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 1899630472  432 VCLVCGEAGKEDTVEEEEGKFNLMLMECSICNEIIHPGCLKIKESEGVVNDELPNCWECPKC 493
Cdd:cd15644      1 VCLVCGEAGKEDTVEEEEGKFNLMLMECSICNEIIHPGCLKVKESDGVVNDELPNCWECPKC 62

F-box domain found in F-box/LRR-repeat protein 10 (FBXL10) and similar proteins; FBXL10 is also called lysine-specific demethylase 2B (KDM2B), CXXC-type zinc finger protein 2 (CXXC2), F-box and leucine-rich repeat protein 10, F-box protein 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. 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 1899630472  834 GAAHVMHREVWMAVFSYLSHRDLCVCMRVCRTWNRWCCDKRLWTR 878
Cdd:cd22180      1 GAAHVMQREVWMAVFSYLSHRDLCVCMRVCRTWNRWCCDKRLWTR 45

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 1899630472    1 MSVKGCFTDFHIDFGGT-SVWYHVFRGGKIfWLIPPTLHNLALYEEW--VLSGKQSD--IFLGDRVERCQ---------R 66
Cdd:pfam02373    4 LGMPFSTTPWHIEDQGLySINYLHFGAPKV-WYIIPPEYAEKFEKVLsdHFGGEQPDdlLHLNTIISPKQlrengipvyR 82

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1899630472   67 IELKQGYTFFIPSGWIHAVYTPVDslvfggNILHSFNV 104
Cdd:pfam02373   83 FVQKPGEFVFTFPGWYHQVFNLGF------NIAEAVNF 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 1899630472  892 LSGIIRRQPVSLDLSWTNISKKQLSWLINrLPGLRDLVLSGCSWIA---VSALCSSsCPLLRTLDVQWVEGLKDAqmrDL 968
Cdd:cd09293     22 LLRILHSGLEWLELYMCPISDPPLDQLSN-CNKLKKLILPGSKLIDdegLIALAQS-CPNLQVLDLRACENITDS---GI 96

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1899630472  969 LSPPTDNRPGQMDNRSKLRNivelrlaGLDITDASLRLIIRHMPLLSKLHLSYCnHVTDQSINLLTAVGTttrDSLTEIN 1048
Cdd:cd09293     97 VALATNCPKLQTINLGRHRN-------GHLITDVSLSALGKNCTFLQTVGFAGC-DVTDKGVWELASGCS---KSLERLS 165

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1899630472 1049 LSDCNKVTDQCLS---FFKRCGNICHIDLRYCKQVT 1081
Cdd:cd09293    166 LNNCRNLTDQSIPailASNYFPNLSVLEFRGCPLIT 201

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 1899630472  432 VCLVCGEAGKEDTVEEEEGKFNLMLMECSICNEIIHPGCLKIKESEGVVNDELPNCWECPKC 493
Cdd:cd15644      1 VCLVCGEAGKEDTVEEEEGKFNLMLMECSICNEIIHPGCLKVKESDGVVNDELPNCWECPKC 62

PHD-finger;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1899630472  427 LPHTAVCLVCGEAGKEDTVEEEEgkFNLMLMECSICNEIIHPGCLKIKESEGVVNDELPNCWECPKCN 494
Cdd:pfam16866    1 LPVTAVCIFCGEDGWEDPPEESE--TPSELMECSICYEIVHPQCAKEQNGEGVVNDDLPNSWECPKCC 66

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 1899630472  386 KCEACLRTE-CGECHFCKDMKKFGGPGRMKQSCIMRQC 422
Cdd:pfam02008   11 VCEGCQRPEdCGQCSFCLDMPKFGGPGKKKQKCRLRRC 48

