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        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 68160937   6 PLAEELSCSICLEPFKEPVTTPCGHNFCGSCLNETWAVQ-GSPYLCPQCRAVYQARPQLHKNTVLCNVVEQ 75
Cdd:cd16597   1 DLEEELTCSICLELFKDPVTLPCGHNFCGVCIEKTWDSQhGSEYSCPQCRATFPRRPELHKNTVLRNIVEQ 71

B-box-type 2 zinc finger found in tripartite motif-containing protein 25 (TRIM25) and similar proteins; TRIM25, also termed estrogen-responsive finger protein (EFP), or ubiquitin/ISG15-conjugating enzyme TRIM25, or zinc finger protein 147 (ZNF147), or E3 ubiquitin/ISG15 ligase TRIM25, is induced by estrogen and particularly abundant in placenta and uterus. It has been implicated in cell proliferation, protein modification, and the retinoic acid inducible gene I (RIG-I)-mediated antiviral signaling pathway. It functions as an E3-ubiquitin ligase able to transfer ubiquitin and ISG15 to target proteins. It binds to mono-ubiquitinated PCNA and promotes the ISG15 modification (ISGylation) of PCNA, suggesting a crucial role in termination of error-prone translesion DNA synthesis. TRIM25 also enhances p53 and Mdm2 abundance by inhibiting their ubiquitination and degradation in 26S proteasomes. It suppresses p53's transcriptional activity and dampens the response to DNA damage. Upon deubiquitylation by ubiquitin-specific peptidase 15 (USP15), it mediates K63-linked polyubiquitination of RIG-I that is crucial for downstream antiviral interferon signaling. TRIM25 is 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- kappa B) and interferon production. It is an RNA binding protein acting as 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 RING finger, Bbox1 and 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
                ....*....|....*....|....*....|....*...
gi 68160937 155 RKCSQHNRLREFFCPEHSECICHICLV-EHKTCSPASL 191
Cdd:cd19776   1 RKCTQHGKLLEFYCKSHSLCICSTCLVkEHKRCELVDI 38

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        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 68160937   6 PLAEELSCSICLEPFKEPVTTPCGHNFCGSCLNETWAVQ-GSPYLCPQCRAVYQARPQLHKNTVLCNVVEQ 75
Cdd:cd16597   1 DLEEELTCSICLELFKDPVTLPCGHNFCGVCIEKTWDSQhGSEYSCPQCRATFPRRPELHKNTVLRNIVEQ 71

B-box-type 1 zinc finger found in tripartite motif-containing proteins, TRIM25, TRIM47 and similar proteins; The family includes tripartite motif-containing proteins, TRIM25 and TRIM47, both of which 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, Bbox1 and Bbox2, and a coiled coil region, as well as a 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. TRIM25, also termed estrogen-responsive finger protein (EFP), or ubiquitin/ISG15-conjugating enzyme TRIM25, or zinc finger protein 147 (ZNF147), or E3 ubiquitin/ISG15 ligase TRIM25, is induced by estrogen and is particularly abundant in placenta and uterus. It has been implicated in cell proliferation, protein modification, and the retinoic acid inducible gene I (RIG-I)-mediated antiviral signaling pathway. It functions as an E3-ubiquitin ligase able to transfer ubiquitin and ISG15 to target proteins. 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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 68160937 106 ACDHCLKE--AAVKTCLVCMASFCQEHLQPHFDSPAFQDHPLQPPVRDL 152
Cdd:cd19842   1 LCDLCLGRelAAAKTCLTCLASFCPEHLEPHLSSPAFRSHRLCPPERDL 49

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68160937     1 MAELCPLAEELSCSICLEPFKEPVTTPCGHNFCGSCLNETWAVQGSpylCPQCRAVYQaRPQLHKNTVLCNVVEQFLQA- 79
Cdd:TIGR00599  17 IPSLYPLDTSLRCHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQPK---CPLCRAEDQ-ESKLRSNWLVSEIVESFKNLr 92

