B-box-type 2 zinc finger found in tripartite motif-containing protein 46 (TRIM46) and similar proteins; TRIM46, also known as gene Y protein (GeneY) or tripartite, fibronectin type-III and C-terminal SPRY motif protein (TRIFIC), is a microtubule-associated protein that specifically localizes to the proximal axon, partly overlaps with the axon initial segment (AIS) at later stages, and organizes uniform microtubule orientation in axons. It controls neuronal polarity and axon specification by driving the formation of parallel microtubule arrays. TRIM46 belongs to the C-I subclass of TRIM (tripartite motif) family of proteins, which 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 COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and 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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1720404171 200 KGLMCPDHKEEVTHYCKTCQRLVCQLCRVRRTHSGHKITPVLSAYQ 245
Cdd:cd19786     1 KGLMCPEHKEEVTHYCKTCQRLVCQLCRVRRTHAGHKITPVLSAYQ 46

TRIM C-terminal subgroup One Signature domain; This domain is found in the C-terminal region of the TRIM subgroup C-1 proteins such as E3 ubiquitin-protein ligase Midline-1 protein which is required for the proper development during embryogenesis. Mutations of MID1 are associated with X-linked Opitz G syndrome, characterized by midline anomalies. This domain is also found in MURF1-3 proteins that do not contain the FNIII and B30.2 domains. MUF1-3 proteins are also associated with microtubules. Deletion of the COS domain does not affect MID1 dimerization but disrupts the localization to the microtubules.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1720404171 350 TDQPCFVQAAKQLHNRIARATEALQTFRPAA--SSSFRHCQLDVGREMKLLT 399
Cdd:pfam18568   1 TDHARFLQTAKNVHERVSMATASSQVLIPDInlNDAFENFALDFSREKKLLE 52

coiled-coil (CC) domain of Drosophila brain tumor (brat) and similar proteins; This family contains the coiled-coil (CC) region of Drosophila brain tumor (Brat), a translational repressor that belongs to the tripartite motif (TRIM) protein superfamily. TRIM proteins play important roles in various cellular processes and are involved in many diseases which consists of two B-box domains and a coiled-coil (CC) domain at the N-terminal region, and an NHL domain at the C-terminus. Brat localizes at the basal cortex during asymmetric division of Drosophila neuroblasts by directly interacting with the scaffolding protein Miranda (Mira), which it does through the CC-NHL domain tandem, indicating that the function of the Brat CC domain is to assemble Brat-NHL in dimeric form which is necessary for Mira binding. Brat CC forms an elongated antiparallel dimer similar to its other TRIM protein counterparts, but the overall length of Brat CC dimer is shorter than the TRIMs.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720404171  247 LKDKLTKSLAYILGNQDTVQTQICELEETIRHTEVSGQQAKEEVSQLVRGLGAVLEEKRASLLQAIEECQQERLSRLSAQ 326
Cdd:smart00502   1 QREALEELLTKLRKKAAELEDALKQLISIIQEVEENAADVEAQIKAAFDELRNALNKRKKQLLEDLEEQKENKLKVLEQQ 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1720404171  327 IHEHQSLLDG-SGLVGYAQEVLKETDQPCFVQAAKQLHNRIARATEA 372
Cdd:smart00502  81 LESLTQKQEKlSHAINFTEEALNSGDPTELLLSKKLIIERLQNLLKQ 127

B-box-type 2 zinc finger found in tripartite motif-containing protein 46 (TRIM46) and similar proteins; TRIM46, also known as gene Y protein (GeneY) or tripartite, fibronectin type-III and C-terminal SPRY motif protein (TRIFIC), is a microtubule-associated protein that specifically localizes to the proximal axon, partly overlaps with the axon initial segment (AIS) at later stages, and organizes uniform microtubule orientation in axons. It controls neuronal polarity and axon specification by driving the formation of parallel microtubule arrays. TRIM46 belongs to the C-I subclass of TRIM (tripartite motif) family of proteins, which 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 COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and 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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1720404171 200 KGLMCPDHKEEVTHYCKTCQRLVCQLCRVRRTHSGHKITPVLSAYQ 245
Cdd:cd19786     1 KGLMCPEHKEEVTHYCKTCQRLVCQLCRVRRTHAGHKITPVLSAYQ 46

TRIM C-terminal subgroup One Signature domain; This domain is found in the C-terminal region of the TRIM subgroup C-1 proteins such as E3 ubiquitin-protein ligase Midline-1 protein which is required for the proper development during embryogenesis. Mutations of MID1 are associated with X-linked Opitz G syndrome, characterized by midline anomalies. This domain is also found in MURF1-3 proteins that do not contain the FNIII and B30.2 domains. MUF1-3 proteins are also associated with microtubules. Deletion of the COS domain does not affect MID1 dimerization but disrupts the localization to the microtubules.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1720404171 350 TDQPCFVQAAKQLHNRIARATEALQTFRPAA--SSSFRHCQLDVGREMKLLT 399
Cdd:pfam18568   1 TDHARFLQTAKNVHERVSMATASSQVLIPDInlNDAFENFALDFSREKKLLE 52

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720404171 421 DQIFLCWRLPPHSP-PAWHYTVEFRRTDvpaqpgPTRWQR--REEVRGTSALLENPDTGSVYVLRVRGCNKAGYGEYSED 497
Cdd:cd00063    15 TSVTLSWTPPEDDGgPITGYVVEYREKG------SGDWKEveVTPGSETSYTLTGLKPGTEYEFRVRAVNGGGESPPSES 88

                  ....*
gi 1720404171 498 VHLHT 502
Cdd:cd00063    89 VTVTT 93

B-Box-type zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1720404171  200 KGLMCPDHKEEVTH-YCKTCQRLVCQLCRvRRTHSGHKITPV 240
Cdd:smart00336   2 RAPKCDSHGDEPAEfFCEECGALLCRTCD-EAEHRGHTVVLL 42

RING-type zinc-finger; This zinc-finger is a typical RING-type of plant ubiquitin ligases.

