UniProtKB - Q9P0N8 (MARH2_HUMAN)
E3 ubiquitin-protein ligase MARCHF2
MARCHF2
Functioni
E3 ubiquitin-protein ligase that may mediate ubiquitination of TFRC and CD86, and promote their subsequent endocytosis and sorting to lysosomes via multivesicular bodies. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates (PubMed:14722266, PubMed:16428329).
Together with GOPC/CAL mediates the ubiquitination and lysosomal degradation of CFTR (PubMed:23818989).
Ubiquitinates and therefore mediates the degradation of DLG1 (PubMed:17980554).
Regulates the intracellular trafficking and secretion of alpha1-antitrypsin/SERPINA1 and HP/haptoglobin via ubiquitination and degradation of the cargo receptor ERGIC3 (PubMed:31142615).
Negatively regulates the antiviral and antibacterial immune response by repression of the NF-kB and type 1 IFN signaling pathways, via MARCHF2-mediated K48-linked polyubiquitination of IKBKG/NEMO, resulting in its proteosomal degradation (PubMed:32935379).
May be involved in endosomal trafficking through interaction with STX6 (PubMed:15689499).
7 Publications(Microbial infection) Positively regulates the degradation of Vesicular stomatitis virus (VSV) G protein via the lysosomal degradation pathway (PubMed:29573664).
Represses HIV-1 viral production and may inhibit the translocation of HIV-1 env to the cell surface, resulting in decreased viral cell-cell transmission (PubMed:29573664).
1 PublicationCatalytic activityi
- S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.3 Publications EC:2.3.2.27
: protein ubiquitination Pathwayi
This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.3 PublicationsView all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 64 | Zinc 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 67 | Zinc 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 80 | Zinc 2PROSITE-ProRule annotation | 1 | |
Metal bindingi | 82 | Zinc 2PROSITE-ProRule annotation | 1 | |
Metal bindingi | 90 | Zinc 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 93 | Zinc 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 106 | Zinc 2PROSITE-ProRule annotation | 1 | |
Metal bindingi | 109 | Zinc 2PROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 56 – 116 | RING-CH-typePROSITE-ProRule annotationAdd BLAST | 61 |
GO - Molecular functioni
- ubiquitin protein ligase activity Source: UniProtKB
- ubiquitin-protein transferase activity Source: GO_Central
- zinc ion binding Source: InterPro
GO - Biological processi
- antibacterial innate immune response Source: UniProtKB
- antiviral innate immune response Source: UniProtKB
- endocytosis Source: UniProtKB-KW
- positive regulation of lysosomal protein catabolic process Source: UniProtKB
- protein ubiquitination Source: UniProtKB
- suppression of viral release by host Source: UniProtKB
Keywordsi
Molecular function | Transferase |
Biological process | Endocytosis, Ubl conjugation pathway |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q9P0N8 |
SignaLinki | Q9P0N8 |
UniPathwayi | UPA00143 |
Protein family/group databases
TCDBi | 8.A.159.1.3, the march ubiquitin ligase (march) family |
Names & Taxonomyi
Protein namesi | Recommended name: E3 ubiquitin-protein ligase MARCHF2 (EC:2.3.2.272 Publications)Alternative name(s): Membrane-associated RING finger protein 2 Membrane-associated RING-CH protein II Short name: MARCH-II RING finger protein 172Imported RING-type E3 ubiquitin transferase MARCHF2Curated |
Gene namesi | ORF Names:HSPC240 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:28038, MARCHF2 |
MIMi | 613332, gene |
neXtProti | NX_Q9P0N8 |
VEuPathDBi | HostDB:ENSG00000099785 |
Subcellular locationi
Lysosome
- Lysosome membrane 1 Publication; Multi-pass membrane protein Sequence analysis
Endoplasmic reticulum
- Endoplasmic reticulum membrane 1 Publication; Multi-pass membrane protein By similarity
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Plasma membrane
- Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication
Golgi apparatus
