MARH6_MOUSE
ID MARH6_MOUSE Reviewed; 909 AA.
AC Q6ZQ89; Q6PCS1; Q80V02; Q80VC7; Q8BJA0; Q8BXX6;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=E3 ubiquitin-protein ligase MARCHF6;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:O60337};
DE AltName: Full=Membrane-associated RING finger protein 6;
DE AltName: Full=Membrane-associated RING-CH protein VI;
DE Short=MARCH-VI;
DE AltName: Full=RING-type E3 ubiquitin transferase MARCHF6 {ECO:0000305};
GN Name=Marchf6; Synonyms=Kiaa0597, March6;
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] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 476-909 (ISOFORM 1).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Cerebellum, and Spleen;
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] OF 348-883 (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 383-909 (ISOFORM 1).
RC STRAIN=Czech II, and FVB/N; TISSUE=Mammary gland;
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).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that promotes 'Lys-48'-linked
CC ubiquitination of target proteins, leading to their proteasomal
CC degradation. Promotes ubiquitination of DIO2, leading to its
CC degradation. Promotes ubiquitination of SQLE, leading to its
CC degradation. E3 ubiquitin ligases accept ubiquitin from an E2
CC ubiquitin-conjugating enzyme in the form of a thioester and then
CC directly transfer the ubiquitin to targeted substrates. May cooperate
CC with UBE2G1. {ECO:0000250|UniProtKB:O60337}.
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:0000250|UniProtKB:O60337};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:O60337}.
CC -!- SUBUNIT: Interacts with DIO2. Interacts with SQLE.
CC {ECO:0000250|UniProtKB:O60337}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:O60337}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:O60337}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6ZQ89-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6ZQ89-2; Sequence=VSP_022702, VSP_022703;
CC Name=3;
CC IsoId=Q6ZQ89-3; Sequence=VSP_022704;
CC -!- DOMAIN: The RING-CH-type zinc finger domain is required for E3 ligase
CC activity. {ECO:0000255|PROSITE-ProRule:PRU00623}.
CC -!- PTM: Auto-ubiquitinated, which results in proteasomal degradation.
CC {ECO:0000250|UniProtKB:O60337}.
CC -!- SIMILARITY: Belongs to the DOA10/MARCHF6 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH37454.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK042980; BAC31427.1; -; mRNA.
DR EMBL; AK089827; BAC40971.1; -; mRNA.
DR EMBL; AK129169; BAC97979.1; -; Transcribed_RNA.
DR EMBL; BC037454; AAH37454.1; ALT_INIT; mRNA.
DR EMBL; BC048816; AAH48816.1; -; mRNA.
DR EMBL; BC059190; AAH59190.2; -; mRNA.
DR CCDS; CCDS37054.1; -. [Q6ZQ89-1]
DR RefSeq; NP_766194.2; NM_172606.2. [Q6ZQ89-1]
DR AlphaFoldDB; Q6ZQ89; -.
DR SMR; Q6ZQ89; -.
DR STRING; 10090.ENSMUSP00000087694; -.
DR iPTMnet; Q6ZQ89; -.
DR PhosphoSitePlus; Q6ZQ89; -.
DR EPD; Q6ZQ89; -.
DR MaxQB; Q6ZQ89; -.
DR PaxDb; Q6ZQ89; -.
DR PeptideAtlas; Q6ZQ89; -.
DR PRIDE; Q6ZQ89; -.
DR ProteomicsDB; 295825; -. [Q6ZQ89-1]
DR ProteomicsDB; 295826; -. [Q6ZQ89-2]
DR ProteomicsDB; 295827; -. [Q6ZQ89-3]
DR Antibodypedia; 22463; 154 antibodies from 29 providers.
DR DNASU; 223455; -.
DR Ensembl; ENSMUST00000090227; ENSMUSP00000087694; ENSMUSG00000039100. [Q6ZQ89-1]
DR GeneID; 223455; -.
DR KEGG; mmu:223455; -.
DR UCSC; uc007vkh.1; mouse. [Q6ZQ89-1]
DR CTD; 10299; -.
DR MGI; MGI:2442773; Marchf6.
DR VEuPathDB; HostDB:ENSMUSG00000039100; -.
DR eggNOG; KOG1609; Eukaryota.
DR GeneTree; ENSGT00940000155171; -.
DR HOGENOM; CLU_006373_1_0_1; -.
DR InParanoid; Q6ZQ89; -.
DR OMA; WLPIRIL; -.
DR OrthoDB; 170933at2759; -.
