RNA recognition motif (RRM) found in Eukaryotic CCR4-NOT transcription complex subunit 4 (NOT4) and similar proteins; This subfamily corresponds to the RRM of NOT4, also termed CCR4-associated factor 4, or E3 ubiquitin-protein ligase CNOT4, or potential transcriptional repressor NOT4Hp, a component of the CCR4-NOT complex, a global negative regulator of RNA polymerase II transcription. NOT4 functions as an ubiquitin-protein ligase (E3). It contains an N-terminal C4C4 type RING finger motif, followed by a RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). The RING fingers may interact with a subset of ubiquitin-conjugating enzymes (E2s), including UbcH5B, and mediate protein-protein interactions. T

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1973916070 102 SVLKRPEYFGKFGKIHKVVINNSTSYAGSQGPSASAYVTYIRSEDALRAIQCVNNVVVDGRTLKASLGTTKYCSYFLK 179
Cdd:cd12438    21 EVLKRPEYFGQYGKIKKIVINRSTSYAGSQGPSASAYVTYSRKEDALRAIQAVDGFVLDGRTLKASFGTTKYCSSFLR 98

RNA recognition motif;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1973916070  107 PEYFGKFGKIHKVVINNSTSYAGSQGpsaSAYVTYIRSEDALRAIQCVNNVVVDGRTLKAS 167
Cdd:smart00361  13 EEYFGEVGKINKIYIDDVGYENHKRG---NVYITFERSEDAARAIVDLNGRYFDGRLVKAE 70

RNA recognition motif (RRM) found in Eukaryotic CCR4-NOT transcription complex subunit 4 (NOT4) and similar proteins; This subfamily corresponds to the RRM of NOT4, also termed CCR4-associated factor 4, or E3 ubiquitin-protein ligase CNOT4, or potential transcriptional repressor NOT4Hp, a component of the CCR4-NOT complex, a global negative regulator of RNA polymerase II transcription. NOT4 functions as an ubiquitin-protein ligase (E3). It contains an N-terminal C4C4 type RING finger motif, followed by a RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). The RING fingers may interact with a subset of ubiquitin-conjugating enzymes (E2s), including UbcH5B, and mediate protein-protein interactions. T

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1973916070 102 SVLKRPEYFGKFGKIHKVVINNSTSYAGSQGPSASAYVTYIRSEDALRAIQCVNNVVVDGRTLKASLGTTKYCSYFLK 179
Cdd:cd12438    21 EVLKRPEYFGQYGKIKKIVINRSTSYAGSQGPSASAYVTYSRKEDALRAIQAVDGFVLDGRTLKASFGTTKYCSSFLR 98

RING/Ubox like zinc-binding domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1973916070  14 CPLCMEPLEIDDINFFPCTCGYQICRFCWHRIRTDENGLCPACRKPY 60
Cdd:pfam14570   1 CPLCDEKLDETDKDFYPCECGYQICRFCYHDILENEGGRCPGCREPY 47

RNA recognition motif (RRM) superfamily; RRM, also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), is a highly abundant domain in eukaryotes found in proteins involved in post-transcriptional gene expression processes including mRNA and rRNA processing, RNA export, and RNA stability. This domain is 90 amino acids in length and consists of a four-stranded beta-sheet packed against two alpha-helices. RRM usually interacts with ssRNA, but is also known to interact with ssDNA as well as proteins. RRM binds a variable number of nucleotides, ranging from two to eight. The active site includes three aromatic side-chains located within the conserved RNP1 and RNP2 motifs of the domain. The RRM domain is found in a variety heterogeneous nuclear ribonucleoproteins (hnRNPs), proteins implicated in regulation of alternative splicing, and protein components of small nuclear ribonucleoproteins (snRNPs).

