MARH2_HUMAN
ID MARH2_HUMAN Reviewed; 246 AA.
AC Q9P0N8; A6NP10; Q5H785; Q8N5A3; Q96B78;
DT 04-JAN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=E3 ubiquitin-protein ligase MARCHF2;
DE EC=2.3.2.27 {ECO:0000269|PubMed:14722266, ECO:0000269|PubMed:16428329};
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:0000312|HGNC:HGNC:28038};
DE AltName: Full=RING-type E3 ubiquitin transferase MARCHF2 {ECO:0000305};
GN Name=MARCHF2 {ECO:0000312|HGNC:HGNC:28038}; Synonyms=MARCH2, RNF172;
GN ORFNames=HSPC240;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
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] (ISOFORM 1).
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT THR-54.
RC TISSUE=Brain, and Skin;
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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=14722266; DOI=10.1128/jvi.78.3.1109-1120.2004;
RA Bartee E., Mansouri M., Hovey Nerenberg B.T., Gouveia K., Frueh K.;
RT "Downregulation of major histocompatibility complex class I by human
RT ubiquitin ligases related to viral immune evasion proteins.";
RL J. Virol. 78:1109-1120(2004).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND 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).
RN [7]
RP FUNCTION, INTERACTION WITH DLG1, AND MUTAGENESIS OF CYS-64; CYS-67; TRP-97;
RP CYS-106; CYS-109 AND 243-GLU--VAL-246.
RX PubMed=17980554; DOI=10.1016/j.cellsig.2007.08.019;
RA Cao Z., Huett A., Kuballa P., Giallourakis C., Xavier R.J.;
RT "DLG1 is an anchor for the E3 ligase MARCH2 at sites of cell-cell
RT contact.";
RL Cell. Signal. 20:73-82(2008).
RN [8]
RP INTERACTION WITH ADRB2, AND SUBCELLULAR LOCATION.
RX PubMed=23166351; DOI=10.1083/jcb.201208192;
RA Han S.O., Xiao K., Kim J., Wu J.H., Wisler J.W., Nakamura N.,
RA Freedman N.J., Shenoy S.K.;
RT "MARCH2 promotes endocytosis and lysosomal sorting of carvedilol-bound
RT beta(2)-adrenergic receptors.";
RL J. Cell Biol. 199:817-830(2012).
RN [9]
RP FUNCTION, INTERACTION WITH CFTR; STX6 AND GOPC, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF CYS-64; CYS-67 AND 244-TYR--VAL-246.
RX PubMed=23818989; DOI=10.1371/journal.pone.0068001;
RA Cheng J., Guggino W.;
RT "Ubiquitination and degradation of CFTR by the E3 ubiquitin ligase MARCH2
RT through its association with adaptor proteins CAL and STX6.";
RL PLoS ONE 8:e68001-e68001(2013).
RN [10]
RP FUNCTION (MICROBIAL INFECTION), INDUCTION BY HIV-1 INFECTION, AND
RP MUTAGENESIS OF CYS-64 AND CYS-67.
RX PubMed=29573664; DOI=10.1016/j.virol.2018.02.003;
RA Zhang Y., Lu J., Liu X.;
RT "MARCH2 is upregulated in HIV-1 infection and inhibits HIV-1 production
RT through envelope protein translocation or degradation.";
RL Virology 518:293-300(2018).
RN [11]
RP FUNCTION, INTERACTION WITH ERGIC3, AND MUTAGENESIS OF CYS-64 AND CYS-67.
RX PubMed=31142615; DOI=10.1074/jbc.ra119.007435;
RA Yoo W., Cho E.B., Kim S., Yoon J.B.;
RT "The E3 ubiquitin ligase MARCH2 regulates ERGIC3-dependent trafficking of
RT secretory proteins.";
RL J. Biol. Chem. 294:10900-10912(2019).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH IKBKG, SUBCELLULAR LOCATION,
RP AND MUTAGENESIS OF CYS-64; CYS-67 AND HIS-90.
