RING finger (Really Interesting New Gene) domain and U-box domain superfamily; 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). C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type RING fingers are closely related to RING-HC fingers. In contrast, C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type RING fingers are more closely related to RING-H2 fingers. However, not all RING finger-containing proteins display regular RING finger features, and the RING finger family has turned out to be multifarious. The degenerate RING fingers of the Siz/PIAS RING (SP-RING) family proteins and sporulation protein RMD5, are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues. They bind only one Zn2+ ion. On the other hand, the RING fingers of the human APC11 and RBX1 proteins can bind a third Zn atom since they harbor four additional Zn ligands. U-box is a modified form of the RING finger domain that lacks metal chelating Cys and His residues. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms. RING finger/U-box-containing proteins are 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 serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enable efficient transfer of ubiquitin from E2 to the substrates.

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gi 2036578835 334 EVCRICHCEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELCKYDFIMETKLKPLRKWE 399
Cdd:cd16806     5 DICRICHCEGDEESPLITPCRCTGTLRFVHQACLHQWIKSSDTRCCELCKYDFIMETKLKPLRKWE 70

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 2036578835 334 EVCRICHCEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELCKYDFIMETKLKPLRKWE 399
Cdd:cd16806     5 DICRICHCEGDEESPLITPCRCTGTLRFVHQACLHQWIKSSDTRCCELCKYDFIMETKLKPLRKWE 70

RING-variant domain;

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                  ....*....|....*....|....*....|....*....|....*..
gi 2036578835 336 CRICHCEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELC 382
Cdd:pfam12906   1 CRICLEEEAEDSPLIHPCRCRGSLKYVHQSCLERWLDTSANTQCEIC 47

LAP/PHD finger-like protein; Provisional

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2036578835 327 DDGSDNLEVCRICHcegDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELCKYDFIMETKLKPLRKW 398
Cdd:PHA02825    2 EDVSLMDKCCWICK---DEYDVVTNYCNCKNENKIVHKECLEEWINTSKNKSCKICNGPYNIKKNYKKCTKW 70

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 2036578835 334 EVCRICHCEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELCKYDFIMETKLKPLRKWE 399
Cdd:cd16806     5 DICRICHCEGDEESPLITPCRCTGTLRFVHQACLHQWIKSSDTRCCELCKYDFIMETKLKPLRKWE 70

RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING finger protein MARCH1, MARCH8, and similar proteins; This subfamily includes the closely related MARCH1 and MARCH8, both of which are located on endosomes and the plasma membrane and are implicated in regulating cell surface expression of their substrates. They ubiquitylate and downregulate many targets, including major histocompatibility complex class II (MHCII), CD86, transferrin receptor, HLA-DM, and Fas from the cell surface. MARCH1 is mainly expressed in cells of the immune system, while MARCH8 is more broadly expressed. Both of them contain 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. The cytoplasmic RING-CH finger participates in the ubiquitin transfer from the E2 to its substrate. The transmembrane domains are implicated in target recognition and dimer formation.

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gi 2036578835 335 VCRICHCEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELCKYDF 386
Cdd:cd16698     1 ICRICHCEGDPENPLITPCYCSGSLKYVHQACLQQWIKSSDTKSCELCKFEF 52

RING-variant domain;

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gi 2036578835 336 CRICHCEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELC 382
Cdd:pfam12906   1 CRICLEEEAEDSPLIHPCRCRGSLKYVHQSCLERWLDTSANTQCEIC 47

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 2036578835 336 CRICHCEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTR---CCELCK 383
Cdd:cd16495     1 CRICLEEEEEGEPLISPCRCKGSLKYVHRECLKRWLTESGNRsntKCEICK 51

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

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gi 2036578835  330 SDNLEVCRICHCEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELCKYDFIMETKLKP 394
Cdd:COG5183      9 NEDKRSCRICRTEDIRDDPLFHPCKCSGSIKYIHRECLMEWMECSGTKKCDICHYEYKFKDIYKE 73

RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH2 (MARCH2); MARCH2, also known as membrane-associated RING finger protein 2, membrane-associated RING-CH protein II (MARCH-II), or RING finger protein 172 (RNF172), 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 (beta2AR) 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. MARCH2 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.

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gi 2036578835 335 VCRICHcEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELCKYDF 386
Cdd:cd16808     2 ICRICH-EGGNGESLLSPCDCTGTLGTVHKSCLEKWLSSSNTSYCELCHTEF 52

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 2036578835 335 VCRICHcEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELCKYDF 386
Cdd:cd16700     1 LCRICF-QGAEQGELLSPCRCDGSVRCTHQPCLLKWISERGSWSCELCYYRY 51

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 2036578835 327 DDGSDNLEVCRICHCEGDE-ESPLITPCRCTGTLRFVHQSCLHQWIKSS--------DTRCCELCKYDFIME 389
Cdd:cd16813     1 EDSEEEGDLCRICQIAGGSpSNPLLEPCGCVGSLQFVHQECLKKWLKVKitsgadlgAVKTCEMCKQGLLVD 72

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 2036578835 336 CRICHcEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELCKYDF 386
Cdd:cd16825     5 CRICF-QGPEQGELLSPCRCDGSVRCTHQPCLIRWISERGSWSCELCYFKY 54

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 2036578835 335 VCRICHcEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELCKYDF 386
Cdd:cd16810     2 ICKICF-QGPEQGELLNPCRCDGSVRYTHQLCLLKWISERGSWTCELCCYRY 52

LAP/PHD finger-like protein; Provisional

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2036578835 327 DDGSDNLEVCRICHcegDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELCKYDFIMETKLKPLRKW 398
Cdd:PHA02825    2 EDVSLMDKCCWICK---DEYDVVTNYCNCKNENKIVHKECLEEWINTSKNKSCKICNGPYNIKKNYKKCTKW 70

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.

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gi 2036578835 336 CRICHCEGDEESPL-ITPCRCTgtlrfVHQSCLHQWIKSSDtRCCELCK 383
Cdd:cd16448     1 CVICLEEFEEGDVVrLLPCGHV-----FHLACILRWLESGN-NTCPLCR 43