                          10        20        30
                  ....*....|....*....|....*....|...
gi 1720404171  10 CPVCQEMYKQPlVLPCTHNVCQACAREVLGQQG 42
Cdd:pfam13445   1 CPICLELFTDP-VLPCGHTFCRECLEEMSQKKG 32

Fibronectin type III domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720404171 421 DQIFLCWRLPPHSP-PAWHYTVEFRRTDvpaqpGPTRWQRREEVRGT-SALLENPDTGSVYVLRVRGCNKAGYGEYS 495
Cdd:pfam00041  14 TSLTVSWTPPPDGNgPITGYEVEYRPKN-----SGEPWNEITVPGTTtSVTLTGLKPGTEYEVRVQAVNGGGEGPPS 85

B-box-type 1 zinc finger found in tripartite motif-containing proteins, TRIM36, TRIM46 and similar proteins; The family includes tripartite motif-containing proteins, TRIM36 and TRIM46, both of which belong to the C-I 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 COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) 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. TRIM36, the human ortholog of mouse Haprin, also known as RING finger protein 98 (RNF98) or zinc-binding protein Rbcc728, is an E3 ubiquitin-protein ligase expressed in the germ plasm. It has been implicated in acrosome reaction, fertilization, and embryogenesis, as well as in carcinogenesis. TRIM36 functions upstream of Wnt/beta-catenin activation, and plays a role in controlling the stability of proteins regulating microtubule polymerization during cortical rotation, and subsequent dorsal axis formation. It is also potentially associated with chromosome segregation by interacting with the kinetochore protein centromere protein-H (CENP-H), and colocalizing with the microtubule protein alpha-tubulin. Its overexpression may cause chromosomal instability and carcinogenesis. It is, thus, a novel regulator affecting cell cycle progression. Moreover, TRIM36 plays a critical role in the arrangement of somites during embryogenesis. TRIM46, also known as gene Y protein (GeneY) or tripartite, fibronectin type-III and C-terminal SPRY motif protein (TRIFIC), is a microtubule-associated protein that specifically localizes to the proximal axon, partly overlaps with the axon initial segment (AIS) at later stages, and organizes uniform microtubule orientation in axons. It controls neuronal polarity and axon specification by driving the formation of parallel microtubule arrays.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1720404171 146 AILCQLCKPPPLEATKGCTECRATFCNECFKLFHPWGTQKAQHEPTLPTLSF 197
Cdd:cd19807     1 AIKCQLCKPPPQEATKSCADCVASFCNECFKVVHPWGTPKAQHEYVGPTNNF 52

B-box-type 1 zinc finger found in tripartite motif-containing protein 36 (TRIM36) and similar proteins; TRIM36, the human ortholog of mouse Haprin, also known as RING finger protein 98 (RNF98) or zinc-binding protein Rbcc728, is an E3 ubiquitin-protein ligase expressed in the germ plasm. It has been implicated in acrosome reaction, fertilization, and embryogenesis, as well as in carcinogenesis. TRIM36 functions upstream of Wnt/beta-catenin activation, and plays a role in controlling the stability of proteins regulating microtubule polymerization during cortical rotation, and subsequent dorsal axis formation. It is also potentially associated with chromosome segregation by interacting with the kinetochore protein centromere protein-H (CENP-H), and colocalizing with the microtubule protein alpha-tubulin. Its overexpression may cause chromosomal instability and carcinogenesis. It is, thus, a novel regulator affecting cell cycle progression. Moreover, TRIM36 plays a critical role in the arrangement of somites during embryogenesis. TRIM36 belongs to the C-I 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 COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1720404171 146 AILCQLCKPPPLEATKGCTECRATFCNECFKLFHPWGTQKAQHEPTLPTLSF 197
Cdd:cd19848     4 AIMCDLCKPPPQESTKSCMDCKASYCNECFKIHHPWGTPKAQHEYVGPTTNF 55

TRIM C-terminal subgroup One Signature domain; This domain is found in the C-terminal region of the TRIM subgroup C-1 proteins such as E3 ubiquitin-protein ligase Midline-1 protein which is required for the proper development during embryogenesis. Mutations of MID1 are associated with X-linked Opitz G syndrome, characterized by midline anomalies. This domain is also found in MURF1-3 proteins that do not contain the FNIII and B30.2 domains. MUF1-3 proteins are also associated with microtubules. Deletion of the COS domain does not affect MID1 dimerization but disrupts the localization to the microtubules.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1720404171 350 TDQPCFVQAAKQLHNRIARATEALQTFRPAA--SSSFRHCQLDVGREMKLLT 399
Cdd:pfam18568   1 TDHARFLQTAKNVHERVSMATASSQVLIPDInlNDAFENFALDFSREKKLLE 52

B-box-type 2 zinc finger (Bbox2); 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 interaction. Based on different consensus sequence and the spacing of the 7-8 zinc-binding residues, B-box-type zinc fingers can be divided into two groups, type 1 (Bbox1: C6H2) and type 2 (Bbox2: CHC3H2). The family corresponds to type 2 B-box (Bbox2).

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1720404171 203 MCPDHKEE-VTHYCKTCQRLVCQLCRVRRTHSGHKITPV 240
Cdd:cd19756     1 LCPEHPEEpLKLFCETCQELVCVLCLLSGEHRGHKVVPL 39

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM9, TRIM67, and similar proteins; Tripartite motif-containing proteins TRIM9 and TRIM67 belong to the C-I subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, consisting of three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. TRIM9 (the human ortholog of rat Spring), also known as RING finger protein 91 (RNF91), is a brain-specific E3 ubiquitin-protein ligase collaborating with an E2 ubiquitin conjugating enzyme UBCH5b. TRIM9 plays an important role in the regulation of neuronal functions and participates in neurodegenerative disorders through its ligase activity. TRIM67, also known as TRIM9-like protein (TNL), is a protein selectively expressed in the cerebellum. It interacts with PRG-1, an important molecule in the control of hippocampal excitability dependent on presynaptic LPA2 receptor signaling, and 80K-H, also known as glucosidase II beta, a protein kinase C substrate.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 1720404171   5 EKELLCPVCQEMYKQPLVLPCTHNVCQACAR 35
Cdd:cd16576     1 EEELKCPVCGSLFTEPVILPCSHNLCLGCAL 31

