PHD finger found in Schizosaccharomyces pombe Set1 complex component ash2 (spAsh2p) and similar proteins; spAsh2p, also termed Set1C component ash2, or COMPASS component ash2, or complex proteins associated with set1 protein ash2, or Lid2 complex component ash2, or Lid2C component ash2, is orthologous to Drosophila melanogaster Ash2 protein. Both spAsh2p and D. melanogaster Ash2 contain a plant homeodomain (PHD) finger and a SPRY domain. In contrast, its counterpart in Saccharomyces cerevisiae, Bre2p, has no PHD finger and is not included in this family. spAsh2p shows histone H3 Lys4 (H3K4) methyltransferase activity through its PHD finger. It also interacts with Lid2p in S. pombe. Human Ash2L contains an atypical PHD finger that lacks part of the Cys4HisCys3 signature characteristic of PHD fingers, it binds to only one zinc ion through the second half of the motif and does not have histone tail binding activity.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 387912535   7 SVDEENGRQLGEVELQCGICTKWFTADTFGIDTSSCLPFMTNYSFHCNVC 56
Cdd:cd15583    1 YCYCGKDRNLGEVELQCSICLKWFHAKCVSIDNGSCLPFMTNYQFVCKRC 50

PHD finger found in Schizosaccharomyces pombe Set1 complex component ash2 (spAsh2p) and similar proteins; spAsh2p, also termed Set1C component ash2, or COMPASS component ash2, or complex proteins associated with set1 protein ash2, or Lid2 complex component ash2, or Lid2C component ash2, is orthologous to Drosophila melanogaster Ash2 protein. Both spAsh2p and D. melanogaster Ash2 contain a plant homeodomain (PHD) finger and a SPRY domain. In contrast, its counterpart in Saccharomyces cerevisiae, Bre2p, has no PHD finger and is not included in this family. spAsh2p shows histone H3 Lys4 (H3K4) methyltransferase activity through its PHD finger. It also interacts with Lid2p in S. pombe. Human Ash2L contains an atypical PHD finger that lacks part of the Cys4HisCys3 signature characteristic of PHD fingers, it binds to only one zinc ion through the second half of the motif and does not have histone tail binding activity.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 387912535   7 SVDEENGRQLGEVELQCGICTKWFTADTFGIDTSSCLPFMTNYSFHCNVC 56
Cdd:cd15583    1 YCYCGKDRNLGEVELQCSICLKWFHAKCVSIDNGSCLPFMTNYQFVCKRC 50

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 387912535  327 WYFEITVDEmPPDTAARLGW---SQPLGNlQAPLGYDKFSYSWRSKKGTKFHQSIGKHYSSG-YGQGDVLGFYINLPEDT 402
Cdd:pfam00622   2 HYFEVEIFG-QDGGGWRVGWatkSVPRKG-ERFLGDESGSWGYDGWTGKKYWASTSPLTGLPlFEPGDVIGCFLDYEAGT 79

PHD finger found in Schizosaccharomyces pombe Set1 complex component ash2 (spAsh2p) and similar proteins; spAsh2p, also termed Set1C component ash2, or COMPASS component ash2, or complex proteins associated with set1 protein ash2, or Lid2 complex component ash2, or Lid2C component ash2, is orthologous to Drosophila melanogaster Ash2 protein. Both spAsh2p and D. melanogaster Ash2 contain a plant homeodomain (PHD) finger and a SPRY domain. In contrast, its counterpart in Saccharomyces cerevisiae, Bre2p, has no PHD finger and is not included in this family. spAsh2p shows histone H3 Lys4 (H3K4) methyltransferase activity through its PHD finger. It also interacts with Lid2p in S. pombe. Human Ash2L contains an atypical PHD finger that lacks part of the Cys4HisCys3 signature characteristic of PHD fingers, it binds to only one zinc ion through the second half of the motif and does not have histone tail binding activity.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 387912535   7 SVDEENGRQLGEVELQCGICTKWFTADTFGIDTSSCLPFMTNYSFHCNVC 56
Cdd:cd15583    1 YCYCGKDRNLGEVELQCSICLKWFHAKCVSIDNGSCLPFMTNYQFVCKRC 50

