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 27-MAR-2024, entry version 175. 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 proteasomal 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. 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; 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; 88. 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; 9606-ENSP00000471536; -. DR PeptideAtlas; Q9P0N8; -. DR Antibodypedia; 2987; 217 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 AGR; HGNC:28038; -. 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; ICHEGAS; -. DR OrthoDB; 1342875at2759; -. DR PhylomeDB; Q9P0N8; -. DR TreeFam; TF319557; -. DR PathwayCommons; Q9P0N8; -. DR SignaLink; Q9P0N8; -. DR SIGNOR; Q9P0N8; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 51257; 8 hits in 926 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 167 other cell types or tissues. DR ExpressionAtlas; Q9P0N8; baseline and differential. 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:HPA. 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: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 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; Q9P0N8; HS. 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 VSVG 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 VSVG 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 //