SPRY domain; SPRY domains, first identified in the SP1A kinase of Dictyostelium and rabbit Ryanodine receptor (hence the name), are homologous to B30.2. SPRY domains have been identified in at least 11 protein families, covering a wide range of functions, including regulation of cytokine signaling (SOCS), RNA metabolism (DDX1 and hnRNP), immunity to retroviruses (TRIM5alpha), intracellular calcium release (ryanodine receptors or RyR) and regulatory and developmental processes (HERC1 and Ash2L). B30.2 also contains residues in the N-terminus that form a distinct PRY domain structure; i.e. B30.2 domain consists of PRY and SPRY subdomains. B30.2 domains comprise the C-terminus of three protein families: BTNs (receptor glycoproteins of immunoglobulin superfamily); several TRIM proteins (composed of RING/B-box/coiled-coil or RBCC core); Stonutoxin (secreted poisonous protein of the stonefish Synanceia horrida). TRIM/RBCC proteins are involved in a variety of processes, including apoptosis, cell cycle regulation, cell growth, senescence, viral response, meiosis, cell differentiation, and vesicular transport. Genes belonging to this family are implicated in several human diseases that vary from cancer to rare genetic syndromes. The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site. While SPRY domains are evolutionarily ancient, B30.2 domains are a more recent adaptation where the SPRY/PRY combination is a possible component of immune defense. Mutations found in the SPRY-containing proteins have shown to cause Mediterranean fever and Opitz syndrome.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 256773195 3504 GTRFLLLRETAHPALQISAN-GTVISFSERRR----LTEIPSVLGEELPACGQHYWETTVADSPAYRLGICTSSAVRAGA 3578
Cdd:cd12898     1 GTRFLLLRETAHPALHISSDrGTVIYFHERRRkmssLTECPSVLGEELPSCGQYYWETTVTRCPAYRLGICSSSASQAGA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 256773195 3579 LGQGETSWYMHC---SEPQRYTFFYSGIVSEVHATERPARVGILLDYTNQRLLFINAESGQLLFIVRHRFNEGVHPAFAL 3655
Cdd:cd12898    81 LGEGSTSWCLHCvptSEPCRYTLLHSGIVSDVFVTERPARVGTLLDYNNGRLIFINAESGQLLGIFRHRFAQPCHPAFAL 160

                         170
                  ....*....|.
gi 256773195 3656 EKPGRCTLHLG 3666
Cdd:cd12898   161 EKPGKLELHMG 171

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 256773195 3321 EPSSATSTTIAVYWSVNKED--VVDSFQVYCVEEPQDD-QEINELVeeyrltVKESCCIFEDLEPDRCYQVWVMAVNFTG 3397
Cdd:cd00063     8 RVTDVTSTSVTLSWTPPEDDggPITGYVVEYREKGSGDwKEVEVTP------GSETSYTLTGLKPGTEYEFRVRAVNGGG 81

                          90
                  ....*....|..
gi 256773195 3398 CSLPSERAIFRT 3409
Cdd:cd00063    82 ESPPSESVTVTT 93

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 256773195   3153 KVQLGEFLENLQEKSLRIEAFVSEIESFFNTIEEKCSKNEKRLEMQNEEMMKRVLAQYDEKAQSFEEVKKKKMEFLHDQM 3232
Cdd:smart00502    2 REALEELLTKLRKKAAELEDALKQLISIIQEVEENAADVEAQIKAAFDELRNALNKRKKQLLEDLEEQKENKLKVLEQQL 81

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*
gi 256773195   3233 VHFLQSMDTAKDTLETIVREAEELDETVFLASFEEINERLLSAME 3277
Cdd:smart00502   82 ESLTQKQEKLSHAINFTEEALNSGDPTELLLSKKLIIERLQNLLK 126

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 256773195 3504 GTRFLLLRETAHPALQISAN-GTVISFSERRR----LTEIPSVLGEELPACGQHYWETTVADSPAYRLGICTSSAVRAGA 3578
Cdd:cd12898     1 GTRFLLLRETAHPALHISSDrGTVIYFHERRRkmssLTECPSVLGEELPSCGQYYWETTVTRCPAYRLGICSSSASQAGA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 256773195 3579 LGQGETSWYMHC---SEPQRYTFFYSGIVSEVHATERPARVGILLDYTNQRLLFINAESGQLLFIVRHRFNEGVHPAFAL 3655
Cdd:cd12898    81 LGEGSTSWCLHCvptSEPCRYTLLHSGIVSDVFVTERPARVGTLLDYNNGRLIFINAESGQLLGIFRHRFAQPCHPAFAL 160

