Golgi CORVET complex core vacuolar protein 8; Vps8 is one of the Golgi complex components necessary for vacuolar sorting. Eukaryotic cells contain a highly dynamic endo-membrane system, in which individual organelles keep their identity despite continuous vesicle generation and fusion. Vesicles that bud from a donor membrane are targeted and delivered to each individual organelle, where they release their cargo after fusion with the acceptor membrane. Vps8 is the core component of the endosomal tethering complex CORVET (class C core vacuole/endosome tethering). Vps8 co-operates with Vps21-GTP to mediate endosomal clustering in a reaction that is dependent on Vps3. Vps8 is the only CORVET subunit that is enriched on late endosomes, suggesting that it is a marker for the maturation of late endosomes. Late endosomes form intralumenal vesicles, and the resulting multivesicular bodies fuse with the vacuole to release their cargoes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1154884864  601 VFLECLEPYILSDKLVGITPQVMKDLIVHFQDKKLMENVEALIVHMDITSLDIQQVVLMCWENRLYDAMIYVYNRGMNEF 680
Cdd:pfam12816    1 IFLETLEPYILSGRIRSLPPEVVKALVEHYASKGRLSRLEELICHLDPSSLDIDQVVKLCKKHGLYDALIYVWNRALNDY 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1154884864  681 ISPMEKLFRVIAPPLNAGKTLTDEQVVMGNKLLVYISCCLAGRAYPLGD-IPEDLVPLVKNQVFEFLI----------RL 749
Cdd:pfam12816   81 VTPLVELLKLIRPLLNEGSDLEEDDEENANKVFPYLSYILTGRQYPTGEgLPEDEASKAKSEIYSFLFsgtsiewppgSG 160

                          170       180       190
                   ....*....|....*....|....*....|....
gi 1154884864  750 HSAEASPEEEIYPYIRTLLHFDTREFLNVLALTF 783
Cdd:pfam12816  161 TTDPDSDDEPSFPYLRLLLKFDAREFLSVLNEAF 194

WD40 repeat [General function prediction only];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1154884864   92 IDTIDSHSYDTSSVA-SSD-------SGDRT----NLKRKKkLPDSFSLHGSVmrhsllkgisaqiVSAAAVS---SLIA 156
Cdd:COG2319    197 LRTLTGHTGAVRSVAfSPDgkllasgSADGTvrlwDLATGK-LLRTLTGHSGS-------------VRSVAFSpdgRLLA 262

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1154884864  157 VGTSHGLALIFDQNQALRLclgsTSVGGQYGAISALSINNDCSRLLCGFAKGQITMWDLASGKLLRSITDAHPPGTAI 234
Cdd:COG2319    263 SGSADGTVRLWDLATGELL----RTLTGHSGGVNSVAFSPDGKLLASGSDDGTVRLWDLATGKLLRTLTGHTGAVRSV 336

Golgi CORVET complex core vacuolar protein 8; Vps8 is one of the Golgi complex components necessary for vacuolar sorting. Eukaryotic cells contain a highly dynamic endo-membrane system, in which individual organelles keep their identity despite continuous vesicle generation and fusion. Vesicles that bud from a donor membrane are targeted and delivered to each individual organelle, where they release their cargo after fusion with the acceptor membrane. Vps8 is the core component of the endosomal tethering complex CORVET (class C core vacuole/endosome tethering). Vps8 co-operates with Vps21-GTP to mediate endosomal clustering in a reaction that is dependent on Vps3. Vps8 is the only CORVET subunit that is enriched on late endosomes, suggesting that it is a marker for the maturation of late endosomes. Late endosomes form intralumenal vesicles, and the resulting multivesicular bodies fuse with the vacuole to release their cargoes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1154884864  601 VFLECLEPYILSDKLVGITPQVMKDLIVHFQDKKLMENVEALIVHMDITSLDIQQVVLMCWENRLYDAMIYVYNRGMNEF 680
Cdd:pfam12816    1 IFLETLEPYILSGRIRSLPPEVVKALVEHYASKGRLSRLEELICHLDPSSLDIDQVVKLCKKHGLYDALIYVWNRALNDY 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1154884864  681 ISPMEKLFRVIAPPLNAGKTLTDEQVVMGNKLLVYISCCLAGRAYPLGD-IPEDLVPLVKNQVFEFLI----------RL 749
Cdd:pfam12816   81 VTPLVELLKLIRPLLNEGSDLEEDDEENANKVFPYLSYILTGRQYPTGEgLPEDEASKAKSEIYSFLFsgtsiewppgSG 160

