B-box-type zinc finger superfamily; 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, B-box-type zinc fingers can be divided into two groups, type 1 (Bbox1: C6H2) and type 2 (Bbox2: CHC3H2).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1572616305  69 LCPEHFEPLSWFCLSERRPVCATCAGFgGRCHRHRIRRAEEHA 111
Cdd:cd19834     2 LCPDHELELDWFCSTERRLVCAQCASL-GTCRGHRVTPLEERA 43

associated with SPRY domains;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1572616305  278 EEVLIDERTVSPLLHLSEDRRTLTFIAKKSkVCSDEPERFDHWPNALAATAF 329
Cdd:smart00589   2 VDVTLDPDTAHPYLLLSEDRRSVRYGDLKQ-SLPDNPERFDSYPCVLGSQGF 52

SPRY-associated domain; PRY is a 50-60 amino acids domain associated with SPRY domains, adjacent to its N-terminal. PRY and SPRY domains are structurally very similar and consist of a beta sandwich fold. Distant homologs are domains in butyrophilin/marenostrin/pyrin, evolutionarily more ancient than SPRY/B30.2 counterpart.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1572616305 280 VLIDERTVSPLLHLSEDRRTLTFIAKKSKVcSDEPERFDHWPNALAATAF 329
Cdd:pfam13765   1 VTLDPNTAHPSLVLSEDLKSVRYGDERQNV-PDNPERFDSWPCVLGSEGF 49

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 1572616305 281 LIDERTVSPLLHLSEDRRTLTFIAKKSKVC-SDEPERFDHWPNALAATAFQTGLHAWIVNVKHSCAYKVGVASDQLPRkg 359
Cdd:cd13734     2 KLDPKTAHRKLRLSNDNLTVEYDPEGSKDQaAVLPRRFTGSPAVLGDVAISSGRHYWEVSVSRSTSYRVGVAYKSAPR-- 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 360 sgnDCRLGHNAFSWVFSRYDQEFCFSHNGYHEPLPLLRCPAQLGMLLDLQAGELVFYEPASGTVLHIHRASFPQVLFPVF 439
Cdd:cd13734    80 ---DEDLGKNSTSWCLSRDNNRYTARHDGKVVDLRVTGHPARIGVLLDYDNGTLSFYDAESKQHLYTFHVDFEGPVCPAF 156

                         170
                  ....*....|
gi 1572616305 440 AVADQLISIV 449
Cdd:cd13734   157 AVWNGSLTLH 166

PRY/SPRY domain in tripartite motif-containing (TRIM) proteins, including TRIM14-like, TRIM16-like, TRIM25-like, TRIM47-like, TRIM65 and RNF135, and stonustoxin; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several Class I TRIM proteins, including TRIM14, TRIM16 and TRIM25, TRIM47 as well as RING finger protein RNF135 and stonustoxin, a secreted poisonous protein of the stonefish Synanceja horrida. TRIM16 (also known as estrogen-responsive B box protein or EBBP) has E3 ubiquitin ligase activity. It is a regulator of keratinocyte differentiation and a tumor suppressor in retinoid-sensitive neuroblastoma. TRIM25 (also called Efp) ubiquitinates the N terminus of the viral RNA receptor retinoic acid-inducible gene-I (RIG-I) in response to viral infection, leading to activation of the RIG-I signaling pathway, thus resulting in type I interferon production to limit viral replication. It has been shown that the influenza A virus targets TRIM25 and disables its antiviral function. TRIM47, also known as GOA (Gene overexpressed in astrocytoma protein) or RNF100 (RING finger protein 100), is highly expressed in kidney tubular cells, but low expressed in most tissue. It is overexpressed in astrocytoma tumor cells and plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis. RNF135 ubiquitinates RIG-I (retinoic acid-inducible gene-I) to promote interferon-beta induction during the early phase of viral infection. Stonustoxin (STNX) is a hypotensive and lethal protein factor that also possesses other biological activities such as species-specific hemolysis (due to its ability to form pores in the cell membrane) and platelet aggregation, edema-induction, and endothelium-dependent vasorelaxation (mediated by the nitric oxide pathway and activation of potassium channels). The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 280 VLIDERTVSPLLHLSEDRRTLTFIAKkSKVCSDEPERFDHWpNALAATAFQTGLHAWIVNVKHSCAYKVGVASDQLPRKG 359
Cdd:cd12891     1 LTLDPNTAHNNLALSGDLKTVTCSSE-NQHYPDSPERFTHS-QVLSTQSFSSGRHYWEVEVSESGGWSVGVAYPSIERKG 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 360 sgNDCRLGHNAFSWVFSRYDQEFCFSHNGYHEPLPLLRCPaQLGMLLDLQAGELVFYEpASGTVLHIHR--ASFPQVLFP 437
Cdd:cd12891    79 --DESRIGRNDKSWCLEWQDKSFSAWHNNEETPLPSVSSR-RLGVYLDYEAGRLSFYE-LSDPIRHLHTftATFTEPLHP 154