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1973916070 108 EYFGKFGKIHKVVINNStsyaGSQGPSASAYVTYIRSEDALRAIQCVNNVVVDGRTLKAS 167
Cdd:cd00590    17 ELFSKFGEVVSVRIVRD----RDGKSKGFAFVEFESPEDAEKALEALNGTELGGRPLKVS 72

RNA recognition motif;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1973916070  108 EYFGKFGKIHKVVINNSTSYAGSQGpsaSAYVTYIRSEDALRAIQCVNNVVVDGRTLK 165
Cdd:smart00360  18 ELFSKFGKVESVRLVRDKETGKSKG---FAFVEFESEEDAEKALEALNGKELDGRPLK 72

RNA recognition motif (RRM) found in THO complex subunit 4 (THOC4) and similar proteins; This subgroup corresponds to the RRM of THOC4, also termed transcriptional coactivator Aly/REF, or ally of AML-1 and LEF-1, or bZIP-enhancing factor BEF, an mRNA transporter protein with a well conserved RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). It is involved in RNA transportation from the nucleus. THOC4 was initially identified as a transcription coactivator of LEF-1 and AML-1 for the TCRalpha enhancer function. In addition, THOC4 specifically binds to rhesus (RH) promoter in erythroid. It might be a novel transcription cofactor for erythroid-specific genes.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1973916070 108 EYFGKFGKIHKVVINnstsYAGSQGPSASAYVTYIRSEDALRAIQCVNNVVVDGRTLKASL 168
Cdd:cd12680    19 ELFAEFGTLKKAAVH----YDRSGRSLGTAEVVFERRADALKAMKQYNGVPLDGRPMKIQL 75

RNA recognition motif 3 (RRM3) found in Saccharomyces cerevisiae protein PES4, protein MIP6 and similar proteins; The family includes PES4 (also called DNA polymerase epsilon suppressor 4) and MIP6 (also called MEX67-interacting protein 6), both of which are predicted RNA binding proteins that may act as regulators of late translation, protection, and mRNA localization. MIP6 acts as a novel factor for nuclear mRNA export, binds to both poly(A)+ RNA and nuclear pores. It interacts with MEX67. Members in this family contain four RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). The model corresponds to the third RRM motif.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1973916070 108 EYFGKFGKIHKVVINNSTSYAgsqgpSASAYVTYIRSEDALRAIQCVNNVVVDGRTLKAS 167
Cdd:cd21603    19 DFFSKVGPIKSVFTSPKYKYN-----SLWAFVTYKKGSDTEKAIKLLNGTLFKGRTIEVT 73

BRcat domain found in RING finger protein 216 (RNF216); RNF216, also called Triad domain-containing protein 3 (Triad3A), ubiquitin-conjugating enzyme 7-interacting protein 1, or zinc finger protein inhibiting NF-kappa-B (ZIN), is an RBR-type E3 ubiquitin-protein ligase that interacts with several components of the Toll-like receptor (TLR) signaling pathway and promotes their proteolytic degradation. It negatively regulates the RIG-I RNA sensing pathway through Lys48-linked, ubiquitin-mediated degradation of the tumor necrosis factor (TNF) receptor-associated factor 3 (TRAF3) adapter following RNA virus infection. It also controls ubiquitination and proteasomal degradation of receptor-interacting protein 1 (RIP1), a serine/threonine protein kinase that is critically involved in TNF receptor-1-induced NF-kappa B activation, following disruption of Hsp90 binding. Moreover, RNF216 is involved in inflammatory diseases by strongly inhibiting autophagy in macrophages. It interacts with and ubiquitinates BECN1, a key regulator in autophagy, thereby contributing to BECN1 degradation. It regulates synaptic strength by ubiquitination of Arc, resulting in its rapid proteasomal degradation. It is also a key negative regulator of sustained 2DL4/KIR2DL4 (killer cell Ig-like receptor with two Ig-like domains and a long cytoplasmic domain 4)-mediated NF-kappaB signaling from internalized 2DL4, which functions by promoting ubiquitylation and degradation of endocytosed receptor from early endosomes. Furthermore, RNF216 interacts with human immunodeficiency virus type 1 (HIV-1) virion infectivity factor (Vif) protein, which is essential for the productive infection of primary human CD4 T lymphocytes and macrophages. Mutations in RNF216 may result in Gordon Holmes syndrome, a condition defined by hypogonadotropic hypogonadism and cerebellar ataxia, as well as in autosomal recessive Huntington-like disorder. RNF216 contains an RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been changed to RING1-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase functions to facilitate the ubiquitination reaction. This model corresponds to the BRcat domain of RNF216 that adopts the same fold as the Rcat domain while lacking the catalytic cysteine residue and ubiquitination activity.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1973916070   9 EDPVECPLCMEPLEIDDINF--FPC---TCGYQICRFC---WHRIRT 47
Cdd:cd20339     2 EGLERCPFCNYAAILDPTEVkvFRCpnpECRKESCRKCkkeWHIPLT 48