- Golgi apparatus membrane 1 Publication; Multi-pass membrane protein Sequence analysis
Endosome
- Endosome membrane 1 Publication; Multi-pass membrane protein By similarity
Cytosol
- cytosol Source: HPA
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB
- endoplasmic reticulum membrane Source: UniProtKB-SubCell
Endosome
- endosome membrane Source: UniProtKB-SubCell
Golgi apparatus
- Golgi membrane Source: UniProtKB
Lysosome
- lysosomal membrane Source: UniProtKB-SubCell
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
- cytoplasmic vesicle Source: UniProtKB
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 138 – 158 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 175 – 195 | HelicalSequence analysisAdd BLAST | 21 |
Keywords - Cellular componenti
Cell membrane, Cytoplasm, Endoplasmic reticulum, Endosome, Golgi apparatus, Lysosome, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 64 | C → S: Abolishes ubiquitination of ERGIC3 and CFTR, and degradation of CFTR; when associated with S-67. Reduces ubiquitination of DLG1 ; when associated with S-67, S-106 and S-109. Reduces inhibition of HIV-1 virus production and VSV G protein expression; when associated with S-67. Abolishes ubiquitination of IKBKG/NEMO; when associated with S-67 and Q-90. 5 Publications | 1 | |
Mutagenesisi | 67 | C → S: Abolishes ubiquitination of ERGIC3 and CFTR, and degradation of CFTR; when associated with S-64. Reduces ubiquitination of DLG1; when associated with S-64, S-106 and S-109. Reduces inhibition of HIV-1 virus production and VSV G protein expression; when associated with S-64. Abolishes ubiquitination of IKBKG/NEMO; when associated with S-64 and Q-90. 5 Publications | 1 | |
Mutagenesisi | 90 | H → Q: Abolishes ubiquitination of IKBKG/NEMO; when associated with S-64 and S-67. | 1 | |
Mutagenesisi | 97 | W → A: Reduces ubiquitination of DLG1. No effect on interaction with DLG1. Abolishes ubiquitination of and interaction with DLG1; when associated with 243-E--V-246 DEL. 1 Publication | 1 | |
Mutagenesisi | 106 | C → S: Reduces ubiquitination of DLG1; when associated with S-64, S-67 and S-109. 1 Publication | 1 | |
Mutagenesisi | 109 | C → S: Reduces ubiquitination of DLG1; when associated with S-64, S-67 and S-106. 1 Publication | 1 | |
Mutagenesisi | 243 – 246 | ETPV → AAAA: Abolishes ubiquitination of and interaction with DLG1; when associated with A-97. 1 Publication | 4 |
Organism-specific databases
DisGeNETi | 51257 |
OpenTargetsi | ENSG00000099785 |
PharmGKBi | PA134993565 |
Miscellaneous databases
Pharosi | Q9P0N8, Tbio |
Genetic variation databases
BioMutai | MARCH2 |
DMDMi | 57012977 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000055925 | 1 – 246 | E3 ubiquitin-protein ligase MARCHF2Add BLAST | 246 |
Proteomic databases
MassIVEi | Q9P0N8 |
PaxDbi | Q9P0N8 |
PeptideAtlasi | Q9P0N8 |
PRIDEi | Q9P0N8 |
ProteomicsDBi | 83585 [Q9P0N8-1] 83586 [Q9P0N8-2] |
PTM databases
iPTMneti | Q9P0N8 |
PhosphoSitePlusi | Q9P0N8 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000099785, Expressed in apex of heart and 211 other tissues |
ExpressionAtlasi | Q9P0N8, baseline and differential |
Genevisiblei | Q9P0N8, HS |
Organism-specific databases
HPAi | ENSG00000099785, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with STX6; the interaction promotes MARCHF2-mediated ubiquitination and degradation of CFTR (PubMed:23818989).
Interacts with MARCHF3 (PubMed:16428329).
Interacts with GOPC/CAL; the interaction leads to CFTR ubiquitination and degradation (PubMed:23818989).
Interacts with CFTR; the interaction leads to CFTR ubiqtuitination and degradation (PubMed:23818989).
Interacts (via PDZ domain) with DLG1 (via PDZ domains); the interaction leads to DLG1 ubiqtuitination and degradation (PubMed:17980554).
Interacts with ERGIC3 (PubMed:31142615).
Interacts with ADRB2 (PubMed:23166351).
Interacts with IKBKG/NEMO; during the late stages of macrophage viral and bacterial infection; the interaction leads to ubiquitination and degradation of IKBKG/NEMO (PubMed:32935379).