                          90       100
                  ....*....|....*....|....*....
gi 68160937    80 ----DLAREPPadvwTPPARA---SAPSP 101
Cdd:TIGR00599  93 psllEFLRIPK----TTPVENpdlAGPEN 117

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

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 68160937    13 CSICLEPFKEPVTtPCGHNFCGSCLNETWAVQGSPYLCP 51
Cdd:pfam13445   1 CPICLELFTDPVL-PCGHTFCRECLEEMSQKKGGKFKCP 38

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 68160937     13 CSICLEPF-KEPVTTPCGHNFCGSCLNETWavQGSPYLCPQC 53
Cdd:smart00184   1 CPICLEEYlKDPVILPCGHTFCRSCIRKWL--ESGNNTCPIC 40

Transforming acidic coiled-coil-containing protein (TACC), C-terminal; This entry represents a C-terminal domain found in the the proteins TACC 1, 2 and 3 (TACC1-3). TACC1 is found concentrated in the centrosomes of eukaryotes which may play a conserved role in organizing centrosomal microtubules. The human TACC proteins have been linked to cancer and TACC2 has been identified as a possible tumour suppressor (AZU-1). TACC 3 from Xenopus laevis, also known as maskin, associates XMAP215 and promotes efficient microtubule elongation during mitosis. Maskin is also found to bind CPEB and elF-4E. Interestingly, the functional homolog (Alp7) in Schizosaccharomyces pombe (not included in this entry) has been shown to be required for organization of bipolar spindles.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68160937   210 YSQINgasraLDDVRNRQQDVRMTA-------NRKVEQLQQEYTEMKALLDASETTSTRKIKEEEKRVNskfdtiyqill 282
Cdd:pfam05010   1 YSQKD-----MDAALEKARNEIEEKeleinelKAKYEELRRENLEMRKIVAEFEKTIAQMIEEKQKQKE----------- 64

                          90       100
                  ....*....|....*....|....
gi 68160937   283 KKKSEIQTLKEEIEQSLTKRDEFE 306
Cdd:pfam05010  65 LEHAEIQKVLEEKDQALADLNSVE 88

E3 ubiquitin-protein ligase RMA2; Provisional

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 68160937   10 ELSCSICLEPFKEPVTTPCGHNFCGSCLNE-TWAVQGS------------PYLCPQCRA 55
Cdd:PLN03208  18 DFDCNICLDQVRDPVVTLCGHLFCWPCIHKwTYASNNSrqrvdqydhkrePPKCPVCKS 76

PRY/SPRY domain, also known as B30.2; This domain contains residues in the N-terminus that form a distinct PRY domain structure such that the B30.2 domain consists of PRY and SPRY subdomains. B30.2 domains comprise the C-terminus of three protein families: BTNs (receptor glycoproteins of immunoglobulin superfamily); several TRIM proteins (composed of RING/B-box/coiled-coil core); Stonutoxin (secreted poisonous protein of the stonefish Synanceia horrida). While SPRY domains are evolutionarily ancient, B30.2 domains are a more recent adaptation where the SPRY/PRY combination is a possible component of immune defense. Among the TRIM proteins, also known as the N-terminal RING finger/B-box/coiled coil (RBCC) family, only Classes I and II contain the B30.2 domain that has evolved under positive selection. Class I TRIM proteins include multiple members involved in antiviral immunity at various levels of interferon signaling cascade. Among the 75 human TRIMs, roughly half enhance immune response, which they do at multiple levels in signaling pathways. The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68160937 459 VILDYNTAHNKVALSECYTVASVAEMPQNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQKNNFCGVGICYGSMNRQGP 538
Cdd:cd12874   1 LTFDPDTAHLNLILSDDLRSVRVGDISQHPPEPPPRFFECWQVLGSQSFSSGRHYWEVDVQDDSSWYVGVTYKSLPRKGK 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68160937 539 ESRLGRNSASWCVEWFNTKISAWHNNVEKTLPSTKATRVGVLLNCDHGFVIFFAVADKVHLMYKFRVDFTEALYPAFWVF 618
Cdd:cd12874  81 MSNLGRNNGSWCLEWRENEFSAWHNNPETRLPVTPPRRLGVFLDCDGGSLSFYGVTDGVQLLYTFKAKFTEPLYPAFWLG 160