RING finger, HC subclass, found in midline-2 (MID2) and similar proteins; MID2, also known as midin-2, midline defect 2, RING finger protein 60 (RNF60), or tripartite motif-containing protein 1 (TRIM1), is a probable E3 ubiquitin-protein ligase and is highly related to MID1 that associates with cytoplasmic microtubules along their length and throughout the cell cycle. Like MID1, MID2 associates with the microtubule network and may at least partially compensate for the loss of MID1. Both MID1 and MID2 interacts with Alpha 4, which is a regulatory subunit of PP2-type phosphatases, such as PP2A, and an integral component of the rapamycin-sensitive signaling pathway. MID2 can also substitute for MID1 to control exocytosis of lytic granules in cytotoxic T cells. Loss-of-function mutations in MID2 lead to the human X-linked intellectual disability (XLID). MID2 belongs to the C-I 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 COS (carboxy-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. MID2 hetero-dimerizes in vitro with its paralog MID1.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1720404171   1 MKNMEKELLCPVCQEMYKQPLVLPCTHNVCQACAREVLGQqgyiGHGGDPSSEPTSPASTPSTR 64
Cdd:cd16754     1 METLESELTCPICLELFEDPLLLPCAHSLCFSCAHRILTS----GCASGESIEPPSAFQCPTCR 60

B-box-type 2 zinc finger found in Xenopus laevis nuclear factor 7 (xNF7) and similar proteins; xNF7 is a maternally expressed novel zinc finger nuclear phosphoprotein. It acts as a transcription factor that determines dorsal-ventral body axis. xNF7 harbors a B-box motif that shows high sequence similarity with B-Box-type zinc finger 2 found in tripartite motif-containing proteins (TRIMs). The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1720404171 203 MCPDHKEEVTHYCKTCQRLVCQLCRVRRTHSGHKITPV 240
Cdd:cd19800     2 VCSEHDEPLKLFCKDDKRLICVICRDSRKHRGHRFLPV 39

RING finger, HC subclass, found in tripartite motif-containing protein TRIM65 and similar proteins; TRIM65 is an E3 ubiquitin-protein ligase that interacts with the innate immune receptor MDA5, enhancing its ability to stimulate interferon-beta signaling. It functions as a potential oncogenic protein that negatively regulates p53 through ubiquitination, providing insight into the development of novel approaches targeting TRIM65 for non-small cell lung carcinoma (NSCLC) treatment, and also overcoming chemotherapy resistance. Moreover, TRIM65 negatively regulates microRNA-driven suppression of mRNA translation by targeting TNRC6 proteins for ubiquitination and degradation. TRIM65 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.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1720404171   5 EKELLCPVCQEMYKQPLVLPCTHNVCQACAREVLGQ 40
Cdd:cd16609     1 EEELTCSICLGLYQDPVTLPCQHSFCRACIEDHWRQ 36

RING finger, HC subclass, found in muscle-specific RING finger protein 2 (MuRF-2) and similar proteins; MuRF-2, also known as tripartite motif-containing protein 55 (TRIM55) or RING finger protein 29 (RNF29), is a muscle-specific E3 ubiquitin-protein ligase in ubiquitin-mediated muscle protein turnover and is also a ligand of the transactivation domain of the serum response transcription factor (SRF). It is predominantly slow-fibre associated and highly expressed in embryonic skeletal muscle. MuRF-2 associates transiently with microtubules, myosin, and titin during sarcomere assembly. It has been implicated in microtubule, intermediate filament, and sarcomeric M-line maintenance in striated muscle development, as well as in signaling from the sarcomere to the nucleus. It plays an important role in the earliest stages of skeletal muscle differentiation and myofibrillogenesis. It is developmentally downregulated and is assembled at the M-line region of the sarcomere and with microtubules. MuRF-2 belongs to the C-II 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 COS (carboxyl-terminal subgroup one signature) box, and an acidic residue-rich (AR) domain. It also harbors a MURF family-specific conserved box (MFC) between its RING-HC finger and Bbox domains.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1720404171   5 EKELLCPVCQEMYKQPLV-LPCTHNVCQACAREVL 38
Cdd:cd16760     1 EKQLICPICLEMFTKPVViLPCQHNLCRKCANDIF 35

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720404171 421 DQIFLCWRLPPHSP-PAWHYTVEFRRTDvpaqpgPTRWQR--REEVRGTSALLENPDTGSVYVLRVRGCNKAGYGEYSED 497
Cdd:cd00063    15 TSVTLSWTPPEDDGgPITGYVVEYREKG------SGDWKEveVTPGSETSYTLTGLKPGTEYEFRVRAVNGGGESPPSES 88

                  ....*
gi 1720404171 498 VHLHT 502
Cdd:cd00063    89 VTVTT 93

RING finger, HC subclass, found in tripartite motif-containing protein 69 (TRIM69) and similar proteins; TRIM69, also known as RFP-like domain-containing protein trimless or RING finger protein 36 (RNF36), is a testis E3 ubiquitin-protein ligase that plays a specific role in apoptosis and may also play an important role in germ cell homeostasis during spermatogenesis. TRIM69 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.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1720404171   7 ELLCPVCQEMYKQPLVLPCTHNVCQACAREVLGQQ 41
Cdd:cd16611     4 ELHCPLCLDFFRDPVMLSCGHNFCQSCITGFWELQ 38

