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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149028240 270 FRLDGSTSHQNLRVEGLSVEWDAMGGKV-QDIKAREKEGKGRTASPVNSPARGtPSPKRTASGRGGRDRFTAESYTVLGD 348
Cdd:cd12901    1 FKLDASSSHQNLKVEDLSVEWDATGGKVlQKIKGRENDGRSRTASPRNSSARC-QSPKRMPSARGGRDRFTAESYTVLGD 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149028240 349 TPIDSGEHYWEVRFEPDSKAFGLGVAYRSLGRFEQLGKTAASWCLHANNWLQASFTAKHANKVKVLDSPVPDCLGVHCDF 428
Cdd:cd12901   80 TLIDGGQHYWEVRAQKDSKAFSVGVAYRSLGKFDQLGKTNASWCLHVNNWLQNSFAAKHNNKAKTLDVPVPDRIGVYCDF 159

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 149028240 429 HQGLLSFYNARTKQLLHTFKTKFTQPLLPAFTVWCGSFQVTTGLQVPS 476
Cdd:cd12901  160 DEGQLSFYNARTKQLLHTFKMKFTQPVLPAFMVWCGGLSVSTGLQVPS 207

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 149028240     4 QREALRKIVTTLAMKNEETQTFIYSLKQMLLNVEANSAKVQEDLEAEFQSLTSVLEELRESMLMKIKQERASRTYELQNQ 83
Cdd:smart00502   1 QREALEELLTKLRKKAAELEDALKQLISIIQEVEENAADVEAQIKAAFDELRNALNKRKKQLLEDLEEQKENKLKVLEQQ 80

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 149028240    84 LTACTRALESSEELLETANQTLQAADREDFPQAAKQI 120
Cdd:smart00502  81 LESLTQKQEKLSHAINFTEEALNSGDPTELLLSKKLI 117

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149028240 270 FRLDGSTSHQNLRVEGLSVEWDAMGGKV-QDIKAREKEGKGRTASPVNSPARGtPSPKRTASGRGGRDRFTAESYTVLGD 348
Cdd:cd12901    1 FKLDASSSHQNLKVEDLSVEWDATGGKVlQKIKGRENDGRSRTASPRNSSARC-QSPKRMPSARGGRDRFTAESYTVLGD 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149028240 349 TPIDSGEHYWEVRFEPDSKAFGLGVAYRSLGRFEQLGKTAASWCLHANNWLQASFTAKHANKVKVLDSPVPDCLGVHCDF 428
Cdd:cd12901   80 TLIDGGQHYWEVRAQKDSKAFSVGVAYRSLGKFDQLGKTNASWCLHVNNWLQNSFAAKHNNKAKTLDVPVPDRIGVYCDF 159

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 149028240 429 HQGLLSFYNARTKQLLHTFKTKFTQPLLPAFTVWCGSFQVTTGLQVPS 476
Cdd:cd12901  160 DEGQLSFYNARTKQLLHTFKMKFTQPVLPAFMVWCGGLSVSTGLQVPS 207

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 149028240 165 PSAPIiNLAESLVADNCVTLVWHMPEED-SKIDHYVLEYRRTNfegpprlkeDHPWMVVEG--IRHTECTLTGLKFDMKY 241
Cdd:cd00063    1 PSPPT-NLRVTDVTSTSVTLSWTPPEDDgGPITGYVVEYREKG---------SGDWKEVEVtpGSETSYTLTGLKPGTEY 70

                         90       100
                 ....*....|....*....|....
gi 149028240 242 mNVRVKACNKAVAGEFSEPVTLET 265
Cdd:cd00063   71 -EFRVRAVNGGGESPPSESVTVTT 93

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149028240  356 HYWEVR-FEPDSKAFGLGVAYRS--LGRFEQLGKTAASWCLHaNNWLQASFTAKHANKVKVLDSPvPDCLGVHCDFHQGL 432
Cdd:pfam00622   2 HYFEVEiFGQDGGGWRVGWATKSvpRKGERFLGDESGSWGYD-GWTGKKYWASTSPLTGLPLFEP-GDVIGCFLDYEAGT 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 149028240  433 LSFYNArTKQLLHTFKT-KFTQPLLPAFTVWCG-SFQVTTGLQ 473
Cdd:pfam00622  80 ISFTKN-GKSLGYAFRDvPFAGPLFPAVSLGAGeGLKFNFGLR 121

