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 2287780865 205 VAICQLCDRTPPEPAATLCEQCDVLYCSACQLKCHPSRGPFAKHRLVQ 252
Cdd:cd19844     1 NARCQLCDRNPPEPAAVLCEQCDVLYCSACQLKCHPTRGPFAKHRLVP 48

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 2287780865   2 EEELKCPVCGSLFREPIILPCSHNVCLPCARTIAVQTPDGEQHLPQ 47
Cdd:cd16758     1 EEELKCPVCGSLFREPIILPCSHNVCLPCARTIAVQTPESEQHLPH 46

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2287780865 526 NSVTLAWRMPPFTHSPVDGYILELDDGAGGQFREVYV--GKETLCTIDGLHFNSTYNARVKAFNSSGVGPYSKTVVLQT 602
Cdd:cd00063    15 TSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVtpGSETSYTLTGLKPGTEYEFRVRAVNGGGESPPSESVTVTT 93

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 2287780865 205 VAICQLCDRTPPEPAATLCEQCDVLYCSACQLKCHPSRGPFAKHRLVQ 252
Cdd:cd19844     1 NARCQLCDRNPPEPAAVLCEQCDVLYCSACQLKCHPTRGPFAKHRLVP 48

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 2287780865   2 EEELKCPVCGSLFREPIILPCSHNVCLPCARTIAVQTPDGEQHLPQ 47
Cdd:cd16758     1 EEELKCPVCGSLFREPIILPCSHNVCLPCARTIAVQTPESEQHLPH 46

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2287780865 526 NSVTLAWRMPPFTHSPVDGYILELDDGAGGQFREVYV--GKETLCTIDGLHFNSTYNARVKAFNSSGVGPYSKTVVLQT 602
Cdd:cd00063    15 TSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVtpGSETSYTLTGLKPGTEYEFRVRAVNGGGESPPSESVTVTT 93

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 2287780865 648 VHYWELHVDRYDNHpDPAFGVARASV--VKDMMLGKDDKAWAMYVDNNRSWfmHCNSHTNRTEGGVCKGATVGVLLDLNK 725
Cdd:pfam00622   1 RHYFEVEIFGQDGG-GWRVGWATKSVprKGERFLGDESGSWGYDGWTGKKY--WASTSPLTGLPLFEPGDVIGCFLDYEA 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 2287780865 726 HTLTFFINGQQQGpTAFSHV--DGVFMPALSLNRNVQVTLHTGL 767
Cdd:pfam00622  78 GTISFTKNGKSLG-YAFRDVpfAGPLFPAVSLGAGEGLKFNFGL 120

Fibronectin type III domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2287780865 511 PPVPLLQLEKccTRNNSVTLAWRMPPFTHSPVDGYILEL-DDGAGGQFREVYVGK-ETLCTIDGLHFNSTYNARVKAFNS 588
Cdd:pfam00041   1 SAPSNLTVTD--VTSTSLTVSWTPPPDGNGPITGYEVEYrPKNSGEPWNEITVPGtTTSVTLTGLKPGTEYEVRVQAVNG 78

                  ....*..
gi 2287780865 589 SGVGPYS 595
Cdd:pfam00041  79 GGEGPPS 85

Fibronectin type 3 domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2287780865 525 NNSVTLAWRmpPFTHSPVDGYILELDDGAGGQFREVY-VGKETLCTIDGLHFNSTYNARVKAFNSSGV-GPYSKTVVLQT 602
Cdd:COG3401   340 SSSITLSWT--ASSDADVTGYNVYRSTSGGGTYTKIAeTVTTTSYTDTGLTPGTTYYYKVTAVDAAGNeSAPSEEVSATT 417

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2287780865 603 SDVA---WFTFDPNSGHRDIILSNDNQTATCSSYDDrVVLGTAAFSKGVHYWELHVDRYDNHPDPAFGVARASVVKD 676
Cdd:COG3401   418 ASAAsgeSLTASVDAVPLTDVAGATAAASAASNPGV-SAAVLADGGDTGNAVPFTTTSSTVTATTTDTTTANLSVTT 493