RING finger, HC subclass, found in muscle-specific RING finger protein 3 (MuRF-3) and similar proteins; MuRF-3, also known as tripartite motif-containing protein 54 (TRIM54), or RING finger protein 30 (RNF30), is an E3 ubiquitin-protein ligase in ubiquitin-mediated muscle protein turnover. It is ubiquitously detected in all fibre types, is developmentally upregulated, associates with microtubules, the sarcomeric M-line and Z-line, and is required for microtubule stability and myogenesis. It associates with glutamylated microtubules during skeletal muscle development, and is required for skeletal myoblast differentiation and development of cellular microtubular networks. MuRF-3 controls the degradation of four-and-a-half LIM domain (FHL2) and gamma-filamin and is required for maintenance of ventricular integrity after myocardial infarction (MI). MuRF-3 belongs to the C-II 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 COS (carboxyl-terminal subgroup one signature) box, and an acidic residue-rich (AR) domain. It also harbors a MURF family-specific conserved box (MFC) between its RING-HC finger and Bbox domains.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1720404171   8 LLCPVCQEMYKQPLV-LPCTHNVCQACAREVL 38
Cdd:cd16761     1 LICPICLEMFTKPVViLPCQHNLCRKCANDVF 32

RING finger, HC subclass, 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 through 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-VII subclass of the TRIM (tripartite motif) family that is 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 filamin-type immunoglobulin (IG-FLMN) domain and NHL repeats positioned C-terminal to the RBCC domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1720404171  10 CPVCQEMYKQPLVLPCTHNVCQACAREvLGQQGYIGHGGDPSSEPTS 56
Cdd:cd16588     3 CPVCGKLFQEPRLLPCLHTLCSPCLRQ-LEPFSVCGLRGGDRSEKSN 48

RING finger, HC subclass, found in muscle-specific RING finger proteins TRIM63/MuRF-1, TRIM55/MuRF-2 and TRIM54/MuRF-3; This subfamily corresponds to a group of striated muscle-specific tripartite motif (TRIM) proteins, including TRIM63/MuRF-1, TRIM55/MuRF-2, and TRIM54/MuRF-3, which function as E3 ubiquitin ligases in ubiquitin-mediated muscle protein turnover. They are tightly developmentally regulated in skeletal muscle and associate with different cytoskeleton components, such as microtubules, Z-disks and M-bands, as well as with metabolic enzymes and nuclear proteins. They also cooperate with diverse proteins implicated in selective protein degradation by the proteasome and autophagosome, and target proteins of metabolic regulation, sarcomere assembly and transcriptional regulation. Moreover, MURFs display variable fibre-type preferences. TRIM63/MuRF-1 is predominantly fast (type II) fibre-associated in skeletal muscle. TRIM55/MuRF-2 is predominantly slow-fibre associated. TRIM54/MuRF-3 is ubiquitously present. They play an active role in microtubule-mediated sarcomere assembly. MuRFs belong to the C-II subclass of the 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 C3HC4-type RING-HC finger, Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, and an acidic residue-rich (AR) domain positioned C-terminal to the RBCC domain. They also harbor a MURF family-specific conserved box (MFC) between its RING-HC finger and Bbox domains.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 1720404171   8 LLCPVCQEMYKQPLV-LPCTHNVCQACAREV 37
Cdd:cd16577     1 LICPICLEMFTKPVViLPCQHNLCRKCANDI 31

RING finger, HC subclass, found in tripartite motif-containing protein TRIM25 and similar proteins; TRIM25, also known as estrogen-responsive finger protein (EFP), RING finger protein 147 (RNF147), or RING-type E3 ubiquitin transferase, is an E3 ubiquitin/ISG15 ligase that is induced by estrogen and is therefore particularly abundant in placenta and uterus. TRIM25 regulates various cellular processes through E3 ubiquitin ligase activity, transferring ubiquitin and ISG15 to target proteins. It mediates K63-linked polyubiquitination of retinoic acid inducible gene I (RIG-I) that is crucial for downstream antiviral interferon signaling. It is also required for melanoma differentiation-associated gene 5 (MDA5) and mitochondrial antiviral signaling (MAVS, also known as IPS-1, VISA, Cardiff) mediated activation of nuclear factor-kappaB (NF-kappaB) and interferon production. Upon UV irradiation, TRIM25 interacts with mono-ubiquitinated PCNA and promotes its ISG15 modification (ISGylation), suggesting a crucial role in termination of error-prone translesion DNA synthesis. TRIM25 also functions as a novel regulator of p53 and Mdm2. It enhances p53 and Mdm2 abundance by inhibiting their ubiquitination and degradation in 26S proteasomes. Meanwhile, it inhibits p53's transcriptional activity and dampens the response to DNA damage, and is essential for medaka development and this dependence is rescued by silencing of p53. Moreover, TRIM25 is involved in the host cellular innate immune response against retroviral infection. It interferes with the late stage of feline leukemia virus (FeLV) replication. Furthermore, TRIM25 acts as an oncogene in gastric cancer. Its blockade by RNA interference inhibits migration and invasion of gastric cancer cells through transforming growth factor-beta (TGF-beta) signaling, suggesting it presents a novel target for the detection and treatment of gastric cancer. In addition, TRIM25 acts as an RNA-specific activator for Lin28a/TuT4-mediated uridylation. TRIM25 belongs to the C-IV 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 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.

                          10        20        30
                  ....*....|....*....|....*....|
gi 1720404171   4 MEKELLCPVCQEMYKQPLVLPCTHNVCQAC 33
Cdd:cd16597     2 LEEELTCSICLELFKDPVTLPCGHNFCGVC 31

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM13, TRIM59 and similar proteins; TRIM13 and TRIM59, two closely related tripartite motif-containing proteins, belong 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, followed by a C-terminal transmembrane domain. TRIM13, also known as B-cell chronic lymphocytic leukemia tumor suppressor Leu5, leukemia-associated protein 5, putative tumor suppressor RFP2, RING finger protein 77 (RNF77), or Ret finger protein 2, is an endoplasmic reticulum (ER) membrane anchored E3 ubiquitin-protein ligase that interacts with proteins localized to the ER, including valosin-containing protein (VCP), a protein indispensable for ER-associated degradation (ERAD). TRIM59, also known as RING finger protein 104 (RNF104) or tumor suppressor TSBF-1, is a putative E3 ubiquitin-protein ligase that functions as a novel multiple cancer biomarker for immunohistochemical detection of early tumorigenesis.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1720404171   7 ELLCPVCQEMYKQPLVLPCTHNVCQACAREVLGQQGY 43
Cdd:cd16581     2 ELTCSICYNIFDDPKILPCSHTFCKNCLEKLLAASGY 38

B-box-type 1 zinc finger found in tripartite motif-containing protein 42 (TRIM42) and similar proteins; TRIM42 belongs to the C-III 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 domain. It also has a novel cysteine-rich motif N-terminal to the RBCC domain, as well as a COS (carboxyl-terminal subgroup one signature) box and a fibronectin type-III (FN3) 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. TRIM42 can interact with TRIM27, a known cancer-associated protein. Its precise biological function remains unclear.

