PRY/SPRY domain in tripartite motif-containing protein 46 (TRIM46); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM46 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 yet been characterized.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1825712672 530 NFFLDNRWGFNRERLAISKDQRAVRSVPGLPMLFAAERLMTSCHLSIDLVIGDVAVTQGRSYWACCVDPSSYLVKVGVGL 609
Cdd:cd12895     1 NFFLDSRWGLHRDRLAISKDQRAVRSVPGLPLLQAADRLLTSCHLSVDLVVGDVAITQGRSYWACSVDPGSYLVKVGVGL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1825712672 610 ESKLQEWFQVPQDVVSPRYDPDSGHDSGAEDTTlDTAPPFAFLTIGMGKILL----SHGVALTSRDPG--NCTVPLPPRV 683
Cdd:cd12895    81 ESKLQEWFQLPQDVVSPRYDPDSGHDSGAEDAT-VESPPFAFLTMGMGKIYLpssvSSGHGLTGRDGPpaGCTVPLPPRL 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1825712672 684 GICLDYERGKVTFFDAVSFRSLWECGIDCSGPVCPAFCFIGGGALHLQEL 733
Cdd:cd12895   160 GICLDYEKGRVSFYDAVSFRPLWECPVDCSGPVCPAFCFIGGGALQLQEL 209

B-box-type 2 zinc finger found in tripartite motif-containing protein 46 (TRIM46) and similar proteins; TRIM46, also known as gene Y protein (GeneY) or tripartite, fibronectin type-III and C-terminal SPRY motif protein (TRIFIC), is a microtubule-associated protein that specifically localizes to the proximal axon, partly overlaps with the axon initial segment (AIS) at later stages, and organizes uniform microtubule orientation in axons. It controls neuronal polarity and axon specification by driving the formation of parallel microtubule arrays. TRIM46 belongs to the C-I subclass of TRIM (tripartite motif) family of proteins, which are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1825712672 222 KGLTCPEHREEVTHYCKSCQRLVCQLCRVRRTHTGHKISPVLSAYQ 267
Cdd:cd19786     1 KGLMCPEHKEEVTHYCKTCQRLVCQLCRVRRTHAGHKITPVLSAYQ 46

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 1825712672 372 TDQPCFVQAAKQLHNRIVRATDSLQVFRPAA--SSSFSHFQVDVSRELKLLT 421
Cdd:pfam18568   1 TDHARFLQTAKNVHERVSMATASSQVLIPDInlNDAFENFALDFSREKKLLE 52

coiled-coil (CC) domain of Drosophila brain tumor (brat) and similar proteins; This family contains the coiled-coil (CC) region of Drosophila brain tumor (Brat), a translational repressor that belongs to the tripartite motif (TRIM) protein superfamily. TRIM proteins play important roles in various cellular processes and are involved in many diseases which consists of two B-box domains and a coiled-coil (CC) domain at the N-terminal region, and an NHL domain at the C-terminus. Brat localizes at the basal cortex during asymmetric division of Drosophila neuroblasts by directly interacting with the scaffolding protein Miranda (Mira), which it does through the CC-NHL domain tandem, indicating that the function of the Brat CC domain is to assemble Brat-NHL in dimeric form which is necessary for Mira binding. Brat CC forms an elongated antiparallel dimer similar to its other TRIM protein counterparts, but the overall length of Brat CC dimer is shorter than the TRIMs.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1825712672  269 LKDKLTKSLTYILSNQDTVQAQISELEETLRLTEANGAQAKEEVARLMRGLSALLEEKQSSLLNAIEECRQDRVSNLRAQ 348
Cdd:smart00502   1 QREALEELLTKLRKKAAELEDALKQLISIIQEVEENAADVEAQIKAAFDELRNALNKRKKQLLEDLEEQKENKLKVLEQQ 80

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1825712672  349 LHEHRAMMEN-SGMVGYTQEVLKETDQPCFVQAAKQL 384
Cdd:smart00502  81 LESLTQKQEKlSHAINFTEEALNSGDPTELLLSKKLI 117

PRY/SPRY domain in tripartite motif-containing protein 46 (TRIM46); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM46 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 yet been characterized.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1825712672 530 NFFLDNRWGFNRERLAISKDQRAVRSVPGLPMLFAAERLMTSCHLSIDLVIGDVAVTQGRSYWACCVDPSSYLVKVGVGL 609
Cdd:cd12895     1 NFFLDSRWGLHRDRLAISKDQRAVRSVPGLPLLQAADRLLTSCHLSVDLVVGDVAITQGRSYWACSVDPGSYLVKVGVGL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1825712672 610 ESKLQEWFQVPQDVVSPRYDPDSGHDSGAEDTTlDTAPPFAFLTIGMGKILL----SHGVALTSRDPG--NCTVPLPPRV 683
Cdd:cd12895    81 ESKLQEWFQLPQDVVSPRYDPDSGHDSGAEDAT-VESPPFAFLTMGMGKIYLpssvSSGHGLTGRDGPpaGCTVPLPPRL 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1825712672 684 GICLDYERGKVTFFDAVSFRSLWECGIDCSGPVCPAFCFIGGGALHLQEL 733
Cdd:cd12895   160 GICLDYEKGRVSFYDAVSFRPLWECPVDCSGPVCPAFCFIGGGALQLQEL 209

