B-box-type 2 zinc finger found in B box and SPRY domain-containing protein (BSPRY) and similar proteins; BSPRY is a regulatory protein for maintaining calcium homeostasis. It may regulate epithelial calcium transport by inhibiting TRPV5 activity. BSPRY is composed of a B-box, an alpha-helical coiled coil and a SPRY domain. The B-box motif 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        40
                 ....*....|....*....|....*....|....*....|...
gi 154354992  21 LCPEHGQALSWFCGSERRPVCAACAGLgGRCRGHRIRRAEERA 63
Cdd:cd19834    2 LCPDHELELDWFCSTERRLVCAQCASL-GTCRGHRVTPLEERA 43

B-box-type 2 zinc finger found in B box and SPRY domain-containing protein (BSPRY) and similar proteins; BSPRY is a regulatory protein for maintaining calcium homeostasis. It may regulate epithelial calcium transport by inhibiting TRPV5 activity. BSPRY is composed of a B-box, an alpha-helical coiled coil and a SPRY domain. The B-box motif 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        40
                 ....*....|....*....|....*....|....*....|...
gi 154354992  21 LCPEHGQALSWFCGSERRPVCAACAGLgGRCRGHRIRRAEERA 63
Cdd:cd19834    2 LCPDHELELDWFCSTERRLVCAQCASL-GTCRGHRVTPLEERA 43

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
                  ....*....|....*....|....*....|....*....|....*..
gi 154354992  235 DERTVSPFLQLSDDRKTLTFSTKKSKaCADGPERFDHWPNALAATSF 281
Cdd:pfam13765   4 DPNTAHPSLVLSEDLKSVRYGDERQN-VPDNPERFDSWPCVLGSEGF 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 154354992 232 IRIDERTVSPFLQLSDDRKTLTFSTKKSKACAD-GPERFDHWPNALAATSFQNGLHAWMVNVQNSCAYKVGVASGHLPRk 310
Cdd:cd13734    1 FKLDPKTAHRKLRLSNDNLTVEYDPEGSKDQAAvLPRRFTGSPAVLGDVAISSGRHYWEVSVSRSTSYRVGVAYKSAPR- 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154354992 311 gsgsDCRLGHNAFSWVFSRYDQEFRFSHNGQHEPLGLLRGPAQLGVVLDLQVQELLFYEPASGTVLCAHHVSFPGPLFPV 390
Cdd:cd13734   80 ----DEDLGKNSTSWCLSRDNNRYTARHDGKVVDLRVTGHPARIGVLLDYDNGTLSFYDAESKQHLYTFHVDFEGPVCPA 155

                        170
                 ....*....|.
gi 154354992 391 FAVADQTISIV 401
Cdd:cd13734  156 FAVWNGSLTLH 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 154354992 235 DERTVSPFLQLSDDRKTLTFSTKkSKACADGPERFDHWpNALAATSFQNGLHAWMVNVQNSCAYKVGVASGHLPRKGSGS 314
Cdd:cd12891    4 DPNTAHNNLALSGDLKTVTCSSE-NQHYPDSPERFTHS-QVLSTQSFSSGRHYWEVEVSESGGWSVGVAYPSIERKGDES 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154354992 315 dcRLGHNAFSWVFSRYDQEFRFSHNGQHEPLGLLRGPaQLGVVLDLQVQELLFYEpASGTVLCAH--HVSFPGPLFPVFA 392
Cdd:cd12891   82 --RIGRNDKSWCLEWQDKSFSAWHNNEETPLPSVSSR-RLGVYLDYEAGRLSFYE-LSDPIRHLHtfTATFTEPLHPAFW 157

