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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 937919416   124 CCRICHLGletaaAESGAGITLGCSCKGDLSYSHKQCAETWFKIRGNKICEIC 176
Cdd:smart00744   1 ICRICHDE-----GDEGDPLVSPCRCKGSLKYVHQECLERWINESGNKTCEIC 48

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 937919416   124 CCRICHLGletaaAESGAGITLGCSCKGDLSYSHKQCAETWFKIRGNKICEIC 176
Cdd:smart00744   1 ICRICHDE-----GDEGDPLVSPCRCKGSLKYVHQECLERWINESGNKTCEIC 48

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 937919416 125 CRICHLGLEtaaaESGAGITlGCSCKGDLSYSHKQCAETWFKIRG---NKICEIC 176
Cdd:cd16495    1 CRICLEEEE----EGEPLIS-PCRCKGSLKYVHRECLKRWLTESGnrsNTKCEIC 50

LAP/PHD finger-like protein; Provisional

                         10        20        30
                 ....*....|....*....|....*....|..
gi 937919416 147 CSCKGDLSYSHKQCAETWFKIRGNKICEICSS 178
Cdd:PHA02825  25 CNCKNENKIVHKECLEEWINTSKNKSCKICNG 56

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 937919416   124 CCRICHLGletaaAESGAGITLGCSCKGDLSYSHKQCAETWFKIRGNKICEIC 176
Cdd:smart00744   1 ICRICHDE-----GDEGDPLVSPCRCKGSLKYVHQECLERWINESGNKTCEIC 48

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 937919416 125 CRICHLGLEtaaaESGAGITlGCSCKGDLSYSHKQCAETWFKIRG---NKICEIC 176
Cdd:cd16495    1 CRICLEEEE----EGEPLIS-PCRCKGSLKYVHRECLKRWLTESGnrsNTKCEIC 50

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 937919416  122 ERCCRICHLGletaaAESGAGITLGCSCKGDLSYSHKQCAETWFKIRGNKICEIC 176
Cdd:COG5183    12 KRSCRICRTE-----DIRDDPLFHPCKCSGSIKYIHRECLMEWMECSGTKKCDIC 61

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 937919416 125 CRICHLGletaaaESGAGITLGCSCKGDLSYSHKQCAETWFKIRGNKICEIC 176
Cdd:cd16699    2 CRICHEG------ESTEDLLSPCECTGTLGLVHRSCLEQWLSSSNTNSCEIC 47

RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH1 (MARCH1); MARCH1, also known as membrane-associated RING finger protein 1, membrane-associated RING-CH protein I (MARCH-I), or RING finger protein 171 (RNF171), is a membrane-anchored E3 ubiquitin ligase that is mainly expressed in cells of the immune system. It regulates antigen presentation and T-cell costimulatory functions of dendritic cells by down-regulating the cell surface expression of major histocompatibility complex class II (MHCII) and CD86 molecules. It mediates ubiquitination of MHCII and CD86 in dendritic cells (DCs). This ubiquitination induces MHCII and CD86 endocytosis, lysosomal transport, and degradation. MARCH1 also plays a regulatory role in T cell activation during immune responses, as well as in splenic DC homeostasis. Moreover, MARCH1 may regulate its own expression through dimerization and autoubiquitination. MARCH1 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 937919416 125 CRICHlgletAAAESGAGITLGCSCKGDLSYSHKQCAETWFKIRGNKICEIC 176
Cdd:cd16806    7 CRICH-----CEGDEESPLITPCRCTGTLRFVHQACLHQWIKSSDTRCCELC 53

RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH7 (MARCH7); MARCH7, also known as membrane-associated RING finger protein 7, membrane-associated RING-CH protein VII (MARCH-VII), RING finger protein 177 (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. Furthermore, it ubiquitinates tau protein in vitro, impairing microtubule binding. Unlike other MARCH proteins, MARCH7 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 937919416 125 CRICHLGletaAAESGAGITLGCSCKGDLSYSHKQCAETWFKIRGN--------KICEIC 176
Cdd:cd16812    7 CRICQMG----MTSSSNPLIEPCKCTGSLQYVHQECMKKWLQAKINsgssleavTTCELC 62

RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH3 (MARCH3); MARCH3, also known as membrane-associated RING finger protein 3, or membrane-associated RING-CH protein III (MARCH-III), or RING finger protein 173 (RNF173), is an E3 ubiquitin-protein ligase that is broadly expressed and is found 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. MARCH3 is the closest homolog of MARCH2 and it is also a functional homolog of K3 and K5 viral ubiquitin E3 ligases related to immune-evasion strategies used by Kaposi's sarcoma-associated herpesvirus (KSHV). Its E2 specificity significantly overlaps that of MARCH2. MARCH3 contains 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. The RING-CH finger and PDZ-binding motif are essential for the subcellular localization of MARCH3 and the inhibitory effect on transferrin uptake.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 937919416 125 CRICHLGletaaaESGAGITLGCSCKGDLSYSHKQCAETWFKIRGNKICEIC 176
Cdd:cd16809    7 CRICHEG------SSQEDLLSPCECTGTLGTIHRSCLEHWLSSSNTSYCELC 52