Modified RING finger, HC subclass (C3HC5-type), found in neuralized-like protein 1B (NEURL1B); NEURL1B, also known as neuralized-2 (NEUR2) or neuralized-like protein 3, is a mammalian homolog of the Drosophila neuralized (D-neu) protein. It functions as an E3 ubiquitin-protein ligase that interacts with and ubiquitinates Delta. Thus, it plays a role in the endocytic pathways for Notch signaling through working cooperatively with another E3 ligase, Mind bomb-1 (Mib1), in Delta endocytosis to hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-positive vesicles. NEURL1B contains two neuralized homology regions (NHRs) responsible for Neural-ligand interactions and a modified C3HC5-type RING-HC finger required for ubiquitin ligase activity. The C3HC5-type RING-HC finger is distinguished from typical C3HC4-type RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1973916070  13 ECPLCMEPlEIDDINFfpcTCGYQ-ICRFCWHRIRTDENGLCPACRKPYPEDPAVYKP 69
Cdd:cd16786     4 ECTVCFDS-EVDTVIY---TCGHMcLCNSCGLKLKRQINACCPICRRVIKDVIKIYRP 57

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1973916070  13 ECPLCMEPLEiDDINFFPCtcGYQICRFCWHRIRTDENgLCPAC 56
Cdd:pfam13923   1 MCPICMDMLK-DPSTTTPC--GHVFCQDCILRALRAGN-ECPLC 40

RING finger, HC subclass, found in tripartite motif-containing protein 26 (TRIM26) and similar proteins; TRIM26, also known as acid finger protein (AFP), RING finger protein 95 (RNF95), or zinc finger protein 173 (ZNF173), is an E3 ubiquitin-protein ligase that negatively regulates interferon-beta production and antiviral response through polyubiquitination and degradation of nuclear transcription factor IRF3. It functions as an important regulator for RNA virus-triggered innate immune response by bridging TBK1 to NEMO (NF-kappaB essential modulator, also known as IKKgamma) and mediating TBK1 activation. It also acts as a novel tumor suppressor of hepatocellular carcinoma by regulating cancer cell proliferation, colony forming ability, migration, and invasion. TRIM26 belongs the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, a B-box, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1973916070   9 EDPVECPLCME----PLEIDdinffpctCGYQICRFCW--HRIRTDENG--LCPACRKPY 60
Cdd:cd16598     2 EEEVTCSICLDylrdPVTID--------CGHNFCRSCItdYCPISGGHErpVCPLCRKPF 53

RNA recognition motif (RRM) found in RNA-binding protein with serine-rich domain 1 (RNPS1) and similar proteins; This subfamily corresponds to the RRM of RNPS1 and its eukaryotic homologs. RNPS1, also termed RNA-binding protein prevalent during the S phase, or SR-related protein LDC2, was originally characterized as a general pre-mRNA splicing activator, which activates both constitutive and alternative splicing of pre-mRNA in vitro.It has been identified as a protein component of the splicing-dependent mRNP complex, or exon-exon junction complex (EJC), and is directly involved in mRNA surveillance. Furthermore, RNPS1 is a splicing regulator whose activator function is controlled in part by CK2 (casein kinase II) protein kinase phosphorylation. It can also function as a squamous-cell carcinoma antigen recognized by T cells-3 (SART3)-binding protein, and is involved in the regulation of mRNA splicing. RNPS1 contains an N-terminal serine-rich (S) domain, a central RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and the C-terminal arginine/serine/proline-rich (RS/P) domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1973916070  96 NRKHLAsvlkrpEYFGKFGKIHKV--VINNstsyaGSQGPSASAYVTYIRSEDALRAIQCVNNVVVDGRTLKAS 167
Cdd:cd12365    11 TKDHLK------EIFSVYGTVKNVdlPIDR-----EPNLPRGYAYVEFESPEDAEKAIKHMDGGQIDGQEVTVE 73

