The RING-variant domain is a C4HC3 zinc-finger like motif found in a number of cellular and viral proteins; Some of these proteins have been shown both in vivo and in vitro to have ubiquitin E3 ligase activity. The RING-variant domain is reminiscent of both the RING and the PHD domains and may represent an evolutionary intermediate. To describe this domain the term PHD/LAP domain has been used in the past. Extended description: The RING-variant (RINGv) domain contains a C4HC3 zinc-finger-like motif similar to the PHD domain, while some of the spacing between the Cys/His residues follow a pattern somewhat closer to that found in the RING domain. The RINGv domain, similar to the RING, PHD and LIM domains, is thought to bind two zinc ions co-ordinated by the highly conserved Cys and His residues. RING variant domain: C-x (2) -C-x(10-45)-C-x (1) -C-x (7) -H-x(2)-C-x(11-25)-C-x(2)-C As opposed to a PHD: C-x(1-2) -C-x (7-13)-C-x(2-4)-C-x(4-5)-H-x(2)-C-x(10-21)-C-x(2)-C Classical RING domain: C-x (2) -C-x (9-39)-C-x(1-3)-H-x(2-3)-C-x(2)-C-x(4-48) -C-x(2)-C

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                   ....*....|....*....|....*....|....*....|....*....
gi 26343457     63 FCRICHEGA-NGENLLSPCGCTGTLGAVHKSCLEKWLSSSNTSYCELCH 110
Cdd:smart00744   1 ICRICHDEGdEGDPLVSPCRCKGSLKYVHQECLERWINESGNKTCEICK 49

E3 ubiquitin-protein ligase DOA10 [Posttranslational modification, protein turnover, chaperones];

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 26343457   64 CRICH-EGANGENLLSPCGCTGTLGAVHKSCLEKWLSSSNTSYCELCHTEF 113
Cdd:COG5183   15 CRICRtEDIRDDPLFHPCKCSGSIKYIHRECLMEWMECSGTKKCDICHYEY 65

RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING finger proteins MARCH2, MARCH3, and similar proteins; MARCH2 and MARCH3 contain a C4HC3-type RING-CH finger, also known as vRING or RINGv, a variant of C3H2C3-type RING-H2 finger, in the N-terminal cytoplasmic region, two transmembrane domains in the middle region, and a PDZ-binding motif at the C-terminus. MARCH2 is a Golgi-localized, membrane-associated E3 ubiquitin-protein ligase that is involved in endosomal trafficking through the binding of syntaxin 6 (STX6). It is involved in the cystic fibrosis transmembrane conductance regulator (CFTR)-associated ligand (CAL)-mediated ubiquitination and lysosomal degradation of mature CFTR through the association with adaptor proteins CAL and STX6. It also reduces the surface expression of CD86 and the transferrin receptor TFRC and regulates cell surface carvedilol-bound beta2-adrenergic receptor (beta2ARs) expression. Moreover, MARCH2 interacts with and ubiquitinates PDZ domains polarity determining scaffold protein DLG1 through its PDZ-binding motif, suggesting it may function as a molecular bridge with ubiquitin ligase activity connecting endocytic tumor suppressor proteins such as syntaxins to DLG1. MARCH3 is an E3 ubiquitin-protein ligase that is broadly expressed at relatively high levels in spleen, colon, and lung. It is localized to early endosomes, binds to MARCH2 and syntaxin 6, and is involved in the regulation of vesicular trafficking and fusion of the transport vesicles in endosomes. Its E2 specificity significantly overlaps that of MARCH2.

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                ....*....|....*....|....*....|....*....|....*....|.
gi 26343457  63 FCRICHEGANGENLLSPCGCTGTLGAVHKSCLEKWLSSSNTSYCELCHTEF 113
Cdd:cd16699   1 FCRICHEGESTEDLLSPCECTGTLGLVHRSCLEQWLSSSNTNSCEICHFEY 51

