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 1958668769  630 VCLVCGEAGKEDTVEEEEGKFNLMLMECSICNEIIHPGCLKIKESEGVVNDELPNCWECPKC 691
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 1958668769  991 GAAHVMHREVWMAVFSYLSHQDLCVCMRVCRTWNRWCCDKRLWTR 1035
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 1958668769  198 YCLMSVKGCFTDFHIDFGGT-SVWYHVFRGGKIfWLIPPTLHNLALYEEW--VLSGKQSD--IFLGDRVERCQ------- 265
Cdd:pfam02373    1 WLYLGMPFSTTPWHIEDQGLySINYLHFGAPKV-WYIIPPEYAEKFEKVLsdHFGGEQPDdlLHLNTIISPKQlrengip 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1958668769  266 --RIELKQGYTFFIPSGWIHAVYTPVDslvfggNILHSFNV 304
Cdd:pfam02373   80 vyRFVQKPGEFVFTFPGWYHQVFNLGF------NIAEAVNF 114

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

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 1958668769  303 NVPMQLRIYEIEDRTRVQPKFRYPFYYEMCWYVLER 338
Cdd:pfam17811    2 NIEMQLRAYEIEKRLKTPDLFKFPNFETICWYVAKH 37

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 1958668769  630 VCLVCGEAGKEDTVEEEEGKFNLMLMECSICNEIIHPGCLKIKESEGVVNDELPNCWECPKC 691
Cdd:cd15644      1 VCLVCGEAGKEDTVEEEEGKFNLMLMECSICNEIIHPGCLKVKESDGVVNDELPNCWECPKC 62

PHD-finger;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958668769  625 LPHTAVCLVCGEAGKEDTVEEEEgkFNLMLMECSICNEIIHPGCLKIKESEGVVNDELPNCWECPKCN 692
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 1958668769  584 KCEACLRTE-CGECHFCKDMKKFGGPGRMKQSCIMRQC 620
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 1958668769  198 YCLMSVKGCFTDFHIDFGGT-SVWYHVFRGGKIfWLIPPTLHNLALYEEW--VLSGKQSD--IFLGDRVERCQ------- 265
Cdd:pfam02373    1 WLYLGMPFSTTPWHIEDQGLySINYLHFGAPKV-WYIIPPEYAEKFEKVLsdHFGGEQPDdlLHLNTIISPKQlrengip 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1958668769  266 --RIELKQGYTFFIPSGWIHAVYTPVDslvfggNILHSFNV 304
Cdd:pfam02373   80 vyRFVQKPGEFVFTFPGWYHQVFNLGF------NIAEAVNF 114

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

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 1958668769  303 NVPMQLRIYEIEDRTRVQPKFRYPFYYEMCWYVLER 338
Cdd:pfam17811    2 NIEMQLRAYEIEKRLKTPDLFKFPNFETICWYVAKH 37

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668769 1034 TRIDLNHCKSITPLmlsgiirRQPVSLDLSWTNISkkQLSWLINRLPGLRDLVLSGCSwiaVSALCS--SSCPLLRTLDV 1111
Cdd:COG4886     99 TELDLSGNEELSNL-------TNLESLDLSGNQLT--DLPEELANLTNLKELDLSNNQ---LTDLPEplGNLTNLKSLDL 166

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668769 1112 QW--VEGLKDA-----QMRDL-LSpptDNR----PGQMdnrSKLRNIVELRLAGLDITDVSLRLiiRHMPLLSKLHLSYc 1179
Cdd:COG4886    167 SNnqLTDLPEElgnltNLKELdLS---NNQitdlPEPL---GNLTNLEELDLSGNQLTDLPEPL--ANLTNLETLDLSN- 237

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1958668769 1180 NHVTD-QSINLLTavgtttrdSLTEINLSDcNKVTDqcLSFFKRCGNICHIDLRYCK 1235
Cdd:COG4886    238 NQLTDlPELGNLT--------NLEELDLSN-NQLTD--LPPLANLTNLKTLDLSNNQ 283

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 1958668769  630 VCLVCGEAGKEDTVEEEEGKFNLMLMECSICNEIIHPGCLKIKESEGVVNDELPNCWECPKC 691
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 1958668769  630 VCLVCGEAGKEDTVEEEEGKFNLMLMECSICNEIIHPGCLKIKESEGVVNDELPNCWECPKC 691
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 1958668769  477 HLTEFELKGLKALVEKLESLPENKKCVPEGIEDPQALLEGVKNVLKEHVDDDPNLAITGVPVVSWP 542
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 1958668769  475 WTHLTEFELKGLKALVEKLESLPENKKCVPEGIEDPQALLEGVKNVLKEHVDDDPNLAITGVPVVSWP 542
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 1958668769  994 HVMHREVWMAVFSYLSHQDLCVCMRVCRTWNRWCCDKRLWTR 1035
Cdd:cd22122      2 HVLPREVWLPVFQYLSPKDLCVCMRVCKTWNRWCCDPSLWKR 43

