C-terminal domain found in Lysine-specific demethylase 2A; Lysine-specific demethylase 2A (KDM2A) is also called CXXC-type zinc finger protein 8, F-box and leucine-rich repeat protein 11 (FBXL11), F-box protein FBL7, F-box protein Lilina, F-box/LRR-repeat protein 11, JmjC domain-containing histone demethylation protein 1A (Jhdm1a), or [Histone-H3]-lysine-36 demethylase 1A. It is a ubiquitously expressed histone H3 lysine 36 (H3K36) demethylase that has been implicated in gene silencing, cell cycle, cell growth, and cancer development. It acts as a key negative regulator of gluconeogenic gene expression and plays a critical role in the invasiveness, proliferation, and anchorage-independent growth of non-small cell lung cancer (NSCLC) cells, as well as in the osteo/dentinogenic differentiation of Mesenchymal stem cells (MSCs). KDM2A regulates rRNA transcription in response to starvation and functions as a negative regulator of NF-kappaB. It is a heterochromatin-associated and HP1-interacting protein that promotes Heterochromatin Protein 1 (HP1) localization to chromatin. It is specifically recruited to CpG islands to define a unique chromatin architecture, which requires direct and specific interaction with linker DNA. It also functions as a H3K4 demethylase that regulates cell proliferation through p15 (INK4B) and p27 (Kip1) in stem cells from apical papilla (SCAPs). KDM2A belongs to the JmjC domain-containing histone demethylase family. KDM2A consists of two Jumonji domains (JmjN and JmjC), a CXXC zinc-finger domain, a plant homeodomain (PHD) finger, an F-box domain, followed by an antagonist of mitotic exit network protein 1 (AMN1) domain. This model corresponds to a small conserved region in KDM2A between the JmjC domain and the CXXC zinc-finger domain, which has been called the C-terminal domain by literature.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767967744 144 QVHLTHFELEGLRCLVDKLESLPLHKKCVPTGIEDEDALIADVKILLEELANSDPKLALTGVPIVQWP 211
Cdd:cd21784    1 QVHLTHFELEGLRCLVDKLESLPLHKKCVPTGIEDEDALIADVKILLEEHANDDPKLALTGVPIVQWP 68

F-box domain found in F-box/LRR-repeat protein 11 (FBXL11) and similar proteins; FBXL11, also called lysine-specific demethylase 2A (KDM2A), CXXC-type zinc finger protein (CXXC8), F-box and leucine-rich repeat protein 11, F-box protein FBL7, F-box protein Lilina, JmjC domain-containing histone demethylation protein 1A (JHDM1A), or [Histone-H3]-lysine-36 demethylase 1A, is a histone H3 lysine 36 (H3K36) demethylase that regulates epithelial mesenchymal transition (EMT) and the metastasis of ovarian cancer. It plays an essential role in embryonic development and homeostasis by regulating cell proliferation and survival. FBXL11 may also recognize and bind to some phosphorylated proteins and promote their ubiquitination and degradation. It associates with centromeres and represses transcription of small non-coding RNAs that are encoded by the clusters of satellite repeats at the centromere. It is required to sustain centromeric integrity and genomic stability, particularly during mitosis. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 767967744 580 QDGDESWMQREVWMSVFRYLSRRELCECMRVCKTWYKWCCDKRLWTK 626
Cdd:cd22181    1 QAGDESWMQKDVWMSVFRYLSRRELCECMRVCKTWYKWCCDKRLWTK 47

Antagonist of mitotic exit network protein 1; Amn1 has been functionally characterized in Saccharomyces cerevisiae as a component of the Antagonist of MEN pathway (AMEN). The AMEN network is activated by MEN (mitotic exit network) via an active Cdc14, and in turn switches off MEN. Amn1 constitutes one of the alternative mechanisms by which MEN may be disrupted. Specifically, Amn1 binds Tem1 (Termination of M-phase, a GTPase that belongs to the RAS superfamily), and disrupts its association with Cdc15, the primary downstream target. Amn1 is a leucine-rich repeat (LRR) protein, with 12 repeats in the S. cerevisiae ortholog. As a negative regulator of the signal transduction pathway MEN, overexpression of AMN1 slows the growth of wild type cells. The function of the vertebrate members of this family has not been determined experimentally, they have fewer LRRs that determine the extent of this model.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767967744 626 KIDLSRCKAIVPQALSGIIKRQPVSLDL-SWTNISKKQLTWLVNRLPGLKDLLLAGC---SWSAVSALSTSsCPLLRTLD 701
Cdd:cd09293   32 WLELYMCPISDPPLDQLSNCNKLKKLILpGSKLIDDEGLIALAQSCPNLQVLDLRACeniTDSGIVALATN-CPKLQTIN 110

