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 1046891570 620 VAWFAFDPGSAHSDIIFSNDNLTVTCSSYDDRVVLGKTGFSKGVHYWELTIDRYDNHPDPAFGVARIDVMKDMMLGKDDK 699
Cdd:cd12889     7 VAWFTFDPSTSHPDIILSNDNMTVTCNSYEDRVVLGSVGFSRGVHYWEVTIDRYDGHPDPAFGVARIDVNKDKMLGKDDK 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046891570 700 AWAMYVDNNRSWFMHNNSHTNRTEGGITKGATIGVLLDLNRKTLTFFVNNEQQGPIAFENVEGLFFPAVSLNRNVQVTLH 779
Cdd:cd12889    87 GWSMYIDNNRSWFLHNNEHSNRTEGGITVGSVVGVLLDLDRHTLSFYVNDEPQGPIAFRNLPGVFYPAVSLNRNVQVTLH 166

                  ....*.
gi 1046891570 780 TGLPVP 785
Cdd:cd12889   167 TGLEPP 172

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 1046891570 223 PRKVSTCTDHELENHSMYCVQCKMPVCYQCLEEGKHSSHEVKALGAMWK 271
Cdd:cd19826     1 PRKISTCTDHELENHSMYCVQCKMPVCYQCLEEGKHSSHEVKALGAMWK 49

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 1046891570   5 EEELKCPVCGSFYREPIILPCSHNLCQACARNILVQTPESESPQS 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 1046891570 620 VAWFAFDPGSAHSDIIFSNDNLTVTCSSYDDRVVLGKTGFSKGVHYWELTIDRYDNHPDPAFGVARIDVMKDMMLGKDDK 699
Cdd:cd12889     7 VAWFTFDPSTSHPDIILSNDNMTVTCNSYEDRVVLGSVGFSRGVHYWEVTIDRYDGHPDPAFGVARIDVNKDKMLGKDDK 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046891570 700 AWAMYVDNNRSWFMHNNSHTNRTEGGITKGATIGVLLDLNRKTLTFFVNNEQQGPIAFENVEGLFFPAVSLNRNVQVTLH 779
Cdd:cd12889    87 GWSMYIDNNRSWFLHNNEHSNRTEGGITVGSVVGVLLDLDRHTLSFYVNDEPQGPIAFRNLPGVFYPAVSLNRNVQVTLH 166

                  ....*.
gi 1046891570 780 TGLPVP 785
Cdd:cd12889   167 TGLEPP 172

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 1046891570 223 PRKVSTCTDHELENHSMYCVQCKMPVCYQCLEEGKHSSHEVKALGAMWK 271
Cdd:cd19826     1 PRKISTCTDHELENHSMYCVQCKMPVCYQCLEEGKHSSHEVKALGAMWK 49

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 1046891570   5 EEELKCPVCGSFYREPIILPCSHNLCQACARNILVQTPESESPQS 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 1046891570  661 KGVHYWELTIDrydnhpDP---AFGVARIDVMKDMM--LGKDDKAWAMYVDNNRSWFMHNNSHTNRTEGgiTKGATIGVL 735
Cdd:smart00449   1 SGRHYFEVEIG------DGghwRVGVATKSVPRGYFalLGEDKGSWGYDGDGGKKYHNSTGPEYGLPLQ--EPGDVIGCF 72

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1046891570  736 LDLNRKTLTFFVNNEQQGPIAFENVE--GLFFPAVSLN 771
Cdd:smart00449  73 LDLEAGTISFYKNGKYLHGLAFFDVKfsGPLYPAFSLG 110

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1046891570  453 THNNSATLSWKQPPLSTVAA--DGYILELDDGSGGQFREVYVGKETMCTVDGLHFNSTYNARVKAFNKTGVS 522
Cdd:smart00060  12 VTSTSVTLSWEPPPDDGITGyiVGYRVEYREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNGAGEG 83

Fibronectin type 3 domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046891570 432 VQVKASSPVPATP-ILQLEEccTHNNSATLSWKQPplSTVAADGYILELDDGSGGQFREVY-VGKETMCTVDGLHFNSTY 509
Cdd:COG3401   318 VSVTTDLTPPAAPsGLTATA--VGSSSITLSWTAS--SDADVTGYNVYRSTSGGGTYTKIAeTVTTTSYTDTGLTPGTTY 393

