RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH5 (MARCH5); MARCH5, also known as membrane-associated RING finger protein 5, membrane-associated RING-CH protein V (MARCH-V), RING finger protein 153 (RNF153), or mitochondrial ubiquitin ligase (MITOL), is a mitochondrial outer membrane-associated E3 ubiquitin-protein ligase that regulates mitochondrial dynamics including mitochondrial morphology, transport, and interaction with endoplasmic reticulum (ER), at least in part, through the ubiquitination of mitochondrial fission factor Drp1, microtubule-associated protein 1B (MAP1B) and mitofusin 2 (Mfn2), respectively. MARCH5 also mediates the cell cycle-dependent degradation of Mitofusin 1 (Mfn1) in G2/M phase, and thus serves as an upstream quality controller of Mitofusin 1 (Mfn1), preventing excessive accumulation of Mfn1 protein under stress conditions, which is crucial for mitochondrial homeostasis and cell viability. Moreover, MARCH5 is involved in maintaining mouse-embryonic stem cell (mESC) pluripotency via suppression of ERK signalling. It is also a positive regulator of Toll-like receptor 7 (TLR7)-mediated NF-kappaB activation in mammals. MARCH5 contains an N-terminal C4HC3-type RING-CH finger, also known as vRING or RINGv, a variant of C3H2C3-type RING-H2 finger, and four C-terminal transmembrane spans.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 256773301  12 RSCWVCFATDEDDRTAEWVRPCRCRGSTKWVHQACLQRWVDEKQRGNSTARVACPQCNAEY 72
Cdd:cd16701    1 RTCWVCFATDEDDRSAEWVRPCRCRGTTKWVHQACLQRWIDEKQKGNSTAKVSCPQCNTEY 61

RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH5 (MARCH5); MARCH5, also known as membrane-associated RING finger protein 5, membrane-associated RING-CH protein V (MARCH-V), RING finger protein 153 (RNF153), or mitochondrial ubiquitin ligase (MITOL), is a mitochondrial outer membrane-associated E3 ubiquitin-protein ligase that regulates mitochondrial dynamics including mitochondrial morphology, transport, and interaction with endoplasmic reticulum (ER), at least in part, through the ubiquitination of mitochondrial fission factor Drp1, microtubule-associated protein 1B (MAP1B) and mitofusin 2 (Mfn2), respectively. MARCH5 also mediates the cell cycle-dependent degradation of Mitofusin 1 (Mfn1) in G2/M phase, and thus serves as an upstream quality controller of Mitofusin 1 (Mfn1), preventing excessive accumulation of Mfn1 protein under stress conditions, which is crucial for mitochondrial homeostasis and cell viability. Moreover, MARCH5 is involved in maintaining mouse-embryonic stem cell (mESC) pluripotency via suppression of ERK signalling. It is also a positive regulator of Toll-like receptor 7 (TLR7)-mediated NF-kappaB activation in mammals. MARCH5 contains an N-terminal C4HC3-type RING-CH finger, also known as vRING or RINGv, a variant of C3H2C3-type RING-H2 finger, and four C-terminal transmembrane spans.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 256773301  12 RSCWVCFATDEDDRTAEWVRPCRCRGSTKWVHQACLQRWVDEKQRGNSTARVACPQCNAEY 72
Cdd:cd16701    1 RTCWVCFATDEDDRSAEWVRPCRCRGTTKWVHQACLQRWIDEKQKGNSTAKVSCPQCNTEY 61

RING-variant domain;

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                  ....*....|....*....|....*....|....*....|....*....|....*
gi 256773301   14 CWVCFATDEDDRtaEWVRPCRCRGSTKWVHQACLQRWVDEKqrGNSTarvaCPQC 68
Cdd:pfam12906   1 CRICLEEEAEDS--PLIHPCRCRGSLKYVHQSCLERWLDTS--ANTQ----CEIC 47

LAP/PHD finger-like protein; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 256773301   9 MLDRSCWVCfaTDEDDRTAEWvrpCRCRGSTKWVHQACLQRWVdekqrgNSTARVACPQCNAEYLI 74
Cdd:PHA02825   6 LMDKCCWIC--KDEYDVVTNY---CNCKNENKIVHKECLEEWI------NTSKNKSCKICNGPYNI 60