B-box-type 2 zinc finger found in tripartite motif-containing protein 46 (TRIM46) and similar proteins; TRIM46, also known as gene Y protein (GeneY) or tripartite, fibronectin type-III and C-terminal SPRY motif protein (TRIFIC), is a microtubule-associated protein that specifically localizes to the proximal axon, partly overlaps with the axon initial segment (AIS) at later stages, and organizes uniform microtubule orientation in axons. It controls neuronal polarity and axon specification by driving the formation of parallel microtubule arrays. TRIM46 belongs to the C-I subclass of TRIM (tripartite motif) family of proteins, which are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1825712672 222 KGLTCPEHREEVTHYCKSCQRLVCQLCRVRRTHTGHKISPVLSAYQ 267
Cdd:cd19786     1 KGLMCPEHKEEVTHYCKTCQRLVCQLCRVRRTHAGHKITPVLSAYQ 46

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 1825712672 372 TDQPCFVQAAKQLHNRIVRATDSLQVFRPAA--SSSFSHFQVDVSRELKLLT 421
Cdd:pfam18568   1 TDHARFLQTAKNVHERVSMATASSQVLIPDInlNDAFENFALDFSREKKLLE 52

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 1825712672 443 DQIFLCWRLPQHSPSAW-HYTVEFRRAEPKGkalklWQR--REEVRGTSAMVEYLDTDCVYVLRVKGYNKAGFGDYSEDI 519
Cdd:cd00063    15 TSVTLSWTPPEDDGGPItGYVVEYREKGSGD-----WKEveVTPGSETSYTLTGLKPGTEYEFRVRAVNGGGESPPSESV 89

                  ....
gi 1825712672 520 YLHT 523
Cdd:cd00063    90 TVTT 93

B-Box-type zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1825712672  222 KGLTCPEHREEVTH-YCKSCQRLVCQLCRvRRTHTGHKISPV 262
Cdd:smart00336   2 RAPKCDSHGDEPAEfFCEECGALLCRTCD-EAEHRGHTVVLL 42

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1825712672  269 LKDKLTKSLTYILSNQDTVQAQISELEETLRLTEANGAQAKEEVARLMRGLSALLEEKQSSLLNAIEECRQDRVSNLRAQ 348
Cdd:smart00502   1 QREALEELLTKLRKKAAELEDALKQLISIIQEVEENAADVEAQIKAAFDELRNALNKRKKQLLEDLEEQKENKLKVLEQQ 80

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1825712672  349 LHEHRAMMEN-SGMVGYTQEVLKETDQPCFVQAAKQL 384
Cdd:smart00502  81 LESLTQKQEKlSHAINFTEEALNSGDPTELLLSKKLI 117

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1825712672  23 SMKNMERELLCPVCKEMYKQPLVLPCMHNVCHICATEVLLQQGY--VCPDPTSEPTSPAST 81
Cdd:COG5432    18 SLKGLDSMLRCRICDCRISIPCETTCGHTFCSLCIRRHLGTQPFcpVCREDPCESRLRGSS 78

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1825712672  666 ALTSRDPGNcTVPLPP-RVGICLDYERGKVTFFDA------VSFRSlwecgIDCSGPVCPAFCFIGGGALHL 730
Cdd:smart00449  52 NSTGPEYGL-PLQEPGdVIGCFLDLEAGTISFYKNgkylhgLAFFD-----VKFSGPLYPAFSLGSGNSVRL 117

PRY/SPRY domain in tripartite motif-containing protein 46 (TRIM46); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM46 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 yet been characterized.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1825712672 530 NFFLDNRWGFNRERLAISKDQRAVRSVPGLPMLFAAERLMTSCHLSIDLVIGDVAVTQGRSYWACCVDPSSYLVKVGVGL 609
Cdd:cd12895     1 NFFLDSRWGLHRDRLAISKDQRAVRSVPGLPLLQAADRLLTSCHLSVDLVVGDVAITQGRSYWACSVDPGSYLVKVGVGL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1825712672 610 ESKLQEWFQVPQDVVSPRYDPDSGHDSGAEDTTlDTAPPFAFLTIGMGKILL----SHGVALTSRDPG--NCTVPLPPRV 683
Cdd:cd12895    81 ESKLQEWFQLPQDVVSPRYDPDSGHDSGAEDAT-VESPPFAFLTMGMGKIYLpssvSSGHGLTGRDGPpaGCTVPLPPRL 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1825712672 684 GICLDYERGKVTFFDAVSFRSLWECGIDCSGPVCPAFCFIGGGALHLQEL 733
Cdd:cd12895   160 GICLDYEKGRVSFYDAVSFRPLWECPVDCSGPVCPAFCFIGGGALQLQEL 209