                          170       180       190
                   ....*....|....*....|....*....|....
gi 1154884864  750 HSAEASPEEEIYPYIRTLLHFDTREFLNVLALTF 783
Cdd:pfam12816  161 TTDPDSDDEPSFPYLRLLLKFDAREFLSVLNEAF 194

WD40 repeat [General function prediction only];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1154884864   92 IDTIDSHSYDTSSVA-SSD-------SGDRT----NLKRKKkLPDSFSLHGSVmrhsllkgisaqiVSAAAVS---SLIA 156
Cdd:COG2319    197 LRTLTGHTGAVRSVAfSPDgkllasgSADGTvrlwDLATGK-LLRTLTGHSGS-------------VRSVAFSpdgRLLA 262

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1154884864  157 VGTSHGLALIFDQNQALRLclgsTSVGGQYGAISALSINNDCSRLLCGFAKGQITMWDLASGKLLRSITDAHPPGTAI 234
Cdd:COG2319    263 SGSADGTVRLWDLATGELL----RTLTGHSGGVNSVAFSPDGKLLASGSDDGTVRLWDLATGKLLRTLTGHTGAVRSV 336

PHD zinc finger; The plant homeodomain (PHD) finger is a C4HC3 zinc-finger-like motif found in nuclear proteins thought to be involved in epigenetics and chromatin-mediated transcriptional regulation. The PHD finger binds two zinc ions using the so-called 'cross-brace' motif and is thus structurally related to the RING finger and the FYVE finger. It is not yet known if PHD fingers have a common molecular function. Several reports suggest that it can function as a protein-protein interacton domain and it was recently demonstrated that the PHD finger of p300 can cooperate with the adjacent BROMO domain in nucleosome binding in vitro. Other reports suggesting that the PHD finger is a ubiquitin ligase have been refuted as these domains were RING fingers misidentified as PHD fingers.

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 1154884864  1244 YCSIClqqykrRQEMADEIIVF--SCGHLYHSFCLQNKECTVEFEGqtRWTCYKC 1296
Cdd:smart00249    1 YCSVC------GKPDDGGELLQcdGCDRWYHQTCLGPPLLEEEPDG--KWYCPKC 47

Golgi CORVET complex core vacuolar protein 8; Vps8 is one of the Golgi complex components necessary for vacuolar sorting. Eukaryotic cells contain a highly dynamic endo-membrane system, in which individual organelles keep their identity despite continuous vesicle generation and fusion. Vesicles that bud from a donor membrane are targeted and delivered to each individual organelle, where they release their cargo after fusion with the acceptor membrane. Vps8 is the core component of the endosomal tethering complex CORVET (class C core vacuole/endosome tethering). Vps8 co-operates with Vps21-GTP to mediate endosomal clustering in a reaction that is dependent on Vps3. Vps8 is the only CORVET subunit that is enriched on late endosomes, suggesting that it is a marker for the maturation of late endosomes. Late endosomes form intralumenal vesicles, and the resulting multivesicular bodies fuse with the vacuole to release their cargoes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1154884864  601 VFLECLEPYILSDKLVGITPQVMKDLIVHFQDKKLMENVEALIVHMDITSLDIQQVVLMCWENRLYDAMIYVYNRGMNEF 680
Cdd:pfam12816    1 IFLETLEPYILSGRIRSLPPEVVKALVEHYASKGRLSRLEELICHLDPSSLDIDQVVKLCKKHGLYDALIYVWNRALNDY 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1154884864  681 ISPMEKLFRVIAPPLNAGKTLTDEQVVMGNKLLVYISCCLAGRAYPLGD-IPEDLVPLVKNQVFEFLI----------RL 749
Cdd:pfam12816   81 VTPLVELLKLIRPLLNEGSDLEEDDEENANKVFPYLSYILTGRQYPTGEgLPEDEASKAKSEIYSFLFsgtsiewppgSG 160

