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 755513742  628 VCLVCGEAGKEDTVEEEEGKFNLMLMECSICNEIIHPGCLKIKESEGVVNDELPNCWECPKC 689
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 755513742 1030 GAAHVMHREVWMAVFSYLSHRDLCVCMRVCRTWNRWCCDKRLWTR 1074
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 755513742   192 YCLMSVKGCFTDFHIDFGGT-SVWYHVFRGGKIfWLIPPTLHNLALYEEW--VLSGKQSD--IFLGDRVERCQ------- 259
Cdd:pfam02373    1 WLYLGMPFSTTPWHIEDQGLySINYLHFGAPKV-WYIIPPEYAEKFEKVLsdHFGGEQPDdlLHLNTIISPKQlrengip 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 755513742   260 --RIELKQGYTFFIPSGWIHAVYTPVDslvfggNILHSFNV 298
Cdd:pfam02373   80 vyRFVQKPGEFVFTFPGWYHQVFNLGF------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 755513742 1077 LNRCKSITPLMLSGIIRRQPV---SLDLSWTNISKKQLSWLINrLPGLRDLVLSGCSWIA---VSALCSSsCPLLRTLDV 1150
Cdd:cd09293     8 LHKLGQITQSNISQLLRILHSgleWLELYMCPISDPPLDQLSN-CNKLKKLILPGSKLIDdegLIALAQS-CPNLQVLDL 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755513742 1151 QWVEGLKDAqmrDLLSPPTDNRPGQMDNRSKLRNivelrlaGLDITDVSLRLIIRHMPLLSKLQLSYCnHINDQS-INLL 1229
Cdd:cd09293    86 RACENITDS---GIVALATNCPKLQTINLGRHRN-------GHLITDVSLSALGKNCTFLQTVGFAGC-DVTDKGvWELA 154

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 755513742 1230 TAVGtttrDSLTEVNLSDCNKVTDLCLS---FFKRCGNICHIDLRYCKQVT 1277
Cdd:cd09293   155 SGCS----KSLERLSLNNCRNLTDQSIPailASNYFPNLSVLEFRGCPLIT 201

104 kDa microneme/rhoptry antigen; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755513742  687 PKCNHAGKTGKaykqKRGPGFKYA-SNLP-----GSLLKEQKMNRDNKEGQEPAKRRSEceEAPRRRSDehPKKVPADGI 760
Cdd:PTZ00449  549 PGETKEGEVGK----KPGPAKEHKpSKIPtlskkPEFPKDPKHPKDPEEPKKPKRPRSA--QRPTRPKS--PKLPELLDI 620

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755513742  761 LRRKSDDVHLRRKRKYEKPQELSGRKRASSLQTSPGSSSHLSPRPPLGSSlspwwrssltyFQQQLKPGKEDKLFRKK-- 838
Cdd:PTZ00449  621 PKSPKRPESPKSPKRPPPPQRPSSPERPEGPKIIKSPKPPKSPKPPFDPK-----------FKEKFYDDYLDAAAKSKet 689

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755513742  839 RRSWKNAEDRLSLANKPLRRFKQEPEDDLPEAPPKtRESDQSRSSSPTAGPST------EGAEGPEEKKKVKMRRKRRLV 912
Cdd:PTZ00449  690 KTTVVLDESFESILKETLPETPGTPFTTPRPLPPK-LPRDEEFPFEPIGDPDAeqpddiEFFTPPEEERTFFHETPADTP 768

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 755513742  913 NKELSKELSKELN-HEIQKTESTLAHESQQPIKSEPESENDEPKRPLshceRPHRfSKGLNGTPRELRHSLGPGLRSP 989
Cdd:PTZ00449  769 LPDILAEEFKEEDiHAETGEPDEAMKRPDSPSEHEDKPPGDHPSLPK----KRHR-LDGLALSTTDLESDAGRIAKDA 841

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 755513742  628 VCLVCGEAGKEDTVEEEEGKFNLMLMECSICNEIIHPGCLKIKESEGVVNDELPNCWECPKC 689
Cdd:cd15644     1 VCLVCGEAGKEDTVEEEEGKFNLMLMECSICNEIIHPGCLKVKESDGVVNDELPNCWECPKC 62