B-box-type 1 zinc finger found in tripartite motif-containing protein 46 (TRIM46) and similar proteins; TRIM46, also known as gene Y protein (GeneY) or tripartite, fibronectin type-III and C-terminal SPRY motif protein (TRIFIC), is a microtubule-associated protein that specifically localizes to the proximal axon, partly overlaps with the axon initial segment (AIS) at later stages, and organizes uniform microtubule orientation in axons. It controls neuronal polarity and axon specification by driving the formation of parallel microtubule arrays. TRIM46 belongs to the C-I subclass of TRIM (tripartite motif) family of proteins, which 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        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1825712672 168 AIMCQFCKPPQLEATKGCTECKSSFCNECFKLYHPWGTQKAQHEPTPPTLTF 219
Cdd:cd19849     1 AIMCQFCKPPQLEATKGCTECRASFCNECFKLYHPWGTQKAQHEPTPPTLTF 52

B-box-type 1 zinc finger found in tripartite motif-containing proteins, TRIM36, TRIM46 and similar proteins; The family includes tripartite motif-containing proteins, TRIM36 and TRIM46, both of which belong to the C-I subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, 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. 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 subsequent 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. TRIM46, also known as gene Y protein (GeneY) or tripartite, fibronectin type-III and C-terminal SPRY motif protein (TRIFIC), is a microtubule-associated protein that specifically localizes to the proximal axon, partly overlaps with the axon initial segment (AIS) at later stages, and organizes uniform microtubule orientation in axons. It controls neuronal polarity and axon specification by driving the formation of parallel microtubule arrays.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1825712672 168 AIMCQFCKPPQLEATKGCTECKSSFCNECFKLYHPWGTQKAQHEPTPPTLTF 219
Cdd:cd19807     1 AIKCQLCKPPPQEATKSCADCVASFCNECFKVVHPWGTPKAQHEYVGPTNNF 52

B-box-type 1 zinc finger 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 subsequent 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 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        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1825712672 166 SAAIMCQFCKPPQLEATKGCTECKSSFCNECFKLYHPWGTQKAQHEPTPPTLTF 219
Cdd:cd19848     2 ATAIMCDLCKPPPQESTKSCMDCKASYCNECFKIHHPWGTPKAQHEYVGPTTNF 55

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 1825712672 372 TDQPCFVQAAKQLHNRIVRATDSLQVFRPAA--SSSFSHFQVDVSRELKLLT 421
Cdd:pfam18568   1 TDHARFLQTAKNVHERVSMATASSQVLIPDInlNDAFENFALDFSREKKLLE 52

RING finger, HC subclass, found in tripartite motif-containing protein 9 (TRIM9) and similar proteins; TRIM9, human ortholog of rat Spring, also known as RING finger protein 91 (RNF91), is a brain-specific E3 ubiquitin-protein ligase collaborating with an E2 ubiquitin conjugating enzyme UBCH5b. TRIM9 plays an important role in the regulation of neuronal functions and participates in the neurodegenerative disorders through its ligase activity. It interacts with the WD repeat region of beta-transducin repeat-containing protein (beta-TrCP) through its N-terminal degron motif depending on the phosphorylation status, and thus negatively regulates nuclear factor-kappaB (NF-kappaB) activation in the NF-kappaB pro-inflammatory signaling pathway. Moreover, TRIM9 acts as a critical catalytic link between Netrin-1 and the exocytic soluble NSF attachment receptor protein (SNARE) machinery in murine cortical neurons. It promotes SNARE-mediated vesicle fusion and axon branching in a Netrin-dependent manner. TRIM9 belongs to the C-I subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1825712672  28 ERELLCPVCKEMYKQPLVLPCMHNVCHICATEVLLQqgyvcpdpTSEPTSPAS 80
Cdd:cd16755     1 EEELKCPVCGSFYREPIILPCSHNLCLACARNILVQ--------TPEAESPQS 45

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        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1825712672  28 ERELLCPVCKEMYKQPLVLPCMHNVCHICATEVLLQQgyvcpdPTSEPTSPASTPAT 84
Cdd:cd16758     1 EEELKCPVCGSLFREPIILPCSHNVCLPCARTIAVQT------PESEQHLPHSSSIT 51

B-box-type 2 zinc finger found in tripartite motif-containing protein 36 (TRIM36) and similar proteins; TRIM36, human ortholog of mouse Haprin, also known as RING finger protein 98 (RNF98) or zinc-binding protein Rbcc728, is an E3 ubiquitin-protein ligase expressed in the germ plasm. It has been implicated in acrosome reaction, fertilization, and embryogenesis, as well as in carcinogenesis. TRIM36 functions upstream of Wnt/beta-catenin activation, and plays a role in controlling the stability of proteins regulating microtubule polymerization during cortical rotation, and subsequently dorsal axis formation. It is also potentially associated with chromosome segregation through interacting with the kinetochore protein centromere protein-H (CENP-H), and colocalizing with the microtubule protein alpha-tubulin. Its overexpression may cause chromosomal instability and carcinogenesis. It is, thus, a novel regulator affecting cell cycle progression. Moreover, TRIM36 plays a critical role in the arrangement of somites during embryogenesis. TRIM36 belongs to the C-I subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1825712672 224 LTCPEHREE-VTHYCKSCQRLVCQLCRVRRTHTGHKISPVLSAY 266
Cdd:cd19778     1 LMCPEHEMEkVNMYCEACRRPVCHLCKLGGSHANHRVTSMSSAY 44

