MGRN1_HUMAN
ID MGRN1_HUMAN Reviewed; 552 AA.
AC O60291; A4URL3; A4URL4; Q86W76;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 25-JUL-2006, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=E3 ubiquitin-protein ligase MGRN1;
DE EC=2.3.2.27;
DE AltName: Full=Mahogunin RING finger protein 1;
DE AltName: Full=RING finger protein 156;
DE AltName: Full=RING-type E3 ubiquitin transferase MGRN1 {ECO:0000305};
GN Name=MGRN1; Synonyms=KIAA0544, RNF156;
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 [MRNA] (ISOFORMS 3 AND 4), FUNCTION, INTERACTION WITH
RP MC1R AND MC4R, AND SUBCELLULAR LOCATION.
RX PubMed=19737927; DOI=10.1074/jbc.m109.028100;
RA Perez-Oliva A.B., Olivares C., Jimenez-Cervantes C., Garcia-Borron J.C.;
RT "Mahogunin ring finger-1 (MGRN1) E3 ubiquitin ligase inhibits signaling
RT from melanocortin receptor by competition with Galphas.";
RL J. Biol. Chem. 284:31714-31725(2009).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Leukocyte;
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 [5]
RP FUNCTION, INTERACTION WITH TSG101, MUTAGENESIS OF 406-PRO--PRO-409, AND
RP SUBCELLULAR LOCATION.
RX PubMed=17229889; DOI=10.1091/mbc.e06-09-0787;
RA Kim B.Y., Olzmann J.A., Barsh G.S., Chin L.S., Li L.;
RT "Spongiform neurodegeneration-associated E3 ligase Mahogunin ubiquitylates
RT TSG101 and regulates endosomal trafficking.";
RL Mol. Biol. Cell 18:1129-1142(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-524, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP FUNCTION, AND INTERACTION WITH TSG101.
RX PubMed=19703557; DOI=10.1016/j.bbadis.2009.08.009;
RA Jiao J., Sun K., Walker W.P., Bagher P., Cota C.D., Gunn T.M.;
RT "Abnormal regulation of TSG101 in mice with spongiform neurodegeneration.";
RL Biochim. Biophys. Acta 1792:1027-1035(2009).
RN [8]
RP MYRISTOYLATION AT GLY-2.
RX PubMed=20213681; DOI=10.1002/pmic.200900783;
RA Suzuki T., Moriya K., Nagatoshi K., Ota Y., Ezure T., Ando E.,
RA Tsunasawa S., Utsumi T.;
RT "Strategy for comprehensive identification of human N-myristoylated
RT proteins using an insect cell-free protein synthesis system.";
RL Proteomics 10:1780-1793(2010).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [10]
RP IDENTIFICATION BY MASS 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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-524, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
CC -!- FUNCTION: E3 ubiquitin-protein ligase. Mediates monoubiquitination at
CC multiple sites of TSG101 in the presence of UBE2D1, but not of UBE2G1,
CC nor UBE2H. Plays a role in the regulation of endosome-to-lysosome
CC trafficking. Impairs MC1R- and MC4R-signaling by competing with GNAS-
CC binding to MCRs and inhibiting agonist-induced cAMP production. Does
CC not inhibit ADRB2-signaling. Does not promote MC1R ubiquitination. Acts
CC also as a negative regulator of hedgehog signaling (By similarity).
CC {ECO:0000250|UniProtKB:Q9D074, ECO:0000269|PubMed:17229889,
CC ECO:0000269|PubMed:19703557, ECO:0000269|PubMed:19737927}.
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: Interacts with MC1R and MC4R, but not with TBXA2R. Interacts
CC with TSG101. Interacts with mislocalized cytosolically exposed PRNP;
CC this interaction alters MGRN1 subcellular location and causes lysosomal
CC enlargement (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC O60291; Q99816: TSG101; NbExp=5; IntAct=EBI-2129851, EBI-346882;
CC -!- SUBCELLULAR LOCATION: Early endosome {ECO:0000269|PubMed:17229889,
CC ECO:0000269|PubMed:19737927}. Note=The endosomal localization is
CC dependent on the interaction with TSG101.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm, cytosol. Nucleus.
CC Note=Translocation from the cytosol to the nucleus is seen only in the
CC presence of MC1R and MC4R, but not TBXA2R. Excluded from nucleoli.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm, cytosol. Nucleus.
