MARH1_HUMAN
ID MARH1_HUMAN Reviewed; 289 AA.
AC Q8TCQ1; D3DP29; Q9NWR0;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=E3 ubiquitin-protein ligase MARCHF1;
DE EC=2.3.2.27;
DE AltName: Full=Membrane-associated RING finger protein 1;
DE AltName: Full=Membrane-associated RING-CH protein I;
DE Short=MARCH-I;
DE AltName: Full=RING finger protein 171;
DE AltName: Full=RING-type E3 ubiquitin transferase MARCHF1 {ECO:0000305};
GN Name=MARCHF1 {ECO:0000312|HGNC:HGNC:26077}; Synonyms=MARCH1, RNF171;
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] (ISOFORM 2).
RC TISSUE=Ileal mucosa;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
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).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=17255932; DOI=10.1038/sj.emboj.7601556;
RA Matsuki Y., Ohmura-Hoshino M., Goto E., Aoki M., Mito-Yoshida M.,
RA Uematsu M., Hasegawa T., Koseki H., Ohara O., Nakayama M., Toyooka K.,
RA Matsuoka K., Hotta H., Yamamoto A., Ishido S.;
RT "Novel regulation of MHC class II function in B cells.";
RL EMBO J. 26:846-854(2007).
RN [6]
RP FUNCTION AS AN E3 UBIQUITIN LIGASE FOR HLA-DR BETA, AND INDUCTION BY IL10.
RX PubMed=18389477; DOI=10.1002/eji.200737902;
RA Thibodeau J., Bourgeois-Daigneault M.C., Huppe G., Tremblay J., Aumont A.,
RA Houde M., Bartee E., Brunet A., Gauvreau M.E., de Gassart A., Gatti E.,
RA Baril M., Cloutier M., Bontron S., Fruh K., Lamarre D., Steimle V.;
RT "Interleukin-10-induced MARCH1 mediates intracellular sequestration of MHC
RT class II in monocytes.";
RL Eur. J. Immunol. 38:1225-1230(2008).
RN [7]
RP FUNCTION AS AN E3 UBIQUITIN LIGASE FOR HLA-DR BETA.
RX PubMed=18305173; DOI=10.1073/pnas.0708874105;
RA De Gassart A., Camosseto V., Thibodeau J., Ceppi M., Catalan N., Pierre P.,
RA Gatti E.;
RT "MHC class II stabilization at the surface of human dendritic cells is the
RT result of maturation-dependent MARCH I down-regulation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:3491-3496(2008).
RN [8]
RP FUNCTION AS AN E3 UBIQUITIN LIGASE FOR HLA-DR ALPHA AND BETA, AND
RP SUBCELLULAR LOCATION.
RX PubMed=19117940; DOI=10.1074/jbc.m805736200;
RA Lapaque N., Jahnke M., Trowsdale J., Kelly A.P.;
RT "The HLA-DRalpha chain is modified by polyubiquitination.";
RL J. Biol. Chem. 284:7007-7016(2009).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination of
CC TFRC, CD86, FAS and MHC class II proteins, such as HLA-DR alpha and
CC beta, and promotes their subsequent endocytosis and sorting to
CC lysosomes via multivesicular bodies. By constitutively ubiquitinating
CC MHC class II proteins in immature dendritic cells, down-regulates their
CC cell surface localization thus sequestering them in the intracellular
CC endosomal system. {ECO:0000269|PubMed:14722266,
CC ECO:0000269|PubMed:18305173, ECO:0000269|PubMed:18389477,
CC ECO:0000269|PubMed:19117940}.
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, trans-Golgi network membrane
CC {ECO:0000250|UniProtKB:Q6NZQ8}; Multi-pass membrane protein
CC {ECO:0000255}. Lysosome membrane {ECO:0000269|PubMed:14722266}; Multi-
CC pass membrane protein {ECO:0000255}. Cytoplasmic vesicle membrane
CC {ECO:0000305}; Multi-pass membrane protein {ECO:0000255}. Late endosome
CC membrane {ECO:0000269|PubMed:19117940}; Multi-pass membrane protein
CC {ECO:0000255}. Early endosome membrane {ECO:0000269|PubMed:14722266,
CC ECO:0000269|PubMed:19117940}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:19117940}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8TCQ1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TCQ1-2; Sequence=VSP_022724, VSP_022725;
CC -!- TISSUE SPECIFICITY: Expressed in antigen presenting cells, APCs,
CC located in lymph nodes and spleen. Also expressed in lung. Expression
CC is high in follicular B-cells, moderate in dendritic cells and low in
CC splenic T-cells. {ECO:0000269|PubMed:14722266,
CC ECO:0000269|PubMed:17255932}.
CC -!- DEVELOPMENTAL STAGE: During maturation of dendritic cells, expression
CC is down-regulated and stabilizes MHC class II proteins accumulate at
CC the plasma membrane.
CC -!- INDUCTION: By IL10/interleukin-10. {ECO:0000269|PubMed:18389477}.
CC -!- DOMAIN: The RING-CH-type zinc finger domain is required for E3 ligase
CC activity. {ECO:0000255|PROSITE-ProRule:PRU00623}.
CC -!- PTM: Has a short half-life. Instability/short half-life permits rapid
CC changes that allow efficient induction of antigen presentation once
CC antigen presenting cells, APCs, receive maturation signals. Small
CC changes in protein levels significantly alter the cell surface display
CC of MHC class II proteins (By similarity). {ECO:0000250}.
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DR EMBL; AK000675; BAA91319.1; -; mRNA.
DR EMBL; AL713759; CAD28529.1; -; mRNA.
DR EMBL; CH471056; EAX04835.1; -; Genomic_DNA.