RING finger, HC subclass, found in midline-1 (MID1) and similar proteins; MID1, also known as midin, midline 1 RING finger protein, putative transcription factor XPRF, RING finger protein 59 (RNF59), or tripartite motif-containing protein 18 (TRIM18), is a microtubule-associated E3 ubiquitin-protein ligase implicated in epithelial-mesenchymal differentiation, cell migration and adhesion, and programmed cell death along specific regions of the ventral midline during embryogenesis. It monoubiquinates the alpha4 subunit of protein phosphatase 2A (PP2A), promoting proteosomal degradation of the catalytic subunit of PP2A (PP2Ac) and preventing the A and B subunits from forming an active complex. It promotes allergen and rhinovirus-induced asthma through the inhibition of PP2A activity. It is strongly upregulated in cytotoxic lymphocytes (CTLs) and directs lytic granule exocytosis and cytotoxicity of killer T cells. Loss-of-function mutations in MID1 lead to the human X-linked Opitz G/BBB (XLOS) syndrome characterized by defective midline development during embryogenesis. MID1 belongs to the C-I subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. MID1 hetero-dimerizes in vitro with its paralog MID2.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1825712672  27 MERELLCPVCKEMYKQPLVLPCMHNVCHICATEVLLQQ 64
Cdd:cd16753     2 LESELTCPICLELFEDPLLLPCAHSLCFNCAHRILVSH 39

PRY/SPRY domain of butyrophilin 3 (BTN3), includes BTN3A1, BTN3A2, BTN3A3 as well as BTN-like 3 (BTNL3); BTN3A also known as CD277; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of butyrophilin family 3A (BTN3A); duplication events have led to three paralogs in primates: BTN3A1, BTN3A2, and BTN3A3. BTNs belong to receptor glycoproteins of immunoglobulin (Ig) superfamily, characterized by the presence of extracellular Ig-like domains (IgV and/or IgC). BTN3 transcripts are ubiquitously present in all immune cells (T cells, B cells, NK cells, monocytes, dendritic cells, and hematopoietic precursors) with different expression levels; BTN3A1 and BTN3A2 are expressed mainly by CD4+ and CD8+ T cells, BTN3A2 is the major form expressed in NK cells, and BTN3A3 is poorly expressed in these immune cells. The PRY/SPRY domain of the BTN3A1 isoform mediates phosphoantigen (pAg)-induced activation by binding directly to the pAg.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1825712672 544 LAISKDQRAV-RSVPGLPMLFAAERL-MTSChlsidlVIGDVAVTQGRSYWAccvdpssylVKVGVgleskLQEWF-QVP 620
Cdd:cd15820    17 LLISEDQRSLqWADEPQNLPDNPKRFdWHYC------VLGCKSFTSGRHFWE---------VEVGD-----RKEWYvGVC 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1825712672 621 QDVVSpRYDPdsghdsgaedttLDTAPPFAFLTIGmgkilLSHG---VALTsrDP-GNCTVPLPP-RVGICLDYERGKVT 695
Cdd:cd15820    77 RENVE-RKLW------------VKMAPENGFWTIG-----LSDGndyQALT--DPrTKLTIANPPqRVGVFLDYETGEVS 136

                         170       180
                  ....*....|....*....|....*.
gi 1825712672 696 FFDAVSFRSLWE-CGIDCSGPVCPAF 720
Cdd:cd15820   137 FYNAMDGSHIYTfPHTSFSGPLYPVF 162

RING finger, HC subclass, found in muscle-specific RING finger protein 1 (MuRF-1) and similar proteins; MuRF-1, also known as tripartite motif-containing protein 63 (TRIM63), RING finger protein 28 (RNF28), iris RING finger protein, or striated muscle RING zinc finger, is an E3 ubiquitin-protein ligase in ubiquitin-mediated muscle protein turnover. It is predominantly fast (type II) fibre-associated in skeletal muscle and can bind to many myofibrillar proteins, including titin, nebulin, the nebulin-related protein NRAP, troponin-I (TnI), troponin-T (TnT), myosin light chain 2 (MLC-2), myotilin, and T-cap. The early and robust upregulation of MuRF-1 is triggered by disuse, denervation, starvation, sepsis, or steroid administration resulting in skeletal muscle atrophy. It also plays a role in maintaining titin M-line integrity. It associates with the periphery of the M-line lattice and may be involved in the regulation of the titin kinase domain. It also participates in muscle stress response pathways and gene expression. MuRF-1 belongs to the C-II 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, and an acidic residue-rich (AR) domain. It also harbors a MURF family-specific conserved box (MFC) between its RING-HC finger and Bbox domains.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1825712672  28 ERELLCPVCKEMYKQPLV-LPCMHNVCHICATEVL 61
Cdd:cd16759     1 EKQLICPICLEMFTKPVViLPCQHNLCRKCANDIF 35