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 1958668769  996 MHREVWMAVFSYLSHQDLCVCMRVCRTWNRWCCDKRLWTR 1035
Cdd:cd22181      8 MQKDVWMSVFRYLSRRELCECMRVCKTWYKWCCDKRLWTK 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 1958668769  584 KCEACLRTE-CGECHFCKDMKKFGGPGRMKQSCIMRQC 620
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 1958668769  198 YCLMSVKGCFTDFHIDFGGT-SVWYHVFRGGKIfWLIPPTLHNLALYEEW--VLSGKQSD--IFLGDRVERCQ------- 265
Cdd:pfam02373    1 WLYLGMPFSTTPWHIEDQGLySINYLHFGAPKV-WYIIPPEYAEKFEKVLsdHFGGEQPDdlLHLNTIISPKQlrengip 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1958668769  266 --RIELKQGYTFFIPSGWIHAVYTPVDslvfggNILHSFNV 304
Cdd:pfam02373   80 vyRFVQKPGEFVFTFPGWYHQVFNLGF------NIAEAVNF 114

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 1958668769  999 EVWMAVFSYLSHQDLCVCMRVCRTWNRWCCDKRLWTRI 1036
Cdd:cd22139      7 ELWLHIFSFLSPKDLCQVALVCRRFNRLASDESLWKQI 44

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 1958668769 1028 CDKRLWTRIDLNHCKSITPLMLSGIirrqpvsldlswTNISKKQLSWLINRLPGLRDLVLSGCSWIA---VSALcSSSCP 1104
Cdd:cd09293     38 CPISDPPLDQLSNCNKLKKLILPGS------------KLIDDEGLIALAQSCPNLQVLDLRACENITdsgIVAL-ATNCP 104

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668769 1105 LLRTLDVQWVEG---LKDAQMRDLlspptdnrpGQmdNRSKLRNIvelRLAGLDITDVSLR-LIIRHMPLLSKLHLSYCN 1180
Cdd:cd09293    105 KLQTINLGRHRNghlITDVSLSAL---------GK--NCTFLQTV---GFAGCDVTDKGVWeLASGCSKSLERLSLNNCR 170

                          170       180       190
                   ....*....|....*....|....*....|....
gi 1958668769 1181 HVTDQSINLLTAVGTTTRDSLTEINlsDCNKVTD 1214
Cdd:cd09293    171 NLTDQSIPAILASNYFPNLSVLEFR--GCPLITD 202

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668769 1034 TRIDLNHCKSITPLmlsgiirRQPVSLDLSWTNISkkQLSWLINRLPGLRDLVLSGCSwiaVSALCS--SSCPLLRTLDV 1111
Cdd:COG4886     99 TELDLSGNEELSNL-------TNLESLDLSGNQLT--DLPEELANLTNLKELDLSNNQ---LTDLPEplGNLTNLKSLDL 166

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958668769 1112 QW--VEGLKDA-----QMRDL-LSpptDNR----PGQMdnrSKLRNIVELRLAGLDITDVSLRLiiRHMPLLSKLHLSYc 1179
Cdd:COG4886    167 SNnqLTDLPEElgnltNLKELdLS---NNQitdlPEPL---GNLTNLEELDLSGNQLTDLPEPL--ANLTNLETLDLSN- 237

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1958668769 1180 NHVTD-QSINLLTavgtttrdSLTEINLSDcNKVTDqcLSFFKRCGNICHIDLRYCK 1235
Cdd:COG4886    238 NQLTDlPELGNLT--------NLEELDLSN-NQLTD--LPPLANLTNLKTLDLSNNQ 283

F-box domain found in Drosophila melanogaster S-phase kinase-associated protein 2 (DmSKP2) and similar proteins; DmSKP2 is a Drosophila F-box protein that regulates cell proliferation by targeting Dacapo (Dap) for ubiquitination and proteasome-mediated degradation. It plays a role in maintaining diploidy of mitotic cells during development. 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 1958668769  999 EVWMAVFSYLSHQDLCVCMRVCRTWNRWCCDKRLWTR 1035
Cdd:cd22149      7 EIILSIFKWLPKKTLARCARVCRRWKRLCFDESLWRR 43

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 1958668769 1002 MAVFSYLSHQDLCVCMRVCRTWNRWCCDKRLWTRID 1037
Cdd:cd22138     10 LKIFSFLSEVDKCLAATVCRSWSELIRSPRLWRTVD 45

