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   27-MAR-2024, entry version 136.
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   BioGRID; 230150; 1.
DR   STRING; 10090.ENSMUSP00000087694; -.
DR   iPTMnet; Q6ZQ89; -.
DR   PhosphoSitePlus; Q6ZQ89; -.
DR   EPD; Q6ZQ89; -.
DR   MaxQB; Q6ZQ89; -.
DR   PaxDb; 10090-ENSMUSP00000087694; -.
DR   PeptideAtlas; Q6ZQ89; -.
DR   ProteomicsDB; 295825; -. [Q6ZQ89-1]
DR   ProteomicsDB; 295826; -. [Q6ZQ89-2]
DR   ProteomicsDB; 295827; -. [Q6ZQ89-3]
DR   Antibodypedia; 22463; 175 antibodies from 29 providers.
DR   DNASU; 223455; -.
DR   Ensembl; ENSMUST00000090227.6; ENSMUSP00000087694.5; ENSMUSG00000039100.11. [Q6ZQ89-1]
DR   GeneID; 223455; -.
DR   KEGG; mmu:223455; -.
DR   UCSC; uc007vkh.1; mouse. [Q6ZQ89-1]
DR   AGR; MGI:2442773; -.
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; WLHYSLV; -.
DR   OrthoDB; 1342875at2759; -.
DR   PhylomeDB; Q6ZQ89; -.
DR   TreeFam; TF105777; -.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 223455; 2 hits in 48 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 259 other cell types or tissues.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR   GO; GO:0016020; C: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   CDD; cd16702; RING_CH-C4HC3_MARCH6; 1.
DR   Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
DR   InterPro; IPR011016; Znf_RING-CH.
DR   InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR   PANTHER; PTHR13145:SF0; E3 UBIQUITIN-PROTEIN LIGASE MARCHF6; 1.
DR   PANTHER; PTHR13145; SSM4 PROTEIN; 1.
DR   Pfam; PF12906; RINGv; 1.
DR   SMART; SM00744; RINGv; 1.
DR   SUPFAM; SSF57850; RING/U-box; 1.
DR   PROSITE; PS51292; ZF_RING_CH; 1.
DR   Genevisible; Q6ZQ89; MM.
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
//