                 ....*....
gi 154354992 393 VADQ-TISI 400
Cdd:cd12891  158 VLEGgWIRI 166

PRY/SPRY domain in tripartite motif-containing protein 35 (TRIM35); This PRY/SPRY domain is found at the C-terminus of the overall domain architecture of tripartite motif 35, TRIM35 (also known as hemopoietic lineage switch protein), which includes a RING finger domain (RING) and a B-box motif (BBOX). TRIM35 may play a role as a tumor suppressor and is implicated in the cell death mechanism.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154354992 235 DERTVSPFLQLSDDRKTLTFSTKKSKaCADGPERFDHWPNALAATSFQNGLHAWMVNVQNSCAYKVGVASGHLPRKGSGS 314
Cdd:cd12893    5 DPNTAHPWLSLSEDLTSVRYSSEKQQ-LPDNPERFDPYPCVLGSEGFTSGKHSWDVEVGDNTSWMLGVAKESVQRKGKFT 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154354992 315 DC-RLGHnafsWVFSRYDQEFRFSHNGQH-EPLGLLRGPAQLGVVLDLQVQELLFYEPASGTVLCAHHVSFPGPLFPVFA 392
Cdd:cd12893   84 LSpESGF----WTIGFSEGKYSARTSPEPrTPLRVKQKPQRIRVQLDWDRGKVSFSDPDTNTHIHTFTHTFTERVFPYFY 159

                 ....*...
gi 154354992 393 VADQTISI 400
Cdd:cd12893  160 TGCKSEPL 167

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154354992 231 DIRIDERTVSPFLQLSDDRKTLTFsTKKSKACADGPERFDHWPNALAATSFqNGLHAWMVNVQNSCAYkVGVASGHLPRK 310
Cdd:cd16040   10 QLTLDPNTAHRNLSLSEGNRKVTR-VKEEQPYPDHPERFDYWPQVLCREGL-SGRCYWEVEWSGGGVD-IAVAYKGISRK 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154354992 311 GSGSDCRLGHNAFSWVFSRYDQEFRFSHNGQHeplGLLRGPAQ----LGVVLDLQVQELLFYEpASGTV--LCAHHVSFP 384
Cdd:cd16040   87 GDGDDSRFGYNDKSWSLECSPSGYSFWHNNKK---TEISVPSSsssrVGVYLDHSAGTLSFYS-VSDTMtlLHTVQTTFT 162

                 ....*....
gi 154354992 385 GPLFPVFAV 393
Cdd:cd16040  163 EPLYPGFGV 171

PRY/SPRY domain in tripartite motif-containing protein 16 (TRIM16); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM16 and TRIM-like proteins. TRIM16 (also known as estrogen-responsive B box protein or EBBP) does not possess a RING domain like the other TRIM proteins, but contains two B-box domains and can heterodimerize with other TRIM proteins such as TRIM24, Promyelocytic leukemia (PML) protein and Midline-1 (MID1 or TRIM18). It is a regulator of keratinocyte differentiation and a tumor suppressor in retinoid-sensitive neuroblastoma. It has been shown that loss of TRIM16 expression plays an important role in the development of cutaneous squamous cell carcinoma (SCC) and is a determinant of retinoid sensitivity. TRIM16 also has E3 ubiquitin ligase activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154354992 231 DIRIDERTVSPFLQLSDDRKTLTFSTKKSKACADGPERFDHWPNALAATSFQNGLHAWMVNVQNSCAYkVGVASGHLPRK 310
Cdd:cd12890   10 PLTFDPDTAHRYLRLTEDNRKVTNTTPWEHPYPDHPERFEHWRQVLSQQSLYLGRYYFEVEISGEGTY-VGLTYKSIDRK 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154354992 311 GSGSDCRLGHNAFSWVFSRYDQEFRFSHNGQHEPLGllRGPAQ-LGVVLDLQVQELLFYEPASGTVLCAHHVS--FPGPL 387
Cdd:cd12890   89 GSESNSCISGNNFSWCLQWNGKEFSAWHSDVETPLK--KGPFTrLGIYLDYPGGTLSFYGVEDDGMTLLHKFQckFTEPL 166

                 ....
gi 154354992 388 FPVF 391
Cdd:cd12890  167 YPAF 170

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 154354992 233 RIDERTVSPFLQLSDDRKTLT---FSTKKSKAcadgPERFDHWPNALAATS--FQNGLHAWMVNVQNSCAYKVGVASGHL 307
Cdd:cd13739    2 KLDPKMAHKKLKISNDGLQMEkdeSSLKKSHT----PERFSGTGCYGAAGNifIDSGCHYWEVVVGSSTWYAIGIAYKSA 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154354992 308 PRKGsgsdcRLGHNAFSWVFSRYDQEFRFSHNGQHEPLGLLRGPAQLGVVLDLQVQELLFYEPASGTVLCAHHVSFPGPL 387
Cdd:cd13739   78 PKNE-----WIGKNSSSWVFSRCNNNFVVRHNNKEMLVDVPPQLKRLGVLLDYDNNMLSFYDPANSLHLHTFEVSFILPV 152