6 PublicationsBinary interactionsi
Q9P0N8
Protein-protein interaction databases
BioGRIDi | 119413, 74 interactors |
IntActi | Q9P0N8, 25 interactors |
STRINGi | 9606.ENSP00000471536 |
Miscellaneous databases
RNActi | Q9P0N8, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 56 – 116 | Required for inhibition of HIV-1 virus production and VSV G protein expression1 PublicationAdd BLAST | 61 | |
Regioni | 121 – 246 | Required for interaction with IKBKG1 PublicationAdd BLAST | 126 |
Domaini
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 56 – 116 | RING-CH-typePROSITE-ProRule annotationAdd BLAST | 61 |
Keywords - Domaini
Transmembrane, Transmembrane helix, Zinc-fingerPhylogenomic databases
eggNOGi | KOG1609, Eukaryota |
GeneTreei | ENSGT00940000158995 |
HOGENOMi | CLU_096532_0_1_1 |
InParanoidi | Q9P0N8 |
OMAi | GSEGSQH |
OrthoDBi | 1373244at2759 |
PhylomeDBi | Q9P0N8 |
TreeFami | TF319557 |
Family and domain databases
Gene3Di | 3.30.40.10, 1 hit |
InterProi | View protein in InterPro IPR001841, Znf_RING IPR011016, Znf_RING-CH IPR013083, Znf_RING/FYVE/PHD |
Pfami | View protein in Pfam PF12906, RINGv, 1 hit |
SMARTi | View protein in SMART SM00744, RINGv, 1 hit |
PROSITEi | View protein in PROSITE PS51292, ZF_RING_CH, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MTTGDCCHLP GSLCDCSGSP AFSKVVEATG LGPPQYVAQV TSRDGRLLST
60 70 80 90 100
VIRALDTPSD GPFCRICHEG ANGECLLSPC GCTGTLGAVH KSCLEKWLSS
110 120 130 140 150
SNTSYCELCH TEFAVEKRPR PLTEWLKDPG PRTEKRTLCC DMVCFLFITP
160 170 180 190 200
LAAISGWLCL RGAQDHLRLH SQLEAVGLIA LTIALFTIYV LWTLVSFRYH
210 220 230 240
CQLYSEWRKT NQKVRLKIRE ADSPEGPQHS PLAAGLLKKV AEETPV
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketM0R0S4 | M0R0S4_HUMAN | E3 ubiquitin-protein ligase MARCHF2 | MARCHF2 | 56 | Annotation score: | ||
M0QXU4 | M0QXU4_HUMAN | E3 ubiquitin-protein ligase MARCHF2 | MARCHF2 | 40 | Annotation score: | ||
M0R138 | M0R138_HUMAN | E3 ubiquitin-protein ligase MARCHF2 | MARCHF2 | 80 | Annotation score: | ||
M0R1P2 | M0R1P2_HUMAN | E3 ubiquitin-protein ligase MARCHF2 | MARCHF2 | 78 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_030303 | 54 | A → T1 PublicationCorresponds to variant dbSNP:rs1133893Ensembl. | 1 | |
Natural variantiVAR_053638 | 219 | R → P. Corresponds to variant dbSNP:rs34099346Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_041478 | 125 – 194 | Missing in isoform 2. CuratedAdd BLAST | 70 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB197929 mRNA Translation: BAD89359.1 AF151074 mRNA Translation: AAF36160.1 AC136469 Genomic DNA No translation available. BC032624 mRNA Translation: AAH32624.1 BC015910 mRNA Translation: AAH15910.1 BC111388 mRNA Translation: AAI11389.1 |
CCDSi | CCDS12202.1 [Q9P0N8-1] CCDS32894.1 [Q9P0N8-2] |
RefSeqi | NP_001005415.1, NM_001005415.1 [Q9P0N8-1] NP_001005416.1, NM_001005416.1 [Q9P0N8-2] NP_057580.3, NM_016496.4 [Q9P0N8-1] XP_006722826.1, XM_006722763.3 XP_016882342.1, XM_017026853.1 |
Genome annotation databases
Ensembli | ENST00000215555; ENSP00000215555; ENSG00000099785 ENST00000381035; ENSP00000370423; ENSG00000099785 [Q9P0N8-2] ENST00000602117; ENSP00000471536; ENSG00000099785 |
GeneIDi | 51257 |
KEGGi | hsa:51257 |
MANE-Selecti | ENST00000215555.7; ENSP00000215555.2; NM_001005415.2; NP_001005415.1 |
