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 1712927948  608 VCLVCGEAGKEDTVEDEEEKFNLMLMECSICNEIVHPNCLKVKDSNGVVNDELPNCWECPKC 669
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 1712927948 1110 EAHVMQREMWMAVFGHLTHRDLCVCMQVCRTWNRWCCDKRLW 1151
Cdd:cd22180      2 AAHVMQREVWMAVFSYLSHRDLCVCMRVCRTWNRWCCDKRLW 43

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 1712927948  202 YCLMSVKGCYTDFHIDFGGT-SVWYHVFKGQKVfWLVPPTKHNLALYEDW--ALSGKQSD--IFLGDRADGCQ------- 269
Cdd:pfam02373    1 WLYLGMPFSTTPWHIEDQGLySINYLHFGAPKV-WYIIPPEYAEKFEKVLsdHFGGEQPDdlLHLNTIISPKQlrengip 79

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1712927948  270 --RVELKQGYTFFIPSGWIHAVYTPEDTLVFGGN 301
Cdd:pfam02373   80 vyRFVQKPGEFVFTFPGWYHQVFNLGFNIAEAVN 113

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 1712927948 1152 KHINLNRCKSITPLMLSGIIRRQPVA---LDLSWTNISKKQLSWLINrLPGLRVLLLSGCSWVA---VSALCtSSCPLLR 1225
Cdd:cd09293      4 LLFILHKLGQITQSNISQLLRILHSGlewLELYMCPISDPPLDQLSN-CNKLKKLILPGSKLIDdegLIALA-QSCPNLQ 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1712927948 1226 TLDVQWVEGLKDAQMRdllspptdnrpgQLDNRSKLRNVVDLRLA--GLDITDTSLRLIIRYMPLLSKLDLSYCnHITDQ 1303
Cdd:cd09293     82 VLDLRACENITDSGIV------------ALATNCPKLQTINLGRHrnGHLITDVSLSALGKNCTFLQTVGFAGC-DVTDK 148

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1712927948 1304 SVnILTAAGTTtrDSLTDINLSVCNRVTDQSLT---YFKRCGSICHIDLRYCKQVT 1356
Cdd:cd09293    149 GV-WELASGCS--KSLERLSLNNCRNLTDQSIPailASNYFPNLSVLEFRGCPLIT 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 1712927948  608 VCLVCGEAGKEDTVEDEEEKFNLMLMECSICNEIVHPNCLKVKDSNGVVNDELPNCWECPKC 669
Cdd:cd15644      1 VCLVCGEAGKEDTVEEEEGKFNLMLMECSICNEIIHPGCLKVKESDGVVNDELPNCWECPKC 62

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 1712927948  451 THLTDFELSGLKTLVDRLESLPENKKCVPQGIEDPQGLLDCMKVILKEHADDDPRLAITGLPVVHWP 517
Cdd:cd21785      1 THLTEFELKGLKALVEKLESLPENKKCVPEGIEDPQALLEDMKNVLKEHADDDPNLAISGVPVVSWP 67

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 1712927948  562 KCEACLRTE-CGECHFCKDMKKFGGPGRMKQSCIMRQC 598
Cdd:pfam02008   11 VCEGCQRPEdCGQCSFCLDMPKFGGPGKKKQKCRLRRC 48

F-box-like; This is an F-box-like family.

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1712927948 1117 EMWMAVFGHLTHRDLCVCMQVCRTWNRWCCDKRLWKHI 1154
Cdd:pfam12937    7 EILLQIFSYLDPKDLLRLALVCRRWRELASDDSLWRRL 44

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        30
                    ....*....|....*....|....*....|....
gi 1712927948   197 PKVQRYCLMSVKGCYTDFHIDFGGTSVWYHVFKG 230
Cdd:smart00558   25 PDVGPYLYMGMAGSTTPWHIDDYDLVNYLHQGAG 58

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        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1712927948   608 VCLVCGEAGKEDTvedeeekfnlmLMECSICNEIVHPNCLKVKDSNGVVNDElpncWECPKC 669
Cdd:smart00249    1 YCSVCGKPDDGGE-----------LLQCDGCDRWYHQTCLGPPLLEEEPDGK----WYCPKC 47

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 1712927948  608 VCLVCGEAGKEDTVEDEEEKFNLMLMECSICNEIVHPNCLKVKDSNGVVNDELPNCWECPKC 669
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 1712927948  608 VCLVCGEAGKEDTVEDEEEKFNLMLMECSICNEIVHPNCLKVKDSNGVVNDELPNCWECPKC 669
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 1712927948  452 HLTDFELSGLKTLVDRLESLPENKKCVPQGIEDPQGLLDCMKVILKEHADDDPRLAITGLPVVHWP 517
Cdd:cd21743      2 HLTQFELEGLKKLVDWLESLPQNKKNVPDLILDPDALLQDLKELLEEHKDDDPSLAITGEPILKWP 67

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 1712927948 1110 EAHVMQREMWMAVFGHLTHRDLCVCMQVCRTWNRWCCDKRLW 1151
Cdd:cd22180      2 AAHVMQREVWMAVFSYLSHRDLCVCMRVCRTWNRWCCDKRLW 43

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 1712927948 1112 HVMQREMWMAVFGHLTHRDLCVCMQVCRTWNRWCCDKRLWKH 1153
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
                   ....*....|....*....|....*....|....*...
gi 1712927948 1114 MQREMWMAVFGHLTHRDLCVCMQVCRTWNRWCCDKRLW 1151
Cdd:cd22181      8 MQKDVWMSVFRYLSRRELCECMRVCKTWYKWCCDKRLW 45

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 1712927948  562 KCEACLRTE-CGECHFCKDMKKFGGPGRMKQSCIMRQC 598
Cdd:pfam02008   11 VCEGCQRPEdCGQCSFCLDMPKFGGPGKKKQKCRLRRC 48

F-box-like; This is an F-box-like family.