                        170
                 ....*....|....
gi 154354992 388 FPVFAVADQTISIV 401
Cdd:cd13739  153 CPTFTIWNKSLMIL 166

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 154354992 231 DIRIDERTVSPFLQLSDDRKTLTFSTKKSKACADgPERFDHWPNALAATSFQNGLHAWMVNVQNSCAYKVGVASGHLPRK 310
Cdd:cd15828   11 DVTLDPETAHPQLTVSEDRKSVLYGEMKQNVCYN-PRRFYLCPAVLGSEGFHSGRQYWEVEVGDKPEWTLGVCQDCLPRN 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154354992 311 GSgsdcrlghNAFS-----WVFSRYdqefrfSHNGqHEPLGLLR-------GPAQLGVVLDLQVQELLFYEPASGTVLCA 378
Cdd:cd15828   90 WS--------NQPSvqdglWAIGRY------SESN-YVALGPKKiqllpkvRPSKIGIFLDYELGEVSFYNMNDRSLLYT 154

                        170
                 ....*....|...
gi 154354992 379 HHVSFPGPLFPVF 391
Cdd:cd15828  155 FSDSFTGTLWPYF 167

PRY/SPRY domain of tripartite motif-binding protein 11 (TRIM11), also known as RING finger protein 92 (RNF92); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM11, also known as RING finger protein 92 (RNF92) or BIA1. TRIM11 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. It localizes to the nucleus and the cytoplasm; it is overexpressed in high-grade gliomas and promotes proliferation, invasion, migration and glial tumor growth. TRIM11 increases expression of dopamine beta-hydroxylase gene by interacting with the homeodomain transcription factor, PHOX2B, via the B30.2/SPRY domain, thus playing a potential role in the specification of noradrenergic (NA) neuron phenotype. It has also been shown that TRIM11 plays a critical role in the clearance of mutant PHOX2B, which causes congenital central hypoventilation syndrome, via the proteasome. TRIM11 binds a key component of the activator-mediated cofactor complex (ARC105), and destabilizes it, through the ubiquitin-proteasome system; ARC105 mediates chromatin-directed transcription activation and is a key regulatory factor for transforming growth factor beta (TGFbeta) signaling.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154354992 231 DIRIDERTVSPFLQLSDDRKTLTFSTKKsKACADGPERFDHWPNALAATSFQNGLHAWMVNVQNSCAYKVGVASGHLPRK 310
Cdd:cd15811    1 DVTLDPDTANPELVLSEDRRSVRRGDLR-QALPDSPERFDPGPCVLGRERFTSGRHYWEVEVGDRTSWALGVCKENVNRK 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154354992 311 GSGsDCRLGHNAFSWVFsrydqeFRFSHNGQHEPLGLLR-GPAQLGVVLDLQVQELLFYEPASGTVLCAH-HVSFPGPLF 388
Cdd:cd15811   80 EKG-ELSAGNGFWILVF------LGNYYSSERRTFAPLRdPPRRVGIFLDYEAGHLSFYSATDGSLLFIFpETPFSGTLR 152

                 ....
gi 154354992 389 PVFA 392
Cdd:cd15811  153 PLFS 156

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 154354992 229 TEDIRIDERTVSPFLQLSDDRKTLTFsTKKSKACADGPERFDHWPNALAATSFQNGLHAWMVNVQNSCAYKVGVASGHLP 308
Cdd:cd15829   18 RVDVTLDPETAHPNLLVSEDKKCVTF-TKKKQRVPDSPKRFTVNPVVLGFPGFHSGRHFWEVEVGDKPEWAVGVCKDSLS 96

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154354992 309 RKGSGSdcRLGHNAfSWVFSRYDQEFRFShnGQHEPLGLLRG-PAQLGVVLDLQVQELLFYEPASGTVLCAHHVSFPGPL 387
Cdd:cd15829   97 TKARRP--PSGQQG-CWRIQLQGGDYDAP--GAVPPPLLLEVkPRGIGVFLDYELGEISFYNMPEKSHIHTFTDTFSGPL 171

