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 998074849  77 YKGHGKNHKDAASVRATHPIPAACGIYYFEVKIVSKGRDGYMGIGLSAQGVNMNRLPG---------------------- 134
Cdd:cd12909    1 YKGPGKTDKDAAAVRANHPIPPQCGIYYFEVKIISKGRDGYIGIGFSTKDVNLNRLPGwephswgyhgddghsfcssgtg 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 998074849 135 ----------------------------------IAFTDLP-ANLYPTVGLQTPGEIVDANFGQ 163
Cdd:cd12909   81 kpygptfttgdvigcginfrdntafytkngvnlgIAFRDIKkGNLYPTVGLRTPGEHVEANFGQ 144

CTLH/CRA C-terminal to LisH motif domain; RanBPM is a scaffolding protein and is important in regulating cellular function in both the immune system and the nervous system. This domain is at the C-terminus of the proteins and is the binding domain for the CRA motif (for CT11-RanBPM), which is comprised of approximately 100 amino acids at the C terminal of RanBPM. It was found to be important for the interaction of RanBPM with fragile X mental retardation protein (FMRP), but its functional significance has yet to be determined. This region contains CTLH and CRA domains annotated by SMART; however, these may be a single domain, and it is refereed to as a C-terminal to LisH motif.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 998074849  235 SIKNRQKIQKLVLEGRVGEAIETTQRFYPGLLEHNPNLLFMLKCRQFVEMVNGTD 289
Cdd:pfam10607   1 VFKERNRILEAILNGDITEAIEWCNENKPELLKINSNLEFELRLQQFIELIRSGK 55

SPRY domain in Ran binding proteins 9 and 10; This family includes SPRY domain in Ran binding protein (RBP or RanBPM) 9 and 10, and similar proteins. RanBP9 (also known as RanBPM), a binding partner of Ran, is a small Ras-like GTPase that exerts multiple functions via interactions with various proteins. RanBP9 and RanBP10 also act as androgen receptor (AR) coactivators. Both consist of the N-terminal proline- and glutamine-rich regions, the SPRY domain, and LisH-CTLH and CRA motifs. SPRY domain of RanBPM forms a complex with CD39, a prototypic member of the NTPDase family, thus down-regulating activity substantially. RanBP10 enhances the transcriptional activity of AR in a ligand-dependent manner and exhibits a protein expression pattern different from RanBPM in various cell lines. RanBP10 is highly expressed in AR-positive prostate cancer LNCaP cells, while RanBPM is abundant in WI-38 and MCF-7 cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 998074849  77 YKGHGKNHKDAASVRATHPIPAACGIYYFEVKIVSKGRDGYMGIGLSAQGVNMNRLPG---------------------- 134
Cdd:cd12909    1 YKGPGKTDKDAAAVRANHPIPPQCGIYYFEVKIISKGRDGYIGIGFSTKDVNLNRLPGwephswgyhgddghsfcssgtg 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 998074849 135 ----------------------------------IAFTDLP-ANLYPTVGLQTPGEIVDANFGQ 163
Cdd:cd12909   81 kpygptfttgdvigcginfrdntafytkngvnlgIAFRDIKkGNLYPTVGLRTPGEHVEANFGQ 144

CTLH/CRA C-terminal to LisH motif domain; RanBPM is a scaffolding protein and is important in regulating cellular function in both the immune system and the nervous system. This domain is at the C-terminus of the proteins and is the binding domain for the CRA motif (for CT11-RanBPM), which is comprised of approximately 100 amino acids at the C terminal of RanBPM. It was found to be important for the interaction of RanBPM with fragile X mental retardation protein (FMRP), but its functional significance has yet to be determined. This region contains CTLH and CRA domains annotated by SMART; however, these may be a single domain, and it is refereed to as a C-terminal to LisH motif.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 998074849  235 SIKNRQKIQKLVLEGRVGEAIETTQRFYPGLLEHNPNLLFMLKCRQFVEMVNGTD 289
Cdd:pfam10607   1 VFKERNRILEAILNGDITEAIEWCNENKPELLKINSNLEFELRLQQFIELIRSGK 55

CTLH/CRA C-terminal to LisH motif domain; RanBPM is a scaffolding protein and is important in regulating cellular function in both the immune system and the nervous system. This domain is at the C-terminus of the proteins and is the binding domain for the CRA motif (for CT11-RanBPM), which is comprised of approximately 100 amino acids at the C terminal of RanBPM. It was found to be important for the interaction of RanBPM with fragile X mental retardation protein (FMRP), but its functional significance has yet to be determined. This region contains CTLH and CRA domains annotated by SMART; however, these may be a single domain, and it is refereed to as a C-terminal to LisH motif.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 998074849  502 EYGK------NLAHTEMLQDAFSLLAYSDPWSC-PVGQQLDPIQREPVCAALNSAILESQNLPKQPPLMLALGQASECL 573
Cdd:pfam10607  61 EYARenlapfNEEHLKELEKLMGLLAFPDPTDSsPYKSLLSPSRWEKLASEFNRAILKLLGLSSESPLEILLKAGLSAL 139

LisH; The LisH (lis homology) domain mediates protein dimerization and tetramerization. The LisH domain is found in Sif2, a component of the Set3 complex which is responsible for repressing meiotic genes. It has been shown that the LisH domain helps mediate interaction with components of the Set3 complex.