                         170
                  ....*....|.
gi 256773195 3656 EKPGRCTLHLG 3666
Cdd:cd12898   161 EKPGKLELHMG 171

ribonuclease E; Reviewed

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 256773195  448 QEKFEPDMEGLEPISTEKTEQASEYVTSSEPIVHREEEHAPEPIVHRE---------EEHAPEPIVHREEEHaPEPIVHR 518
Cdd:PRK10811  856 EEQREAEEVQVQPVVAEVPVAAAVEPVVSAPVVEAVAEVVEEPVVVAEpqpeevvvvETTHPEVIAAPVTEQ-PQVITES 934

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 256773195  519 EEEHAPESIVHREEEHAPESIVQREEEHAPEPESIVHREEEHAPGPVPIVHREEEHVPElESIVHRGEEHAPEPIVHRDE 598
Cdd:PRK10811  935 DVAVAQEVAEHAEPVVEPQDETADIEEAAETAEVVVAEPEVVAQPAAPVVAEVAAEVET-VTAVEPEVAPAQVPEATVEH 1013

                         170       180
                  ....*....|....*....|....
gi 256773195  599 GHAPEPIVHR-EEEHVPEPIVHRD 621
Cdd:PRK10811 1014 NHATAPMTRApAPEYVPEAPRHSD 1037

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 256773195 3321 EPSSATSTTIAVYWSVNKED--VVDSFQVYCVEEPQDD-QEINELVeeyrltVKESCCIFEDLEPDRCYQVWVMAVNFTG 3397
Cdd:cd00063     8 RVTDVTSTSVTLSWTPPEDDggPITGYVVEYREKGSGDwKEVEVTP------GSETSYTLTGLKPGTEYEFRVRAVNGGG 81

                          90
                  ....*....|..
gi 256773195 3398 CSLPSERAIFRT 3409
Cdd:cd00063    82 ESPPSESVTVTT 93

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 256773195 3416 IHVEDCTvcWNTATVRWRPANPEATE--TYTLEYCRQHSPEGEGLRSfSGIKGLQLKV-NLPPNDNYFFYVRATNASGTS 3492
Cdd:cd00063     7 LRVTDVT--STSVTLSWTPPEDDGGPitGYVVEYREKGSGDWKEVEV-TPGSETSYTLtGLKPGTEYEFRVRAVNGGGES 83

                          90
                  ....*....|
gi 256773195 3493 EQSEAALIST 3502
Cdd:cd00063    84 PPSESVTVTT 93

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 256773195   3416 IHVEDCTvcWNTATVRWRPANPEATETYTLEYCRQHSPEGEGLRSFSGI-KGLQLKV-NLPPNDNYFFYVRATNASGTS 3492
Cdd:smart00060    7 LRVTDVT--STSVTLSWEPPPDDGITGYIVGYRVEYREEGSEWKEVNVTpSSTSYTLtGLKPGTEYEFRVRAVNGAGEG 83

Fibronectin type III domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 256773195  3323 SSATSTTIAVYWS--VNKEDVVDSFQVYC--VEEPQDDQEINELVEEYRLTVKesccifeDLEPDRCYQVWVMAVNFTGC 3398
Cdd:pfam00041    9 TDVTSTSLTVSWTppPDGNGPITGYEVEYrpKNSGEPWNEITVPGTTTSVTLT-------GLKPGTEYEVRVQAVNGGGE 81