CC Note=Translocation from the cytosol to the nucleus is seen only in the
CC presence of MC1R and MC4R, but not TBXA2R. Excluded from nucleoli.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm, cytosol. Cell membrane.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Cytoplasm, cytosol. Cell membrane.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=(+)S;
CC IsoId=O60291-1; Sequence=Displayed;
CC Name=2; Synonyms=(+)L;
CC IsoId=O60291-2; Sequence=VSP_019853;
CC Name=3; Synonyms=(-)L;
CC IsoId=O60291-3; Sequence=VSP_036462, VSP_019853;
CC Name=4; Synonyms=(-)S;
CC IsoId=O60291-4; Sequence=VSP_036462;
CC -!- DOMAIN: The RING finger is required for ubiquitin ligase activity.
CC {ECO:0000250}.
CC -!- PTM: Autoubiquitinated in vitro. {ECO:0000250}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA25470.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; EF471397; ABO69623.2; -; mRNA.
DR EMBL; EF471398; ABO69624.2; -; mRNA.
DR EMBL; AB011116; BAA25470.1; ALT_INIT; mRNA.
DR EMBL; AC023830; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC050389; AAH50389.1; -; mRNA.
DR CCDS; CCDS42115.1; -. [O60291-2]
DR CCDS; CCDS45401.2; -. [O60291-4]
DR CCDS; CCDS45402.1; -. [O60291-1]
DR CCDS; CCDS59256.1; -. [O60291-3]
DR RefSeq; NP_001135761.2; NM_001142289.2. [O60291-3]
DR RefSeq; NP_001135762.1; NM_001142290.2. [O60291-1]
DR RefSeq; NP_001135763.2; NM_001142291.2. [O60291-4]
DR RefSeq; NP_056061.1; NM_015246.3. [O60291-2]
DR RefSeq; XP_005255277.1; XM_005255220.3.
DR RefSeq; XP_005255278.1; XM_005255221.3.
DR AlphaFoldDB; O60291; -.
DR BioGRID; 116890; 149.
DR ELM; O60291; -.
DR IntAct; O60291; 33.
DR MINT; O60291; -.
DR STRING; 9606.ENSP00000262370; -.
DR iPTMnet; O60291; -.
DR PhosphoSitePlus; O60291; -.
DR BioMuta; MGRN1; -.
DR EPD; O60291; -.
DR jPOST; O60291; -.
DR MassIVE; O60291; -.
DR MaxQB; O60291; -.
DR PaxDb; O60291; -.
DR PeptideAtlas; O60291; -.
DR PRIDE; O60291; -.
DR ProteomicsDB; 49319; -. [O60291-1]
DR ProteomicsDB; 49320; -. [O60291-2]
DR ProteomicsDB; 49321; -. [O60291-3]
DR ProteomicsDB; 49322; -. [O60291-4]
DR Antibodypedia; 2013; 263 antibodies from 28 providers.
DR DNASU; 23295; -.
DR Ensembl; ENST00000262370.12; ENSP00000262370.6; ENSG00000102858.13. [O60291-2]
DR Ensembl; ENST00000399577.9; ENSP00000382487.4; ENSG00000102858.13. [O60291-1]
DR Ensembl; ENST00000415496.5; ENSP00000393311.2; ENSG00000102858.13. [O60291-4]
DR Ensembl; ENST00000586183.5; ENSP00000465860.1; ENSG00000102858.13. [O60291-4]
DR Ensembl; ENST00000588994.5; ENSP00000468819.1; ENSG00000102858.13. [O60291-3]
DR GeneID; 23295; -.
DR KEGG; hsa:23295; -.
DR MANE-Select; ENST00000262370.12; ENSP00000262370.6; NM_015246.4; NP_056061.1. [O60291-2]
DR UCSC; uc002cwz.4; human. [O60291-1]
DR CTD; 23295; -.
DR DisGeNET; 23295; -.
DR GeneCards; MGRN1; -.
DR HGNC; HGNC:20254; MGRN1.
DR HPA; ENSG00000102858; Low tissue specificity.
DR MIM; 607559; gene.
DR neXtProt; NX_O60291; -.
DR OpenTargets; ENSG00000102858; -.
DR PharmGKB; PA134941221; -.