                          10        20
                  ....*....|....*....|...
gi 998074849  201 LQNMVSSYLVHHGYCATATAFAR 223
Cdd:pfam08513   2 LNRLIYDYLVKEGYEETAEAFEK 24

SPRY domain in Ran binding proteins 9 and 10; This family includes SPRY domain in Ran binding protein (RBP or RanBPM) 9 and 10, and similar proteins. RanBP9 (also known as RanBPM), a binding partner of Ran, is a small Ras-like GTPase that exerts multiple functions via interactions with various proteins. RanBP9 and RanBP10 also act as androgen receptor (AR) coactivators. Both consist of the N-terminal proline- and glutamine-rich regions, the SPRY domain, and LisH-CTLH and CRA motifs. SPRY domain of RanBPM forms a complex with CD39, a prototypic member of the NTPDase family, thus down-regulating activity substantially. RanBP10 enhances the transcriptional activity of AR in a ligand-dependent manner and exhibits a protein expression pattern different from RanBPM in various cell lines. RanBP10 is highly expressed in AR-positive prostate cancer LNCaP cells, while RanBPM is abundant in WI-38 and MCF-7 cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 998074849  77 YKGHGKNHKDAASVRATHPIPAACGIYYFEVKIVSKGRDGYMGIGLSAQGVNMNRLPG---------------------- 134
Cdd:cd12909    1 YKGPGKTDKDAAAVRANHPIPPQCGIYYFEVKIISKGRDGYIGIGFSTKDVNLNRLPGwephswgyhgddghsfcssgtg 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 998074849 135 ----------------------------------IAFTDLP-ANLYPTVGLQTPGEIVDANFGQ 163
Cdd:cd12909   81 kpygptfttgdvigcginfrdntafytkngvnlgIAFRDIKkGNLYPTVGLRTPGEHVEANFGQ 144

SPRY domain in Ran binding proteins, SSH4, HECT E3 and SPRYD3; This family includes SPRY domains found in Ran binding proteins (RBP or RanBPM) 9 and 10, SSH4 (suppressor of SHR3 null mutation protein 4), SPRY domain-containing protein 3 (SPRYD3) as well as HECT, a C-terminal catalytic domain of a subclass of ubiquitin-protein ligase (E3). RanBP9 and RanBP10 act as androgen receptor (AR) coactivators. Both consist of the N-terminal proline- and glutamine-rich regions, the SPRY domain, and LisH-CTLH and CRA motifs. The SPRY domain in SSH4 may be involved in cargo recognition, either directly or by combination with other adaptors, possibly leading to a higher selectivity. SPRYD3 is highly expressed in most tissues in humans, possibly involved in important cellular processes. HECT E3 mediates the direct transfer of ubiquitin from E2 to substrate.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 998074849  88 ASVRATHPIPAACGIYYFEVKIVSKGRDGYMGIGLSAQGVNMNRLPG--------------------------------- 134
Cdd:cd12885    1 GSVRADHPIPPKVPVFYFEVTILDLGEKGIVSIGFCTSGFPLNRMPGwedgsygyhgddgrvylgggegenygppfgtgd 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 998074849 135 -----------------------IAFTDL-PANLYPTVGLQTPGEIVDANFG 162
Cdd:cd12885   81 vvgcginfktgevfftkngellgTAFENVvKGRLYPTVGLGSPGVKVRVNFG 132

C-terminal to LisH motif; Alpha-helical motif of unknown function.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 998074849   235 SIKNRQKIQKLVLEGRVGEAIETTQRFYPGLLEHNPNLLFMLKCRQFVEMVNGTDSE 291
Cdd:smart00668   1 EFDERKRIRELILKGDWDEALEWLSSLKPPLLERNSKLEFELRKQKFLELVRQGKLE 57

SPRY domain-containing protein 3; This family contains SPRY domain-containing protein 3 (SPRYD3). In humans, it is highly expressed in most tissues, including brain, kidney, heart, intestine, skeletal muscle, and testis. It also has cross-species conservation, suggesting that it is likely to carry out important cellular processes.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 998074849  80 HGKNHKDAASVRATHPI-PAACgiyYFEVKIVSKGRDGYMGIGLSAQGVNMNRLPG 134
Cdd:cd12908   17 HGRGIGDVGLAQARRPLsPDNH---YFEVEIVDPGVRCYIAIGLAPQDYPLDRHPG 69

LisH; The LisH (lis homology) domain mediates protein dimerization and tetramerization. The LisH domain is found in Sif2, a component of the Set3 complex which is responsible for repressing meiotic genes. It has been shown that the LisH domain helps mediate interaction with components of the Set3 complex.

                          10        20
                  ....*....|....*....|...
gi 998074849  201 LQNMVSSYLVHHGYCATATAFAR 223
Cdd:pfam08513   2 LNRLIYDYLVKEGYEETAEAFEK 24