The RING-variant domain is a C4HC3 zinc-finger like motif found in a number of cellular and viral proteins; Some of these proteins have been shown both in vivo and in vitro to have ubiquitin E3 ligase activity. The RING-variant domain is reminiscent of both the RING and the PHD domains and may represent an evolutionary intermediate. To describe this domain the term PHD/LAP domain has been used in the past. Extended description: The RING-variant (RINGv) domain contains a C4HC3 zinc-finger-like motif similar to the PHD domain, while some of the spacing between the Cys/His residues follow a pattern somewhat closer to that found in the RING domain. The RINGv domain, similar to the RING, PHD and LIM domains, is thought to bind two zinc ions co-ordinated by the highly conserved Cys and His residues. RING variant domain: C-x (2) -C-x(10-45)-C-x (1) -C-x (7) -H-x(2)-C-x(11-25)-C-x(2)-C As opposed to a PHD: C-x(1-2) -C-x (7-13)-C-x(2-4)-C-x(4-5)-H-x(2)-C-x(10-21)-C-x(2)-C Classical RING domain: C-x (2) -C-x (9-39)-C-x(1-3)-H-x(2-3)-C-x(2)-C-x(4-48) -C-x(2)-C

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gi 26343457     63 FCRICHEGA-NGENLLSPCGCTGTLGAVHKSCLEKWLSSSNTSYCELCH 110
Cdd:smart00744   1 ICRICHDEGdEGDPLVSPCRCKGSLKYVHQECLERWINESGNKTCEICK 49

RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH proteins (MARCH); This family of membrane-associated E3 ubiquitin ligases consists of 11 members in mammals (MARCH1-11), which are characterized by containing an N-terminal C4HC3-type RING-CH finger, also known as vRING or RINGv, a variant of the C3H2C3-type RING-H2 finger). Most family members have hydrophobic transmembrane regions and are localized to the plasma membrane and intracellular organelle membrane. Only MARCH7 and MARCH10 are predicted to have no transmembrane spanning region. MARCH proteins have been implicated in mediating the ubiquitination and subsequent down-regulation of cell-surface immune regulatory molecules, such as major histocompatibility complex class II and CD86, as well as in endoplasmic reticulum-associated degradation, endosomal protein trafficking, mitochondrial dynamics, and spermatogenesis.

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                ....*....|....*....|....*....|....*....|....*....|.
gi 26343457  64 CRICHEGA-NGENLLSPCGCTGTLGAVHKSCLEKWLSSSN---TSYCELCH 110
Cdd:cd16495   1 CRICLEEEeEGEPLISPCRCKGSLKYVHRECLKRWLTESGnrsNTKCEICK 51

RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH8 (MARCH8); MARCH8, also known as membrane-associated RING finger protein 8, membrane-associated RING-CH protein VIII (MARCH-VIII), RING finger protein 178 (RNF178), or cellular modulator of immune recognition (c-MIR), is a membrane-anchored E3 ubiquitin ligase that is broadly expressed. It is a functional homolog of Kaposi"s sarcoma associated-herpes virus encoded proteins, modulator of immune recognition (MIR) 1 and 2, which are involved in the evasion of host immunity. MARCH8 mediates the ubiquitination and down-regulation of immune regulatory cell surface molecules, including major histocompatibility complex class II (MHCII), CD86, transferrin receptor, HLA-DM, and Fas in immune cells. Moreover, MARCH8 controls cell surface expression of some additional proteins. It regulates the ubiquitination and lysosomal degradation of the transferrin receptor (TfR). Tumor necrosis factor-related apoptosis inducing ligand receptor 1 (TRAIL-R1) is also a physiological substrate of the endogenous MARCH8, which regulates the steady-state cell surface expression of TRAIL-R1. Meanwhile, it negatively regulates interleukin-1 (IL-1) beta-induced NF-kappaB activation by targeting the IL-1 receptor accessory protein (IL1RAP) coreceptor for ubiquitination and degradation. Furthermore, MARCH8 functions in the embryo to modulate the strength of cell adhesion by regulating the localization of E-cadherin. In addition, MARCH8 plays a role in the inhibition of inflammatory cytokine production, suggesting a new therapeutic approach to the treatment of rheumatoid arthritis (RA). MARCH8 contains an N-terminal cytoplasmic C4HC3-type RING-CH finger, also known as vRING or RINGv, a variant of C3H2C3-type RING-H2 finger and two transmembrane domains.