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        40
                   ....*....|....*....|....*....|....*....|
gi 1958668769  996 MHREVWMAVFSYLSHQDLCVCMRVCRTWNRWCCDKRLWTR 1035
Cdd:pfam00646    4 LPDDLLLEILSRLDPKDLLRLSLVSKRWRSLVDSLKLWKK 43

F-box domain found in F-box only protein 11 (FBXO11) and similar proteins; FBXO11, also called FBX11, protein arginine N-methyltransferase 9 (PRMT9), or vitiligo-associated protein 1 (VIT-1), 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, such as DTL/CDT2, BCL6 and PRDM1/BLIMP1. 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 1958668769  999 EVWMAVFSYLSHQDLCVCMRVCRTWNRWCCDKRLWTRI 1036
Cdd:cd22091      7 EVLLKIFSYLLEQDLCRAAQVCKRFNTLANDPELWKRL 44

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 1958668769  999 EVWMAVFSYLSHQDLCVCMRVCRTWN 1024
Cdd:cd22090      8 ELWRLILAYLPVRDLCRCCQVCRAWY 33

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 1958668769  998 REVWMAVFSYLSHQDLCVCMRVCRTWNRWCCDKRLWTRI 1036
Cdd:cd22134      9 RELALKIFQYLSVTDLCRCAQVSKSWKSLAEDELLWYRI 47

F-box domain found in F-box only protein 13 (FBXO13) and similar proteins; FBXO13, also called FBX13, F-box/LRR-repeat protein 17 (FBL17), or F-box and leucine-rich repeat protein 17 (FBXL17), is the substrate-recognition component of 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        40
                   ....*....|....*....|....*....|....*....|
gi 1958668769 1000 VWMAVFSYLSHQDLCVCM-RVCRTWNRWCCDKRLWTRIDL 1038
Cdd:cd22092      9 ILLKIFSYLSLQERCLSAsLVCKYWRDLCLDSQFWKQIDL 48

F-box domain found in F-box/WD repeat-containing protein 5 (FBXW5) and similar proteins; FBXW5, also called F-box and WD-40 domain-containing protein 5, is the substrate-recognition component of both SCF (SKP1-CUL1-F-box protein) and DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes. 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 1958668769 1004 VFSYLSHQDLCVCMRVCRTWNRWCCDKRLWTRI 1036
Cdd:cd22132     12 IFSYLSPKDLLAAGQVCKQWYRVSRDEFLWKEL 44

F-box domain found in F-box/LRR-repeat protein 2 (FBXL2), F-box/LRR-repeat protein 20 (FBXL20) and similar proteins; The family includes FBXL2 and FBXL30. FBXL2, also called F-box and leucine-rich repeat protein 2, or F-box protein FBL2/FBL3, is a calcium-activated substrate-recognition component of an SCF (SKP1-cullin-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Unlike many F-box proteins, FBXL2 does not seem to target phosphodegron within its substrates but rather calmodulin-binding motifs and is thereby antagonized by calmodulin. FBXL20, also called SCRAPPER, F-box and leucine-rich repeat protein 20, or F-box/LRR-repeat protein 2-like, is a component of a synapse-localized SCF-type E3 ubiquitin ligase which regulates neural transmission. It is widely expressed in the central nervous system and plays an important role in the ubiquitin-dependent degradation of regulating synaptic membrane exocytosis 1 (RIM1), which is an important factor in the release of synaptic vesicles. It may also mediate the ubiquitin degradation of E-cadherin resulting in an increased invasive ability of malignant cells. 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 1958668769  998 REVWMAVFSYLSHQDLCVCMRVCRTWNRWCCDKRLW 1033
Cdd:cd22115      9 KELLLRIFSFLDVVTLCRCAQVSKYWNVLALDGSNW 44

F-box domain found in F-box/LRR-repeat protein 1 (FBXL1) and similar proteins; FBXL1, also called S-phase kinase-associated protein 2, cyclin-A/CDK2-associated protein p45, F-box protein Skp2, or p45skp2, 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 involved in cell cycle progression, signal transduction and transcription. It specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. 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 1958668769  999 EVWMAVFSYLSHQDLCVCMRVCRTWNRWCCDKRLW 1033
Cdd:cd22114      7 ELLLGIFSCLCLPDLLKVSQVCKRWYRLASDESLW 41

F-box domain found in the early mitotic inhibitor (EMI) family of F-box proteins; The EMI family includes FBX5 (EMI1) and FBX43 (EMI2), which are anaphase-promoting complex/cyclosome (APC/C) inhibitors that bind APC/C-CCD20 (Cell division cycle protein 20) and/or APC/C-CDH1 (CDC20 homologue 1) complexes. 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 1958668769 1004 VFSYLSHQDLCVCMRVCRTWNRWC-CDKRLWTRI 1036
Cdd:cd22086     15 ILSYLSPEDLCRVSCVSKTWRQIClSDPKANRRR 48