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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767983319   295 PSAPViNPQVPNSaTGSSVRVCWSLYSDDTVESYQLSYRpVQDSSPGTDQAEFTVTVKETYCSVTNLVPNTQYEFWVTAH 374
Cdd:smart00060   1 PSPPS-NLRVTDV-TSTSVTLSWEPPPDDGITGYIVGYR-VEYREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAV 77

                   ....*.
gi 767983319   375 NRAGPS 380
Cdd:smart00060  78 NGAGEG 83

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

                         10        20
                 ....*....|....*....|....*...
gi 767983319 178 VFCVTCKTPIRAFQKVFDEHKEHEVIPL 205
Cdd:cd19788   12 IYCLTCEVPTCSMCKVFGAHKDCEVAPL 39

Domain in SPla and the RYanodine Receptor; Domain of unknown function. Distant homologues are domains in butyrophilin/marenostrin/pyrin homologues.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767983319   542 RGHHYWEVEVDEHLDYRVGVAFADVR--KQEDLGANCLSWCMRhtfASSRHKYeflHNRTTPDIRITV--PPKKIGILLD 617
Cdd:smart00449   1 SGRHYFEVEIGDGGHWRVGVATKSVPrgYFALLGEDKGSWGYD---GDGGKKY---HNSTGPEYGLPLqePGDVIGCFLD 74

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 767983319   618 YEHSKLSFFNV-DLSQHLYTFSCQLHEFVHPCFSLEKPGCLKV 659
Cdd:smart00449  75 LEAGTISFYKNgKYLHGLAFFDVKFSGPLYPAFSLGSGNSVRL 117

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 767983319 295 PSAPViNPQVpNSATGSSVRVCWSLYSDDT--VESYQLSYRPVQDSSPGTDQaefTVTVKETYCSVTNLVPNTQYEFWVT 372
Cdd:cd00063    1 PSPPT-NLRV-TDVTSTSVTLSWTPPEDDGgpITGYVVEYREKGSGDWKEVE---VTPGSETSYTLTGLKPGTEYEFRVR 75

                         90
                 ....*....|....*...
gi 767983319 373 AHNRAGPSPSSERAVYMT 390
Cdd:cd00063   76 AVNGGGESPPSESVTVTT 93

Fibronectin type 3 domain [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767983319 294 APSAPViNPQVpNSATGSSVRVCWSLYSDDTVESYQLsYRpvQDSSPGTdqaeFTV--TVKETYCSVTNLVPNTQYEFWV 371
Cdd:COG3401  232 PPSAPT-GLTA-TADTPGSVTLSWDPVTESDATGYRV-YR--SNSGDGP----FTKvaTVTTTSYTDTGLTNGTTYYYRV 302

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767983319 372 TAHNRAG----PSPSSERAVYMTAPSPPIIKTKEIRSCEEAVLIcWESGNLNPVDSYTVELTQAESPEASGVTESVVGip 447
Cdd:COG3401  303 TAVDAAGnesaPSNVVSVTTDLTPPAAPSGLTATAVGSSSITLS-WTASSDADVTGYNVYRSTSGGGTYTKIAETVTT-- 379

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 767983319 448 TCESVVQLQPGRSYIIYVRALNMGGP-SVRSEPATVHT 484
Cdd:COG3401  380 TSYTDTGLTPGTTYYYKVTAVDAAGNeSAPSEEVSATT 417

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 767983319 392 PSPPI-IKTKEIRSceEAVLICWE--SGNLNPVDSYTVELTQAESPEASGVTESVVGIPTCEsVVQLQPGRSYIIYVRAL 468
Cdd:cd00063    1 PSPPTnLRVTDVTS--TSVTLSWTppEDDGGPITGYVVEYREKGSGDWKEVEVTPGSETSYT-LTGLKPGTEYEFRVRAV 77

                         90
                 ....*....|....*.
gi 767983319 469 NMGGPSVRSEPATVHT 484
Cdd:cd00063   78 NGGGESPPSESVTVTT 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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767983319   392 PSPPIIKTKEIRSceEAVLICWESGNLNPVDSYTVELTQAESPEASGVTESVVGIPTCESVVQ-LQPGRSYIIYVRALNM 470
Cdd:smart00060   2 SPPSNLRVTDVTS--TSVTLSWEPPPDDGITGYIVGYRVEYREEGSEWKEVNVTPSSTSYTLTgLKPGTEYEFRVRAVNG 79

