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 2528974297  32 FKLEEKTAHSSLALFRDDTGVKYGLVGLEPTKVALNVERFREWAVVLADTAVTSGRHYWEVTVKRSQQFRIGVADVDMSR 111
Cdd:cd12903     1 FKLDERTAHSSLDLFKKDTGVIYRMLGVDPTKVPQNPERFRDWAVVLGDTPVTSGRHYWEVTVKRSQEFRIGVADVDMSR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297 112 DSCIGVDDRSWVFTYAQRKWYTMLANEKAPVEGIGQPEKVGLLLEYEAQKLSLVDVSQVSVVHTLQTDFRGPVVPAFALW 191
Cdd:cd12903    81 DECIGTNESSWVFAYAQRKWYAMVANETVPVPLVGKPDRVGLLLDYEAGKLSLVDVEKNSVVHTMSAEFRGPVVPAFALW 160

                  ....*....
gi 2528974297 192 DGELLTHSG 200
Cdd:cd12903   161 DGELLTHSG 169

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 2528974297  32 FKLEEKTAHSSLALFRDDTGVKYGLVGLEPTKVALNVERFREWAVVLADTAVTSGRHYWEVTVKRSQQFRIGVADVDMSR 111
Cdd:cd12903     1 FKLDERTAHSSLDLFKKDTGVIYRMLGVDPTKVPQNPERFRDWAVVLGDTPVTSGRHYWEVTVKRSQEFRIGVADVDMSR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297 112 DSCIGVDDRSWVFTYAQRKWYTMLANEKAPVEGIGQPEKVGLLLEYEAQKLSLVDVSQVSVVHTLQTDFRGPVVPAFALW 191
Cdd:cd12903    81 DECIGTNESSWVFAYAQRKWYAMVANETVPVPLVGKPDRVGLLLDYEAGKLSLVDVEKNSVVHTMSAEFRGPVVPAFALW 160

                  ....*....
gi 2528974297 192 DGELLTHSG 200
Cdd:cd12903   161 DGELLTHSG 169

SPRY domain; SPRY Domain is named from SPla and the RYanodine Receptor and it is found in many eukaryotic proteins with a wide range of functions. It is a protein-interaction module involved in many important signalling pathways like RNA processing, regulation of histone H3 methylation, innate immunity or embryonic development. It can be divided into 11 subfamilies based on amino acid sequence similarity or the presence of additional protein domains. The greater SPRY family is divided into the SPRY/B30.2 (which contains a PRY extension at the N-terminal) and SPRY-only sub-families which are preceded by a subdomain that is structurally similar to the PRY region. SPRY/B30.2 structures revealed a bent beta-sandwich fold comprised of two beta-sheets. Distant homologs are domains in butyrophilin/ marenostrin/pyrin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297  87 RHYWEVTV--KRSQQFRIGVA--DVDMSRDSCIGVDDRSWVF--TYAQRKWYTMlaNEKAPVEGIGQPEKVGLLLEYEAQ 160
Cdd:pfam00622   1 RHYFEVEIfgQDGGGWRVGWAtkSVPRKGERFLGDESGSWGYdgWTGKKYWAST--SPLTGLPLFEPGDVIGCFLDYEAG 78

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2528974297 161 KLSLVDVSQvSVVHTLQT-DFRGPVVPAFAL 190
Cdd:pfam00622  79 TISFTKNGK-SLGYAFRDvPFAGPLFPAVSL 108

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 2528974297  32 FKLEEKTAHSSLALFRDDTGVKYGLVGLEPTKVALNVERFREWAVVLADTAVTSGRHYWEVTVKRSQQFRIGVADVDMSR 111
Cdd:cd12903     1 FKLDERTAHSSLDLFKKDTGVIYRMLGVDPTKVPQNPERFRDWAVVLGDTPVTSGRHYWEVTVKRSQEFRIGVADVDMSR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297 112 DSCIGVDDRSWVFTYAQRKWYTMLANEKAPVEGIGQPEKVGLLLEYEAQKLSLVDVSQVSVVHTLQTDFRGPVVPAFALW 191
Cdd:cd12903    81 DECIGTNESSWVFAYAQRKWYAMVANETVPVPLVGKPDRVGLLLDYEAGKLSLVDVEKNSVVHTMSAEFRGPVVPAFALW 160

