PRY/SPRY domain of TRIM18/MID1, also known as FXY or RNF59; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is at the C-terminus of the overall domain architecture of MID1 (also known as FXY, RNF59, TRIM18) gene represented by a RING finger domain (RING), two B-box motifs (BBOX), coiled-coil C-terminal to Bbox domain (BBC) and fibronectin type 3 domain (FN3). Mutations in the human MID1 gene result in X-linked Opitz G/BBB syndrome (OS), a disorder affecting development of midline structures, causing craniofacial, urogenital, gastrointestinal and cardiovascular abnormalities. A unique MID1 gene mutation located in a variable loop in the SPRY domain alters conformation of the binding pocket and may affect the binding affinity to the PRY/SPRY domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499 485 PFKLDPKSAHRKLKVSHDNLTVERDESSSKKSHTPERFTSQGSYGVAGNVFIDSGRHYWEVVISGSTWYAIGLAYKSAPK 564
Cdd:cd12892    1 PFKLDPKSAHRKLKVSHDNLTVERDETSSKKSHTPERFTSQGSYGVAGNVFIDSGRHYWEVVISGSTWYAIGIAYKSAPK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499 565 HEWIGKNSASWALCRCNNNWVVRHNSKEIPIEPAPHLRRVGILLDYDNGSIAFYDALNSIHLYTFDVAFAQPVCPTFTVW 644
Cdd:cd12892   81 HEWIGKNSASWVLCRCNNNWVVRHNSKEIPIEPSPHLRRVGILLDYDNGSLSFYDALNSIHLYTFDIAFAQPVCPTFTVW 160

                        170
                 ....*....|....*..
gi 148833499 645 NKCLTIITGLPIPDHLD 661
Cdd:cd12892  161 NKCLTILTGLPIPDHLD 177

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        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 148833499 115 EKVLCQFCDQDPAQDAVKTCVTCEVSYCDECLKATHPNKKPFTGHRLIEP 164
Cdd:cd19836    1 EKVLCQFCDQDPAQDAVKTCVTCEVSYCDECLKATHPNKKPFTGHRLIEP 50

B-box-type 2 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. It heterodimerizes in vitro with its paralog MID2. 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 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 148833499 168 SHIRGLMCLEHEDEKVNMYCVTDDQLICALCKLVGRHRDHQVAALSE 214
Cdd:cd19822    1 SHIRGLMCLEHEDEKVNMYCVTDDQLICALCKLVGRHRDHQVAALSD 47

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499 381 APNPPTIREelctASYDTITVHWT--SDDEFSVVSYELQYTIftgqanvvslcNSADSWMIV--PNIKQNHYTVHGLQSG 456
Cdd:cd00063    3 PPTNLRVTD----VTSTSVTLSWTppEDDGGPITGYVVEYRE-----------KGSGDWKEVevTPGSETSYTLTGLKPG 67

                         90       100
                 ....*....|....*....|....*.
gi 148833499 457 TKYIFMVKAINQAG-SRSSEPGKLKT 481
Cdd:cd00063   68 TEYEFRVRAVNGGGeSPPSESVTVTT 93

PRY/SPRY domain of TRIM18/MID1, also known as FXY or RNF59; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is at the C-terminus of the overall domain architecture of MID1 (also known as FXY, RNF59, TRIM18) gene represented by a RING finger domain (RING), two B-box motifs (BBOX), coiled-coil C-terminal to Bbox domain (BBC) and fibronectin type 3 domain (FN3). Mutations in the human MID1 gene result in X-linked Opitz G/BBB syndrome (OS), a disorder affecting development of midline structures, causing craniofacial, urogenital, gastrointestinal and cardiovascular abnormalities. A unique MID1 gene mutation located in a variable loop in the SPRY domain alters conformation of the binding pocket and may affect the binding affinity to the PRY/SPRY domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499 485 PFKLDPKSAHRKLKVSHDNLTVERDESSSKKSHTPERFTSQGSYGVAGNVFIDSGRHYWEVVISGSTWYAIGLAYKSAPK 564
Cdd:cd12892    1 PFKLDPKSAHRKLKVSHDNLTVERDETSSKKSHTPERFTSQGSYGVAGNVFIDSGRHYWEVVISGSTWYAIGIAYKSAPK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499 565 HEWIGKNSASWALCRCNNNWVVRHNSKEIPIEPAPHLRRVGILLDYDNGSIAFYDALNSIHLYTFDVAFAQPVCPTFTVW 644
Cdd:cd12892   81 HEWIGKNSASWVLCRCNNNWVVRHNSKEIPIEPSPHLRRVGILLDYDNGSLSFYDALNSIHLYTFDIAFAQPVCPTFTVW 160

