PRY/SPRY domain in tripartite motif-containing proteins, TRIM9 and TRIM67; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM9 proteins. TRIM9 protein is expressed mainly in the cerebral cortex, and functions as an E3 ubiquitin ligase. It has been shown that TRIM9 is localized to the neurons in the normal human brain and its immunoreactivity in affected brain areas in Parkinson's disease and dementia with Lewy bodies is severely decreased, possibly playing an important role in the regulation of neuronal function and participating in pathological process of Lewy body disease through its ligase. TRIM67 negatively regulates Ras activity via degradation of 80K-H, leading to neural differentiation, including neuritogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498460 545 QTlATVAWFTFDSASAHPDIILSNDNLTVTCNSYDDRVVMGNTGFSRGVHYWEMTIDRYDNHPDPAFGVARADVMKDVML 624
Cdd:cd12889    3 QT-AEVAWFTFDPSTSHPDIILSNDNMTVTCNSYEDRVVLGSVGFSRGVHYWEVTIDRYDGHPDPAFGVARIDVNKDKML 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498460 625 GKDDKAWAMYVDNNRSWFMHNNSHTNRTDGGISKGATVGVLLDFTRGILLFLINDEQQGPVAFNTLEGMYYPAISLNRNV 704
Cdd:cd12889   82 GKDDKGWSMYIDNNRSWFLHNNEHSNRTEGGITVGSVVGVLLDLDRHTLSFYVNDEPQGPIAFRNLPGVFYPAVSLNRNV 161

                        170
                 ....*....|.
gi 528498460 705 QVTLHSGLPIP 715
Cdd:cd12889  162 QVTLHTGLEPP 172

B-box-type 1 zinc finger found in tripartite motif-containing protein 9 (TRIM9) and similar proteins; TRIM9 (the human ortholog of rat Spring), also termed 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. It interacts with the WD repeat region of beta-transducer repeat-containing protein (beta-TCP) through its N-terminal degron motif depending on the phosphorylation status, and thus negatively regulate nuclear factor-kappaB (NF-kappaB) activation in the NF-kappaB pro-inflammatory signaling pathway. Moreover, TRIM9 acts as a critical catalytic link between Netrin-1 and exocytosis soluble NSF attachment receptor protein (SNARE) machinery in murine cortical neurons. It promotes SNARE-mediated vesicle fusion and axon branching in a Netrin-dependent manner. TRIM9 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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 528498460 172 LKCQLCEKSPREATVMCEQCDVFYCDPCRLRCHPPRGPLAKHRLVPP 218
Cdd:cd19843    1 LKCQLCEKSPKEATVMCEQCDVFYCDPCRLRCHPPRGPLAKHRLVPP 47

RING finger, HC subclass, found in tripartite motif-containing protein 9 (TRIM9) and similar proteins; TRIM9, 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 the neurodegenerative disorders through its ligase activity. It interacts with the WD repeat region of beta-transducin repeat-containing protein (beta-TrCP) through its N-terminal degron motif depending on the phosphorylation status, and thus negatively regulates nuclear factor-kappaB (NF-kappaB) activation in the NF-kappaB pro-inflammatory signaling pathway. Moreover, TRIM9 acts as a critical catalytic link between Netrin-1 and the exocytic soluble NSF attachment receptor protein (SNARE) machinery in murine cortical neurons. It promotes SNARE-mediated vesicle fusion and axon branching in a Netrin-dependent manner. TRIM9 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 (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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 528498460   5 EEELKCPVCGSFFREPIILPCSHNICLACARNILVQTPDAESPQS 49
Cdd:cd16755    1 EEELKCPVCGSFYREPIILPCSHNLCLACARNILVQTPEAESPQS 45