                  ....*....
gi 2528974297 192 DGELLTHSG 200
Cdd:cd12903   161 DGELLTHSG 169

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 2528974297  34 LEEKTAHSSLALFRDDTGVKYGLVGLE-PtkvaLNVERFrEWAVVLADTAVTSGRHYWEVTVKRSQQFRIGVADVDMSR- 111
Cdd:cd12891     3 LDPNTAHNNLALSGDLKTVTCSSENQHyP----DSPERF-THSQVLSTQSFSSGRHYWEVEVSESGGWSVGVAYPSIERk 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297 112 --DSCIGVDDRSWVFTYAQRKWYTMLANEKAPVEGiGQPEKVGLLLEYEAQKLSLVDVS-QVSVVHTLQTDFRGPVVPAF 188
Cdd:cd12891    78 gdESRIGRNDKSWCLEWQDKSFSAWHNNEETPLPS-VSSRRLGVYLDYEAGRLSFYELSdPIRHLHTFTATFTEPLHPAF 156

                  ....*....
gi 2528974297 189 ALWDGELLT 197
Cdd:cd12891   157 WVLEGGWIR 165

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297  32 FKLEEKTAHSSLALFRDDTGVKYGLVGLEPTKVALNVERFREWAVVLADTAVTSGRHYWEVTVKRSQQFRIGVADVDMSR 111
Cdd:cd12899     2 FHLNEDTAHPLLSISEDGFTVVYGEEELPARDLSFSDNSFTRCVAVMGSLIPVRGKHYWEVEVDEQTEYRVGVAFEDTQR 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297 112 DSCIGVDDRSW----VFTYAQRKwYTMLANEKAP-VEGIGQPEKVGLLLEYEAQKLSLVDVSQVSVVHTLQTDFRGPVVP 186
Cdd:cd12899    82 NGYLGANNTSWcmrhIITPSRHK-YEFLHNGWTPdIRITVPPKKIGILLDYDSGRLSFFNVDLAQHLYTFSCQFQHFVHP 160

                         170
                  ....*....|....*.
gi 2528974297 187 AFALWD-GELLTHSGL 201
Cdd:cd12899   161 CFSLEKpGALKVHNGI 176

PRY/SPRY domain of tripartite motif-binding protein 1 (TRIM1) or MID2; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM1 (also known as MID2 or midline 2). 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. MID2 and MID1 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 MID1 have shown to cause Opitz syndrome, a disorder causing congenital anomalies such as cleft lip and palate as well as heart defects.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297  32 FKLEEKTAHSSLALFRDDTGVKYGLVGLEPTKVAlnvERFREWAVVLA--DTAVTSGRHYWEVTVKRSQQFRIGVADVDM 109
Cdd:cd13739     1 FKLDPKMAHKKLKISNDGLQMEKDESSLKKSHTP---ERFSGTGCYGAagNIFIDSGCHYWEVVVGSSTWYAIGIAYKSA 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297 110 SRDSCIGVDDRSWVFTYAQRKWYTMLANEKAPVEGIGQPEKVGLLLEYEAQKLSLVDVSQVSVVHTLQTDFRGPVVPAFA 189
Cdd:cd13739    78 PKNEWIGKNSSSWVFSRCNNNFVVRHNNKEMLVDVPPQLKRLGVLLDYDNNMLSFYDPANSLHLHTFEVSFILPVCPTFT 157

                         170
                  ....*....|..
gi 2528974297 190 LWDGELLTHSGL 201
Cdd:cd13739   158 IWNKSLMILSGL 169

SPRY domain in Ro-Ret family; This domain, named BSPRY, has been identified in the Ro-Ret family, since the protein is composed of a B-box, an alpha-helical coiled coil and a SPRY domain. The gene for BSPRY resides on human chromosome 9 and is specifically expressed in testis. The function of BSPRY is not known, but several related proteins of the RING-Box-coiled-coil (RBCC) family have been implicated in cell transformation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297  69 ERFREWAVVLADTAVTSGRHYWEVTVKRSQQFRIGVADVDMSR-----DSCIGVDDRSWVFTYAQRKWYTMLANEKAPVE 143
Cdd:cd12904    37 ERFDHWPNALASLSFSSGTHAWVVDVGKSCAYKVGVCYGSLERkgsgnEARLGYNAFSWVFSRYDGEFSFSHNGQHVPLE 116