                   ....
gi 256773195  3399 SLPS 3402
Cdd:pfam00041   82 GPPS 85

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 256773195 3504 GTRFLLLRETAHPALQISAN-GTVISFSERRR----LTEIPSVLGEELPACGQHYWETTVADSPAYRLGICTSSAVRAGA 3578
Cdd:cd12898     1 GTRFLLLRETAHPALHISSDrGTVIYFHERRRkmssLTECPSVLGEELPSCGQYYWETTVTRCPAYRLGICSSSASQAGA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 256773195 3579 LGQGETSWYMHC---SEPQRYTFFYSGIVSEVHATERPARVGILLDYTNQRLLFINAESGQLLFIVRHRFNEGVHPAFAL 3655
Cdd:cd12898    81 LGEGSTSWCLHCvptSEPCRYTLLHSGIVSDVFVTERPARVGTLLDYNNGRLIFINAESGQLLGIFRHRFAQPCHPAFAL 160

                         170
                  ....*....|.
gi 256773195 3656 EKPGRCTLHLG 3666
Cdd:cd12898   161 EKPGKLELHMG 171

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 256773195 3507 FLLLRETAHPALQISANGTVISFSERR-----------RLTEIPSVLGEELPACGQHYWETTVADSPAYRLGICTSSAVR 3575
Cdd:cd12899     2 FHLNEDTAHPLLSISEDGFTVVYGEEElpardlsfsdnSFTRCVAVMGSLIPVRGKHYWEVEVDEQTEYRVGVAFEDTQR 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 256773195 3576 AGALGQGETSWYM-HCSEPQR--YTFFYSGIVSEVHATERPARVGILLDYTNQRLLFINAESGQLLFIVRHRFNEGVHPA 3652
Cdd:cd12899    82 NGYLGANNTSWCMrHIITPSRhkYEFLHNGWTPDIRITVPPKKIGILLDYDSGRLSFFNVDLAQHLYTFSCQFQHFVHPC 161

                         170
                  ....*....|....*
gi 256773195 3653 FALEKPGRCTLHLGL 3667
Cdd:cd12899   162 FSLEKPGALKVHNGI 176

PRY/SPRY domain, also known as B30.2; This domain contains residues in the N-terminus that form a distinct PRY domain structure such that the B30.2 domain consists of PRY and SPRY subdomains. B30.2 domains comprise the C-terminus of three protein families: BTNs (receptor glycoproteins of immunoglobulin superfamily); several TRIM proteins (composed of RING/B-box/coiled-coil core); Stonutoxin (secreted poisonous protein of the stonefish Synanceia horrida). While SPRY domains are evolutionarily ancient, B30.2 domains are a more recent adaptation where the SPRY/PRY combination is a possible component of immune defense. Among the TRIM proteins, also known as the N-terminal RING finger/B-box/coiled coil (RBCC) family, only Classes I and II contain the B30.2 domain that has evolved under positive selection. Class I TRIM proteins include multiple members involved in antiviral immunity at various levels of interferon signaling cascade. Among the 75 human TRIMs, roughly half enhance immune response, which they do at multiple levels in signaling pathways. The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 256773195 3512 ETAHPALQISANGTVIS--------FSERRRLTEIPSVLGEELPACGQHYWETTVADSPAYRLGICTSSAVRAGA---LG 3580
Cdd:cd12874     6 DTAHLNLILSDDLRSVRvgdisqhpPEPPPRFFECWQVLGSQSFSSGRHYWEVDVQDDSSWYVGVTYKSLPRKGKmsnLG 85

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 256773195 3581 QGETSWYMHCSEpQRYTFFYSGIVSEVHATErPARVGILLDYTNQRLLFIN-AESGQLLFIVRHRFNEGVHPAFAL 3655
Cdd:cd12874    86 RNNGSWCLEWRE-NEFSAWHNNPETRLPVTP-PRRLGVFLDCDGGSLSFYGvTDGVQLLYTFKAKFTEPLYPAFWL 159

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 256773195 3534 RLTEIPSVLGEELPACGQHYWETTVADSPAYRLGICTSSAVRAGALGQGETSW---YMHcsepQRYTFFYSGIVSEVHAT 3610
Cdd:cd12903    39 RFRDWAVVLGDTPVTSGRHYWEVTVKRSQEFRIGVADVDMSRDECIGTNESSWvfaYAQ----RKWYAMVANETVPVPLV 114

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 256773195 3611 ERPARVGILLDYTNQRLLFINAESGQLLFIVRHRFNEGVHPAFAL 3655
Cdd:cd12903   115 GKPDRVGLLLDYEAGKLSLVDVEKNSVVHTMSAEFRGPVVPAFAL 159