PRY/SPRY domain in tripartite motif-containing proteins, TRIM9 and TRIM67; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM9 proteins. TRIM9 protein is expressed mainly in the cerebral cortex, and functions as an E3 ubiquitin ligase. It has been shown that TRIM9 is localized to the neurons in the normal human brain and its immunoreactivity in affected brain areas in Parkinson's disease and dementia with Lewy bodies is severely decreased, possibly playing an important role in the regulation of neuronal function and participating in pathological process of Lewy body disease through its ligase. TRIM67 negatively regulates Ras activity via degradation of 80K-H, leading to neural differentiation, including neuritogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498460 545 QTlATVAWFTFDSASAHPDIILSNDNLTVTCNSYDDRVVMGNTGFSRGVHYWEMTIDRYDNHPDPAFGVARADVMKDVML 624
Cdd:cd12889    3 QT-AEVAWFTFDPSTSHPDIILSNDNMTVTCNSYEDRVVLGSVGFSRGVHYWEVTIDRYDGHPDPAFGVARIDVNKDKML 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498460 625 GKDDKAWAMYVDNNRSWFMHNNSHTNRTDGGISKGATVGVLLDFTRGILLFLINDEQQGPVAFNTLEGMYYPAISLNRNV 704
Cdd:cd12889   82 GKDDKGWSMYIDNNRSWFLHNNEHSNRTEGGITVGSVVGVLLDLDRHTLSFYVNDEPQGPIAFRNLPGVFYPAVSLNRNV 161

                        170
                 ....*....|.
gi 528498460 705 QVTLHSGLPIP 715
Cdd:cd12889  162 QVTLHTGLEPP 172

B-box-type 1 zinc finger found in tripartite motif-containing protein 9 (TRIM9) and similar proteins; TRIM9 (the human ortholog of rat Spring), also termed 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. It interacts with the WD repeat region of beta-transducer repeat-containing protein (beta-TCP) through its N-terminal degron motif depending on the phosphorylation status, and thus negatively regulate nuclear factor-kappaB (NF-kappaB) activation in the NF-kappaB pro-inflammatory signaling pathway. Moreover, TRIM9 acts as a critical catalytic link between Netrin-1 and exocytosis soluble NSF attachment receptor protein (SNARE) machinery in murine cortical neurons. It promotes SNARE-mediated vesicle fusion and axon branching in a Netrin-dependent manner. TRIM9 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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 528498460 172 LKCQLCEKSPREATVMCEQCDVFYCDPCRLRCHPPRGPLAKHRLVPP 218
Cdd:cd19843    1 LKCQLCEKSPKEATVMCEQCDVFYCDPCRLRCHPPRGPLAKHRLVPP 47

RING finger, HC subclass, found in tripartite motif-containing protein 9 (TRIM9) and similar proteins; TRIM9, 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 the neurodegenerative disorders through its ligase activity. It interacts with the WD repeat region of beta-transducin repeat-containing protein (beta-TrCP) through its N-terminal degron motif depending on the phosphorylation status, and thus negatively regulates nuclear factor-kappaB (NF-kappaB) activation in the NF-kappaB pro-inflammatory signaling pathway. Moreover, TRIM9 acts as a critical catalytic link between Netrin-1 and the exocytic soluble NSF attachment receptor protein (SNARE) machinery in murine cortical neurons. It promotes SNARE-mediated vesicle fusion and axon branching in a Netrin-dependent manner. TRIM9 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 (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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 528498460   5 EEELKCPVCGSFFREPIILPCSHNICLACARNILVQTPDAESPQS 49
Cdd:cd16755    1 EEELKCPVCGSFYREPIILPCSHNLCLACARNILVQTPEAESPQS 45

Domain in SPla and the RYanodine Receptor; Domain of unknown function. Distant homologues are domains in butyrophilin/marenostrin/pyrin homologues.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498460   591 RGVHYWEMTIDrydnhpDP---AFGVARADV--MKDVMLGKDDKAWAMYVDNNRSWFMHNNSHTNRTDGGisKGATVGVL 665
Cdd:smart00449   1 SGRHYFEVEIG------DGghwRVGVATKSVprGYFALLGEDKGSWGYDGDGGKKYHNSTGPEYGLPLQE--PGDVIGCF 72