DR CCDS; CCDS3806.1; -. [Q8TCQ1-2]
DR CCDS; CCDS54814.1; -. [Q8TCQ1-1]
DR RefSeq; NP_001159845.1; NM_001166373.1. [Q8TCQ1-1]
DR RefSeq; NP_060393.1; NM_017923.3. [Q8TCQ1-2]
DR RefSeq; XP_016863823.1; XM_017008334.1. [Q8TCQ1-1]
DR AlphaFoldDB; Q8TCQ1; -.
DR SMR; Q8TCQ1; -.
DR BioGRID; 120348; 85.
DR IntAct; Q8TCQ1; 1.
DR STRING; 9606.ENSP00000427223; -.
DR TCDB; 8.A.159.1.1; the march ubiquitin ligase (march) family.
DR GlyGen; Q8TCQ1; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q8TCQ1; -.
DR PhosphoSitePlus; Q8TCQ1; -.
DR BioMuta; MARCH1; -.
DR DMDM; 74762613; -.
DR jPOST; Q8TCQ1; -.
DR MassIVE; Q8TCQ1; -.
DR PaxDb; Q8TCQ1; -.
DR PeptideAtlas; Q8TCQ1; -.
DR PRIDE; Q8TCQ1; -.
DR ProteomicsDB; 74150; -. [Q8TCQ1-1]
DR ProteomicsDB; 74151; -. [Q8TCQ1-2]
DR Antibodypedia; 3022; 164 antibodies from 26 providers.
DR DNASU; 55016; -.
DR Ensembl; ENST00000274056.11; ENSP00000274056.7; ENSG00000145416.14. [Q8TCQ1-1]
DR Ensembl; ENST00000339875.9; ENSP00000345676.5; ENSG00000145416.14. [Q8TCQ1-2]
DR Ensembl; ENST00000503008.5; ENSP00000427223.1; ENSG00000145416.14. [Q8TCQ1-1]
DR GeneID; 55016; -.
DR KEGG; hsa:55016; -.
DR UCSC; uc003iqr.3; human. [Q8TCQ1-1]
DR CTD; 55016; -.
DR DisGeNET; 55016; -.
DR GeneCards; MARCHF1; -.
DR HGNC; HGNC:26077; MARCHF1.
DR HPA; ENSG00000145416; Tissue enhanced (lymphoid tissue, retina).
DR MIM; 613331; gene.
DR neXtProt; NX_Q8TCQ1; -.
DR OpenTargets; ENSG00000145416; -.
DR PharmGKB; PA134986392; -.
DR VEuPathDB; HostDB:ENSG00000145416; -.
DR eggNOG; KOG1609; Eukaryota.
DR GeneTree; ENSGT00940000159346; -.
DR HOGENOM; CLU_070599_0_1_1; -.
DR InParanoid; Q8TCQ1; -.
DR OMA; KYDFVME; -.
DR PhylomeDB; Q8TCQ1; -.
DR TreeFam; TF319557; -.
DR PathwayCommons; Q8TCQ1; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 55016; 3 hits in 888 CRISPR screens.
DR ChiTaRS; MARCH1; human.
DR GenomeRNAi; 55016; -.
DR Pharos; Q8TCQ1; Tbio.
DR PRO; PR:Q8TCQ1; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q8TCQ1; protein.
DR Bgee; ENSG00000145416; Expressed in monocyte and 161 other tissues.
DR ExpressionAtlas; Q8TCQ1; baseline and differential.
DR Genevisible; Q8TCQ1; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0031902; C:late endosome membrane; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032588; C:trans-Golgi network membrane; ISS:UniProtKB.
DR GO; GO:0042287; F:MHC protein binding; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0002495; P:antigen processing and presentation of peptide antigen via MHC class II; IDA:UniProtKB.
DR GO; GO:0006955; P:immune response; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA: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; Cytoplasmic vesicle; Endosome;
KW Golgi apparatus; Immunity; Lysosome; Membrane; Metal-binding;
KW Reference proteome; Transferase; Transmembrane; Transmembrane helix;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..289
FT /note="E3 ubiquitin-protein ligase MARCHF1"
FT /id="PRO_0000274365"
FT TRANSMEM 155..175
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 197..217
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ZN_FING 72..133
FT /note="RING-CH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT REGION 1..66
FT /note="Responsible for low stability"
FT /evidence="ECO:0000250"
FT REGION 13..69
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 222..279
FT /note="Responsible for down-regulation of CD86 and MHC
FT class II cell surface expression"
FT /evidence="ECO:0000250"
FT COMPBIAS 14..69
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 80
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 83
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 97
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 99
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 107
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 110
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 123
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 126
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT VAR_SEQ 1..18
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_022724"
FT VAR_SEQ 19..54
FT /note="TRTPEISGDLADASQTSTLNEKSPGRSASRSSNISK -> MTSSHVCCNFLN
FT MWKKSKISTMYYLNQDAKLSNLFLQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_022725"
SQ SEQUENCE 289 AA; 32308 MW; 923E1809AB3D7087 CRC64;
MLGWCEAIAR NPHRIPNNTR TPEISGDLAD ASQTSTLNEK SPGRSASRSS NISKASSPTT
GTAPRSQSRL SVCPSTQDIC RICHCEGDEE SPLITPCRCT GTLRFVHQSC LHQWIKSSDT
RCCELCKYDF IMETKLKPLR KWEKLQMTTS ERRKIFCSVT FHVIAITCVV WSLYVLIDRT
AEEIKQGNDN GVLEWPFWTK LVVVAIGFTG GLVFMYVQCK VYVQLWRRLK AYNRVIFVQN
CPDTAKKLEK NFSCNVNTDI KDAVVVPVPQ TGANSLPSAE GGPPEVVSV