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1046891570 510 NARVKAFNKTGV-SPYSKTLVLQTSEDTDSEEQTLPFPVP 548
Cdd:COG3401   394 YYKVTAVDAAGNeSAPSEEVSATTASAASGESLTASVDAV 433

B-Box-type zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1046891570  163 AAALKCQLCEKAPkeATVMCEQCDVFYCDPCRLRCHpprgplAKHRLVP 211
Cdd:smart00336   1 QRAPKCDSHGDEP--AEFFCEECGALLCRTCDEAEH------RGHTVVL 41

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
                  ....*....|....*....|....*....|....*....
gi 1046891570   4 MEEELKCPVCGSFYREPIILPCSHNLCQACARNILVQTP 42
Cdd:TIGR00599  23 LDTSLRCHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQP 61

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
                   ....*....|....*....|....*....|
gi 1046891570   10 CPVC-GSFYREPIILPCSHNLCQACARNIL 38
Cdd:smart00184   1 CPIClEEYLKDPVILPCGHTFCRSCIRKWL 30

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 1046891570 620 VAWFAFDPGSAHSDIIFSNDNLTVTCSSYDDRVVLGKTGFSKGVHYWELTIDRYDNHPDPAFGVARIDVMKDMMLGKDDK 699
Cdd:cd12889     7 VAWFTFDPSTSHPDIILSNDNMTVTCNSYEDRVVLGSVGFSRGVHYWEVTIDRYDGHPDPAFGVARIDVNKDKMLGKDDK 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046891570 700 AWAMYVDNNRSWFMHNNSHTNRTEGGITKGATIGVLLDLNRKTLTFFVNNEQQGPIAFENVEGLFFPAVSLNRNVQVTLH 779
Cdd:cd12889    87 GWSMYIDNNRSWFLHNNEHSNRTEGGITVGSVVGVLLDLDRHTLSFYVNDEPQGPIAFRNLPGVFYPAVSLNRNVQVTLH 166

                  ....*.
gi 1046891570 780 TGLPVP 785
Cdd:cd12889   167 TGLEPP 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 1046891570  273 HKSQLSQALNGLSDRAKEAKEFLVQLRTMVQQIQENSVEFEACLVAQCDALIDALNRRKAQLLARVNKEHEHKLKVVRDQ 352
Cdd:smart00502   1 QREALEELLTKLRKKAAELEDALKQLISIIQEVEENAADVEAQIKAAFDELRNALNKRKKQLLEDLEEQKENKLKVLEQQ 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1046891570  353 ISHCTVKLRQTTGLMEYCLEVIKENDPSGFLQISDALIRRVHLTEDQ 399
Cdd:smart00502  81 LESLTQKQEKLSHAINFTEEALNSGDPTELLLSKKLIIERLQNLLKQ 127

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 1046891570 166 LKCQLCEKAPKEATVMCEQCDVFYCDPCRLRCHPPRGPLAKHRLVPP 212
Cdd:cd19843     1 LKCQLCEKSPKEATVMCEQCDVFYCDPCRLRCHPPRGPLAKHRLVPP 47

B-box-type 2 zinc finger found in tripartite motif-containing protein 67 (TRIM67) and similar proteins; 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. TRIM67 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 1046891570 228 TCTDHELENHSMYCVQCKMPVCYQCLEEGKHSSHEVKALGAMWK 271
Cdd:cd19827     2 TCAEHELENYSMYCASCRTPVCYQCLEEGKHAKHEVKALGAMWK 45

B-box-type 1 zinc finger found in tripartite motif-containing protein 67 (TRIM67) and similar proteins; 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. TRIM67 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 1046891570 165 ALKCQLCEKAP-KEATVMCEQCDVFYCDPCRLRCHPPRGPLAKHRLVPP 212
Cdd:cd19844     1 NARCQLCDRNPpEPAAVLCEQCDVLYCSACQLKCHPTRGPFAKHRLVPP 49

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 1046891570 663 VHYWELTIDRYDNHpDPAFGVARIDVM--KDMMLGKDDKAWAMYVDNNRSWfmHNNSHTNRTEGGITKGATIGVLLDLNR 740
Cdd:pfam00622   1 RHYFEVEIFGQDGG-GWRVGWATKSVPrkGERFLGDESGSWGYDGWTGKKY--WASTSPLTGLPLFEPGDVIGCFLDYEA 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1046891570 741 KTLTFFVNNEQQGpIAFENV--EGLFFPAVSLNRNVQVTLHTGLP 783
Cdd:pfam00622  78 GTISFTKNGKSLG-YAFRDVpfAGPLFPAVSLGAGEGLKFNFGLR 121