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 528498460   666 LDFTRGILLFLINDEQQGPVAFNTLE--GMYYPAISLN 701
Cdd:smart00449  73 LDLEAGTISFYKNGKYLHGLAFFDVKfsGPLYPAFSLG 110

Fibronectin type III domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498460  443 PAAPILQLEEccTQTSSATLSWKQPPLSTIAVDGYILEL-DDGTGGQFREVYV-GTEMICTVDGLHFNSTYKSRVKAFNS 520
Cdd:pfam00041   1 SAPSNLTVTD--VTSTSLTVSWTPPPDGNGPITGYEVEYrPKNSGEPWNEITVpGTTTSVTLTGLKPGTEYEVRVQAVNG 78

                  ....*..
gi 528498460  521 SGVGQYS 527
Cdd:pfam00041  79 GGEGPPS 85

B-box zinc finger;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 528498460  230 RKISTCTEHELENLSMYCVQCKTPVCYQCLEdGKHSTHEVKAL 272
Cdd:pfam00643   1 SKERLCPEHEEEPLTLYCNDCQELLCEECSV-GEHRGHTVVPL 42

B-Box-type zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 528498460   169 AAALKCQLCEKSPreATVMCEQCDVFYCDPCRLRCHpprgplAKHRLVP 217
Cdd:smart00336   1 QRAPKCDSHGDEP--AEFFCEECGALLCRTCDEAEH------RGHTVVL 41

zinc finger of C3HC4-type, RING; This is a family of primate-specific Ret finger protein-like (RFPL) zinc-fingers of the C3HC4 type. Ret finger protein-like proteins are primate-specific target genes of Pax6, a key transcription factor for pancreas, eye and neocortex development. This domain is likely to be DNA-binding. This zinc-finger domain together with the RDM domain, pfam11002, forms a large zinc-finger structure of the RING/U-Box superfamily. RING-containing proteins are known to exert an E3 ubiquitin protein ligase activity with the zinc-finger structure being mandatory for binding to the E2 ubiquitin-conjugating enzyme.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 528498460   10 CPVCGSFFREPIILPCSHNICLACArNILVQTPDAES 46
Cdd:pfam15227   1 CPICLDYLEKPVSIECGHSFCLSCI-NSLQKEPDGES 36

RING-finger-containing E3 ubiquitin ligase [Signal transduction mechanisms];

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 528498460   3 EMEEELKCPVCGSFFREPIILPCSHNICLACARNILVQTPDA----ESPQSSRASGSGVSDYD 61
Cdd:COG5432   21 GLDSMLRCRICDCRISIPCETTCGHTFCSLCIRRHLGTQPFCpvcrEDPCESRLRGSSGSREI 83

PRY/SPRY domain in tripartite motif-containing proteins, TRIM9 and TRIM67; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM9 proteins. TRIM9 protein is expressed mainly in the cerebral cortex, and functions as an E3 ubiquitin ligase. It has been shown that TRIM9 is localized to the neurons in the normal human brain and its immunoreactivity in affected brain areas in Parkinson's disease and dementia with Lewy bodies is severely decreased, possibly playing an important role in the regulation of neuronal function and participating in pathological process of Lewy body disease through its ligase. TRIM67 negatively regulates Ras activity via degradation of 80K-H, leading to neural differentiation, including neuritogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498460 545 QTlATVAWFTFDSASAHPDIILSNDNLTVTCNSYDDRVVMGNTGFSRGVHYWEMTIDRYDNHPDPAFGVARADVMKDVML 624
Cdd:cd12889    3 QT-AEVAWFTFDPSTSHPDIILSNDNMTVTCNSYEDRVVLGSVGFSRGVHYWEVTIDRYDGHPDPAFGVARIDVNKDKML 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498460 625 GKDDKAWAMYVDNNRSWFMHNNSHTNRTDGGISKGATVGVLLDFTRGILLFLINDEQQGPVAFNTLEGMYYPAISLNRNV 704
Cdd:cd12889   82 GKDDKGWSMYIDNNRSWFLHNNEHSNRTEGGITVGSVVGVLLDLDRHTLSFYVNDEPQGPIAFRNLPGVFYPAVSLNRNV 161