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 1825712672 543 RLAISKDQRAVR------SVPGLPMLFAAERlmtsChlsidlVIGDVAVTQGRSYWACCVDPSSYLVkVGVGLES-KLQE 615
Cdd:cd12888    12 RLVLSEDRKSVRwgdtrqDLPDNPERFDTWP----C------VLGCEGFTSGRHYWEVEVGDGGGWA-VGVARESvRRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1825712672 616 WFqvpqdvvspRYDPDSGhdsgaedttldtappfafltI-GMGkilLSHG--VALTSRDPgncTVPLPP---RVGICLDY 689
Cdd:cd12888    81 EI---------SFSPEEG--------------------IwAVG---QWGGqyWALTSPET---PLPLSEvprRIRVYLDY 125

                         170
                  ....*....|..
gi 1825712672 690 ERGKVTFFDAVS 701
Cdd:cd12888   126 EGGQVAFFDADN 137

B-box-type 2 zinc finger found in Xenopus laevis nuclear factor 7 (xNF7) and similar proteins; xNF7 is a maternally expressed novel zinc finger nuclear phosphoprotein. It acts as a transcription factor that determines dorsal-ventral body axis. xNF7 harbors a B-box motif that shows high sequence similarity with B-Box-type zinc finger 2 found in tripartite motif-containing proteins (TRIMs). The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1825712672 226 CPEHREEVTHYCKSCQRLVCQLCRVRRTHTGHKISPV 262
Cdd:cd19800     3 CSEHDEPLKLFCKDDKRLICVICRDSRKHRGHRFLPV 39

RING finger, HC subclass, found in tripartite motif-containing protein 69 (TRIM69) and similar proteins; TRIM69, also known as RFP-like domain-containing protein trimless or RING finger protein 36 (RNF36), is a testis E3 ubiquitin-protein ligase that plays a specific role in apoptosis and may also play an important role in germ cell homeostasis during spermatogenesis. TRIM69 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1825712672  30 ELLCPVCKEMYKQPLVLPCMHNVCHICATEVLLQQG--YVCPD 70
Cdd:cd16611     4 ELHCPLCLDFFRDPVMLSCGHNFCQSCITGFWELQAedTTCPE 46

RING finger, HC subclass, found in tripartite motif-containing protein 8 (TRIM8) and similar proteins; TRIM8, also known as glioblastoma-expressed RING finger protein (GERP) or RING finger protein 27 (RNF27), is a probable E3 ubiquitin-protein ligase that may promote proteasomal degradation of suppressor of cytokine signaling 1 (SOCS1) and further regulate interferon-gamma signaling. It functions as a new p53 modulator that stabilizes p53 impairing its association with MDM2 and inducing the reduction of cell proliferation. TRIM8 deficit dramatically impairs p53 stabilization and activation in response to chemotherapeutic drugs. TRIM8 also modulates tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta)-triggered nuclear factor-kappaB (NF- kappa B) activation by targeting transforming growth factor beta (TGFbeta) activated kinase 1 (TAK1) for K63-linked polyubiquitination. Moreover, TRIM8 modulates translocation of phosphorylated STAT3 into the nucleus through interaction with Hsp90beta and consequently regulates transcription of Nanog in embryonic stem cells. It also interacts with protein inhibitor of activated STAT3 (PIAS3), which inhibits IL-6-dependent activation of STAT3. TRIM8 belongs to the C-V 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 domain, as well as an uncharacterized region positioned C-terminal to the RBCC domain. The coiled coil domain is required for homodimerization and the region immediately C-terminal to the RING motif is sufficient to mediate the interaction with SOCS1.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1825712672  28 ERELLCPVCKEMYKQPLVLPCMHNVCHICATE 59
Cdd:cd16580     9 EEELICPICLHVFVEPVQLPCKHNFCRGCIGE 40

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
                  ....*....|....*....|....*....|....*.
gi 1825712672 169 IMCQFCK--PPQlEATKGCTECKSSFCNECFKLYHP 202
Cdd:cd19836     3 VLCQFCDqdPAQ-DAVKTCVTCEVSYCDECLKATHP 37

RING finger, HC subclass, found in muscle-specific RING finger protein 3 (MuRF-3) and similar proteins; MuRF-3, also known as tripartite motif-containing protein 54 (TRIM54), or RING finger protein 30 (RNF30), is an E3 ubiquitin-protein ligase in ubiquitin-mediated muscle protein turnover. It is ubiquitously detected in all fibre types, is developmentally upregulated, associates with microtubules, the sarcomeric M-line and Z-line, and is required for microtubule stability and myogenesis. It associates with glutamylated microtubules during skeletal muscle development, and is required for skeletal myoblast differentiation and development of cellular microtubular networks. MuRF-3 controls the degradation of four-and-a-half LIM domain (FHL2) and gamma-filamin and is required for maintenance of ventricular integrity after myocardial infarction (MI). MuRF-3 belongs to the C-II 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, and an acidic residue-rich (AR) domain. It also harbors a MURF family-specific conserved box (MFC) between its RING-HC finger and Bbox domains.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1825712672  31 LLCPVCKEMYKQPLV-LPCMHNVCHICATEVL 61
Cdd:cd16761     1 LICPICLEMFTKPVViLPCQHNLCRKCANDVF 32