SPRY domain associated with DEAD box gene DDX1; This SPRY domain is associated with the DEAD box gene, DDX1, an RNA-dependent ATPase involved in HIV-1 Rev function and virus replication. It is suggested that DDX1 acts as a cellular cofactor by promoting oligomerization of Rev on the Rev response element (RRE). DDX1 RNA is overexpressed in breast cancer, data showing a strong and independent association between poor prognosis and deregulation of the DEAD box protein DDX1, thus potentially serving as an effective prognostic biomarker for early recurrence in primary breast cancer. DDX1 also interacts with RelA and enhances nuclear factor kappaB-mediated transcription. DEAD-box proteins are associated with all levels of RNA metabolism and function, and have been implicated in translation initiation, transcription, RNA splicing, ribosome assembly, RNA transport, and RNA decay.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 387912535 293 DRAPQLKISDDRLTV--VGEKGYSMVRASHGVR-KGAWYFEITVDEmppDTAARLGWSQPLGNLQapLGYDKFSYSWrSK 369
Cdd:cd12873    5 DRDAALAISPDGLLCqsREEKGWQGCRATKGVKgKGKYYYEVTVTD---EGLCRVGWSTEDASLD--LGTDKFGFGY-GG 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 387912535 370 KGTKFHQSIGKHYSSGYGQGDVLGFYINLPE----------DTETAKSLPDTYKDKAL 417
Cdd:cd12873   79 TGKKSHGRQFDDYGEPFGLGDVIGCYLDLDNgtisfskngkDLGKAFDIPPHLRNSAL 136

SPRY domain 2 (SPRY2) of ryanodine receptor (RyR); This SPRY domain (SPRY2) is the second of three structural repeats in all three isoforms of the ryanodine receptor (RyR), which are the major Ca2+ release channels in the membranes of sarcoplasmic reticulum (SR). There are three RyR genes in mammals; the skeletal RyR1, the cardiac RyR2 and the brain RyR3. The three SPRY domains are located in the N-terminal part of the cytoplasmic region of the RyRs, The SPRY2 domain has been shown to bind to the dihydropryidine receptor (DHPR) II-III loop and the ASI region of RyR1

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 387912535 316 VRASHGVRKGAWYFE---ITVDEMppdtaaRLGWSQPLGNLQAPLGYDKFSYSWRSKKGTKFHQSiGKHYSSGYGQGDVL 392
Cdd:cd12878    5 AEKTYAVTSGKWYFEfevLTSGYM------RVGWARPGFRPDLELGSDDLSYAFDGFLARKWHQG-SESFGKQWQPGDVV 77

                         90
                 ....*....|
gi 387912535 393 GFYINLPEDT 402
Cdd:cd12878   78 GCMLDLVDRT 87

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 387912535 325 GAWYFEITVDEMPPdTAARLGWSQPLGNLQA--PLGYDKFSYSWRSKKGTKFHQSIGKHYSSGYGQGDVLGFYINL 398
Cdd:cd11709    1 GKWYWEVRVDSGNG-GLIQVGWATKSFSLDGegGVGDDEESWGYDGSRLRKGHGGSSGPGGRPWKSGDVVGCLLDL 75

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 387912535 314 SMVRASHGV--RKGAWYFEITVDEMPPDTAARLGWSQPLGNLQAPLGYDKFSYSWRSKKGTKFH-QSIGKHYSSGYGQGD 390
Cdd:cd12885    1 GSVRADHPIppKVPVFYFEVTILDLGEKGIVSIGFCTSGFPLNRMPGWEDGSYGYHGDDGRVYLgGGEGENYGPPFGTGD 80

                         90
                 ....*....|
gi 387912535 391 VLGFYINLPE 400
Cdd:cd12885   81 VVGCGINFKT 90