PHD-finger;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 755513742   623 LPHTAVCLVCGEAGKEDTVEEEEgkFNLMLMECSICNEIIHPGCLKIKESEGVVNDELPNCWECPKCN 690
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 755513742   582 KCEACLRTE-CGECHFCKDMKKFGGPGRMKQSCIMRQC 618
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 755513742   192 YCLMSVKGCFTDFHIDFGGT-SVWYHVFRGGKIfWLIPPTLHNLALYEEW--VLSGKQSD--IFLGDRVERCQ------- 259
Cdd:pfam02373    1 WLYLGMPFSTTPWHIEDQGLySINYLHFGAPKV-WYIIPPEYAEKFEKVLsdHFGGEQPDdlLHLNTIISPKQlrengip 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 755513742   260 --RIELKQGYTFFIPSGWIHAVYTPVDslvfggNILHSFNV 298
Cdd:pfam02373   80 vyRFVQKPGEFVFTFPGWYHQVFNLGF------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 755513742 1077 LNRCKSITPLMLSGIIRRQPV---SLDLSWTNISKKQLSWLINrLPGLRDLVLSGCSWIA---VSALCSSsCPLLRTLDV 1150
Cdd:cd09293     8 LHKLGQITQSNISQLLRILHSgleWLELYMCPISDPPLDQLSN-CNKLKKLILPGSKLIDdegLIALAQS-CPNLQVLDL 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755513742 1151 QWVEGLKDAqmrDLLSPPTDNRPGQMDNRSKLRNivelrlaGLDITDVSLRLIIRHMPLLSKLQLSYCnHINDQS-INLL 1229
Cdd:cd09293    86 RACENITDS---GIVALATNCPKLQTINLGRHRN-------GHLITDVSLSALGKNCTFLQTVGFAGC-DVTDKGvWELA 154

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 755513742 1230 TAVGtttrDSLTEVNLSDCNKVTDLCLS---FFKRCGNICHIDLRYCKQVT 1277
Cdd:cd09293   155 SGCS----KSLERLSLNNCRNLTDQSIPailASNYFPNLSVLEFRGCPLIT 201

104 kDa microneme/rhoptry antigen; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755513742  687 PKCNHAGKTGKaykqKRGPGFKYA-SNLP-----GSLLKEQKMNRDNKEGQEPAKRRSEceEAPRRRSDehPKKVPADGI 760
Cdd:PTZ00449  549 PGETKEGEVGK----KPGPAKEHKpSKIPtlskkPEFPKDPKHPKDPEEPKKPKRPRSA--QRPTRPKS--PKLPELLDI 620

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755513742  761 LRRKSDDVHLRRKRKYEKPQELSGRKRASSLQTSPGSSSHLSPRPPLGSSlspwwrssltyFQQQLKPGKEDKLFRKK-- 838
Cdd:PTZ00449  621 PKSPKRPESPKSPKRPPPPQRPSSPERPEGPKIIKSPKPPKSPKPPFDPK-----------FKEKFYDDYLDAAAKSKet 689

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755513742  839 RRSWKNAEDRLSLANKPLRRFKQEPEDDLPEAPPKtRESDQSRSSSPTAGPST------EGAEGPEEKKKVKMRRKRRLV 912
Cdd:PTZ00449  690 KTTVVLDESFESILKETLPETPGTPFTTPRPLPPK-LPRDEEFPFEPIGDPDAeqpddiEFFTPPEEERTFFHETPADTP 768

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 755513742  913 NKELSKELSKELN-HEIQKTESTLAHESQQPIKSEPESENDEPKRPLshceRPHRfSKGLNGTPRELRHSLGPGLRSP 989
Cdd:PTZ00449  769 LPDILAEEFKEEDiHAETGEPDEAMKRPDSPSEHEDKPPGDHPSLPK----KRHR-LDGLALSTTDLESDAGRIAKDA 841

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 755513742  628 VCLVCGEAGKEDTVEEEEGKFNLMLMECSICNEIIHPGCLKIKESEGVVNDELPNCWECPKC 689
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 755513742  628 VCLVCGEAGKEDTVEEEEGKFNLMLMECSICNEIIHPGCLKIKESEGVVNDELPNCWECPKC 689
Cdd:cd15645     1 VCLACGEAGKEDTAEGEEEKFDLSLMECTICNEIIHPGCLKMGKAEGVINAEIPNCWECPKC 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 755513742 1030 GAAHVMHREVWMAVFSYLSHRDLCVCMRVCRTWNRWCCDKRLWTR 1074
Cdd:cd22180     1 GAAHVMQREVWMAVFSYLSHRDLCVCMRVCRTWNRWCCDKRLWTR 45