                ....*....
gi 68160937 619 SaGATLSIC 627
Cdd:cd12874 161 E-GSTLSIC 168

Stonustoxin subunit alpha or SNTX subunit alpha; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of Stonustoxin alpha proteins. Stonustoxin (SNTX) is a multifunctional lethal protein isolated from venom elaborated by the stonefish. It comprises two subunits, termed alpha and beta. SNTX elicits an array of biological responses, particularly a potent hypotension and respiratory difficulties.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68160937 449 RPELLEYYIKVILDYNTAHNKVALSECYTVASVAEMPQNYRPHPQRFTYCSQVL---GLhcykKGIHYWEVELQKNNFCg 525
Cdd:cd16040   1 REEFLKYACQLTLDPNTAHRNLSLSEGNRKVTRVKEEQPYPDHPERFDYWPQVLcreGL----SGRCYWEVEWSGGGVD- 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68160937 526 VGICYGSMNRQG--PESRLGRNSASWCVEWFNTKISAWHNNVEK--TLPSTKATRVGVLLNCDHGFVIFFAVADKVHLMY 601
Cdd:cd16040  76 IAVAYKGISRKGdgDDSRFGYNDKSWSLECSPSGYSFWHNNKKTeiSVPSSSSSRVGVYLDHSAGTLSFYSVSDTMTLLH 155

                       170       180
                ....*....|....*....|....*.
gi 68160937 602 KFRVDFTEALYPAFWVFSaGATLSIC 627
Cdd:cd16040 156 TVQTTFTEPLYPGFGVGY-GSSVKLC 180

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        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 68160937   6 PLAEELSCSICLEPFKEPVTTPCGHNFCGSCLNETWAVQ-GSPYLCPQCRAVYQARPQLHKNTVLCNVVEQ 75
Cdd:cd16597   1 DLEEELTCSICLELFKDPVTLPCGHNFCGVCIEKTWDSQhGSEYSCPQCRATFPRRPELHKNTVLRNIVEQ 71

PRY/SPRY domain in tripartite motif-containing proteins 1, 9, 18, 36, 46, 67,76 (TRIM1, TRIM9, TRIM18, TRIM36, TRIM46, TRIM67, TRIM76); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several Class I TRIM proteins, including TRIM1, TRIM9, TRIM18, TRIM36, TRIM46, TRIM67 and TRIM76. TRIM1 (also known as MID2) and its close homolog, TRIM18 (also known as MID1), both contain a B30.2-like domain at their C-terminus and a single fibronectin type III (FN3) motif between it and their N-terminal RBCC domain. Their coiled-coil motifs mediate both homo- and heterodimerization, a prerequisite for association of the rapamycin-sensitive PP2A regulatory subunit Alpha 4 with microtubules. Mutations in TRIM18 have shown to cause Opitz syndrome, a disorder causing congenital anomalies such as cleft lip and palate as well as heart defects. TRIM9 is expressed mainly in the cerebral cortex, and functions as an E3 ubiquitin ligase. Its immunoreactivity is severely decreased in affected brain areas in Parkinson's disease and dementia with Lewy bodies, possibly playing an important role in the regulation of neuronal function and participating in pathological process of Lewy body disease through its ligase. TRIM36 interacts with centromere protein-H, one of the kinetochore proteins and possibly associates with chromosome segregation; an excess of TRIM36 may cause chromosomal instability. TRIM46 has not yet been characterized. TRIM67 negatively regulates Ras activity via degradation of 80K-H, leading to neural differentiation, including neuritogenesis. TRIM76 (also known as cardiomyopathy-associated protein 5 or CMYA5) is a muscle-specific member of the TRIM superfamily, but lacks the RING domain. It is possibly involved in protein kinase A signaling as well as vesicular trafficking. It has also been implicated in Duchenne muscular dystrophy and cardiac disease. The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68160937 461 LDYNTAHNKVALSE-CYTVASVAE-MPQNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQKNNFCGVGICYGSMNRqgp 538
Cdd:cd13734   3 LDPKTAHRKLRLSNdNLTVEYDPEgSKDQAAVLPRRFTGSPAVLGDVAISSGRHYWEVSVSRSTSYRVGVAYKSAPR--- 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68160937 539 ESRLGRNSASWCVEWFNTKISAWHNNVEKTLPST-KATRVGVLLNCDHGFVIFFAVADKVHLmYKFRVDFTEALYPAFWV 617
Cdd:cd13734  80 DEDLGKNSTSWCLSRDNNRYTARHDGKVVDLRVTgHPARIGVLLDYDNGTLSFYDAESKQHL-YTFHVDFEGPVCPAFAV 158