RING finger, HC subclass, found in tripartite motif-containing proteins, TRIM7, TRIM11 and TRIM27, and similar proteins; TRIM7, TRIM11 and TRIM27, closely related tripartite motif-containing proteins, belong to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. TRIM7, also known as glycogenin-interacting protein (GNIP) or RING finger protein 90 (RNF90), is an E3 ubiquitin-protein ligase that mediates c-Jun/AP-1 activation by Ras signalling. Its phosphorylation and activation by MSK1 in response to direct activation by the Ras-Raf-MEK-ERK pathway can stimulate TRIM7 E3 ubiquitin ligase activity in mediating Lys63-linked ubiquitination of the AP-1 coactivator RACO-1, leading to RACO-1 protein stabilization. Moreover, TRIM7 binds and activates glycogenin, the self-glucosylating initiator of glycogen biosynthesis. TRIM11, also known as protein BIA1, or RING finger protein 92 (RNF92), is an E3 ubiquitin-protein ligase involved in the development of the central nervous system. It is overexpressed in high-grade gliomas and promotes proliferation, invasion, migration and glial tumor growth. TRIM11 acts as a potential therapeutic target for congenital central hypoventilation syndrome (CCHS) by mediating the degradation of CCHS-associated polyalanine-expanded Phox2b. TRIM11 modulates the function of neurogenic transcription factor Pax6 through the ubiquitin-proteosome system, and thus plays an essential role for Pax6-dependent neurogenesis. It also binds to and destabilizes a key component of the activator-mediated cofactor complex (ARC105), humanin, a neuroprotective peptide against Alzheimer's disease-relevant insults, and further regulates ARC105 function in transforming growth factor beta (TGFbeta) signaling. Moreover, TRIM11 negatively regulates retinoic acid-inducible gene-I (RIG-I)-mediated interferon-beta (IFNbeta) production and antiviral activity by targeting TANK-binding kinase-1 (TBK1). It may contribute to the endogenous restriction of retroviruses in cells. It enhances N-tropic murine leukemia virus (N-MLV) entry by interfering with Ref1 restriction. It also suppresses the early steps of human immunodeficiency virus HIV-1 transduction, resulting in decreased reverse transcripts. TRIM27, also known as RING finger protein 76 (RNF76), RET finger protein (RFP), or zinc finger protein RFP, is a nuclear E3 ubiquitin-protein ligase that is highly expressed in testis and in various tumor cell lines. Expression of TRIM27 is associated with prognosis of colon and endometrial cancers. TRIM27 was first identified as a fusion partner of the RET receptor tyrosine kinase. It functions as a transcriptional repressor and associates with several proteins involved in transcriptional activity, such as enhancer of polycomb 1 (Epc1), a member of the Polycomb group proteins, and Mi-2beta, a main component of the nucleosome remodeling and deacetylase (NuRD) complex, and the cell cycle regulator retinoblastoma protein (RB1). It also interacts with HDAC1, leading to downregulation of thioredoxin binding protein 2 (TBP-2), which inhibits the function of thioredoxin. Moreover, TRIM27 mediates Pax7-induced ubiquitination of MyoD in skeletal muscle atrophy. In addition, it inhibits muscle differentiation by modulating serum response factor (SRF) and Epc1. TRIM27 promotes a non-canonical polyubiquitination of PTEN, a lipid phosphatase that catalyzes PtdIns(3,4,5)P3 (PIP3) to PtdIns(4,5)P2 (PIP2). It is an IKKepsilon-interacting protein that regulates IkappaB kinase (IKK) function and negatively regulates signaling involved in the antiviral response and inflammation. TRIM27 also forms a protein complex with MBD4 or MBD2 or MBD3, and thus plays an important role in the enhancement of transcriptional repression through MBD proteins in tumorigenesis, spermatogenesis, and embryogenesis. It is a component of an estrogen receptor 1 (ESR1) regulatory complex that is involved in estrogen receptor-mediated transcription in MCF-7 cells.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1973916070  14 CPLCME----PLEIDdinffpctCGYQICRFC----WHRirTDENGLCPACRKPYPEDP 64
Cdd:cd16594     8 CPICLDyftdPVTLD--------CGHSFCRACiarcWEE--PETSASCPQCRETCPQRN 56