                  ....
gi 1572616305 438 VFAV 441
Cdd:cd12891   155 AFWV 158

PRY/SPRY domain of tripartite motif-binding protein 14 (TRIM14); This is a TRIM14 domain family 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. TRIM14 domains have yet to be characterized. These B30.2 domains are a more recent adaptation where the SPRY/PRY combination is a possible component of immune defense. It belongs to Class IV TRIM protein family which has members involved in antiviral immunity at various levels of interferon signaling cascade.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 282 IDERTVSPLLHLSEDRRTLTfIAKKSKVCSDEPERFDHWPNALAATAFQTGLHAWIVNVKHSCA-YKVGVASDQLPRKGS 360
Cdd:cd13738     3 LEPDTLHPRLRLSDDRLTVS-CGWLGTLGLCPPQRFDKLWQVLSRDSFFSGRHYWEVDLQEAGAgWWVGAAYPSIGRKGD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 361 GNDCRLGHNAFSWVFSRYDQEFCFSHNGYHEPLPLLRCPAQLGMLLDLQAGELVFYEPASG-TVLHIHRASFPQVLFPVF 439
Cdd:cd13738    82 SEAARLGWNRQSWCLKRYDLEYWAFHDGQRSRLRPEDDPDRLGVFLDYEAGILSFYDVTGGmTHLHTFRATFQEPLYPAL 161

                         170
                  ....*....|.
gi 1572616305 440 AVADQLISIVR 450
Cdd:cd13738   162 RLWEGSISICK 172

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 1572616305 280 VLIDERTVSPLLHLSEDRRTLTFIAKKSKVCsDEPERFDHWPNALAATAFQTGLHAWIVNVK----HSCAykVGVASDQL 355
Cdd:cd15826     2 VTLDPQTASGSLVLSEDRKSVRYTRQKQNLP-DSPLRFDGLPAVLGSPGFSSGRHRWQVEVQlgdgGGCT--VGVAGESV 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 356 PRKGSgndcrLGHNAFSWVFS-RYDQEFCFSHNGYHEPLPLLRCPAQLGMLLDLQAGELVFYEPASGTVLHIHRASFPQV 434
Cdd:cd15826    79 RRKGE-----MGLSAEDGVWAvILSHQQCWASTSPGTDLPLSEIPRRVGVALDYEAGTVTLTNAETQEPIFTFTASFSGK 153

                  ....*..
gi 1572616305 435 LFPVFAV 441
Cdd:cd15826   154 VFPFFAV 160

PRY/SPRY domain of tripartite motif-binding protein 60 and 75 (TRIM60 and TRIM75); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM60 and TRIM75, both composed of RING/B-box/coiled-coil core and also known as RBCC proteins. TRIM60 domain is also known as RING finger protein 33 (RNF33) or 129 (RNF129). Based on its expression profile, RNF33 likely plays an important role in the spermatogenesis process, the development of the pre-implantation embryo, and in testicular functions; Rnf33 is temporally transcribed in the unfertilized egg and the pre-implantation embryo, and is permanently silenced before the blastocyst stage. Mice experiments have shown that RNF33 associates with the cytoplasmic motor proteins, kinesin-2 family members 3A (KIF3A) and 3B (KIF3B), suggesting possible contribution to cargo movement along the microtubule in the expressed sites. TRIM75, also known as Gm794, has a single site of positive selection in its RING domain associated with E3 ubiquitin ligase activity. It has not been detectably expressed experimentally due to their constant turnover by the proteasome, and therefore not been characterized.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 279 EVLIDERTVSPLLHLSEDRRTLTFIAKKSKVCsDEPERFDHWPNALAATAFQTGLHAWIVNVKHSCAYKVGVASDQLPRK 358
Cdd:cd15817     1 DLILDPETAHPNLIVSEDRKAVRYRRMKPNCP-YDPRRFTVYPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSLPRN 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 359 GSGNDCRLGHnafSWVFSRYDQEFCFSHNGYhEPLPLLRCPAQLGMLLDLQAGELVFYEPASGTVLHIHRASFPQVLFPV 438
Cdd:cd15817    80 AQDPPSPLGG---CWQIGRYMSGYVASGPKT-TQLLPVVKPSRIGIFLDYELGEVSFYNMNDRSHLYTFTDTFTGKLIPY 155