DR PhylomeDB; Q6ZQ89; -.
DR TreeFam; TF105777; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 223455; 2 hits in 46 CRISPR screens.
DR ChiTaRS; March6; mouse.
DR PRO; PR:Q6ZQ89; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q6ZQ89; protein.
DR Bgee; ENSMUSG00000039100; Expressed in extensor digitorum longus and 255 other tissues.
DR Genevisible; Q6ZQ89; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; ISO:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISO:MGI.
DR GO; GO:1990381; F:ubiquitin-specific protease binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0010498; P:proteasomal protein catabolic process; ISO:MGI.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISS: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 2: Evidence at transcript level;
KW Acetylation; Alternative splicing; Endoplasmic reticulum; Membrane;
KW Metal-binding; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix; Ubl conjugation; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..909
FT /note="E3 ubiquitin-protein ligase MARCHF6"
FT /id="PRO_0000274299"
FT TOPO_DOM 1..91
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O60337"
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..631
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 632..652
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 653..677
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 678..698
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 699..720
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 721..741
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 742..763
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 764..784
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 785..814
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 815..835
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 836..847
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 848..868
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 869..909
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O60337"
FT ZN_FING 1..62
FT /note="RING-CH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT REGION 186..256
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 225..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:0000250|UniProtKB:O60337"
FT VAR_SEQ 625..821
FT /note="PLNFPLRIFLLIVFMCITLLIASLICLTLPVFAGRWLMSFWTGTAKIHELYT
FT AACGLYVCWLTIRAVTVLVAWMPQGRRVIFQKVKEWSLMIMKTLIVAVLLAGVVPLLLG
FT LLFELVIVAPLRVPLDQTPLFYPWQDWALGVLHAKIIAAITLMGPQWWLKTVIEQVYAN
FT GIRNIDLHYIIRKLAAPVISVLLLSLC -> LPRWAPSHWQGLLSCVLCPVAFRKMMSS
FT WGFIVHNIC (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_022702"
FT VAR_SEQ 683..708
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14621295"
FT /id="VSP_022704"
FT VAR_SEQ 822..909
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_022703"
FT CONFLICT 476
FT /note="H -> N (in Ref. 1; BAC31427)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 909 AA; 102273 MW; DC46CB2A34B6F749 CRC64;
MDTAEEDICR VCRSEGTPEK PLYHPCVCTG SIKFIHQECL VQWLKHSRKE YCELCKHRFA
FTPIYSPDMP SRLPIQDIFA GLVTSIGTAI RYWFHYTLVA FAWLGVVPLT ACRIYKCLFT
GSVSSLLTLP LDMLSTENLL ADCLQGCFVV TCTLCAFISL VWLREQIVHG GAPIWLEHAA
PPFNAAGHHQ NEAPVGGNGA ENPAADQPAN PAGENAVLGE NPDAQDGQAE EEEEDNEEED
DAGVEDAADA NNGAQDDMNW NALEWDRAAE ELTWERMLGL DGSLVFLEHV FWVVSLNTLF
ILVFAFCPYH IGHFSLVGLG FEEHVQASHF EGLITTIVGY ILLAITLIIC HALATLVKFH
RSRRLLGVCY IVVKVSLLVV VEIGVFPLIC GWWLDICSLE MFDATLKDRE LSFQSAPGTT
MFLHWLVGMV YVFYFASFIL LLREVLRPGV LWFLRNLNDP DFNPVQEMIH LPIYRHLRRF
ILSVIVFGSI VLLMLWLPIR IIKSLLPNFL PYNVMLYSDA PVSELSLELL LLQVVLPALL
EQGHTRQWLK GLVRAWTVTA GYLLDLHSYL LGDQEENENS ANQQVNNNQP ARNNNAVPAG
EGLHAAHQAI LQQGGPVGFQ PYRRPLNFPL RIFLLIVFMC ITLLIASLIC LTLPVFAGRW
LMSFWTGTAK IHELYTAACG LYVCWLTIRA VTVLVAWMPQ GRRVIFQKVK EWSLMIMKTL
IVAVLLAGVV PLLLGLLFEL VIVAPLRVPL DQTPLFYPWQ DWALGVLHAK IIAAITLMGP
QWWLKTVIEQ VYANGIRNID LHYIIRKLAA PVISVLLLSL CVPYVIASGA VPLLGVTAEM
QNLVHRRIYP FLLMVVVLMG ILSFQVRQFK RLYEHIKNDK YLVGQRLVNY ERKSGKQGPS
TPPPVSSQE
