second RING finger, H2 subclass, found in RING finger protein 32 (RNF32) and similar proteins; RNF32 is mainly expressed in testis spermatogenesis, most likely in spermatocytes and/or in spermatids, suggesting a possible role in sperm formation. RNF32 contains two C3H2C3-type RING-H2 fingers separated by an IQ domain of unknown function. Although the biological function of RNF32 remains unclear, proteins with double RING-H2 fingers may act as scaffolds for binding several proteins that function in the same pathway. This model corresponds to the second RING-H2 finger.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720414423 128 ECSICLTPLSFHGDGRQAAIGTSsqrpRETVLLSCAHLFHNACLLALEEFSLGDnapFHVCPLCRSCY 195
Cdd:cd16678     1 DCPICLTPLQSSGDSSDAKRVSS----RPTVLLSCSHVFHATCLEAFEEFSVGE---ELVCPVCRSHY 61

second RING finger, H2 subclass, found in RING finger protein 32 (RNF32) and similar proteins; RNF32 is mainly expressed in testis spermatogenesis, most likely in spermatocytes and/or in spermatids, suggesting a possible role in sperm formation. RNF32 contains two C3H2C3-type RING-H2 fingers separated by an IQ domain of unknown function. Although the biological function of RNF32 remains unclear, proteins with double RING-H2 fingers may act as scaffolds for binding several proteins that function in the same pathway. This model corresponds to the second RING-H2 finger.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720414423 128 ECSICLTPLSFHGDGRQAAIGTSsqrpRETVLLSCAHLFHNACLLALEEFSLGDnapFHVCPLCRSCY 195
Cdd:cd16678     1 DCPICLTPLQSSGDSSDAKRVSS----RPTVLLSCSHVFHATCLEAFEEFSVGE---ELVCPVCRSHY 61

RING-finger-containing E3 ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720414423  97 ILQQLDERCG--QIITKEDWEKIQA-QAAHHEIYECSICLTPLSfhgdgrqaaigTSSQRPretvllsCAHLFHNACLla 173
Cdd:COG5574   183 ILQPSNNLHTlfQVITKENLSKKNGlPFIPLADYKCFLCLEEPE-----------VPSCTP-------CGHLFCLSCL-- 242

                          90       100
                  ....*....|....*....|....*...
gi 1720414423 174 leeFSLGDNAPFHVCPLCRS-CYQKKIV 200
Cdd:COG5574   243 ---LISWTKKKYEFCPLCRAkVYPKKVI 267

Calmodulin-binding motif; Short calmodulin-binding motif containing conserved Ile and Gln residues.

                           10        20
                   ....*....|....*....|
gi 1720414423   24 KCATRIQAYWRGYIVRKWYR 43
Cdd:smart00015   4 RAAIIIQAAWRGYLARKRYK 23

second RING finger, H2 subclass, found in RING finger protein 32 (RNF32) and similar proteins; RNF32 is mainly expressed in testis spermatogenesis, most likely in spermatocytes and/or in spermatids, suggesting a possible role in sperm formation. RNF32 contains two C3H2C3-type RING-H2 fingers separated by an IQ domain of unknown function. Although the biological function of RNF32 remains unclear, proteins with double RING-H2 fingers may act as scaffolds for binding several proteins that function in the same pathway. This model corresponds to the second RING-H2 finger.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720414423 128 ECSICLTPLSFHGDGRQAAIGTSsqrpRETVLLSCAHLFHNACLLALEEFSLGDnapFHVCPLCRSCY 195
Cdd:cd16678     1 DCPICLTPLQSSGDSSDAKRVSS----RPTVLLSCSHVFHATCLEAFEEFSVGE---ELVCPVCRSHY 61

IQ (isoleucine-glutamine) motif containing D (IQCD); IQCD, also called dynein regulatory complex protein 10 (DRC10), belongs to the IQ motif-containing protein family which contains a C-terminal conserved IQ motif domain and two coiled-coil domains. The IQ motif ([ILV]QxxxRxxxx[RK]), where x stands for any amino-acid residue, interacts with calmodulin (CaM) in a calcium-independent manner and is present in proteins with a wide diversity of biological functions. The IQCD protein was found to primarily accumulate in the acrosome area of round and elongating spermatids of the testis during late stage of spermiogenesis and was then localized to the acrosome and tail regions of mature spermatozoa. The expression of IQCD follows the trajectory of acrosome development during spermatogenesis. IQCD is associated with neuroblastoma and neurodegenerative diseases, and is reported to interact with the nuclear retinoid X receptor in the presence of 9-cis-retinoic acid, thereby activating the transcriptional activity of the receptor.