                   ....
gi 767983319   471 GGPS 474
Cdd:smart00060  80 AGEG 83

B-box-type 2 zinc finger found in muscle-specific RING finger protein (MuRF) family; This family corresponds to a group of striated muscle-specific tripartite motif (TRIM) proteins, including TRIM63/MuRF-1, TRIM55/MuRF-2, and TRIM54/MuRF-3, which function as E3 ubiquitin ligases in ubiquitin-mediated muscle protein turnover. They are tightly developmentally regulated in skeletal muscle and associate with different cytoskeleton components, such as microtubules, Z-disks and M-bands, as well as with metabolic enzymes and nuclear proteins. They also cooperate with diverse proteins implicated in selective protein degradation by the proteasome and autophagosome, and target proteins of metabolic regulation, sarcomere assembly and transcriptional regulation. Moreover, MURFs display variable fibre-type preferences. TRIM63/MuRF-1 is predominantly fast (type II) fibre-associated in skeletal muscle. TRIM55/MuRF-2 is predominantly slow-fibre associated. TRIM54/MuRF-3 is ubiquitously present. They play an active role in microtubule-mediated sarcomere assembly. MuRFs belong to the C-II subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, and an acidic residue-rich (AR) domain positioned C-terminal to the RBCC domain. They also harbor a MURF family-specific conserved box (MFC) between its RING-HC finger and Bbox domains. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                         10        20
                 ....*....|....*....|....*...
gi 767983319 178 VFCVTCKTPIRAFQKVFDEHKEHEVIPL 205
Cdd:cd19788   12 IYCLTCEVPTCSMCKVFGAHKDCEVAPL 39

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 767983319 489 FRLNKDTCHPWLTISEDGLTAVRSERRTPARElSPSDTHFTRCVAVMGNLIPVRGHHYWEVEVDEHLDYRVGVAFADVRK 568
Cdd:cd13734    1 FKLDPKTAHRKLRLSNDNLTVEYDPEGSKDQA-AVLPRRFTGSPAVLGDVAISSGRHYWEVSVSRSTSYRVGVAYKSAPR 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767983319 569 QEDLGANCLSWCMRHTFassrHKYEFLHNRTTPDIRITVPPKKIGILLDYEHSKLSFFNVDLSQHLYTFSCQLHEFVHPC 648
Cdd:cd13734   80 DEDLGKNSTSWCLSRDN----NRYTARHDGKVVDLRVTGHPARIGVLLDYDNGTLSFYDAESKQHLYTFHVDFEGPVCPA 155

                        170
                 ....*....|..
gi 767983319 649 FSLEkPGCLKVH 660
Cdd:cd13734  156 FAVW-NGSLTLH 166

PRY/SPRY domain in tripartite motif-containing (TRIM) proteins, including TRIM5, TRIM6, TRIM7, TRIM10, TRIM11, TRIM17, TRIM20, TRIM21, TRIM27, TRIM35, TRIM38, TRIM41, TRIM50, TRIM58, TRIM60, TRIM62, TRIM69, TRIM72, NF7 and bloodthirsty; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several Class IV TRIM proteins, including TRIM7, TRIM35, TRIM41, TRIM50, TRIM62, TRIM69, TRIM72, TRIM protein NF7 and bloodthirsty (bty). TRIM7 interacts with glycogenin and stimulates its self-glucosylating activity via its SPRY domain. TRIM35 may play a role as a tumor suppressor and is implicated in the cell death mechanism. TRIM41 is localized to speckles in the cytoplasm and nucleus, and functions as an E3 ligase that catalyzes the ubiquitin-mediated degradation of protein kinase C. 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. TRIM62 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. 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. TRIM72 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. 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 767983319 494 DTCHPWLTISEDGlTAVRseRRTPARELSPSDTHFTRCVAVMGNLIPVRGHHYWEVEVDEHLDYRVGVAFADV-RKqedl 572
Cdd:cd13733    7 DTAHPNLILSEDL-KSVR--YGDKRQNLPDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVnRK---- 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767983319 573 GANCLS-----WCMRHTfasSRHKYEFLHNRTTPdIRITVPPKKIGILLDYEHSKLSFFNVDLSQHLYTFSCQLHEFVHP 647
Cdd:cd13733   80 GKITLSpengyWTVGLR---NGNEYKALTSPSTP-LSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDCFTEKLYP 155