JmjC domain, hydroxylase; The JmjC domain belongs to the Cupin superfamily. JmjC-domain proteins may be protein hydroxylases that catalyze a novel histone modification. This is confirmed to be a hydroxylase: the human JmjC protein named Tyw5p unexpectedly acts in the biosynthesis of a hypermodified nucleoside, hydroxy-wybutosine, in tRNA-Phe by catalysing hydroxylation.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1899630472    1 MSVKGCFTDFHIDFGGT-SVWYHVFRGGKIfWLIPPTLHNLALYEEW--VLSGKQSD--IFLGDRVERCQ---------R 66
Cdd:pfam02373    4 LGMPFSTTPWHIEDQGLySINYLHFGAPKV-WYIIPPEYAEKFEKVLsdHFGGEQPDdlLHLNTIISPKQlrengipvyR 82

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1899630472   67 IELKQGYTFFIPSGWIHAVYTPVDslvfggNILHSFNV 104
Cdd:pfam02373   83 FVQKPGEFVFTFPGWYHQVFNLGF------NIAEAVNF 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 1899630472  892 LSGIIRRQPVSLDLSWTNISKKQLSWLINrLPGLRDLVLSGCSWIA---VSALCSSsCPLLRTLDVQWVEGLKDAqmrDL 968
Cdd:cd09293     22 LLRILHSGLEWLELYMCPISDPPLDQLSN-CNKLKKLILPGSKLIDdegLIALAQS-CPNLQVLDLRACENITDS---GI 96

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1899630472  969 LSPPTDNRPGQMDNRSKLRNivelrlaGLDITDASLRLIIRHMPLLSKLHLSYCnHVTDQSINLLTAVGTttrDSLTEIN 1048
Cdd:cd09293     97 VALATNCPKLQTINLGRHRN-------GHLITDVSLSALGKNCTFLQTVGFAGC-DVTDKGVWELASGCS---KSLERLS 165

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1899630472 1049 LSDCNKVTDQCLS---FFKRCGNICHIDLRYCKQVT 1081
Cdd:cd09293    166 LNNCRNLTDQSIPailASNYFPNLSVLEFRGCPLIT 201

104 kDa microneme/rhoptry antigen; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1899630472  491 PKCNHAGKTGKaykqKRGPGFKYA-SNLP-----GSLLKEQKMNRDNKEgPEPAKRRSECEEAPRRRSDEHPKKVA-PDG 563
Cdd:PTZ00449   549 PGETKEGEVGK----KPGPAKEHKpSKIPtlskkPEFPKDPKHPKDPEE-PKKPKRPRSAQRPTRPKSPKLPELLDiPKS 623

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1899630472  564 ILRRKSDdvhlRRKRKYEKPQEPSGRKRASTLQTSPGSSSHLSPRPPLGSSlspwwrssltyFQQQLKPGKEDKLFRKK- 642
Cdd:PTZ00449   624 PKRPESP----KSPKRPPPPQRPSSPERPEGPKIIKSPKPPKSPKPPFDPK-----------FKEKFYDDYLDAAAKSKe 688

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1899630472  643 -RRSWKNAEDRIALANKPLRRFKQEPEDDLPEAPPK---TRESDHSRSSSPTAgPSTEGAE---GPEEKKKVKMRRKRRL 715
Cdd:PTZ00449   689 tKTTVVLDESFESILKETLPETPGTPFTTPRPLPPKlprDEEFPFEPIGDPDA-EQPDDIEfftPPEEERTFFHETPADT 767

                          250
                   ....*....|..
gi 1899630472  716 PNRELSKELSKE 727
Cdd:PTZ00449   768 PLPDILAEEFKE 779

A Receptor for Ubiquitination Targets;

                            10        20
                    ....*....|....*....|....*.
gi 1899630472   842 EVWMAVFSYLSHRDLCVCMRVCRTWN 867
Cdd:smart00256    4 EILEEILSKLDPKDLLRLRKVSRKWR 29