                          10        20
                  ....*....|....*....|....*.
gi 1720414423  22 RVKCATRIQAYWRGYIVRKWYRNLRK 47
Cdd:cd23767     8 MNRAATLIQALWRGYKVRKELKKKKK 33

RING-finger-containing E3 ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720414423  97 ILQQLDERCG--QIITKEDWEKIQA-QAAHHEIYECSICLTPLSfhgdgrqaaigTSSQRPretvllsCAHLFHNACLla 173
Cdd:COG5574   183 ILQPSNNLHTlfQVITKENLSKKNGlPFIPLADYKCFLCLEEPE-----------VPSCTP-------CGHLFCLSCL-- 242

                          90       100
                  ....*....|....*....|....*...
gi 1720414423 174 leeFSLGDNAPFHVCPLCRS-CYQKKIV 200
Cdd:COG5574   243 ---LISWTKKKYEFCPLCRAkVYPKKVI 267

IQ (isoleucine-glutamine) motif containing G (IQCG); IQCG, also called dynein regulatory complex protein 9 (DRC9), belongs to the IQ motif-containing protein family which contains a C-terminal conserved IQ (isoleucine-glutamine) motif and a coiled-coil domain. The IQ motif ([ILV]QxxxRxxxx[RK]), where x stands for any amino-acid residue, interacts with calmodulin (CaM) in a calcium-independent manner and is present in proteins with a wide diversity of biological functions. The expression of IQCG is reduced in the sperm of human asthenospermia patients whose sperm have reduced mobility. It has also been shown to have a role in the calmodulin-mediated calcium signaling pathway in zebrafish haematopoietic development. The human IQCG gene was first reported to be involved in chromosome translocation in a case of acute lymphoid/myeloid leukemia. It expresses predominantly at mice testis during spermatogenesis which interacts with calmodulin in a calcium-dependent manner in the mouse testis. IQCG knockout mice are sterile due to the total immobility of their spermatozoa.

                          10
                  ....*....|....*....
gi 1720414423  22 RVKCATRIQAYWRGYIVRK 40
Cdd:cd23766    10 ELRAAIKIQAWWRGIMVRK 28

RING finger, H2 subclass, found in E3 ubiquitin-protein ligase Deltex2 (DTX2) and similar proteins; DTX2, also known as RING finger protein 58, together with DTX1 and DTX4, forms a family of related proteins that are the mammalian homologs of Drosophila Deltex, a known regulator of Notch signals. Like DTX1 and DTX4, DTX2 is expressed in thymocytes. It interacts with the intracellular domain of Notch receptors and acts as a negative regulator of Notch signals in T cells. However, the endogenous levels of DTX1 and DTX2 is not important for regulating Notch signals during thymocyte development. DTX2 contains two Notch-binding WWE domains at the N-terminus that physically interact with the Notch ankyrin domains, a proline-rich motif that shares homology with SH3-binding domains, and a C3H2C3-type RING-H2 finger at the C-terminus. It also harbors two nuclear localization signals.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720414423 128 ECSICLTPLSFhGDGRQAAIGTSSQRPrETV--LLSCAHLFHNACLLALeeFSLGDNAPFHVCPLCRSCYQKK 198
Cdd:cd16672     1 DCIICMEKLSC-ASGYSDVSESKTIQP-SAVgkLTKCGHTFHLLCMLAM--YNNGNKDGSLQCPSCKTIYGEK 69

RING finger, H2 subclass, found in E3 ubiquitin-protein ligase Deltex1 (DTX1), Deltex2 (DTX2), Deltex4 (DTX4), and similar proteins; This subfamily contains the vertebrate homologs of Drosophila melanogaster Deltex, specifically DTX1, DTX2, and DTX4, and other similar proteins mainly from eumetazoa. The vertebrate homologs of Deltex are involved in Notch signaling and neurogenesis. Mammalian DTX1 is most closely related to the Drosophila Deltex. Both of them bind to SH3-domain containing protein Grb2 and further inhibit E2A. DTX1 functions as a Notch downstream transcription regulator. It interacts with the transcription coactivator p300 and inhibits transcription activation mediated by the neural specific transcription factor MASH1. It is also a transcription target of nuclear factor of activated T cells (NFAT) and participates in T cell anergy and Foxp3 protein level maintenance in vivo. Moreover, DTX1 promotes protein kinase C theta degradation and sustains Casitas B-lineage lymphoma expression. DTX4, also known as RING finger protein 155, shares the highest degree of sequence similarity with DTX1. So it likely interacts with the intracellular domain of Notch as well. Like DTX1 and DTX4, DTX2 is expressed in thymocytes. It interacts with the intracellular domain of Notch receptors and acts as a negative regulator of Notch signals in T cells. However, the endogenous levels of DTX1 and DTX2 is not important for regulating Notch signals during thymocyte development. In contrast to other DTXs, DTX3 does not contain two Notch-binding WWE domains at the N-terminus, but rather a short unique N-terminal domain. It does not interact with the intracellular domain of Notch. In addition, it has a different class of RING finger (C3HC4 type or RING-HC subclass), compared with the other DTXs which harbor a C3H2C3-type RING-H2 finger. Thus DTX3 is not included in this subfamily. Drosophila melanogaster Deltex also does not belong to this subfamily.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1720414423 128 ECSICLTPLSfhgdGRQAAIGTSSQRPRETVLLS-CAHLFHNACLLALEEFSLGDNApfHVCPLCRSCY 195
Cdd:cd16459     1 DCPICCEPLC----VASGYEESKLEGSKVVVRLKkCSHMYHKACLVAMYSNGAKDGS--LQCPTCKTIY 63

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        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1720414423 129 CSICLTPLsfhgdgrqaaigtssQRPRETVLLSCAHLFHNACLLALEEFSlgdnapFHVCPLCR 192
Cdd:cd16448     1 CVICLEEF---------------EEGDVVRLLPCGHVFHLACILRWLESG------NNTCPLCR 43