                          10        20        30
                  ....*....|....*....|....*....|...
gi 1720404171 147 ILCQLCKPPPLEATKGCTECRATFCNECFKLFH 179
Cdd:cd19808     2 IFCQICTQKRESAVKRCITCRLNLCNKCLRKLH 34

RING finger, HC subclass, found in tripartite motif-containing protein 59 (TRIM59) and similar proteins; TRIM59, also known as RING finger protein 104 (RNF104) or tumor suppressor TSBF-1, is a putative E3 ubiquitin-protein ligase that functions as a novel multiple cancer biomarker for immunohistochemical detection of early tumorigenesis. It is upregulated in gastric cancer and promotes gastric carcinogenesis by interacting with and targeting the P53 tumor suppressor for its ubiquitination and degradation. It also acts as a novel accessory molecule involved in cytotoxicity of BCG-activated macrophages (BAM). Moreover, TRIM59 may serve as a multifunctional regulator for innate immune signaling pathways. It interacts with ECSIT and negatively regulates nuclear factor-kappaB (NF- kappa B) and interferon regulatory factor (IRF)-3/7-mediated signal pathways. TRIM59 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. In addition, TRIM59 contains a C-terminal transmembrane domain.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 1720404171   5 EKELLCPVCQEMYKQPLVLPCTHNVCQACAREVL 38
Cdd:cd16763     1 EEDLTCSVCYSLFEDPRVLPCSHTFCRNCLENIL 34

B-box-type 1 zinc finger found in midline-1 (MID1) and similar proteins; MID1, also termed midin, or midline 1 RING finger protein, or putative transcription factor XPRF, or RING finger protein 59 (RNF59), or tripartite motif-containing protein 18 (TRI18), is a microtubule-associated E3 ubiquitin-protein ligase implicated in epithelial-mesenchymal differentiation, cell migration and adhesion, and programmed cell death along specific regions of the ventral midline during embryogenesis. It monoubiquinates the alpha4 subunit of protein phosphatase 2A (PP2A), promoting proteosomal degradation of the catalytic subunit of PP2A (PP2Ac) and preventing the A and B subunits from forming an active complex. It promotes allergen and rhinovirus-induced asthma through the inhibition of PP2A activity. It is strongly upregulated in cytotoxic lymphocytes (CTLs) and directs lytic granule exocytosis and cytotoxicity of killer T cells. Loss-of-function mutations in MID1 lead to the human X-linked Opitz G/BBB (XLOS) syndrome characterized by defective midline development during embryogenesis. MID1 belongs to the C-I 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 COS (carboxyl-terminal subgroup one signature) box, the fibronectin type III domain and the SPRY/B30.2 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. MID1 heterodimerizes in vitro with its paralog MID2.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1720404171 147 ILCQLC-KPPPLEATKGCTECRATFCNECFKLFHP 180
Cdd:cd19836     3 VLCQFCdQDPAQDAVKTCVTCEVSYCDECLKATHP 37

B-box-type 1 zinc finger found in the midline (MID) family; The MID family includes MID1 and MID2. MID1, also known as midin, midline 1 RING finger protein, putative transcription factor XPRF, RING finger protein 59 (RNF59), or tripartite motif-containing protein 18 (TRIM18), is a microtubule-associated E3 ubiquitin-protein ligase implicated in epithelial-mesenchymal differentiation, cell migration and adhesion, and programmed cell death along specific regions of the ventral midline during embryogenesis. MID2, also known as midin-2, midline defect 2, RING finger protein 60 (RNF60), or tripartite motif-containing protein 1 (TRIM1), is highly related to MID1. It associates with the microtubule network and may at least partially compensate for the loss of MID1. Both MID1 and MID2 interacts with alpha4, a regulatory subunit of PP2-type phosphatases, such as PP2A, and an integral component of the rapamycin-sensitive signaling pathway. They also play a central role in the regulation of granule exocytosis, and functional redundancy exists between MID1 and MID2 in cytotoxic lymphocytes (CTL). Both MID1 and MID2 belong to the C-I 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 COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) 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.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1720404171 147 ILCQLC-KPPPLEATKGCTECRATFCNECFKLFHP 180
Cdd:cd19801     2 VPCDVCeKEPPRKAVKTCLTCEVSYCKRCLEATHP 36

B-Box-type zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1720404171  200 KGLMCPDHKEEVTH-YCKTCQRLVCQLCRvRRTHSGHKITPV 240
Cdd:smart00336   2 RAPKCDSHGDEPAEfFCEECGALLCRTCD-EAEHRGHTVVLL 42