                  ...
gi 1572616305 439 FAV 441
Cdd:cd15817   156 FYV 158

PRY/SPRY domain of tripartite motif-binding protein 60 (TRIM60) also known as RING finger protein 33 (RNF33); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM60, which is also known as RING finger protein 33 (RNF33) or 129 (RNF129). TRIM60 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. Based on its expression profile, RNF33 likely plays an important role in the spermatogenesis process, the development of the pre-implantation embryo, and in testicular functions; Rnf33 is temporally transcribed in the unfertilized egg and the pre-implantation embryo, and is permanently silenced before the blastocyst stage. Mice experiments have shown that RNF33 associates with the cytoplasmic motor proteins, kinesin-2 family members 3A (KIF3A) and 3B (KIF3B), suggesting possible contribution to cargo movement along the microtubule in the expressed sites.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 279 EVLIDERTVSPLLHLSEDRRTLTFIAKKSKVCSDePERFDHWPNALAATAFQTGLHAWIVNVKHSCAYKVGVASDQLPRK 358
Cdd:cd15828    11 DVTLDPETAHPQLTVSEDRKSVLYGEMKQNVCYN-PRRFYLCPAVLGSEGFHSGRQYWEVEVGDKPEWTLGVCQDCLPRN 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 359 GSgndcrlghNAFS-----WVFSRYdqefcfSHNGY-------HEPLPLLRcPAQLGMLLDLQAGELVFYEPASGTVLHI 426
Cdd:cd15828    90 WS--------NQPSvqdglWAIGRY------SESNYvalgpkkIQLLPKVR-PSKIGIFLDYELGEVSFYNMNDRSLLYT 154

                         170
                  ....*....|...
gi 1572616305 427 HRASFPQVLFPVF 439
Cdd:cd15828   155 FSDSFTGTLWPYF 167

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 1572616305 307 SKVcSDEPERFDHWPNALAATAFQTGLHAWIVNVKHSCAYKVGVASDQLPRkgsgNDCrLGHNAFSWVFSRYDQEFCFSH 386
Cdd:cd12903    31 TKV-PQNPERFRDWAVVLGDTPVTSGRHYWEVTVKRSQEFRIGVADVDMSR----DEC-IGTNESSWVFAYAQRKWYAMV 104

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1572616305 387 NGYHEPLPLLRCPAQLGMLLDLQAGELVFYEPASGTVLHIHRASFPQVLFPVFAVAD 443
Cdd:cd12903   105 ANETVPVPLVGKPDRVGLLLDYEAGKLSLVDVEKNSVVHTMSAEFRGPVVPAFALWD 161

butyrophilin subfamily member A1 and A2 (BTN1A and BTN2A); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of butyrophilin family 1A and 2A (BTN1A and BTN2A). BTNs belong to receptor glycoproteins of immunoglobulin (Ig) superfamily, characterized by the presence of extracellular Ig-like domains (IgV and/or IgC). BTN1A plays a role in the secretion, formation and stabilization of milk fat globules. The B30.2 domain of BTN1A1 binds the enzyme xanthine oxidoreductase (XOR) in order to participate in milk fat globule secretion; this interaction may lead to the production of reactive oxygen species, which have immunomodulatory and antimicrobial functions. Duplication events have led to three paralogs of BTN2A in primates: BTN2A1, BTN2A2, and BTN2A3. In humans, only BTN2A1 has been functionally characterized; it has been detected on epithelial cells and leukocytes, and identified as a novel ligand of dendritic cell-specific ICAM-3 grabbing nonintegrin (DCSIGN), a C-type lectin receptor that acts as an internalization receptor for HIV-1, HCV, and other pathogens. BTN2A2 mRNA has been shown to be expressed in circulating human immune cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 280 VLIDERTVSPLLHLSEDRRTLTFIAKKSKVCSDePERFDHWPNALAATAFQTGLHAWIVNVKHSCAYKVGVASDQLPRKG 359
Cdd:cd15819     4 VTLDPDTAHPALILSEDGRSVTWGETRQDLPEN-PERFDSLPCVLGQEGFTSGRHYWEVEVGDRTSWDLGVCRDNVMRKG 82