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767967744 702 LRWAVG---IKDPQIRDLltppadkpGQDNRsklrNMTDFRLAGLDITDATLR-LIIRHMPLLSRLDLSHCSHLTDQSsn 777
Cdd:cd09293  111 LGRHRNghlITDVSLSAL--------GKNCT----FLQTVGFAGCDVTDKGVWeLASGCSKSLERLSLNNCRNLTDQS-- 176

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767967744 778 lLTAVGSSTRYS-LTELNMAGCNKLTDqtliyLRRIANVTLIDLRGCKQITRKACE 832
Cdd:cd09293  177 -IPAILASNYFPnLSVLEFRGCPLITD-----FSRIILFKLWQPRLNKPILVEWCE 226

C-terminal domain found in Lysine-specific demethylase 2A; Lysine-specific demethylase 2A (KDM2A) is also called CXXC-type zinc finger protein 8, F-box and leucine-rich repeat protein 11 (FBXL11), F-box protein FBL7, F-box protein Lilina, F-box/LRR-repeat protein 11, JmjC domain-containing histone demethylation protein 1A (Jhdm1a), or [Histone-H3]-lysine-36 demethylase 1A. It is a ubiquitously expressed histone H3 lysine 36 (H3K36) demethylase that has been implicated in gene silencing, cell cycle, cell growth, and cancer development. It acts as a key negative regulator of gluconeogenic gene expression and plays a critical role in the invasiveness, proliferation, and anchorage-independent growth of non-small cell lung cancer (NSCLC) cells, as well as in the osteo/dentinogenic differentiation of Mesenchymal stem cells (MSCs). KDM2A regulates rRNA transcription in response to starvation and functions as a negative regulator of NF-kappaB. It is a heterochromatin-associated and HP1-interacting protein that promotes Heterochromatin Protein 1 (HP1) localization to chromatin. It is specifically recruited to CpG islands to define a unique chromatin architecture, which requires direct and specific interaction with linker DNA. It also functions as a H3K4 demethylase that regulates cell proliferation through p15 (INK4B) and p27 (Kip1) in stem cells from apical papilla (SCAPs). KDM2A belongs to the JmjC domain-containing histone demethylase family. KDM2A consists of two Jumonji domains (JmjN and JmjC), a CXXC zinc-finger domain, a plant homeodomain (PHD) finger, an F-box domain, followed by an antagonist of mitotic exit network protein 1 (AMN1) domain. This model corresponds to a small conserved region in KDM2A between the JmjC domain and the CXXC zinc-finger domain, which has been called the C-terminal domain by literature.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767967744 144 QVHLTHFELEGLRCLVDKLESLPLHKKCVPTGIEDEDALIADVKILLEELANSDPKLALTGVPIVQWP 211
Cdd:cd21784    1 QVHLTHFELEGLRCLVDKLESLPLHKKCVPTGIEDEDALIADVKILLEEHANDDPKLALTGVPIVQWP 68

F-box domain found in F-box/LRR-repeat protein 11 (FBXL11) and similar proteins; FBXL11, also called lysine-specific demethylase 2A (KDM2A), CXXC-type zinc finger protein (CXXC8), F-box and leucine-rich repeat protein 11, F-box protein FBL7, F-box protein Lilina, JmjC domain-containing histone demethylation protein 1A (JHDM1A), or [Histone-H3]-lysine-36 demethylase 1A, is a histone H3 lysine 36 (H3K36) demethylase that regulates epithelial mesenchymal transition (EMT) and the metastasis of ovarian cancer. It plays an essential role in embryonic development and homeostasis by regulating cell proliferation and survival. FBXL11 may also recognize and bind to some phosphorylated proteins and promote their ubiquitination and degradation. It associates with centromeres and represses transcription of small non-coding RNAs that are encoded by the clusters of satellite repeats at the centromere. It is required to sustain centromeric integrity and genomic stability, particularly during mitosis. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 767967744 580 QDGDESWMQREVWMSVFRYLSRRELCECMRVCKTWYKWCCDKRLWTK 626
Cdd:cd22181    1 QAGDESWMQKDVWMSVFRYLSRRELCECMRVCKTWYKWCCDKRLWTK 47