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 1046891570   5 EEELKCPVCGSFYREPIILPCSHNLCQACARNILVQTP 42
Cdd:cd16576     1 EEELKCPVCGSLFTEPVILPCSHNLCLGCALNIQLTCP 38

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 1046891570  661 KGVHYWELTIDrydnhpDP---AFGVARIDVMKDMM--LGKDDKAWAMYVDNNRSWFMHNNSHTNRTEGgiTKGATIGVL 735
Cdd:smart00449   1 SGRHYFEVEIG------DGghwRVGVATKSVPRGYFalLGEDKGSWGYDGDGGKKYHNSTGPEYGLPLQ--EPGDVIGCF 72

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1046891570  736 LDLNRKTLTFFVNNEQQGPIAFENVE--GLFFPAVSLN 771
Cdd:smart00449  73 LDLEAGTISFYKNGKYLHGLAFFDVKfsGPLYPAFSLG 110

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 1046891570 634 IIFSNDNLTVTCSS-YddRVVLGKTGFSKGVHYWELTIDRYDNHPDPA--FGVARIDVMKDMMLGKDDKAWAmYVDNNRS 710
Cdd:cd12872     1 LKLSEDRLTVTGEKgY--RMARANHGVREGKWYFEVKILEGGGTETGHvrVGWSRREASLQAPVGYDKYSYA-IRDKDGS 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046891570 711 WFmHNNSHTNRTEGGITKGATIGVLLDLNRktLTFFVNNEQQGPiAFENV--EGLFFPAVSLNRNVQVTLHTGlpvPDFY 788
Cdd:cd12872    78 KF-HQSRGKPYGEPGFKEGDVIGFLITLPK--IEFFKNGKSQGV-AFEDIygTGGYYPAVSLYKGATVTINFG---PDFK 150

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 1046891570 625 FDPGSAHSDIIFSNDNLTVTCSSYDDRV-----------VLGKTGFSKGVHYWELTIdryDNHPDPAFGVA--RIDVMKD 691
Cdd:cd12891     3 LDPNTAHNNLALSGDLKTVTCSSENQHYpdsperfthsqVLSTQSFSSGRHYWEVEV---SESGGWSVGVAypSIERKGD 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1046891570 692 M-MLGKDDKAWAMYVDNNRSWFMHNNshtNRTEGGITKGATIGVLLDLNRKTLTFF 746
Cdd:cd12891    80 EsRIGRNDKSWCLEWQDKSFSAWHNN---EETPLPSVSSRRLGVYLDYEAGRLSFY 132

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 1046891570 625 FDPGSAHSDIIFSNDNLTVTCSSYDDR------------VVLGKTGFSKGVHYWELTIdrYDNHpDPAFGVA-----RID 687
Cdd:cd12874     3 FDPDTAHLNLILSDDLRSVRVGDISQHppeppprffecwQVLGSQSFSSGRHYWEVDV--QDDS-SWYVGVTykslpRKG 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1046891570 688 VMkdMMLGKDDKAWAMYVDNNRSWFMHNNShtnRTEGGITKGATIGVLLDLNRKTLTFF 746
Cdd:cd12874    80 KM--SNLGRNNGSWCLEWRENEFSAWHNNP---ETRLPVTPPRRLGVFLDCDGGSLSFY 133

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        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1046891570   5 EEELKCPVCGSFYREPIILPCSHNLCQACARNILVQTPES--ESPQSRRA 52
Cdd:cd16609     1 EEELTCSICLGLYQDPVTLPCQHSFCRACIEDHWRQKDEGsfSCPECRAP 50

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 1046891570   1 MEEMEEELKCPVCGSFYREPIILPCSHNLCQACARNILV 39
Cdd:cd16754     1 METLESELTCPICLELFEDPLLLPCAHSLCFSCAHRILT 39

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1046891570  453 THNNSATLSWKQPPLSTVAA--DGYILELDDGSGGQFREVYVGKETMCTVDGLHFNSTYNARVKAFNKTGVS 522
Cdd:smart00060  12 VTSTSVTLSWEPPPDDGITGyiVGYRVEYREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNGAGEG 83