                        170
                 ....*....|....*..
gi 148833499 645 NKCLTIITGLPIPDHLD 661
Cdd:cd12892  161 NKCLTILTGLPIPDHLD 177

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        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 148833499 115 EKVLCQFCDQDPAQDAVKTCVTCEVSYCDECLKATHPNKKPFTGHRLIEP 164
Cdd:cd19836    1 EKVLCQFCDQDPAQDAVKTCVTCEVSYCDECLKATHPNKKPFTGHRLIEP 50

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 148833499  323 NDHARFLQTAKNITERVSMATASSQVLIPEINLNDTFDTFALDFSREKKLLE 374
Cdd:pfam18568   1 TDHARFLQTAKNVHERVSMATASSQVLIPDINLNDAFENFALDFSREKKLLE 52

B-box-type 2 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. It heterodimerizes in vitro with its paralog MID2. 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 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 148833499 168 SHIRGLMCLEHEDEKVNMYCVTDDQLICALCKLVGRHRDHQVAALSE 214
Cdd:cd19822    1 SHIRGLMCLEHEDEKVNMYCVTDDQLICALCKLVGRHRDHQVAALSD 47

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499 381 APNPPTIREelctASYDTITVHWT--SDDEFSVVSYELQYTIftgqanvvslcNSADSWMIV--PNIKQNHYTVHGLQSG 456
Cdd:cd00063    3 PPTNLRVTD----VTSTSVTLSWTppEDDGGPITGYVVEYRE-----------KGSGDWKEVevTPGSETSYTLTGLKPG 67

                         90       100
                 ....*....|....*....|....*.
gi 148833499 457 TKYIFMVKAINQAG-SRSSEPGKLKT 481
Cdd:cd00063   68 TEYEFRVRAVNGGGeSPPSESVTVTT 93

Fibronectin type 3 domain [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499 380 TAPNPPTireELcTASYDT---ITVHWTSDDEFSVVSYELQYTIftgqanvvslcNSADSWMIVPNIKQNHYTVHGLQSG 456
Cdd:COG3401  231 TPPSAPT---GL-TATADTpgsVTLSWDPVTESDATGYRVYRSN-----------SGDGPFTKVATVTTTSYTDTGLTNG 295

                         90       100       110
                 ....*....|....*....|....*....|.
gi 148833499 457 TKYIFMVKAINQAGSRS--SEPGKLKTNSQP 485
Cdd:COG3401  296 TTYYYRVTAVDAAGNESapSNVVSVTTDLTP 326

Fibronectin type III domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499  381 APNPPTIREelctASYDTITVHWTSDDEFS--VVSYELQYtiftgqanvvSLCNSADSW--MIVPNIkQNHYTVHGLQSG 456
Cdd:pfam00041   2 APSNLTVTD----VTSTSLTVSWTPPPDGNgpITGYEVEY----------RPKNSGEPWneITVPGT-TTSVTLTGLKPG 66

                          90
                  ....*....|....
gi 148833499  457 TKYIFMVKAINQAG 470
Cdd:pfam00041  67 TEYEVRVQAVNGGG 80

E3 ubiquitin-protein ligase RMA2; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499   7 ELTCPICLELFEDPLLLPCAHSLCFNCAHRILVshcATNESVESITAF-------QCPTCRHVITlsqrgldglkrNVTL 79
Cdd:PLN03208  18 DFDCNICLDQVRDPVVTLCGHLFCWPCIHKWTY---ASNNSRQRVDQYdhkreppKCPVCKSDVS-----------EATL 83

                         90
                 ....*....|....*....
gi 148833499  80 QNIIDRFQKASVSGPNSPS 98
Cdd:PLN03208  84 VPIYGRGQKAPQSGSNVPS 102

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 148833499    10 CPICLELF-EDPLLLPCAHSLCFNCAHRILVSHCATnesvesitafqCPTC 59
Cdd:smart00184   1 CPICLEEYlKDPVILPCGHTFCRSCIRKWLESGNNT-----------CPIC 40