RING finger, HC subclass, found in SH3 domain-containing RING finger protein 2 (SH3RF2) and similar proteins; SH3RF2, also known as heart protein phosphatase 1-binding protein (HEPP1), plenty of SH3s (POSH)-eliminating RING protein (POSHER), protein phosphatase 1 regulatory subunit 39, or RING finger protein 158 (RNF158), is a putative E3 ubiquitin-protein ligase that acts as an anti-apoptotic regulator for the c-Jun N-terminal kinase (JNK) pathway by binding to and promoting the proteasomal degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal C3HC4-type RING-HC finger responsible for the E3 ligase activity and four Src Homology 3 (SH3) domains, which are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1973916070  12 VECPLCMEPLEIdDINFFPCTcgYQICRFCWHRIRTDENGL-CPACRKP 59
Cdd:cd16749     1 LECPVCFEKLDV-TAKVLPCQ--HTFCKPCLQRIFKARKELrCPECRTP 46

RNA recognition motif 2 (RRM2) found in HIV Tat-specific factor 1 (Tat-SF1) and similar proteins; This subfamily corresponds to the RRM2 of Tat-SF1 and CUS2. Tat-SF1 is the cofactor for stimulation of transcriptional elongation by human immunodeficiency virus-type 1 (HIV-1) Tat. It is a substrate of an associated cellular kinase. Tat-SF1 contains two RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), and a highly acidic carboxyl-terminal half. The family also includes CUS2, a yeast homolog of human Tat-SF1. CUS2 interacts with U2 RNA in splicing extracts and functions as a splicing factor that aids assembly of the splicing-competent U2 snRNP in vivo. CUS2 also associates with PRP11 that is a subunit of the conserved splicing factor SF3a. Like Tat-SF1, CUS2 contains two RRMs as well.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1973916070 112 KFGKIHKVVINnstsyagSQGPSASAYVTYIRSEDALRAIQCVNNVVVDGRTLKASL--GTTKY 173
Cdd:cd12282    35 KFGQVKKVVVF-------DRHPDGVASVKFKEPEEADKCIQALNGRWFAGRKLEAETwdGKTDY 91

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1973916070   14 CPLCMEPLEIDdinFFPCTCGYQICRFCWHRIRTDENGLCPAC 56
Cdd:smart00184   1 CPICLEEYLKD---PVILPCGHTFCRSCIRKWLESGNNTCPIC 40

RNA recognition motif 2 (RRM2) found in vertebrate RNA-binding protein RBM23, RBM39 and similar proteins; This subfamily corresponds to the RRM2 of RBM39 (also termed HCC1), a nuclear autoantigen that contains an N-terminal arginine/serine rich (RS) motif and three RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). An octapeptide sequence called the RS-ERK motif is repeated six times in the RS region of RBM39. Although the cellular function of RBM23 remains unclear, it shows high sequence homology to RBM39 and contains two RRMs. It may possibly function as a pre-mRNA splicing factor.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1973916070 110 FGKFGKIHKVVINNSTSYAGSQGpsaSAYVTYIRSEDALRAIQCVNNVVVDGRTLKASLGTTK 172
Cdd:cd12284    19 FEPFGKIEFVQLQKDPETGRSKG---YGFIQFRDAEDAKKALEQLNGFELAGRPMKVGHVTER 78