Fibronectin type III domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 149028240  182 VTLVWHMPEE-DSKIDHYVLEYRRTNfegpprlKEDHPWMVVEGIRHTECTLTGLKFDMKYmNVRVKACNKAVAGEFS 258
Cdd:pfam00041  16 LTVSWTPPPDgNGPITGYEVEYRPKN-------SGEPWNEITVPGTTTSVTLTGLKPGTEY-EVRVQAVNGGGEGPPS 85

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149028240   2 EDQREALRKIVTTLAMKNEETQTFIYSLKQMLLNVEAnsAKVQEDLEAEFQSLTSVLEELREsmlmKIKQERasrtyELQ 81
Cdd:COG4717   94 QEELEELEEELEELEAELEELREELEKLEKLLQLLPL--YQELEALEAELAELPERLEELEE----RLEELR-----ELE 162

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 149028240  82 NQLTACTRALESSEELLETANQTLQAADREDFPQAAKQIKD 122
Cdd:COG4717  163 EELEELEAELAELQEELEELLEQLSLATEEELQDLAEELEE 203

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149028240     1 MEDQREALRKIVTTLAMKneetqtfiysLKQMLLNVEANSAKVQ------EDLEAEFQSLTSVLEELRESMLMKIKQERA 74
Cdd:TIGR02168  370 LESRLEELEEQLETLRSK----------VAQLELQIASLNNEIErlearlERLEDRRERLQQEIEELLKKLEEAELKELQ 439

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149028240    75 SRT-------YELQNQLTACTRALESSEELLETANQTLQAADR-------------------EDFPQAAKQIK------- 121
Cdd:TIGR02168  440 AELeeleeelEELQEELERLEEALEELREELEEAEQALDAAERelaqlqarldslerlqenlEGFSEGVKALLknqsgls 519

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 149028240   122 -------DGVTMAPAFRLSLKAKVSDNMSHLMV-DFTQERQMLQALK--------FLPVPSAP 168
Cdd:TIGR02168  520 gilgvlsELISVDEGYEAAIEAALGGRLQAVVVeNLNAAKKAIAFLKqnelgrvtFLPLDSIK 582

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149028240 270 FRLDGSTSHQNLRVEGLSVEWDAMGGKV-QDIKAREKEGKGRTASPVNSPARGtPSPKRTASGRGGRDRFTAESYTVLGD 348
Cdd:cd12901    1 FKLDASSSHQNLKVEDLSVEWDATGGKVlQKIKGRENDGRSRTASPRNSSARC-QSPKRMPSARGGRDRFTAESYTVLGD 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149028240 349 TPIDSGEHYWEVRFEPDSKAFGLGVAYRSLGRFEQLGKTAASWCLHANNWLQASFTAKHANKVKVLDSPVPDCLGVHCDF 428
Cdd:cd12901   80 TLIDGGQHYWEVRAQKDSKAFSVGVAYRSLGKFDQLGKTNASWCLHVNNWLQNSFAAKHNNKAKTLDVPVPDRIGVYCDF 159

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 149028240 429 HQGLLSFYNARTKQLLHTFKTKFTQPLLPAFTVWCGSFQVTTGLQVPS 476
Cdd:cd12901  160 DEGQLSFYNARTKQLLHTFKMKFTQPVLPAFMVWCGGLSVSTGLQVPS 207

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 149028240 327 RTASGRGGRDRFTAESYTVLGDTPIDSGEHYWEVRFEpDSKAFGLGVAYRSLGRF---EQLGKTAASWCLHannWLQASF 403
Cdd:cd12874   25 DISQHPPEPPPRFFECWQVLGSQSFSSGRHYWEVDVQ-DDSSWYVGVTYKSLPRKgkmSNLGRNNGSWCLE---WRENEF 100

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 149028240 404 TAKHANKVKVLDSPVPDCLGVHCDFHQGLLSFYN-ARTKQLLHTFKTKFTQPLLPAFTVWCGS 465
Cdd:cd12874  101 SAWHNNPETRLPVTPPRRLGVFLDCDGGSLSFYGvTDGVQLLYTFKAKFTEPLYPAFWLGEGS 163