B-box-type 2 zinc finger found in tripartite motif-containing protein 8 (TRIM8) and similar proteins; TRIM8, also known as glioblastoma-expressed RING finger protein (GERP) or RING finger protein 27 (RNF27), is a probable E3 ubiquitin-protein ligase that may promote proteasomal degradation of suppressor of cytokine signaling 1 (SOCS1) and further regulate interferon-gamma signaling. It functions as a new p53 modulator that stabilizes p53, impairing its association with MDM2 and inducing the reduction of cell proliferation. TRIM8 deficit dramatically impairs p53 stabilization and activation in response to chemotherapeutic drugs. TRIM8 also modulates tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta)-triggered nuclear factor-kappaB (NF-kappa B) activation by targeting transforming growth factor beta (TGFbeta) activated kinase 1 (TAK1) for K63-linked polyubiquitination. Moreover, TRIM8 modulates translocation of phosphorylated STAT3 into the nucleus through interaction with Hsp90beta and consequently regulates transcription of Nanog in embryonic stem cells. It also interacts with protein inhibitor of activated STAT3 (PIAS3), which inhibits IL-6-dependent activation of STAT3. TRIM8 belongs to the C-V subclass of nuclear 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 domain, as well as an uncharacterized region positioned C-terminal to the RBCC domain. The coiled coil domain is required for homodimerization and the region immediately C-terminal to the RING motif is sufficient to mediate the interaction with SOCS1. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 1720404171 204 CPDHKEEVTHYCKTCQRLVCQLCRVRRTHSGHKI 237
Cdd:cd19763     4 CPQHDAYRLYHCEAEQVAVCEYCCYEGTHQGHSI 37

RING finger, HC subclass, found in RING finger protein 138 (RNF138) and similar proteins; RNF138, also known as Nemo-like kinase-associated RING finger protein (NARF) or NLK-associated RING finger protein, is an E3 ubiquitin-protein ligase that plays an important role in glioma cell proliferation, apoptosis, and cell cycle. It specifically cooperates with the E2 conjugating enzyme E2-25K (Hip-2/UbcH1), regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF), and further suppresses Wnt-beta-catenin signaling. RNF138, together with three closely related proteins: RNF114, RNF125 and RNF166, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM).

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1720404171   7 ELLCPVCQEMYKQPLVL-PCTHNVCQACAREVLGQQGY 43
Cdd:cd16544     2 ELTCPVCQEVLKDPVELpPCRHIFCKACILLALRSSGA 39

B-box-type 2 zinc finger found in tripartite motif-containing protein TRIM50, TRIM73, TRIM74 and similar proteins; TRIM50 is a stomach-specific E3 ubiquitin-protein ligase, encoded by the Williams-Beuren syndrome (WBS) TRIM50 gene, which regulates vesicular trafficking for acid secretion in gastric parietal cells. It colocalizes, interacts with, and increases the level of p62/SQSTM1, a multifunctional adaptor protein implicated in various cellular processes including the autophagy clearance of polyubiquitinated protein aggregates. It also promotes the formation and clearance of aggresome-associated polyubiquitinated proteins through the interaction with the histone deacetylase 6 (HDAC6), a tubulin specific deacetylase that regulates microtubule-dependent aggresome formation. TRIM50 can be acetylated by PCAF and p300. TRIM50 belongs to the C-IV 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, 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. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif. The family also includes two paralogs of TRIM50, tripartite motif-containing protein 73 (TRIM73), also known as tripartite motif-containing protein 50B (TRIM50B), and tripartite motif-containing protein 74 (TRIM74), also known as tripartite motif-containing protein 50C (TRIM50C), both of which are WBS-related genes encoding proteins and may also act as E3 ligases. In contrast with TRIM50, TRIM73 and TRIM74 belong to the C-V subclass of TRIM family of proteins that are defined by the N-terminal RBCC domains only.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1720404171 204 CPDHKEEVTHYCKTCQRLVCQLCRVRRTHSGHKITPV 240
Cdd:cd19787     3 CPHHHNPLSLFCEKDQEVICGLCGLIGSHRQHKITPV 39

RING finger, HC subclass, 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 cell 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 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
                  ....*....|....*....|....*....
gi 1720404171   5 EKELLCPVCQEMYKQPLVLPCTHNVCQAC 33
Cdd:cd16579     2 FKFLRCPGCKAEYKCPKLLPCLHTVCSGC 30

B-box-type 2 zinc finger found in tripartite motif-containing protein 11 (TRIM11) and similar proteins; 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) through 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. TRIM11 belongs to the C-IV 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, Bbox2, and a coiled coil region, as well as a SPRY/B30.2 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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1720404171 203 MCPDHKEEVTHYCKTCQRLVCQLCRVRRTHSGHKITPVLSAYQ 245
Cdd:cd19766     2 LCGKHREPLKLFCKDHEALLCVVCERSREHWGHRVVPAEEAAQ 44

B-box-type zinc finger superfamily; 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, B-box-type zinc fingers can be divided into two groups, type 1 (Bbox1: C6H2) and type 2 (Bbox2: CHC3H2).

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1720404171 203 MCPDHKEE-VTHYCKTCQRLVCQLCRVRRTHSGHKITP 239
Cdd:cd00021     1 MCQEHDEEkANKYCVTCEVLYCALCKKSGAHPDHEVAP 38

B-Box C-terminal domain; Coiled coil region C-terminal to (some) B-Box domains

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720404171  247 LKDKLTKSLAYILGNQDTVQTQICELEETIRHTEVSGQQAKEEVSQLVRGLGAVLEEKRASLLQAIEECQQERLSRLSAQ 326
Cdd:smart00502   1 QREALEELLTKLRKKAAELEDALKQLISIIQEVEENAADVEAQIKAAFDELRNALNKRKKQLLEDLEEQKENKLKVLEQQ 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1720404171  327 IHEHQSLLDG-SGLVGYAQEVLKETDQPCFVQAAKQLHNRIARATEA 372
Cdd:smart00502  81 LESLTQKQEKlSHAINFTEEALNSGDPTELLLSKKLIIERLQNLLKQ 127

DNA repair protein rad18; All proteins in this family for which functions are known are involved in nucleotide excision repair.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720404171   1 MKNMEKELLCPVCQEMYKQPLVLPCTHNVCQACAREVLgqqgyighggdpSSEPTSPASTPSTRSPRLSRRTL 73
Cdd:TIGR00599  20 LYPLDTSLRCHICKDFFDVPVLTSCSHTFCSLCIRRCL------------SNQPKCPLCRAEDQESKLRSNWL 80