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 (PubMed:14722266, PubMed:16428329). Together with GOPC/CAL
CC mediates the ubiquitination and lysosomal degradation of CFTR
CC (PubMed:23818989). Ubiquitinates and therefore mediates the degradation
CC of DLG1 (PubMed:17980554). Regulates the intracellular trafficking and
CC secretion of alpha1-antitrypsin/SERPINA1 and HP/haptoglobin via
CC ubiquitination and degradation of the cargo receptor ERGIC3
CC (PubMed:31142615). Negatively regulates the antiviral and antibacterial
CC immune response by repression of the NF-kB and type 1 IFN signaling
CC pathways, via MARCHF2-mediated K48-linked polyubiquitination of
CC IKBKG/NEMO, resulting in its proteosomal degradation (PubMed:32935379).
CC May be involved in endosomal trafficking through interaction with STX6
CC (PubMed:15689499). {ECO:0000269|PubMed:14722266,
CC ECO:0000269|PubMed:15689499, ECO:0000269|PubMed:16428329,
CC ECO:0000269|PubMed:17980554, ECO:0000269|PubMed:23818989,
CC ECO:0000269|PubMed:31142615, ECO:0000269|PubMed:32935379}.
CC -!- FUNCTION: (Microbial infection) Positively regulates the degradation of
CC Vesicular stomatitis virus (VSV) G protein via the lysosomal
CC degradation pathway (PubMed:29573664). Represses HIV-1 viral production
CC and may inhibit the translocation of HIV-1 env to the cell surface,
CC resulting in decreased viral cell-cell transmission (PubMed:29573664).
CC {ECO:0000269|PubMed:29573664}.
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:14722266,
CC ECO:0000269|PubMed:16428329, ECO:0000269|PubMed:32935379};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:17980554, ECO:0000269|PubMed:23818989,
CC ECO:0000269|PubMed:31142615}.
CC -!- SUBUNIT: Interacts with STX6; the interaction promotes MARCHF2-mediated
CC ubiquitination and degradation of CFTR (PubMed:23818989). Interacts
CC with MARCHF3 (PubMed:16428329). Interacts with GOPC/CAL; the
CC interaction leads to CFTR ubiquitination and degradation
CC (PubMed:23818989). Interacts with CFTR; the interaction leads to CFTR
CC ubiqtuitination and degradation (PubMed:23818989). Interacts (via PDZ
CC domain) with DLG1 (via PDZ domains); the interaction leads to DLG1
CC ubiqtuitination and degradation (PubMed:17980554). Interacts with
CC ERGIC3 (PubMed:31142615). Interacts with ADRB2 (PubMed:23166351).
CC Interacts with IKBKG/NEMO; during the late stages of macrophage viral
CC and bacterial infection; the interaction leads to ubiquitination and
CC degradation of IKBKG/NEMO (PubMed:32935379).
CC {ECO:0000269|PubMed:16428329, ECO:0000269|PubMed:17980554,
CC ECO:0000269|PubMed:23166351, ECO:0000269|PubMed:23818989,
CC ECO:0000269|PubMed:31142615, ECO:0000269|PubMed:32935379}.
