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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923613   57 PSTQDICRICHCEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELCKYDFIMETKLKPLRKWE 126
Cdd:cd16806   1 PSTQDICRICHCEGDEESPLITPCRCTGTLRFVHQACLHQWIKSSDTRCCELCKYDFIMETKLKPLRKWE 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923613   57 PSTQDICRICHCEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELCKYDFIMETKLKPLRKWE 126
Cdd:cd16806   1 PSTQDICRICHCEGDEESPLITPCRCTGTLRFVHQACLHQWIKSSDTRCCELCKYDFIMETKLKPLRKWE 70

RING-variant domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 8923613     63 CRICHCEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELC 109
Cdd:pfam12906   1 CRICLEEEAEDSPLIHPCRCRGSLKYVHQSCLERWLDTSANTQCEIC 47

LAP/PHD finger-like protein; Provisional

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 8923613    80 CRCTGTLRFVHQSCLHQWIKSSDTRCCELCKYDFIMETKLKPLRKW 125
Cdd:PHA02825  25 CNCKNENKIVHKECLEEWINTSKNKSCKICNGPYNIKKNYKKCTKW 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923613   57 PSTQDICRICHCEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELCKYDFIMETKLKPLRKWE 126
Cdd:cd16806   1 PSTQDICRICHCEGDEESPLITPCRCTGTLRFVHQACLHQWIKSSDTRCCELCKYDFIMETKLKPLRKWE 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 8923613   62 ICRICHCEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELCKYDF 113
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 8923613   62 ICRICHCEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELCKY 111
Cdd:cd16702   1 ICRVCRGEGTPDRPLFHPCKCSGSIKYVHQECLLQWLKHSRKEYCELCKH 50

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 8923613    62 ICRICHCEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELCKYDFIMETKLKP 121
Cdd:COG5183   14 SCRICRTEDIRDDPLFHPCKCSGSIKYIHRECLMEWMECSGTKKCDICHYEYKFKDIYKE 73

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 8923613   62 ICRICHcEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELCKYDF 113
Cdd:cd16699   1 FCRICH-EGESTEDLLSPCECTGTLGLVHRSCLEQWLSSSNTNSCEICHFEY 51

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 8923613   62 ICRICHcEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELCKYDF 113
Cdd:cd16808   2 ICRICH-EGGNGESLLSPCDCTGTLGTVHKSCLEKWLSSSNTSYCELCHTEF 52

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
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 8923613   61 DICRICHC-EGDEESPLITPCRCTGTLRFVHQSCLHQWIKS--------SDTRCCELCK 110
Cdd:cd16812   5 DLCRICQMgMTSSSNPLIEPCKCTGSLQYVHQECMKKWLQAkinsgsslEAVTTCELCK 63

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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 8923613   61 DICRICHCEGDE-ESPLITPCRCTGTLRFVHQSCLHQWIKSS--------DTRCCELCKYDFIME 116
Cdd:cd16813   8 DLCRICQIAGGSpSNPLLEPCGCVGSLQFVHQECLKKWLKVKitsgadlgAVKTCEMCKQGLLVD 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 8923613   63 CRICHcEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELCKYDF 113
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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 8923613   62 ICRICHcEGDEESPLITPCRCTGTLRFVHQSCLHQWIKSSDTRCCELCKYDF 113
Cdd:cd16810   2 ICKICF-QGPEQGELLNPCRCDGSVRYTHQLCLLKWISERGSWTCELCCYRY 52

LAP/PHD finger-like protein; Provisional

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 8923613    80 CRCTGTLRFVHQSCLHQWIKSSDTRCCELCKYDFIMETKLKPLRKW 125
Cdd:PHA02825  25 CNCKNENKIVHKECLEEWINTSKNKSCKICNGPYNIKKNYKKCTKW 70