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 1899630472  432 VCLVCGEAGKEDTVEEEEGKFNLMLMECSICNEIIHPGCLKIKESEGVVNDELPNCWECPKC 493
Cdd:cd15644      1 VCLVCGEAGKEDTVEEEEGKFNLMLMECSICNEIIHPGCLKVKESDGVVNDELPNCWECPKC 62

PHD finger found in F-box and leucine-rich repeat protein 19 (FBXL19); FBXL19, also termed F-box/LRR-repeat protein 19, is a novel homolog of KDM2A and KDM2B. It belongs to the Skp1-Cullin-F-box (SCF) family of E3 ubiquitin ligases. FBXL19 mediates ubiquitination and interleukin 33 (IL-33)-induced degradation of ST2L receptor in lung epithelia, blocks IL-33-mediated apoptosis, and prevents endotoxin-induced acute lung injury. It also functions as a RhoA antagonist during cell proliferation and cytoskeleton rearrangement, and regulates RhoA ubiquitination and degradation in lung epithelial cells. Moreover, FBXL19 regulates cell migration by targeting Rac1 for its polyubiquitination and proteasomal degradation. It plays an essential role in regulating TGFbeta1-induced E-cadherin down-regulation by mediating Rac3 site-specific ubiquitination and stability. FBXL19 consists of 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 1899630472  432 VCLVCGEAGKEDTVEEEEGKFNLMLMECSICNEIIHPGCLKIKESEGVVNDELPNCWECPKC 493
Cdd:cd15645      1 VCLACGEAGKEDTAEGEEEKFDLSLMECTICNEIIHPGCLKMGKAEGVINAEIPNCWECPKC 62

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 1899630472  279 HLTEFELKGLKALVEKLESLPENKKCVPEGIEDPQALLEGVKNVLKEHADDDPSLAITGVPIVTWP 344
Cdd:cd21743      2 HLTQFELEGLKKLVDWLESLPQNKKNVPDLILDPDALLQDLKELLEEHKDDDPSLAITGEPILKWP 67

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 1899630472  277 WTHLTEFELKGLKALVEKLESLPENKKCVPEGIEDPQALLEGVKNVLKEHADDDPSLAITGVPIVTWP 344
Cdd:cd21784      1 QVHLTHFELEGLRCLVDKLESLPLHKKCVPTGIEDEDALIADVKILLEEHANDDPKLALTGVPIVQWP 68

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 1899630472  837 HVMHREVWMAVFSYLSHRDLCVCMRVCRTWNRWCCDKRLWTR 878
Cdd:cd22122      2 HVLPREVWLPVFQYLSPKDLCVCMRVCKTWNRWCCDPSLWKR 43

PHD finger found in Lysine-specific demethylase 2A (KDM2A); KDM2A, also termed CXXC-type zinc finger protein 8, or F-box and leucine-rich repeat protein 11 (FBXL11), or F-box protein FBL7, or F-box protein Lilina, or F-box/LRR-repeat protein 11, or JmjC domain-containing histone demethylation protein 1A (Jhdm1a), or [Histone-H3]-lysine-36 demethylase 1A, 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). It regulates rRNA transcription in response to starvation. Meanwhile, it is a negative regulator of NFkappaB. Moreover, KDM2A is a heterochromatin-associated and HP1-interacting protein that promotes 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 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 1899630472  433 CLVCGEAGKEDTVEEEEGKfnlmLMECSICNEIIHPGCLKIkESEGVVNDELPNCWECPKC 493
Cdd:cd15643      2 CALCGEVDQNEDTQDFEKK----LMECCICNEIVHPGCLQM-DGEGLLNDELPNCWECPKC 57

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 1899630472  386 KCEACLRTE-CGECHFCKDMKKFGGPGRMKQSCIMRQC 422
Cdd:pfam02008   11 VCEGCQRPEdCGQCSFCLDMPKFGGPGKKKQKCRLRRC 48