DR VEuPathDB; HostDB:ENSG00000102858; -.
DR eggNOG; KOG4265; Eukaryota.
DR GeneTree; ENSGT00390000009925; -.
DR InParanoid; O60291; -.
DR OMA; CAQSGPP; -.
DR OrthoDB; 883624at2759; -.
DR PhylomeDB; O60291; -.
DR TreeFam; TF314969; -.
DR PathwayCommons; O60291; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; O60291; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 23295; 22 hits in 1125 CRISPR screens.
DR ChiTaRS; MGRN1; human.
DR GenomeRNAi; 23295; -.
DR Pharos; O60291; Tbio.
DR PRO; PR:O60291; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; O60291; protein.
DR Bgee; ENSG00000102858; Expressed in right hemisphere of cerebellum and 166 other tissues.
DR ExpressionAtlas; O60291; baseline and differential.
DR Genevisible; O60291; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0008333; P:endosome to lysosome transport; IMP:UniProtKB.
DR GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; IDA:UniProtKB.
DR GO; GO:0045744; P:negative regulation of G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; ISS:UniProtKB.
DR GO; GO:0006513; P:protein monoubiquitination; IMP:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IEA:Ensembl.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR CDD; cd16789; mRING-HC-C3HC5_MGRN1_like---blasttree; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR045194; MGRN1/RNF157-like.
DR InterPro; IPR045195; MGRN1/RNF157_mRING_C3HC5.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR22996; PTHR22996; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cytoplasm; Endosome; Lipoprotein;
KW Membrane; Metal-binding; Myristate; Nucleus; Phosphoprotein;
KW Reference proteome; Transferase; Ubl conjugation; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..552
FT /note="E3 ubiquitin-protein ligase MGRN1"
FT /id="PRO_0000246687"
FT ZN_FING 278..317
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 355..384
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 439..552
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 406..409
FT /note="Required for TSG101-binding"
FT COMPBIAS 443..458
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 491..522
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 411
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9D074"
FT MOD_RES 471
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D074"
FT MOD_RES 524
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:20213681"
FT VAR_SEQ 356..377
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:19737927"
FT /id="VSP_036462"
FT VAR_SEQ 540..552
FT /note="ALGPDSCSVGIDE -> GRPTSMETAHGLATTSPTWPPLGGPSPDPSAAELT
FT PL (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:19737927"
FT /id="VSP_019853"
FT MUTAGEN 406..409
FT /note="PSAP->ASAA: Loss of TSG101-binding and drastic
FT reduction of TSG101-ubiquitination."
FT /evidence="ECO:0000269|PubMed:17229889"
FT CONFLICT 248
FT /note="Y -> H (in Ref. 1; ABO69623/ABO69624)"
FT /evidence="ECO:0000305"
FT CONFLICT 537
FT /note="Y -> H (in Ref. 1; ABO69623/ABO69624)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 552 AA; 60753 MW; 1F923D25FB49DB4D CRC64;
MGSILSRRIA GVEDIDIQAN SAYRYPPKSG NYFASHFFMG GEKFDTPHPE GYLFGENMDL
NFLGSRPVQF PYVTPAPHEP VKTLRSLVNI RKDSLRLVRY KDDADSPTED GDKPRVLYSL
EFTFDADARV AITIYCQASE EFLNGRAVYS PKSPSLQSET VHYKRGVSQQ FSLPSFKIDF
SEWKDDELNF DLDRGVFPVV IQAVVDEGDV VEVTGHAHVL LAAFEKHMDG SFSVKPLKQK
QIVDRVSYLL QEIYGIENKN NQETKPSDDE NSDNSNECVV CLSDLRDTLI LPCRHLCLCT
SCADTLRYQA NNCPICRLPF RALLQIRAVR KKPGALSPVS FSPVLAQSLE HDEHSCPFKK
SKPHPASLAS KKPKRETNSD SVPPGYEPIS LLEALNGLRA VSPAIPSAPL YEEITYSGIS
DGLSQASCPL AAIDHILDSS RQKGRPQSKA PDSTLRSPSS PIHEEDEEKL SEDVDAPPPL
GGAELALRES SSPESFITEE VDESSSPQQG TRAASIENVL QDSSPEHCGR GPPADIYLPA
LGPDSCSVGI DE