                        170
                 ....*....|.
gi 528498460 705 QVTLHSGLPIP 715
Cdd:cd12889  162 QVTLHTGLEPP 172

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498460   279 HKGQLSQALNVLSDRATEAKEFLVQLRNMVQHIQENGVEFEACLVAQCDALIEALNRRKAQLLSRVTKEHEHKLSVVRDQ 358
Cdd:smart00502   1 QREALEELLTKLRKKAAELEDALKQLISIIQEVEENAADVEAQIKAAFDELRNALNKRKKQLLEDLEEQKENKLKVLEQQ 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 528498460   359 ISHCTVKLRQTTGLMEYCLEVIKENDPSGFLQISDALIRRVHMTENQ 405
Cdd:smart00502  81 LESLTQKQEKLSHAINFTEEALNSGDPTELLLSKKLIIERLQNLLKQ 127

B-box-type 2 zinc finger found in tripartite motif-containing protein 9 (TRIM9) and similar proteins; TRIM9 (the human ortholog of rat Spring), also termed 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 the neurodegenerative disorders through its ligase activity. It interacts with the WD repeat region of beta-transducer repeat-containing protein (beta-TCP) through its N-terminal degron motif (DSGXXS) depending on the phosphorylation status, and thus negatively regulate nuclear factor-kappaB (NF-kappaB) activation in the NF-kappaB pro-inflammatory signaling pathway. Moreover, TRIM9 acts as a critical catalytic link between Netrin-1 and exocytosis soluble NSF attachment receptor protein (SNARE) machinery in murine cortical neurons. It promotes SNARE-mediated vesicle fusion and axon branching in a Netrin-dependent manner. TRIM9 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 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 528498460 229 PRKISTCTEHELENLSMYCVQCKTPVCYQCLEDGKHSTHEVKALGAMWK 277
Cdd:cd19826    1 PRKISTCTDHELENHSMYCVQCKMPVCYQCLEEGKHSSHEVKALGAMWK 49

B-box-type 1 zinc finger found in tripartite motif-containing proteins, TRIM9, TRIM67 and similar proteins; This family includes a group of tripartite motif-containing proteins, including TRIM9 and TRIM67, 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, consisting of 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. 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. It plays an important role in the regulation of neuronal functions and participates in the neurodegenerative disorders through its ligase activity. TRIM67, also termed 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. It negatively regulates Ras signaling in cell proliferation via degradation of 80K-H, leading to neural differentiation including neuritogenesis.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 528498460 173 KCQLCEKSP-REATVMCEQCDVFYCDPCRLRCHPPRGPLAKHRLVPP 218
Cdd:cd19803    1 RCQLCEKSPpKEASVFCEQCEVFYCDSCRESCHPPRGPLAKHTLVSP 47

RING finger, HC subclass, found in tripartite motif-containing protein 67 (TRIM67) and similar proteins; TRIM67, also known as TRIM9-like protein (TNL), is 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. It negatively regulates Ras signaling in cell proliferation via degradation of 80K-H, leading to neural differentiation including neuritogenesis. TRIM67 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 (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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 528498460   5 EEELKCPVCGSFFREPIILPCSHNICLACARNILVQTPDAES--PQSS 50
Cdd:cd16758    1 EEELKCPVCGSLFREPIILPCSHNVCLPCARTIAVQTPESEQhlPHSS 48

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 528498460   5 EEELKCPVCGSFFREPIILPCSHNICLACARNILVQTP 42
Cdd:cd16576    1 EEELKCPVCGSLFTEPVILPCSHNLCLGCALNIQLTCP 38

