UBR-box found in RING-type E3 ubiquitin-protein ligase UBR7 and similar proteins; UBR7 (EC 2.3.2.27; also called N-recognin-7) is a RING-type E3 ubiquitin ligase of the Arg/N-end rule degradation pathway. It recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. UBR7 may play an important role in spermiogenesis and fertilization.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 145333865  41 ECTFPKGYmKRQAIFSCITCTPEG---NAGICTACCLSCHDGHELLELWTKRNFRCDCGNSKFGTLACKLLP 109
Cdd:cd19677    1 ECTYSKGY-IRQAVYACLTCTPAGadqPAGICLACSLSCHEGHELEELYTKRNFRCDCGNSKFPSNPCKLFP 71

UBR-box found in RING-type E3 ubiquitin-protein ligase UBR7 and similar proteins; UBR7 (EC 2.3.2.27; also called N-recognin-7) is a RING-type E3 ubiquitin ligase of the Arg/N-end rule degradation pathway. It recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. UBR7 may play an important role in spermiogenesis and fertilization.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 145333865  41 ECTFPKGYmKRQAIFSCITCTPEG---NAGICTACCLSCHDGHELLELWTKRNFRCDCGNSKFGTLACKLLP 109
Cdd:cd19677    1 ECTYSKGY-IRQAVYACLTCTPAGadqPAGICLACSLSCHEGHELEELYTKRNFRCDCGNSKFPSNPCKLFP 71

Putative zinc finger in N-recognin (UBR box); This region is found in E3 ubiquitin ligases that recognize N-recognins.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 145333865   52 QAIFSCITCTPEGNAGICTACCLSC-HDGHElLELWTKRN-FRCDCGNSKF 100
Cdd:pfam02207   9 QPVYRCLTCSLDPTCVICYSCFINCdHEGHD-YELFTSRGgGCCDCGDPEA 58

UBR-box found in RING-type E3 ubiquitin-protein ligase UBR7 and similar proteins; UBR7 (EC 2.3.2.27; also called N-recognin-7) is a RING-type E3 ubiquitin ligase of the Arg/N-end rule degradation pathway. It recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. UBR7 may play an important role in spermiogenesis and fertilization.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 145333865  41 ECTFPKGYmKRQAIFSCITCTPEG---NAGICTACCLSCHDGHELLELWTKRNFRCDCGNSKFGTLACKLLP 109
Cdd:cd19677    1 ECTYSKGY-IRQAVYACLTCTPAGadqPAGICLACSLSCHEGHELEELYTKRNFRCDCGNSKFPSNPCKLFP 71

UBR-box found in UBR4, UBR5, UBR6/FBOX11, UBR7 and similar proteins; This family includes UBR4 (EC 2.3.2.27), UBR5 (EC 2.3.2.26), UBR6/FBOX11 and UBR7 (EC 2.3.2.27). Both UBR4 (also called 600 kDa retinoblastoma protein-associated factor, or N-recognin-4, or retinoblastoma-associated factor of 600 kDa, or RBAF600, or p600, or zinc finger UBR1-type protein 1) and UBR7 (also called N-recognin-7) are RING-type E3 ubiquitin ligases of the Arg/N-end rule degradation pathway. They recognize and bind to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. UBR5 (also called E3 ubiquitin-protein ligase, HECT domain-containing 1, E3 ligase identified by differential display (EDD), hyperplastic discs protein homolog (HYD), progestin-induced protein, or N-recognin-5) is a HECT (homologous to E6-AP C-terminus)-type E3 ubiquitin-protein ligase that acts as a key regulator of the ubiquitin proteasome system in both cancer and developmental biology. It is required for Wnt signal responses in Drosophila and human cell lines downstream of activated Armadillo/beta-catenin. It also plays a key role in ciliogenesis by regulating centriolar satellite stability and primary cilia. UBR6 (also called FBOX11, protein arginine N-methyltransferase 9 (PRMT9), or vitiligo-associated protein 1 (VIT-1)), is an E3 ubiquitin ligase and a type II methyltransferase, which functions as a key regulator of tumor initiation and progression. UBR6 is a substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as DTL/CDT2, BCL6 and PRDM1/BLIMP1. UBR6 does not bind N-terminal signals.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145333865  42 CTFPK--GYMKRQAIFSCITCTPEGNAGICTACCLSCHDGHELLELwTKRNFRCDCGNSKFGTlaCKLLP 109
Cdd:cd19671    1 CTFEKtgRKYIKQPWYHCYTCGLIDGLGVCEACARKCHKGHDLVYI-GYSNFYCDCGSSGPGK--CKCES 67