CXXC zinc finger domain; This domain contains eight conserved cysteine residues that bind to two zinc ions. The CXXC domain is found in a variety of chromatin-associated proteins. This domain binds to nonmethyl-CpG dinucleotides. The domain is characterized by two repeats, and shows a peculiar internal duplication in which the second unit is inserted into the first one. Each of these units is characterized by four conserved cysteines, displaying a CXXCXXCX(n)C motif that chelate a Zn+2 ion. The DNA binding interface has been identified by NMR. In eukaryotes, the CXXC domain is found in stramenopiles, plants and metazoans. Plants possess a mono-CXXC domain that is present in distinct chromatin proteins. Structural comparisons show that the mono-CXXC is homologous to the structural-zinc binding domain of medium chain dehydrogenases.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 767967744  270 ACVQGE-CGVCHYCRDMKKFGGPGRMKQSCVLRQC 303
Cdd:pfam02008  14 GCQRPEdCGQCSFCLDMPKFGGPGKKKQKCRLRRC 48

Antagonist of mitotic exit network protein 1; Amn1 has been functionally characterized in Saccharomyces cerevisiae as a component of the Antagonist of MEN pathway (AMEN). The AMEN network is activated by MEN (mitotic exit network) via an active Cdc14, and in turn switches off MEN. Amn1 constitutes one of the alternative mechanisms by which MEN may be disrupted. Specifically, Amn1 binds Tem1 (Termination of M-phase, a GTPase that belongs to the RAS superfamily), and disrupts its association with Cdc15, the primary downstream target. Amn1 is a leucine-rich repeat (LRR) protein, with 12 repeats in the S. cerevisiae ortholog. As a negative regulator of the signal transduction pathway MEN, overexpression of AMN1 slows the growth of wild type cells. The function of the vertebrate members of this family has not been determined experimentally, they have fewer LRRs that determine the extent of this model.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767967744 626 KIDLSRCKAIVPQALSGIIKRQPVSLDL-SWTNISKKQLTWLVNRLPGLKDLLLAGC---SWSAVSALSTSsCPLLRTLD 701
Cdd:cd09293   32 WLELYMCPISDPPLDQLSNCNKLKKLILpGSKLIDDEGLIALAQSCPNLQVLDLRACeniTDSGIVALATN-CPKLQTIN 110

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767967744 702 LRWAVG---IKDPQIRDLltppadkpGQDNRsklrNMTDFRLAGLDITDATLR-LIIRHMPLLSRLDLSHCSHLTDQSsn 777
Cdd:cd09293  111 LGRHRNghlITDVSLSAL--------GKNCT----FLQTVGFAGCDVTDKGVWeLASGCSKSLERLSLNNCRNLTDQS-- 176

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767967744 778 lLTAVGSSTRYS-LTELNMAGCNKLTDqtliyLRRIANVTLIDLRGCKQITRKACE 832
Cdd:cd09293  177 -IPAILASNYFPnLSVLEFRGCPLITD-----FSRIILFKLWQPRLNKPILVEWCE 226

PHD zinc finger; The plant homeodomain (PHD) finger is a C4HC3 zinc-finger-like motif found in nuclear proteins thought to be involved in epigenetics and chromatin-mediated transcriptional regulation. The PHD finger binds two zinc ions using the so-called 'cross-brace' motif and is thus structurally related to the RING finger and the FYVE finger. It is not yet known if PHD fingers have a common molecular function. Several reports suggest that it can function as a protein-protein interacton domain and it was recently demonstrated that the PHD finger of p300 can cooperate with the adjacent BROMO domain in nucleosome binding in vitro. Other reports suggesting that the PHD finger is a ubiquitin ligase have been refuted as these domains were RING fingers misidentified as PHD fingers.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 767967744   313 TCSLCGEVDQNEEtqdfekkLMECCICNEIVHPGCLQMDGEGLLNEElpnCWECPKC 369
Cdd:smart00249   1 YCSVCGKPDDGGE-------LLQCDGCDRWYHQTCLGPPLLEEEPDG---KWYCPKC 47