RING finger, HC subclass, found in tripartite motif-containing protein TRIM50, TRIM73, TRIM74 and similar proteins; TRIM50 is a stomach-specific E3 ubiquitin-protein ligase, encoded by the Williams-Beuren syndrome (WBS) TRIM50 gene, which regulates vesicular trafficking for acid secretion in gastric parietal cells. It colocalizes, interacts with, and increases the level of p62/SQSTM1, a multifunctional adaptor protein implicated in various cellular processes including the autophagy clearance of polyubiquitinated protein aggregates. It also promotes the formation and clearance of aggresome-associated polyubiquitinated proteins through the interaction with histone deacetylase 6 (HDAC6), a tubulin specific deacetylase that regulates microtubule-dependent aggresome formation. TRIM50 can be acetylated by PCAF and p300. TRIM50 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. This subfamily also includes two paralogs of TRIM50, tripartite motif-containing protein 73 (TRIM73), also known as tripartite motif-containing protein 50B (TRIM50B), and tripartite motif-containing protein 74 (TRIM74), also known as tripartite motif-containing protein 50C (TRIM50C), both of which are WBS-related genes encoding proteins that may also act as E3 ligases. In contrast with TRIM50, TRIM73 and TRIM74 belong to the C-V subclass of TRIM family of proteins that are defined by N-terminal RBCC domains only.

                          10        20
                  ....*....|....*....|....*.
gi 1720404171   8 LLCPVCQEMYKQPLVLPCTHNVCQAC 33
Cdd:cd16605     1 LLCPICLEVFKEPLMLQCGHSYCKSC 26

B-box-type 2 zinc finger found in B box and SPRY domain-containing protein (BSPRY) and similar proteins; BSPRY is a regulatory protein for maintaining calcium homeostasis. It may regulate epithelial calcium transport by inhibiting TRPV5 activity. BSPRY is composed of a B-box, an alpha-helical coiled coil and a SPRY domain. The B-box motif shows high sequence similarity with B-Box-type zinc finger 2 found in tripartite motif-containing proteins (TRIMs). The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1720404171 204 CPDHKEEVTHYCKTCQRLVCQLCRVRRTHSGHKITPV 240
Cdd:cd19834     3 CPDHELELDWFCSTERRLVCAQCASLGTCRGHRVTPL 39

B-box-type 2 zinc finger found in tripartite motif-containing proteins, TRIM4, TRIM17, TRIM41, TRIM52 and similar proteins; This family includes a group of tripartite motif-containing proteins, including TRIM4, TRIM17, TRIM41 and TRIM52. TRIM4, also known as RING finger protein 87 (RNF87), is a cytoplasmic E3 ubiquitin-protein ligase that recently evolved and is present only in higher mammals. It transiently interacts with mitochondria, induces mitochondrial aggregation and sensitizes the cells to hydrogen peroxide (H2O2) induced death. Its interaction with peroxiredoxin 1 (PRX1) is critical for the regulation of H2O2 induced cell death. Moreover, TRIM4 functions as a positive regulator of RIG-I-mediated type I interferon induction. It regulates the K63-linked ubiquitination of RIG-1 and assembly of antiviral signaling complex at mitochondria. TRIM17, also known as RING finger protein 16 (RNF16) or testis RING finger protein (Terf), is a crucial E3 ubiquitin ligase that is necessary and sufficient for neuronal apoptosis and contributes to Mcl-1 ubiquitination in cerebellar granule neurons (CGNs). It interacts in a SUMO-dependent manner with nuclear factor of activated T cell NFATc3 transcription factor, and thus inhibits the activity of NFATc3 by preventing its nuclear localization. In contrast, it binds to and inhibits NFATc4 transcription factor in a SUMO-independent manner. Moreover, TRIM17 stimulates degradation of kinetochore protein ZW10 interacting protein (ZWINT), a known component of the kinetochore complex required for mitotic spindle checkpoint, and negatively regulates cell proliferation. TRIM41, also known as RING finger-interacting protein with C kinase (RINCK), is an E3 ubiquitin-protein ligase that promotes the ubiquitination of protein kinase C (PKC) isozymes in cells. It specifically recognizes the C1 domain of PKC isozymes. It controls the amplitude of PKC signaling by controlling the amount of PKC in the cell. TRIM52, also known as RING finger protein 102 (RNF102), is encoded by a novel, noncanonical antiviral TRIM52 gene in primate genomes with unique specificity determined by the rapidly evolving RING domain. TRIM4, TRIM17 and TRIM41 belong to the C-IV 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, 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. In contrast, TRIM52 lacks the putative viral recognition SPRY/B30.2 domain, and thus has been classified to the C-V subclass of TRIM family that contains only RBCC domains. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1720404171 203 MCPDHKEEVTHYCKTCQRLVCQLCRVRRTHSGHKITPV 240
Cdd:cd19760     2 LCEKHQEPLKLFCEEDEALICVICRESRAHRAHTVVPI 39

RING finger, HC subclass, found in tripartite motif-containing protein 47 (TRIM47) and similar proteins; TRIM47, also known as gene overexpressed in astrocytoma protein (GOA) or RING finger protein 100 (RNF100), 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, 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. It plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis. This subfamily also includes RING finger protein 135 (RNF135). RNF135, also known as RIG-I E3 ubiquitin ligase (REUL) or Riplet, is a widely expressed E3 ubiquitin-protein ligase that consists of an N-terminal C3HC4-type RING-HC finger and C-terminal B30.2/SPRY and PRY motifs, but lacks the B-box and coiled-coil domains that are also typically present in TRIM proteins. RNF135 serves as a specific retinoic acid-inducible gene-I (RIG-I)-interacting protein that ubiquitinates RIG-I and specifically stimulates RIG-I-mediated innate antiviral activity to produce antiviral type-I interferon (IFN) during the early phase of viral infection. It also has been identified as a bio-marker and therapy target of glioblastoma. It associates with the ERK signal transduction pathway and plays a role in glioblastoma cell proliferation, migration and cell cycle.