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gi 26343457  64 CRICH-EGANGENLLSPCGCTGTLGAVHKSCLEKWLSSSNTSYCELCHTEFAVEKR 118
Cdd:cd16807   8 CRICHcEGDDESPLITPCHCTGSLRFVHQACLQQWIKSSDTRCCELCKYEFIMETK 63

E3 ubiquitin-protein ligase DOA10 [Posttranslational modification, protein turnover, chaperones];

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 26343457   64 CRICH-EGANGENLLSPCGCTGTLGAVHKSCLEKWLSSSNTSYCELCHTEF 113
Cdd:COG5183   15 CRICRtEDIRDDPLFHPCKCSGSIKYIHRECLMEWMECSGTKKCDICHYEY 65

RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH4 (MARCH4); MARCH4, also known as membrane-associated RING finger protein 4, membrane-associated RING-CH protein IV (MARCH-IV), or RING finger protein 174 (RNF174), is a transmembrane E3 ubiquitin-protein ligase that down-regulates the tetraspanin CD81 and major histocompatibility complex-I (MHC). It also associates with Mult1, suppressing Mult1 expression at the cell surface in a lysine-dependent manner that can be reversed by heat shocking the cells. MARCH4 contains an N-terminal C4HC3-type RING-CH finger, also known as vRING or RINGv, a variant of C3H2C3-type RING-H2 finger, followed by two transmembrane regions.

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gi 26343457  62 PFCRICHEGANGENLLSPCGCTGTLGAVHKSCLEKWLSSSNTSYCELCHTEF 113
Cdd:cd16824   5 PLCRICFQGPEQGELLSPCRCDGSVRCTHQPCLIKWISERGSWSCELCYYKY 56

RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING finger proteins MARCH4, MARCH9, MARCH11, and similar proteins; MARCH4 and MARCH9 are closely related to each other. They downregulate major histocompatibility complex-I (MHC-I). Moreover, MARCH4 and MARCH9, but not other MARCH proteins, can associate with Mult1 and prevent Mult1 expression at the cell surface in a lysine-dependent manner that can be reversed by heat shocking the cells. MARCH11 is a transmembrane RING-finger ubiquitin ligase that is predominantly expressed in developing spermatids in a stage-specific manner and is localized to trans-Golgi network (TGN) vesicles and multivesicular bodies (MVBs). It mediates selective protein sorting via the TGN-MVB transport pathway through its ubiquitin ligase activity. SAMT family proteins have been identified as substrates of MARCH11 in mouse spermatids, suggesting that MARCH11 plays a role in mammalian spermiogenesis. Moreover, MARCH11 targets CD4 for ubiquitination. It also forms complexes with the adaptor protein complex-1 and with fucose-containing glycoproteins including ubiquitinated forms. All subfamily members contain an N-terminal C4HC3-type RING-CH finger, also known as vRING or RINGv, a variant of C3H2C3-type RING-H2 finger, followed by two transmembrane regions.

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gi 26343457  64 CRICHEGANGENLLSPCGCTGTLGAVHKSCLEKWLSSSNTSYCELCHTEF 113
Cdd:cd16700   2 CRICFQGAEQGELLSPCRCDGSVRCTHQPCLLKWISERGSWSCELCYYRY 51

RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated MARCH7, MARCH10, and similar proteins; This subfamily includes two closely related membrane-associated RING-CH proteins, MARCH7 and MARCH10, both of which are predicted to have no transmembrane spanning region, but do harbor a C4HC3-type RING-CH finger, also known as vRING or RINGv, a variant of C3H2C3-type RING-H2 finger, that is responsible for E3 activity. MARCH7, also known as MARCH-VII, RNF177, or axotrophin, is a ubiquitin E3 ligase expressed in multiple types of cells and tissues, including stem cells and precursor cells, and is predominantly localized on the plasma membrane, and cytoplasm. MARCH7 is involved in T cell proliferation and neuronal development. It also participates in the regulation of cytoskeleton re-organization, cellular migration and invasion, cell proliferation, and tumorigenesis in ovarian carcinoma cells. Moreover, MARCH7 modulates nuclear factor kappaB (NF-kappaB) and Wnt/beta-catenin pathways. It has been identified as an authentic target of miR-101. It ubiquitinates tau protein in vitro, impairing microtubule binding. MARCH10, also known as MARCH-X or RNF190, is a microtubule-associated E3 ubiquitin ligase of developing spermatids and is involved in spermiogenesis by regulating the formation and maintenance of the flagella. It is localized to the principal piece of elongating spermatids. in developing spermatids.