C-terminal domain found in Lysine-specific demethylase 2A; Lysine-specific demethylase 2A (KDM2A) is also called CXXC-type zinc finger protein 8, F-box and leucine-rich repeat protein 11 (FBXL11), F-box protein FBL7, F-box protein Lilina, F-box/LRR-repeat protein 11, JmjC domain-containing histone demethylation protein 1A (Jhdm1a), or [Histone-H3]-lysine-36 demethylase 1A. It is a ubiquitously expressed histone H3 lysine 36 (H3K36) demethylase that has been implicated in gene silencing, cell cycle, cell growth, and cancer development. It acts as a key negative regulator of gluconeogenic gene expression and plays a critical role in the invasiveness, proliferation, and anchorage-independent growth of non-small cell lung cancer (NSCLC) cells, as well as in the osteo/dentinogenic differentiation of Mesenchymal stem cells (MSCs). KDM2A regulates rRNA transcription in response to starvation and functions as a negative regulator of NF-kappaB. It is a heterochromatin-associated and HP1-interacting protein that promotes Heterochromatin Protein 1 (HP1) localization to chromatin. It is specifically recruited to CpG islands to define a unique chromatin architecture, which requires direct and specific interaction with linker DNA. It also functions as a H3K4 demethylase that regulates cell proliferation through p15 (INK4B) and p27 (Kip1) in stem cells from apical papilla (SCAPs). KDM2A belongs to the JmjC domain-containing histone demethylase family. KDM2A consists of two Jumonji domains (JmjN and JmjC), a CXXC zinc-finger domain, a plant homeodomain (PHD) finger, an F-box domain, followed by an antagonist of mitotic exit network protein 1 (AMN1) domain. This model corresponds to a small conserved region in KDM2A between the JmjC domain and the CXXC zinc-finger domain, which has been called the C-terminal domain by literature.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767967744 144 QVHLTHFELEGLRCLVDKLESLPLHKKCVPTGIEDEDALIADVKILLEELANSDPKLALTGVPIVQWP 211
Cdd:cd21784    1 QVHLTHFELEGLRCLVDKLESLPLHKKCVPTGIEDEDALIADVKILLEEHANDDPKLALTGVPIVQWP 68

C-terminal domain found in lysine-specific demethylase KDM2A, KDM2B, and similar proteins; This family includes lysine-specific demethylases KDM2A and KDM2B, as well as Drosophila melanogaster JmjC domain-containing histone demethylation protein 1 (Jhd1). KDM2A is a ubiquitously expressed histone H3 lysine 36 (H3K36) demethylase that has been implicated in gene silencing, cell cycle, cell growth, and cancer development. KDM2B is a ubiquitously expressed histone H3 lysine 4 (H3K4me2) or histone H3 lysine 36 (H3K36me2) demethylase that functions as a regulator of chemokine expression, cellular morphology, and the metabolome of fibroblasts. Jhd1, also called lysine (K)-specific demethylase 2 (KDM2), or [Histone-H3]-lysine-36 demethylase 1, is a histone demethylase (EC 1.14.11.27) that specifically demethylates 'Lys-36' of histone H3, thereby playing a central role in the histone code. Members in this family belong to the JmjC domain-containing histone demethylase family. They consist of two Jumonji domains (JmjN and JmjC), a CXXC zinc-finger domain, a plant homeodomain (PHD) finger, an F-box domain, followed by an antagonist of mitotic exit network protein 1 (AMN1) domain. This model corresponds to a small conserved region between the JmjC domain and the CXXC zinc-finger domain, which has been called the C-terminal domain by literature.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767967744 145 VHLTHFELEGLRCLVDKLESLPLHKKCVPTGIEDEDALIADVKILLEELANSDPKLALTGVPIVQWP 211
Cdd:cd21743    1 VHLTQFELEGLKKLVDWLESLPQNKKNVPDLILDPDALLQDLKELLEEHKDDDPSLAITGEPILKWP 67

