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 18398630    265 VCRICLVElGEDSEAFKMECLCRGELALAHKECTIKWFTIKGNRTCDVCK 314
Cdd:smart00744   1 ICRICHDE-GDEGDPLVSPCRCKGSLKYVHQECLERWINESGNKTCEICK 49

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 18398630    265 VCRICLVElGEDSEAFKMECLCRGELALAHKECTIKWFTIKGNRTCDVCK 314
Cdd:smart00744   1 ICRICHDE-GDEGDPLVSPCRCKGSLKYVHQECLERWINESGNKTCEICK 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 18398630 266 CRICLVElGEDSEAFKMECLCRGELALAHKECTIKWFTIKGNR---TCDVCK 314
Cdd:cd16495   1 CRICLEE-EEEGEPLISPCRCKGSLKYVHRECLKRWLTESGNRsntKCEICK 51

LAP/PHD finger-like protein; Provisional

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                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 18398630  257 EDVPEEEAVCRIClvelGEDSEAFKMECLCRGELALAHKECTIKWFTIKGNRTCDVCKQE 316
Cdd:PHA02825   2 EDVSLMDKCCWIC----KDEYDVVTNYCNCKNENKIVHKECLEEWINTSKNKSCKICNGP 57

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 18398630    265 VCRICLVElGEDSEAFKMECLCRGELALAHKECTIKWFTIKGNRTCDVCK 314
Cdd:smart00744   1 ICRICHDE-GDEGDPLVSPCRCKGSLKYVHQECLERWINESGNKTCEICK 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 18398630 266 CRICLVElGEDSEAFKMECLCRGELALAHKECTIKWFTIKGNR---TCDVCK 314
Cdd:cd16495   1 CRICLEE-EEEGEPLISPCRCKGSLKYVHRECLKRWLTESGNRsntKCEICK 51

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

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 18398630  261 EEEAVCRICLVELGEDSEAFKmECLCRGELALAHKECTIKWFTIKGNRTCDVCKQEV-----------QNLPVTLL 325
Cdd:COG5183   10 EDKRSCRICRTEDIRDDPLFH-PCKCSGSIKYIHRECLMEWMECSGTKKCDICHYEYkfkdiykedmpQIIPFSIL 84

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18398630 261 EEEAVCRICLVELGEDSEAFKMECLCRGELALAHKECTIKWFTIKGN--------RTCDVCKQ 315
Cdd:cd16812   2 EEGDLCRICQMGMTSSSNPLIEPCKCTGSLQYVHQECMKKWLQAKINsgssleavTTCELCKE 64

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 18398630 266 CRICLVELGEDSEAFKMECLCRGELALAHKECTIKWFTIKGN--------RTCDVCK 314
Cdd:cd16703   5 CRICQTAGDSTSNQLIEPCQCTGSLQLVHQECLKKWLISKIQsgaeldavKTCEMCK 61

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 18398630 260 PEEEAVCRICLVElGEDSEAFKMECLCRGELALAHKECTIKWFTIKGNRTCDVCKQE 316
Cdd:cd16806   1 PSTQDICRICHCE-GDEESPLITPCRCTGTLRFVHQACLHQWIKSSDTRCCELCKYD 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 18398630 265 VCRICLveLGEDSEAFKMECLCRGELALAHKECTIKWFTIKGNRTCDVC 313
Cdd:cd16700   1 LCRICF--QGAEQGELLSPCRCDGSVRCTHQPCLLKWISERGSWSCELC 47

RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING finger protein MARCH4, MARCH9, and similar proteins; This subfamily includes the closely related MARCH4 and MARCH9, both belonging to the family of MARCH E3 ligases. They downregulate major histocompatibility complex-I (MHC-I). In the presence of MARCH4 or MARCH9, MHC-I can be ubiquitinated and rapidly internalized by endocytosis, whereas MHC-I molecules lacking lysines in their cytoplasmic tail are resistant to downregulation. 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. Both MARCH4 and MARCH9 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 18398630 266 CRICLveLGEDSEAFKMECLCRGELALAHKECTIKWFTIKGNRTCDVC 313
Cdd:cd16811   2 CRICF--QGPEQGELLSPCRCDGSVRCTHQPCLIKWISERGSWSCELC 47

RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH9 (MARCH9); MARCH9, also known as membrane-associated RING finger protein 9, membrane-associated RING-CH protein IX (MARCH-IX), or RING finger protein 179 (RNF179), is a transmembrane E3 ubiquitin-protein ligase that down-regulates Mult1, CD4, major histocompatibility complex-I (MHC), and intercellular adhesion molecule (ICAM-1). It may also interact with receptor-type protein-tyrosine phosphatases (e.g. PTPRJ/CD148) as well as Fc gamma receptor IIB (CD32B), HLA-DQ, signaling lymphocytic activation molecule (CD150), and polio virus receptor (CD155). MARCH9 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 18398630 266 CRICLveLGEDSEAFKMECLCRGELALAHKECTIKWFTIKGNRTCDVC 313
Cdd:cd16825   5 CRICF--QGPEQGELLSPCRCDGSVRCTHQPCLIRWISERGSWSCELC 50

