MARH4_HUMAN
ID MARH4_HUMAN Reviewed; 410 AA.
AC Q9P2E8; Q4KMN7; Q86WR8;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=E3 ubiquitin-protein ligase MARCHF4;
DE EC=2.3.2.27;
DE AltName: Full=Membrane-associated RING finger protein 4;
DE AltName: Full=Membrane-associated RING-CH protein IV;
DE Short=MARCH-IV;
DE AltName: Full=RING finger protein 174;
DE AltName: Full=RING-type E3 ubiquitin transferase MARCHF4 {ECO:0000305};
DE Flags: Precursor;
GN Name=MARCHF4 {ECO:0000312|HGNC:HGNC:29269};
GN Synonyms=KIAA1399, MARCH4, RNF174;
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 [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI. The
RT complete sequences of 150 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver, and Pancreas;
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, 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).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that may mediate ubiquitination
CC of MHC-I and CD4, 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. {ECO:0000269|PubMed:14722266}.
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;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:14722266}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:14722266}.
CC -!- TISSUE SPECIFICITY: Expressed in brain and placenta.
CC {ECO:0000269|PubMed:14722266}.
CC -!- DOMAIN: The RING-CH-type zinc finger domain is required for E3 ligase
CC activity.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA92637.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB037820; BAA92637.1; ALT_INIT; mRNA.
DR EMBL; BC048793; AAH48793.1; -; mRNA.
DR EMBL; BC098448; AAH98448.1; -; mRNA.
DR CCDS; CCDS33376.1; -.
DR RefSeq; NP_065865.1; NM_020814.2.
DR AlphaFoldDB; Q9P2E8; -.
DR BioGRID; 121627; 128.
DR STRING; 9606.ENSP00000273067; -.
DR iPTMnet; Q9P2E8; -.
DR PhosphoSitePlus; Q9P2E8; -.
DR BioMuta; MARCH4; -.
DR DMDM; 59798475; -.
DR PaxDb; Q9P2E8; -.
DR PeptideAtlas; Q9P2E8; -.
DR PRIDE; Q9P2E8; -.
DR Antibodypedia; 3020; 185 antibodies from 27 providers.
DR DNASU; 57574; -.
DR Ensembl; ENST00000273067.5; ENSP00000273067.3; ENSG00000144583.5.
DR GeneID; 57574; -.
DR KEGG; hsa:57574; -.
DR MANE-Select; ENST00000273067.5; ENSP00000273067.3; NM_020814.3; NP_065865.1.
DR UCSC; uc002vgb.4; human.
DR CTD; 57574; -.
DR DisGeNET; 57574; -.
DR GeneCards; MARCHF4; -.
DR HGNC; HGNC:29269; MARCHF4.
DR HPA; ENSG00000144583; Group enriched (brain, pituitary gland).
DR MIM; 608208; gene.
DR neXtProt; NX_Q9P2E8; -.
DR OpenTargets; ENSG00000144583; -.
DR VEuPathDB; HostDB:ENSG00000144583; -.
DR eggNOG; KOG1609; Eukaryota.
DR GeneTree; ENSGT00940000158179; -.
DR HOGENOM; CLU_045217_0_1_1; -.
DR InParanoid; Q9P2E8; -.
DR OMA; CCGLCTP; -.
DR OrthoDB; 1014283at2759; -.
DR PhylomeDB; Q9P2E8; -.
DR TreeFam; TF319557; -.
DR PathwayCommons; Q9P2E8; -.
DR SignaLink; Q9P2E8; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 57574; 10 hits in 1056 CRISPR screens.
DR ChiTaRS; MARCH4; human.
DR GenomeRNAi; 57574; -.
DR Pharos; Q9P2E8; Tbio.
DR PRO; PR:Q9P2E8; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9P2E8; protein.
DR Bgee; ENSG00000144583; Expressed in cortical plate and 58 other tissues.
DR Genevisible; Q9P2E8; HS.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005795; C:Golgi stack; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005802; C:trans-Golgi network; IDA:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR046356; MARCHF4/9/11.
DR InterPro; IPR011016; Znf_RING-CH.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR46053; PTHR46053; 1.
DR Pfam; PF12906; RINGv; 1.
DR SMART; SM00744; RINGv; 1.
DR PROSITE; PS51292; ZF_RING_CH; 1.
PE 2: Evidence at transcript level;
KW Golgi apparatus; Membrane; Metal-binding; Reference proteome; Signal;
KW Transferase; Transmembrane; Transmembrane helix; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..410
FT /note="E3 ubiquitin-protein ligase MARCHF4"
FT /id="PRO_0000055930"
FT TRANSMEM 238..258
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 272..292
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ZN_FING 155..215
FT /note="RING-CH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT REGION 92..136
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 324..372
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 390..410
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 98..115
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 330..353
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 163
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 166
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 179
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 181
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 189
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 192
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 205
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 208
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
SQ SEQUENCE 410 AA; 45528 MW; BC812496FCCC2930 CRC64;
MLMPLCGLLW WWWCCCSGWY CYGLCAPAPQ MLRHQGLLKC RCRMLFNDLK VFLLRRPPQA
PLPMHGDPQP PGLAANNTLP ALGAGGWAGW RGPREVVGRE PPPVPPPPPL PPSSVEDDWG
GPATEPPASL LSSASSDDFC KEKTEDRYSL GSSLDSGMRT PLCRICFQGP EQGELLSPCR
CDGSVKCTHQ PCLIKWISER GCWSCELCYY KYHVIAISTK NPLQWQAISL TVIEKVQVAA
AILGSLFLIA SISWLIWSTF SPSARWQRQD LLFQICYGMY GFMDVVCIGL IIHEGPSVYR
IFKRWQAVNQ QWKVLNYDKT KDLEDQKAGG RTNPRTSSST QANIPSSEEE TAGTPAPEQG
PAQAAGHPSG PLSHHHCAYT ILHILSHLRP HEQRSPPGSS RELVMRVTTV