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2528974297 144 GIGQPEKVGLLLEYEAQKLSLVDVSQVSVVHTLQTDFRGPVVPAFALWD 192
Cdd:cd12904   117 LLKCPARVGVLLDWPSQELLFYDPDSCTVLHSHREAFAAPLLPVFAVAD 165

Fibronectin type III and SPRY containing 1 (FSD1) domain includes PRY at the N-terminus; This domain is part of the fibronectin type III and SPRY domain containing 1 (FSD1) and FSD1-like (FSD1L) proteins. These are centrosome-associated proteins that are characterized by an N-terminal coiled-coil region downstream of B-box (BBC) domain, a central fibronectin type III (FN3) domain, and C-terminal repeats in PRY/SPRY domain. The FSD1 protein associates with a subset of microtubules and may be involved in the stability and organization of microtubules during cytokinesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297  69 ERFR-EWAVVLADTAVTSGRHYWEVTV-KRSQQFRIGVADVDMSRDSCIGVDDRSWVFTYAQRKWYTMLA--NEKAPVEG 144
Cdd:cd12901    67 DRFTaESYTVLGDTLIDGGQHYWEVRAqKDSKAFSVGVAYRSLGKFDQLGKTNASWCLHVNNWLQNSFAAkhNNKAKTLD 146

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297 145 IGQPEKVGLLLEYEAQKLSLVDVSQVSVVHTLQTDFRGPVVPAFALWDGELLTHSGLEVP 204
Cdd:cd12901   147 VPVPDRIGVYCDFDEGQLSFYNARTKQLLHTFKMKFTQPVLPAFMVWCGGLSVSTGLQVP 206

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 2528974297  29 GVSFKLEEKTAHSSLALFRDDTGVKYglVGLEPTKVALNVErfreWAVVLADTAVTSGRHYWEVTVKRSQQFRIGVADVD 108
Cdd:cd12898     1 GTRFLLLRETAHPALHISSDRGTVIY--FHERRRKMSSLTE----CPSVLGEELPSCGQYYWETTVTRCPAYRLGICSSS 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297 109 MSRDSCIGVDDRSW----VFTYAQRKWYTMLANEKAPVEGIGQPEKVGLLLEYEAQKLSLVDVSQVSVVHTLQTDFRGPV 184
Cdd:cd12898    75 ASQAGALGEGSTSWclhcVPTSEPCRYTLLHSGIVSDVFVTERPARVGTLLDYNNGRLIFINAESGQLLGIFRHRFAQPC 154

                  ....*.
gi 2528974297 185 VPAFAL 190
Cdd:cd12898   155 HPAFAL 160

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 2528974297  34 LEEKTAHSSLALFRDDTGVKYGLvglEPTKVALNVERFREWAVVLADTAVTSGRHYWEVTVKRSQQFRIGVADVDMSRDS 113
Cdd:cd15820     8 LDPDTANPILLISEDQRSLQWAD---EPQNLPDNPKRFDWHYCVLGCKSFTSGRHFWEVEVGDRKEWYVGVCRENVERKL 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297 114 CIGVDDRS--WVFTYAQRKWYTMLANEKAPVEGIGQPEKVGLLLEYEAQKLSLVDVSQVSVVHT-LQTDFRGPVVPAFAL 190
Cdd:cd15820    85 WVKMAPENgfWTIGLSDGNDYQALTDPRTKLTIANPPQRVGVFLDYETGEVSFYNAMDGSHIYTfPHTSFSGPLYPVFRL 164

                  ....*....
gi 2528974297 191 --WDGELLT 197
Cdd:cd15820   165 lsWDPTALT 173

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 2528974297  34 LEEKTAHSSLALFRDDTGVKYGlvglePTKVAL--NVERFREWAVVLADTAVTSGRHYWEVTVKRSQQFRIGVADVDMSR 111
Cdd:cd15818    17 LDPKTAHPNLILSEDLTCVWHG-----DTKQMLpdNPERFDSSVAVLGSEGFTSGKHYWEVEVAKKTKWTLGVVRESINR 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297 112 DSCIgvddrswVFTYAQRKWYTMLANE---KA---PVEGI---GQPEKVGLLLEYEAQKLSLVDVSQVSVVHTLQTDFRG 182
Cdd:cd15818    92 KGNC-------PLSPEDGFWLLRLRNQnelKAldvPSFSLtltSNLNKVGIYLDYEGGQVSFYNANTMSHIYTFSDTFTE 164