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 256773195 3512 ETAHPALQISANGTVISFSERR--------RLTEIPSVLGEELPACGQHYWETTVADSPAYRLGICTSSAVRAG--ALGQ 3581
Cdd:cd13745    10 DTAHPNLVLSEDRKSVRHGDTRqdlpdnpeRFDTYPCVLGAEGFTGGRHYWEVEVGDKTEWTLGVCRESVSRKGevTLSP 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 256773195 3582 GETSW--------YMHCSEPqrytffysgiVSEVHATERPARVGILLDYTNQRLLFINAESGQLLFIVRHRFNEGVHPAF 3653
Cdd:cd13745    90 ENGYWtvwlrdgkYEALTSP----------PTPLPVSVRPSRVGIFLDYEAGEVSFYNVTDRSHLFTFTDTFSGTLRPYF 159

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 256773195 3512 ETAHPALQISANGTVISFSERR--------RLTEIPSVLGEELPACGQHYWETTVADSPAYRLGICTSSAVRAG--ALGQ 3581
Cdd:cd15829    26 ETAHPNLLVSEDKKCVTFTKKKqrvpdspkRFTVNPVVLGFPGFHSGRHFWEVEVGDKPEWAVGVCKDSLSTKArrPPSG 105

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 256773195 3582 GETSWymhCSEPQRYTFFYSGIV-SEVHATERPARVGILLDYTNQRLLFINAESGQLLFIVRHRFNEGVHPAF 3653
Cdd:cd15829   106 QQGCW---RIQLQGGDYDAPGAVpPPLLLEVKPRGIGVFLDYELGEISFYNMPEKSHIHTFTDTFSGPLRPYF 175

PRY/SPRY domain in tripartite motif-binding protein 50 (TRIM50); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM50. TRIM50, an E3 ubiquitin ligase, is deleted in Williams-Beuren (WBS) syndrome, a multi-system neurodevelopmental disorder caused by the deletion of contiguous genes at chromosome region 7q11.23. It is specifically expressed in gastric parietal cells and may play an essential role in tubulovesicular dynamics. It also interacts with and increases the level of p62, a multifunctional adaptor protein that is implicated in various cellular processes such as the autophagy clearance of polyubiquitinated protein aggregates.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 256773195 3513 TAHPALQISANGTVIS---FSERR-----RLTEIPSVLGEELPACGQHYWETTVADSPAYRLGICTSSAVRAGALGQGET 3584
Cdd:cd13743    20 TAHPMLELSKGNTVVEcglLAQRLpsnpeRFDYSNCVLASRGFSSGKHYWEVVVGSKSKWRLGLIKGTTSRKGKLNKSPE 99

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 256773195 3585 S--WYMHCSEPQRYTFFYSGIVSeVHATERPARVGILLDYTNQRLLFINAESGQ-LLFI--VRHRFNEGVHPAF 3653
Cdd:cd13743   100 NgvWLIGLKEGRVYEAFANPRVP-LPLSTRPQRIGVFLDYEKGELTFYNADSPDeLVPIytFQAEFQGKLYPLL 172

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 256773195 3508 LLLRETAHPALQISANGTVISFSER--------RRLTEIPSVLGEELPACGQHYWETTVADSPAYRLGICTSS------- 3572
Cdd:cd15828    13 TLDPETAHPQLTVSEDRKSVLYGEMkqnvcynpRRFYLCPAVLGSEGFHSGRQYWEVEVGDKPEWTLGVCQDClprnwsn 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 256773195 3573 --AVRAG--ALGQGETSWYMHCSePQRytffySGIVSEVhateRPARVGILLDYTNQRLLFINAESGQLLFIVRHRFNEG 3648
Cdd:cd15828    93 qpSVQDGlwAIGRYSESNYVALG-PKK-----IQLLPKV----RPSKIGIFLDYELGEVSFYNMNDRSLLYTFSDSFTGT 162