CC -!- INTERACTION:
CC Q9P0N8; Q13520: AQP6; NbExp=3; IntAct=EBI-10317612, EBI-13059134;
CC Q9P0N8; P13236: CCL4; NbExp=3; IntAct=EBI-10317612, EBI-2873970;
CC Q9P0N8; P11912: CD79A; NbExp=3; IntAct=EBI-10317612, EBI-7797864;
CC Q9P0N8; Q96BA8: CREB3L1; NbExp=3; IntAct=EBI-10317612, EBI-6942903;
CC Q9P0N8; Q9Y282: ERGIC3; NbExp=8; IntAct=EBI-10317612, EBI-781551;
CC Q9P0N8; Q9Y624: F11R; NbExp=3; IntAct=EBI-10317612, EBI-742600;
CC Q9P0N8; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-10317612, EBI-18304435;
CC Q9P0N8; Q969F0: FATE1; NbExp=6; IntAct=EBI-10317612, EBI-743099;
CC Q9P0N8; P48165: GJA8; NbExp=3; IntAct=EBI-10317612, EBI-17458373;
CC Q9P0N8; Q8TED1: GPX8; NbExp=3; IntAct=EBI-10317612, EBI-11721746;
CC Q9P0N8; Q8N6L0: KASH5; NbExp=3; IntAct=EBI-10317612, EBI-749265;
CC Q9P0N8; Q5T700: LDLRAD1; NbExp=7; IntAct=EBI-10317612, EBI-10173166;
CC Q9P0N8; Q9BXB1-2: LGR4; NbExp=3; IntAct=EBI-10317612, EBI-17443382;
CC Q9P0N8; P15941-11: MUC1; NbExp=3; IntAct=EBI-10317612, EBI-17263240;
CC Q9P0N8; O00623: PEX12; NbExp=3; IntAct=EBI-10317612, EBI-594836;
CC Q9P0N8; Q96GM1: PLPPR2; NbExp=3; IntAct=EBI-10317612, EBI-12955265;
CC Q9P0N8; Q9NY72: SCN3B; NbExp=3; IntAct=EBI-10317612, EBI-17247926;
CC Q9P0N8; Q8WWF3: SSMEM1; NbExp=3; IntAct=EBI-10317612, EBI-17280858;
CC Q9P0N8; Q8N205: SYNE4; NbExp=3; IntAct=EBI-10317612, EBI-7131783;
CC Q9P0N8; Q9BVX2: TMEM106C; NbExp=3; IntAct=EBI-10317612, EBI-2821497;
CC Q9P0N8; Q7Z7N9: TMEM179B; NbExp=3; IntAct=EBI-10317612, EBI-11724423;
CC Q9P0N8; Q4KMG9: TMEM52B; NbExp=3; IntAct=EBI-10317612, EBI-18178701;
CC Q9P0N8; Q8N661: TMEM86B; NbExp=3; IntAct=EBI-10317612, EBI-2548832;
CC Q9P0N8; O95859: TSPAN12; NbExp=3; IntAct=EBI-10317612, EBI-2466403;
CC Q9P0N8; Q5TGU0: TSPO2; NbExp=3; IntAct=EBI-10317612, EBI-12195249;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:14722266}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q5I0I2}. Lysosome membrane
CC {ECO:0000269|PubMed:14722266}; Multi-pass membrane protein
CC {ECO:0000255}. Endosome membrane {ECO:0000269|PubMed:23166351}; Multi-
CC pass membrane protein {ECO:0000250|UniProtKB:Q5I0I2}. Golgi apparatus
CC membrane {ECO:0000269|PubMed:23818989}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasm {ECO:0000269|PubMed:32935379}. Cell membrane
CC {ECO:0000269|PubMed:32935379}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:32935379}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9P0N8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9P0N8-2; Sequence=VSP_041478;
CC -!- TISSUE SPECIFICITY: Broadly expressed. {ECO:0000269|PubMed:14722266}.
CC -!- INDUCTION: (Microbial infection) Induced by HIV-1 infection.
CC {ECO:0000269|PubMed:29573664}.
CC -!- DOMAIN: The RING-CH-type zinc finger domain is required for E3 ligase
CC activity.
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DR EMBL; AB197929; BAD89359.1; -; mRNA.
DR EMBL; AF151074; AAF36160.1; -; mRNA.
DR EMBL; AC136469; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC032624; AAH32624.1; -; mRNA.
DR EMBL; BC015910; AAH15910.1; -; mRNA.
DR EMBL; BC111388; AAI11389.1; -; mRNA.