RING finger, H2 subclass, found in RING finger protein 111 (RNF111) and similar proteins; RNF111, also known as Arkadia, is a nuclear E3 ubiquitin-protein ligase that targets intracellular effectors and modulators of transforming growth factor beta (TGF-beta)/Nodal-related signaling for polyubiquitination and proteasome-dependent degradation. It acts as an amplifier of Nodal signals, and enhances the dorsalizing activity of limiting amounts of Xnr1, a Nodal homolog, and requires Nodal signaling for its function. The loss of RNF111 results in early embryonic lethality, with defects attributed to compromised Nodal signaling. RNF111 also regulates tumor metastasis by modulation of the TGF-beta pathway. Its ubiquitination can be modulated by the four and a half LIM-only protein 2 (FHL2) that activates TGF-beta signal transduction. Furthermore, RNF111 interacts with the clathrin-adaptor 2 (AP2) complex and regulates endocytosis of certain cell surface receptors, leading to modulation of epidermal growth factor (EGF) and possibly other signaling pathways. In addition, RNF111 has been identified as a small ubiquitin-like modifier (SUMO)-binding protein with clustered SUMO-interacting motifs (SIMs) that together form a SUMO-binding domain (SBD). It thus functions as a SUMO-targeted ubiquitin ligase (STUbL) that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response, as well as triggers degradation of signal-induced polysumoylated proteins, such as the promyelocytic leukemia protein (PML). The N-terminal half of RNF111 harbors three SIMs. Its C-terminal half show high sequence similarity with RING finger protein 165 (RNF165), where it contains two serine rich domains, two nuclear localization signals, an NRG-TIER domain, and a C-terminal C3H2C3-type RING-H2 finger that is required for polyubiqutination and proteasome-dependent degradation of phosphorylated forms of Smad2/3 and three major negative regulators of TGF-beta signaling, Smad7, SnoN and c-Ski.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18398630 254 DGAEDVPEEEavCRICLVELGEDSEAFKMEClcrgeLALAHKECTIKWFTIkgNRTCDVCKQEVQ 318
Cdd:cd16681   3 EGTEEDTEEK--CTICLSILEEGEDVRRLPC-----MHLFHQVCVDQWLIT--NKKCPICRVDIE 58

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 18398630 265 VCRICLveLGEDSEAFKMECLCRGELALAHKECTIKWFTIKGNRTCDVC 313
Cdd:cd16810   2 ICKICF--QGPEQGELLNPCRCDGSVRYTHQLCLLKWISERGSWTCELC 48

Modified RING-CH finger, H2 subclass (C4HC2H-type), found in the ZNRF family; The ZNRF family includes zinc/RING finger proteins ZNRF1, ZNRF2, and similar proteins. It has been characterized by containing a unique combination of zinc finger-RING finger motifs in the C-terminal region, which is evolutionarily conserved in a wide range of species, including Caenorhabditis elegans and Drosophila. ZNRF proteins function as E3 ubiquitin ligases and are highly expressed in central nervous system (CNS) and peripheral nervous system (PNS) neurons, particularly during development and in adulthood. ZNRF1 and ZNRF2 are differentially localized within the synaptic region. ZNRF1 is associated with synaptic vesicle membranes, whereas ZNRF2 is present in presynaptic plasma membranes. They are N-myrisotoylated and also located in the endosome-lysosome compartment in fibroblasts. ZNRF proteins may play a role in the establishment and maintenance of neuronal transmission and plasticity via their ubiquitin ligase activity, as well as in regulating Ca2+-dependent exocytosis. The RING fingers found in ZNRF proteins are modified as C4HC2H-type RING-CH finger, rather than the typical C4HC3-type RING-CH finger, which is a variant of the RING-H2 finger.

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                ....*....|....*....|....*....|....*....|....*
gi 18398630 266 CRICLVELGEDSEAFKMECLCRgelalAHKECTIKWFTIkgNRTC 310
Cdd:cd16489   2 CVICLEELEAGDTIARLPCLCI-----YHKKCIDDWFEV--NRSC 39

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.

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                ....*....|....*....|....*....|....*....|....*....|..
gi 18398630 262 EEAVCRIClvELGEDSEAFKMECLCRGELALAHKECTIKWFTIKGNRTCDVC 313
Cdd:cd16809   3 DRPMCRIC--HEGSSQEDLLSPCECTGTLGTIHRSCLEHWLSSSNTSYCELC 52