                          10        20
                  ....*....|....*....|....*.
gi 1720404171   8 LLCPVCQEMYKQPLVLPCTHNVCQAC 33
Cdd:cd16604     1 LSCPICLDLLKDPVTLPCGHSFCMGC 26

B-box-type 2 zinc finger found in muscle-specific RING finger protein 3 (MuRF-3) and similar proteins; MuRF-3, also known as tripartite motif-containing protein 54 (TRIM54), or RING finger protein 30 (RNF30), is an E3 ubiquitin-protein ligase in ubiquitin-mediated muscle protein turnover. It is ubiquitously detected in all fibre types, and is developmentally upregulated, associates with microtubules, the sarcomeric M-line and Z-line, and is required for microtubule stability and myogenesis. It associates with glutamylated microtubules during skeletal muscle development, and is required for skeletal myoblast differentiation and development of cellular microtubular networks. MuRF-3 controls the degradation of four-and-a-half LIM domain (FHL2) and gamma-filamin and is required for maintenance of ventricular integrity after myocardial infarction (MI). MuRF-3 belongs to the C-II 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, Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, and an acidic residue-rich (AR) domain. It also harbors a MURF family-specific conserved box (MFC) between its RING-HC finger and Bbox domains. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

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gi 1720404171 202 LMCPDHKEE-VTHYCKTCQRLVCQLCRVRRTHSGHKITPV 240
Cdd:cd19833     1 LMCEEHEEEkINIYCLSCEVPTCSLCKVFGAHKDCEVAPL 40

B-box-type 2 zinc finger found in tripartite motif-containing proteins TRIM7, TRIM27 and similar proteins; The family includes TRIM7 and TRIM27, both of which belong to the C-IV subclass of TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, 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. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif. 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. TRIM27, also termed RING finger protein 76 (RNF76), or 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. It also inhibits muscle differentiation by modulating serum response factor (SRF) and Epc1. Furthermore, TRIM27 promotes 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. In addition, TRIM27 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 also a component of an estrogen receptor 1 (ESR1) regulatory complex, and is involved in estrogen receptor-mediated transcription in MCF-7 cells. Meanwhile, TRIM27 interacts with the hinge region of chromosome 3 protein (SMC3), a component of the multimeric cohesin complex that holds sister chromatids together and prevents their premature separation during mitosis.

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gi 1720404171 203 MCPDHKEEVTHYCKTCQRLVCQLCRVRRTHSGHKITPVLSAYQ 245
Cdd:cd19762     2 VCEKHQEPLKLFCKEDKRPICVVCDRSREHRHHTVLPVEEAAQ 44

RING finger, HC subclass, found in RING finger protein 213 (RNF213) and similar proteins; RNF213, also known as ALK lymphoma oligomerization partner on chromosome 17 or Moyamoya steno-occlusive disease-associated AAA+ and RING finger protein (mysterin), is an intracellular soluble protein that functions as an E3 ubiquitin-protein ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell. It plays a unique role in endothelial cells for proper gene expression in response to inflammatory signals from the environment. Mutations in RNF213 may be associated with Moyamoya disease (MMD), an idiopathic cerebrovascular occlusive disorder prevalent in East Asia. It also acts as a nuclear marker for acanthomorph phylogeny. RNF213 contains two tandem enzymatically active AAA+ ATPase modules and a C3HC4-type RING-HC finger. It can form a huge ring-shaped oligomeric complex.

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gi 1720404171  10 CPVCQEMYKQPLVLPCTHNVCQACAREVLGQQ 41
Cdd:cd16561     5 CSICLEDLNDPVKLPCDHVFCEECIRQWLPGQ 36

B-box-type 1 zinc finger found in midline-2 (MID2) and similar proteins; MID2, also known as midin-2, midline defect 2, RING finger protein 60 (RNF60), or tripartite motif-containing protein 1 (TRIM1), is a probable E3 ubiquitin-protein ligase that is highly related to MID1, which associates with cytoplasmic microtubules along their length and throughout the cell cycle. Like MID1, MID2 associates with the microtubule network and may at least partially compensate for the loss of MID1. Both MID1 and MID2 interacts with alpha4, a regulatory subunit of PP2-type phosphatases, such as PP2A, and an integral component of the rapamycin-sensitive signaling pathway. MID2 can also substitute for MID1 to control exocytosis of lytic granules in cytotoxic T cells. Loss-of-function mutations in MID2 lead to human X-linked intellectual disability (XLID). MID2 belongs to the C-I 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 COS (carboxy-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) 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. MID2 heterodimerizes in vitro with its paralog MID1.

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gi 1720404171 147 ILCQLC-KPPPLEATKGCTECRATFCNECFKLFHP 180
Cdd:cd19837     3 IACQFCeQEPPRDAVKTCITCEVSYCDRCLRATHP 37

second RING finger, HC subclass, found in Arabidopsis thaliana ORTHRUS and similar proteins; This subfamily includes Arabidopsis thaliana ORTHRUS 1-5. They are E3 ubiquitin-protein ligases that may participate in CpG methylation-dependent transcriptional regulation and/or epigenetic transcriptional silencing. ORTHRUS 1 mediates ubiquitination with the E2 ubiquitin-conjugating enzymes UBC11, UBC8 and UBC8 homologs (e.g. UBC10, UBC11, UBC28 and UBC29) but not with UBC27, UBC30, UBC32, UBC34 and UBC36. ORTHRUS 2 and 5 mediate ubiquitination with the E2 ubiquitin-conjugating enzyme UBC11. ORTHRUS 1 and 2 promote methylation-mediated gene silencing leading, for example, to early flowering. They can bind to CpG, CpNpG, and CpNpN DNA motifs, with a strong preference for methylated forms, and with highest affinity for CpG substrates. Members of this subfamily contain two typical C3HC4-type RING-HC fingers. This model corresponds to the second one.

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gi 1720404171   6 KELLCPVCQEMYKQPLVLPCTHNVCQAC 33
Cdd:cd23139     4 KEFGCQICKKVLSLPVSTPCGHNFCKAC 31