                  ....*
gi 256773195 3649 VHPAF 3653
Cdd:cd15828   163 LWPYF 167

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 256773195 3512 ETAHPALQISANGTVISFSER--------RRLTEIPSVLGEELPACGQHYWETTVADSPAYRLGICTSSAVRA------- 3576
Cdd:cd15817     7 ETAHPNLIVSEDRKAVRYRRMkpncpydpRRFTVYPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSLPRNaqdppsp 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 256773195 3577 ----GALGQGETSWymHCSEPqrytfFYSGIVSEVhateRPARVGILLDYTNQRLLFINAESGQLLFIVRHRFNEGVHPA 3652
Cdd:cd15817    87 lggcWQIGRYMSGY--VASGP-----KTTQLLPVV----KPSRIGIFLDYELGEVSFYNMNDRSHLYTFTDTFTGKLIPY 155

                  .
gi 256773195 3653 F 3653
Cdd:cd15817   156 F 156

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 256773195 3512 ETAHPALQISANGTVISFSERR--------RLTEIPSVLGEELPACGQHYWETTVADSPAYRLGICTSSAVR--AGALGQ 3581
Cdd:cd15811     7 DTANPELVLSEDRRSVRRGDLRqalpdspeRFDPGPCVLGRERFTSGRHYWEVEVGDRTSWALGVCKENVNRkeKGELSA 86

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 256773195 3582 GETSWYMhcsepqrytFFYSGIVSEVHAT-----ERPARVGILLDYTNQRLLFINAESGQLLFI 3640
Cdd:cd15811    87 GNGFWIL---------VFLGNYYSSERRTfaplrDPPRRVGIFLDYEAGHLSFYSATDGSLLFI 141

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 256773195 3512 ETAHPALQISANGTVISFSERR--------RLTEIPSVLGEELPACGQHYWETTVADSPAYRLGICTSSAVRAGALgqge 3583
Cdd:cd15819     9 DTAHPALILSEDGRSVTWGETRqdlpenpeRFDSLPCVLGQEGFTSGRHYWEVEVGDRTSWDLGVCRDNVMRKGRV---- 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 256773195 3584 tswymhCSEPQ-------RYTFFYSGIVS-EVHAT--ERPARVGILLDYTNQRLLFINAESGQLLFIVRH-RFNEGVHPA 3652
Cdd:cd15819    85 ------TLSPEngfwairLYGNEYWALTSpETPLTlkEPPRRVGIFLDYEAGDVSFYNMTDGSHIYTFPQtAFSGPLRPF 158

                  ...
gi 256773195 3653 FAL 3655
Cdd:cd15819   159 FRL 161

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 256773195 3509 LLRETAHPALQISANGTVI---SFSERR-----RLTEIPSVLGEELPACGQHYWETTVADSPAYRLGICTSSAVRAGA-- 3578
Cdd:cd15821     8 LDVDTANNYLIISEDLRSVrcgCFRQNRkelaeRFDDALCVLGSPRFTSGRHYWEVDVGTSTEWDLGVCRESVNRQGPie 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 256773195 3579 LGQGETSWYMHCSEPQRYtffysgIVSEVHAT-----ERPARVGILLDYTNQRLLFINAESGQLLFIVRHRFNEG-VHPA 3652
Cdd:cd15821    88 LSPEHGFWTVSLRDGSVF------FASTVPLTvlwvnPRLHRVGIFLDMEMGTISFYDVSDGSHIFTFTKISAEEpLRPF 161

                         170
                  ....*....|
gi 256773195 3653 FAlekPGRCT 3662
Cdd:cd15821   162 FA---PANPY 168

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 256773195 3512 ETAHPALQISANGTVISFSERR--------RLTEIPSVLGEELPACGQHYWETTVADSPAYRLGICTSSAVRAGA--LGQ 3581
Cdd:cd12888     7 DTAHPRLVLSEDRKSVRWGDTRqdlpdnpeRFDTWPCVLGCEGFTSGRHYWEVEVGDGGGWAVGVARESVRRKGEisFSP 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 256773195 3582 GETSWYMHCSEPQRYTFFYSGIVSEVHatERPARVGILLDYTNQRLLFINAESGQLLFIVRHRFNEG--VHPAFALEKPG 3659
Cdd:cd12888    87 EEGIWAVGQWGGQYWALTSPETPLPLS--EVPRRIRVYLDYEGGQVAFFDADNEAPIFTFPPASFAGerIFPWFWVGKGS 164

                  ....
gi 256773195 3660 RCTL 3663
Cdd:cd12888   165 QLKL 168