                 ....
gi 767983319 648 CFSL 651
Cdd:cd13733  156 YFSP 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 767983319 491 LNKDTCHPWLTISEDGLTAVRSERR-----TPARelspsdthFTRCVAVMGNLIPVRGHHYWEVEVDEHLDYRVGVAFAD 565
Cdd:cd13745    7 LDPDTAHPNLVLSEDRKSVRHGDTRqdlpdNPER--------FDTYPCVLGAEGFTGGRHYWEVEVGDKTEWTLGVCRES 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767983319 566 V-RKQE-DLGANCLSWCMRHtfasSRHKYEFLHNRTTPdIRITVPPKKIGILLDYEHSKLSFFNVDLSQHLYTFSCQLHE 643
Cdd:cd13745   79 VsRKGEvTLSPENGYWTVWL----RDGKYEALTSPPTP-LPVSVRPSRVGIFLDYEAGEVSFYNVTDRSHLFTFTDTFSG 153

                        170
                 ....*....|..
gi 767983319 644 FVHPCFSlekPG 655
Cdd:cd13745  154 TLRPYFY---PG 162

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767983319 491 LNKDTCHPWLTISEDGLTAVRSERRTpareLSPSDT-HFTRCVAVMGNLIPVRGHHYWEVEVDEH-LDYRVGVAFADVRK 568
Cdd:cd13738    3 LEPDTLHPRLRLSDDRLTVSCGWLGT----LGLCPPqRFDKLWQVLSRDSFFSGRHYWEVDLQEAgAGWWVGAAYPSIGR 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767983319 569 QED-----LGANCLSWCMRhtfassRHKYEF--LHNRTTPDIRITVPPKKIGILLDYEHSKLSFFNVDLS-QHLYTFSCQ 640
Cdd:cd13738   79 KGDseaarLGWNRQSWCLK------RYDLEYwaFHDGQRSRLRPEDDPDRLGVFLDYEAGILSFYDVTGGmTHLHTFRAT 152

                        170
                 ....*....|.
gi 767983319 641 LHEFVHPCFSL 651
Cdd:cd13738  153 FQEPLYPALRL 163

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 767983319 491 LNKDTCHPWLTISEDgLTAVRSERrtPARELSPSDTHFTRCVAVMGNLIPVRGHHYWEVEVDEHLDYRVGVAFADVRKQE 570
Cdd:cd12874    3 FDPDTAHLNLILSDD-LRSVRVGD--ISQHPPEPPPRFFECWQVLGSQSFSSGRHYWEVDVQDDSSWYVGVTYKSLPRKG 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767983319 571 D---LGANCLSWC---MRHTFASSrhkyeflHNRTTPDIRITvPPKKIGILLDYEHSKLSFFNV-DLSQHLYTFSCQLHE 643
Cdd:cd12874   80 KmsnLGRNNGSWClewRENEFSAW-------HNNPETRLPVT-PPRRLGVFLDCDGGSLSFYGVtDGVQLLYTFKAKFTE 151

                 ....*...
gi 767983319 644 FVHPCFSL 651
Cdd:cd12874  152 PLYPAFWL 159

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 767983319 491 LNKDTCHPWLTISEDgLTAVRSERRTPARELSPSdtHFTRCVAVMGNLIPVRGHHYWEVEVDEHLDYRVGVAFADVRKQe 570
Cdd:cd15813   13 LDPETAHPNLIFSDD-LKSVRLGNKWDRLPDNPE--RFDSCIIVLGSPSFTSGRHYWEVEVGDKTGWILGVCKASVSRK- 88