B-Box-type zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 148833499   114 AEKVLCQFCDQdpaQDAVKTCVTCEVSYCDECLKATHpnkkpfTGHR 160
Cdd:smart00336   1 QRAPKCDSHGD---EPAEFFCEECGALLCRTCDEAEH------RGHT 38

PRY/SPRY domain of TRIM18/MID1, also known as FXY or RNF59; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is at the C-terminus of the overall domain architecture of MID1 (also known as FXY, RNF59, TRIM18) gene represented by a RING finger domain (RING), two B-box motifs (BBOX), coiled-coil C-terminal to Bbox domain (BBC) and fibronectin type 3 domain (FN3). Mutations in the human MID1 gene result in X-linked Opitz G/BBB syndrome (OS), a disorder affecting development of midline structures, causing craniofacial, urogenital, gastrointestinal and cardiovascular abnormalities. A unique MID1 gene mutation located in a variable loop in the SPRY domain alters conformation of the binding pocket and may affect the binding affinity to the PRY/SPRY domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499 485 PFKLDPKSAHRKLKVSHDNLTVERDESSSKKSHTPERFTSQGSYGVAGNVFIDSGRHYWEVVISGSTWYAIGLAYKSAPK 564
Cdd:cd12892    1 PFKLDPKSAHRKLKVSHDNLTVERDETSSKKSHTPERFTSQGSYGVAGNVFIDSGRHYWEVVISGSTWYAIGIAYKSAPK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499 565 HEWIGKNSASWALCRCNNNWVVRHNSKEIPIEPAPHLRRVGILLDYDNGSIAFYDALNSIHLYTFDVAFAQPVCPTFTVW 644
Cdd:cd12892   81 HEWIGKNSASWVLCRCNNNWVVRHNSKEIPIEPSPHLRRVGILLDYDNGSLSFYDALNSIHLYTFDIAFAQPVCPTFTVW 160

                        170
                 ....*....|....*..
gi 148833499 645 NKCLTIITGLPIPDHLD 661
Cdd:cd12892  161 NKCLTILTGLPIPDHLD 177

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 148833499 486 FKLDPKSAHRKLKVSHDNLTVERDESSSKKSHTPERFTSQGSYGVAGNVFIDSGRHYWEVVISGSTWYAIGLAYKSAPKH 565
Cdd:cd13734    1 FKLDPKTAHRKLRLSNDNLTVEYDPEGSKDQAAVLPRRFTGSPAVLGDVAISSGRHYWEVSVSRSTSYRVGVAYKSAPRD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499 566 EWIGKNSASWALCRCNNNWVVRHNSKEIPIEPAPHLRRVGILLDYDNGSIAFYDALNSIHLYTFDVAFAQPVCPTFTVWN 645
Cdd:cd13734   81 EDLGKNSTSWCLSRDNNRYTARHDGKVVDLRVTGHPARIGVLLDYDNGTLSFYDAESKQHLYTFHVDFEGPVCPAFAVWN 160

                 ....*
gi 148833499 646 KCLTI 650
Cdd:cd13734  161 GSLTL 165

RING finger, HC subclass, found in midline-2 (MID2) and similar proteins; MID2, also known as midin-2, midline defect 2, RING finger protein 60 (RNF60), or tripartite motif-containing protein 1 (TRIM1), is a probable E3 ubiquitin-protein ligase and is highly related to MID1 that associates with cytoplasmic microtubules along their length and throughout the cell cycle. Like MID1, MID2 associates with the microtubule network and may at least partially compensate for the loss of MID1. Both MID1 and MID2 interacts with Alpha 4, which is a regulatory subunit of PP2-type phosphatases, such as PP2A, and an integral component of the rapamycin-sensitive signaling pathway. MID2 can also substitute for MID1 to control exocytosis of lytic granules in cytotoxic T cells. Loss-of-function mutations in MID2 lead to the human X-linked intellectual disability (XLID). MID2 belongs to the C-I subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxy-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. MID2 hetero-dimerizes in vitro with its paralog MID1.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499   1 METLESELTCPICLELFEDPLLLPCAHSLCFNCAHRILVSHCATNESVESITAFQCPTCRHVITLSQRGL 70
Cdd:cd16754    1 METLESELTCPICLELFEDPLLLPCAHSLCFSCAHRILTSGCASGESIEPPSAFQCPTCRYVISLNHRGL 70