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gi 26343457  64 CRICH-EGANGEN-LLSPCGCTGTLGAVHKSCLEKWLSSSNTS--------YCELC 109
Cdd:cd16703   5 CRICQtAGDSTSNqLIEPCQCTGSLQLVHQECLKKWLISKIQSgaeldavkTCEMC 60

RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH11 (MARCH11); MARCH11, also known as membrane-associated RING finger protein 11, or membrane-associated RING-CH protein XI (MARCH-XI), is a transmembrane RING-finger ubiquitin ligase that is predominantly expressed in developing spermatids in a stage-specific manner and is localized to trans-Golgi network (TGN) vesicles and multivesicular bodies (MVBs). It mediates selective protein sorting via the TGN-MVB transport pathway through its ubiquitin ligase activity. SAMT family proteins have been identified as substrates of MARCH11 in mouse spermatids, suggesting that MARCH11 plays a role in mammalian spermiogenesis. Moreover, MARCH11 targets CD4 for ubiquitination. It also forms complexes with the adaptor protein complex-1 and with fucose-containing glycoproteins including ubiquitinated forms. MARCH11 contains an N-terminal C4HC3-type RING-CH finger, also known as vRING or RINGv, a variant of C3H2C3-type RING-H2 finger, and two transmembrane domains. In addition, it harbors a proline-rich region, a tyrosine-based motif, and a PDZ binding motif.

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gi 26343457  62 PFCRICHEGANGENLLSPCGCTGTLGAVHKSCLEKWLSSSNTSYCELCHTEFAV 115
Cdd:cd16810   1 PICKICFQGPEQGELLNPCRCDGSVRYTHQLCLLKWISERGSWTCELCCYRYHV 54

RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH10 (MARCH10); MARCH10, also known as membrane-associated RING finger protein 10, membrane-associated RING-CH protein X (MARCH-X), or RING finger protein 190 (RNF190), is a microtubule-associated E3 ubiquitin ligase in developing spermatids and is involved in spermiogenesis by regulating the formation and maintenance of the flagella. It is localized to the principal piece of elongating spermatids. Unlike other MARCH proteins, MARCH10 is predicted to have no transmembrane spanning region. It harbors a C4HC3-type RING-CH finger, also known as vRING or RINGv, a variant of C3H2C3-type RING-H2 finger, that is responsible for its E3 activity.

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gi 26343457  56 DSQSDCPFCRICH--EGANGENLLSPCGCTGTLGAVHKSCLEKWLSSSNTSYCEL 108
Cdd:cd16813   2 DSEEEGDLCRICQiaGGSPSNPLLEPCGCVGSLQFVHQECLKKWLKVKITSGADL 56

RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH5 (MARCH5); MARCH5, also known as membrane-associated RING finger protein 5, membrane-associated RING-CH protein V (MARCH-V), RING finger protein 153 (RNF153), or mitochondrial ubiquitin ligase (MITOL), is a mitochondrial outer membrane-associated E3 ubiquitin-protein ligase that regulates mitochondrial dynamics including mitochondrial morphology, transport, and interaction with endoplasmic reticulum (ER), at least in part, through the ubiquitination of mitochondrial fission factor Drp1, microtubule-associated protein 1B (MAP1B) and mitofusin 2 (Mfn2), respectively. MARCH5 also mediates the cell cycle-dependent degradation of Mitofusin 1 (Mfn1) in G2/M phase, and thus serves as an upstream quality controller of Mitofusin 1 (Mfn1), preventing excessive accumulation of Mfn1 protein under stress conditions, which is crucial for mitochondrial homeostasis and cell viability. Moreover, MARCH5 is involved in maintaining mouse-embryonic stem cell (mESC) pluripotency via suppression of ERK signalling. It is also a positive regulator of Toll-like receptor 7 (TLR7)-mediated NF-kappaB activation in mammals. MARCH5 contains an N-terminal C4HC3-type RING-CH finger, also known as vRING or RINGv, a variant of C3H2C3-type RING-H2 finger, and four C-terminal transmembrane spans.

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gi 26343457  64 CRICHEGANGENL---LSPCGCTGTLGAVHKSCLEKWLS------SSNTSYCELCHTEF 113
Cdd:cd16701   3 CWVCFATDEDDRSaewVRPCRCRGTTKWVHQACLQRWIDekqkgnSTAKVSCPQCNTEY 61