PRY/SPRY domain of tripartite motif-binding protein 5, 6, 22 and 34 (TRIM5, TRIM6, TRIM22 and TRIM34); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of very close paralogs, TRIM5, TRIM6, TRIM22 and TRIM34. These domains are composed of RING/B-box/coiled-coil core and are also known as RBCC proteins. They form a locus of four closely related TRIM genes within an olfactory receptor-rich region on chromosome 11 of the human genome. Genetic analysis of this locus indicates that these four genes have evolved by gene duplication from a common ancestral gene. All genes in the TRIM6/TRIM34/TRIM5/TRIM22 locus are type I interferon inducible, with TRIM5 and TRIM22 possessing antiviral properties. TRIM5 promotes innate immune signaling by activating the TAK1 kinase complex by cooperating with the heterodimeric E2, UBC13/UEV1A. It also stimulates NFkB and AP-1 signaling, and the transcription of inflammatory cytokines and chemokines, amplifying these activities upon retroviral infection. Interaction of its PRY-SPRY or cyclophilin domains with the retroviral capsid lattice stimulates the formation of a complementary lattice by TRIM5, with greatly increased TRIM5 E3 activity, and host cell signal transduction. TRIM6 is selectively expressed in embryonic stem (ES) cells and interacts with the proto-oncogene product Myc, maintaining the pluripotency of the ES cells. TRIM6, together with E2 Ubiquitin conjugase (UbE2K) and K48-linked poly-Ub chains, is critical for the IkappaB kinase epsilon (IKKepsilon) branch of type I interferon (IFN-I) signaling pathway and subsequent establishment of a protective antiviral response. TRIM22 plays an integral role in the host innate immune response to viruses; it has been shown to inhibit the replication of a number of viruses, including HIV-1, hepatitis B, and influenza A. Altered TRIM22 expression has also been associated with multiple sclerosis, cancer, and autoimmune disease. While the PRY-SPRY domain of TRIM5a provides specificity and the capsid recognition motif to retroviral restriction, TRIM34 binds HIV-1 capsid but does not restrict HIV-1 infection.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1825712672 544 LAISKDQRAVRSVPGLPMLFAAERLMTSCHlsidlVIGDVAVTQGRSYW-------------ACCVDPSSYLVKVGVGLE 610
Cdd:cd15810    13 IVISEDQRQVRIVPPQTSGQALTNNNYDFG-----VLGSQYFSSGKHYWevdvskksawilgVCSHKRSDAMTKSNANQI 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1825712672 611 SKlqewfqvpQDVVSpRYDPDSGhdsgaedttldtappfaFLTIGmgkilLSHGVALT------SRDPGNCT--VPLPP- 681
Cdd:cd15810    88 NH--------QNVYS-RYQPQYG-----------------YWVIG-----LQNESEYNafedssSFNPHVLTlsVTVPPh 136

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 1825712672 682 RVGICLDYERGKVTFFDAVSFRSLWECGIDC--SGPVCPAF 720
Cdd:cd15810   137 RVGVFLDYEAGTVSFFNVTNHGSLIYKFSKCcfSTTVCPYF 177

RING finger, HC subclass, found in muscle-specific RING finger proteins TRIM63/MuRF-1, TRIM55/MuRF-2 and TRIM54/MuRF-3; This subfamily corresponds to a group of striated muscle-specific tripartite motif (TRIM) proteins, including TRIM63/MuRF-1, TRIM55/MuRF-2, and TRIM54/MuRF-3, which function as E3 ubiquitin ligases in ubiquitin-mediated muscle protein turnover. They are tightly developmentally regulated in skeletal muscle and associate with different cytoskeleton components, such as microtubules, Z-disks and M-bands, as well as with metabolic enzymes and nuclear proteins. They also cooperate with diverse proteins implicated in selective protein degradation by the proteasome and autophagosome, and target proteins of metabolic regulation, sarcomere assembly and transcriptional regulation. Moreover, MURFs display variable fibre-type preferences. TRIM63/MuRF-1 is predominantly fast (type II) fibre-associated in skeletal muscle. TRIM55/MuRF-2 is predominantly slow-fibre associated. TRIM54/MuRF-3 is ubiquitously present. They play an active role in microtubule-mediated sarcomere assembly. MuRFs belong to the C-II subclass of the TRIM 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, and an acidic residue-rich (AR) domain positioned C-terminal to the RBCC domain. They also harbor a MURF family-specific conserved box (MFC) between its RING-HC finger and Bbox domains.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1825712672  31 LLCPVCKEMYKQPLV-LPCMHNVCHICATEVLLQQGYVCPDPTS 73
Cdd:cd16577     1 LICPICLEMFTKPVViLPCQHNLCRKCANDIFQARNPYWPTTTM 44