                 ....*.
gi 154354992 388 FPVFAV 393
Cdd:cd15829  172 RPYFYV 177

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 154354992 235 DERTVSPFLQLSDDRKTLTFSTKKsKACADGPERFD--HWpnaLAATSFQNGLHAWMVNVQNSCAYKVGVASghlprKGS 312
Cdd:cd12902    4 DLRSLSCSLEVSEDSRKVTVSHGP-QAYAWSPDRFSisQV---LCSQAFSSGQHYWEVDTRQCSHWAVGVAS-----WEM 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154354992 313 GSDCRLGHNAFSWVFS-RYDQEFRFSHNGQHEPLGLLRgPAQLGVVLDLQVQELLFYEPASG-TVLCAHHVSFPGPLFPV 390
Cdd:cd12902   75 SRDQMLGRTMDSWCIEwKGTGQLSAWHMNKETVLGSDK-PRVVGIWLDLEEGKLAFYSVANQeRLLHECEVSASSPLHPA 153

                 .
gi 154354992 391 F 391
Cdd:cd12902  154 F 154

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 154354992 231 DIRIDERTVSPFLQLSDDRKTLTFSTKKSKACADgPERFDHWPNALAATSFQNGLHAWMVNVQNSCAYKVGVASGHLPRK 310
Cdd:cd15819    3 NVTLDPDTAHPALILSEDGRSVTWGETRQDLPEN-PERFDSLPCVLGQEGFTSGRHYWEVEVGDRTSWDLGVCRDNVMRK 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154354992 311 gsGSDCRLGHNAFsWVFSRYDQEFRfSHNGQHEPLGLLRGPAQLGVVLDLQVQELLFYEPASGTvlcaH-----HVSFPG 385
Cdd:cd15819   82 --GRVTLSPENGF-WAIRLYGNEYW-ALTSPETPLTLKEPPRRVGIFLDYEAGDVSFYNMTDGS----HiytfpQTAFSG 153

                 ....*.
gi 154354992 386 PLFPVF 391
Cdd:cd15819  154 PLRPFF 159

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 154354992 232 IRIDERTVSPFLQLSDDRKTLTFSTKKSKAcADGPERFDHWPNALAATSFQNGLHAWMVNVQNSCAYKVGVASGHLPRKG 311
Cdd:cd12900    5 ITLDPDTANPWLILSKDRRQVRLGDTHQNV-PENEERFDNYPMVLGAQRFNSGKHYWEVDVTGKEAWDLGVCRDSVRRKG 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154354992 312 SGSDCrlGHNAFsWVFSRYDQEFRFSHNGQhEPLGLLRGPAQLGVVLDLQVQELLFYEPASGTVL------CAhhvsFPG 385
Cdd:cd12900   84 QFLLS--PENGF-WTIWLWNKKYEAGTSPQ-TTLHLQVPPCQVGIFLDYEAGVVSFYNITDHGSLiytfseCA----FTG 155

                 ....*...
gi 154354992 386 PLFPVFAV 393
Cdd:cd12900  156 PLRPFFNP 163

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 154354992 231 DIRIDERTVSPFLQLSDDRKTLTFSTKKsKACADGPERFDHWPNALAATSFQNGLHAWMVNVQNSCAYKVGVASGHLPRK 310
Cdd:cd12888    1 NVTLDPDTAHPRLVLSEDRKSVRWGDTR-QDLPDNPERFDTWPCVLGCEGFTSGRHYWEVEVGDGGGWAVGVARESVRRK 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154354992 311 GsgsDCRLGHNAFSWVFSRYDQEFRFSHNGQhEPLGLLRGPAQLGVVLDLQVQELLFYEPASGTVLCAH-HVSFPGP-LF 388
Cdd:cd12888   80 G---EISFSPEEGIWAVGQWGGQYWALTSPE-TPLPLSEVPRRIRVYLDYEGGQVAFFDADNEAPIFTFpPASFAGErIF 155