RNA recognition motif 3 (RRM3) found in RNA-binding protein 19 (RBM19) and RNA recognition motif 2 found in multiple RNA-binding domain-containing protein 1 (MRD1); This subfamily corresponds to the RRM3 of RBM19 and RRM2 of MRD1. RBM19, also termed RNA-binding domain-1 (RBD-1), is a nucleolar protein conserved in eukaryotes involved in ribosome biogenesis by processing rRNA and is essential for preimplantation development. It has a unique domain organization containing 6 conserved RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains). MRD1 is encoded by a novel yeast gene MRD1 (multiple RNA-binding domain). It is well conserved in yeast and its homologs exist in all eukaryotes. MRD1 is present in the nucleolus and the nucleoplasm. It interacts with the 35 S precursor rRNA (pre-rRNA) and U3 small nucleolar RNAs (snoRNAs). It is essential for the initial processing at the A0-A2 cleavage sites in the 35 S pre-rRNA. MRD1 contains 5 conserved RRMs, which may play an important structural role in organizing specific rRNA processing events.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1973916070 108 EYFGKFGKIHKVVINNSTSYAGSQGpsaSAYVTYIRSEDALRAIQCVNNVVVDGRTL 164
Cdd:cd12316    18 ELFEAFGKISEVHIPLDKQTKRSKG---FAFVLFVIPEDAVKAYQELDGSIFQGRLL 71

Modified RING finger, HC subclass (C4C4-type), found in Arabidopsis thaliana cellulose synthase A (CesA) catalytic subunits 1-10, and similar proteins from plants; This subfamily includes plant catalytic subunits of cellulose synthase terminal complexes ("rosettes") required for beta-1,4-glucan microfibril crystallization, a major mechanism of cell wall formation. CesA1, also known as protein RADIALLY SWOLLEN 1 (RSW1), is required during embryogenesis for cell elongation, orientation of cell expansion and complex cell wall formations, such as interdigitated pattern of epidermal pavement cells, stomatal guard cells, and trichomes. It plays a role in lateral roots formation, but seems unnecessary for the development of tip-growing cells such as root hairs. CesA2, also known as Ath-A, is involved in the primary cell wall formation. It forms a homodimer. CesA3, also known as constitutive expression of VSP1 protein 1, isoxaben-resistant protein 1, Ath-B, protein ECTOPIC LIGNIN 1, or protein RADIALLY SWOLLEN 5 (RSW5), is involved in primary cell wall formation, especially in roots. CesA4, also known as protein IRREGULAR XYLEM 5 (IRX5), is involved in the secondary cell wall formation, and required for xylem cell wall thickening. CesA5 may be partially redundant with CesA6. CesA6, also known as AraxCelA, isoxaben-resistant protein 2, protein PROCUSTE 1, or protein QUILL, is involved in primary cell wall formation. Like CesA1, CesA6 is critical for cell expansion. CESA6-dependent cell elongation seems to be independent of gibberellic acid, auxin, and ethylene. CesA6 interacts with and moves along cortical microtubules for the process of cellulose deposition. CesA7, also known as protein FRAGILE FIBER 5, or protein IRREGULAR XYLEM 3 (IRX3), and CesA8, also known as protein IRREGULAR XYLEM 1 (IRX1) or protein LEAF WILTING 2, are both involved in secondary cell wall formation and also required for xylem cell wall thickening. The biological function of CesA9 and CesA10 remain unclear. CesA1, CesA3, and CesA6 form a functional complex essential for primary cell wall cellulose synthesis, while CesA4, CesA7, and CesA8 form a functional complex located in secondary cell wall deposition sites. All family members contain an N-terminal C4C4-type RING-HC finger and a C-terminal glycosyltransferase family A (GT-A) domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1973916070  14 CPLCMEPLEIDDIN--FFPCT-CGYQICRFCWHRIRTDENGLCPACRKP 59
Cdd:cd16617     3 CQICGDEIGLTVNGelFVACNeCGFPVCRPCYEYERKEGNQCCPQCKTR 51

