MARH2_MOUSE
ID MARH2_MOUSE Reviewed; 246 AA.
AC Q99M02; Q8C4Q5;
DT 04-JAN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 149.
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 AltName: Full=RING-type E3 ubiquitin transferase MARCHF2 {ECO:0000305};
GN Name=Marchf2; Synonyms=March2, Rnf172;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Head, and Urinary bladder;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH IKBKG, INDUCTION BY VIRAL
RP AND BACTERIAL INFECTION, AND DISRUPTION PHENOTYPE.
RX PubMed=32935379; DOI=10.15252/embj.2020105139;
RA Chathuranga K., Kim T.H., Lee H., Park J.S., Kim J.H., Chathuranga W.A.G.,
RA Ekanayaka P., Choi Y.J., Lee C.H., Kim C.J., Jung J.U., Lee J.S.;
RT "Negative regulation of NEMO signaling by the ubiquitin E3 ligase MARCH2.";
RL EMBO J. 39:e105139-e105139(2020).
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 (PubMed:32935379). May be involved in endosomal
CC trafficking through interaction with STX6.
CC {ECO:0000250|UniProtKB:Q9P0N8, ECO:0000269|PubMed:32935379}.
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:0000269|PubMed:32935379};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:32935379}.
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
CC (PubMed:32935379). {ECO:0000250|UniProtKB:Q9P0N8,
CC ECO:0000269|PubMed:32935379}.
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:Q9P0N8}; Multi-
CC pass membrane protein {ECO:0000250|UniProtKB:Q5I0I2}. Golgi apparatus
CC membrane {ECO:0000250|UniProtKB:Q9P0N8}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9P0N8}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9P0N8}. Cell membrane
CC {ECO:0000250|UniProtKB:Q9P0N8}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- INDUCTION: Induced in macrophages by viral or bacterial infection.
CC {ECO:0000269|PubMed:32935379}.
CC -!- DOMAIN: The RING-CH-type zinc finger domain is required for E3 ligase
CC activity. {ECO:0000255|PROSITE-ProRule:PRU00623}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice are phenotypically normal
CC (PubMed:32935379). Increase in cytokine production following viral and
CC bacterial challenge, including increases in Ifnb1, Il6, Il12, Ccl5,
CC Cxcl10 and Tnf protein abundance (PubMed:32935379). Increase in
CC survival following exposure to a lethal dose of L.monocytogenes and
CC decrease in bacterial load in the spleen and liver (PubMed:32935379).
CC Increase in susceptibility to endotoxin shock (PubMed:32935379).
CC {ECO:0000269|PubMed:32935379}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC38235.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK079234; BAC37584.1; -; mRNA.
DR EMBL; AK081495; BAC38235.1; ALT_FRAME; mRNA.
DR EMBL; BC002144; AAH02144.1; -; mRNA.
DR CCDS; CCDS57064.1; -.
DR RefSeq; NP_001239409.1; NM_001252480.1.
DR AlphaFoldDB; Q99M02; -.
DR SMR; Q99M02; -.
DR STRING; 10090.ENSMUSP00000065225; -.
DR PhosphoSitePlus; Q99M02; -.
DR PaxDb; Q99M02; -.
DR PRIDE; Q99M02; -.
DR ProteomicsDB; 292169; -.
DR Antibodypedia; 2987; 197 antibodies from 26 providers.
DR DNASU; 224703; -.
DR Ensembl; ENSMUST00000172767; ENSMUSP00000134220; ENSMUSG00000079557.
DR GeneID; 224703; -.
DR KEGG; mmu:224703; -.
DR UCSC; uc008bzk.2; mouse.
DR CTD; 51257; -.
DR MGI; MGI:1925915; Marchf2.
DR VEuPathDB; HostDB:ENSMUSG00000079557; -.
DR eggNOG; KOG1609; Eukaryota.
DR GeneTree; ENSGT00940000158995; -.
DR InParanoid; Q99M02; -.
DR OMA; FWEGTGL; -.
DR PhylomeDB; Q99M02; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 224703; 1 hit in 17 CRISPR screens.
DR ChiTaRS; March2; mouse.
DR PRO; PR:Q99M02; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q99M02; protein.
DR Bgee; ENSMUSG00000079557; Expressed in blood and 267 other tissues.
DR ExpressionAtlas; Q99M02; baseline and differential.
DR Genevisible; Q99M02; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
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:MGI.
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; IMP:UniProtKB.
DR GO; GO:0140374; P:antiviral innate immune response; IMP:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:1905167; P:positive regulation of lysosomal protein catabolic process; ISO:MGI.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0044790; P:suppression of viral release by host; ISO:MGI.
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_0000055926"
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; 27186 MW; DC4A6EE34B8AE897 CRC64;
MTTGDCCHLP GSLCDCSSSP AFSKVVEATG LGPPQYVAQV TSRDGRLLST VIRALDSQSD
CPFCRICHEG ANGENLLSPC GCTGTLGAVH KSCLEKWLSS SNTSYCELCH TEFAVEKRPR
PLTEWLKDPG PRTEKRTLCC DMVCFVFITP LAAISGWLCL RGAQDHLRLH SRLEAVGLIA
LTIALFTIYV LWTLVSFRYH CQLYSEWRKT NQKVRLKIRE ADGSEDPHHS LLATGLLKKV
AEETPV