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767983319 571 dlGANCLS-----WCMRHTfasSRHKYEFLHNRTTPdIRITVPPKKIGILLDYEHSKLSFFNVDLSQHLYTFSC 639
Cdd:cd15813   89 --GSMTLSpengyWVVMMT---KRNEYQASTSPPTR-LWLREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTS 156

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 767983319 491 LNKDTCHPWLTISEDGLTAVRSERRTPARelsPSDTHFTRCVAVMGNLIPVRGHHYWEVEVDEHLDYRVGVAFADVRKQE 570
Cdd:cd12905    8 FDPETAHPSLILSRDLTAVTESDEMQPYP---RSPKRFLQCVNVLASQGFQSGRHYWEVWVGSKTKWDLGVASESVDRQA 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767983319 571 --DLGANCLSWCMRhtfassrhkyefLHNR------TTPDIRITV--PPKKIGILLDYEHSKLSFFNVDLSQHLYTFS-- 638
Cdd:cd12905   85 rvKLCPENGYWTLR------------LRNGdeywagTQPWTRLRVtsRPQRIGVFLDCEERKVSFYNADDMSLLYSFHqg 152

                        170
                 ....*....|....
gi 767983319 639 --CQLHEFVHPCFS 650
Cdd:cd12905  153 prGKVFPFFSTCFS 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 767983319 491 LNKDTCHPWLTISEDgLTAVR--SERRT----PARelspsdthFTRCVAVMGNLIPVRGHHYWEVEVDEHLDYRVGVAFA 564
Cdd:cd12893    4 LDPNTAHPWLSLSED-LTSVRysSEKQQlpdnPER--------FDPYPCVLGSEGFTSGKHSWDVEVGDNTSWMLGVAKE 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767983319 565 DVRKQEDLGANCLS--WCMRHtfasSRHKYEFLHNrTTPDIRITV--PPKKIGILLDYEHSKLSFFNVDLSQHLYTFScq 640
Cdd:cd12893   75 SVQRKGKFTLSPESgfWTIGF----SEGKYSARTS-PEPRTPLRVkqKPQRIRVQLDWDRGKVSFSDPDTNTHIHTFT-- 147

                        170
                 ....*....|....*....
gi 767983319 641 lHEFVH---PCFSlekPGC 656
Cdd:cd12893  148 -HTFTErvfPYFY---TGC 162

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 767983319 534 VMGNLIPVRGHHYWEVEVDEHLDYRVGVAFADVRKQEDLGANCLSWcmrhTFA-SSRHKYEFLHNRTTPdIRITVPPKKI 612
Cdd:cd12903   46 VLGDTPVTSGRHYWEVTVKRSQEFRIGVADVDMSRDECIGTNESSW----VFAyAQRKWYAMVANETVP-VPLVGKPDRV 120

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 767983319 613 GILLDYEHSKLSFFNVDLSQHLYTFSCQLHEFVHPCFSLEKpGCLKVHNG 662
Cdd:cd12903  121 GLLLDYEAGKLSLVDVEKNSVVHTMSAEFRGPVVPAFALWD-GELLTHSG 169

PRY/SPRY domain in tripartite motif-binding protein 41 (TRIM41); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of tripartite motif-containing protein 41 (TRIM41). TRIM41 (also known as RING finger-interacting protein with C kinase or RINCK) is localized to speckles in the cytoplasm and nucleus, and functions as an E3 ligase that catalyzes the ubiquitin-mediated degradation of protein kinase C.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767983319 491 LNKDTCHPWLTISEDGLTAVRSERRtpaRELSPSDTHFTRCVAVMGNLIPVRGHHYWEVEVDEHLDYRVGVAFADVRKQE 570
Cdd:cd13741    4 LDPDTAHPALLLSPDRRGVRLAERR---QEVPEHPKRFSADCCVLGAQGFRSGRHYWEVEVGGRRGWAVGAARESTHHKE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767983319 571 DLGANCLSWCMRHTFASS-RHKYEFLHNRTTPDIRITV-------------------------PPKKIGILLDYEHSKLS 624
Cdd:cd13741   81 KVGSGGSSVSSGDASSSRhHHRRRRLHLPQQPLLQREVwcvgtngkryqaqssteqtllspseKPRRFGVYLDYEAGRLG 160