RING finger, HC subclass, found in tripartite motif-containing protein 40 (TRIM40) and similar proteins; TRIM40, also known as probable E3 NEDD8-protein ligase or RING finger protein 35 (RNF35), is highly expressed in the gastrointestinal tract including the stomach, small intestine, and large intestine. It enhances neddylation of inhibitor of nuclear factor kappaB kinase subunit gamma (IKKgamma), inhibits the activity of nuclear factor-kappaB (NF-kappaB)-mediated transcription, and thus prevents inflammation-associated carcinogenesis in the gastrointestinal tract. TRIM40 belongs to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as an uncharacterized region positioned C-terminal to the RBCC domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1973916070  14 CPLCMEPLEiddiNFFPCTCGYQICRFCW--HRIRTDENGL--CPACRKPYPE 62
Cdd:cd16583     8 CPICQEPLK----EAVSTDCGHLFCRMCLtqHAKKASASGVfsCPVCRKPCSE 56

RING finger, HC subclass, found in Arabidopsis thaliana proteolysis 1 protein (PRT1) and similar proteins; PRT1, also called RING-type E3 ubiquitin transferase PRT1, is an E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. It functions in the N-end rule pathway of protein degradation, where it specifically recognizes and ubiquitinates proteins with an N-terminal bulky aromatic amino acid (Phe). It does not act on aliphatic hydrophobic and basic N-terminal residues (Arg or Leu) containing proteins. PRT1 contains a typical C3HC4-type RING-HC finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1973916070  13 ECPLCMEPLEIDDINffpcTCGYQICRFCWHRIR--TDENgLCPACRKPY 60
Cdd:cd23132     4 LCCICLDLLYKPVVL----ECGHVFCFWCVHRCMngYDES-HCPLCRRPY 48

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM5, TRIM6, TRIM22, TRIM34 and similar proteins; TRIM5, TRIM6, TRIM22, and TRIM34, four closely related tripartite motif-containing proteins, belong to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. TRIM5, also known as RING finger protein 88 (RNF88), is a capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses in a species-specific manner by binding to and destabilizing the retroviral capsid lattice before reverse transcription is completed. Its retroviral restriction activity correlates with the ability to activate TAK1-dependent innate immune signaling. TRIM5 also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Moreover, TRIM5 plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2. It also plays a role in autophagy by acting as a selective autophagy receptor which recognizes and targets HIV-1 capsid protein p24 for autophagic destruction. TRIM6, also known as RING finger protein 89 (RNF89), is an E3-ubiquitin ligase that cooperates with the E2-ubiquitin conjugase UbE2K to catalyze the synthesis of unanchored K48-linked polyubiquitin chains, and further stimulates the interferon-I kappa B kinase epsilon (IKKepsilon) kinase-mediated antiviral response. It also regulates the transcriptional activity of Myc during the maintenance of embryonic stem (ES) cell pluripotency, and may act as a novel regulator for Myc-mediated transcription in ES cells. TRIM22, also known as 50 kDa-stimulated trans-acting factor (Staf-50) or RING finger protein 94 (RNF94), is an E3 ubiquitin-protein ligase that plays an integral role in the host innate immune response to viruses. It has been shown to inhibit the replication of a number of viruses, including HIV-1, hepatitis B, and influenza A. TRIM22 acts as a suppressor of basal HIV-1 long terminal repeat (LTR)-driven transcription by preventing the transcription factor specificity protein 1 (Sp1) binding to the HIV-1 promoter. It also controls FoxO4 activity and cell survival by directing Toll-like receptor 3 (TLR3)-stimulated cells toward type I interferon (IFN) type I gene induction or apoptosis. Moreover, TRIM22 can activate the noncanonical nuclear factor-kappaB (NF-kappaB) pathway by activating I kappa B kinase alpha (IKKalpha). It also regulates nucleotide binding oligomerization domain containing 2 (NOD2)-dependent activation of interferon-beta signaling and nuclear factor-kappaB. TRIM34, also known as interferon-responsive finger protein 1 or RING finger protein 21 (RNF21), may function as antiviral protein that contribute to the defense against retroviral infections.