Fibronectin type 3 domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2287780865 525 NNSVTLAWRMPPFTHspVDGYILELDDGAGGQFREVYVGKETLCTIDGLHFNSTYNARVKAFNSSGV-GPYSKTVVLQTS 603
Cdd:COG3401   246 PGSVTLSWDPVTESD--ATGYRVYRSNSGDGPFTKVATVTTTSYTDTGLTNGTTYYYRVTAVDAAGNeSAPSNVVSVTTD 323

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 2287780865   1 MEEELKCPVCGSLFREPIILPCSHNVCLPCART 33
Cdd:TIGR00599  23 LDTSLRCHICKDFFDVPVLTSCSHTFCSLCIRR 55

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2287780865 608 FTFDPNSGHRDIILSNDNQTATCSSY--------------DDRVVLGTAAFSKGVHYWELHVDRYdnhPDPAFGVARASV 673
Cdd:cd13734     1 FKLDPKTAHRKLRLSNDNLTVEYDPEgskdqaavlprrftGSPAVLGDVAISSGRHYWEVSVSRS---TSYRVGVAYKSA 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2287780865 674 VKDMMLGKDDKAWAMYVDNNRSWFMHCNS-HTNRTEGgvcKGATVGVLLDLNKHTLTFFINGQQQGPTAFSHVD-GVFMP 751
Cdd:cd13734    78 PRDEDLGKNSTSWCLSRDNNRYTARHDGKvVDLRVTG---HPARIGVLLDYDNGTLSFYDAESKQHLYTFHVDFeGPVCP 154

                         170
                  ....*....|...
gi 2287780865 752 ALSLNrNVQVTLH 764
Cdd:cd13734   155 AFAVW-NGSLTLH 166

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 2287780865 301 PTCPEHEMENYSMYCVSCRTPVCYLCLEEGRHAKHEVKPLGAMWK 345
Cdd:cd19827     1 PTCAEHELENYSMYCASCRTPVCYQCLEEGKHAKHEVKALGAMWK 45

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2287780865  347 HKAQLSQALNGVSDKAKEAKEFLVQLKNILQQIQENGLDYEACLVAQCDALVDALTRQKAKLLTKVTKEREHKLKMVWDQ 426
Cdd:smart00502   1 QREALEELLTKLRKKAAELEDALKQLISIIQEVEENAADVEAQIKAAFDELRNALNKRKKQLLEDLEEQKENKLKVLEQQ 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 2287780865  427 INHCTLKLRQSTGLMEYCLEVIKENDPSGFLQISDALIKRVQVSQEQ 473
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 2287780865 298 RKFPTCPEHEMENYSMYCVSCRTPVCYLCLEEGRHAKHEVKPLGAMWK 345
Cdd:cd19826     2 RKISTCTDHELENHSMYCVQCKMPVCYQCLEEGKHSSHEVKALGAMWK 49

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 2287780865 208 CQLCDRTPPEpAATLCEQCDVLYCSACQLKCHPSRGPFAKHRLV 251
Cdd:cd19843     3 CQLCEKSPKE-ATVMCEQCDVFYCDPCRLRCHPPRGPLAKHRLV 45

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 2287780865   2 EEELKCPVCGSLFREPIILPCSHNVCLPCARTIAVQTP 39
Cdd:cd16576     1 EEELKCPVCGSLFTEPVILPCSHNLCLGCALNIQLTCP 38

