B-box-type 2 zinc finger found in Ras guanine nucleotide exchange factor O (GefO) and similar proteins; Ras guanine-nucleotide exchange factors (RasGEFs) activate Ras by catalyzing the replacement of GDP with GTP, and thus lie near the top of many signaling pathways. They are important for signaling in development and chemotaxis in many organisms. Ras guanine nucleotide exchange factor O (GefO), also known as RasGEF domain-containing protein O, is faintly expressed during development of Dictyostelium discoideum. It contains a C3HC4-type RING finger, a B-box motif that shows high sequence similarity with B-Box-type zinc finger 2 found in tripartite motif-containing proteins (TRIMs), a REM (Ras exchanger motif) domain, and a # RasGEF domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 669326311 729 ELCSQHNVSMA-KFCVSCSASVCEQCVLESHAEHNTEPVS 767
Cdd:cd20207    1 VVCSKHNEHMLdKFCKDCSAPVCENCVLTTHAGHNVEPIT 40

RING finger (Really Interesting New Gene) domain and U-box domain superfamily; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers: some have different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type RING fingers are closely related to RING-HC fingers. In contrast, C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type RING fingers are more closely related to RING-H2 fingers. However, not all RING finger-containing proteins display regular RING finger features, and the RING finger family has turned out to be multifarious. The degenerate RING fingers of the Siz/PIAS RING (SP-RING) family proteins and sporulation protein RMD5, are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues. They bind only one Zn2+ ion. On the other hand, the RING fingers of the human APC11 and RBX1 proteins can bind a third Zn atom since they harbor four additional Zn ligands. U-box is a modified form of the RING finger domain that lacks metal chelating Cys and His residues. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms. RING finger/U-box-containing proteins are a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enable efficient transfer of ubiquitin from E2 to the substrates.

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                 ....*....|....*....|....*....|....*
gi 669326311 620 LFCRKCDERINGGAKILPCFHILCSPCFKQQLVSR 654
Cdd:cd16749    1 LECPVCFEKLDVTAKVLPCQHTFCKPCLQRIFKAR 35

B-box-type 2 zinc finger found in Ras guanine nucleotide exchange factor O (GefO) and similar proteins; Ras guanine-nucleotide exchange factors (RasGEFs) activate Ras by catalyzing the replacement of GDP with GTP, and thus lie near the top of many signaling pathways. They are important for signaling in development and chemotaxis in many organisms. Ras guanine nucleotide exchange factor O (GefO), also known as RasGEF domain-containing protein O, is faintly expressed during development of Dictyostelium discoideum. It contains a C3HC4-type RING finger, a B-box motif that shows high sequence similarity with B-Box-type zinc finger 2 found in tripartite motif-containing proteins (TRIMs), a REM (Ras exchanger motif) domain, and a # RasGEF domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 669326311 729 ELCSQHNVSMA-KFCVSCSASVCEQCVLESHAEHNTEPVS 767
Cdd:cd20207    1 VVCSKHNEHMLdKFCKDCSAPVCENCVLTTHAGHNVEPIT 40

B-Box-type zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 669326311   726 KKAELCSQHNVSMAK-FCVSCSASVCEQCVLESHAEHNTEPV 766
Cdd:smart00336   1 QRAPKCDSHGDEPAEfFCEECGALLCRTCDEAEHRGHTVVLL 42

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
                 ....*....|....*....|....*....|....*
gi 669326311 620 LFCRKCDERINGGAKILPCFHILCSPCFKQQLVSR 654
Cdd:cd16749    1 LECPVCFEKLDVTAKVLPCQHTFCKPCLQRIFKAR 35

B-box-type 2 zinc finger found in Ras guanine nucleotide exchange factor O (GefO) and similar proteins; Ras guanine-nucleotide exchange factors (RasGEFs) activate Ras by catalyzing the replacement of GDP with GTP, and thus lie near the top of many signaling pathways. They are important for signaling in development and chemotaxis in many organisms. Ras guanine nucleotide exchange factor O (GefO), also known as RasGEF domain-containing protein O, is faintly expressed during development of Dictyostelium discoideum. It contains a C3HC4-type RING finger, a B-box motif that shows high sequence similarity with B-Box-type zinc finger 2 found in tripartite motif-containing proteins (TRIMs), a REM (Ras exchanger motif) domain, and a # RasGEF domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 669326311 729 ELCSQHNVSMA-KFCVSCSASVCEQCVLESHAEHNTEPVS 767
Cdd:cd20207    1 VVCSKHNEHMLdKFCKDCSAPVCENCVLTTHAGHNVEPIT 40