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gi 1973916070   9 EDPVECPLC----MEPLEIDdinffpctCGYQICRFCWHR-----IRTDENGLCPACRKPYP 61
Cdd:cd16591     4 KEEVTCPIClellTEPLSLD--------CGHSFCQACITAnhkesVNQEGESSCPVCRTSYQ 57

cellulose synthase-like protein

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gi 1973916070    1 MSRSPDAKEDPVECPLC----MEPLEIDDInfFPCTCGYQICRFCWHRIRTDEnGLCPACRKPY 60
Cdd:PLN02248   116 HPQMAGAKGSSCAMPGCdgkvMRDERGEDL--LPCECGFKICRDCYIDAVKSG-GICPGCKEPY 176

RING finger, HC subclass, found in two RING fingers and DRIL [double RING finger linked] 1 (TRIAD1); TRIAD1, also known as ariadne-2 (ARI-2), protein ariadne-2 homolog, Ariadne RBR E3 ubiquitin protein ligase 2 (ARIH2), or UbcM4-interacting protein 48, is an RBR-type E3 ubiquitin-protein ligase that catalyzes the formation of polyubiquitin chains linked via lysine-48, as well as lysine-63 residues. Its auto-ubiquitylation can be catalyzed by the E2 conjugating enzyme UBCH7. TRIAD1 has been implicated in hematopoiesis, specifically in myelopoiesis, as well as in embryogenesis. It functions as a regulator of endosomal transport and is required for the proper function of multivesicular bodies. It also acts as a novel ubiquitination target for proteasome-dependent degradation by murine double minute 2 (MDM2). As a proapoptotic protein, TRIAD1 promotes p53 activation, and inhibits MDM2-mediated p53 ubiquitination and degradation. Furthermore, TRIAD1 can inhibit the ubiquitination and proteasomal degradation of growth factor independence 1 (Gfi1), a transcriptional repressor essential for the function and development of many different hematopoietic lineages. TRIAD1 contains an RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction. This model corresponds to the RING domain, a C3HC4-type RING-HC finger required for RBR-mediated ubiquitination.

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gi 1973916070  12 VECPLCMEPLEIDdiNFFPCTCGYQICRFCWH 43
Cdd:cd16773     1 VTCGVCCEDVPKD--ELFSLACGHYFCNDCWK 30

RING finger, HC subclass, found in tripartite motif-containing protein TRIM21 and similar proteins; TRIM21, also known as 52 kDa Ro protein, 52 kDa ribonucleoprotein autoantigen Ro/SS-A, Ro(SS-A), RING finger protein 81 (RNF81), or Sjoegren syndrome type A antigen (SS-A), is a ubiquitously expressed E3 ubiquitin-protein ligase and a high affinity antibody receptor uniquely expressed in the cytosol of mammalian cells. As a cytosolic Fc receptor, TRIM21 binds the Fc of virus-associated antibodies and targets the complex in the cytosol for proteasomal degradation in a process known as antibody-dependent intracellular neutralization (ADIN), and provides an intracellular immune response to protect host defense against pathogen infection. It shows remarkably broad isotype specificity as it does not only bind IgG, but also IgM and IgA. Moreover, TRIM21 promotes the cytosolic DNA sensor cGAS and the cytosolic RNA sensor RIG-I sensing of viral genomes during infection by antibody-opsonized virus. It stimulates inflammatory signaling and activates innate transcription factors, such as nuclear factor-kappaB (NF-kappaB). TRIM21 also plays an essential role in p62-regulated redox homeostasis, suggesting it may be a viable target for treating pathological conditions resulting from oxidative damage. Furthermore, TRIM21 may have implications for various autoimmune diseases associated with uncontrolled antiviral signaling through the regulation of Nmi-IFI35 complex-mediated inhibition of innate antiviral response. TRIM21 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

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gi 1973916070  12 VECPLCMEPLeiddINFFPCTCGYQICRFCWHRIRTDENGLCPACRKPY 60
Cdd:cd16596    10 VTCPICLDPF----VEPVSIECGHSFCQECISQVGKGGGSVCPVCRQRF 54