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 148833499 488 LDPKSAHRKLKVSHDNLTVERDESSSKKSHTPERFTSqgSYGVAGNVFIDSGRHYWEVVISGSTWYAIGLAYKSAPKHEW 567
Cdd:cd12874    3 FDPDTAHLNLILSDDLRSVRVGDISQHPPEPPPRFFE--CWQVLGSQSFSSGRHYWEVDVQDDSSWYVGVTYKSLPRKGK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499 568 ---IGKNSASWALCRCNNNWVVRHNSKEIPIEPAPHlRRVGILLDYDNGSIAFYDALNSI-HLYTFDVAFAQPVCPTFTV 643
Cdd:cd12874   81 msnLGRNNGSWCLEWRENEFSAWHNNPETRLPVTPP-RRLGVFLDCDGGSLSFYGVTDGVqLLYTFKAKFTEPLYPAFWL 159

                 .
gi 148833499 644 W 644
Cdd:cd12874  160 G 160

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499 485 PFKLDPKSAHRKLKVSHDNLTVERDESSSKKSHTPERFTSqgSYGVAGNVFIDSGRHYWEVVISGSTWYAIGLAYKSAPK 564
Cdd:cd13733    1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERFDT--CVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNR 78

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 148833499 565 HEWIGKNSAS--WALCRCNNNWVVRHNSKEIPIEPAPHLRRVGILLDYDNGSIAFYDALNSIHLYTFDVAFAQPVCPTF 641
Cdd:cd13733   79 KGKITLSPENgyWTVGLRNGNEYKALTSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDCFTEKLYPYF 157

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        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 148833499 115 EKVLCQFCDQDPAQDAVKTCVTCEVSYCDECLKATHPNKKPFTGHRLIEP 164
Cdd:cd19836    1 EKVLCQFCDQDPAQDAVKTCVTCEVSYCDECLKATHPNKKPFTGHRLIEP 50

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 148833499   538 SGRHYWEVVISGSTWYAIGLAYKSAPKHE--WIGKNSASWALCRCNNNWVVRHNSKEIPIEPAPHLRRVGILLDYDNGSI 615
Cdd:smart00449   1 SGRHYFEVEIGDGGHWRVGVATKSVPRGYfaLLGEDKGSWGYDGDGGKKYHNSTGPEYGLPLQEPGDVIGCFLDLEAGTI 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 148833499   616 AFYDALNSIHLYTF-DVAFAQPVCPTFTVWNKCLTIITGLPI 656
Cdd:smart00449  81 SFYKNGKYLHGLAFfDVKFSGPLYPAFSLGSGNSVRLNFGPL 122

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 148833499  323 NDHARFLQTAKNITERVSMATASSQVLIPEINLNDTFDTFALDFSREKKLLE 374
Cdd:pfam18568   1 TDHARFLQTAKNVHERVSMATASSQVLIPDINLNDAFENFALDFSREKKLLE 52

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499 486 FKLDPKSAHRKLK-------VSHDNLTVErdesSSKKSHTPERFTSQGSygVAGNVFIDSGRHYWEVVISGSTWYAIGLA 558
Cdd:cd12903    1 FKLDERTAHSSLDlfkkdtgVIYRMLGVD----PTKVPQNPERFRDWAV--VLGDTPVTSGRHYWEVTVKRSQEFRIGVA 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499 559 YKSAPKHEWIGKNSASWALCRCNNNWVVRHNSKEIPIEPAPHLRRVGILLDYDNGSIAFYDALNSIHLYTFDVAFAQPVC 638
Cdd:cd12903   75 DVDMSRDECIGTNESSWVFAYAQRKWYAMVANETVPVPLVGKPDRVGLLLDYEAGKLSLVDVEKNSVVHTMSAEFRGPVV 154