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1572616305 360 SgnDCRLGHNAFsWVFSRYDQEFcFSHNGYHEPLPLLRCPAQLGMLLDLQAGELVFYEPASGTvlHIHraSFPQVLF 436
Cdd:cd15819    83 R--VTLSPENGF-WAIRLYGNEY-WALTSPETPLTLKEPPRRVGIFLDYEAGDVSFYNMTDGS--HIY--TFPQTAF 151

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 1572616305 278 EEVLIDERTVSPLLHLSEDRRTLTFiAKKSKVCSDEPERFDHWPNALAATAFQTGLHAWIVNVKHSCAYKVGVASDQLPR 357
Cdd:cd15820     4 ADVILDPDTANPILLISEDQRSLQW-ADEPQNLPDNPKRFDWHYCVLGCKSFTSGRHFWEVEVGDRKEWYVGVCRENVER 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 358 KGSGNdcRLGHNAFsWVFSRYDQefcfshNGYH---EP---LPLLRCPAQLGMLLDLQAGELVFYEPASGTvlHIH---R 428
Cdd:cd15820    83 KLWVK--MAPENGF-WTIGLSDG------NDYQaltDPrtkLTIANPPQRVGVFLDYETGEVSFYNAMDGS--HIYtfpH 151

                         170
                  ....*....|.
gi 1572616305 429 ASFPQVLFPVF 439
Cdd:cd15820   152 TSFSGPLYPVF 162

PRY/SPRY domain of tripartite motif-binding protein 75 (TRIM75); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM75, also known as Gm794. TRIM75 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. TRIM75 has a single site of positive selection in its RING domain associated with E3 ubiquitin ligase activity. It has not been detectably expressed experimentally due to their constant turnover by the proteasome, and therefore not been characterized.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 278 EEVLIDERTVSPLLHLSEDRRTLTFIAKKSKVcSDEPERFDHWPNALAATAFQTGLHAWIVNVKHSCAYKVGVASDQLPR 357
Cdd:cd15829    19 VDVTLDPETAHPNLLVSEDKKCVTFTKKKQRV-PDSPKRFTVNPVVLGFPGFHSGRHFWEVEVGDKPEWAVGVCKDSLST 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 358 KG----SGNDCRlghnafsWVFSRYDqefcfshNGYHE------PLPLLRCPAQLGMLLDLQAGELVFYEPASGTVLHIH 427
Cdd:cd15829    98 KArrppSGQQGC-------WRIQLQG-------GDYDApgavppPLLLEVKPRGIGVFLDYELGEISFYNMPEKSHIHTF 163

                         170
                  ....*....|....
gi 1572616305 428 RASFPQVLFPVFAV 441
Cdd:cd15829   164 TDTFSGPLRPYFYV 177

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 1572616305 279 EVLIDERTVSPLLHLSEDRRTLTFIAKKSKVcSDEPERFDHWPNALAATAFQTGLHAWIVNV--KHSCAykVGVASDQLP 356
Cdd:cd12888     1 NVTLDPDTAHPRLVLSEDRKSVRWGDTRQDL-PDNPERFDTWPCVLGCEGFTSGRHYWEVEVgdGGGWA--VGVARESVR 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 357 RKGsgnDCRLGHNAFSWVFSRYDQEFCFSHNgYHEPLPLLRCPAQLGMLLDLQAGELVFYEPASGTVLHIHRASFP--QV 434
Cdd:cd12888    78 RKG---EISFSPEEGIWAVGQWGGQYWALTS-PETPLPLSEVPRRIRVYLDYEGGQVAFFDADNEAPIFTFPPASFagER 153

                  ....*...
gi 1572616305 435 LFPVFAVA 442
Cdd:cd12888   154 IFPWFWVG 161

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 283 DERTVSPLLHLSEDRRTLTfIAKKSKVCSDEPERFD--HWpnaLAATAFQTGLHAWIVNVKHSCAYKVGVASdqlprKGS 360
Cdd:cd12902     4 DLRSLSCSLEVSEDSRKVT-VSHGPQAYAWSPDRFSisQV---LCSQAFSSGQHYWEVDTRQCSHWAVGVAS-----WEM 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 361 GNDCRLGHNAFSWVFS-RYDQEFCFSHNGYHEPLPLlRCPAQLGMLLDLQAGELVFYEPASG-TVLHIHRASFPQVLFPV 438
Cdd:cd12902    75 SRDQMLGRTMDSWCIEwKGTGQLSAWHMNKETVLGS-DKPRVVGIWLDLEEGKLAFYSVANQeRLLHECEVSASSPLHPA 153