RING finger, HC subclass, found in midline-1 (MID1) and similar proteins; 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. It monoubiquinates the alpha4 subunit of protein phosphatase 2A (PP2A), promoting proteosomal degradation of the catalytic subunit of PP2A (PP2Ac) and preventing the A and B subunits from forming an active complex. It promotes allergen and rhinovirus-induced asthma through the inhibition of PP2A activity. It is strongly upregulated in cytotoxic lymphocytes (CTLs) and directs lytic granule exocytosis and cytotoxicity of killer T cells. Loss-of-function mutations in MID1 lead to the human X-linked Opitz G/BBB (XLOS) syndrome characterized by defective midline development during embryogenesis. MID1 belongs to the C-I subclass of 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. MID1 hetero-dimerizes in vitro with its paralog MID2.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1046891570   4 MEEELKCPVCGSFYREPIILPCSHNLCQACARNILVQTPESESP 47
Cdd:cd16753     2 LESELTCPICLELFEDPLLLPCAHSLCFNCAHRILVSHCASNES 45

RING finger, HC subclass, found in tripartite motif-containing protein 59 (TRIM59) and similar proteins; TRIM59, also known as RING finger protein 104 (RNF104) or tumor suppressor TSBF-1, is a putative E3 ubiquitin-protein ligase that functions as a novel multiple cancer biomarker for immunohistochemical detection of early tumorigenesis. It is upregulated in gastric cancer and promotes gastric carcinogenesis by interacting with and targeting the P53 tumor suppressor for its ubiquitination and degradation. It also acts as a novel accessory molecule involved in cytotoxicity of BCG-activated macrophages (BAM). Moreover, TRIM59 may serve as a multifunctional regulator for innate immune signaling pathways. It interacts with ECSIT and negatively regulates nuclear factor-kappaB (NF- kappa B) and interferon regulatory factor (IRF)-3/7-mediated signal pathways. TRIM59 belongs to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region. In addition, TRIM59 contains a C-terminal transmembrane domain.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 1046891570   5 EEELKCPVCGSFYREPIILPCSHNLCQACARNIL 38
Cdd:cd16763     1 EEDLTCSVCYSLFEDPRVLPCSHTFCRNCLENIL 34

RING finger, HC subclass, found in tripartite motif-containing protein 13 (TRIM13) and similar proteins; 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). It also targets the known ER proteolytic substrate CD3-delta, but not the N-end rule substrate Ub-R-YFP (yellow fluorescent protein) for degradation. Moreover, TRIM13 regulates ubiquitination and degradation of NEMO to suppress tumor necrosis factor (TNF) induced nuclear factor-kappaB (NF- kappa B) activation. It is also involved in NF-kappaB p65 activation and nuclear factor of activated T-cells (NFAT)-dependent activation of c-Rel upon T-cell receptor engagement. Furthermore, TRIM13 negatively regulates melanoma differentiation-associated gene 5 (MDA5)-mediated type I interferon production. It also regulates caspase-8 ubiquitination, translocation to autophagosomes, and activation during ER stress induced cell death. Meanwhile, TRIM13 enhances ionizing radiation-induced apoptosis by increasing p53 stability and decreasing AKT kinase activity through MDM2 and AKT degradation. TRIM13 belongs to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region. In addition, TRIM13 contains a C-terminal transmembrane domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1046891570   5 EEELKCPVCGSFYREPIILPCSHNLCQACARNILvqtPESESPQSRRAS 53
Cdd:cd16762     1 EEDLTCPICCCLFDDPRVLPCSHNFCKKCLEGIL---EGNVRTMLWRPP 46

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 1046891570   6 EELKCPVCGSFYREPIILPCSHNLCQACARNIL 38
Cdd:cd16581     1 EELTCSICYNIFDDPKILPCSHTFCKNCLEKLL 33