                 ....*..
gi 148833499 639 PTFTVWN 645
Cdd:cd12903  155 PAFALWD 161

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 148833499 488 LDPKSAHRKLKVSHDNLTVERDESSSKKSHTPERFTSqgSYGVAGNVFIDSGRHYWEV-VISGSTWyAIGLAYKSAPKHE 566
Cdd:cd12888    4 LDPDTAHPRLVLSEDRKSVRWGDTRQDLPDNPERFDT--WPCVLGCEGFTSGRHYWEVeVGDGGGW-AVGVARESVRRKG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499 567 WIGKNSAS--WALCRCNN-NWVVrhNSKEIPIEPAPHLRRVGILLDYDNGSIAFYDALNSIHLYTFDVAF--AQPVCPTF 641
Cdd:cd12888   81 EISFSPEEgiWAVGQWGGqYWAL--TSPETPLPLSEVPRRIRVYLDYEGGQVAFFDADNEAPIFTFPPASfaGERIFPWF 158

                 ...
gi 148833499 642 TVW 644
Cdd:cd12888  159 WVG 161

PRY/SPRY domain in tripartite motif-containing protein 76 (TRIM76)-like; This domain is similar to the distinct PRY/SPRY subdomain found at the C-terminus of TRIM76, a Class I TRIM protein. TRIM76 (also known as cardiomyopathy-associated protein 5 or CMYA5 or myospryn or SPRYD2) is a muscle-specific member of the TRIM superfamily, but lacks the RING domain. It has been suggested that TRIM76 is involved in two distinct processes, protein kinase A signaling and vesicular trafficking.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499 486 FKLDPKSAHRKLKVSHDNLTVERDESSSKKSHTPE---RFTSqgSYGVAGNVFIDSGRHYWEVVISGSTWYAIGLAYKSA 562
Cdd:cd12899    2 FHLNEDTAHPLLSISEDGFTVVYGEEELPARDLSFsdnSFTR--CVAVMGSLIPVRGKHYWEVEVDEQTEYRVGVAFEDT 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499 563 PKHEWIGKNSASWA----LCRCNNNWVVRHNSKEIPIEPAPHLRRVGILLDYDNGSIAFYDALNSIHLYTFDVAFAQPVC 638
Cdd:cd12899   80 QRNGYLGANNTSWCmrhiITPSRHKYEFLHNGWTPDIRITVPPKKIGILLDYDSGRLSFFNVDLAQHLYTFSCQFQHFVH 159

                        170
                 ....*....|....*..
gi 148833499 639 PTFTVWNK-CLTIITGL 654
Cdd:cd12899  160 PCFSLEKPgALKVHNGI 176

B-box-type 1 zinc finger found in the midline (MID) family; The MID family includes MID1 and MID2. MID1, also known as midin, midline 1 RING finger protein, putative transcription factor XPRF, RING finger protein 59 (RNF59), or tripartite motif-containing protein 18 (TRIM18), is a microtubule-associated E3 ubiquitin-protein ligase implicated in epithelial-mesenchymal differentiation, cell migration and adhesion, and programmed cell death along specific regions of the ventral midline during embryogenesis. MID2, also known as midin-2, midline defect 2, RING finger protein 60 (RNF60), or tripartite motif-containing protein 1 (TRIM1), is highly related to MID1. It associates with the microtubule network and may at least partially compensate for the loss of MID1. Both MID1 and MID2 interacts with alpha4, a regulatory subunit of PP2-type phosphatases, such as PP2A, and an integral component of the rapamycin-sensitive signaling pathway. They also play a central role in the regulation of granule exocytosis, and functional redundancy exists between MID1 and MID2 in cytotoxic lymphocytes (CTL). Both MID1 and MID2 belong to the C-I subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. The type 1 B-box (Bbox1) zinc finger is characterized by a C6H2 zinc-binding consensus motif.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 148833499 116 KVLCQFCDQDPAQDAVKTCVTCEVSYCDECLKATHPNKKPFTGHRLIEP 164
Cdd:cd19801    1 LVPCDVCEKEPPRKAVKTCLTCEVSYCKRCLEATHPNRGPFATHRLVEP 49

B-box-type 2 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. It heterodimerizes in vitro with its paralog MID2. 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 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 148833499 168 SHIRGLMCLEHEDEKVNMYCVTDDQLICALCKLVGRHRDHQVAALSE 214
Cdd:cd19822    1 SHIRGLMCLEHEDEKVNMYCVTDDQLICALCKLVGRHRDHQVAALSD 47