B-box-type 1 zinc finger found in transcription intermediary factor 1-beta (TIF1-beta); TIF1-beta, also known as Kruppel-associated Box (KRAB)-associated protein 1 (KAP-1), KRAB-interacting protein 1 (KRIP-1), nuclear co-repressor KAP-1, RING finger protein 96, tripartite motif-containing protein 28 (TRIM28), or E3 SUMO-protein ligase TRIM28, belongs to the C-VI subclass of 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 RING finger, Bbox1 and Bbox2, and a coiled coil region, as well as a plant homeodomain (PHD), and a bromodomain (Bromo) positioned C-terminal to the RBCC domain. The type 1 B-box (Bbox1) zinc finger is characterized by a C6H2 zinc-binding consensus motif. TIF1-beta/KAP-1 acts as a nuclear co-repressor that plays a role in transcription and in the DNA damage response. Upon DNA damage, the phosphorylation of KAP-1 on serine 824 by the ataxia telangiectasia-mutated (ATM) kinase enhances cell survival and facilitates chromatin relaxation and heterochromatic DNA repair. It also regulates CHD3 nucleosome remodeling during the DNA double-strand break (DSB) response. Meanwhile, KAP-1 can be dephosphorylated by protein phosphatase PP4C in the DNA damage response. Moreover, KAP-1 is a co-activator of the orphan nuclear receptor NGFI-B (or Nur77) and is involved in NGFI-B-dependent transcription. It is also a coiled-coil binding partner, substrate and activator of the c-Fes protein tyrosine kinase. The N-terminal RBCC domains of TIF1-beta are responsible for the interaction with KRAB zinc finger proteins (KRAB-ZFPs), MDM2, MM1, C/EBPbeta, and the regulation of homo- and heterodimerization. The C-terminal PHD/Bromo domains are involved in interacting with SETDB1, Mi-2alpha and other proteins to form complexes with histone deacetylase or methyltransferase activity.

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                 ....*....|....*....|....*....|....*....|...
gi 669326311 682 CVICEN--VASYFCENCEDNLCERCSQAHLLVKYTRDHVMRQA 722
Cdd:cd19846    6 CTSCEDnaPATSYCVECSEPLCETCVEAHQRVKYTKDHTVRVK 48

B-box-type 1 zinc finger (Bbox1); The B-box-type zinc finger is a short zinc binding domain of around 40 amino acid residues in length. It has been found in transcription factors, ribonucleoproteins and proto-oncoproteins, such as in TRIM (tripartite motif) proteins that consist of an N-terminal RING finger (originally called an A-box), followed by 1-2 B-box domains and a coiled-coil domain (also called RBCC for Ring, B-box, Coiled-Coil). The B-box-type zinc finger often presents in combination with other motifs, like RING zinc finger, NHL motif, coiled-coil or RFP domain, in functionally unrelated proteins, most likely mediating protein-protein interactions. Based on different consensus sequences and the spacing of the 7-8 zinc-binding residues, the B-box-type zinc fingers can be divided into two groups, type 1 (Bbox1: C6H2) and type 2 (Bbox2: CHC3H2). This family corresponds to the type 1 B-box (Bbox1).

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                 ....*....|....*....|....*....|....*....|.
gi 669326311 681 VCVICE-NVASYFCENCEDNLCERCSQA-HLLVKYTRDHVM 719
Cdd:cd19757    1 LCDECEeREATVYCLECEEFLCDDCSDAiHRRGKLTRSHKL 41

B-box zinc finger;

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                  ....*....|....*....|....*....|....*...
gi 669326311  730 LCSQHNVSMAK-FCVSCSASVCEQCVLESHAEHNTEPV 766
Cdd:pfam00643   5 LCPEHEEEPLTlYCNDCQELLCEECSVGEHRGHTVVPL 42

B-box-type 1 zinc finger found in tripartite motif-containing protein 71 (TRIM71) and similar proteins; TRIM71, also known as protein lineage variant 41 (lin-41), is an E3 ubiquitin-protein ligase that may play essential roles in embryonic stem cells, cellular reprogramming, and the timing of embryonic neurogenesis. It was first identified in the nematode Caenorhabditis elegans as a target of the differentiation-associated microRNA (miRNA) let-7 (lethal 7) and therefore part of a heterochronic gene network that controls larval development. In humans, it regulates let-7 microRNA biogenesis via modulation of Lin28B protein polyubiquitination. TRIM71 localizes to cytoplasmic P-bodies and directly interacts with the miRNA pathway proteins Argonaute 2 (AGO2) and DICER. It represses miRNA activity by promoting degradative ubiquitination of AGO2. Moreover, TRIM71 associates with SHCBP1, a novel component of the fibroblast growth factor (FGF) signaling pathway, and regulates its non-degradative polyubiquitination. It is also involved in the post-transcriptional regulation of the CDKN1A, RBL1 and RBL2 or EGR1 mRNAs by mediating RNA-binding in embryonic stem cells. TRIM71 belongs to the C-VII subclass of the TRIM (tripartite motif) family of proteins that is defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and a coiled coil domain, as well as a NHL (named after proteins NCL-1, HT2A and Lin-41 that contain repeats folded into a six-bladed beta propeller) repeat domain positioned C-terminal to the RBCC domain. The type 1 B-box (Bbox1) zinc finger is characterized by a C6H2 zinc-binding consensus motif.