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1712927948 1117 EMWMAVFGHLTHRDLCVCMQVCRTWNRWCCDKRLWKHI 1154
Cdd:pfam12937    7 EILLQIFSYLDPKDLLRLALVCRRWRELASDDSLWRRL 44

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 1712927948 1117 EMWMAVFGHLTHRDLCVCMQVCRTWNRWCCDKRLWKHI 1154
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 1712927948 1152 KHINLNRCKSITPLMLSGIIRRQPVA---LDLSWTNISKKQLSWLINrLPGLRVLLLSGCSWVA---VSALCtSSCPLLR 1225
Cdd:cd09293      4 LLFILHKLGQITQSNISQLLRILHSGlewLELYMCPISDPPLDQLSN-CNKLKKLILPGSKLIDdegLIALA-QSCPNLQ 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1712927948 1226 TLDVQWVEGLKDAQMRdllspptdnrpgQLDNRSKLRNVVDLRLA--GLDITDTSLRLIIRYMPLLSKLDLSYCnHITDQ 1303
Cdd:cd09293     82 VLDLRACENITDSGIV------------ALATNCPKLQTINLGRHrnGHLITDVSLSALGKNCTFLQTVGFAGC-DVTDK 148

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1712927948 1304 SVnILTAAGTTtrDSLTDINLSVCNRVTDQSLT---YFKRCGSICHIDLRYCKQVT 1356
Cdd:cd09293    149 GV-WELASGCS--KSLERLSLNNCRNLTDQSIPailASNYFPNLSVLEFRGCPLIT 201

F-box domain superfamily; This short domain is commonly found at the N-terminus of various proteins, and typically co-occurs with one or more other conserved domains or motifs, such as leucine rich repeats, WD40 repeats, kelch, tub, spry, and others. 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. One of the best researched roles of F-box proteins is their participation in SCF (Skp1-Cul1-F-box protein), a multi-protein complex that functions as a ubiquitin E3 ligase, where the role of the F-box protein is to recruit target substrates. Gene families containing the F-box are found greatly expanded in narrow taxonomic lineages, such as flowering plants and nematodes. In this hierarchical classification, many of the subfamilies are named according to their domain architectures.

                           10        20        30
                   ....*....|....*....|....*....|
gi 1712927948 1117 EMWMAVFGHLTHRDLCVCMQVCRTWNRWCC 1146
Cdd:cd09917      6 EILLKILSYLDPRDLLRLSLVCKRWRELAS 35

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 1712927948 1117 EMWMAVFGHLTHRDLCVCMQVCRTWNRWCCDKRLWKHINLN 1157
Cdd:cd22117      7 ELIQLILSYLDLPSLCRLSQTCKLFRKHCYDPLLWKELNLQ 47

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 1712927948 1117 EMWMAVFGHLTHRDLCVCMQVCRTWNRWCCDKRLWKH 1153
Cdd:pfam00646    7 DLLLEILSRLDPKDLLRLSLVSKRWRSLVDSLKLWKK 43

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 1712927948 1122 VFGHLTHRDLCVCMQVCRTWNRWCCDKRLWKHI 1154
Cdd:cd22120     12 IFSHLPTNQLCRCARVCRRWYNLAWDPRLWTTI 44

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 1712927948 1122 VFGHLTHRDLCVCMQVCRTWNRWCCDKRLWK 1152
Cdd:cd22148     13 ILSYLSPKELLIASQVSKTWRRLASSNELWK 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 1712927948 1116 REMWMAVFGHLTHRDLCVCMQVCRTWNRWCCDKRLWKHI 1154
Cdd:cd22134      9 RELALKIFQYLSVTDLCRCAQVSKSWKSLAEDELLWYRI 47

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        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1712927948   608 VCLVCGEAGKEDTvedeeekfnlmLMECSICNEIVHPNCLKVKDSNGVVNDElpncWECPKC 669
Cdd:smart00249    1 YCSVCGKPDDGGE-----------LLQCDGCDRWYHQTCLGPPLLEEEPDGK----WYCPKC 47

F-box domain found in F-box only protein 48 (FBXO48) and similar proteins; FBXO48, also called FBX48, is one of the paralogs of the F-box only protein 7 (FBXO7), which is the causative gene for PARK15 (also known as Parkinsonian-pyramidal disease, PPD). 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 1712927948 1117 EMWMAVFGHLTHRDLCVCMQVCRTWNRWCCDK-RLWKH 1153
Cdd:cd22113      7 EMSLRIFSQLDVQSLCRASQTCKTWNDLIENSdYLWRP 44

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 1712927948 1122 VFGHLTHRDLCVCMQVCRTWNRWCCDKRLWK 1152
Cdd:cd22123     12 ILSYLPVRDLLRISRVCKRWRRLVYDKTLWR 42