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 27-MAR-2024, entry version 158. 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 proteasomal 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 10090-ENSMUSP00000065225; -. DR ProteomicsDB; 292169; -. DR Antibodypedia; 2987; 217 antibodies from 26 providers. DR DNASU; 224703; -. DR Ensembl; ENSMUST00000172767.9; ENSMUSP00000134220.2; ENSMUSG00000079557.12. DR GeneID; 224703; -. DR KEGG; mmu:224703; -. DR UCSC; uc008bzk.2; mouse. DR AGR; MGI:1925915; -. DR MGI; MGI:1925915; Marchf2. DR VEuPathDB; HostDB:ENSMUSG00000079557; -. DR eggNOG; KOG1609; Eukaryota. DR GeneTree; ENSGT00940000158995; -. DR InParanoid; Q99M02; -. DR OMA; ICHEGAS; -. DR OrthoDB; 1342875at2759; -. 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 270 other cell types or tissues. DR ExpressionAtlas; Q99M02; baseline and differential. 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: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 CDD; cd16808; RING_CH-C4HC3_MARCH2; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR011016; Znf_RING-CH. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR46065; E3 UBIQUITIN-PROTEIN LIGASE MARCH 2/3 FAMILY MEMBER; 1. DR PANTHER; PTHR46065:SF4; E3 UBIQUITIN-PROTEIN LIGASE MARCHF2; 1. DR Pfam; PF12906; RINGv; 1. DR SMART; SM00744; RINGv; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR PROSITE; PS51292; ZF_RING_CH; 1. DR Genevisible; Q99M02; MM. 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 //