                        170       180       190
                 ....*....|....*....|....*....|..
gi 767983319 625 FFNVDLSQHLYTFSCQLH-EFVHPCFSLEKPG 655
Cdd:cd13741  161 FYNAETLAHVHTFSAAFLgERVFPFFRVLSKG 192

Domain in SPla and the RYanodine Receptor; Domain of unknown function. Distant homologues are domains in butyrophilin/marenostrin/pyrin homologues.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767983319   542 RGHHYWEVEVDEHLDYRVGVAFADVR--KQEDLGANCLSWCMRhtfASSRHKYeflHNRTTPDIRITV--PPKKIGILLD 617
Cdd:smart00449   1 SGRHYFEVEIGDGGHWRVGVATKSVPrgYFALLGEDKGSWGYD---GDGGKKY---HNSTGPEYGLPLqePGDVIGCFLD 74

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 767983319   618 YEHSKLSFFNV-DLSQHLYTFSCQLHEFVHPCFSLEKPGCLKV 659
Cdd:smart00449  75 LEAGTISFYKNgKYLHGLAFFDVKFSGPLYPAFSLGSGNSVRL 117

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 767983319 491 LNKDTCHPWLTISEDGlTAVRSERRTpaRELSPSDTHFTRCVAVMGNLIPVRGHHYWEVEVDEHLDYRVGV---AFADVR 567
Cdd:cd15828   14 LDPETAHPQLTVSEDR-KSVLYGEMK--QNVCYNPRRFYLCPAVLGSEGFHSGRQYWEVEVGDKPEWTLGVcqdCLPRNW 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767983319 568 KQEDLGANCLsWCMRHTFASSrhkYEFLHNRTTpDIRITVPPKKIGILLDYEHSKLSFFNVDLSQHLYTFSCQLHEFVHP 647
Cdd:cd15828   91 SNQPSVQDGL-WAIGRYSESN---YVALGPKKI-QLLPKVRPSKIGIFLDYELGEVSFYNMNDRSLLYTFSDSFTGTLWP 165

                 ...
gi 767983319 648 CFS 650
Cdd:cd15828  166 YFY 168

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 767983319 487 SYFRLNKDTCHPWLTISEDGLTAvrserrtparelspSDTHFTRCVaVMGNLIPVRGHHYWEVEVDE---HLDYRVGVAF 563
Cdd:cd12889    8 AWFTFDPSTSHPDIILSNDNMTV--------------TCNSYEDRV-VLGSVGFSRGVHYWEVTIDRydgHPDPAFGVAR 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767983319 564 ADVRKQEDLGANCLSWCMrhTFASSRHkyEFLHN-----RTtpDIRITVpPKKIGILLDYEHSKLSFFNVDLSQHLYTFS 638
Cdd:cd12889   73 IDVNKDKMLGKDDKGWSM--YIDNNRS--WFLHNnehsnRT--EGGITV-GSVVGVLLDLDRHTLSFYVNDEPQGPIAFR 145

                        170       180
                 ....*....|....*....|....*...
gi 767983319 639 cQLHEFVHPCFSLEKPGCLKVHNGISMP 666
Cdd:cd12889  146 -NLPGVFYPAVSLNRNVQVTLHTGLEPP 172

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 767983319 486 GSYFRLNKDTCHPWLTISEDgltavRSERR---TPaRELSPSDTHFTRCVAVMGNLIPVRGHHYWEVEVDEHLDYRVGVA 562
Cdd:cd12900    2 MVHITLDPDTANPWLILSKD-----RRQVRlgdTH-QNVPENEERFDNYPMVLGAQRFNSGKHYWEVDVTGKEAWDLGVC 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767983319 563 FADVRKQedlGANCLS-----WcmrhTFASSRHKYEFLHNRTTPdIRITVPPKKIGILLDYEHSKLSFFNV-DLSQHLYT 636
Cdd:cd12900   76 RDSVRRK---GQFLLSpengfW----TIWLWNKKYEAGTSPQTT-LHLQVPPCQVGIFLDYEAGVVSFYNItDHGSLIYT 147