PRY/SPRY domain in tripartite motif-containing (TRIM) proteins, including TRIM14-like, TRIM16-like, TRIM25-like, TRIM47-like, TRIM65 and RNF135, and stonustoxin; 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 TRIM14, TRIM16 and TRIM25, TRIM47 as well as RING finger protein RNF135 and stonustoxin, a secreted poisonous protein of the stonefish Synanceja horrida. TRIM16 (also known as estrogen-responsive B box protein or EBBP) has E3 ubiquitin ligase activity. It is a regulator of keratinocyte differentiation and a tumor suppressor in retinoid-sensitive neuroblastoma. 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. TRIM47, also known as GOA (Gene overexpressed in astrocytoma protein) or RNF100 (RING finger protein 100), is highly expressed in kidney tubular cells, but low 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. RNF135 ubiquitinates RIG-I (retinoic acid-inducible gene-I) to promote interferon-beta induction during the early phase of viral infection. Stonustoxin (STNX) is a hypotensive and lethal protein factor that also possesses other biological activities such as species-specific hemolysis (due to its ability to form pores in the cell membrane) and platelet aggregation, edema-induction, and endothelium-dependent vasorelaxation (mediated by the nitric oxide pathway and activation of potassium channels). 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 528498460 554 TFDSASAHPDIILSNDNLTVTCNSYDDRV-----------VMGNTGFSRGVHYWEMTIdryDNHPDPAFGVARADVMK-- 620
Cdd:cd12891    2 TLDPNTAHNNLALSGDLKTVTCSSENQHYpdsperfthsqVLSTQSFSSGRHYWEVEV---SESGGWSVGVAYPSIERkg 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 528498460 621 -DVMLGKDDKAWAMYVDNNRSWFMHNNshtNRTDGGISKGATVGVLLDFTRGILLF 675
Cdd:cd12891   79 dESRIGRNDKSWCLEWQDKSFSAWHNN---EETPLPSVSSRRLGVYLDYEAGRLSF 131

SPRY domain; SPRY Domain is named from SPla and the RYanodine Receptor and it is found in many eukaryotic proteins with a wide range of functions. It is a protein-interaction module involved in many important signalling pathways like RNA processing, regulation of histone H3 methylation, innate immunity or embryonic development. It can be divided into 11 subfamilies based on amino acid sequence similarity or the presence of additional protein domains. The greater SPRY family is divided into the SPRY/B30.2 (which contains a PRY extension at the N-terminal) and SPRY-only sub-families which are preceded by a subdomain that is structurally similar to the PRY region. SPRY/B30.2 structures revealed a bent beta-sandwich fold comprised of two beta-sheets. Distant homologs are domains in butyrophilin/ marenostrin/pyrin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498460  593 VHYWEMTIDRYDNHpDPAFGVARADVM--KDVMLGKDDKAWAMYVDNNRSWfmHNNSHTNRTDGGISKGATVGVLLDFTR 670
Cdd:pfam00622   1 RHYFEVEIFGQDGG-GWRVGWATKSVPrkGERFLGDESGSWGYDGWTGKKY--WASTSPLTGLPLFEPGDVIGCFLDYEA 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 528498460  671 GILLFLINDEQQGpVAFN--TLEGMYYPAISLNRNVQVTLHSGLP 713
Cdd:pfam00622  78 GTISFTKNGKSLG-YAFRdvPFAGPLFPAVSLGAGEGLKFNFGLR 121