                  ....*.
gi 2528974297 183 PVVPAF 188
Cdd:cd15818   165 KIYPYF 170

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 2528974297  27 QRGVSFKLEekTAHSSLALFRDDTGVKYGLvglEPTKVALNVERFREWAVVLADTAVTSGRHYWEVTVKRSQQFRIGVAD 106
Cdd:cd15828     9 QVDVTLDPE--TAHPQLTVSEDRKSVLYGE---MKQNVCYNPRRFYLCPAVLGSEGFHSGRQYWEVEVGDKPEWTLGVCQ 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297 107 VDMSRD--SCIGVDDRSW-VFTYAQRKwYTMLANEKAPVEGIGQPEKVGLLLEYEAQKLSLVDVSQVSVVHTLQTDFRGP 183
Cdd:cd15828    84 DCLPRNwsNQPSVQDGLWaIGRYSESN-YVALGPKKIQLLPKVRPSKIGIFLDYELGEVSFYNMNDRSLLYTFSDSFTGT 162

                  ....*
gi 2528974297 184 VVPAF 188
Cdd:cd15828   163 LWPYF 167

PRY/SPRY domain in tripartite motif-containing proteins, TRIM9 and TRIM67; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM9 proteins. TRIM9 protein is expressed mainly in the cerebral cortex, and functions as an E3 ubiquitin ligase. It has been shown that TRIM9 is localized to the neurons in the normal human brain and its immunoreactivity in affected brain areas in Parkinson's disease and dementia with Lewy bodies is severely decreased, possibly playing an important role in the regulation of neuronal function and participating in pathological process of Lewy body disease through its ligase. TRIM67 negatively regulates Ras activity via degradation of 80K-H, leading to neural differentiation, including neuritogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297  76 VVLADTAVTSGRHYWEVTVKR---SQQFRIGVADVDMSRDSCIGVDDRSW-VFTYAQRKWYtMLANEKAP-VE-GIGQPE 149
Cdd:cd12889    39 VVLGSVGFSRGVHYWEVTIDRydgHPDPAFGVARIDVNKDKMLGKDDKGWsMYIDNNRSWF-LHNNEHSNrTEgGITVGS 117

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2528974297 150 KVGLLLEYEAQKLS--LVDVSQVSVVHtlqTDFRGPVVPAFALWDGELLT-HSGLEVP 204
Cdd:cd12889   118 VVGVLLDLDRHTLSfyVNDEPQGPIAF---RNLPGVFYPAVSLNRNVQVTlHTGLEPP 172

PRY/SPRY domain in tripartite motif-binding protein 20 (TRIM20), also known as pyrin; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM20, which is also known as pyrin or marenostrin. Unlike TRIM domains that are composed of RING/B-box/coiled-coil core, the N-terminal RING domain in TRIM20 is exchanged by a PYRIN domain (PYD), a prime mediator of protein interactions necessary for apoptosis, inflammation and innate immune signaling pathway, and it also harbors a C-terminal B30.2 domain. Mutations in pyrin (TRIM20) are associated with familial Mediterranean fever (FMF), a recessively hereditary periodic fever syndrome, characterized by episodes of inflammation and fever. These mutations cluster in the C-terminal B30.2 domain and therefore it is assumed that pyrin plays a role in the innate immune system by possibly effecting caspase-1-dependent IL-1beta maturation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297  30 VSFKLEEKTAHSSLALFRDDTGVKyglVGLEPTKVALNVERFREWAVVLADTAVTSGRHYWEVTVKRSQQFRIGVADVDM 109
Cdd:cd15813     9 VNVTLDPETAHPNLIFSDDLKSVR---LGNKWDRLPDNPERFDSCIIVLGSPSFTSGRHYWEVEVGDKTGWILGVCKASV 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297 110 SRDSCIGVDDRS--WVFTYAQRKWYTMLANEKAPVEGIGQPEKVGLLLEYEAQKLSLVDVSQVSVVHTLqTDF--RGPVV 185
Cdd:cd15813    86 SRKGSMTLSPENgyWVVMMTKRNEYQASTSPPTRLWLREPPRRVGIFLDYEAGDISFYNVTAKSHIYTF-TSFssSGPLQ 164