PHD-finger;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767967744  308 LPHSVTCSLCGEVDQNE--ETQDFEKKLMECCICNEIVHPGCLQM-DGEGLLNEELPNCWECPKCY 370
Cdd:pfam16866   1 LPVTAVCIFCGEDGWEDppEESETPSELMECSICYEIVHPQCAKEqNGEGVVNDDLPNSWECPKCC 66

C-terminal domain found in Lysine-specific demethylase 2B; Lysine-specific demethylase 2B (KDM2B) is also called Ndy1, CXXC-type zinc finger protein 2, F-box and leucine-rich (LRR) repeat protein 10 (FBXL10), F-box protein FBL10, JmjC domain-containing histone demethylation protein 1B (Jhdm1b), Jumonji domain-containing EMSY-interactor methyltransferase motif protein (protein JEMMA), or [Histone-H3]-lysine-36 demethylase 1B. It is a ubiquitously expressed histone H3 lysine 4 (H3K4me2) or histone H3 lysine 36 (H3K36me2) demethylase that functions as a regulator of chemokine expression, cellular morphology, and the metabolome of fibroblasts. It regulates the differentiation of Mesenchymal Stem Cells (MSCs) and has been implicated in cell cycle regulation by de-repressing cyclin-dependent kinase inhibitor 2B (CDKN2B or p15INK4B). It also plays a role in recruiting polycomb repressive complex 1 (PRC1) to CpG islands (CGIs) of developmental genes and regulates lysine 119 monoubiquitylation on H2A (H2AK119ub1) in embryonic stem cells (ESCs). KDM2B also acts as an oncogene that plays a critical role in leukemia development and maintenance. It consists of two Jumonji domains (JmjN and JmjC), a CXXC zinc-finger domain, a plant homeodomain (PHD) finger, an F-box domain, followed by an antagonist of mitotic exit network protein 1 (AMN1) domain. This model corresponds to a small conserved region in KDM2B between the JmjC domain and the CXXC zinc-finger domain, which has been called the C-terminal domain by literature.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767967744 145 VHLTHFELEGLRCLVDKLESLPLHKKCVPTGIEDEDALIADVKILLEELANSDPKLALTGVPIVQWP 211
Cdd:cd21785    1 THLTEFELKGLKALVEKLESLPENKKCVPEGIEDPQALLEDMKNVLKEHADDDPNLAISGVPVVSWP 67

F-box domain found in the JmjC domain-containing histone demethylation protein (JHDM) family; The JHDM family includes F-box/LRR-repeat proteins FBXL10, FBXL11 and FBXL19. FBXL10 is also called lysine-specific demethylase 2B (KDM2B), CXXC-type zinc finger protein 2 (CXXC2), F-box and leucine-rich repeat protein 10 (FBL10), JmjC domain-containing histone demethylation protein 1B (JHDM1B), Jumonji domain-containing EMSY-interactor methyltransferase motif protein, protein JEMMA, protein-containing CXXC domain 2, [Histone-H3]-lysine-36 demethylase 1B, or NDY1. It is a histone demethylase that catalyzes the demethylation of H3K4me3 and H3K36me2, thereby playing a central role in the histone code. It preferentially binds the transcribed region of ribosomal RNA and represses the transcription of ribosomal RNA genes which inhibits cell growth and proliferation. FBXL10 may also serve as the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. FBXL11, also called KDM2A, CXXC8, F-box and leucine-rich repeat protein 11, F-box protein FBL7, F-box protein Lilina, JmjC domain-containing histone demethylation protein 1A (JHDM1A), or [Histone-H3]-lysine-36 demethylase 1A, is a histone H3 lysine 36 (H3K36) demethylase that regulates epithelial mesenchymal transition (EMT) and the metastasis of ovarian cancer. It plays an essential role in embryonic development and homeostasis by regulating cell proliferation and survival. FBXL11 may also recognize and bind to some phosphorylated proteins and promote their ubiquitination and degradation. It associates with centromeres and represses transcription of small non-coding RNAs that are encoded by the clusters of satellite repeats at the centromere. It is required to sustain centromeric integrity and genomic stability, particularly during mitosis. FBXL19, also called F-box and leucine-rich repeat protein 19, is the substrate-recognition component of an SCF-type E3 ubiquitin ligase complex. It acts as a CpG island-binding protein in mouse embryonic stem (ES) cells and has been shown to associate with the CDK-Mediator complex. It promotes H2Bub1 at the promoters of CpG island-containing genes by interacting with RNF20. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 767967744 584 ESWMQREVWMSVFRYLSRRELCECMRVCKTWYKWCCDKRLWT 625
Cdd:cd22122    1 NHVLPREVWLPVFQYLSPKDLCVCMRVCKTWNRWCCDPSLWK 42

