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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 544583444 356 STSGDVCRICHCEGDDESPLITPCHCTGSLHFVHQACLQQWIKSSDTRCCELCKYEFIMETKL 418
Cdd:cd16807    2 PSNQDICRICHCEGDDESPLITPCHCTGSLRFVHQACLQQWIKSSDTRCCELCKYEFIMETKL 64

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 544583444 356 STSGDVCRICHCEGDDESPLITPCHCTGSLHFVHQACLQQWIKSSDTRCCELCKYEFIMETKL 418
Cdd:cd16807    2 PSNQDICRICHCEGDDESPLITPCHCTGSLRFVHQACLQQWIKSSDTRCCELCKYEFIMETKL 64

RING-variant domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 544583444  362 CRICHCEGDDESPLITPCHCTGSLHFVHQACLQQWIKSSDTRCCELC 408
Cdd:pfam12906   1 CRICLEEEAEDSPLIHPCRCRGSLKYVHQSCLERWLDTSANTQCEIC 47

LAP/PHD finger-like protein; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 544583444 355 VSTSGDVCRICHcegDDESPLITPCHCTGSLHFVHQACLQQWIKSSDTRCCELCKYEFIMETKLKPLRKW 424
Cdd:PHA02825   4 VSLMDKCCWICK---DEYDVVTNYCNCKNENKIVHKECLEEWINTSKNKSCKICNGPYNIKKNYKKCTKW 70

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 544583444 356 STSGDVCRICHCEGDDESPLITPCHCTGSLHFVHQACLQQWIKSSDTRCCELCKYEFIMETKL 418
Cdd:cd16807    2 PSNQDICRICHCEGDDESPLITPCHCTGSLRFVHQACLQQWIKSSDTRCCELCKYEFIMETKL 64

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 544583444 361 VCRICHCEGDDESPLITPCHCTGSLHFVHQACLQQWIKSSDTRCCELCKYEF 412
Cdd:cd16698    1 ICRICHCEGDPENPLITPCYCSGSLKYVHQACLQQWIKSSDTKSCELCKFEF 52

RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH6 (MARCH6); MARCH6, also known as membrane-associated RING finger protein 6, membrane-associated RING-CH protein VI (MARCH-VI), RING finger protein 176 (RNF176), protein TEB-4, or Doa10 homolog, is an endoplasmic reticulum (ER)-localized E3 ubiquitin ligase that ubiquitinates ER-associated proteins with a cytoplasmic domain in a ubiquitin-conjugating enzyme 7 (UBC7)-dependent manner), such as Mps2, UBC6, and Ste6. It also regulates its own UBC7-mediated degradation. MARCH6 interacts with ubiquitin-specific protease USP19, which deubiquitinates and stabilizes MARCH6 and inhibits p97-dependent proteasomal degradation. It is also involved in the cholesterol synthesis pathway by controlling the degradation of squalene monooxygenase (SM), and affects 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR). Furthermore, it may be a key regulator of thyroid hormone activation in a number of tissues, since it mediates the proteasomal degradation of type 2 iodothyronine deiodinase (D2). MARCH6 contains 14 transmembrane helices and a conserved N-terminal C4HC3-type RING-CH finger, also known as vRING or RINGv, a variant of C3H2C3-type RING-H2 finger, that catalyzes ubiquitin Lys48-specific ligation.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 544583444 361 VCRICHCEGDDESPLITPCHCTGSLHFVHQACLQQWIKSSDTRCCELCKY 410
Cdd:cd16702    1 ICRVCRGEGTPDRPLFHPCKCSGSIKYVHQECLLQWLKHSRKEYCELCKH 50

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 544583444 362 CRICHCEGDDESPLITPCHCTGSLHFVHQACLQQWIKSSDTR---CCELCK 409
Cdd:cd16495    1 CRICLEEEEEGEPLISPCRCKGSLKYVHRECLKRWLTESGNRsntKCEICK 51

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 544583444  353 SPVSTSGDVCRICHCEGDDESPLITPCHCTGSLHFVHQACLQQWIKSSDTRCCELCKYEFIMETKLKP 420
Cdd:COG5183     6 TPMNEDKRSCRICRTEDIRDDPLFHPCKCSGSIKYIHRECLMEWMECSGTKKCDICHYEYKFKDIYKE 73

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 544583444 361 VCRICHcEGDDESPLITPCHCTGSLHFVHQACLQQWIKSSDTRCCELCKYEF 412
Cdd:cd16809    6 MCRICH-EGSSQEDLLSPCECTGTLGTIHRSCLEHWLSSSNTSYCELCHFRF 56

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 544583444 359 GDVCRICHC-EGDDESPLITPCHCTGSLHFVHQACLQQWIKS--------SDTRCCELCK 409
Cdd:cd16812    4 GDLCRICQMgMTSSSNPLIEPCKCTGSLQYVHQECMKKWLQAkinsgsslEAVTTCELCK 63

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 544583444 361 VCRICHcEGDDESPLITPCHCTGSLHFVHQACLQQWIKSSDTRCCELCKYEF 412
Cdd:cd16700    1 LCRICF-QGAEQGELLSPCRCDGSVRCTHQPCLLKWISERGSWSCELCYYRY 51

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 544583444 362 CRICHcEGDDESPLITPCHCTGSLHFVHQACLQQWIKSSDTRCCELCKYEF 412
Cdd:cd16825    5 CRICF-QGPEQGELLSPCRCDGSVRCTHQPCLIRWISERGSWSCELCYFKY 54

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 544583444 361 VCRICHcEGDDESPLITPCHCTGSLHFVHQACLQQWIKSSDTRCCELCKYEF 412
Cdd:cd16824    6 LCRICF-QGPEQGELLSPCRCDGSVRCTHQPCLIKWISERGSWSCELCYYKY 56

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
                 ....*....|....*....|....*....|....*....|....*....
gi 544583444 362 CRICHCEGDDESPL-ITPCHctgslHFVHQACLQQWIKSSDtRCCELCK 409
Cdd:cd16448    1 CVICLEEFEEGDVVrLLPCG-----HVFHLACILRWLESGN-NTCPLCR 43

5L protein; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 544583444 360 DVCRICHCEGDDESPLitpCHCTGSLHFVHQACLQQWIKSSDTRCCELCKYEFIMETKLKPLRKWE 425
Cdd:PHA02862   3 DICWICNDVCDERNNF---CGCNEEYKVVHIKCMQLWINYSKKKECNLCKTKYNIKKTYVSFKKWN 65

RING finger, H2 subclass, found in RING finger protein 145 (RNF145) and similar proteins; RNF145 is an uncharacterized RING finger protein encoded by the RNF145 gene, which is expressed in T lymphocytes, and its expression is altered in acute myelomonocytic and acute promyelocytic leukemias. Although its biological function remains unclear, RNF145 shows high sequence similarity with RNF139, an endoplasmic reticulum (ER)-resident multi-transmembrane protein that functions as a potent growth suppressor in mammalian cells, inducing G2/M arrest, decreased DNA synthesis and increased apoptosis. Like RNF139, RNF145 contains a C3H2C3-type RING-H2 finger with possible E3-ubiquitin ligase activity.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 544583444 360 DVCRICHceGDDESPLITPCHctgslHFVHQACLQQWIKSSDTrcCELC 408
Cdd:cd16684    3 DICSICY--QDMKSAVITPCS-----HFFHAGCLKKWLYVQET--CPLC 42