JmjC domain, hydroxylase; The JmjC domain belongs to the Cupin superfamily. JmjC-domain proteins may be protein hydroxylases that catalyze a novel histone modification. This is confirmed to be a hydroxylase: the human JmjC protein named Tyw5p unexpectedly acts in the biosynthesis of a hypermodified nucleoside, hydroxy-wybutosine, in tRNA-Phe by catalysing hydroxylation.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1899630472    1 MSVKGCFTDFHIDFGGT-SVWYHVFRGGKIfWLIPPTLHNLALYEEW--VLSGKQSD--IFLGDRVERCQ---------R 66
Cdd:pfam02373    4 LGMPFSTTPWHIEDQGLySINYLHFGAPKV-WYIIPPEYAEKFEKVLsdHFGGEQPDdlLHLNTIISPKQlrengipvyR 82

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1899630472   67 IELKQGYTFFIPSGWIHAVYTPVDslvfggNILHSFNV 104
Cdd:pfam02373   83 FVQKPGEFVFTFPGWYHQVFNLGF------NIAEAVNF 114

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

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 1899630472  103 NVPMQLRIYEIEDRTRVQPKFRYPFYYEMCWYVLER 138
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 1899630472  871 CDKRLWTRIDLNHCKSITPLMLSGIirrqpvsldlswTNISKKQLSWLINRLPGLRDLVLSGCSWIAVSALCS--SSCPL 948
Cdd:cd09293     38 CPISDPPLDQLSNCNKLKKLILPGS------------KLIDDEGLIALAQSCPNLQVLDLRACENITDSGIVAlaTNCPK 105

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1899630472  949 LRTLDVQWVEG---LKDAQMRDLLSpptdnrpgqmdNRSKLRNIvelRLAGLDITDASLR-LIIRHMPLLSKLHLSYCNH 1024
Cdd:cd09293    106 LQTINLGRHRNghlITDVSLSALGK-----------NCTFLQTV---GFAGCDVTDKGVWeLASGCSKSLERLSLNNCRN 171

                          170       180       190
                   ....*....|....*....|....*....|...
gi 1899630472 1025 VTDQSINLLTAVGTTTRDSLTEINlsDCNKVTD 1057
Cdd:cd09293    172 LTDQSIPAILASNYFPNLSVLEFR--GCPLITD 202

Leucine-rich repeat (LRR) protein [Transcription];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1899630472  877 TRIDLNHCKSITPLmlsgiirRQPVSLDLSWTNISkkQLSWLINRLPGLRDLVLSGCSwiaVSALCS--SSCPLLRTLDV 954
Cdd:COG4886     99 TELDLSGNEELSNL-------TNLESLDLSGNQLT--DLPEELANLTNLKELDLSNNQ---LTDLPEplGNLTNLKSLDL 166

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1899630472  955 QW--VEGLKDA-----QMRDL-LSpptDNR----PGQMdnrSKLRNIVELRLAGLDITDasLRLIIRHMPLLSKLHLSYc 1022
Cdd:COG4886    167 SNnqLTDLPEElgnltNLKELdLS---NNQitdlPEPL---GNLTNLEELDLSGNQLTD--LPEPLANLTNLETLDLSN- 237

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1899630472 1023 NHVTD-QSINLLTavgtttrdSLTEINLSDcNKVTDqcLSFFKRCGNICHIDLRYCK 1078
Cdd:COG4886    238 NQLTDlPELGNLT--------NLEELDLSN-NQLTD--LPPLANLTNLKTLDLSNNQ 283

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 1899630472  847 VFSYLSHRDLCVCMRVCRTWNRWCCDKRLWTRI 879
Cdd:cd22120     12 IFSHLPTNQLCRCARVCRRWYNLAWDPRLWTTI 44