PHD finger found in Lysine-specific demethylase 2B (KDM2B); KDM2B, also termed Ndy1, or CXXC-type zinc finger protein 2, or F-box and leucine-rich (LRR) repeat protein 10 (FBXL10), or F-box protein FBL10, or JmjC domain-containing histone demethylation protein 1B (Jhdm1b), or Jumonji domain-containing EMSY-interactor methyltransferase motif protein (Protein JEMMA), or [Histone-H3]-lysine-36 demethylase 1B, is a ubiquitously expressed histone H3 lysine 4 (H3K4me2) or histone H3 lysine 36 (H3K36me2) demethylase that functions as a regulator of chemokine expression, cellular morphology, and the metabolome of fibroblasts. It regulates the differentiation of Mesenchymal Stem Cells (MSCs) and has been implicated in cell cycle regulation by de-repressing cyclin-dependent kinase inhibitor 2B (CDKN2B or p15INK4B). It also plays a role in recruiting polycomb repressive complex 1 (PRC1) to CpG islands (CGIs) of developmental genes and regulates lysine 119 monoubiquitylation on H2A (H2AK119ub1) in embryonic stem cells (ESCs). Moreover, it acts as an oncogene that plays a critical role in leukemia development and maintenance. KDM2B consists of two Jumonji C (JmjC) domains, and FBXHA and FBXHB domains. A CXXC zinc-finger domain, followed by a plant homeodomain (PHD) finger, is located within the FBXHA domain, and an F-box domain, followed by an antagonist of mitotic exit network protein 1 (AMN1) domain, is located within the FBXHB domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767967744 314 CSLCGEVDQNEETQDFEKK----LMECCICNEIVHPGCLQM-DGEGLLNEELPNCWECPKC 369
Cdd:cd15644    2 CLVCGEAGKEDTVEEEEGKfnlmLMECSICNEIIHPGCLKVkESDGVVNDELPNCWECPKC 62

CXXC zinc finger domain; This domain contains eight conserved cysteine residues that bind to two zinc ions. The CXXC domain is found in a variety of chromatin-associated proteins. This domain binds to nonmethyl-CpG dinucleotides. The domain is characterized by two repeats, and shows a peculiar internal duplication in which the second unit is inserted into the first one. Each of these units is characterized by four conserved cysteines, displaying a CXXCXXCX(n)C motif that chelate a Zn+2 ion. The DNA binding interface has been identified by NMR. In eukaryotes, the CXXC domain is found in stramenopiles, plants and metazoans. Plants possess a mono-CXXC domain that is present in distinct chromatin proteins. Structural comparisons show that the mono-CXXC is homologous to the structural-zinc binding domain of medium chain dehydrogenases.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 767967744  270 ACVQGE-CGVCHYCRDMKKFGGPGRMKQSCVLRQC 303
Cdd:pfam02008  14 GCQRPEdCGQCSFCLDMPKFGGPGKKKQKCRLRRC 48

Antagonist of mitotic exit network protein 1; Amn1 has been functionally characterized in Saccharomyces cerevisiae as a component of the Antagonist of MEN pathway (AMEN). The AMEN network is activated by MEN (mitotic exit network) via an active Cdc14, and in turn switches off MEN. Amn1 constitutes one of the alternative mechanisms by which MEN may be disrupted. Specifically, Amn1 binds Tem1 (Termination of M-phase, a GTPase that belongs to the RAS superfamily), and disrupts its association with Cdc15, the primary downstream target. Amn1 is a leucine-rich repeat (LRR) protein, with 12 repeats in the S. cerevisiae ortholog. As a negative regulator of the signal transduction pathway MEN, overexpression of AMN1 slows the growth of wild type cells. The function of the vertebrate members of this family has not been determined experimentally, they have fewer LRRs that determine the extent of this model.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767967744 626 KIDLSRCKAIVPQALSGIIKRQPVSLDL-SWTNISKKQLTWLVNRLPGLKDLLLAGC---SWSAVSALSTSsCPLLRTLD 701
Cdd:cd09293   32 WLELYMCPISDPPLDQLSNCNKLKKLILpGSKLIDDEGLIALAQSCPNLQVLDLRACeniTDSGIVALATN-CPKLQTIN 110

