPLMSQASGRVLSQN 73

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1029201558 107 SYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKDkgdsnSSAGWKNSIRHNLSLHTRFIRVQNEGT--GKSSWWMLNP 184
Cdd:cd20027     7 SYIALIAMAIKSAPDQKVTLNGIYQFIMDRFPYYHD-----NKQGWQNSIRHNLSLNDCFVKVPREKGrpGKGNYWTLDP 81

                          90
                  ....*....|....*
gi 1029201558 185 EGGKM---GKGPRRR 196
Cdd:cd20027    82 DCEEMfenGNYRRRK 96

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 1029201558 107 SYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKDKgdsnsSAGWKNSIRHNLSLHTRFIRVQNE--GTGKSSWWMLNP 184
Cdd:cd20046     5 SYIALITMAILQSPKKRLTLSEICEFISNRFPYYREK-----FPAWQNSIRHNLSLNDCFVKIPREpgNPGKGNYWTLDP 79

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1029201558 185 EGGKMgkgprrravsMDNGTkYLKSRGRVSR 215
Cdd:cd20046    80 ESADM----------FDNGS-FLRRRKRFKR 99

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1029201558 107 SYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKdkgdsNSSAGWKNSIRHNLSLHTRFIRVQN 171
Cdd:cd20067     5 TYASLIRQAILETPDRQLTLNEIYNWFTRMFAYFR-----RNTATWKNAVRHNLSLHKCFVRVEN 64

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 1029201558 107 SYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKDkgdsnSSAGWKNSIRHNLSLHTRFIRV--QNEGTGKSSWWML 182
Cdd:cd20017     5 SYIALIAMAIQNAPDKKITLNGIYQFIMDRFPFYRE-----NKQGWQNSIRHNLSLNECFVKVprDDKKPGKGSYWTL 77

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 1029201558 107 SYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKDKgdsnsSAGWKNSIRHNLSLHTRFIRVQNE--GTGKSSWWMLNP 184
Cdd:cd20048     5 SYIALITMAILQSPHKRLTLSGICAFISGRFPYYRRK-----FPAWQNSIRHNLSLNDCFVKIPREpgHPGKGNYWSLDP 79

                          90
                  ....*....|....*
gi 1029201558 185 EGGKM---GKGPRRR 196
Cdd:cd20048    80 ASQDMfdnGSFLRRR 94

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 1029201558 641 RLQSELEMDVHQSSLDCDVESILLNDFMDStEGMDFNFDGS 681
Cdd:pfam16676   1 RLPSDLDLDMFQGSLECDVDSIIRNDLMDG-DGLDFNFDSM 40

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 1029201558 107 SYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFkdkgdSNSSAGWKNSIRHNLSLHTRFIRV--QNEGTGKSSWWMLNP 184
Cdd:cd20053     8 SYSALIAMAIHGAPDKRLTLSQIYQYVADNFPFY-----NKSKAGWQNSIRHNLSLNDCFKKVprDEDDPGKGNYWTLDP 82

                  ....*
gi 1029201558 185 EGGKM 189
Cdd:cd20053    83 NCEKM 87

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1029201558 107 SYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKdkgdsNSSAGWKNSIRHNLSLHTRFIRVQN--EGTGKSSWWMLNP 184
Cdd:cd20041     5 SYISLITMAIQNSPNKMVTLSEIYQFIMDLFPFYR-----QNQQRWQNSIRHSLSFNDCFVKVPRtpDKPGKGSFWTLHP 79

                  ....*
gi 1029201558 185 EGGKM 189
Cdd:cd20041    80 DSGNM 84

Forkhead (FH) domain found in Forkhead box protein A3 (FOXA3) and similar proteins; FOXA3, also called hepatocyte nuclear factor 3-gamma (HNF-3-gamma or HNF-3G), fork head-related protein FKH H3, or transcription factor 3G (TCF-3G), acts as an essential transcriptional regulator engaged in adipogenesis and energy 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 1029201558 107 SYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKDkgdsnSSAGWKNSIRHNLSLHTRFIRVQN--EGTGKSSWWMLNP 184
Cdd:cd20040     7 SYISLITMAIQQAPSKMLTLNEIYQWIMDLFPYYRE-----NQQRWQNSIRHSLSFNDCFVKVARspDKPGKGSYWALHP 81