                 ....*.
gi 154354992 389 PVFAVA 394
Cdd:cd12888  156 PWFWVG 161

PRY/SPRY domain in tripartite motif-binding protein 72 (TRIM72); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM72. Muscle-specific TRIM72 (also known as Mitsugumin 53 or MG53) has been shown to perform a critical function in membrane repair following acute muscle injury by nucleating the assembly of the repair machinery at injury sites. It is expressed specifically in skeletal muscle and heart, and tethered to the plasma membrane and cytoplasmic vesicles via its interaction with phosphatidylserine. TRIM72 interacts with dysferlin, a sarcolemmal protein whose deficiency causes Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B); this coordination plays an important role in the repair of sarcolemma damage.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154354992 230 EDIRIDERTVSPFLQLSDDRKTLTFSTKKSKACADGPERFDHWPNALAATSFQNGLHAWMVNVQNSCAYKVGVASGHLPR 309
Cdd:cd13742   12 ENLTFDPDTAHPYLVVSSDGKRVECADQKQAVSSDDPNRFDKANCVVSHQSFSEGEHYWEVIVGDKPRWALGVISAEAGR 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154354992 310 KGSGSdcRLGHNAFsWVFSRYDQEFRFSHNGQHEP--LGLLRGPAQLGVVLDLQVQELLFY---EPASGTVLCAHHVSFP 384
Cdd:cd13742   92 KGRLH--ALPSNGF-WLLGCKEGKVYEAHVEHKEPraLRVEGRPTRIGVYLSFSDGVLSFYdasDEDNLVQLFAFHERFP 168

                 ....*....
gi 154354992 385 GPLFPVFAV 393
Cdd:cd13742  169 GPLYPFFDV 177

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 154354992 231 DIRIDERTVSPFLQLSDDRKTLTFSTKKsKACADGPERFDHWPNALAATSFQNGLHAWMVNVQNSCAYKVGVASGHLPRK 310
Cdd:cd15814    3 DVTLDPDTAYPSLILSDNLRQVRYSYLQ-QDLPDNPERFNLFPCVLGSPCFIAGRHYWEVEVGDKAKWTIGVCEDSVCRK 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154354992 311 GSGSDCRlgHNAFSWVFSRYDQEFRfshnGQHEPLGL--LRGPAQ-LGVVLDLQVQELLFYEPASGT-VLCAHHVSFPGP 386
Cdd:cd15814   82 GGVTSAP--QNGFWAVSLWYGKEYW----ALTSPMTAlpLRTPLQrVGIFLDYDAGEVSFYNVTERChTFTFSHATFCGP 155

                 ....*...
gi 154354992 387 LFPVFAVA 394
Cdd:cd15814  156 VRPYFSLS 163

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 154354992 231 DIRIDERTVSPFLQLSDDRKTLTFSTKKsKACADGPERFDHWPNALAATSFQNGLHAWMVNVQNSCAYKVGVASGHLPRK 310
Cdd:cd13745    4 DVTLDPDTAHPNLVLSEDRKSVRHGDTR-QDLPDNPERFDTYPCVLGAEGFTGGRHYWEVEVGDKTEWTLGVCRESVSRK 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154354992 311 gsgsdcrlGHNAFS-----WVFSRYDQEFR-----FShngqhePLGLLRGPAQLGVVLDLQVQELLFYEPASGTVLCAHH 380
Cdd:cd13745   83 --------GEVTLSpengyWTVWLRDGKYEaltspPT------PLPVSVRPSRVGIFLDYEAGEVSFYNVTDRSHLFTFT 148

                        170
                 ....*....|.
gi 154354992 381 VSFPGPLFPVF 391
Cdd:cd13745  149 DTFSGTLRPYF 159

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
                  ....*....|....*....|....*....|....*....|....*..
gi 154354992  235 DERTVSPFLQLSDDRKTLTFSTKKSKaCADGPERFDHWPNALAATSF 281
Cdd:pfam13765   4 DPNTAHPSLVLSEDLKSVRYGDERQN-VPDNPERFDSWPCVLGSEGF 49

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 154354992 231 DIRIDERTVSPFLQLSDDRKTLTFStKKSKACADGPERFDHWPNALAATSFQNGLHAWMVNVQNSCAYKVGVASGHLPRK 310
Cdd:cd15813   10 NVTLDPETAHPNLIFSDDLKSVRLG-NKWDRLPDNPERFDSCIIVLGSPSFTSGRHYWEVEVGDKTGWILGVCKASVSRK 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154354992 311 GSGSDCRlgHNAFSWVFSRYDQEFRFSHNGQhEPLGLLRGPAQLGVVLDLQVQELLFYE-PASGTVLCAHHVSFPGPLFP 389
Cdd:cd15813   89 GSMTLSP--ENGYWVVMMTKRNEYQASTSPP-TRLWLREPPRRVGIFLDYEAGDISFYNvTAKSHIYTFTSFSSSGPLQP 165

                 ..
gi 154354992 390 VF 391
Cdd:cd15813  166 IF 167