SPRY domain in Ash2; This SPRY domain is found at the C-terminus of Ash2 (absent, small, or homeotic discs 2) -like proteins, core components of all mixed-lineage leukemia (MLL) family histone methyltransferases. Ash2 is a member of the trithorax group of transcriptional regulators of the Hox genes. Recent studies show that the SPRY domain of Ash2 mediates the interaction with RbBP5 and has an important role in regulating the methyltransferase activity of MLL complexes. In yeast, Ash2 is involved in histone methylation and is required for the earliest stages of embryogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498460 564 IILSNDNLTVTCNS-YddRVVMGNTGFSRGVHYWEMTIDRYDNHPDPA--FGVAR--ADVmkDVMLGKDDKAWAmYVDNN 638
Cdd:cd12872    1 LKLSEDRLTVTGEKgY--RMARANHGVREGKWYFEVKILEGGGTETGHvrVGWSRreASL--QAPVGYDKYSYA-IRDKD 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498460 639 RSWFmHNNSHTNRTDGGISKGATVGVLLDFTRgiLLFLINDEQQGpVAFNTL--EGMYYPAISLNRNVQVTLHSGlpiPD 716
Cdd:cd12872   76 GSKF-HQSRGKPYGEPGFKEGDVIGFLITLPK--IEFFKNGKSQG-VAFEDIygTGGYYPAVSLYKGATVTINFG---PD 148

                 ..
gi 528498460 717 FY 718
Cdd:cd12872  149 FK 150

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 528498460 553 FTFDSASAHPDIILSNDNLTVTC-----NSYDD-------RVVMGNTGFSRGVHYWEMTIdrYDNHpDPAFGVARADVMK 620
Cdd:cd12874    1 LTFDPDTAHLNLILSDDLRSVRVgdisqHPPEPpprffecWQVLGSQSFSSGRHYWEVDV--QDDS-SWYVGVTYKSLPR 77

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 528498460 621 D---VMLGKDDKAWAMYVDNNRSWFMHNNShtnRTDGGISKGATVGVLLDFTRGILLF 675
Cdd:cd12874   78 KgkmSNLGRNNGSWCLEWRENEFSAWHNNP---ETRLPVTPPRRLGVFLDCDGGSLSF 132

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        40
                 ....*....|....*....|....*....|....*....|....*..
gi 528498460 173 KCQLCEKSP-REATVMCEQCDVFYCDPCRLRCHPPRGPLAKHRLVPP 218
Cdd:cd19801    3 PCDVCEKEPpRKAVKTCLTCEVSYCKRCLEATHPNRGPFATHRLVEP 49

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
                 ....*....|....*....|....*....|....*....
gi 528498460   1 MDEMEEELKCPVCGSFFREPIILPCSHNICLACARNILV 39
Cdd:cd16754    1 METLESELTCPICLELFEDPLLLPCAHSLCFSCAHRILT 39

SPRY domain in Ran binding proteins, SSH4, HECT E3 and SPRYD3; This family includes SPRY domains found in Ran binding proteins (RBP or RanBPM) 9 and 10, SSH4 (suppressor of SHR3 null mutation protein 4), SPRY domain-containing protein 3 (SPRYD3) as well as HECT, a C-terminal catalytic domain of a subclass of ubiquitin-protein ligase (E3). RanBP9 and RanBP10 act as androgen receptor (AR) coactivators. Both consist of the N-terminal proline- and glutamine-rich regions, the SPRY domain, and LisH-CTLH and CRA motifs. The SPRY domain in SSH4 may be involved in cargo recognition, either directly or by combination with other adaptors, possibly leading to a higher selectivity. SPRYD3 is highly expressed in most tissues in humans, possibly involved in important cellular processes. HECT E3 mediates the direct transfer of ubiquitin from E2 to substrate.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498460 590 SRGVHYWEMTIDRYDNHPDPAFGVARADVMKDVMLGKDDKAWAMYVDNNRswFMHNNSHTNRTDGGISKGATVGVLLDFT 669
Cdd:cd12885   12 KVPVFYFEVTILDLGEKGIVSIGFCTSGFPLNRMPGWEDGSYGYHGDDGR--VYLGGGEGENYGPPFGTGDVVGCGINFK 89

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 528498460 670 RGILLFLINDEQQGPVAFNTLEGMYYPAISLN-RNVQVTLHSG 711
Cdd:cd12885   90 TGEVFFTKNGELLGTAFENVVKGRLYPTVGLGsPGVKVRVNFG 132