F-box domain found in uncharacterized F-box protein group similar to F-box only protein 13 (FBXO13); The family corresponds to a group of uncharacterized F-box proteins which show sequence similarity to F-box only protein 13 (FBXO13). FBXO13, also called FBX13, or F-box/LRR-repeat protein 17 (FBL17), or F-box and leucine-rich repeat protein 17 (FBXL17), is the substrate-recognition component of the SCF(FBXL17) E3 ubiquitin ligase complex, a key component of a quality control pathway required to ensure functional dimerization of BTB domain-containing proteins (dimerization quality control, DQC). 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 1899630472  845 MAVFSYLSHRDLCVCMRVCRTWNRWCCDKRLWTRID 880
Cdd:cd22138     10 LKIFSFLSEVDKCLAATVCRSWSELIRSPRLWRTVD 45

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
                   ....*....|....*....|....*....|....
gi 1899630472  843 VWMAVFSYLSHRDLCVCMRVCRTWNRWCCDKRLW 876
Cdd:cd22123      8 VLLEILSYLPVRDLLRISRVCKRWRRLVYDKTLW 41

F-box domain found in F-box only protein 41 (FBXO41) and similar proteins; FBXO41, also called FBX41, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. It acts as a novel central nervous system (CNS)-specific F-box protein that localizes to the centrosome and the cytoplasm of neurons and promotes neuronal migration. 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 1899630472  841 REVWMAVFSYLSHRDLCVCMRVCRTWNRWCCDKRLWTRI 879
Cdd:cd22109      8 RDALFCVFSYLDTKSLLRCAEVCREWRDVSRHPALWQRV 46

F-box domain found in Dictyostelium discoideum Rho GTPase-activating protein gacFF (DdgacFF) and similar proteins; DdgacFF, also called GTPase activating factor for raC protein FF, is a Rho GTPase-activating protein involved in the signal transduction pathway. 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 1899630472  847 VFSYLSHRDLCVCMRVCRTWNRWCCDKRLWTR 878
Cdd:cd22148     13 ILSYLSPKELLIASQVSKTWRRLASSNELWKA 44

104 kDa microneme/rhoptry antigen; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1899630472  491 PKCNHAGKTGKaykqKRGPGFKYA-SNLP-----GSLLKEQKMNRDNKEgPEPAKRRSECEEAPRRRSDEHPKKVA-PDG 563
Cdd:PTZ00449   549 PGETKEGEVGK----KPGPAKEHKpSKIPtlskkPEFPKDPKHPKDPEE-PKKPKRPRSAQRPTRPKSPKLPELLDiPKS 623

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1899630472  564 ILRRKSDdvhlRRKRKYEKPQEPSGRKRASTLQTSPGSSSHLSPRPPLGSSlspwwrssltyFQQQLKPGKEDKLFRKK- 642
Cdd:PTZ00449   624 PKRPESP----KSPKRPPPPQRPSSPERPEGPKIIKSPKPPKSPKPPFDPK-----------FKEKFYDDYLDAAAKSKe 688

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1899630472  643 -RRSWKNAEDRIALANKPLRRFKQEPEDDLPEAPPK---TRESDHSRSSSPTAgPSTEGAE---GPEEKKKVKMRRKRRL 715
Cdd:PTZ00449   689 tKTTVVLDESFESILKETLPETPGTPFTTPRPLPPKlprDEEFPFEPIGDPDA-EQPDDIEfftPPEEERTFFHETPADT 767

                          250
                   ....*....|..
gi 1899630472  716 PNRELSKELSKE 727
Cdd:PTZ00449   768 PLPDILAEEFKE 779

Cupin-like domain; This cupin like domain shares similarity to the JmjC domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1899630472   15 GGTSVWYH---------VFRGGKIFWLIPPT-LHNLALYEEWVLSGKQS----DIFLGD--------RVERCQRIELKQG 72
Cdd:pfam13621  139 GRSVTSLHydhyenlycVVRGRKRFTLFPPSdVPNLYPGPLEPTPEGQVfslvDPLAPDferfprfrDAARPLVVTLNPG 218

                           90
                   ....*....|...
gi 1899630472   73 YTFFIPSGWIHAV 85
Cdd:pfam13621  219 DVLYLPALWWHHV 231

A domain family that is part of the cupin metalloenzyme superfamily; Probable enzymes, but of unknown functions, that regulate chromatin reorganisation processes (Clissold and Ponting, in press).