RING finger, HC subclass, found in tripartite motif-containing protein 36 (TRIM36) and similar proteins; TRIM36, the human ortholog of mouse Haprin, also known as RING finger protein 98 (RNF98) or zinc-binding protein Rbcc728, is an E3 ubiquitin-protein ligase expressed in the germ plasm. It has been implicated in acrosome reaction, fertilization, and embryogenesis, as well as in carcinogenesis. TRIM36 functions upstream of Wnt/beta-catenin activation, and plays a role in controlling the stability of proteins regulating microtubule polymerization during cortical rotation, and subsequently dorsal axis formation. It is also potentially associated with chromosome segregation by interacting with the kinetochore protein centromere protein-H (CENP-H), and colocalizing with the microtubule protein alpha-tubulin. Its overexpression may cause chromosomal instability and carcinogenesis. It is, thus, a novel regulator affecting cell cycle progression. Moreover, TRIM36 plays a critical role in the arrangement of somites during embryogenesis. TRIM36 belongs to the C-I subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, a PRY domain and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1046891570   5 EEELKCPVCGSFYREPIILPCSHNLCQACARNILVQTP 42
Cdd:cd16756     1 ERELICPSCKELFTHPLILPCQHSVCHKCVKELLTTFP 38

Fibronectin type 3 domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046891570 432 VQVKASSPVPATP-ILQLEEccTHNNSATLSWKQPplSTVAADGYILELDDGSGGQFREVY-VGKETMCTVDGLHFNSTY 509
Cdd:COG3401   318 VSVTTDLTPPAAPsGLTATA--VGSSSITLSWTAS--SDADVTGYNVYRSTSGGGTYTKIAeTVTTTSYTDTGLTPGTTY 393

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1046891570 510 NARVKAFNKTGV-SPYSKTLVLQTSEDTDSEEQTLPFPVP 548
Cdd:COG3401   394 YYKVTAVDAAGNeSAPSEEVSATTASAASGESLTASVDAV 433

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 1046891570 229 CTDHELENHSMYCVQCKMPVCYQCLEEGKHSSHEVKAL 266
Cdd:cd19756     2 CPEHPEEPLKLFCETCQELVCVLCLLSGEHRGHKVVPL 39

SPRY domain 2 (SPRY2) of ryanodine receptor (RyR); This SPRY domain (SPRY2) is the second of three structural repeats in all three isoforms of the ryanodine receptor (RyR), which are the major Ca2+ release channels in the membranes of sarcoplasmic reticulum (SR). There are three RyR genes in mammals; the skeletal RyR1, the cardiac RyR2 and the brain RyR3. The three SPRY domains are located in the N-terminal part of the cytoplasmic region of the RyRs, The SPRY2 domain has been shown to bind to the dihydropryidine receptor (DHPR) II-III loop and the ASI region of RyR1

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046891570 681 FGVARIDVMKDMMLGKDDKAWAMYVDNNRSWfmHNNSHTNRTEGGitKGATIGVLLDLNRKTLTFFVNNE-----QQGPI 755
Cdd:cd12878    30 VGWARPGFRPDLELGSDDLSYAFDGFLARKW--HQGSESFGKQWQ--PGDVVGCMLDLVDRTISFTLNGEllidsSGSEV 105

                          90       100
                  ....*....|....*....|....*...
gi 1046891570 756 AFENVEGL--FFPAVSLNRNVQVTLHTG 781
Cdd:cd12878   106 AFKDIEIGegFVPACSLGVGQKGRLNLG 133

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 1046891570   3 EMEEELKCPVCGSFYREPIILPCSHNLCQAC 33
Cdd:cd16594     1 SLQEELTCPICLDYFTDPVTLDCGHSFCRAC 31

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 1046891570 625 FDPGSAHSDIIFSNDNLTVTCSS-----------YD-DRVVLGKTGFSKGVHYWELTIDRYDNHpdpAFGVARIDVMK-- 690
Cdd:cd12888     4 LDPDTAHPRLVLSEDRKSVRWGDtrqdlpdnperFDtWPCVLGCEGFTSGRHYWEVEVGDGGGW---AVGVARESVRRkg 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046891570 691 DMMLGKDDKAWAMYVDNNRSWFMHNNSHTNRTEGGITKgatIGVLLDLNRKTLTFFvNNEQQGPIaFEnveglfFPAVSL 770
Cdd:cd12888    81 EISFSPEEGIWAVGQWGGQYWALTSPETPLPLSEVPRR---IRVYLDYEGGQVAFF-DADNEAPI-FT------FPPASF 149

                  ..
gi 1046891570 771 NR 772
Cdd:cd12888   150 AG 151

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 1046891570 229 CTDHELENHSMYCVQCKMPVCYQCLEEGKHSSHEVKALGAMWK 271
Cdd:cd19778     3 CPEHEMEKVNMYCEACRRPVCHLCKLGGSHANHRVTSMSSAYK 45