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 528498460 235 CTEHELENLSMYCVQCKTPVCYQCLEDGKHSTHEVKAL 272
Cdd:cd19756    2 CPEHPEEPLKLFCETCQELVCVLCLLSGEHRGHKVVPL 39

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 528498460 172 LKCQLCEKSP-REATVMCEQCDVFYCDPCRLRCHPPRGPLAKHRLVPP 218
Cdd:cd19837    3 IACQFCEQEPpRDAVKTCITCEVSYCDRCLRATHPNKKPFTSHRLVEP 50

Fibronectin type III domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498460  443 PAAPILQLEEccTQTSSATLSWKQPPLSTIAVDGYILEL-DDGTGGQFREVYV-GTEMICTVDGLHFNSTYKSRVKAFNS 520
Cdd:pfam00041   1 SAPSNLTVTD--VTSTSLTVSWTPPPDGNGPITGYEVEYrPKNSGEPWNEITVpGTTTSVTLTGLKPGTEYEVRVQAVNG 78

                  ....*..
gi 528498460  521 SGVGQYS 527
Cdd:pfam00041  79 GGEGPPS 85

PRY/SPRY domain containing protein 4 (SPRYD4); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain and is encoded by the SPRYD4 gene. SPRYD4 (SPRY containing domain 4) is ubiquitously expressed in many human tissues, most strongly in kidney, bladder, brain, thymus and stomach. Subcellular localization demonstrates that SPRYD4 protein is localized in the nucleus when overexpressed in COS-7 green monkey cell. It has remained uncharacterized thus far.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498460 582 VVMGNTGFSRGVHYWEMTIDRYDNHpdpAFGVARADVMKDVMLGKDDKAWAM-YVDnnRSWF-MHNNSHTNRTdgGISKG 659
Cdd:cd12903   45 VVLGDTPVTSGRHYWEVTVKRSQEF---RIGVADVDMSRDECIGTNESSWVFaYAQ--RKWYaMVANETVPVP--LVGKP 117

                         90
                 ....*....|....
gi 528498460 660 ATVGVLLDFTRGIL 673
Cdd:cd12903  118 DRVGLLLDYEAGKL 131

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 528498460   5 EEELKCPVCGSFFREPIILPCSHNICLACARNILVQTPD 43
Cdd:cd16609    1 EEELTCSICLGLYQDPVTLPCQHSFCRACIEDHWRQKDE 39

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 528498460   6 EELKCPVCGSFFREPIILPCSHNICLACARNIL 38
Cdd:cd16581    1 EELTCSICYNIFDDPKILPCSHTFCKNCLEKLL 33

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 528498460   3 EMEEELKCPVCGSFFREPIILPCSHNICLAC 33
Cdd:cd16597    1 DLEEELTCSICLELFKDPVTLPCGHNFCGVC 31

B-box-type 2 zinc finger found in tripartite motif-containing protein 36 (TRIM36) and similar proteins; TRIM36, 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 subsequently dorsal axis formation. It is also potentially associated with chromosome segregation through 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 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 528498460 235 CTEHELENLSMYCVQCKTPVCYQCLEDGKHSTHEVKALGAMWK 277
Cdd:cd19778    3 CPEHEMEKVNMYCEACRRPVCHLCKLGGSHANHRVTSMSSAYK 45

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

                         10        20        30
                 ....*....|....*....|....*....|.
gi 528498460   3 EMEEELKCPVCGSFFREPIILPCSHNICLAC 33
Cdd:cd16594    1 SLQEELTCPICLDYFTDPVTLDCGHSFCRAC 31

