MARH1_MOUSE
ID MARH1_MOUSE Reviewed; 289 AA.
AC Q6NZQ8; Q3U7M8; Q3UVF8; Q8C294; Q8CBA1;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 140.
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-type E3 ubiquitin transferase MARCHF1 {ECO:0000305};
GN Name=Marchf1; Synonyms=March1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 4 AND 5).
RC STRAIN=C57BL/6J, and NOD;
RC TISSUE=Aorta, Bone, Bone marrow, Cerebellum, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 AS AN E3 UBIQUITIN LIGASE FOR HLA-DRB.
RX PubMed=17051151; DOI=10.1038/nature05261;
RA Shin J.S., Ebersold M., Pypaert M., Delamarre L., Hartley A., Mellman I.;
RT "Surface expression of MHC class II in dendritic cells is controlled by
RT regulated ubiquitination.";
RL Nature 444:115-118(2006).
RN [4]
RP FUNCTION AS AN E3 UBIQUITIN LIGASE FOR HLA-DRB, AND DISRUPTION PHENOTYPE.
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 [5]
RP FUNCTION AS REGULATOR OF ANTIGEN PRESENTATION, PTM, MUTAGENESIS OF TRP-114;
RP LEU-225 AND TYR-232, AND SUBCELLULAR LOCATION.
RX PubMed=19880452; DOI=10.4049/jimmunol.0901521;
RA Jabbour M., Campbell E.M., Fares H., Lybarger L.;
RT "Discrete domains of MARCH1 mediate its localization, functional
RT interactions, and posttranscriptional control of expression.";
RL J. Immunol. 183:6500-6512(2009).
RN [6]
RP FUNCTION AS AN E3 UBIQUITIN LIGASE FOR HLA-DR AND REGULATOR OF ANTIGEN
RP PRESENTATION, AND DISRUPTION PHENOTYPE.
RX PubMed=19917682; DOI=10.4049/jimmunol.0902178;
RA Ohmura-Hoshino M., Matsuki Y., Mito-Yoshida M., Goto E., Aoki-Kawasumi M.,
RA Nakayama M., Ohara O., Ishido S.;
RT "Requirement of MARCH-I-mediated MHC II ubiquitination for the maintenance
RT of conventional dendritic cells.";
RL J. Immunol. 183:6893-6897(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:17051151,
CC ECO:0000269|PubMed:17255932, ECO:0000269|PubMed:19880452,
CC ECO:0000269|PubMed:19917682}.
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: Cytoplasmic vesicle membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000255}. Late endosome membrane
CC {ECO:0000269|PubMed:19880452}; Multi-pass membrane protein
CC {ECO:0000255}. Early endosome membrane {ECO:0000269|PubMed:19880452};
CC Multi-pass membrane protein {ECO:0000255}. Golgi apparatus, trans-Golgi
CC network membrane {ECO:0000269|PubMed:19880452}; Multi-pass membrane
CC protein {ECO:0000255}. Lysosome membrane {ECO:0000269|PubMed:19880452};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q6NZQ8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6NZQ8-2; Sequence=VSP_022726;
CC Name=3;
CC IsoId=Q6NZQ8-3; Sequence=VSP_022727;
CC Name=4;
CC IsoId=Q6NZQ8-4; Sequence=VSP_022726, VSP_022728;
CC Name=5;
CC IsoId=Q6NZQ8-5; Sequence=VSP_022728;
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.
CC -!- DISRUPTION PHENOTYPE: Shows increase in the cell surface expression or
CC half-life of MHC class II. Null cells have accumulated MHC class II and
CC CD86 at the cell surface and a low antigen-presenting ability for
CC exogenous antigens, in conventional dendritic cells (PubMed:19917682).
CC Null cells have high antigen-presenting ability for exogenous antigens
CC in B-cells (PubMed:17255932). {ECO:0000269|PubMed:17255932,
CC ECO:0000269|PubMed:19917682}.
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DR EMBL; AK036489; BAC29449.1; -; mRNA.
DR EMBL; AK089040; BAC40715.1; -; mRNA.
DR EMBL; AK137337; BAE23311.1; -; mRNA.
DR EMBL; AK152592; BAE31341.1; -; mRNA.
DR EMBL; AK163081; BAE37183.1; -; mRNA.
DR EMBL; BC066008; AAH66008.1; -; mRNA.
DR CCDS; CCDS22333.1; -. [Q6NZQ8-3]
DR CCDS; CCDS52560.1; -. [Q6NZQ8-5]
DR CCDS; CCDS52561.1; -. [Q6NZQ8-4]
DR CCDS; CCDS80884.1; -. [Q6NZQ8-1]
DR RefSeq; NP_001159844.1; NM_001166372.1. [Q6NZQ8-5]
DR RefSeq; NP_001159847.1; NM_001166375.1. [Q6NZQ8-4]
DR RefSeq; NP_001280713.1; NM_001293784.1. [Q6NZQ8-1]
DR RefSeq; NP_780397.2; NM_175188.4. [Q6NZQ8-3]
DR RefSeq; XP_006509821.1; XM_006509758.1.
DR RefSeq; XP_017168467.1; XM_017312978.1. [Q6NZQ8-3]
DR AlphaFoldDB; Q6NZQ8; -.
DR SMR; Q6NZQ8; -.
DR STRING; 10090.ENSMUSP00000044070; -.
DR iPTMnet; Q6NZQ8; -.
DR PhosphoSitePlus; Q6NZQ8; -.
DR PaxDb; Q6NZQ8; -.
DR PRIDE; Q6NZQ8; -.