PRY/SPRY domain of tripartite motif-binding protein 14 (TRIM14); This is a TRIM14 domain family contains residues in the N-terminus that form a distinct PRY domain structure such that the B30.2 domain consists of PRY and SPRY subdomains. TRIM14 domains have yet to be characterized. These B30.2 domains are a more recent adaptation where the SPRY/PRY combination is a possible component of immune defense. It belongs to Class IV TRIM protein family which has members involved in antiviral immunity at various levels of interferon signaling cascade.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68160937 460 ILDYNTAHNKVALSECYTVASVAEMPQNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQkNNFCG--VGICYGSMNRQG 537
Cdd:cd13738   2 TLEPDTLHPRLRLSDDRLTVSCGWLGTLGLCPPQRFDKLWQVLSRDSFFSGRHYWEVDLQ-EAGAGwwVGAAYPSIGRKG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68160937 538 PE--SRLGRNSASWCVEWFNTKISAWHNNvEKT--LPSTKATRVGVLLNCDHGFVIFFAVADKVHLMYKFRVDFTEALYP 613
Cdd:cd13738  81 DSeaARLGWNRQSWCLKRYDLEYWAFHDG-QRSrlRPEDDPDRLGVFLDYEAGILSFYDVTGGMTHLHTFRATFQEPLYP 159

                       170
                ....*....|....*.
gi 68160937 614 AF--WvfsaGATLSIC 627
Cdd:cd13738 160 ALrlW----EGSISIC 171

PRY/SPRY domain in tripartite motif-containing domain 25 (TRIM25)-like; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of proteins similar to TRIM25 (composed of RING/B-box/coiled-coil core and also known as RBCC proteins). TRIM25 (also called Efp) ubiquitinates the N terminus of the viral RNA receptor retinoic acid-inducible gene-I (RIG-I) in response to viral infection, leading to activation of the RIG-I signaling pathway, thus resulting in type I interferon production to limit viral replication. It has been shown that the influenza A virus targets TRIM25 and disables its antiviral function.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68160937 461 LDYNTAHNKVAL-SECYTVASVAEMPQNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQKNNFCgVGICYGSMNRQGPE 539
Cdd:cd13737   3 FDPNTASEELFLfKETHSVLNMGILLESFFGPCQGFNHWPQVLCTRSLCEGCHYWEAEVSNSWVC-LGVTYSYSHPTGKS 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68160937 540 S---RLGRNSASWCVEWFNTKISAWHNNVEKTLPSTKATRVGVLLNCDHGFVIFFAVADKVHLMYKFRVDFTEALYPAFW 616
Cdd:cd13737  82 CifyLIGRNPYSWCLEWDSLKFSVWHNNIQTVVHGSYYKTIGVLLDYAAGSLTFYGVANTMNLIYRFLTTFTEPLYPAVM 161

                       170
                ....*....|
gi 68160937 617 VfSAGATLSI 626
Cdd:cd13737 162 V-SSGASVTL 170