                  ....*
gi 1029201558 185 EGGKM 189
Cdd:cd20040    82 NSGNM 86

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 1029201558 107 SYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKdkgdsNSSAGWKNSIRHNLSLHTRFIRV--QNEGTGKSSWWMLNP 184
Cdd:cd20055     7 SYAQLIVQAITMAPDKQLTLNGIYTHITKNYPYYR-----TADKGWQNSIRHNLSLNRYFIKVprSQEEPGKGSFWRIDP 81

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 1029201558 107 SYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKdkgdsNSSAGWKNSIRHNLSLHTRFIRVQN--EGTGKSSWWMLNP 184
Cdd:cd20049     4 SYIALIVMAIQSSPTKRLTLSEIYQFLQSRFPFFR-----GSYQGWKNSVRHNLSLNECFIKLPKglGRPGKGHYWTIDP 78

                          90
                  ....*....|....*.
gi 1029201558 185 ------EGGKMGKGPR 194
Cdd:cd20049    79 asefmfEEGSFRRRPR 94

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 1029201558 107 SYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKdkgdsNSSAGWKNSIRHNLSLHTRFIRVQNEGTG----KSSWWML 182
Cdd:cd20030     5 SYSCLIAMALKNSRTGCLPVSEIYSFMCENFPYFK-----TAPDGWKNSVRHNLSLNKCFEKIERPDGNgssrKGCLWAL 79

                  ..
gi 1029201558 183 NP 184
Cdd:cd20030    80 NP 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 1029201558 107 SYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKDKgdsnsSAGWKNSIRHNLSLHTRFIRVQNE--GTGKSSWWMLN 183
Cdd:cd20018     5 SYIALITMAILQSPQKKLTLSGICEFIMNRFPYYREK-----FPAWQNSIRHNLSLNDCFVKIPREpgNPGKGNYWTLD 78

Forkhead (FH) domain found in Forkhead box protein B1 (FOXB1) and similar proteins; FOXB1, also called transcription factor FKH-5, is a winged helix transcription factor that controls development of mammary glands and regions of the central nervous system (CNS) that regulate the milk-ejection reflex. It is essential for access of mammillothalamic axons to the thalamus. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1029201558 107 SYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKDkgdsnSSAGWKNSIRHNLSLHTRFIRV--QNEGTGKSSWWMLNP 184
Cdd:cd20042    10 SYISLTAMAIQSSPEKMLPLSEIYKFIMDRFPYYRE-----NTQRWQNSLRHNLSFNDCFIKIprRPDQPGKGSFWALHP 84

                  ....*
gi 1029201558 185 EGGKM 189
Cdd:cd20042    85 SCGDM 89

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1029201558 107 SYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKdkgdsNSSAGWKNSIRHNLSLHTRFIRVQNE---GTGKSSWW 180
Cdd:cd20022     5 SYLAMIALAIQNSPEKRLTLSEIIKALSTMFPFFK-----GEYKGWKDSVRHNLSSNDCFVKVLKDpgkPQAKGNYW 76

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 1029201558  93 RKSKSSRRNAWGNQSYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKDkgdsnSSAGWKNSIRHNLSLHTRFIRV--Q 170
Cdd:cd20043     3 RPGKNSYSDQKPPYSYISLTAMAIQSSQEKMLPLSDIYKFIMDRFPYYRE-----NTQRWQNSLRHNLSFNDCFIKIprR 77

                          90       100
                  ....*....|....*....|....*....
gi 1029201558 171 NEGTGKSSWWMLNPEGGKM---GKGPRRR 196
Cdd:cd20043    78 PDQPGKGSFWALHPDCGDMfenGSFLRRR 106

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 1029201558 107 SYADLITRAIESTPEKRLTLSQIYDWMVRFVPYFKDKGDsnssaGWKNSIRHNLSLHTRFIRVQNEGTG---KSSWWMLN 183
Cdd:cd20057    10 SYSCLIAMALKNSKTGSLPVSEIYSFMKEHFPYFKTAPD-----GWKNSVRHNLSLNKCFEKVENKMSGssrKGCLWALN 84

                  .
gi 1029201558 184 P 184
Cdd:cd20057    85 P 85