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 1034572553  433 QVHLTHFELEGLRCLVDKLESLPLHKKCVPTGIEDEDALIADVKILLEELANSDPKLALTGVPIVQWP 500
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 1034572553  869 QDGDESWMQREVWMSVFRYLSRRELCECMRVCKTWYKWCCDKRLWTK 915
Cdd:cd22181      1 QAGDESWMQKDVWMSVFRYLSRRELCECMRVCKTWYKWCCDKRLWTK 47

RmlC-like cupin superfamily; This superfamily contains proteins similar to the RmlC (dTDP (deoxythymidine diphosphates)-4-dehydrorhamnose 3,5-epimerase)-like cupins. RmlC is a dTDP-sugar isomerase involved in the synthesis of L-rhamnose, a saccharide required for the virulence of some pathogenic bacteria. Cupins are a functionally diverse superfamily originally discovered based on the highly conserved motif found in germin and germin-like proteins. This conserved motif forms a beta-barrel fold found in all of the cupins, giving rise to the name cupin ('cupa' is the Latin term for small barrel). The active site of members of this superfamily is generally located at the center of a conserved barrel and usually includes a metal ion. The different functional classes in this superfamily include single domain bacterial isomerases and epimerases involved in the modification of cell wall carbohydrates, two domain bicupins such as the desiccation-tolerant seed storage globulins, and multidomain nuclear transcription factors involved in legume root nodulation.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034572553  182 YCLMSVRGCYTDFHVDFGGT-SVWYHIHQGGKVFWLIPP-TAHNLELYENWLLSGKQGD--IFLGDRVSDCQ-------- 249
Cdd:pfam02373    1 WLYLGMPFSTTPWHIEDQGLySINYLHFGAPKVWYIIPPeYAEKFEKVLSDHFGGEQPDdlLHLNTIISPKQlrengipv 80

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1034572553  250 -RIELKQGYTFVIPSGWIHAVYTPTDTLVFGGNF 282
Cdd:pfam02373   81 yRFVQKPGEFVFTFPGWYHQVFNLGFNIAEAVNF 114

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 1034572553  915 KIDLSRCKAIVPQALSGIIKRQPVSLDL-SWTNISKKQLTWLVNRLPGLKDLLLAGC---SWSAVSALSTSsCPLLRTLD 990
Cdd:cd09293     32 WLELYMCPISDPPLDQLSNCNKLKKLILpGSKLIDDEGLIALAQSCPNLQVLDLRACeniTDSGIVALATN-CPKLQTIN 110

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034572553  991 LRWAVG---IKDPQIRDLltppadkpGQDNRsklrNMTDFRLAGLDITDATLR-LIIRHMPLLSRLDLSHCSHLTDQSsn 1066
Cdd:cd09293    111 LGRHRNghlITDVSLSAL--------GKNCT----FLQTVGFAGCDVTDKGVWeLASGCSKSLERLSLNNCRNLTDQS-- 176

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034572553 1067 lLTAVGSSTRYS-LTELNMAGCNKLTDqtliyLRRIANVTLIDLRGCKQITRKACE 1121
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 1034572553  433 QVHLTHFELEGLRCLVDKLESLPLHKKCVPTGIEDEDALIADVKILLEELANSDPKLALTGVPIVQWP 500
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 1034572553  869 QDGDESWMQREVWMSVFRYLSRRELCECMRVCKTWYKWCCDKRLWTK 915
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 1034572553  559 ACVQGE-CGVCHYCRDMKKFGGPGRMKQSCVLRQC 592
Cdd:pfam02008   14 GCQRPEdCGQCSFCLDMPKFGGPGKKKQKCRLRRC 48

Jumonji helical domain; This 4-helix bundle domain is associated with the Jumonji domain pfam02373.

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 1034572553  287 NIPMQLKIYNIEDRTRVPNKFRYPFYYEMCWYVLER 322
Cdd:pfam17811    2 NIEMQLRAYEIEKRLKTPDLFKFPNFETICWYVAKH 37

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 1034572553  915 KIDLSRCKAIVPQALSGIIKRQPVSLDL-SWTNISKKQLTWLVNRLPGLKDLLLAGC---SWSAVSALSTSsCPLLRTLD 990
Cdd:cd09293     32 WLELYMCPISDPPLDQLSNCNKLKKLILpGSKLIDDEGLIALAQSCPNLQVLDLRACeniTDSGIVALATN-CPKLQTIN 110

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034572553  991 LRWAVG---IKDPQIRDLltppadkpGQDNRsklrNMTDFRLAGLDITDATLR-LIIRHMPLLSRLDLSHCSHLTDQSsn 1066
Cdd:cd09293    111 LGRHRNghlITDVSLSAL--------GKNCT----FLQTVGFAGCDVTDKGVWeLASGCSKSLERLSLNNCRNLTDQS-- 176

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034572553 1067 lLTAVGSSTRYS-LTELNMAGCNKLTDqtliyLRRIANVTLIDLRGCKQITRKACE 1121
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 1034572553   602 TCSLCGEVDQNEEtqdfekkLMECCICNEIVHPGCLQMDGEGLLNEElpnCWECPKC 658
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 1034572553  433 QVHLTHFELEGLRCLVDKLESLPLHKKCVPTGIEDEDALIADVKILLEELANSDPKLALTGVPIVQWP 500
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 1034572553  434 VHLTHFELEGLRCLVDKLESLPLHKKCVPTGIEDEDALIADVKILLEELANSDPKLALTGVPIVQWP 500
Cdd:cd21743      1 VHLTQFELEGLKKLVDWLESLPQNKKNVPDLILDPDALLQDLKELLEEHKDDDPSLAITGEPILKWP 67