PRY/SPRY domain in tripartite motif-binding protein 7 (TRIM7)-like, including TRIM7, TRIM10, TRIM15, TRIM26, TRIM39, TRIM41; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several tripartite motif-containing (TRIM) proteins, including TRIM7 (also referred to as glycogenin-interacting protein, RING finger protein 90 or RNF90), TRIM10, TRIM15, TRIM26, TRIM39 and TRIM41. TRIM7 or GNIP interacts with glycogenin and stimulates its self-glucosylating activity via its SPRY domain. TRIM10 (also known as hematopoietic RING finger 1 (HERF1) or TRIM10/HERF1) plays a key role in definitive erythroid development; downregulation of the Spi-1/PU.1 oncogene induces the expression of TRIM10/HERF1, a key factor required for terminal erythroid cell differentiation and survival. Antiviral activity of TRIM15 is dependent on the ability of its B-box to interact with the MLV Gag precursor protein; downregulation of TRIM15, along with TRIM11, enhances virus release suggesting that these proteins contribute to the endogenous restriction of retroviruses in cells. Tripartite motif-containing 26 (TRIM26) function is as yet unknown; however, since it is localized in the human histocompatibility complex (MHC) class I region, TRIM26 may play a role in immune response although studies show no association between TRIM26 polymorphisms and the risk of aspirin-exacerbated respiratory disease. TRIM39 is a MOAP-1 (Modulator of Apoptosis)-binding protein that stabilizes MOAP-1 through inhibition of its poly-ubiquitination process. TRIM41 (also known as RING finger-interacting protein with C kinase or RINCK) functions as an E3 ligase that catalyzes the ubiquitin-mediated degradation of protein kinase C.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68160937 458 KVILDYNTAHNKVALSE-CYTVaSVAEMPQNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQKNNFCGVGICYGSMNRQ 536
Cdd:cd12888   1 NVTLDPDTAHPRLVLSEdRKSV-RWGDTRQDLPDNPERFDTWPCVLGCEGFTSGRHYWEVEVGDGGGWAVGVARESVRRK 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68160937 537 GpESRLGRNSASWCVEWFNTKISAWHNNVEKTLPSTKATRVGVLLNCDHGFVIFFAVADKVHLmYKFRVDF--TEALYPA 614
Cdd:cd12888  80 G-EISFSPEEGIWAVGQWGGQYWALTSPETPLPLSEVPRRIRVYLDYEGGQVAFFDADNEAPI-FTFPPASfaGERIFPW 157

                       170
                ....*....|...
gi 68160937 615 FWVFSaGATLSIC 627
Cdd:cd12888 158 FWVGK-GSQLKLC 169

PRY/SPRY domain in tripartite motif-containing protein 35 (TRIM35); This PRY/SPRY domain is found at the C-terminus of the overall domain architecture of tripartite motif 35, TRIM35 (also known as hemopoietic lineage switch protein), which includes a RING finger domain (RING) and a B-box motif (BBOX). TRIM35 may play a role as a tumor suppressor and is implicated in the cell death mechanism.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68160937 459 VILDYNTAHNKVALSECYTVASVAEMPQNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQKNNFCGVGICYGSMNRQGp 538
Cdd:cd12893   2 VTLDPNTAHPWLSLSEDLTSVRYSSEKQQLPDNPERFDPYPCVLGSEGFTSGKHSWDVEVGDNTSWMLGVAKESVQRKG- 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68160937 539 ESRLGRNSASWCVEWFNTKISAWHNNVEKTL--PSTKATRVGVLLNCDHGFVIFFAVADKVHLmYKFRVDFTEALYPAFW 616
Cdd:cd12893  81 KFTLSPESGFWTIGFSEGKYSARTSPEPRTPlrVKQKPQRIRVQLDWDRGKVSFSDPDTNTHI-HTFTHTFTERVFPYFY 159

                       170
                ....*....|.
gi 68160937 617 VFSAGATLSIC 627
Cdd:cd12893 160 TGCKSEPLRIL 170