RING-CH finger, H2 subclass (C4HC3-type), found in membrane-associated RING-CH5 (MARCH5); MARCH5, also known as membrane-associated RING finger protein 5, membrane-associated RING-CH protein V (MARCH-V), RING finger protein 153 (RNF153), or mitochondrial ubiquitin ligase (MITOL), is a mitochondrial outer membrane-associated E3 ubiquitin-protein ligase that regulates mitochondrial dynamics including mitochondrial morphology, transport, and interaction with endoplasmic reticulum (ER), at least in part, through the ubiquitination of mitochondrial fission factor Drp1, microtubule-associated protein 1B (MAP1B) and mitofusin 2 (Mfn2), respectively. MARCH5 also mediates the cell cycle-dependent degradation of Mitofusin 1 (Mfn1) in G2/M phase, and thus serves as an upstream quality controller of Mitofusin 1 (Mfn1), preventing excessive accumulation of Mfn1 protein under stress conditions, which is crucial for mitochondrial homeostasis and cell viability. Moreover, MARCH5 is involved in maintaining mouse-embryonic stem cell (mESC) pluripotency via suppression of ERK signalling. It is also a positive regulator of Toll-like receptor 7 (TLR7)-mediated NF-kappaB activation in mammals. MARCH5 contains an N-terminal C4HC3-type RING-CH finger, also known as vRING or RINGv, a variant of C3H2C3-type RING-H2 finger, and four C-terminal transmembrane spans.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 256773301  12 RSCWVCFATDEDDRTAEWVRPCRCRGSTKWVHQACLQRWVDEKQRGNSTARVACPQCNAEY 72
Cdd:cd16701    1 RTCWVCFATDEDDRSAEWVRPCRCRGTTKWVHQACLQRWIDEKQKGNSTAKVSCPQCNTEY 61

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 256773301  14 CWVCFATDEDDRtaEWVRPCRCRGSTKWVHQACLQRWVDEKqrgNSTARVACPQCN 69
Cdd:cd16495    1 CRICLEEEEEGE--PLISPCRCKGSLKYVHRECLKRWLTES---GNRSNTKCEICK 51

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 256773301   11 DRSCWVCFAtdEDDRTAEWVRPCRCRGSTKWVHQACLQRWVDekqrgnSTARVACPQCNAEY 72
Cdd:COG5183    12 KRSCRICRT--EDIRDDPLFHPCKCSGSIKYIHRECLMEWME------CSGTKKCDICHYEY 65

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
                 ....*....|....*....|....*....|....*...
gi 256773301  14 CWVCFATDEDDRTAEWvrPCRCRGSTKWVHQACLQRWV 51
Cdd:cd16702    2 CRVCRGEGTPDRPLFH--PCKCSGSIKYVHQECLLQWL 37

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 256773301  14 CWVCFATDEDdrtAEWVRPCRCRGSTKWVHQACLQRWVDEK 54
Cdd:cd16811    2 CRICFQGPEQ---GELLSPCRCDGSVRCTHQPCLIKWISER 39

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 256773301  13 SCWVCfatDEDDRTAEWVRPCRCRGSTKWVHQACLQRWVDEKqrgNSTarvACPQCNAEY 72
Cdd:cd16699    1 FCRIC---HEGESTEDLLSPCECTGTLGLVHRSCLEQWLSSS---NTN---SCEICHFEY 51

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 256773301  14 CWVCFAtdEDDRTAEWVRPCRCRGSTKWVHQACLQRWVdekqrgNSTARVACPQCNAEYlIVFPKLGPV 82
Cdd:cd16806    7 CRICHC--EGDEESPLITPCRCTGTLRFVHQACLHQWI------KSSDTRCCELCKYDF-IMETKLKPL 66

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
                 ....*....|....*....|....*....|....*....|.
gi 256773301  14 CWVCFATDEDdrtAEWVRPCRCRGSTKWVHQACLQRWVDEK 54
Cdd:cd16825    5 CRICFQGPEQ---GELLSPCRCDGSVRCTHQPCLIRWISER 42

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 256773301  13 SCWVCfATDEDDRTAEWVRPCRCRGSTKWVHQACLQRWVDEK-QRGNSTARV-ACPQC 68
Cdd:cd16703    4 LCRIC-QTAGDSTSNQLIEPCQCTGSLQLVHQECLKKWLISKiQSGAELDAVkTCEMC 60

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 256773301  16 VCFATDEDDRTAEWVRPCRCRGSTKWVHQACLQRWVdekqrgNSTARVACPQCNAEY 72
Cdd:cd16808    2 ICRICHEGGNGESLLSPCDCTGTLGTVHKSCLEKWL------SSSNTSYCELCHTEF 52