DR CCDS; CCDS12202.1; -. [Q9P0N8-1]
DR CCDS; CCDS32894.1; -. [Q9P0N8-2]
DR RefSeq; NP_001005415.1; NM_001005415.1. [Q9P0N8-1]
DR RefSeq; NP_001005416.1; NM_001005416.1. [Q9P0N8-2]
DR RefSeq; NP_057580.3; NM_016496.4. [Q9P0N8-1]
DR RefSeq; XP_006722826.1; XM_006722763.3.
DR RefSeq; XP_016882342.1; XM_017026853.1.
DR AlphaFoldDB; Q9P0N8; -.
DR SMR; Q9P0N8; -.
DR BioGRID; 119413; 87.
DR IntAct; Q9P0N8; 25.
DR STRING; 9606.ENSP00000471536; -.
DR TCDB; 8.A.159.1.3; the march ubiquitin ligase (march) family.
DR iPTMnet; Q9P0N8; -.
DR PhosphoSitePlus; Q9P0N8; -.
DR BioMuta; MARCH2; -.
DR DMDM; 57012977; -.
DR EPD; Q9P0N8; -.
DR MassIVE; Q9P0N8; -.
DR PaxDb; Q9P0N8; -.
DR PeptideAtlas; Q9P0N8; -.
DR PRIDE; Q9P0N8; -.
DR ProteomicsDB; 83585; -. [Q9P0N8-1]
DR ProteomicsDB; 83586; -. [Q9P0N8-2]
DR Antibodypedia; 2987; 197 antibodies from 26 providers.
DR DNASU; 51257; -.
DR Ensembl; ENST00000215555.7; ENSP00000215555.2; ENSG00000099785.11. [Q9P0N8-1]
DR Ensembl; ENST00000381035.8; ENSP00000370423.3; ENSG00000099785.11. [Q9P0N8-2]
DR Ensembl; ENST00000602117.1; ENSP00000471536.1; ENSG00000099785.11. [Q9P0N8-1]
DR GeneID; 51257; -.
DR KEGG; hsa:51257; -.
DR MANE-Select; ENST00000215555.7; ENSP00000215555.2; NM_001005415.2; NP_001005415.1.
DR UCSC; uc002mjw.4; human. [Q9P0N8-1]
DR CTD; 51257; -.
DR DisGeNET; 51257; -.
DR GeneCards; MARCHF2; -.
DR HGNC; HGNC:28038; MARCHF2.
DR HPA; ENSG00000099785; Low tissue specificity.
DR MIM; 613332; gene.
DR neXtProt; NX_Q9P0N8; -.
DR OpenTargets; ENSG00000099785; -.
DR VEuPathDB; HostDB:ENSG00000099785; -.
DR eggNOG; KOG1609; Eukaryota.
DR GeneTree; ENSGT00940000158995; -.
DR HOGENOM; CLU_096532_0_1_1; -.
DR InParanoid; Q9P0N8; -.
DR OMA; FWEGTGL; -.
DR OrthoDB; 1373244at2759; -.
DR PhylomeDB; Q9P0N8; -.
DR TreeFam; TF319557; -.
DR PathwayCommons; Q9P0N8; -.
DR SignaLink; Q9P0N8; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 51257; 7 hits in 894 CRISPR screens.
DR ChiTaRS; MARCH2; human.
DR GeneWiki; MARCH2; -.
DR GenomeRNAi; 51257; -.
DR Pharos; Q9P0N8; Tbio.
DR PRO; PR:Q9P0N8; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9P0N8; protein.
DR Bgee; ENSG00000099785; Expressed in apex of heart and 165 other tissues.
DR ExpressionAtlas; Q9P0N8; baseline and differential.