RING finger, HC subclass, found in midline-1 (MID1), midline-2 (MID2) and similar proteins; MID1, also known as midin, midline 1 RING finger protein, putative transcription factor XPRF, RING finger protein 59 (RNF59), or tripartite motif-containing protein 18 (TRIM18), is a microtubule-associated E3 ubiquitin-protein ligase implicated in epithelial-mesenchymal differentiation, cell migration and adhesion, and programmed cell death along specific regions of the ventral midline during embryogenesis. MID2, also known as midin-2, midline defect 2, RING finger protein 60 (RNF60), or tripartite motif-containing protein 1 (TRIM1), 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. They also play a central role in the regulation of granule exocytosis. Functional redundancy exists between MID1 and MID2 in cytotoxic lymphocytes (CTL). Both MID1 and MID2 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, 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        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1825712672  31 LLCPVCKEMYKQPLVLPCMHNVCHICATEVLLQqgYVCPDPTSEPTSPASTPATR 85
Cdd:cd16575     1 LTCPICLELFEDPLLLPCAHSLCFNCAHRILVS--HCASNESVESITAFQCPTCR 53

B-box-type 2 zinc finger found in tripartite motif-containing protein 11 (TRIM11) and similar proteins; TRIM11, also known as protein BIA1, or RING finger protein 92 (RNF92), is an E3 ubiquitin-protein ligase involved in the development of the central nervous system. It is overexpressed in high-grade gliomas and promotes proliferation, invasion, migration and glial tumor growth. TRIM11 acts as a potential therapeutic target for congenital central hypoventilation syndrome (CCHS) through mediating the degradation of CCHS-associated polyalanine-expanded Phox2b. Trim11 modulates the function of neurogenic transcription factor Pax6 through the ubiquitin-proteosome system, and thus plays an essential role for Pax6-dependent neurogenesis. It also binds to and destabilizes a key component of the activator-mediated cofactor complex (ARC105), humanin, a neuroprotective peptide against Alzheimer's disease-relevant insults, and further regulates ARC105 function in transforming growth factor beta (TGFbeta) signaling. Moreover, TRIM11 negatively regulates retinoic acid-inducible gene-I (RIG-I)-mediated interferon-beta (IFNbeta) production and antiviral activity by targeting TANK-binding kinase-1 (TBK1). It may contribute to the endogenous restriction of retroviruses in cells. It enhances N-tropic murine leukemia virus (N-MLV) entry by interfering with Ref1 restriction. It also suppresses the early steps of human immunodeficiency virus HIV-1 transduction, resulting in decreased reverse transcripts. TRIM11 belongs to the C-IV subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1825712672 226 CPEHREEVTHYCKSCQRLVCQLCRVRRTHTGHKISPVLSAYQ 267
Cdd:cd19766     3 CGKHREPLKLFCKDHEALLCVVCERSREHWGHRVVPAEEAAQ 44

RING finger, HC subclass, found in promyelocytic leukemia protein (PML) and similar proteins; Protein PML, also known as RING finger protein 71 (RNF71) or tripartite motif-containing protein 19 (TRIM19), is predominantly a nuclear protein with a broad intrinsic antiviral activity. It is the eponymous component of PML nuclear bodies (PML NBs) and has been implicated in a wide variety of cell processes, including DNA damage signaling, apoptosis, and transcription. PML interferes with the replication of many unrelated viruses, including human immunodeficiency virus 1 (HIV-1), human foamy virus (HFV), poliovirus, influenza virus, rabies virus, EMCV, adeno-associated virus (AAV), and vesicular stomatitis virus (VSV). It also selectively interacts with misfolded proteins through distinct substrate recognition sites and conjugates these proteins with the small ubiquitin-like modifiers (SUMOs) through its SUMO ligase activity. PML 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, as well as an uncharacterized region positioned C-terminal to the RBCC domain.

                          10        20
                  ....*....|....*....|....*.
gi 1825712672  31 LLCPVCKEMYKQPLVLPCMHNVCHIC 56
Cdd:cd16579     5 LRCPGCKAEYKCPKLLPCLHTVCSGC 30

B-box-type 2 zinc finger found in tripartite motif-containing protein TRIM50, TRIM73, TRIM74 and similar proteins; TRIM50 is a stomach-specific E3 ubiquitin-protein ligase, encoded by the Williams-Beuren syndrome (WBS) TRIM50 gene, which regulates vesicular trafficking for acid secretion in gastric parietal cells. It colocalizes, interacts with, and increases the level of p62/SQSTM1, a multifunctional adaptor protein implicated in various cellular processes including the autophagy clearance of polyubiquitinated protein aggregates. It also promotes the formation and clearance of aggresome-associated polyubiquitinated proteins through the interaction with the histone deacetylase 6 (HDAC6), a tubulin specific deacetylase that regulates microtubule-dependent aggresome formation. TRIM50 can be acetylated by PCAF and p300. TRIM50 belongs to the C-IV subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, 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. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif. The family also includes two paralogs of TRIM50, tripartite motif-containing protein 73 (TRIM73), also known as tripartite motif-containing protein 50B (TRIM50B), and tripartite motif-containing protein 74 (TRIM74), also known as tripartite motif-containing protein 50C (TRIM50C), both of which are WBS-related genes encoding proteins and may also act as E3 ligases. In contrast with TRIM50, TRIM73 and TRIM74 belong to the C-V subclass of TRIM family of proteins that are defined by the N-terminal RBCC domains only.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1825712672 225 TCPEHREEVTHYCKSCQRLVCQLCRVRRTHTGHKISPV 262
Cdd:cd19787     2 SCPHHHNPLSLFCEKDQEVICGLCGLIGSHRQHKITPV 39