Putative zinc finger in N-recognin (UBR box); This region is found in E3 ubiquitin ligases that recognize N-recognins.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 145333865   52 QAIFSCITCTPEGNAGICTACCLSC-HDGHElLELWTKRN-FRCDCGNSKF 100
Cdd:pfam02207   9 QPVYRCLTCSLDPTCVICYSCFINCdHEGHD-YELFTSRGgGCCDCGDPEA 58

Putative zinc finger in N-recognin, a recognition component of the N-end rule pathway; Domain is involved in recognition of N-end rule substrates in yeast Ubr1p

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 145333865    40 DECTFPKGYMKRqaIFSCITCTPEGNAGICTACCL-SCHDGHELLELWTKRNFRCDCGNS--KFGTLACKLL 108
Cdd:smart00396   1 DVCGYKFTGGEV--IYRCKTCGLDPTCVLCSDCFRpSCHKGHDVSLKTSRGSGICDCGDKeaWNEDLKCKAH 70

PHD finger found in PHF2, PHF8 and KDM7; This family includes PHF2, PHF8, KDM7, and similar proteins. PHF2, also termed GRC5, or PHD finger protein 2, is a histone lysine demethylase ubiquitously expressed in various tissues. PHF8, also termed PHD finger protein 8, or KDM7B, is a monomethylated histone H4 lysine 20(H4K20me1) demethylase that transcriptionally regulates many cell cycle genes. It also preferentially acts on H3K9me2 and H3K9me1. PHF8 is modulated by CDC20-containing anaphase-promoting complex (APC (cdc20)) and plays an important role in the G2/M transition. It acts as a critical molecular sensor for mediating retinoic acid (RA) treatment response in RAR alpha-fusion-induced leukemia. Moreover, PHF8 is essential for cytoskeleton dynamics and is associated with X-linked mental retardation. KDM7, also termed JmjC domain-containing histone demethylation protein 1D (JHDM1D), or KIAA1718, is a dual histone demethylase that catalyzes demethylation of monomethylated and dimethylated H3K9 (H3K9me2/me1) and H3K27 (H3K27me2/me1), which functions as an eraser of silencing marks on chromatin during brain development. It also plays a tumor-suppressive role by regulating angiogenesis. All family members contain a plant homeodomain (PHD) finger and a JmjC domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 145333865 128 YCTCDRPYpdpnvEEQVEMIQCCLCEDWFHeehlgltpsdsvGSQIPRDEESEPIYEDFICQNC 191
Cdd:cd15554    1 YCICRQPY-----DVTRFMIECDVCKDWFH------------GSCVGVEEHQANDIERYHCPNC 47

UBR-box found in F-box only protein 11 (FBXO11) and similar proteins; FBXO11 (also called UBR6, protein arginine N-methyltransferase 9 (PRMT9), or vitiligo-associated protein 1 (VIT-1)) is an E3 ubiquitin ligase and a type II methyltransferase, which functions as a key regulator of tumor initiation and progression. FBXO11 is a substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as DTL/CDT2, BCL6 and PRDM1/BLIMP1. FBXO11 does not bind N-terminal signals.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 145333865  55 FSCITCTPEGNAGICTACCLSCHDGHElLELWTKRNFRCDCG 96
Cdd:cd19676   17 YRCLTCNTTDRNAICVNCIKKCHEGHD-VEFIRHDRFFCDCG 57

PHD finger 3 found in Lysine-specific demethylase 5A (KDM5A), 5B (KDM5B), and similar proteins; The family includes KDM5A and KDM5B, both of which belong to the JARID subfamily within the JmjC proteins. KDM5A, also termed Histone demethylase JARID1A, or Jumonji/ARID domain-containing protein 1A, or Retinoblastoma-binding protein 2 (RBBP-2 or RBP2), was originally identified as a retinoblastoma protein (Rb)-binding partner and its inactivation may be important for Rb to promote differentiation. It is involved in transcription through interacting with TBP, p107, nuclear receptors, Myc, Sin3/HDAC, Mad1, RBP-J, CLOCK and BMAL1. KDM5A functions as the trimethylated histone H3 lysine 4 (H3K4me3) demethylase. It also displays DNA-binding activities that can recognize the specific DNA sequence CCGCCC. KDM5B, also termed Cancer/testis antigen 31 (CT31), or Histone demethylase JARID1B, or Jumonji/ARID domain-containing protein 1B (JARID1B), or PLU-1, or retinoblastoma-binding protein 2 homolog 1 (RBP2-H1 or RBBP2H1A), has a restricted expression pattern in the testis, ovary, and transiently in the mammary gland of the pregnant female and has been shown to be upregulated in breast cancer, prostate cancer, and lung cancer, suggesting a potential role in tumorigenesis. KDM5B acts as a histone demethylase that catalyzes the removal of trimethylation of lysine 4 on histone H3 (H3K4me3), induced by polychlorinated biphenyls (PCBs). It also mediates demethylation of H3K4me2 and H3K4me1. Moreover, KDM5B functions as a negative regulator of hematopoietic stem cell (HSC) self-renewal and progenitor cell activity. KDM5B has also been shown to interact with the DNA binding transcription factors BF-1 and PAX9, as well asTIEG1/KLF10 (transforming growth factor-beta inducible early gene-1/Kruppel-like transcription factor 10), and possibly function as a transcriptional corepressor. The family also includes the Drosophila melanogaster protein little imaginal discs (Lid) that functions as a JmjC-dependent trimethyl histone H3K4 (H3K4me3) demethylase, which is required for dMyc-induced cell growth. It positively regulates Hox gene expression in S2 cells. Members in this family contain the catalytic JmjC domain, JmjN, the BRIGHT domain, which is an AT-rich interacting domain (ARID), and a Cys5HisCys2 zinc finger, as well as three plant homeodomain (PHD) fingers. This model corresponds to the third PHD finger.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 145333865 131 CDRPYPDpnveeQVEMIQCCLCEDWFHEEHLGLTPSDsvgsqiPRDEesepiyEDFICQNC 191
Cdd:cd15610    7 CLKPTGD-----EVNWVQCDGCEEWFHLLCVGLSPEE------VAED------EDYICPSC 50