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 149028240 330 SGRGGRDRFTAESytVLGDTPIDSGEHYWEVRFEpDSKAFGLGVAYRSLGRFE---QLGKTAASWCLHannWLQASFTAK 406
Cdd:cd12891   29 HYPDSPERFTHSQ--VLSTQSFSSGRHYWEVEVS-ESGGWSVGVAYPSIERKGdesRIGRNDKSWCLE---WQDKSFSAW 102

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 149028240 407 HANKVKVLDSPVPDCLGVHCDFHQGLLSFYNAR-TKQLLHTFKTKFTQPLLPAFTVWCGS 465
Cdd:cd12891  103 HNNEETPLPSVSSRRLGVYLDYEAGRLSFYELSdPIRHLHTFTATFTEPLHPAFWVLEGG 162

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 149028240 270 FRLDGSTSHQNLRV--EGLSVEWDamggkvqdikarekegkgrtaspvNSPARGTPSPKRTaSGRGgrdrftaeSYTVLG 347
Cdd:cd13739    1 FKLDPKMAHKKLKIsnDGLQMEKD------------------------ESSLKKSHTPERF-SGTG--------CYGAAG 47

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149028240 348 DTPIDSGEHYWEVRFEpDSKAFGLGVAYRSLGRFEQLGKTAASWCLHANNwlqASFTAKHANKVKVLD-SPVPDCLGVHC 426
Cdd:cd13739   48 NIFIDSGCHYWEVVVG-SSTWYAIGIAYKSAPKNEWIGKNSSSWVFSRCN---NNFVVRHNNKEMLVDvPPQLKRLGVLL 123

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 149028240 427 DFHQGLLSFYNARTKQLLHTFKTKFTQPLLPAFTVWCGSFQVTTGL 472
Cdd:cd13739  124 DYDNNMLSFYDPANSLHLHTFEVSFILPVCPTFTIWNKSLMILSGL 169

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 149028240 336 DRFTAESytVLGDTPIDSGEHYWEVRFEpDSKAFGLGVAYRSLGRFEQLGKTAASWCLHannWLQAS-FTAKHANKVKVL 414
Cdd:cd12902   35 DRFSISQ--VLCSQAFSSGQHYWEVDTR-QCSHWAVGVASWEMSRDQMLGRTMDSWCIE---WKGTGqLSAWHMNKETVL 108

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 149028240 415 DSPVPDCLGVHCDFHQGLLSFYN-ARTKQLLHTFKTKFTQPLLPAF 459
Cdd:cd12902  109 GSDKPRVVGIWLDLEEGKLAFYSvANQERLLHECEVSASSPLHPAF 154

PRY/SPRY domain in tripartite motif-containing protein 76 (TRIM76), also called cardiomyopathy-associated protein 5; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM76, a Class I TRIM protein. TRIM76 (also known as cardiomyopathy-associated protein 5 or CMYA5 or myospryn or SPRYD2) is a muscle-specific member of the TRIM superfamily, but lacks the RING domain. It has been suggested that TRIM76 is involved in two distinct processes, protein kinase A signaling and vesicular trafficking. It has also been implicated in Duchenne muscular dystrophy and cardiac disease; gene polymorphism of TRIM76 is associated with left ventricular wall thickness in patients with hypertension while its interactions with M-band titin and calpain 3 link it to tibial and limb-girdle muscular dystrophies.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149028240 340 AESYTVLGDTPIDSGEHYWEVRFEpDSKAFGLGVAYRSLGRFEQLGKTAASWCLHANNWLQAS-FTAKHANKVK-VLDSP 417
Cdd:cd12898   38 TECPSVLGEELPSCGQYYWETTVT-RCPAYRLGICSSSASQAGALGEGSTSWCLHCVPTSEPCrYTLLHSGIVSdVFVTE 116

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 149028240 418 VPDCLGVHCDFHQGLLSFYNARTKQLLHTFKTKFTQPLLPAF 459
Cdd:cd12898  117 RPARVGTLLDYNNGRLIFINAESGQLLGIFRHRFAQPCHPAF 158

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 149028240 345 VLGDTPIDSGEHYWEVRFEpDSKAFGLGVAYRSLGRFEQLGKTAASWCLhanNWLQASFTAKHANKVkvldSPV-----P 419
Cdd:cd12903   46 VLGDTPVTSGRHYWEVTVK-RSQEFRIGVADVDMSRDECIGTNESSWVF---AYAQRKWYAMVANET----VPVplvgkP 117