                  ...
gi 2528974297 186 PAF 188
Cdd:cd15813   165 PIF 167

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 2528974297  31 SFKLEEKTAHSSLALFRDDTGVKYGlvGLEPTKVALNVERFREWAVVLADTAVTSGRHYWEVTVKRSQQFRIGVADVDMS 110
Cdd:cd13744    13 ALTLDPVTAHQRLILSDDCTIVAYG--NLHPQPLQDSPKRFDVEVSVLGSEGFSGGVHYWEVVVSEKTQWMIGLAHEAVS 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297 111 RDSCIGVDdrswvftyAQRKWYTMLANEKAPVEGIGQP----------EKVGLLLEYEAQKLSLVDVSQVSVVHTLQTDF 180
Cdd:cd13744    91 RKGSIQIQ--------PGRGFYCIVMHDGNQYSACTEPwtrlnvksklEKVGVYLDYDKGLLIFYNADDMSWLYTFREKF 162

                  ....*....
gi 2528974297 181 RGPVVPAFA 189
Cdd:cd13744   163 PGKLCSYFS 171

PRY/SPRY domain in tripartite motif-binding protein 21 (TRIM21) also known as 52kD Ribonucleoprotein Autoantigen (Ro52); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM21, which is also known as Sjogren Syndrome Antigen A (SSA), SSA1, 52kD Ribonucleoprotein Autoantigen (Ro52, Ro/SSA, SS-A/Ro) or RING finger protein 81 (RNF81). TRIM21 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. As an E3 ligase, TRIM21 mediates target specificity in ubiquitination; it regulates type 1 interferon and proinflammatory cytokines via ubiquitination of interferon regulatory factors (IRFs). It is up-regulated at the site of autoimmune inflammation, such as cutaneous lupus lesions, indicating a central role in the tissue destructive inflammatory process. It interacts with auto-antigens in patients with Sjogren syndrome and systemic lupus erythematosus, a chronic systemic autoimmune disease characterized by the presence of autoantibodies against the protein component of the human intracellular ribonucleoprotein-RNA complexes and more specifically TRIM21, Ro60/TROVE2 and La/SSB proteins. It binds the Fc part of IgG molecules via its PRY-SPRY domain with unexpectedly high affinity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297  29 GVSFKLEEKTAHSSLALFRDDTGVKyglVGLEPTKVALNVERFREWAVVLADTAVTSGRHYWEVTVKRSQQFRIGVADVD 108
Cdd:cd12900     2 MVHITLDPDTANPWLILSKDRRQVR---LGDTHQNVPENEERFDNYPMVLGAQRFNSGKHYWEVDVTGKEAWDLGVCRDS 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297 109 MSRDSCIGVDDRSWVFT-YAQRKWYTMLANEKAPVEGIGQPEKVGLLLEYEAQKLSLVDVSQV-SVVHTL-QTDFRGPVV 185
Cdd:cd12900    79 VRRKGQFLLSPENGFWTiWLWNKKYEAGTSPQTTLHLQVPPCQVGIFLDYEAGVVSFYNITDHgSLIYTFsECAFTGPLR 158

                  ...
gi 2528974297 186 PAF 188
Cdd:cd12900   159 PFF 161

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297  34 LEEKTAHSSLALFRDDTGVKYGlvglePTKVAL--NVERFREWAVVLADTAVTSGRHYWEVTVKRSQQFRIGVAdvdmsR 111
Cdd:cd13745     7 LDPDTAHPNLVLSEDRKSVRHG-----DTRQDLpdNPERFDTYPCVLGAEGFTGGRHYWEVEVGDKTEWTLGVC-----R 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297 112 DScigVDDRSWVFT------YAQRKW---YTMLANEKAPVEGIGQPEKVGLLLEYEAQKLSLVDVSQVSVVHTLQTDFRG 182
Cdd:cd13745    77 ES---VSRKGEVTLspengyWTVWLRdgkYEALTSPPTPLPVSVRPSRVGIFLDYEAGEVSFYNVTDRSHLFTFTDTFSG 153

                  ....*.
gi 2528974297 183 PVVPAF 188
Cdd:cd13745   154 TLRPYF 159

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 2528974297  34 LEEKTAHSSLALFRDDTGVkygLVGLEPTKVALNVERFREWAVVLADTAVTSGRHYWEVTVKRSQQFRIGVADVDMSRDS 113
Cdd:cd12905     8 FDPETAHPSLILSRDLTAV---TESDEMQPYPRSPKRFLQCVNVLASQGFQSGRHYWEVWVGSKTKWDLGVASESVDRQA 84