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 755513742  473 WTHLTEFELKGLKALVEKLESLPENKKCVPEGIEDPQALLEGVKNVLKEHVDDDPTLAITGVPVVSWP 540
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 755513742 1033 HVMHREVWMAVFSYLSHRDLCVCMRVCRTWNRWCCDKRLWTR 1074
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 755513742 1035 MHREVWMAVFSYLSHRDLCVCMRVCRTWNRWCCDKRLWTR 1074
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 755513742   582 KCEACLRTE-CGECHFCKDMKKFGGPGRMKQSCIMRQC 618
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 755513742   192 YCLMSVKGCFTDFHIDFGGT-SVWYHVFRGGKIfWLIPPTLHNLALYEEW--VLSGKQSD--IFLGDRVERCQ------- 259
Cdd:pfam02373    1 WLYLGMPFSTTPWHIEDQGLySINYLHFGAPKV-WYIIPPEYAEKFEKVLsdHFGGEQPDdlLHLNTIISPKQlrengip 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 755513742   260 --RIELKQGYTFFIPSGWIHAVYTPVDslvfggNILHSFNV 298
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 755513742   297 NVPMQLRIYEIEDRTRVQPKFRYPFYYEMCWYVLER 332
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 755513742 1077 LNRCKSITPLMLSGIIRRQPV---SLDLSWTNISKKQLSWLINrLPGLRDLVLSGCSWIA---VSALCSSsCPLLRTLDV 1150
Cdd:cd09293     8 LHKLGQITQSNISQLLRILHSgleWLELYMCPISDPPLDQLSN-CNKLKKLILPGSKLIDdegLIALAQS-CPNLQVLDL 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755513742 1151 QWVEGLKDAqmrDLLSPPTDNRPGQMDNRSKLRNivelrlaGLDITDVSLRLIIRHMPLLSKLQLSYCnHINDQS-INLL 1229
Cdd:cd09293    86 RACENITDS---GIVALATNCPKLQTINLGRHRN-------GHLITDVSLSALGKNCTFLQTVGFAGC-DVTDKGvWELA 154

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 755513742 1230 TAVGtttrDSLTEVNLSDCNKVTDLCLS---FFKRCGNICHIDLRYCKQVT 1277
Cdd:cd09293   155 SGCS----KSLERLSLNNCRNLTDQSIPailASNYFPNLSVLEFRGCPLIT 201

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 755513742 1067 CDKRLWTRIDLNRCKSITPLMLSGIirrqpvsldlswTNISKKQLSWLINRLPGLRDLVLSGCSWIA---VSALcSSSCP 1143
Cdd:cd09293    38 CPISDPPLDQLSNCNKLKKLILPGS------------KLIDDEGLIALAQSCPNLQVLDLRACENITdsgIVAL-ATNCP 104

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755513742 1144 LLRTLDVQWVEG---LKDAQMRDLlspptdnrpGQmdNRSKLRNIvelRLAGLDITDVSLR-LIIRHMPLLSKLQLSYCN 1219
Cdd:cd09293   105 KLQTINLGRHRNghlITDVSLSAL---------GK--NCTFLQTV---GFAGCDVTDKGVWeLASGCSKSLERLSLNNCR 170

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 755513742 1220 HINDQSINLLTAVGTTTRdsLTEVNLSDCNKVTDL 1254
Cdd:cd09293   171 NLTDQSIPAILASNYFPN--LSVLEFRGCPLITDF 203

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 755513742 1043 VFSYLSHRDLCVCMRVCRTWNRWCCDKRLWTRI 1075
Cdd:cd22120    12 IFSHLPTNQLCRCARVCRRWYNLAWDPRLWTTI 44

F-box domain found in F-box/LRR-repeat protein 5 (FBXL5) and similar proteins; FBXL5, also called F-box and leucine-rich repeat protein 5, F-box protein FBL4/FBL5, or p45SKP2-like protein, is the substrate-recognition component of an SCF (SKP1-cullin-F-box) protein ligase complex that plays a central role in iron homeostasis by promoting the ubiquitination and subsequent degradation of IREB2/IRP2. 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 755513742 1038 EVWMAVFSYLSHRDLCVCMRVCRTWNRWCCDKRLW 1072
Cdd:cd22118     7 EIMLKIFSYLNPQDLCRCAQVCTKWSQLARDGSLW 41