DR ProteomicsDB; 295790; -. [Q6NZQ8-1]
DR ProteomicsDB; 295791; -. [Q6NZQ8-2]
DR ProteomicsDB; 295792; -. [Q6NZQ8-3]
DR ProteomicsDB; 295793; -. [Q6NZQ8-4]
DR ProteomicsDB; 295794; -. [Q6NZQ8-5]
DR Antibodypedia; 3022; 164 antibodies from 26 providers.
DR DNASU; 72925; -.
DR Ensembl; ENSMUST00000039540; ENSMUSP00000044070; ENSMUSG00000036469. [Q6NZQ8-4]
DR Ensembl; ENSMUST00000072482; ENSMUSP00000072302; ENSMUSG00000036469. [Q6NZQ8-3]
DR Ensembl; ENSMUST00000098708; ENSMUSP00000096305; ENSMUSG00000036469. [Q6NZQ8-5]
DR Ensembl; ENSMUST00000110253; ENSMUSP00000105882; ENSMUSG00000036469. [Q6NZQ8-2]
DR Ensembl; ENSMUST00000110255; ENSMUSP00000105884; ENSMUSG00000036469. [Q6NZQ8-5]
DR Ensembl; ENSMUST00000110258; ENSMUSP00000105887; ENSMUSG00000036469. [Q6NZQ8-1]
DR Ensembl; ENSMUST00000110259; ENSMUSP00000105888; ENSMUSG00000036469. [Q6NZQ8-3]
DR Ensembl; ENSMUST00000178982; ENSMUSP00000136545; ENSMUSG00000036469. [Q6NZQ8-1]
DR GeneID; 72925; -.
DR KEGG; mmu:72925; -.
DR UCSC; uc009lvj.2; mouse. [Q6NZQ8-1]
DR UCSC; uc009lvk.2; mouse. [Q6NZQ8-5]
DR UCSC; uc009lvl.2; mouse. [Q6NZQ8-3]
DR UCSC; uc009lvm.2; mouse. [Q6NZQ8-2]
DR UCSC; uc009lvn.2; mouse. [Q6NZQ8-4]
DR CTD; 55016; -.
DR MGI; MGI:1920175; Marchf1.
DR VEuPathDB; HostDB:ENSMUSG00000036469; -.
DR eggNOG; KOG1609; Eukaryota.
DR GeneTree; ENSGT00940000159346; -.
DR HOGENOM; CLU_070599_0_1_1; -.
DR InParanoid; Q6NZQ8; -.
DR OMA; KYDFVME; -.
DR PhylomeDB; Q6NZQ8; -.
DR TreeFam; TF319557; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 72925; 0 hits in 19 CRISPR screens.
DR ChiTaRS; March1; mouse.
DR PRO; PR:Q6NZQ8; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q6NZQ8; protein.
DR Bgee; ENSMUSG00000036469; Expressed in rostral migratory stream and 137 other tissues.
DR ExpressionAtlas; Q6NZQ8; baseline and differential.
DR Genevisible; Q6NZQ8; MM.
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; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0031902; C:late endosome membrane; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0032588; C:trans-Golgi network membrane; IDA:UniProtKB.
DR GO; GO:0042287; F:MHC protein binding; ISS:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase 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; IMP: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; Cytoplasmic vesicle; Endosome; Golgi apparatus;
KW Immunity; Lysosome; Membrane; Metal-binding; Reference proteome;
KW Transferase; Transmembrane; Transmembrane helix; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1..289
FT /note="E3 ubiquitin-protein ligase MARCHF1"
FT /id="PRO_0000274366"
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 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 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..54
FT /note="MLGWCEAIARNPHRIPNTTRTPETSGDVADASQTSTLNEKSPGRSASRSSNI
FT SK -> MNLTMSNMTSSHICCNFLNMWKKSKISTMYYLNQDAKLSNLFLQ (in
FT isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_022726"
FT VAR_SEQ 1..37
FT /note="MLGWCEAIARNPHRIPNTTRTPETSGDVADASQTSTL -> MPLHQISVIPA
FT RETASNGRSSMGRNKEKNKEVE (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_022727"
FT VAR_SEQ 187..190
FT /note="Missing (in isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_022728"
FT MUTAGEN 114
FT /note="W->A: Loss of ubiquitin ligase activity and loss of
FT down-regulation of CD86 cell surface expression."
FT /evidence="ECO:0000269|PubMed:19880452"
FT MUTAGEN 225
FT /note="L->S: Partial loss of down-regulation of CD86 cell
FT surface expression. Almost complete loss of down-regulation
FT of CD86 cell surface expression; when associated with F-
FT 232."
FT /evidence="ECO:0000269|PubMed:19880452"
FT MUTAGEN 232
FT /note="Y->F: Almost complete loss of down-regulation of
FT CD86 cell surface expression; when associated with S-225."
FT /evidence="ECO:0000269|PubMed:19880452"
FT CONFLICT 85
FT /note="C -> Y (in Ref. 1; BAE31341)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 289 AA; 32347 MW; 0DBE9A308D5ED0CE CRC64;
MLGWCEAIAR NPHRIPNTTR TPETSGDVAD ASQTSTLNEK SPGRSASRSS NISKASSPTT
GTAPRSQSRL SVCPSTQDIC RICHCEGDEE SPLITPCRCT GTLRFVHQSC LHQWIKSSDT
RCCELCKYDF IMETKLKPLR KWEKLQMTTS ERRKIFCSVT FHVIAVTCVV WSLYVLIDRT
AEEIKQGNDN GVLEWPFWTK LVVVAIGFTG GLVFMYVQCK VYVQLWRRLK AYNRVIFVQN
CPDTANKLEK NFPCNVNTEI KDAVVVPVPQ TGSNTLPTAE GAPPEVIPV