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 149028240 420 DCLGVHCDFHQGLLSFYNARTKQLLHTFKTKFTQPLLPAFTVWCG 464
Cdd:cd12903  118 DRVGLLLDYEAGKLSLVDVEKNSVVHTMSAEFRGPVVPAFALWDG 162

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 149028240 337 RFTaESYTVLGDTPIDSGEHYWEVRFEpDSKAFGLGVAYRSLGRFEQLGKTAAS--WCLhannWLqasftaKHANKVKVL 414
Cdd:cd13733   37 RFD-TCVCVLGSEGFSSGRHYWEVEVG-GKTDWDLGVARESVNRKGKITLSPENgyWTV----GL------RNGNEYKAL 104

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 149028240 415 DSPV--------PDCLGVHCDFHQGLLSFYNARTKQLLHTFKTKFTQPLLPAF 459
Cdd:cd13733  105 TSPStplslrekPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDCFTEKLYPYF 157

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 149028240 337 RFTAESyTVLGDTPIDSGEHYWEVRFEpDSKAFGLGVAYRSLGRFEQLGKTAAS--WCLHannWLQASFTAKHANKVKVL 414
Cdd:cd15829   56 RFTVNP-VVLGFPGFHSGRHFWEVEVG-DKPEWAVGVCKDSLSTKARRPPSGQQgcWRIQ---LQGGDYDAPGAVPPPLL 130

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 149028240 415 DSPVPDCLGVHCDFHQGLLSFYNARTKQLLHTFKTKFTQPLLPAFTVWCGS 465
Cdd:cd15829  131 LEVKPRGIGVFLDYELGEISFYNMPEKSHIHTFTDTFSGPLRPYFYVGPDS 181

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 149028240 337 RFTaESYTVLGDTPIDSGEHYWEVRFEpDSKAFGLGVAYRSLGRFEQLGKTAAS--WCL-HANNWLQASFTAKHANKVKV 413
Cdd:cd12893   37 RFD-PYPCVLGSEGFTSGKHSWDVEVG-DNTSWMLGVAKESVQRKGKFTLSPESgfWTIgFSEGKYSARTSPEPRTPLRV 114

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 149028240 414 ldSPVPDCLGVHCDFHQGLLSFYNARTKQLLHTFKTKFTQPLLPAFTVWCGSF 466
Cdd:cd12893  115 --KQKPQRIRVQLDWDRGKVSFSDPDTNTHIHTFTHTFTERVFPYFYTGCKSE 165

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149028240 345 VLGDTPIDSGEHYWEVRFEPDSKaFGLGVAYRSLGRFEQLGKTAASWCL--------HANNWLQASFTAKhankVKVLDS 416
Cdd:cd12899   47 VMGSLIPVRGKHYWEVEVDEQTE-YRVGVAFEDTQRNGYLGANNTSWCMrhiitpsrHKYEFLHNGWTPD----IRITVP 121

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 149028240 417 PVPdcLGVHCDFHQGLLSFYNARTKQLLHTFKTKFTQPLLPAFTV-WCGSFQVTTGL 472
Cdd:cd12899  122 PKK--IGILLDYDSGRLSFFNVDLAQHLYTFSCQFQHFVHPCFSLeKPGALKVHNGI 176

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 149028240 345 VLGDTPIDSGEHYWEVrfepDSKAFG--LGVAYRSLGRFEQ-----LGKTAASWCLHannWLQASFTAKHANKVKVLDSP 417
Cdd:cd12890   54 VLSQQSLYLGRYYFEV----EISGEGtyVGLTYKSIDRKGSesnscISGNNFSWCLQ---WNGKEFSAWHSDVETPLKKG 126

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 149028240 418 VPDCLGVHCDFHQGLLSFY--NARTKQLLHTFKTKFTQPLLPAF 459
Cdd:cd12890  127 PFTRLGIYLDYPGGTLSFYgvEDDGMTLLHKFQCKFTEPLYPAF 170

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149028240 337 RFTAEsYTVLGDTPIDSGEHYWEVRFEpDSKAFGLGVAYRSLGRFE--QLGKTAASWCLHANNWLQASFTAKHANKVKVL 414
Cdd:cd13744   50 RFDVE-VSVLGSEGFSGGVHYWEVVVS-EKTQWMIGLAHEAVSRKGsiQIQPGRGFYCIVMHDGNQYSACTEPWTRLNVK 127