DR Genevisible; Q9P0N8; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA: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; IDA:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA: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; IMP:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0044790; P:suppression of viral release by host; IMP: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 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cytoplasm; Endocytosis;
KW Endoplasmic reticulum; Endosome; Golgi apparatus; Lysosome; Membrane;
KW Metal-binding; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..246
FT /note="E3 ubiquitin-protein ligase MARCHF2"
FT /id="PRO_0000055925"
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 56..116
FT /note="Required for inhibition of HIV-1 virus production
FT and VSV G protein expression"
FT /evidence="ECO:0000269|PubMed:29573664"
FT REGION 121..246
FT /note="Required for interaction with IKBKG"
FT /evidence="ECO:0000269|PubMed:32935379"
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"
FT VAR_SEQ 125..194
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_041478"
FT VARIANT 54
FT /note="A -> T (in dbSNP:rs1133893)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030303"
FT VARIANT 219
FT /note="R -> P (in dbSNP:rs34099346)"
FT /id="VAR_053638"
FT MUTAGEN 64
FT /note="C->S: Abolishes ubiquitination of ERGIC3 and CFTR,
FT and degradation of CFTR; when associated with S-67. Reduces
FT ubiquitination of DLG1 ; when associated with S-67, S-106
FT and S-109. Reduces inhibition of HIV-1 virus production and
FT VSV G protein expression; when associated with S-67.
FT Abolishes ubiquitination of IKBKG/NEMO; when associated
FT with S-67 and Q-90."
FT /evidence="ECO:0000269|PubMed:17980554,
FT ECO:0000269|PubMed:23818989, ECO:0000269|PubMed:29573664,
FT ECO:0000269|PubMed:31142615, ECO:0000269|PubMed:32935379"
FT MUTAGEN 67
FT /note="C->S: Abolishes ubiquitination of ERGIC3 and CFTR,
FT and degradation of CFTR; when associated with S-64. Reduces
FT ubiquitination of DLG1; when associated with S-64, S-106
FT and S-109. Reduces inhibition of HIV-1 virus production and
FT VSV G protein expression; when associated with S-64.
FT Abolishes ubiquitination of IKBKG/NEMO; when associated
FT with S-64 and Q-90."
FT /evidence="ECO:0000269|PubMed:17980554,
FT ECO:0000269|PubMed:23818989, ECO:0000269|PubMed:29573664,
FT ECO:0000269|PubMed:31142615, ECO:0000269|PubMed:32935379"
FT MUTAGEN 90
FT /note="H->Q: Abolishes ubiquitination of IKBKG/NEMO; when
FT associated with S-64 and S-67."
FT MUTAGEN 97
FT /note="W->A: Reduces ubiquitination of DLG1. No effect on
FT interaction with DLG1. Abolishes ubiquitination of and
FT interaction with DLG1; when associated with 243-E--V-246
FT DEL."
FT /evidence="ECO:0000269|PubMed:17980554"
FT MUTAGEN 106
FT /note="C->S: Reduces ubiquitination of DLG1; when
FT associated with S-64, S-67 and S-109."
FT /evidence="ECO:0000269|PubMed:17980554"
FT MUTAGEN 109
FT /note="C->S: Reduces ubiquitination of DLG1; when
FT associated with S-64, S-67 and S-106."
FT /evidence="ECO:0000269|PubMed:17980554"
FT MUTAGEN 243..246
FT /note="ETPV->AAAA: Abolishes ubiquitination of and
FT interaction with DLG1; when associated with A-97."
FT /evidence="ECO:0000269|PubMed:17980554"
SQ SEQUENCE 246 AA; 26995 MW; FBD877D55211C929 CRC64;
MTTGDCCHLP GSLCDCSGSP AFSKVVEATG LGPPQYVAQV TSRDGRLLST VIRALDTPSD
GPFCRICHEG ANGECLLSPC GCTGTLGAVH KSCLEKWLSS SNTSYCELCH TEFAVEKRPR
PLTEWLKDPG PRTEKRTLCC DMVCFLFITP LAAISGWLCL RGAQDHLRLH SQLEAVGLIA
LTIALFTIYV LWTLVSFRYH CQLYSEWRKT NQKVRLKIRE ADSPEGPQHS PLAAGLLKKV
AEETPV