                            10        20
                    ....*....|....*....|....*.
gi 1899630472     1 MSVKGCFTDFHIDFGGTSVWYHVFRG 26
Cdd:smart00558   33 MGMAGSTTPWHIDDYDLVNYLHQGAG 58

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        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1899630472  432 VCLVCGEAGKEDTVeeeegkfnlmLMECSICNEIIHPGCLKIKESEGVVNDElpncWECPKC 493
Cdd:cd15489      1 SCIVCGKGGDLGGE----------LLQCDGCGKWFHADCLGPPLSSFVPNGK----WICPVC 48

A Receptor for Ubiquitination Targets;

                            10        20
                    ....*....|....*....|....*.
gi 1899630472   842 EVWMAVFSYLSHRDLCVCMRVCRTWN 867
Cdd:smart00256    4 EILEEILSKLDPKDLLRLRKVSRKWR 29

F-box domain found in F-box/LRR-repeat protein 13 (FBXL13) and similar proteins; FBXL13, also called F-box and leucine-rich repeat protein 13, or dynein regulatory complex subunit 6, is a component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes. It is also the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. 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 1899630472  841 REVWMAVFSYLSHRDLCVCMRVCRTW 866
Cdd:cd22124      6 RKAALKIFSYLDLRDLARCAQVCRSW 31

PHD finger 1 found in histone-lysine N-methyltransferase 2A (KMT2A) and 2B (KMT2B); This family includes histone-lysine N-methyltransferase trithorax (Trx) like proteins, KMT2A (MLL1) and KMT2B (MLL2), which comprise the mammalian Trx branch of the COMPASS family, and are both essential for mammalian embryonic development. KMT2A regulates chromatin-mediated transcription through the catalysis of methylation of histone 3 lysine 4 (H3K4), and is frequently rearranged in acute leukemia. KMT2A functions as the catalytic subunit in the MLL1 complex. KMT2B is a second human homolog of Drosophila trithorax, located on chromosome 19 and functions as the catalytic subunit in the MLL2 complex. It plays a critical role in memory formation through mediating hippocampal H3K4 di- and trimethylation. It is also required for RNA polymerase II association and protection from DNA methylation at the MagohB CpG island promoter. Both KMT2A and KMT2B contain a CxxC (x for any residue) zinc finger domain, three plant homeodomain (PHD) fingers, an extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, two FY (phenylalanine tyrosine)-rich domains, and a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain. This model corresponds to the first PHD finger.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1899630472  432 VCLVCGEAGKEDtveeeegkfnlmLMECSICNEIIHPGCLkiKESEGVVNDELPNcWECPKC 493
Cdd:cd15506      1 LCFLCGSAGLNE------------LLYCSVCCEPYHTFCL--EEAERPLNINKDN-WCCRRC 47

F-box domain found in F-box only protein 3 (FBXO3) and similar proteins; FBXO3, also called FBX3, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. It 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 1899630472  847 VFSYLSHRDLCVCMRVCRTWNRWCCDKRLWTRidlnHCK 885
Cdd:cd22084     12 ILSFLDYRDLISCSQVCRRLNQLCSHDPLWKR----LCK 46

F-box domain found in F-box only protein 33 (FBXO33) and similar proteins; FBXO33, also called FBX33, 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 target proteins. It exerts similar functions as F-box involved in polyQ pathogenesis (FipoQ) in modulating the ubiquitination and solubility of expanded SCA3-polyQ 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
                   ....*....|....*....|....*....|....*.
gi 1899630472  847 VFSYLSHRDLCVCMRVCRTWNRWCCDKRLWTRIDLN 882
Cdd:cd22104     12 IFSYLPPRDRLRASSTCRRWREALFHPSLWRSLRLH 47