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 149028240 415 DSPvpDCLGVHCDFHQGLLSFYNARTKQLLHTFKTKFTQPLLPAFT 460
Cdd:cd13744  128 SKL--EKVGVYLDYDKGLLIFYNADDMSWLYTFREKFPGKLCSYFS 171

PRY/SPRY domain in tripartite motif-binding protein 58 (TRIM58), also known as BIA2; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM58, also known as BIA2. TRIM58 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins.It is implicated by genome-wide association studies (GWAS) to regulate erythrocyte traits, including cell size and number. Trim58 facilitates erythroblast enucleation by inducing proteolytic degradation of the microtubule motor dynein.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149028240 345 VLGDTPIDSGEHYWEVRFEpDSKAFGLGVAYRSLGRfeqLGKTAAS--------WCLHANNWLQASftakhANKVKVLDS 416
Cdd:cd15816   44 VLGLQSFSSGRHYWEVAVG-EKAEWGLGVCQDSAPR---KGETTPSpengvwavWLLKGNEYMVLA-----SPSVPLLQL 114

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 149028240 417 PVPDCLGVHCDFHQGLLSFYNARTKQLLHTFKTKFTQPLLPAFTV 461
Cdd:cd15816  115 RRPRRVGVFLDYEAGEISFYNVTAGSHIYTFRQLFSGILRPYFFV 159

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 149028240 305 KEGKGRTASPvNSPARGTPSPkrtasgrggrdrftaesyTVLGDTPIDSGEHYWEVRFEpDSKAFGLGVAYRSLGRFEQl 384
Cdd:cd15811   23 RRGDLRQALP-DSPERFDPGP------------------CVLGRERFTSGRHYWEVEVG-DRTSWALGVCKENVNRKEK- 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149028240 385 GKTAAswclhANNWLQASFTAKHANKVKVLDSPV---PDCLGVHCDFHQGLLSFYNARTKQLLHTF-KTKFTQPLLPAFT 460
Cdd:cd15811   82 GELSA-----GNGFWILVFLGNYYSSERRTFAPLrdpPRRVGIFLDYEAGHLSFYSATDGSLLFIFpETPFSGTLRPLFS 156

PRY/SPRY domain in tripartite motif-binding protein 15 (TRIM15); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of tripartite motif-containing protein 15 (TRIM15), also referred to as RING finger protein 93 (RNF93) or Zinc finger protein B7 or 178 (ZNFB7 or ZNF178). TRIM15 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. The PRY and SPRY/B30.2 domains can function as immune defense components and in pathogen sensing. TRIM15 has been shown to regulate inflammatory and innate immune signaling, in addition to displaying antiviral activities. Down-regulation of TRIM15, as well as TRIM11, enhances virus release, suggesting that these proteins contribute to the endogenous restriction of retroviruses in cells. TRIM15 is also a regulatory component of focal adhesion turnover and cell migration.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149028240 337 RFTAESyTVLGDTPIDSGEHYWEVRFE-PDSKAFGLGVAYRSLGRFEQLGKTAAS--WCL---HANNWlqasftAKHANK 410
Cdd:cd15826   37 RFDGLP-AVLGSPGFSSGRHRWQVEVQlGDGGGCTVGVAGESVRRKGEMGLSAEDgvWAVilsHQQCW------ASTSPG 109

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 149028240 411 VKVLDSPVPDCLGVHCDFHQGLLSFYNARTKQLLHTFKTKFTQPLLPAFTVW 462
Cdd:cd15826  110 TDLPLSEIPRRVGVALDYEAGTVTLTNAETQEPIFTFTASFSGKVFPFFAVW 161

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149028240  356 HYWEVR-FEPDSKAFGLGVAYRS--LGRFEQLGKTAASWCLHaNNWLQASFTAKHANKVKVLDSPvPDCLGVHCDFHQGL 432
Cdd:pfam00622   2 HYFEVEiFGQDGGGWRVGWATKSvpRKGERFLGDESGSWGYD-GWTGKKYWASTSPLTGLPLFEP-GDVIGCFLDYEAGT 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 149028240  433 LSFYNArTKQLLHTFKT-KFTQPLLPAFTVWCG-SFQVTTGLQ 473
Cdd:pfam00622  80 ISFTKN-GKSLGYAFRDvPFAGPLFPAVSLGAGeGLKFNFGLR 121