MARH2_RAT
ID MARH2_RAT Reviewed; 246 AA.
AC Q5I0I2;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 125.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP INTERACTION WITH STX6, AND FUNCTION.
RC TISSUE=Small intestine;
RX PubMed=15689499; DOI=10.1091/mbc.e04-03-0216;
RA Nakamura N., Fukuda H., Kato A., Hirose S.;
RT "MARCH-II is a syntaxin-6-binding protein involved in endosomal
RT trafficking.";
RL Mol. Biol. Cell 16:1696-1710(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thymus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP INTERACTION WITH MARCHF3.
RX PubMed=16428329; DOI=10.1093/jb/mvj012;
RA Fukuda H., Nakamura N., Hirose S.;
RT "MARCH-III is a novel component of endosomes with properties similar to
RT those of MARCH-II.";
RL J. Biochem. 139:137-145(2006).
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, ECO:0000269|PubMed:15689499}.
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 (PubMed:15689499). Interacts
CC with MARCHF3 (PubMed:16428329). Interacts with GOPC/CAL; the
CC interaction leads to CFTR ubiquitination and degradation (By
CC similarity). Interacts with CFTR; the interaction leads to CFTR
CC ubiqtuitination and degradation (By similarity). Interacts (via PDZ
CC domain) with DLG1 (via PDZ domains); the interaction leads to DLG1
CC ubiqtuitination and degradation (By similarity). Interacts with ERGIC3
CC (By similarity). Interacts with ADRB2 (By similarity). Interacts with
CC IKBKG/NEMO; during the late stages of macrophage viral and bacterial
CC infection; the interaction leads to ubiquitination and degradation of
CC IKBKG/NEMO (By similarity). {ECO:0000250|UniProtKB:Q9P0N8,
CC ECO:0000269|PubMed:15689499, ECO:0000269|PubMed:16428329}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:15689499}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:15689499}. Lysosome membrane
CC {ECO:0000250|UniProtKB:Q9P0N8}; Multi-pass membrane protein
CC {ECO:0000255}. Endosome membrane {ECO:0000269|PubMed:15689499}; Multi-
CC pass membrane protein {ECO:0000269|PubMed:15689499}. 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 -!- TISSUE SPECIFICITY: Ubiquitously expressed. Present in liver (at
CC protein level). {ECO:0000269|PubMed:15689499}.
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; AB048838; BAD89357.1; -; mRNA.
DR EMBL; BC088286; AAH88286.1; -; mRNA.
DR RefSeq; NP_001029280.1; NM_001034108.1.
DR AlphaFoldDB; Q5I0I2; -.
DR SMR; Q5I0I2; -.
DR BioGRID; 263774; 7.
DR STRING; 10116.ENSRNOP00000010399; -.
DR PaxDb; Q5I0I2; -.
DR PRIDE; Q5I0I2; -.
DR Ensembl; ENSRNOT00000010399; ENSRNOP00000010399; ENSRNOG00000007769.
DR GeneID; 362849; -.
DR KEGG; rno:362849; -.
DR UCSC; RGD:1306395; rat.
DR CTD; 51257; -.
DR RGD; 1306395; March2.
DR eggNOG; KOG1609; Eukaryota.
DR GeneTree; ENSGT00940000158995; -.
DR HOGENOM; CLU_096532_0_0_1; -.
DR InParanoid; Q5I0I2; -.
DR OMA; FWEGTGL; -.
DR OrthoDB; 1373244at2759; -.
DR PhylomeDB; Q5I0I2; -.
DR TreeFam; TF319557; -.
DR UniPathway; UPA00143; -.
DR PRO; PR:Q5I0I2; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000007769; Expressed in skeletal muscle tissue and 19 other tissues.
DR ExpressionAtlas; Q5I0I2; baseline and differential.
DR Genevisible; Q5I0I2; RN.
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; ISO:RGD.
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:1905167; P:positive regulation of lysosomal protein catabolic process; ISO:RGD.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0044790; P:suppression of viral release by host; ISO:RGD.
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 1: Evidence at protein 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..246
FT /note="E3 ubiquitin-protein ligase MARCHF2"
FT /id="PRO_0000274503"
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..246
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 246 AA; 27169 MW; 346711F2FF28FF25 CRC64;
MTTGDCCHLP GSLCDCSSSP AFSKVVEATG LGPPQYVAQV TSRDGRLLST VIRALDTPSD
CPFCRICHEG ANGENLLSPC GCTGTLGAVH KSCLEKWLSS SNTSYCELCH TEFAVEKRPR
PLTEWLKDPG PRTEKRTLCC DMVCFVFITP LAAISGWLCL RGAQDHLRLH SRLEAVGLIA
LTIALFTIYV LWTLVSFRYH CQLYSEWRKT NQKVRLKIRE ADGSEDPHHS LLATGLLKKV
AEETPV