PHD-finger;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034572553  597 LPHSVTCSLCGEVDQNE--ETQDFEKKLMECCICNEIVHPGCLQM-DGEGLLNEELPNCWECPKCY 659
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 1034572553  434 VHLTHFELEGLRCLVDKLESLPLHKKCVPTGIEDEDALIADVKILLEELANSDPKLALTGVPIVQWP 500
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 1034572553  873 ESWMQREVWMSVFRYLSRRELCECMRVCKTWYKWCCDKRLWT 914
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 1034572553  603 CSLCGEVDQNEETQDFEKK----LMECCICNEIVHPGCLQM-DGEGLLNEELPNCWECPKC 658
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 1034572553  559 ACVQGE-CGVCHYCRDMKKFGGPGRMKQSCVLRQC 592
Cdd:pfam02008   14 GCQRPEdCGQCSFCLDMPKFGGPGKKKQKCRLRRC 48

Jumonji helical domain; This 4-helix bundle domain is associated with the Jumonji domain pfam02373.

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 1034572553  287 NIPMQLKIYNIEDRTRVPNKFRYPFYYEMCWYVLER 322
Cdd:pfam17811    2 NIEMQLRAYEIEKRLKTPDLFKFPNFETICWYVAKH 37

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 1034572553  915 KIDLSRCKAIVPQALSGIIKRQPVSLDL-SWTNISKKQLTWLVNRLPGLKDLLLAGC---SWSAVSALSTSsCPLLRTLD 990
Cdd:cd09293     32 WLELYMCPISDPPLDQLSNCNKLKKLILpGSKLIDDEGLIALAQSCPNLQVLDLRACeniTDSGIVALATN-CPKLQTIN 110

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034572553  991 LRWAVG---IKDPQIRDLltppadkpGQDNRsklrNMTDFRLAGLDITDATLR-LIIRHMPLLSRLDLSHCSHLTDQSsn 1066
Cdd:cd09293    111 LGRHRNghlITDVSLSAL--------GKNCT----FLQTVGFAGCDVTDKGVWeLASGCSKSLERLSLNNCRNLTDQS-- 176

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034572553 1067 lLTAVGSSTRYS-LTELNMAGCNKLTDqtliyLRRIANVTLIDLRGCKQITRKACE 1121
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 1034572553  879 EVWMSVFRYLSRRELCECMRVCKTWYKWCCDKRLWTKI 916
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 1034572553  879 EVWMSVFRYLSRRELCECMRVCKTWYKWCCDKRLWTKI 916
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 1034572553  879 EVWMSVFRYLSRRELCECMRVCKTWYKWCCDKRLWTK 915
Cdd:pfam00646    7 DLLLEILSRLDPKDLLRLSLVSKRWRSLVDSLKLWKK 43

F-box domain found in F-box/WD repeat-containing protein 8 (FBXW8) and similar proteins; FBXW8, also called F-box and WD-40 domain-containing protein 8, or F-box only protein 29 (FBXO29), is the substrate-recognition component of a Cul7-RING ubiquitin-protein ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as GORASP1, IRS1, MAP4K1/HPK1. 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 1034572553  878 REVWMSVFRYLSRRELCECMRVCKTWYKWCCDKRLWTKI 916
Cdd:cd22134      9 RELALKIFQYLSVTDLCRCAQVSKSWKSLAEDELLWYRI 47

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 1034572553  879 EVWMSVFRYLSRRELCECMRVCKTWY 904
Cdd:cd22090      8 ELWRLILAYLPVRDLCRCCQVCRAWY 33

PHD finger superfamily; The PHD finger superfamily includes a canonical plant homeodomain (PHD) finger typically characterized as Cys4HisCys3, and a non-canonical extended PHD finger, characterized as Cys2HisCys5HisCys2His. Variations include the RAG2 PHD finger characterized by Cys3His2Cys2His and the PHD finger 5 found in nuclear receptor-binding SET domain-containing proteins characterized by Cys4HisCys2His. The PHD finger is also termed LAP (leukemia-associated protein) motif or TTC (trithorax consensus) domain. Single or multiple copies of PHD fingers have been found in a variety of eukaryotic proteins involved in the control of gene transcription and chromatin dynamics. PHD fingers can recognize the unmodified and modified histone H3 tail, and some have been found to interact with non-histone proteins. They also function as epigenome readers controlling gene expression through molecular recruitment of multi-protein complexes of chromatin regulators and transcription factors. The PHD finger domain SF is structurally similar to the RING and FYVE_like superfamilies.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034572553  602 TCSLCGEVDQNEEtqdfekKLMECCICNEIVHPGCLQMDGEgllNEELPNCWECPKC 658
Cdd:cd15489      1 SCIVCGKGGDLGG------ELLQCDGCGKWFHADCLGPPLS---SFVPNGKWICPVC 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 1034572553   602 TCSLCGEVDQNEEtqdfekkLMECCICNEIVHPGCLQMDGEGLLNEElpnCWECPKC 658
Cdd:smart00249    1 YCSVCGKPDDGGE-------LLQCDGCDRWYHQTCLGPPLLEEEPDG---KWYCPKC 47

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 1034572553  879 EVWMSVFRYLSRRELCECMRVCKTWYKWCCDK-RLWTKIDL 918
Cdd:cd22142      8 DILPLIFQKFSTKELITLSHVCSSWRAKILDFpHLWKTVEL 48

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 1034572553  879 EVWMSVFRYLSRRELCECMRVCKTWYKWCCDKRLWTKIDL 918
Cdd:cd22117      7 ELIQLILSYLDLPSLCRLSQTCKLFRKHCYDPLLWKELNL 46