PHD finger found in PHD finger protein 3 (PHF3), and death-inducer obliterator variants Dido1, Dido2, and Dido3; PHF3 is a human homolog of yeast protein bypass of Ess1 (Bye1), a nuclear protein with a domain resembling the central domain in the transcription elongation factor TFIIS. It is ubiquitously expressed in normal tissues including brain, but its expression is significantly reduced or lost in glioblastomas. PHF3 contains an N-terminal plant homeodomain (PHD) finger, a central RNA polymerase II (Pol II)-binding TFIIS-like domain (TLD) domain, and a C-terminal Spen paralogue and orthologue C-terminal (SPOC) domain. This family also includes Dido gene encoding three alternative splicing variants (Dido1, 2, and 3), which have been implicated in a number of cellular processes such as apoptosis and chromosomal segregation, particularly in the hematopoietic system. Dido1 is important for maintaining embryonic stem (ES) cells and directly regulates the expression of pluripotency factors. It is the shortest isoform that contains only a highly conserved PHD finger responsible for the binding of histone H3 with a higher affinity for trimethylated lysine4 (H3K4me3). Gene Dido1 is a Bone morphogenetic protein (BMP) target gene and promotes BMP-induced melanoma progression. It also triggers apoptosis after nuclear translocation and caspase upregulation. Dido3 is the largest isoform and is ubiquitously expressed in all human tissues. It is dispensable for ES cell self-renewal and pluripotency, but is involved in the maintenance of stem cell genomic stability and tumorigenesis. Dido3 contains a PHD finger, a transcription elongation factor S-II subunit M (TFSIIM) domain, a SPOC module, and a long C-terminal region (CT) of unknown homology.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 145333865 128 YCTCDRPYPDpnveeqVEMIQCCLCEDWFHEEHLGLTPsdsvgSQIPRDEESEpiyEDFICQNC 191
Cdd:cd15552    1 YCICRKPHNN------RFMICCDRCEEWFHGDCVGITE-----AQGKEMEENI---EEYVCPKC 50

PHD finger 2 found in Lysine-specific demethylase 5A (KDM5A); KDM5A (also termed Histone demethylase JARID1A, Jumonji/ARID domain-containing protein 1A, or Retinoblastoma-binding protein 2 (RBBP-2 or RBP2)) was originally identified as a retinoblastoma protein (Rb)-binding partner and its inactivation may be important for Rb to promote differentiation. It is involved in transcription through interacting with TBP, p107, nuclear receptors, Myc, Sin3/HDAC, Mad1, RBP-J, CLOCK, and BMAL1. KDM5A functions as a trimethylated histone H3 lysine 4 (H3K4me3) demethylase that belongs to the JARID subfamily within the JmjC proteins. It also displays DNA-binding activities that can recognize the specific DNA sequence CCGCCC. KDM5A contains the catalytic JmjC domain, JmjN, the BRIGHT domain, which is an AT-rich interacting domain (ARID), and a Cys5HisCys2 zinc finger, as well as three plant homeodomain (PHD) fingers. This model corresponds to the second PHD finger.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 145333865 128 YCTCDRPYPDpnveeqvEMIQCCLCEDWFHEEHLGLtPSDSVGSQIPRDEESEPIYEDFICQNC 191
Cdd:cd15606    1 YCICRKPFSG-------FMLQCELCKDWFHSSCVPL-PKSSSQKKGGNGSGQGAKELKFLCPLC 56