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767967744 702 LRWAVG---IKDPQIRDLltppadkpGQDNRsklrNMTDFRLAGLDITDATLR-LIIRHMPLLSRLDLSHCSHLTDQSsn 777
Cdd:cd09293  111 LGRHRNghlITDVSLSAL--------GKNCT----FLQTVGFAGCDVTDKGVWeLASGCSKSLERLSLNNCRNLTDQS-- 176

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767967744 778 lLTAVGSSTRYS-LTELNMAGCNKLTDqtliyLRRIANVTLIDLRGCKQITRKACE 832
Cdd:cd09293  177 -IPAILASNYFPnLSVLEFRGCPLITD-----FSRIILFKLWQPRLNKPILVEWCE 226

F-box domain found in uncharacterized F-box protein group similar to F-box only protein 3 (FBXO3); This subfamily corresponds to a group of uncharacterized F-box proteins which show sequence similarity to F-box only protein 3 (FBXO3). FBXO3, also called FBX3, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex, that mediates the ubiquitination of HIPK2 and probably that of EP300, leading to rapid degradation by the proteasome. It also promotes ubiquitylation and transcriptional activity of AIRE (autoimmune regulator). The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 767967744 590 EVWMSVFRYLSRRELCECMRVCKTWYKWCCDKRLWTKI 627
Cdd:cd22139    7 ELWLHIFSFLSPKDLCQVALVCRRFNRLASDESLWKQI 44

F-box domain found in F-box/LRR-repeat protein 7 (FBXL7) and similar proteins; FBXL7, also called F-box and leucine-rich repeat protein 7, or F-box protein FBL6/FBL7, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of Aurora kinase A (AURKA) during mitosis, causing mitotic arrest. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 767967744 590 EVWMSVFRYLSRRELCECMRVCKTWYKWCCDKRLWTKI 627
Cdd:cd22120    7 DVILQIFSHLPTNQLCRCARVCRRWYNLAWDPRLWTTI 44

F-box domain; This domain is approximately 50 amino acids long, and is usually found in the N-terminal half of a variety of proteins. Two motifs that are commonly found associated with the F-box domain are the leucine rich repeats (LRRs; pfam00560 and pfam07723) and the WD repeat (pfam00400). The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 767967744  590 EVWMSVFRYLSRRELCECMRVCKTWYKWCCDKRLWTK 626
Cdd:pfam00646   7 DLLLEILSRLDPKDLLRLSLVSKRWRSLVDSLKLWKK 43

Antagonist of mitotic exit network protein 1; Amn1 has been functionally characterized in Saccharomyces cerevisiae as a component of the Antagonist of MEN pathway (AMEN). The AMEN network is activated by MEN (mitotic exit network) via an active Cdc14, and in turn switches off MEN. Amn1 constitutes one of the alternative mechanisms by which MEN may be disrupted. Specifically, Amn1 binds Tem1 (Termination of M-phase, a GTPase that belongs to the RAS superfamily), and disrupts its association with Cdc15, the primary downstream target. Amn1 is a leucine-rich repeat (LRR) protein, with 12 repeats in the S. cerevisiae ortholog. As a negative regulator of the signal transduction pathway MEN, overexpression of AMN1 slows the growth of wild type cells. The function of the vertebrate members of this family has not been determined experimentally, they have fewer LRRs that determine the extent of this model.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767967744 684 SAVSALSTSSCPLLRTLDLRwavgikdpqIRDLLTPPADKpgQDNRSKLRNMTdfrLAG-LDITDATLRLIIRHMPLLSR 762
Cdd:cd09293   17 SNISQLLRILHSGLEWLELY---------MCPISDPPLDQ--LSNCNKLKKLI---LPGsKLIDDEGLIALAQSCPNLQV 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767967744 763 LDLSHCSHLTDQSsnlLTAVGSSTRYsLTELNM---AGCNKLTDQTLIYL-RRIANVTLIDLRGCkQITRKA-------C 831
Cdd:cd09293   83 LDLRACENITDSG---IVALATNCPK-LQTINLgrhRNGHLITDVSLSALgKNCTFLQTVGFAGC-DVTDKGvwelasgC 157