SPRY domain; SPRY domains, first identified in the SP1A kinase of Dictyostelium and rabbit Ryanodine receptor (hence the name), are homologous to B30.2. SPRY domains have been identified in at least 11 protein families, covering a wide range of functions, including regulation of cytokine signaling (SOCS), RNA metabolism (DDX1 and hnRNP), immunity to retroviruses (TRIM5alpha), intracellular calcium release (ryanodine receptors or RyR) and regulatory and developmental processes (HERC1 and Ash2L). B30.2 also contains residues in the N-terminus that form a distinct PRY domain structure; i.e. 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 or RBCC core); Stonutoxin (secreted poisonous protein of the stonefish Synanceia horrida). TRIM/RBCC proteins are involved in a variety of processes, including apoptosis, cell cycle regulation, cell growth, senescence, viral response, meiosis, cell differentiation, and vesicular transport. Genes belonging to this family are implicated in several human diseases that vary from cancer to rare genetic syndromes. The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site. 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. Mutations found in the SPRY-containing proteins have shown to cause Mediterranean fever and Opitz syndrome.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2287780865 647 GVHYWELHVDRyDNHPDPAFGVARASVV--KDMMLGKDDKAWAMYVDNNRSWFMHCNSHTNR--TEGGVckgatVGVLLD 722
Cdd:cd11709     1 GKWYWEVRVDS-GNGGLIQVGWATKSFSldGEGGVGDDEESWGYDGSRLRKGHGGSSGPGGRpwKSGDV-----VGCLLD 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2287780865 723 LNKHTLTFFINGQQQGpTAFSHVD---GVFMPALSLNRNVQVTLH 764
Cdd:cd11709    75 LDEGTLSFSLNGKDLG-VAFTNLFlkgGGLYPAVSLGSGQGVTIN 118

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2287780865 526 NSVTLAWRMPPFTHSPVDGYILELDDGAGGQFREVYV--GKETLCTIDGLHFNSTYNARVKAFNSSGVGPYSKTVVLQT 602
Cdd:cd00063    15 TSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVtpGSETSYTLTGLKPGTEYEFRVRAVNGGGESPPSESVTVTT 93

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 2287780865 648 VHYWELHVDRYDNHpDPAFGVARASV--VKDMMLGKDDKAWAMYVDNNRSWfmHCNSHTNRTEGGVCKGATVGVLLDLNK 725
Cdd:pfam00622   1 RHYFEVEIFGQDGG-GWRVGWATKSVprKGERFLGDESGSWGYDGWTGKKY--WASTSPLTGLPLFEPGDVIGCFLDYEA 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 2287780865 726 HTLTFFINGQQQGpTAFSHV--DGVFMPALSLNRNVQVTLHTGL 767
Cdd:pfam00622  78 GTISFTKNGKSLG-YAFRDVpfAGPLFPAVSLGAGEGLKFNFGL 120

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 2287780865 619 IILSNDNQTATCSS-YddRVVLGTAAFSKGVHYWELHVDRYDNHPDPA--FGVAR--ASVvkDMMLGKDDKAWAmYVDNN 693
Cdd:cd12872     1 LKLSEDRLTVTGEKgY--RMARANHGVREGKWYFEVKILEGGGTETGHvrVGWSRreASL--QAPVGYDKYSYA-IRDKD 75

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2287780865 694 RSWFmHCNSHTNRTEGGVCKGATVGVLLDLNKhtLTFFINGQQQGpTAFSHVD--GVFMPALSLNRNVQVTLHTG 766
Cdd:cd12872    76 GSKF-HQSRGKPYGEPGFKEGDVIGFLITLPK--IEFFKNGKSQG-VAFEDIYgtGGYYPAVSLYKGATVTINFG 146

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 2287780865 208 CQLCDRTPPEPAATLCEQCDVLYCSACQLKCHPSRGPFAKHRLVQ 252
Cdd:cd19837     5 CQFCEQEPPRDAVKTCITCEVSYCDRCLRATHPNKKPFTSHRLVE 49

