MARH6_HUMAN
ID MARH6_HUMAN Reviewed; 910 AA.
AC O60337; A5PKZ4; B4DKJ2; B4DT33; D3DTC8; O14670; Q86X77;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=E3 ubiquitin-protein ligase MARCHF6;
DE EC=2.3.2.27 {ECO:0000269|PubMed:15673284, ECO:0000269|PubMed:24449766};
DE AltName: Full=Doa10 homolog;
DE AltName: Full=Membrane-associated RING finger protein 6;
DE AltName: Full=Membrane-associated RING-CH protein VI;
DE Short=MARCH-VI {ECO:0000303|PubMed:16373356};
DE AltName: Full=Protein TEB-4 {ECO:0000303|PubMed:15673284, ECO:0000303|PubMed:16373356, ECO:0000303|PubMed:19651899};
DE AltName: Full=RING finger protein 176;
DE AltName: Full=RING-type E3 ubiquitin transferase MARCHF6 {ECO:0000305};
GN Name=MARCHF6 {ECO:0000312|HGNC:HGNC:30550};
GN Synonyms=KIAA0597, MARCH6, RNF176, TEB4;
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 1).
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 379-910 (ISOFORM 1), AND VARIANT LEU-622.
RA Simmons A.D., Lovett M.L.;
RT "High resolution physical and transcription maps of the Cri-du-chat
RT critical region.";
RL Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP IDENTIFICATION.
RX PubMed=11641273; DOI=10.1101/gad.933301;
RA Swanson R., Locher M., Hochstrasser M.;
RT "A conserved ubiquitin ligase of the nuclear envelope/endoplasmic reticulum
RT that functions in both ER-associated and Matalpha2 repressor degradation.";
RL Genes Dev. 15:2660-2674(2001).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, TOPOLOGY,
RP UBIQUITINATION, MUTAGENESIS OF CYS-9, DOMAIN, AND PATHWAY.
RX PubMed=15673284; DOI=10.1042/bj20041241;
RA Hassink G., Kikkert M., van Voorden S., Lee S.-J., Spaapen R., van Laar T.,
RA Coleman C.S., Bartee E., Frueh K., Chau V., Wiertz E.;
RT "TEB4 is a C4HC3 RING finger-containing ubiquitin ligase of the endoplasmic
RT reticulum.";
RL Biochem. J. 388:647-655(2005).
RN [9]
RP TOPOLOGY.
RX PubMed=16373356; DOI=10.1074/jbc.m512215200;
RA Kreft S.G., Wang L., Hochstrasser M.;
RT "Membrane topology of the yeast endoplasmic reticulum-localized ubiquitin
RT ligase Doa10 and comparison with its human ortholog TEB4 (MARCH-VI).";
RL J. Biol. Chem. 281:4646-4653(2006).
RN [10]
RP FUNCTION AS AN E3 UBIQUITIN LIGASE FOR DIO2, AND INTERACTION WITH DIO2.
RX PubMed=19651899; DOI=10.1128/mcb.01498-08;
RA Zavacki A.M., Arrojo E Drigo R., Freitas B.C., Chung M., Harney J.W.,
RA Egri P., Wittmann G., Fekete C., Gereben B., Bianco A.C.;
RT "The E3 ubiquitin ligase TEB4 mediates degradation of type 2 iodothyronine
RT deiodinase.";
RL Mol. Cell. Biol. 29:5339-5347(2009).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH SQLE, MUTAGENESIS OF CYS-9,
RP AND DOMAIN.
RX PubMed=24449766; DOI=10.1128/mcb.01140-13;
RA Zelcer N., Sharpe L.J., Loregger A., Kristiana I., Cook E.C., Phan L.,
RA Stevenson J., Brown A.J.;
RT "The E3 ubiquitin ligase MARCH6 degrades squalene monooxygenase and affects
RT 3-hydroxy-3-methyl-glutaryl coenzyme A reductase and the cholesterol
RT synthesis pathway.";
RL Mol. Cell. Biol. 34:1262-1270(2014).
RN [13]
RP INVOLVEMENT IN FAME3.
RX PubMed=31664039; DOI=10.1038/s41467-019-12763-9;
RG FAME consortium;
RA Florian R.T., Kraft F., Leitao E., Kaya S., Klebe S., Magnin E.,
RA van Rootselaar A.F., Buratti J., Kuehnel T., Schroeder C., Giesselmann S.,
RA Tschernoster N., Altmueller J., Lamiral A., Keren B., Nava C.,
RA Bouteiller D., Forlani S., Jornea L., Kubica R., Ye T., Plassard D.,
RA Jost B., Meyer V., Deleuze J.F., Delpu Y., Avarello M.D.M.,
RA Vijfhuizen L.S., Rudolf G., Hirsch E., Kroes T., Reif P.S., Rosenow F.,
RA Ganos C., Vidailhet M., Thivard L., Mathieu A., Bourgeron T., Kurth I.,
RA Rafehi H., Steenpass L., Horsthemke B., LeGuern E., Klein K.M., Labauge P.,
RA Bennett M.F., Bahlo M., Gecz J., Corbett M.A., Tijssen M.A.J.,
RA van den Maagdenberg A.M.J.M., Depienne C.;
RT "Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial
RT Adult Myoclonic Epilepsy type 3.";
RL Nat. Commun. 10:4919-4919(2019).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that promotes 'Lys-48'-linked
CC ubiquitination of target proteins, leading to their proteasomal
CC degradation (PubMed:15673284). Promotes ubiquitination of DIO2, leading
CC to its degradation (PubMed:19651899). Promotes ubiquitination of SQLE,
CC leading to its degradation (PubMed:24449766). 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. May cooperate with UBE2G1 (PubMed:15673284).
CC {ECO:0000269|PubMed:15673284, ECO:0000269|PubMed:19651899,
CC ECO:0000269|PubMed:24449766}.
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; Evidence={ECO:0000269|PubMed:15673284};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:15673284}.
CC -!- SUBUNIT: Interacts with DIO2 (PubMed:19651899). Interacts with SQLE
CC (PubMed:24449766). {ECO:0000269|PubMed:19651899,
CC ECO:0000269|PubMed:24449766}.
CC -!- INTERACTION:
CC O60337; Q9UHX3: ADGRE2; NbExp=3; IntAct=EBI-2684600, EBI-11277970;
CC O60337; P41220-1: RGS2; NbExp=3; IntAct=EBI-2684600, EBI-16037474;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:15673284}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:15673284}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O60337-4; Sequence=Displayed;
CC Name=2;
CC IsoId=O60337-5; Sequence=VSP_047036;
CC Name=3;
CC IsoId=O60337-6; Sequence=VSP_047035;
CC -!- TISSUE SPECIFICITY: Present in brain (at protein level).
CC {ECO:0000269|PubMed:15673284}.
CC -!- DOMAIN: The RING-CH-type zinc finger domain is required for E3 ligase
CC activity. {ECO:0000269|PubMed:15673284, ECO:0000269|PubMed:24449766}.
CC -!- PTM: Auto-ubiquitinated, which results in proteasomal degradation.
CC {ECO:0000269|PubMed:15673284}.
CC -!- DISEASE: Epilepsy, familial adult myoclonic, 3 (FAME3) [MIM:613608]: A
CC form of familial myoclonic epilepsy, a neurologic disorder
CC characterized by cortical hand tremors, myoclonic jerks and occasional
CC generalized or focal seizures with a non-progressive or very slowly
CC progressive disease course. Usually, myoclonic tremor is the presenting
CC symptom, characterized by tremulous finger movements and myoclonic
CC jerks of the limbs increased by action and posture. In a minority of
CC patients, seizures are the presenting symptom. Some patients exhibit
CC mild cognitive impairment. FAME3 inheritance is autosomal dominant.
CC {ECO:0000269|PubMed:31664039}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB66840.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAB66840.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAA25523.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB011169; BAA25523.1; ALT_INIT; mRNA.
DR EMBL; AK296585; BAG59204.1; -; mRNA.
DR EMBL; AK300034; BAG61845.1; -; mRNA.
DR EMBL; AC012640; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC092336; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471102; EAX08065.1; -; Genomic_DNA.
DR EMBL; CH471102; EAX08066.1; -; Genomic_DNA.
DR EMBL; BC046148; AAH46148.1; -; mRNA.
DR EMBL; BC136461; AAI36462.1; -; mRNA.
DR EMBL; BC136462; AAI36463.1; -; mRNA.
DR EMBL; BC142679; AAI42680.1; -; mRNA.
DR EMBL; BC142694; AAI42695.1; -; mRNA.
DR EMBL; AF009301; AAB66840.1; ALT_SEQ; mRNA.
DR CCDS; CCDS34135.1; -. [O60337-4]
DR CCDS; CCDS59487.1; -. [O60337-5]
DR CCDS; CCDS59488.1; -. [O60337-6]
DR PIR; T00268; T00268.
DR RefSeq; NP_001257589.1; NM_001270660.1. [O60337-5]
DR RefSeq; NP_001257590.1; NM_001270661.1. [O60337-6]
DR RefSeq; NP_005876.2; NM_005885.3. [O60337-4]
DR AlphaFoldDB; O60337; -.
DR SMR; O60337; -.
DR BioGRID; 115587; 55.
DR DIP; DIP-56134N; -.
DR IntAct; O60337; 19.
DR MINT; O60337; -.
DR STRING; 9606.ENSP00000274140; -.
DR iPTMnet; O60337; -.
DR PhosphoSitePlus; O60337; -.
DR BioMuta; MARCH6; -.
DR EPD; O60337; -.
DR jPOST; O60337; -.
DR MassIVE; O60337; -.
DR MaxQB; O60337; -.
DR PaxDb; O60337; -.
DR PeptideAtlas; O60337; -.
DR PRIDE; O60337; -.
DR ProteomicsDB; 4463; -.
DR ProteomicsDB; 49363; -. [O60337-4]
DR ProteomicsDB; 5070; -.
DR Antibodypedia; 22463; 154 antibodies from 29 providers.
DR DNASU; 10299; -.
DR Ensembl; ENST00000274140.10; ENSP00000274140.4; ENSG00000145495.16. [O60337-4]
DR Ensembl; ENST00000449913.6; ENSP00000414643.2; ENSG00000145495.16. [O60337-5]
DR Ensembl; ENST00000503788.5; ENSP00000425930.1; ENSG00000145495.16. [O60337-6]
DR GeneID; 10299; -.
DR KEGG; hsa:10299; -.
DR MANE-Select; ENST00000274140.10; ENSP00000274140.4; NM_005885.4; NP_005876.2.
DR UCSC; uc003jet.3; human. [O60337-4]
DR CTD; 10299; -.
DR DisGeNET; 10299; -.
DR GeneCards; MARCHF6; -.
DR HGNC; HGNC:30550; MARCHF6.
DR HPA; ENSG00000145495; Low tissue specificity.
DR MalaCards; MARCHF6; -.
DR MIM; 613297; gene.
DR MIM; 613608; phenotype.
DR neXtProt; NX_O60337; -.
DR OpenTargets; ENSG00000145495; -.
DR Orphanet; 86814; Benign adult familial myoclonic epilepsy.
DR VEuPathDB; HostDB:ENSG00000145495; -.
DR eggNOG; KOG1609; Eukaryota.
DR GeneTree; ENSGT00940000155171; -.
DR HOGENOM; CLU_006373_1_0_1; -.
DR InParanoid; O60337; -.
DR OMA; WLPIRIL; -.
DR OrthoDB; 170933at2759; -.
DR PhylomeDB; O60337; -.
DR TreeFam; TF105777; -.
DR BioCyc; MetaCyc:ENSG00000145495-MON; -.
DR BRENDA; 2.3.2.27; 2681.
DR PathwayCommons; O60337; -.
DR Reactome; R-HSA-901032; ER Quality Control Compartment (ERQC).
DR SignaLink; O60337; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 10299; 39 hits in 1066 CRISPR screens.
DR ChiTaRS; MARCH6; human.
DR GeneWiki; MARCH6; -.
DR GenomeRNAi; 10299; -.
DR Pharos; O60337; Tbio.
DR PRO; PR:O60337; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; O60337; protein.
DR Bgee; ENSG00000145495; Expressed in Brodmann (1909) area 23 and 208 other tissues.
DR ExpressionAtlas; O60337; baseline and differential.
DR Genevisible; O60337; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0044322; C:endoplasmic reticulum quality control compartment; IEA:GOC.
DR GO; GO:0000835; C:ER ubiquitin ligase complex; IC:ParkinsonsUK-UCL.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; IPI:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:1990381; F:ubiquitin-specific protease binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:1904380; P:endoplasmic reticulum mannose trimming; TAS:Reactome.
DR GO; GO:0036503; P:ERAD pathway; TAS:ParkinsonsUK-UCL.
DR GO; GO:0010498; P:proteasomal protein catabolic process; IDA:ParkinsonsUK-UCL.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IBA:GO_Central.
DR Gene3D; 3.30.40.10; -; 1.
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 Acetylation; Alternative splicing; Endoplasmic reticulum; Epilepsy;
KW Membrane; Metal-binding; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix; Ubl conjugation; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..910
FT /note="E3 ubiquitin-protein ligase MARCHF6"
FT /id="PRO_0000274298"
FT TOPO_DOM 1..91
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:15673284,
FT ECO:0000305|PubMed:16373356"
FT TRANSMEM 92..112
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 113..142
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 143..163
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 164..283
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 284..304
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 305..336
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 337..357
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 358..376
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 377..397
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 398..421
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 422..442
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 443..480
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 481..501
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 502..519
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 520..540
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 541..632
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 633..653
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 654..678
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 679..699
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 700..721
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 722..742
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 743..764
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 765..785
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 786..815
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 816..836
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 837..848
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 849..869
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 870..910
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:16373356"
FT ZN_FING 1..62
FT /note="RING-CH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT REGION 185..256
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 224..246
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 9
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 12
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 26
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 28
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 36
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 39
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 52
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 55
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT VAR_SEQ 7..112
FT /note="DICRVCRSEGTPEKPLYHPCVCTGSIKFIHQECLVQWLKHSRKEYCELCKHR
FT FAFTPIYSPDMPSRLPIQDIFAGLVTSIGTAIRYWFHYTLVAFAWLGVVPLTAC -> G
FT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_047035"
FT VAR_SEQ 64..112
FT /note="IYSPDMPSRLPIQDIFAGLVTSIGTAIRYWFHYTLVAFAWLGVVPLTAC ->
FT S (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_047036"
FT VARIANT 622
FT /note="P -> L (in dbSNP:rs1062914)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_030251"
FT MUTAGEN 9
FT /note="C->A: Abolishes auto-ubiquitination. Loss of
FT ubiquitin ligase activity."
FT /evidence="ECO:0000269|PubMed:15673284,
FT ECO:0000269|PubMed:24449766"
FT CONFLICT 380
FT /note="V -> VG (in Ref. 6; AAB66840)"
FT /evidence="ECO:0000305"
FT CONFLICT 384
FT /note="G -> GS (in Ref. 6; AAB66840)"
FT /evidence="ECO:0000305"
FT CONFLICT 390
FT /note="C -> WW (in Ref. 6; AAB66840)"
FT /evidence="ECO:0000305"
FT CONFLICT 395
FT /note="D -> G (in Ref. 6; AAB66840)"
FT /evidence="ECO:0000305"
FT CONFLICT 399
FT /note="L -> LG (in Ref. 6; AAB66840)"
FT /evidence="ECO:0000305"
FT CONFLICT 546
FT /note="R -> K (in Ref. 6; AAB66840)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 910 AA; 102545 MW; C7A96FEA45B5CA8D CRC64;
MDTAEEDICR VCRSEGTPEK PLYHPCVCTG SIKFIHQECL VQWLKHSRKE YCELCKHRFA
FTPIYSPDMP SRLPIQDIFA GLVTSIGTAI RYWFHYTLVA FAWLGVVPLT ACRIYKCLFT
GSVSSLLTLP LDMLSTENLL ADCLQGCFVV TCTLCAFISL VWLREQIVHG GAPIWLEHAA
PPFNAAGHHQ NEAPAGGNGA ENVAADQPAN PPAENAVVGE NPDAQDDQAE EEEEDNEEED
DAGVEDAADA NNGAQDDMNW NALEWDRAAE ELTWERMLGL DGSLVFLEHV FWVVSLNTLF
ILVFAFCPYH IGHFSLVGLG FEEHVQASHF EGLITTIVGY ILLAITLIIC HGLATLVKFH
RSRRLLGVCY IVVKVSLLVV VEIGVFPLIC GWWLDICSLE MFDATLKDRE LSFQSAPGTT
MFLHWLVGMV YVFYFASFIL LLREVLRPGV LWFLRNLNDP DFNPVQEMIH LPIYRHLRRF
ILSVIVFGSI VLLMLWLPIR IIKSVLPNFL PYNVMLYSDA PVSELSLELL LLQVVLPALL
EQGHTRQWLK GLVRAWTVTA GYLLDLHSYL LGDQEENENS ANQQVNNNQH ARNNNAIPVV
GEGLHAAHQA ILQQGGPVGF QPYRRPLNFP LRIFLLIVFM CITLLIASLI CLTLPVFAGR
WLMSFWTGTA KIHELYTAAC GLYVCWLTIR AVTVMVAWMP QGRRVIFQKV KEWSLMIMKT
LIVAVLLAGV VPLLLGLLFE LVIVAPLRVP LDQTPLFYPW QDWALGVLHA KIIAAITLMG
PQWWLKTVIE QVYANGIRNI DLHYIVRKLA APVISVLLLS LCVPYVIASG VVPLLGVTAE
MQNLVHRRIY PFLLMVVVLM AILSFQVRQF KRLYEHIKND KYLVGQRLVN YERKSGKQGS
SPPPPQSSQE