                          170       180       190
                   ....*....|....*....|....*....|....
gi 1154884864  750 HSAEASPEEEIYPYIRTLLHFDTREFLNVLALTF 783
Cdd:pfam12816  161 TTDPDSDDEPSFPYLRLLLKFDAREFLSVLNEAF 194

RING finger, H2 subclass, found in vacuolar protein sorting-associated proteins Vps8, Vps11, Vps18, Vps41, and similar proteins; This subfamily corresponds to a group of vacuolar protein sorting-associated proteins containing a C-terminal C3H2C3-type RING-H2 finger, which includes Vps8, Vps11, Vps18, and Vps41. Vps11 and Vps18 associate with Vps16 and Vps33 to form a Class C Vps core complex that is required for soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE)-mediated membrane fusion at the lysosome-like yeast vacuole. The core complex, together with two additional compartment-specific subunits, forms the tethering complexes HOPS (homotypic vacuole fusion and protein sorting) and CORVET (class C core vacuole/endosome transport). CORVET contains the additional Vps3 and Vps8 subunits. It operates at endosomes, controls traffic into late endosomes and interacts with the Rab5/Vps21-GTP form. HOPS contains the additional Vps39 and Vps41 subunits. It operates at the lysosomal vacuole, controls all traffic from late endosomes into the vacuole and interacts with the Rab7/Ypt7-GTP form.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1154884864 1244 YCSICLQQYKRR-QEMADEIIVFSCGHLYHSFCLQNKECtvefegqTRWTCYKCS 1297
Cdd:cd16484      1 KCPICTLPLKESdVGANSPVVVFFCGHMFHKFCLPELSM-------TEAACPICL 48

RING finger, H2 subclass, found in RING finger protein 167 (RNF167) and similar proteins; RNF167, also known as RING105, is an endosomal/lysosomal E3 ubiquitin-protein ligase involved in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) ubiquitination. It ubiquitinates AMPA-type glutamate receptor subunit GluA2 and regulates its surface expression, and thus acts as a selective regulator of AMPAR-mediated neurotransmission. It acts as an endosomal membrane protein which ubiquitylates vesicle-associated membrane protein 3 (VAMP3) and regulates endosomal trafficking. Moreover, RNF167 plays a role in the regulation of TSSC5 (tumor-suppressing subchromosomal transferable fragment cDNA, also known as ORCTL2/IMPT1/BWR1A/SLC22A1L), which can function in concert with the ubiquitin-conjugating enzyme UbcH6. RNF167 is widely conserved in metazoans and contains an N-terminal signal peptide, a protease-associated (PA) domain, two transmembrane domains (TM1 and TM2), and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1154884864 1243 DYCSICLQQYkrrqEMADEIIVFSCGHLYHSFCLQnkectvEFEGQTRWTCYKC 1296
Cdd:cd16797      1 DVCAICLDEY----EEGDKLRVLPCSHAYHSKCVD------PWLTQTKKTCPVC 44

WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from its N-terminus and the WD dipeptide at its C-terminus and is 40 residues long, hence the name WD40; between GH and WD lies a conserved core; serves as a stable propeller-like platform to which proteins can bind either stably or reversibly; forms a propeller-like structure with several blades where each blade is composed of a four-stranded anti-parallel b-sheet; instances with few detectable copies are hypothesized to form larger structures by dimerization; each WD40 sequence repeat forms the first three strands of one blade and the last strand in the next blade; the last C-terminal WD40 repeat completes the blade structure of the first WD40 repeat to create the closed ring propeller-structure; residues on the top and bottom surface of the propeller are proposed to coordinate interactions with other proteins and/or small ligands; 7 copies of the repeat are present in this alignment.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1154884864  184 GQYGAISALSINNDCSRLLCGFAKGQITMWDLASGKLLRSITdAHPpgTAILHIKFTDDPTLAICNDSGGSVfeltfkRV 263
Cdd:cd00200    175 GHTGEVNSVAFSPDGEKLLSSSSDGTIKLWDLSTGKCLGTLR-GHE--NGVNSVAFSPDGYLLASGSEDGTI------RV 245

                           90       100
                   ....*....|....*....|..
gi 1154884864  264 MGVRTCESRCLFSGSKGEVCCI 285
Cdd:cd00200    246 WDLRTGECVQTLSGHTNSVTSL 267

H2 subclass of RING (RING-H2) fingers and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers: some have different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). This family corresponds to the H2 subclass of RING (RING-H2) finger proteins that are characterized by containing C3H2C3-type canonical RING-H2 fingers or noncanonical RING-H2 finger variants, including C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type modified RING-H2 fingers. The canonical RING-H2 finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-H-X2-C-X(4-48)-C-X2-C, X is any amino acid and the number of X residues varies in different fingers. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-H2 finger can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serves as a scaffold for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.

                           10        20        30
                   ....*....|....*....|....*....|....
gi 1154884864 1245 CSICLQQYkrrqEMADEIIVFSCGHLYHSFCLQN 1278
Cdd:cd16448      1 CVICLEEF----EEGDVVRLLPCGHVFHLACILR 30

PHD zinc finger; The plant homeodomain (PHD) finger is a C4HC3 zinc-finger-like motif found in nuclear proteins thought to be involved in epigenetics and chromatin-mediated transcriptional regulation. The PHD finger binds two zinc ions using the so-called 'cross-brace' motif and is thus structurally related to the RING finger and the FYVE finger. It is not yet known if PHD fingers have a common molecular function. Several reports suggest that it can function as a protein-protein interacton domain and it was recently demonstrated that the PHD finger of p300 can cooperate with the adjacent BROMO domain in nucleosome binding in vitro. Other reports suggesting that the PHD finger is a ubiquitin ligase have been refuted as these domains were RING fingers misidentified as PHD fingers.

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 1154884864  1244 YCSIClqqykrRQEMADEIIVF--SCGHLYHSFCLQNKECTVEFEGqtRWTCYKC 1296
Cdd:smart00249    1 YCSVC------GKPDDGGELLQcdGCDRWYHQTCLGPPLLEEEPDG--KWYCPKC 47

RING finger, H2 subclass, found in RING finger proteins RNF139, RNF145, and similar proteins; RNF139, also known as translocation in renal carcinoma on chromosome 8 protein (TRC8), is an endoplasmic reticulum (ER)-resident multi-transmembrane protein that functions as a potent growth suppressor in mammalian cells, inducing G2/M arrest, decreased DNA synthesis and increased apoptosis. It is a tumor suppressor that has been implicated in a novel regulatory relationship linking the cholesterol/lipid biosynthetic pathway with cellular growth control. A mutation in RNF139 has been identified in families with hereditary renal (RCC) and thyroid cancers. RNF145 is an uncharacterized RING finger protein encoded by the RNF145 gene, which is expressed in T lymphocytes, and its expression is altered in acute myelomonocytic and acute promyelocytic leukemias. Although its biological function remains unclear, RNF145 shows high sequence similarity with RNF139. Both RNF139 and RNF145 contain a C3H2C3-type RING-H2 finger with possible E3-ubiquitin ligase activity.

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1154884864 1243 DYCSICLQQYKrrqemadEIIVFSCGHLYHSFCLQ 1277
Cdd:cd16476      1 DVCAICYQEMK-------EARITPCNHFFHGLCLR 28