B-box-type 1 zinc finger found in midline-1 (MID1) and similar proteins; MID1, also termed midin, or midline 1 RING finger protein, or putative transcription factor XPRF, or RING finger protein 59 (RNF59), or tripartite motif-containing protein 18 (TRI18), is a microtubule-associated E3 ubiquitin-protein ligase implicated in epithelial-mesenchymal differentiation, cell migration and adhesion, and programmed cell death along specific regions of the ventral midline during embryogenesis. It monoubiquinates the alpha4 subunit of protein phosphatase 2A (PP2A), promoting proteosomal degradation of the catalytic subunit of PP2A (PP2Ac) and preventing the A and B subunits from forming an active complex. It promotes allergen and rhinovirus-induced asthma through the inhibition of PP2A activity. It is strongly upregulated in cytotoxic lymphocytes (CTLs) and directs lytic granule exocytosis and cytotoxicity of killer T cells. Loss-of-function mutations in MID1 lead to the human X-linked Opitz G/BBB (XLOS) syndrome characterized by defective midline development during embryogenesis. MID1 belongs to the C-I subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, the fibronectin type III domain and the SPRY/B30.2 domain positioned C-terminal to the RBCC domain. The type 1 B-box (Bbox1) zinc finger is characterized by a C6H2 zinc-binding consensus motif. MID1 heterodimerizes in vitro with its paralog MID2.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 2287780865 208 CQLCDRTPPEPAATLCEQCDVLYCSACQLKCHPSRGPFAKHRLVQ 252
Cdd:cd19836     5 CQFCDQDPAQDAVKTCVTCEVSYCDECLKATHPNKKPFTGHRLIE 49

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
                  ....*....|....*....|....*....|....*
gi 2287780865 303 CPEHEMENYSMYCVSCRTPVCYLCLEEGRHAKHEV 337
Cdd:cd19778     3 CPEHEMEKVNMYCEACRRPVCHLCKLGGSHANHRV 37

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2287780865 609 TFDPNSGHRDIILSNDNQTATCS----SYDD--------RVVLGTAAFSkGVHYWElhVDRYDNHPDPA---FGVARASV 673
Cdd:cd16040    12 TLDPNTAHRNLSLSEGNRKVTRVkeeqPYPDhperfdywPQVLCREGLS-GRCYWE--VEWSGGGVDIAvayKGISRKGD 88

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2287780865 674 VKDMMLGKDDKAWAMYVDNNRSWFMHcNSHTNRTEGGVCKGATVGVLLDLNKHTLTFF 731
Cdd:cd16040    89 GDDSRFGYNDKSWSLECSPSGYSFWH-NNKKTEISVPSSSSSRVGVYLDHSAGTLSFY 145

Fibronectin type III domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2287780865 511 PPVPLLQLEKccTRNNSVTLAWRMPPFTHSPVDGYILEL-DDGAGGQFREVYVGK-ETLCTIDGLHFNSTYNARVKAFNS 588
Cdd:pfam00041   1 SAPSNLTVTD--VTSTSLTVSWTPPPDGNGPITGYEVEYrPKNSGEPWNEITVPGtTTSVTLTGLKPGTEYEVRVQAVNG 78

                  ....*..
gi 2287780865 589 SGVGPYS 595
Cdd:pfam00041  79 GGEGPPS 85

PRY/SPRY domain in RING finger protein RNF135; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of the RING finger protein RNF135 (also known as Riplet/RNF135), which ubiquitinates RIG-I (retinoic acid-inducible gene-I) to promote interferon-beta induction during the early phase of viral infection. Normally, RIG-I is activated by TRIM25 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. However, RNF135, consisting of an N-terminal RING finger domain, C-terminal SPRY and PRY motifs and showing sequence similarity to TRIM25, acts as an alternative factor that promotes RIG-I activation independent of TRIM25.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2287780865 609 TFDPNSGHRDIILSNDNQTATCSS-------YDDRV----VLGTAAFSKGVHYWElhVD-RYDNHpdPAFGVARASVVKD 676
Cdd:cd12902     2 TFDLRSLSCSLEVSEDSRKVTVSHgpqayawSPDRFsisqVLCSQAFSSGQHYWE--VDtRQCSH--WAVGVASWEMSRD 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2287780865 677 MMLGKDDKAWAMyvdnnrSW---FMHCNSHTNR-TEGGVCKGATVGVLLDLNKHTLTFFINGQQQ 737
Cdd:cd12902    78 QMLGRTMDSWCI------EWkgtGQLSAWHMNKeTVLGSDKPRVVGIWLDLEEGKLAFYSVANQE 136