                  .
gi 1572616305 439 F 439
Cdd:cd12902   154 F 154

PRY/SPRY domain in tripartite motif-containing protein 76 (TRIM76), also called cardiomyopathy-associated protein 5; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is 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. It has also been implicated in Duchenne muscular dystrophy and cardiac disease; gene polymorphism of TRIM76 is associated with left ventricular wall thickness in patients with hypertension while its interactions with M-band titin and calpain 3 link it to tibial and limb-girdle muscular dystrophies.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 286 TVSPLLHLSEDRRTLTFIAKKSKVCSDEPErfdhWPNALAATAFQTGLHAWIVNVKHSCAYKVGVASDQLPRKGSgndcr 365
Cdd:cd12898    10 TAHPALHISSDRGTVIYFHERRRKMSSLTE----CPSVLGEELPSCGQYYWETTVTRCPAYRLGICSSSASQAGA----- 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 366 LGHNAFSW----VFSRYDQEFCFSHNGYHEPLPLLRCPAQLGMLLDLQAGELVFYEPASGTVLHIHRASFPQVLFPVFAV 441
Cdd:cd12898    81 LGEGSTSWclhcVPTSEPCRYTLLHSGIVSDVFVTERPARVGTLLDYNNGRLIFINAESGQLLGIFRHRFAQPCHPAFAL 160

PRY/SPRY domain in tripartite motif-binding protein 69 (TRIM69), also known as RING finger protein 36 (RNF36); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM69, which is also known as RING finger protein 36 (RNF36) or testis-specific ring finger (Trif). TRIM69 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. It 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. The mouse ortholog of this gene is specifically expressed in germ cells at the round spermatid stages during spermatogenesis and, when overexpressed, induces apoptosis. TRIM69 has been shown to be a novel regulator of mitotic spindle assembly in tumor cells; it associates with spindle poles and promotes centrosomal clustering, and is therefore essential for formation of a bipolar spindle.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 276 GVEEVLIDERTVSPLLHLSEDRRTLTFIAKKsKVCSDEPERFDHWPNALAATAFQTGLHAWIVNVKHSCAYKVGVASDQL 355
Cdd:cd15818    11 GLSLITLDPKTAHPNLILSEDLTCVWHGDTK-QMLPDNPERFDSSVAVLGSEGFTSGKHYWEVEVAKKTKWTLGVVRESI 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 356 PRKGSgndCRLGHNAFSWVFSRYDQEFCFSHNGYHEPLPLLRCPAQLGMLLDLQAGELVFYEPASGTVLHIHRASFPQVL 435
Cdd:cd15818    90 NRKGN---CPLSPEDGFWLLRLRNQNELKALDVPSFSLTLTSNLNKVGIYLDYEGGQVSFYNANTMSHIYTFSDTFTEKI 166

                  ....
gi 1572616305 436 FPVF 439
Cdd:cd15818   167 YPYF 170

PRY/SPRY domain in tripartite motif-binding protein 41 (TRIM41); 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 41 (TRIM41). TRIM41 (also known as RING finger-interacting protein with C kinase or RINCK) 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 279 EVLIDERTVSPLLHLSEDRRTLTFIAKKSKVcSDEPERFDHWPNALAATAFQTGLHAWIVNVKHSCAYKVGVASDQLPRK 358
Cdd:cd13741     1 DLTLDPDTAHPALLLSPDRRGVRLAERRQEV-PEHPKRFSADCCVLGAQGFRSGRHYWEVEVGGRRGWAVGAARESTHHK 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 359 ----------GSGNDCRLGHNAFSWVFSRYDQE------FCFSHNGY---------HEPLPLLRCPAQLGMLLDLQAGEL 413
Cdd:cd13741    80 ekvgsggssvSSGDASSSRHHHRRRRLHLPQQPllqrevWCVGTNGKryqaqssteQTLLSPSEKPRRFGVYLDYEAGRL 159

                         170       180
                  ....*....|....*....|....*....
gi 1572616305 414 VFYEPASGTVLHIHRASF-PQVLFPVFAV 441
Cdd:cd13741   160 GFYNAETLAHVHTFSAAFlGERVFPFFRV 188

PRY/SPRY domain in tripartite motif-containing protein 27 (TRIM27), also known as RING finger protein 76 (RNF76); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM27, also known as RING finger protein 76 (RNF76) or RET finger protein (RFP). TRIM27 domain is composed of RING/B-box/coiled-coil core and also known as RBCC proteins. It is highly expressed in the spleen, thymus and in cells of the hematopoietic compartment. TRIM27 exhibits either nuclear or cytosolic localization depending on the cell type. TRIM27 negatively regulates nucleotide-binding oligomerization domain containing 2 (NOD2)-mediated signaling by proteasomal degradation of NOD2, suggesting that TRIM27 could be a new target for therapeutic intervention in NOD2-associated diseases such as Crohn's. High expression of TRIM27 is observed in several human cancers, including breast and endometrial cancer, where elevated TRIM27 expression predicts poor prognosis. Also, TRIM27 forms an oncogenic fusion protein with Ret proto-oncogene. It is involved in different stages of spermatogenesis and its significant expression in male germ cells and seminomas, suggests that TRIM27 may be associated with the regulation of testicular germ cell proliferation and histological-type of germ cell tumors. TRIM27 could also be a predictive marker for chemoresistance in ovarian cancer patients. In the neurotoxin model of Parkinson's disease (PD), deficiency of TRIM27 decreases apoptosis and protects dopaminergic neurons, making TRIM27 an effective potential target during the treatment of PD.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 279 EVLIDERTVSPLLHLSEDRRTLTFIAKKSKVcSDEPERFDHWPNALAATAFQTGLHAWIVNVKHSCAYKVGVASDQLPRK 358
Cdd:cd15814     3 DVTLDPDTAYPSLILSDNLRQVRYSYLQQDL-PDNPERFNLFPCVLGSPCFIAGRHYWEVEVGDKAKWTIGVCEDSVCRK 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1572616305 359 GSGNDCRlgHNAFSWVFSRYDQEFcFSHNGYHEPLPlLRCPAQ-LGMLLDLQAGELVFY 416
Cdd:cd15814    82 GGVTSAP--QNGFWAVSLWYGKEY-WALTSPMTALP-LRTPLQrVGIFLDYDAGEVSFY 136

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 1572616305 283 DERTVSPLLHLSEDRRTLTFIAKKSKVCSDePERFDHWPNALAATAFQTGLHAWIVNVKHSCAYKVGVASDQLPRKGSGN 362
Cdd:cd12905     9 DPETAHPSLILSRDLTAVTESDEMQPYPRS-PKRFLQCVNVLASQGFQSGRHYWEVWVGSKTKWDLGVASESVDRQARVK 87

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1572616305 363 DCRlgHNAFsWVFSRYDQEFCFSHNGYHEPLPLLRCPAQLGMLLDLQAGELVFYEPASGTVLHIHRASFPQVLFPVFA 440
Cdd:cd12905    88 LCP--ENGY-WTLRLRNGDEYWAGTQPWTRLRVTSRPQRIGVFLDCEERKVSFYNADDMSLLYSFHQGPRGKVFPFFS 162

PRY/SPRY domain in tripartite motif-binding protein 62 (TRIM62); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM62. It is also called DEAR1 ductal epithelium (associated RING chromosome 1) and 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 and thus, making TRIM62 a predictive biomarker. Non-small cell lung cancer lesions show a step-wise loss of TRIM62 levels during disease progression, indicating that it may play a role in the evolution of lung cancer. Decreased levels of TRIM62 also represent an independent adverse prognostic factor in AML.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 282 IDERTVSPLLHLSEDRRTLTFIAKKSKVCSDEPERFDHWPNALAATAFQTGLHAWIVNVKHSCAYKVGVASDQLPRKGS- 360
Cdd:cd13744    16 LDPVTAHQRLILSDDCTIVAYGNLHPQPLQDSPKRFDVEVSVLGSEGFSGGVHYWEVVVSEKTQWMIGLAHEAVSRKGSi 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1572616305 361 ------GNDCRLGHNAfswvfSRYdqefcfshNGYHEPLPLLRCPAQL---GMLLDLQAGELVFYEPASGTVLHIHRASF 431
Cdd:cd13744    96 qiqpgrGFYCIVMHDG-----NQY--------SACTEPWTRLNVKSKLekvGVYLDYDKGLLIFYNADDMSWLYTFREKF 162