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 755513742  1035 MHREVWMAVFSYLSHRDLCVCMRVCRTWNRWCCDKRLWTR 1074
Cdd:pfam00646    4 LPDDLLLEILSRLDPKDLLRLSLVSKRWRSLVDSLKLWKK 43

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755513742    54 DFNYEYVqreALRVPLVFRD-----------KDGLG---IKMPDPDFTVRDVKLLVGSRRLV---DVMDVNTQKGTEMSM 116
Cdd:pfam13621    3 EFFREYV---AKNKPVVIRGavkdwpavqkwTDSSLldyLKDKYGDVEVTVEVTPDGRADRLfynDDFTFVNPKEERMPF 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755513742   117 SQFVRYYETPEAQRDKLY-----NVISLEFSHtkLEHLVKRPtvvdlvdwvdnmWPQHLKEKQTEATNalaemkypkvkk 191
Cdd:pfam13621   80 GEFLDRLEAGEDTDTAPYaylqsDNLRSEFPE--LLEDNDLP------------FATEAFGGEPDAVN------------ 133

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755513742   192 yclmsvkgcftdFHIDFGGTSVWYH---------VFRGGKIFWLIPPT-LHNLALYEEWVLSGKQS----DIFLGD---- 253
Cdd:pfam13621  134 ------------LWMGNGRSVTSLHydhyenlycVVRGRKRFTLFPPSdVPNLYPGPLEPTPEGQVfslvDPLAPDferf 201

                          250       260       270
                   ....*....|....*....|....*....|
gi 755513742   254 ----RVERCQRIELKQGYTFFIPSGWIHAV 279
Cdd:pfam13621  202 prfrDAARPLVVTLNPGDVLYLPALWWHHV 231

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 755513742 1038 EVWMAVFSYLSHRDLCVCMRVCRTWN 1063
Cdd:cd22090     8 ELWRLILAYLPVRDLCRCCQVCRAWY 33

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 755513742 1043 VFSYLSHRDLCVCMRVCRTWNRWCCDKRLWTR 1074
Cdd:cd22148    13 ILSYLSPKELLIASQVSKTWRRLASSNELWKA 44

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 755513742 1038 EVWMAVFSYLSHRDLCVCMRVCRTWNRWCCDKRLWTRIDLN 1078
Cdd:cd22117     7 ELIQLILSYLDLPSLCRLSQTCKLFRKHCYDPLLWKELNLQ 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 755513742 1039 VWMAVFSYLSHRDLCVCM-RVCRTWNRWCCDKRLWTRIDL 1077
Cdd:cd22092     9 ILLKIFSYLSLQERCLSAsLVCKYWRDLCLDSQFWKQIDL 48

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 755513742  628 VCLVCGEAGKEDtveeeegkfnlmLMECSICNEIIHPGCLkiKESEGVVNDELPNcWECPKC 689
Cdd:cd15506     1 LCFLCGSAGLNE------------LLYCSVCCEPYHTFCL--EEAERPLNINKDN-WCCRRC 47

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 755513742 1037 REVWMAVFSYLSHRDLCVCMRVCRTW 1062
Cdd:cd22124     6 RKAALKIFSYLDLRDLARCAQVCRSW 31

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 755513742 1043 VFSYLSHRDLCVCMRVCRTWNRWC-CDKRLWTRI 1075
Cdd:cd22086    15 ILSYLSPEDLCRVSCVSKTWRQIClSDPKANRRR 48

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 755513742 1043 VFSYLSHRDLCVCMRVCRTWNRWCCDKRLWTRIDLN 1078
Cdd:cd22104    12 IFSYLPPRDRLRASSTCRRWREALFHPSLWRSLRLH 47

F-box domain found in F-box/WD repeat-containing protein 7 (FBXW7) and similar proteins; FBXW7, also called Archipelago homolog (Ago), F-box and WD-40 domain-containing protein 7, F-box protein FBX30, SEL-10, or Cdc4, 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 cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch intracellular domain (NICD), NOTCH2, MCL1, and probably PSEN1. 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 755513742 1037 REVWMAVFSYLSHRDLCVCMRVCRTWNRWCCDKRLW 1072
Cdd:cd22133    23 KELALYVLSFLEPKDLLQAAQTCRYWRILAEDNLLW 58