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2528974297 114 CIGV--DDRSWVFTYAQRKWYTMLANEKAPVEGIGQPEKVGLLLEYEAQKLSLVDVSQVSVVHTLQTDFRGPVVPAFA 189
Cdd:cd12905    85 RVKLcpENGYWTLRLRNGDEYWAGTQPWTRLRVTSRPQRIGVFLDCEERKVSFYNADDMSLLYSFHQGPRGKVFPFFS 162

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 2528974297  34 LEEKTAHSSLALFRDDTGVKYGLVGlepTKVALNVERFREWAVVLADTAVTSGRHYWEVTVKRSQQFRIGVADVDMSRDS 113
Cdd:cd15817     4 LDPETAHPNLIVSEDRKAVRYRRMK---PNCPYDPRRFTVYPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSLPRNA 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2528974297 114 CI--GVDDRSWVFTyAQRKWYTMLANEKAPVEGIGQPEKVGLLLEYEAQKLSLVDVSQVSVVHTLQTDFRGPVVPAF 188
Cdd:cd15817    81 QDppSPLGGCWQIG-RYMSGYVASGPKTTQLLPVVKPSRIGIFLDYELGEVSFYNMNDRSHLYTFTDTFTGKLIPYF 156

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 2528974297  30 VSFKLEEKTAHSSLALFRDDTGVKYGLVGLEPTKVAlnvERFREWAVVLADTAVTSGRHYWEVTVKRSQQFRIGV----- 104
Cdd:cd15821     4 VDMTLDVDTANNYLIISEDLRSVRCGCFRQNRKELA---ERFDDALCVLGSPRFTSGRHYWEVDVGTSTEWDLGVcresv 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297 105 ---ADVDMSRDS---CIGVDDRSWVFtyAQRKWYTMLanekaPVEgiGQPEKVGLLLEYEAQKLSLVDVSQVSVVHT-LQ 177
Cdd:cd15821    81 nrqGPIELSPEHgfwTVSLRDGSVFF--ASTVPLTVL-----WVN--PRLHRVGIFLDMEMGTISFYDVSDGSHIFTfTK 151

                         170
                  ....*....|..
gi 2528974297 178 TDFRGPVVPAFA 189
Cdd:cd15821   152 ISAEEPLRPFFA 163

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 2528974297  34 LEEKTAHSSLALFRDDTGVKYglvglepTK----VALNVERFREWAVVLADTAVTSGRHYWEVTVKRSQQFRIGVADVDM 109
Cdd:cd15829    23 LDPETAHPNLLVSEDKKCVTF-------TKkkqrVPDSPKRFTVNPVVLGFPGFHSGRHFWEVEVGDKPEWAVGVCKDSL 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297 110 SRDScigvddRSWVfTYAQRKWYTMLANE--------KAPVEGIGQPEKVGLLLEYEAQKLSLVDVSQVSVVHTLQTDFR 181
Cdd:cd15829    96 STKA------RRPP-SGQQGCWRIQLQGGdydapgavPPPLLLEVKPRGIGVFLDYELGEISFYNMPEKSHIHTFTDTFS 168

                  ....*..
gi 2528974297 182 GPVVPAF 188
Cdd:cd15829   169 GPLRPYF 175

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 2528974297  38 TAHSSLALFRDDTGVKYGLVglePTKVALNVERFREWAVVLADTAVTSGRHYWEVTVKRSQQFRIGVADVDMSRDSCIGV 117
Cdd:cd12888     8 TAHPRLVLSEDRKSVRWGDT---RQDLPDNPERFDTWPCVLGCEGFTSGRHYWEVEVGDGGGWAVGVARESVRRKGEISF 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2528974297 118 D--DRSWvftyAQRKW---YTMLANEKAPVEGIGQPEKVGLLLEYEAQKLSLVDVSQVSVVHTLQTDF--RGPVVPAFAL 190
Cdd:cd12888    85 SpeEGIW----AVGQWggqYWALTSPETPLPLSEVPRRIRVYLDYEGGQVAFFDADNEAPIFTFPPASfaGERIFPWFWV 160

                  ....*..
gi 2528974297 191 WDGELLT 197
Cdd:cd12888   161 GKGSQLK 167