UCSCi | uc002mjw.4, human [Q9P0N8-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB197929 mRNA Translation: BAD89359.1 AF151074 mRNA Translation: AAF36160.1 AC136469 Genomic DNA No translation available. BC032624 mRNA Translation: AAH32624.1 BC015910 mRNA Translation: AAH15910.1 BC111388 mRNA Translation: AAI11389.1 |
CCDSi | CCDS12202.1 [Q9P0N8-1] CCDS32894.1 [Q9P0N8-2] |
RefSeqi | NP_001005415.1, NM_001005415.1 [Q9P0N8-1] NP_001005416.1, NM_001005416.1 [Q9P0N8-2] NP_057580.3, NM_016496.4 [Q9P0N8-1] XP_006722826.1, XM_006722763.3 XP_016882342.1, XM_017026853.1 |
3D structure databases
SMRi | Q9P0N8 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 119413, 74 interactors |
IntActi | Q9P0N8, 25 interactors |
STRINGi | 9606.ENSP00000471536 |
Protein family/group databases
TCDBi | 8.A.159.1.3, the march ubiquitin ligase (march) family |
PTM databases
iPTMneti | Q9P0N8 |
PhosphoSitePlusi | Q9P0N8 |
Genetic variation databases
BioMutai | MARCH2 |
DMDMi | 57012977 |
Proteomic databases
MassIVEi | Q9P0N8 |
PaxDbi | Q9P0N8 |
PeptideAtlasi | Q9P0N8 |
PRIDEi | Q9P0N8 |
ProteomicsDBi | 83585 [Q9P0N8-1] 83586 [Q9P0N8-2] |
Protocols and materials databases
Antibodypediai | 2987, 195 antibodies from 25 providers |
DNASUi | 51257 |
Genome annotation databases
Ensembli | ENST00000215555; ENSP00000215555; ENSG00000099785 ENST00000381035; ENSP00000370423; ENSG00000099785 [Q9P0N8-2] ENST00000602117; ENSP00000471536; ENSG00000099785 |
GeneIDi | 51257 |
KEGGi | hsa:51257 |
MANE-Selecti | ENST00000215555.7; ENSP00000215555.2; NM_001005415.2; NP_001005415.1 |
UCSCi | uc002mjw.4, human [Q9P0N8-1] |
Organism-specific databases
CTDi | 51257 |
DisGeNETi | 51257 |
GeneCardsi | MARCHF2 |
HGNCi | HGNC:28038, MARCHF2 |
HPAi | ENSG00000099785, Low tissue specificity |
MIMi | 613332, gene |
neXtProti | NX_Q9P0N8 |
OpenTargetsi | ENSG00000099785 |
PharmGKBi | PA134993565 |
VEuPathDBi | HostDB:ENSG00000099785 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1609, Eukaryota |
GeneTreei | ENSGT00940000158995 |
HOGENOMi | CLU_096532_0_1_1 |
InParanoidi | Q9P0N8 |
OMAi | GSEGSQH |
OrthoDBi | 1373244at2759 |
PhylomeDBi | Q9P0N8 |
TreeFami | TF319557 |
Enzyme and pathway databases
UniPathwayi | UPA00143 |
PathwayCommonsi | Q9P0N8 |
SignaLinki | Q9P0N8 |
Miscellaneous databases
BioGRID-ORCSi | 51257, 3 hits in 885 CRISPR screens |
ChiTaRSi | MARCH2, human |
GeneWikii | MARCH2 |
GenomeRNAii | 51257 |
Pharosi | Q9P0N8, Tbio |
PROi | PR:Q9P0N8 |
RNActi | Q9P0N8, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000099785, Expressed in apex of heart and 211 other tissues |
ExpressionAtlasi | Q9P0N8, baseline and differential |
Genevisiblei | Q9P0N8, HS |
Family and domain databases
Gene3Di | 3.30.40.10, 1 hit |
InterProi | View protein in InterPro IPR001841, Znf_RING IPR011016, Znf_RING-CH IPR013083, Znf_RING/FYVE/PHD |
Pfami | View protein in Pfam PF12906, RINGv, 1 hit |
SMARTi | View protein in SMART SM00744, RINGv, 1 hit |
PROSITEi | View protein in PROSITE PS51292, ZF_RING_CH, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | MARH2_HUMAN | |
Accessioni | Q9P0N8Primary (citable) accession number: Q9P0N8 Secondary accession number(s): A6NP10 Q96B78 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 4, 2005 |
Last sequence update: | October 1, 2000 | |
Last modified: | February 23, 2022 | |
This is version 164 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways