MARH9_HUMAN
ID MARH9_HUMAN Reviewed; 346 AA.
AC Q86YJ5; B2R9U9; Q86VN5; Q96GG2;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=E3 ubiquitin-protein ligase MARCHF9;
DE EC=2.3.2.27;
DE AltName: Full=Membrane-associated RING finger protein 9;
DE AltName: Full=Membrane-associated RING-CH protein IX;
DE Short=MARCH-IX;
DE AltName: Full=RING finger protein 179;
DE AltName: Full=RING-type E3 ubiquitin transferase MARCHF9 {ECO:0000305};
GN Name=MARCHF9 {ECO:0000312|HGNC:HGNC:25139}; Synonyms=MARCH9, RNF179;
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=Brain;
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 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS
RP HIS-257 AND PRO-307.
RC TISSUE=Brain, and Lung;
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 [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 FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND MUTAGENESIS OF ASP-231.
RX PubMed=17174307; DOI=10.1016/j.febslet.2006.11.075;
RA Hoer S., Smith L., Lehner P.J.;
RT "MARCH-IX mediates ubiquitination and downregulation of ICAM-1.";
RL FEBS Lett. 581:45-51(2007).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that may mediate ubiquitination
CC of MHC-I, CD4 and ICAM1, and promote their subsequent endocytosis and
CC sorting to lysosomes via multivesicular bodies. E3 ubiquitin ligases
CC accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of
CC a thioester and then directly transfer the ubiquitin to targeted
CC substrates. {ECO:0000269|PubMed:14722266, ECO:0000269|PubMed:17174307}.
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 -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:17174307}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:14722266}; Multi-pass membrane protein
CC {ECO:0000255}. Lysosome membrane {ECO:0000269|PubMed:17174307}; Multi-
CC pass membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q86YJ5-1; Sequence=Displayed;
CC Name=2; Synonyms=RINGless;
CC IsoId=Q86YJ5-2; Sequence=VSP_022697;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:14722266}.
CC -!- DOMAIN: The RING-CH-type zinc finger domain is required for E3 ligase
CC activity.
CC -!- MISCELLANEOUS: [Isoform 2]: Has no E3 activity due to lack of RINGv-
CC type zinc finger domain but is able to dimerize with and stabilize
CC isoform 1. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH50397.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK313925; BAG36646.1; -; mRNA.
DR EMBL; CH471054; EAW97065.1; -; Genomic_DNA.
DR EMBL; BC009489; AAH09489.1; -; mRNA.
DR EMBL; BC036455; AAH36455.2; -; mRNA.
DR EMBL; BC050397; AAH50397.1; ALT_INIT; mRNA.
DR CCDS; CCDS31847.1; -. [Q86YJ5-1]
DR RefSeq; NP_612405.2; NM_138396.5. [Q86YJ5-1]
DR AlphaFoldDB; Q86YJ5; -.
DR BioGRID; 124992; 7.
DR IntAct; Q86YJ5; 5.
DR MINT; Q86YJ5; -.
DR STRING; 9606.ENSP00000266643; -.
DR iPTMnet; Q86YJ5; -.
DR PhosphoSitePlus; Q86YJ5; -.
DR BioMuta; MARCH9; -.
DR DMDM; 74759533; -.
DR jPOST; Q86YJ5; -.
DR MassIVE; Q86YJ5; -.
DR PaxDb; Q86YJ5; -.
DR PeptideAtlas; Q86YJ5; -.
DR PRIDE; Q86YJ5; -.
DR ProteomicsDB; 70419; -. [Q86YJ5-1]
DR ProteomicsDB; 70420; -. [Q86YJ5-2]
DR Antibodypedia; 28932; 163 antibodies from 21 providers.
DR DNASU; 92979; -.
DR Ensembl; ENST00000266643.6; ENSP00000266643.5; ENSG00000139266.6. [Q86YJ5-1]
DR Ensembl; ENST00000548358.1; ENSP00000446758.1; ENSG00000139266.6. [Q86YJ5-2]
DR GeneID; 92979; -.
DR KEGG; hsa:92979; -.
DR MANE-Select; ENST00000266643.6; ENSP00000266643.5; NM_138396.6; NP_612405.2.
DR UCSC; uc001spx.3; human. [Q86YJ5-1]
DR CTD; 92979; -.
DR DisGeNET; 92979; -.
DR GeneCards; MARCHF9; -.
DR HGNC; HGNC:25139; MARCHF9.
DR HPA; ENSG00000139266; Low tissue specificity.
DR MIM; 613336; gene.
DR neXtProt; NX_Q86YJ5; -.
DR OpenTargets; ENSG00000139266; -.
DR PharmGKB; PA134920045; -.
DR VEuPathDB; HostDB:ENSG00000139266; -.
DR eggNOG; KOG1609; Eukaryota.
DR GeneTree; ENSGT00940000158208; -.
DR HOGENOM; CLU_045217_0_0_1; -.
DR InParanoid; Q86YJ5; -.
DR OMA; CHSRDDE; -.
DR PhylomeDB; Q86YJ5; -.
DR TreeFam; TF319557; -.
DR PathwayCommons; Q86YJ5; -.
DR SignaLink; Q86YJ5; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 92979; 48 hits in 1059 CRISPR screens.
DR ChiTaRS; MARCH9; human.
DR GenomeRNAi; 92979; -.
DR Pharos; Q86YJ5; Tbio.
DR PRO; PR:Q86YJ5; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q86YJ5; protein.
DR Bgee; ENSG00000139266; Expressed in adenohypophysis and 126 other tissues.
DR Genevisible; Q86YJ5; 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:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005802; C:trans-Golgi network; 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 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 1: Evidence at protein level;
KW Alternative splicing; Golgi apparatus; Lysosome; Membrane; Metal-binding;
KW Reference proteome; Transferase; Transmembrane; Transmembrane helix;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..346
FT /note="E3 ubiquitin-protein ligase MARCHF9"
FT /id="PRO_0000274282"
FT TRANSMEM 185..205
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 219..239
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ZN_FING 102..162
FT /note="RING-CH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT REGION 20..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 47..92
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 273..301
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 326..346
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..71
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 75..91
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 282..300
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 113
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
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 BINDING 128
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 136
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 139
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 152
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 155
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..170
FT /note="MLKSRLRMFLNELKLLVLTGGGRPRAEPQPRGGRGGGCGWAPFAGCSTRDGD
FT GDEEEYYGSEPRARGLAGDKEPRAGPLPPPAPPLPPPGALDALSLSSSLDSGLRTPQCR
FT ICFQGPEQGELLSPCRCDGSVRCTHQPCLIRWISERGSWSCELCYFKYQVLAISTKNPL
FT -> MVSDKCHILDLIKAQRRQMLILPEGFREGSWSTLLFRATHHLALHPFLGLFGALSP
FT T (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_022697"
FT VARIANT 257
FT /note="Q -> H (in dbSNP:rs17856312)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030246"
FT VARIANT 307
FT /note="T -> P (in dbSNP:rs17850517)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030247"
FT MUTAGEN 231
FT /note="D->N: Diminishes ability to promote MHC-I
FT internalization."
FT /evidence="ECO:0000269|PubMed:17174307"
SQ SEQUENCE 346 AA; 37772 MW; FA6142B973A359B8 CRC64;
MLKSRLRMFL NELKLLVLTG GGRPRAEPQP RGGRGGGCGW APFAGCSTRD GDGDEEEYYG
SEPRARGLAG DKEPRAGPLP PPAPPLPPPG ALDALSLSSS LDSGLRTPQC RICFQGPEQG
ELLSPCRCDG SVRCTHQPCL IRWISERGSW SCELCYFKYQ VLAISTKNPL QWQAISLTVI
EKVQIAAIVL GSLFLVASIS WLIWSSLSPS AKWQRQDLLF QICYGMYGFM DVVCIGLIIH
EGSSVYRIFK RWQAVNQQWK VLNYDKTKDI GGDAGGGTAG KSGPRNSRTG PTSGATSRPP
AAQRMRTLLP QRCGYTILHL LGQLRPPDAR SSSHSGREVV MRVTTV