B-box-type 1 zinc finger found in tripartite motif-containing proteins, TRIM25, TRIM47 and similar proteins; The family includes tripartite motif-containing proteins, TRIM25 and TRIM47, both of which 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, Bbox1 and Bbox2, and a coiled coil region, as well as a 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. TRIM25, also termed estrogen-responsive finger protein (EFP), or ubiquitin/ISG15-conjugating enzyme TRIM25, or zinc finger protein 147 (ZNF147), or E3 ubiquitin/ISG15 ligase TRIM25, is induced by estrogen and is particularly abundant in placenta and uterus. It has been implicated in cell proliferation, protein modification, and the retinoic acid inducible gene I (RIG-I)-mediated antiviral signaling pathway. It functions as an E3-ubiquitin ligase able to transfer ubiquitin and ISG15 to target proteins. 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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 68160937 106 ACDHCLKE--AAVKTCLVCMASFCQEHLQPHFDSPAFQDHPLQPPVRDL 152
Cdd:cd19842   1 LCDLCLGRelAAAKTCLTCLASFCPEHLEPHLSSPAFRSHRLCPPERDL 49

SPRY domain in Ro-Ret family; This domain, named BSPRY, has been identified in the Ro-Ret family, since the protein is composed of a B-box, an alpha-helical coiled coil and a SPRY domain. The gene for BSPRY resides on human chromosome 9 and is specifically expressed in testis. The function of BSPRY is not known, but several related proteins of the RING-Box-coiled-coil (RBCC) family have been implicated in cell transformation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68160937 486 QNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQKNNFCGVGICYGSMNRQGP--ESRLGRNSASWCVEWFNTKISAWHN 563
Cdd:cd12904  30 QSPPDDPERFDHWPNALASLSFSSGTHAWVVDVGKSCAYKVGVCYGSLERKGSgnEARLGYNAFSWVFSRYDGEFSFSHN 109

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 68160937 564 NVEKTLPSTKA-TRVGVLLNCDHGFVIFFAvADKVHLMYKFRVDFTEALYPAFWVfsAGATLSI 626
Cdd:cd12904 110 GQHVPLELLKCpARVGVLLDWPSQELLFYD-PDSCTVLHSHREAFAAPLLPVFAV--ADQSISI 170

Fibronectin type III and SPRY containing 1 (FSD1) domain includes PRY at the N-terminus; This domain is part of the fibronectin type III and SPRY domain containing 1 (FSD1) and FSD1-like (FSD1L) proteins. These are centrosome-associated proteins that are characterized by an N-terminal coiled-coil region downstream of B-box (BBC) domain, a central fibronectin type III (FN3) domain, and C-terminal repeats in PRY/SPRY domain. The FSD1 protein associates with a subset of microtubules and may be involved in the stability and organization of microtubules during cytokinesis.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68160937 494 RFTYCS-QVLGLHCYKKGIHYWEVELQKNnfC---GVGICYGSMnrqGPESRLGRNSASWCVE---WFNTKISAWHNNVE 566
Cdd:cd12901  68 RFTAESyTVLGDTLIDGGQHYWEVRAQKD--SkafSVGVAYRSL---GKFDQLGKTNASWCLHvnnWLQNSFAAKHNNKA 142

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 68160937 567 KTLPSTKATRVGVLLNCDHGFVIFFAVADKVhLMYKFRVDFTEALYPAFWVFSAGATLS 625
Cdd:cd12901 143 KTLDVPVPDRIGVYCDFDEGQLSFYNARTKQ-LLHTFKMKFTQPVLPAFMVWCGGLSVS 200

