MARH2_BOVIN
ID MARH2_BOVIN Reviewed; 245 AA.
AC Q32L65;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=E3 ubiquitin-protein ligase MARCHF2;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q9P0N8};
DE AltName: Full=Membrane-associated RING finger protein 2;
DE AltName: Full=Membrane-associated RING-CH protein II;
DE Short=MARCH-II;
DE AltName: Full=RING finger protein 172 {ECO:0000250|UniProtKB:Q9P0N8};
DE Short=RNF172;
DE AltName: Full=RING-type E3 ubiquitin transferase MARCHF2 {ECO:0000305};
GN Name=MARCHF2; Synonyms=MARCH2, RNF172;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Liver;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: E3 ubiquitin-protein ligase that may mediate ubiquitination
CC of TFRC and CD86, and promote their subsequent endocytosis and sorting
CC to lysosomes via multivesicular bodies. E3 ubiquitin ligases accept
CC ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a
CC thioester and then directly transfer the ubiquitin to targeted
CC substrates. Together with GOPC/CAL mediates the ubiquitination and
CC lysosomal degradation of CFTR (By similarity). Ubiquitinates and
CC therefore mediates the degradation of DLG1 (By similarity). Regulates
CC the intracellular trafficking and secretion of alpha1-
CC antitrypsin/SERPINA1 and HP/haptoglobin via ubiquitination and
CC degradation of the cargo receptor ERGIC3 (By similarity). Negatively
CC regulates the antiviral and antibacterial immune response by repression
CC of the NF-kB and type 1 IFN signaling pathways, via MARCHF2-mediated
CC K48-linked polyubiquitination of IKBKG/NEMO, resulting in its
CC proteosomal degradation (By similarity). May be involved in endosomal
CC trafficking through interaction with STX6.
CC {ECO:0000250|UniProtKB:Q9P0N8}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000250|UniProtKB:Q9P0N8};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q9P0N8}.
CC -!- SUBUNIT: Interacts with STX6; the interaction promotes MARCHF2-mediated
CC ubiquitination and degradation of CFTR (By similarity). Interacts with
CC MARCHF3 (By similarity). Interacts with GOPC/CAL; the interaction leads
CC to CFTR ubiquitination and degradation (By similarity). Interacts with
CC CFTR; the interaction leads to CFTR ubiqtuitination and degradation (By
CC similarity). Interacts (via PDZ domain) with DLG1 (via PDZ domains);
CC the interaction leads to DLG1 ubiqtuitination and degradation (By
CC similarity). Interacts with ERGIC3 (By similarity). Interacts with
CC ADRB2 (By similarity). Interacts with IKBKG/NEMO; during the late
CC stages of macrophage viral and bacterial infection; the interaction
CC leads to ubiquitination and degradation of IKBKG/NEMO (By similarity).
CC {ECO:0000250|UniProtKB:Q9P0N8}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9P0N8}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q5I0I2}. Lysosome membrane
CC {ECO:0000250|UniProtKB:Q9P0N8}; Multi-pass membrane protein
CC {ECO:0000255}. Endosome membrane {ECO:0000250|UniProtKB:Q5I0I2}; Multi-
CC pass membrane protein {ECO:0000250|UniProtKB:Q5I0I2}. Golgi apparatus
CC membrane {ECO:0000250|UniProtKB:Q9P0N8}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasm {ECO:0000250|UniProtKB:Q9P0N8}. Cell membrane
CC {ECO:0000250|UniProtKB:Q9P0N8}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- DOMAIN: The RING-CH-type zinc finger domain is required for E3 ligase
CC activity. {ECO:0000255|PROSITE-ProRule:PRU00623}.
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DR EMBL; BC109744; AAI09745.1; -; mRNA.
DR RefSeq; NP_001032678.1; NM_001037589.1.
DR RefSeq; XP_005208918.1; XM_005208861.3.
DR RefSeq; XP_015327531.1; XM_015472045.1.
DR AlphaFoldDB; Q32L65; -.
DR SMR; Q32L65; -.
DR STRING; 9913.ENSBTAP00000028017; -.
DR PaxDb; Q32L65; -.
DR GeneID; 508949; -.
DR KEGG; bta:508949; -.
DR CTD; 51257; -.
DR eggNOG; KOG1609; Eukaryota.
DR HOGENOM; CLU_096532_0_0_1; -.
DR InParanoid; Q32L65; -.
DR OrthoDB; 1373244at2759; -.
DR TreeFam; TF319557; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0140367; P:antibacterial innate immune response; ISS:UniProtKB.
DR GO; GO:0140374; P:antiviral innate immune response; ISS:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR011016; Znf_RING-CH.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF12906; RINGv; 1.
DR SMART; SM00744; RINGv; 1.
DR PROSITE; PS51292; ZF_RING_CH; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Cytoplasm; Endocytosis; Endoplasmic reticulum; Endosome;
KW Golgi apparatus; Lysosome; Membrane; Metal-binding; Reference proteome;
KW Transferase; Transmembrane; Transmembrane helix; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1..245
FT /note="E3 ubiquitin-protein ligase MARCHF2"
FT /id="PRO_0000274502"
FT TRANSMEM 138..158
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 175..195
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ZN_FING 56..116
FT /note="RING-CH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT REGION 121..245
FT /note="Required for interaction with IKBKG"
FT /evidence="ECO:0000250|UniProtKB:Q9P0N8"
FT BINDING 64
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 67
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 80
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 82
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 90
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 93
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 106
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 109
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
SQ SEQUENCE 245 AA; 26875 MW; FF764CDFB98C8C3D CRC64;
MTTGDCCHLP GSLCDCSDSP AFSKVVEATG LGPPQYVAQV TSRDGRLLST VIRALETPSD
GPFCRICHEG ANGESLLSPC GCSGTLGAVH KSCLERWLSS SNTSYCELCH TEFAVEKRSR
SLTEWLKDPG PRTEKRTLCC DVVCFLFITP LAAISGWLCL RGAQDHLRLH SHLEALGLIA
LTIALFTIYV LWTLVSFRYH CQLYSEWRRT NQKVRLKMQA DGSEGSQHSP LAAGLLKKVA
EETPV