                        170
                 ....*....|....*..
gi 767967744 832 EHFISDLSINSLYCLSD 848
Cdd:cd09293  158 SKSLERLSLNNCRNLTD 174

F-box domain found in F-box only protein 10 (FBXO10) and similar proteins; FBXO10, also called FBX10, or PRMT11, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. The SCF(FBXO10) complex mediates ubiquitination and degradation of BCL2, an anti-apoptotic protein, thereby playing a role in apoptosis by controlling the stability of BCL2. It also associates with the receptor for advanced glycation end products (RAGE) to mediate its ubiquitination and degradation. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20
                 ....*....|....*....|....*.
gi 767967744 590 EVWMSVFRYLSRRELCECMRVCKTWY 615
Cdd:cd22090    8 ELWRLILAYLPVRDLCRCCQVCRAWY 33

F-box domain found in F-box/LRR-repeat protein 12 (FBXL12) and similar proteins; FBXL12, also called F-box and leucine-rich repeat protein 12, or F-box protein FBL12, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. It mediates the polyubiquitination and proteasomal degradation of calcium/calmodulin dependent protein kinase I (CAMK1) leading to disruption of cyclin D1/CDK4 complex assembly, which results in G1 cell cycle arrest in lung epithelia. It regulates T-cell differentiation in a cell-autonomous manner. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 767967744 585 SWMQREVWMSVFRYLSRRELCECMRVCKTWYKWCCDKRLW 624
Cdd:cd22123    2 DQLPENVLLEILSYLPVRDLLRISRVCKRWRRLVYDKTLW 41

F-box domain found in Saccharomyces cerevisiae protein Digs into agar protein 2 (ScDIA2) and similar proteins; ScDIA2 is a replication origin-binding protein that plays a role in regulating DNA replication. It is a component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 767967744 590 EVWMSVFRYLSRRELCECMRVCKTWYKWCCDK-RLWTKIDL 629
Cdd:cd22142    8 DILPLIFQKFSTKELITLSHVCSSWRAKILDFpHLWKTVEL 48

PHD zinc finger; The plant homeodomain (PHD) finger is a C4HC3 zinc-finger-like motif found in nuclear proteins thought to be involved in epigenetics and chromatin-mediated transcriptional regulation. The PHD finger binds two zinc ions using the so-called 'cross-brace' motif and is thus structurally related to the RING finger and the FYVE finger. It is not yet known if PHD fingers have a common molecular function. Several reports suggest that it can function as a protein-protein interacton domain and it was recently demonstrated that the PHD finger of p300 can cooperate with the adjacent BROMO domain in nucleosome binding in vitro. Other reports suggesting that the PHD finger is a ubiquitin ligase have been refuted as these domains were RING fingers misidentified as PHD fingers.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 767967744   313 TCSLCGEVDQNEEtqdfekkLMECCICNEIVHPGCLQMDGEGLLNEElpnCWECPKC 369
Cdd:smart00249   1 YCSVCGKPDDGGE-------LLQCDGCDRWYHQTCLGPPLLEEEPDG---KWYCPKC 47

F-box domain found in F-box/LRR-repeat protein 4 (FBXL4) and similar proteins; FBXL4, also called F-box and leucine-rich repeat protein 4, or F-box protein FBL4/FBL5, is part of an SCF (SKP1-cullin-F-box) protein ligase complex. It serves as a clock output molecule that regulates sleep through promotion of rhythmic degradation of the GABA(A) receptor. Biallelic pathogenic variants in FBXL4 are associated with an encephalopathic mtDNA maintenance defect syndrome that is a multi-system disease characterized by lactic acidemia, developmental delay, and hypotonia. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 767967744 590 EVWMSVFRYLSRRELCECMRVCKTWYKWCCDKRLWTKIDL 629
Cdd:cd22117    7 ELIQLILSYLDLPSLCRLSQTCKLFRKHCYDPLLWKELNL 46