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 2287780865   1 MEEELKCPVCGSLFREPIILPCSHNVCLPC 30
Cdd:cd16597     2 LEEELTCSICLELFKDPVTLPCGHNFCGVC 31

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2287780865 608 FTFDPNSGHRDIILSNDNQTATCSS-----------YDDRV-VLGTAAFSKGVHYWELHVdryDNHPDPAFGVARASV 673
Cdd:cd13733     2 VTLDPDTAHPNLILSEDLKSVRYGDkrqnlpdnperFDTCVcVLGSEGFSSGRHYWEVEV---GGKTDWDLGVARESV 76

zinc-binding protein A33-like; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM69 and TRIM proteins NF7 and bloodthirsty (bty). 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2287780865 606 AWFTFDPNSGHRDIILSNDnQTATCSSYDDRV-------------VLGTAAFSKGVHYWELHVdryDNHPDPAFGVARAS 672
Cdd:cd12905     4 APLTFDPETAHPSLILSRD-LTAVTESDEMQPyprspkrflqcvnVLASQGFQSGRHYWEVWV---GSKTKWDLGVASES 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2287780865 673 VVKDMM--LGKDDKAWAMYVDNNRSWFMHCNSHTN-RTEGGVCKgatVGVLLDLNKHTLTFF 731
Cdd:cd12905    80 VDRQARvkLCPENGYWTLRLRNGDEYWAGTQPWTRlRVTSRPQR---IGVFLDCEERKVSFY 138

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 2287780865 666 FGVARASVVKDMMLGKDDKAWAMYVDNNRSWFMHcNSHTNRTEGgvcKGATVGVLLDLNKHTLTFFINGQ-----QQGPT 740
Cdd:cd12878    30 VGWARPGFRPDLELGSDDLSYAFDGFLARKWHQG-SESFGKQWQ---PGDVVGCMLDLVDRTISFTLNGEllidsSGSEV 105

                          90       100
                  ....*....|....*....|....*...
gi 2287780865 741 AFSHVDGV--FMPALSLNRNVQVTLHTG 766
Cdd:cd12878   106 AFKDIEIGegFVPACSLGVGQKGRLNLG 133

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
                  ....*....|....*....|....*....|...
gi 2287780865   2 EEELKCPVCGSLFREPIILPCSHNVCLPCARTI 34
Cdd:cd16762     1 EEDLTCPICCCLFDDPRVLPCSHNFCKKCLEGI 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 2287780865   2 EEELKCPVCGSLFREPIILPCSHNVCLPCARTIAVQTP 39
Cdd:cd16756     1 ERELICPSCKELFTHPLILPCQHSVCHKCVKELLTTFP 38

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 2287780865   2 EEELKCPVCGSLFREPIILPCSHNVCLPCARTI 34
Cdd:cd16763     1 EEDLTCSVCYSLFEDPRVLPCSHTFCRNCLENI 33

Fibronectin type 3 domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2287780865 525 NNSVTLAWRmpPFTHSPVDGYILELDDGAGGQFREVY-VGKETLCTIDGLHFNSTYNARVKAFNSSGV-GPYSKTVVLQT 602
Cdd:COG3401   340 SSSITLSWT--ASSDADVTGYNVYRSTSGGGTYTKIAeTVTTTSYTDTGLTPGTTYYYKVTAVDAAGNeSAPSEEVSATT 417