PRY/SPRY domain in tripartite motif-containing domain 65 (TRIM65); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM65 proteins (composed of RING/B-box/coiled-coil core and also known as RBCC proteins). The SPRY/PRY combination is a possible component of immune defense. This protein family has not been characterized.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499 477 GKLKTNSQPFKLDPKSAHRKLKVSHDNLTVERDESSSKKshTPERFTSQGSYGVAGNVFIDSGRHYWEVVISgSTWYAIG 556
Cdd:cd12896    3 AELWKDYRNLTFDPRTANKYLELSRQNRRAKHGRSAARG--VPASPGSFELWQVQCTQSFQHGHHYWEVEVS-SHSVTLG 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499 557 LAYKSAPKHEW------IGKNSASWALC---RCNNNWvvrHNSKEIPIePAPHLRRVGILLDYDNGSIAFY-DALNSIHL 626
Cdd:cd12896   80 VTYPGLPRHKQgghkdnIGRNPCSWGLQiqeDSLQAW---HNGRAQKL-QGVSYRLLGVDLDLEAGTLTFYgLEPGTQRL 155

                        170
                 ....*....|....*
gi 148833499 627 YTFDVAFAQPVCPTF 641
Cdd:cd12896  156 HTFHAIFTQPLYPVF 170

PRY/SPRY domain in tripartite motif-binding protein 39 (TRIM39) and TRIM39-like; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of pyrin, several tripartite motif-containing proteins (TRIMs), including E3 ubiquitin-protein ligase (TRIM21), RET finger protein (RFP)/tripartite motif protein 27 (TRIM27), as well as butyrophilin (Btns) and butyrophilin-like (Btnl) family members, with the exception of Btnl2. Btn and Btnl family members are novel regulators of immune responses, with many of the genes located within the MHC. They are implicated in T-cell inhibition and modulation of epithelial cell-T cell interactions. TRIM21 (also known as RO52, SSA1 or RNF81) is a major autoantigen in autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and Sjorgen's syndrome. TRIM27 (also known as Ret finger protein, RFP or RNF76) negatively regulates CD4 T-cells by ubiquitinating and inhibiting the class II phosphatidylinositol 3 kinase C2beta (PI3K-C2beta), a kinase critical for KCa3.1 channel activation. The PRY/SPRY domain of Pyrin, which is mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1beta processing.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499 488 LDPKSAHRKLKVSHDNLTVERDESSSKKSHTPERFTSQGSygVAGNVFIDSGRHYWEVVISGSTWYAIGLAYKSAPKHEW 567
Cdd:cd13745    7 LDPDTAHPNLVLSEDRKSVRHGDTRQDLPDNPERFDTYPC--VLGAEGFTGGRHYWEVEVGDKTEWTLGVCRESVSRKGE 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499 568 IgknsaswALCRCNNNWVVRHNSKE--------IPIEPAPHLRRVGILLDYDNGSIAFYDALNSIHLYTFDVAFAQPVCP 639
Cdd:cd13745   85 V-------TLSPENGYWTVWLRDGKyealtsppTPLPVSVRPSRVGIFLDYEAGEVSFYNVTDRSHLFTFTDTFSGTLRP 157

                 ..
gi 148833499 640 TF 641
Cdd:cd13745  158 YF 159

B-box-type 2 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 that associate 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. It heterodimerizes in vitro with its paralog MID1. Loss-of-function mutations in MID2 lead to the 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 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 148833499 173 LMCLEHEDEKVNMYCVTDDQLICALCKLVGRHRDHQVAAL 212
Cdd:cd19823    1 LTCLEHENEKVNMYCVVDDQLICALCKLVGRHRDHQVASL 40

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 148833499 485 PFKLDPKSAHRKLKVSHDNLTVERDESSSKKSHTPERFtSQgSYGVAGNVFIDSGRHYWEVVISGSTWYAIGLAyksapk 564
Cdd:cd12905    5 PLTFDPETAHPSLILSRDLTAVTESDEMQPYPRSPKRF-LQ-CVNVLASQGFQSGRHYWEVWVGSKTKWDLGVA------ 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148833499 565 HEWIGKnSASWALCRCNNNWVVR-HNSKE--------IPIEPAPHLRRVGILLDYDNGSIAFYDALNSIHLYTFDVAFAQ 635
Cdd:cd12905   77 SESVDR-QARVKLCPENGYWTLRlRNGDEywagtqpwTRLRVTSRPQRIGVFLDCEERKVSFYNADDMSLLYSFHQGPRG 155

                 ....*..
gi 148833499 636 PVCPTFT 642
Cdd:cd12905  156 KVFPFFS 162