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 386770888  42 ICRICHCESDPQNPLLTPCYCSGSLKYVHQACLQQWLTASETNSCELCKFPF 93
Cdd:cd16698    1 ICRICHCEGDPENPLITPCYCSGSLKYVHQACLQQWIKSSDTKSCELCKFEF 52

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 386770888  42 ICRICHCESDPQNPLLTPCYCSGSLKYVHQACLQQWLTASETNSCELCKFPF 93
Cdd:cd16698    1 ICRICHCEGDPENPLITPCYCSGSLKYVHQACLQQWIKSSDTKSCELCKFEF 52

RING-variant domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 386770888   43 CRICHCESDPQNPLLTPCYCSGSLKYVHQACLQQWLTASETNSCELC 89
Cdd:pfam12906   1 CRICLEEEAEDSPLIHPCRCRGSLKYVHQSCLERWLDTSANTQCEIC 47

5L protein; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 386770888  41 DICRICHCESDPQNPLltpCYCSGSLKYVHQACLQQWLTASETNSCELCKFPFIMHTKIKPFNEWR 106
Cdd:PHA02862   3 DICWICNDVCDERNNF---CGCNEEYKVVHIKCMQLWINYSKKKECNLCKTKYNIKKTYVSFKKWN 65

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 386770888  42 ICRICHCESDPQNPLLTPCYCSGSLKYVHQACLQQWLTASETNSCELCKFPF 93
Cdd:cd16698    1 ICRICHCEGDPENPLITPCYCSGSLKYVHQACLQQWIKSSDTKSCELCKFEF 52

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386770888  38 NSGDICRICHCESDPQNPLLTPCYCSGSLKYVHQACLQQWLTASETNSCELCKFPFIMHTKIKPFNEW 105
Cdd:cd16806    2 STQDICRICHCEGDEESPLITPCRCTGTLRFVHQACLHQWIKSSDTRCCELCKYDFIMETKLKPLRKW 69

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
                 ....*....|....*....|....*....|....*....|....*....
gi 386770888  42 ICRICHCESDPQNPLLTPCYCSGSLKYVHQACLQQWLTASETNSCELCK 90
Cdd:cd16702    1 ICRVCRGEGTPDRPLFHPCKCSGSIKYVHQECLLQWLKHSRKEYCELCK 49

RING-variant domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 386770888   43 CRICHCESDPQNPLLTPCYCSGSLKYVHQACLQQWLTASETNSCELC 89
Cdd:pfam12906   1 CRICLEEEAEDSPLIHPCRCRGSLKYVHQSCLERWLDTSANTQCEIC 47

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 386770888  42 ICRICHcESDPQNPLLTPCYCSGSLKYVHQACLQQWLTASETNSCELCKFPF 93
Cdd:cd16699    1 FCRICH-EGESTEDLLSPCECTGTLGLVHRSCLEQWLSSSNTNSCEICHFEY 51

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 386770888  38 NSGDICRICHcESDPQNPLLTPCYCSGSLKYVHQACLQQWLTASETNSCELCKFPF 93
Cdd:cd16809    2 NDRPMCRICH-EGSSQEDLLSPCECTGTLGTIHRSCLEHWLSSSNTSYCELCHFRF 56

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 386770888  42 ICRICHcESDPQNPLLTPCYCSGSLKYVHQACLQQWLTASETNSCELCKFPF 93
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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 386770888  42 ICRICHcESDPQNPLLTPCYCSGSLKYVHQACLQQWLTASETNSCELCKFPF 93
Cdd:cd16700    1 LCRICF-QGAEQGELLSPCRCDGSVRCTHQPCLLKWISERGSWSCELCYYRY 51

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 386770888  42 ICRICHcESDPQNPLLTPCYCSGSLKYVHQACLQQWLTASETNSCELCKFPF 93
Cdd:cd16824    6 LCRICF-QGPEQGELLSPCRCDGSVRCTHQPCLIKWISERGSWSCELCYYKY 56

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 386770888  43 CRICHcESDPQNPLLTPCYCSGSLKYVHQACLQQWLTASETNSCELCKFPF 93
Cdd:cd16825    5 CRICF-QGPEQGELLSPCRCDGSVRCTHQPCLIRWISERGSWSCELCYFKY 54

LAP/PHD finger-like protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386770888  36 SQNSGDICRIChceSDPQNPLLTPCYCSGSLKYVHQACLQQWLTASETNSCELCKFPFIMHTKIKPFNEWRsLDISGIER 115
Cdd:PHA02825   4 VSLMDKCCWIC---KDEYDVVTNYCNCKNENKIVHKECLEEWINTSKNKSCKICNGPYNIKKNYKKCTKWR-CSFRDCHD 79

                         90
                 ....*....|.
gi 386770888 116 RRLCYSVLFHC 126
Cdd:PHA02825  80 SAIVNSLLCLI 90

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 386770888  43 CRICHCE-SDPQNPLLTPCYCsgslkYVHQACLQQWLtASETNSCELCK 90
Cdd:cd16448    1 CVICLEEfEEGDVVRLLPCGH-----VFHLACILRWL-ESGNNTCPLCR 43