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                 ....*....|....*....|....*....|....*....|...
gi 669326311 682 CVICE--NVASYFCENCEDNLCERCSQAHLLVKYTRDHVMRQA 722
Cdd:cd19812    2 CSSCDegNAATSRCKDCNEYLCDNCVRAHQRVRLTKDHFIVRF 44

B-box-type 2 zinc finger found in tripartite motif-containing proteins, TRIM16, TRIM29, TRIM47 and similar proteins; This family includes a group of tripartite motif-containing proteins, such as TRIM16, TRIM29 and TRIM47. TRIM16, also termed estrogen-responsive B box protein (EBBP), is a regulator that may play a role in the regulation of keratinocyte differentiation. It may also act as a tumor suppressor through affecting cell proliferation and migration or tumorigenicity in carcinogenesis. TRIM29, also termed ataxia telangiectasia group D-associated protein (ATDC), plays a crucial role in the regulation of macrophage activation in response to viral or bacterial infections within the respiratory tract. TRIM47, also known as gene overexpressed in astrocytoma protein (GOA) or RING finger protein 100 (RNF100), plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis. TRIM16 and TRIM29 belong to an unclassified TRIM (tripartite motif) family of proteins that do not have RING fingers and thus lack the characteristic tripartite (RING (R), B-box, and coiled coil (CC)) RBCC motif. TRIM47 belongs to the C-IV subclass of TRIM family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

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                 ....*....|....*....|....*....|....*..
gi 669326311 730 LCSQHNVSMAKFCVSCSASVCEQCVLESHAEHNTEPV 766
Cdd:cd19769    2 VCPIHKKPLELFCRTDQMCICELCAKEEHRGHDVVTV 38

B-box-type 1 zinc finger found in tripartite motif-containing protein 45 (TRIM45) and similar proteins; TRIM45, also known as RING finger protein 99 (RNF99), is a novel receptor for activated C-kinase (RACK1)-interacting protein that suppresses transcriptional activities of Elk-1 and AP-1, and downregulates mitogen-activated protein kinase (MAPK) signal transduction by inhibiting RACK1/PKC (protein kinase C) complex formation. It also negatively regulates tumor necrosis factor alpha (TNFalpha)-induced nuclear factor-kappaB (NF-kappa B)-mediated transcription, and suppresses cell proliferation. TRIM45 belongs to the C-X subclass of the TRIM (tripartite motif) family of proteins that is defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and a coiled coil region, as well as a filamin-type immunoglobulin (IG-FLMN) domain and NHL repeats positioned C-terminal to the RBCC domain. The type 1 B-box (Bbox1) zinc finger is characterized by a C6H2 zinc-binding consensus motif.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 669326311 681 VCVICE---NVASYFCENCEDNLCERCSQAHLLVKYTRDHVMR 720
Cdd:cd19809    2 LCDLCTdgnSSAEYRCFDCSENLCEFCKQAHRRQRKTASHRII 44

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
                 ....*....|....*....|....*....|....*
gi 669326311 620 LFCRKCDERINGGAKILPCFHILCSPCFKQQLVSR 654
Cdd:cd16749    1 LECPVCFEKLDVTAKVLPCQHTFCKPCLQRIFKAR 35

B-box-type 1 zinc finger found in promyelocytic leukemia protein (PML) and similar proteins; Protein PML, also known as RING finger protein 71 (RNF71) or tripartite motif-containing protein 19 (TRIM19), is predominantly a nuclear protein with a broad intrinsic antiviral activity. It is the eponymous component of PML nuclear bodies (PML NBs) and has been implicated in a wide variety of cellular processes, including DNA damage signaling, apoptosis, and transcription. PML interferes with the replication of many unrelated viruses, including human immunodeficiency virus 1 (HIV-1), human foamy virus (HFV), poliovirus, influenza virus, rabies virus, EMCV, adeno-associated virus (AAV), and vesicular stomatitis virus (VSV). It also selectively interacts with misfolded proteins through distinct substrate recognition sites, and conjugates these proteins with the small ubiquitin-like modifiers (SUMOs) through its SUMO ligase activity. PML belongs to the C-V 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 RING finger, Bbox1 and Bbox2, and a coiled coil region, as well as an uncharacterized region positioned C-terminal to the RBCC domain. The type 1 B-box (Bbox1) zinc finger is characterized by a C6H2 zinc-binding consensus motif.

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                 ....*....|....*....|....*....
gi 669326311 681 VCVIC-ENVASYFCENCEDNLCERCSQAH 708
Cdd:cd19804    3 MCNRCsESEAEFWCSECEEFLCRKCFEAH 31