SPRY domain in Fbxo45 and suppressors of cytokine signaling (SOCS) proteins; This family consists of the SPRY domain-containing SOCS box protein family (SPSB1-4, also known as SSB-1 to -4) as well as F-box protein 45 (Fbxo45), a novel synaptic E3 and ubiquitin ligase. The SPSB protein is composed of a central SPRY protein interaction domain and a C-terminal SOCS box. SPSB1, SPSB2, and SPSB4 interact with prostate apoptosis response protein 4 (Par-4) and are negative regulators that recruit the ECS E3 ubiquitin ligase complex to polyubiquitinate inducible nitric-oxide synthase (iNOS), resulting in its proteasomal degradation. Fbxo45 is related to this family; it is located N-terminal to the SPRY domain, and known to induce the degradation of a synaptic vesicle-priming factor, Munc13-1, via the SPRY domain, thus playing an important role in the regulation of neurotransmission by modulating Munc13-1 at the synapse. Suppressor of cytokine signaling (SOCS) proteins negatively regulate signaling from JAK-associated cytokine receptor complexes, and play key roles in the regulation of immune homeostasis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498460 585 GNTGFSRGVHYWEMT--IDRYDNHPDPAFGVARADVMKD---VMLGKDDKAWAMYVDNNRswFMHNNSHTNRT----DGG 655
Cdd:cd12875   35 GKKGYTRGLHAWEVKwiSRPRGSHAVVGVATKDAPLQCDgyvTLLGSNSESWGWDLGDNK--LYHNGKKVIGSypakSEN 112

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 528498460 656 ISKGATVGVLLDFTRGILLFLINDEQQGpVAFNTLEG-MYYPAIS 699
Cdd:cd12875  113 YQVPDRILVILDMEDGTLAFEANGEYLG-VAFRGLPGkLLYPAVS 156

PRY/SPRY domain in tripartite motif-containing (TRIM) proteins, including TRIM5, TRIM6, TRIM7, TRIM10, TRIM11, TRIM17, TRIM20, TRIM21, TRIM27, TRIM35, TRIM38, TRIM41, TRIM50, TRIM58, TRIM60, TRIM62, TRIM69, TRIM72, NF7 and bloodthirsty; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several Class IV TRIM proteins, including TRIM7, TRIM35, TRIM41, TRIM50, TRIM62, TRIM69, TRIM72, TRIM protein NF7 and bloodthirsty (bty). TRIM7 interacts with glycogenin and stimulates its self-glucosylating activity via its SPRY domain. TRIM35 may play a role as a tumor suppressor and is implicated in the cell death mechanism. TRIM41 is localized to speckles in the cytoplasm and nucleus, and functions as an E3 ligase that catalyzes the ubiquitin-mediated degradation of protein kinase C. TRIM50, an E3 ubiquitin ligase, is deleted in Williams-Beuren (WBS) syndrome, a multi-system neurodevelopmental disorder caused by the deletion of contiguous genes at chromosome region 7q11.23. TRIM62 is involved in the morphogenesis of the mammary gland; loss of TRIM62 gene expression in breast is associated with increased risk of recurrence in early-onset breast cancer. TRIM69 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. TRIM protein NF7, which also contains a chromodomain (CHD) at the N-terminus and an RFP (Ret finger protein)-like domain at the C-terminus, is required for its association with transcriptional units of RNA polymerase II which is mediated by a trimeric B box. In Xenopus oocyte, xNF7 has been identified as a nuclear microtubule-associated protein (MAP) whose microtubule-bundling activity, but not E3-ligase activity, contributes to microtubule organization and spindle integrity. Bloodthirsty (bty) is a novel gene identified in zebrafish and has been shown to likely play a role in in regulation of the terminal steps of erythropoiesis. TRIM72 has been shown to perform a critical function in membrane repair following acute muscle injury by nucleating the assembly of the repair machinery at injury sites. 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 528498460 553 FTFDSASAHPDIILSNDNLTVTCNS-----------YDDRV-VMGNTGFSRGVHYWEMTIdryDNHPDPAFGVARADVMK 620
Cdd:cd13733    2 VTLDPDTAHPNLILSEDLKSVRYGDkrqnlpdnperFDTCVcVLGSEGFSSGRHYWEVEV---GGKTDWDLGVARESVNR 78