PRY/SPRY domain in tripartite motif-containing protein 47 (TRIM47), also known as RING finger protein 100 (RNF100) or Gene overexpressed in astrocytoma protein (GOA); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM47, also known as GOA (Gene overexpressed in astrocytoma protein) or RNF100 (RING finger protein 100). TRIM47 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. It is highly expressed in kidney tubular cells, but lowly expressed in most tissue. It is overexpressed in astrocytoma tumor cells and plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis; astrocytoma, also known as cerebral astrocytoma, is a malignant glioma that arises from astrocytes. Genome wide studies on white matter lesions have identified a novel locus on chromosome 17q25 harboring several genes such as TRIM47 and TRIM65 which pinpoints to possible novel mechanisms leading to these lesions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68160937 454 EYYIK----VILDYNTAHNKVALSECYTVASVAeMPQNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQKnNFCGVGIC 529
Cdd:cd15808   1 DYFLKfafiVDLDSDTADKFLQLFGTKGVKRVL-CPISYPESPTRFTHCEQVLGEGALDRGTYYWEVEIIE-GWVSVGVM 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68160937 530 YGSMNRQGP--ESRLGRNSASWCVEWFNTKISAWHNNVEKTLPSTKATRVGVLLNCDHGFVIFFAVAD-KVHLMYKFRVD 606
Cdd:cd15808  79 AEDFSPREPydRGRLGRNAHSCCLQWNGRNFSVWFHGLEAPLPHPFSPTVGVCLEYADRALAFYAVRDgKVSLLRRLKAS 158

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 68160937 607 --------------------------FTEALYPAFWVFSAGATLSI 626
Cdd:cd15808 159 rprrggppaspldpfqsrldshfpglFSHRLKPAFFLESVDAHLQI 204

PRY/SPRY domain in tripartite motif-binding protein 69 (TRIM69), also known as RING finger protein 36 (RNF36); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM69, which is also known as RING finger protein 36 (RNF36) or testis-specific ring finger (Trif). TRIM69 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. It is a novel testis E3 ubiquitin ligase that may function to ubiquitinate its particular substrates during spermatogenesis. In humans, TRIM69 localizes in the cytoplasm and nucleus, and requires an intact RING finger domain to function. The mouse ortholog of this gene is specifically expressed in germ cells at the round spermatid stages during spermatogenesis and, when overexpressed, induces apoptosis. TRIM69 has been shown to be a novel regulator of mitotic spindle assembly in tumor cells; it associates with spindle poles and promotes centrosomal clustering, and is therefore essential for formation of a bipolar spindle.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68160937 459 VILDYNTAHNKVALSECYTVASVAEMPQNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQKNNFCGVGICYGSMNRQGp 538
Cdd:cd15818  15 ITLDPKTAHPNLILSEDLTCVWHGDTKQMLPDNPERFDSSVAVLGSEGFTSGKHYWEVEVAKKTKWTLGVVRESINRKG- 93

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 68160937 539 ESRLGRNSASWCVEWFN-TKISAWHNNVEKTLPSTKATRVGVLLNCDHGFVIFFAVADKVHLmYKFRVDFTEALYPAF 615
Cdd:cd15818  94 NCPLSPEDGFWLLRLRNqNELKALDVPSFSLTLTSNLNKVGIYLDYEGGQVSFYNANTMSHI-YTFSDTFTEKIYPYF 170

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        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 68160937   7 LAEELSCSICLEPFKEPVTTPCGHNFCGSCLNETWAVQGSPYLCPQCRAVYQARP 61
Cdd:cd16611   1 LTEELHCPLCLDFFRDPVMLSCGHNFCQSCITGFWELQAEDTTCPECRELCQYRN 55

PRY/SPRY domain in tripartite motif-binding protein 15 (TRIM15); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of tripartite motif-containing protein 15 (TRIM15), also referred to as RING finger protein 93 (RNF93) or Zinc finger protein B7 or 178 (ZNFB7 or ZNF178). TRIM15 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. The PRY and SPRY/B30.2 domains can function as immune defense components and in pathogen sensing. TRIM15 has been shown to regulate inflammatory and innate immune signaling, in addition to displaying antiviral activities. Down-regulation of TRIM15, as well as TRIM11, enhances virus release, suggesting that these proteins contribute to the endogenous restriction of retroviruses in cells. TRIM15 is also a regulatory component of focal adhesion turnover and cell migration.