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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958761368 564 GDLCRICQMAAASSSNLLIEPCKCTGSLQYVHQECMKKWLQAKINSGSSLEAVTTCELCKEK 625
Cdd:cd16812     4 GDLCRICQMGMTSSSNPLIEPCKCTGSLQYVHQECMKKWLQAKINSGSSLEAVTTCELCKEK 65

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958761368 564 GDLCRICQMAAASSSNLLIEPCKCTGSLQYVHQECMKKWLQAKINSGSSLEAVTTCELCKEK 625
Cdd:cd16812     4 GDLCRICQMGMTSSSNPLIEPCKCTGSLQYVHQECMKKWLQAKINSGSSLEAVTTCELCKEK 65

RING-variant domain;

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                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958761368 567 CRICQMAAASSSNLlIEPCKCTGSLQYVHQECMKKWLQAKINsgssleavTTCELC 622
Cdd:pfam12906   1 CRICLEEEAEDSPL-IHPCRCRGSLKYVHQSCLERWLDTSAN--------TQCEIC 47

LAP/PHD finger-like protein; Provisional

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                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958761368 567 CRICQMAAASSSNLliepCKCTGSLQYVHQECMKKWLQAKINsgssleavTTCELCKEK 625
Cdd:PHA02825   11 CWICKDEYDVVTNY----CNCKNENKIVHKECLEEWINTSKN--------KSCKICNGP 57

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958761368 564 GDLCRICQMAAASSSNLLIEPCKCTGSLQYVHQECMKKWLQAKINSGSSLEAVTTCELCKEK 625
Cdd:cd16812     4 GDLCRICQMGMTSSSNPLIEPCKCTGSLQYVHQECMKKWLQAKINSGSSLEAVTTCELCKEK 65

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958761368 564 GDLCRICQMAAASSSNLLIEPCKCTGSLQYVHQECMKKWLQAKINSGSSLEAVTTCELCKEKLQLNLEDF 633
Cdd:cd16813     7 GDLCRICQIAGGSPSNPLLEPCGCVGSLQFVHQECLKKWLKVKITSGADLGAVKTCEMCKQGLLVDLGDF 76

The RING-variant domain is a C4HC3 zinc-finger like motif found in a number of cellular and viral proteins; Some of these proteins have been shown both in vivo and in vitro to have ubiquitin E3 ligase activity. The RING-variant domain is reminiscent of both the RING and the PHD domains and may represent an evolutionary intermediate. To describe this domain the term PHD/LAP domain has been used in the past. Extended description: The RING-variant (RINGv) domain contains a C4HC3 zinc-finger-like motif similar to the PHD domain, while some of the spacing between the Cys/His residues follow a pattern somewhat closer to that found in the RING domain. The RINGv domain, similar to the RING, PHD and LIM domains, is thought to bind two zinc ions co-ordinated by the highly conserved Cys and His residues. RING variant domain: C-x (2) -C-x(10-45)-C-x (1) -C-x (7) -H-x(2)-C-x(11-25)-C-x(2)-C As opposed to a PHD: C-x(1-2) -C-x (7-13)-C-x(2-4)-C-x(4-5)-H-x(2)-C-x(10-21)-C-x(2)-C Classical RING domain: C-x (2) -C-x (9-39)-C-x(1-3)-H-x(2-3)-C-x(2)-C-x(4-48) -C-x(2)-C

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gi 1958761368  567 CRICQMAAaSSSNLLIEPCKCTGSLQYVHQECMKKWLQAKINsgssleavTTCELCK 623
Cdd:smart00744   2 CRICHDEG-DEGDPLVSPCRCKGSLKYVHQECLERWINESGN--------KTCEICK 49

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.

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gi 1958761368 567 CRICQMAAASSSNLLiEPCKCTGSLQYVHQECMKKWLQakiNSGSsleavTTCELCK 623
Cdd:cd16702     2 CRVCRGEGTPDRPLF-HPCKCSGSIKYVHQECLLQWLK---HSRK-----EYCELCK 49

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958761368 566 LCRICQmAAASSSNLLIEPCKCTGSLQYVHQECMKKWLQAkinsgsslEAVTTCELCK 623
Cdd:cd16698     1 ICRICH-CEGDPENPLITPCYCSGSLKYVHQACLQQWIKS--------SDTKSCELCK 49

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958761368 565 DLCRICQMAAASSSNLlIEPCKCTGSLQYVHQECMKKWLQAkinsgsslEAVTTCELCK 623
Cdd:cd16806     5 DICRICHCEGDEESPL-ITPCRCTGTLRFVHQACLHQWIKS--------SDTRCCELCK 54

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1958761368 566 LCRICQMAAASSSnlLIEPCKCTGSLQYVHQECMKKWLQAKinsGSsleavTTCELC 622
Cdd:cd16700     1 LCRICFQGAEQGE--LLSPCRCDGSVRCTHQPCLLKWISER---GS-----WSCELC 47

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958761368 566 LCRICQmaAASSSNLLIEPCKCTGSLQYVHQECMKKWLQAKINSgssleavtTCELCKEKL 626
Cdd:cd16809     6 MCRICH--EGSSQEDLLSPCECTGTLGTIHRSCLEHWLSSSNTS--------YCELCHFRF 56

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958761368 566 LCRICQMAAASSSnlLIEPCKCTGSLQYVHQECMKKWLQAKinsGSsleavTTCELCKEK 625
Cdd:cd16811     1 LCRICFQGPEQGE--LLSPCRCDGSVRCTHQPCLIKWISER---GS-----WSCELCYYK 50

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.

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                  ....*....|....*....|....*....|....*....|....*
gi 1958761368 578 SNLLIEPCKCTGSLQYVHQECMKKWLQAKINsGSSLEAVtTCELC 622
Cdd:cd16701    15 SAEWVRPCRCRGTTKWVHQACLQRWIDEKQK-GNSTAKV-SCPQC 57

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958761368 567 CRICQMAAASSSnlLIEPCKCTGSLQYVHQECMKKWLQAKinsGSsleavTTCELCKEK 625
Cdd:cd16825     5 CRICFQGPEQGE--LLSPCRCDGSVRCTHQPCLIRWISER---GS-----WSCELCYFK 53

RING-CH finger, H2 subclass (C4HC3-type), found in zinc finger SWIM domain-containing protein 2 (ZSWIM2) and similar proteins; ZSWIM2, also known as MEKK1-related protein X (MEX) or ZZ-type zinc finger-containing protein 2, is a testis-specific E3 ubiquitin ligase that promotes death receptor-induced apoptosis through Fas, death receptor (DR) 3, and DR4 signaling. ZSWIM2 is self-ubiquitinated and targeted for degradation through the proteasome pathway. It also acts as an E3 ubiquitin ligase, through the E2, Ub-conjugating enzymes UbcH5a, UbcH5c, or UbcH6. ZSWIM2 contains four putative zinc-binding domains including an N-terminal SWIM (SWI2/SNF2 and MuDR) domain critical for its ubiquitination and two RING fingers separated by a ZZ zinc finger domain, which was required for interaction with UbcH5a and its self-association. This model corresponds to the first RING finger, which is a C4HC3-type RING-CH finger, also known as vRING or RINGv, rather than the canonical C3H2C3-type RING-H2 finger.

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gi 1958761368 564 GDLCRICQ--MAAASssnlliEP---CK--CTGSlqyVHQECMKKWLQAKINSGSsleaVTTCELCKEK 625
Cdd:cd16494     1 EDDCPICYeeMLEKG------EPltyCRfgCGNN---VHIHCMKVWAEHQRQSDE----PVTCPLCRSD 56