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 24639506  39 RICWICFATSEDNPHAHWVQPCQCRGDTKWVHQSCLYRWIDEKQLGDRRQTVICQQCQTEY 99
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 24639506  39 RICWICFATSEDNPHAHWVQPCQCRGDTKWVHQSCLYRWIDEKQLGDRRQTVICQQCQTEY 99
Cdd:cd16701   1 RTCWVCFATDEDDRSAEWVRPCRCRGTTKWVHQACLQRWIDEKQKGNSTAKVSCPQCNTEY 61

RING-variant domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 24639506    41 CWICFAtsEDNPHAHWVQPCQCRGDTKWVHQSCLYRWIDEKqlgdrrQTVICQQC 95
Cdd:pfam12906   1 CRICLE--EEAEDSPLIHPCRCRGSLKYVHQSCLERWLDTS------ANTQCEIC 47

LAP/PHD finger-like protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639506   33 SNADgeRICWICfaTSEDNPHAHWvqpCQCRGDTKWVHQSCLYRWIDEkqlgDRRQTviCQQCQTEYiMVFPQMNPIAR- 111
Cdd:PHA02825   5 SLMD--KCCWIC--KDEYDVVTNY---CNCKNENKIVHKECLEEWINT----SKNKS--CKICNGPY-NIKKNYKKCTKw 70

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24639506  112 VLEKLDYAVRRICpflVLGMFLcCIYWIALTYGAFTIIQVVGQDRAMQLMenKVILLVG--LPFIpVGLILF 181
Cdd:PHA02825  71 RCSFRDCHDSAIV---NSLLCL-IVGGITYLLVSFNIKKLIESEENSDLI--KLFLVVAylLPFV-VTFITV 135

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 24639506  39 RICWICFATSEDNPHAHWVQPCQCRGDTKWVHQSCLYRWIDEKQLGDRRQTVICQQCQTEY 99
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 24639506  41 CWICFATSEDNphAHWVQPCQCRGDTKWVHQSCLYRWIDEKQLGDRRQtviCQQCQ 96
Cdd:cd16495   1 CRICLEEEEEG--EPLISPCRCKGSLKYVHRECLKRWLTESGNRSNTK---CEICK 51

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 24639506  40 ICWICFATSEDnpHAHWVQPCQCRGDTKWVHQSCLYRWIDEKqlgdrrQTVICQQCQTEYIM 101
Cdd:cd16807   7 ICRICHCEGDD--ESPLITPCHCTGSLRFVHQACLQQWIKSS------DTRCCELCKYEFIM 60

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 24639506  39 RICWICfATSEDNPhahWVQPCQCRGDTKWVHQSCLYRWIDEK-QLGDRRQTV-ICQQCQ 96
Cdd:cd16812   8 RICQMG-MTSSSNP---LIEPCKCTGSLQYVHQECMKKWLQAKiNSGSSLEAVtTCELCK 63

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639506   34 NADgERICWICFA-TSEDNPHAHwvqPCQCRGDTKWVHQSCLYRWIDEKqlgdrrQTVICQQCQTEYIM--VFPQMNPia 110
Cdd:COG5183    9 NED-KRSCRICRTeDIRDDPLFH---PCKCSGSIKYIHRECLMEWMECS------GTKKCDICHYEYKFkdIYKEDMP-- 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 24639506  111 rvlekldyavrRICPFLVLGMFLCCIYW----IALTYGAFTIIQVVG 153
Cdd:COG5183   77 -----------QIIPFSILIRKVADTGWkatrVLLTIGLWCVLQMVK 112

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 24639506  40 ICWICFA-TSEDNPHAHwvqPCQCRGDTKWVHQSCLYRWI 78
Cdd:cd16702   1 ICRVCRGeGTPDRPLFH---PCKCSGSIKYVHQECLLQWL 37

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 24639506  40 ICWICfatSEDNPHAHWVQPCQCRGDTKWVHQSCLYRWIDEKqlgdrrQTVICQQCQTEY 99
Cdd:cd16699   1 FCRIC---HEGESTEDLLSPCECTGTLGLVHRSCLEQWLSSS------NTNSCEICHFEY 51

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24639506  40 ICWICFATSE-DNPhahWVQPCQCRGDTKWVHQSCLYRWIDEKqlgdrrQTVICQQCQTEY 99
Cdd:cd16698   1 ICRICHCEGDpENP---LITPCYCSGSLKYVHQACLQQWIKSS------DTKSCELCKFEF 52

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639506  40 ICWICFATSEdnpHAHWVQPCQCRGDTKWVHQSCLYRWIDEkqlgdrRQTVICQQCQTEY 99
Cdd:cd16824   6 LCRICFQGPE---QGELLSPCRCDGSVRCTHQPCLIKWISE------RGSWSCELCYYKY 56

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24639506  31 ELSNADGE--RICWICfATSEDNPhahWVQPCQCRGDTKWVHQSCLYRWIDEK-----QLGDRRQTVICQQ 94
Cdd:cd16813   1 EDSEEEGDlcRICQIA-GGSPSNP---LLEPCGCVGSLQFVHQECLKKWLKVKitsgaDLGAVKTCEMCKQ 67

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 24639506  40 ICWICfatSEDNPHAHWVQPCQCRGDTKWVHQSCLYRWIDEKqlgdrrQTVICQQCQTEY 99
Cdd:cd16809   6 MCRIC---HEGSSQEDLLSPCECTGTLGTIHRSCLEHWLSSS------NTSYCELCHFRF 56