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

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1825712672   33 CPVCKE-MYKQPLVLPCMHNVCHICATEVLLQQGYVCP 69
Cdd:smart00184   1 CPICLEeYLKDPVILPCGHTFCRSCIRKWLESGNNTCP 38

Ret finger protein-like (RFPL), includes RFP1, 2, 3, 4; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of RFPL protein family, which includes RFPL1, RFPL2, RFPL3 and RFPL4. In humans, RFPL transcripts can be detected at the onset of neurogenesis in differentiating human embryonic stem cells, and in the developing human neocortex. The human RFPL1, 2, 3 genes have a role in neocortex development. RFPL1 is a primate-specific target gene of Pax6, a key transcription factor for pancreas, eye and neocortex development; human RFPL1 decreases cell number through its RFPL-defining motif (RDM) and SPRY domains. The RFPL4 (also known as RFPL4A) gene encodes a putative E3 ubiquitin-protein ligase expressed in adult germ cells and interacts with oocyte proteins of the ubiquitin-proteasome degradation pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1825712672 543 RLAISKDQRAVRS--VPGLPMLfAAERLMTS-ChlsidlVIGDVAVTQGRSYWaccvdpssylvKVGVGlesKLQEWfqv 619
Cdd:cd15821    16 YLIISEDLRSVRCgcFRQNRKE-LAERFDDAlC------VLGSPRFTSGRHYW-----------EVDVG---TSTEW--- 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1825712672 620 pqDVVSPRydpDSGHDSGaeDTTLdtAPPFAFLTIGM--GKILLSHGVALTsrdpGNCTVPLPPRVGICLDYERGKVTFF 697
Cdd:cd15821    72 --DLGVCR---ESVNRQG--PIEL--SPEHGFWTVSLrdGSVFFASTVPLT----VLWVNPRLHRVGIFLDMEMGTISFY 138

                         170       180       190
                  ....*....|....*....|....*....|..
gi 1825712672 698 DAvsfrslwECG--------IDCSGPVCPAFC 721
Cdd:cd15821   139 DV-------SDGshiftftkISAEEPLRPFFA 163

B-box-type 1 zinc finger (Bbox1); The B-box-type zinc finger is a short zinc binding domain of around 40 amino acid residues in length. It has been found in transcription factors, ribonucleoproteins and proto-oncoproteins, such as in TRIM (tripartite motif) proteins that consist of an N-terminal RING finger (originally called an A-box), followed by 1-2 B-box domains and a coiled-coil domain (also called RBCC for Ring, B-box, Coiled-Coil). The B-box-type zinc finger often presents in combination with other motifs, like RING zinc finger, NHL motif, coiled-coil or RFP domain, in functionally unrelated proteins, most likely mediating protein-protein interactions. Based on different consensus sequences and the spacing of the 7-8 zinc-binding residues, the B-box-type zinc fingers can be divided into two groups, type 1 (Bbox1: C6H2) and type 2 (Bbox2: CHC3H2). This family corresponds to the type 1 B-box (Bbox1).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1825712672 170 MCQFCKppQLEATKGCTECKSSFCNECFKLYHPWGTQKAQHEPTP 214
Cdd:cd19757     1 LCDECE--EREATVYCLECEEFLCDDCSDAIHRRGKLTRSHKLVP 43

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1825712672 544 LAISKDQRAVR------SVPGLPMLFAAErlmtschlsiDLVIGDVAVTQGRSYWaccvdpssylvKVGVGLESKLQEWF 617
Cdd:cd15826    13 LVLSEDRKSVRytrqkqNLPDSPLRFDGL----------PAVLGSPGFSSGRHRW-----------QVEVQLGDGGGCTV 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1825712672 618 QVPQDVVSPRYDPDSGhdsgAEDttldtappfafltiGMGKILLSHGVALTSRDPGNCTVP--LPPRVGICLDYERGKVT 695
Cdd:cd15826    72 GVAGESVRRKGEMGLS----AED--------------GVWAVILSHQQCWASTSPGTDLPLseIPRRVGVALDYEAGTVT 133

                         170       180
                  ....*....|....*....|....*
gi 1825712672 696 FFDAVSFRSLWECGIDCSGPVCPAF 720
Cdd:cd15826   134 LTNAETQEPIFTFTASFSGKVFPFF 158

B-box-type 1 zinc finger found in tripartite motif-containing protein 42 (TRIM42) and similar proteins; TRIM42 belongs to the C-III 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 domain. It also has a novel cysteine-rich motif N-terminal to the RBCC domain, as well as a COS (carboxyl-terminal subgroup one signature) box and a fibronectin type-III (FN3) 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. TRIM42 can interact with TRIM27, a known cancer-associated protein. Its precise biological function remains unclear.

                          10        20        30
                  ....*....|....*....|....*....|...
gi 1825712672 169 IMCQFCKPPQLEATKGCTECKSSFCNECFKLYH 201
Cdd:cd19808     2 IFCQICTQKRESAVKRCITCRLNLCNKCLRKLH 34