O60291 (MGRN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase MGRN1
EC=6.3.2.-

Alternative name(s):
Mahogunin RING finger protein 1
RING finger protein 156

Gene names

Name:	MGRN1
Synonyms:	KIAA0544, RNF156

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	552 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	E3 ubiquitin-protein ligase. Mediates monoubiquitination at multiple sites of TSG101 in the presence of UBE2D1, but not of UBE2G1, nor UBE2H. Plays a role in the regulation of endosome-to-lysosome trafficking. Impairs MC1R- and MC4R-signaling by competing with GNAS-binding to MCRs and inhibiting agonist-induced cAMP production. Does not inhibit ADRB2-signaling. Does not promote MC1R ubiquitination. Ref.1 Ref.5 Ref.7
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with MC1R and MC4R, but not with TBXA2R. Interacts with TSG101. Interacts with mislocalized cytosolically exposed PRNP; this interaction alters MGRN1 subcellular location and causes lysosomal enlargement By similarity. Ref.1 Ref.5 Ref.7
Subcellular location	Early endosome. Note: The endosomal localization is dependent on the interaction with TSG101. Ref.1 Ref.5 Isoform 1: Cytoplasm › cytosol. Nucleus. Note: Translocation from the cytosol to the nucleus is seen only in the presence of MC1R and MC4R, but not TBXA2R. Excluded from nucleoli. Ref.1 Ref.5 Isoform 2: Cytoplasm › cytosol. Nucleus. Note: Translocation from the cytosol to the nucleus is seen only in the presence of MC1R and MC4R, but not TBXA2R. Excluded from nucleoli. Ref.1 Ref.5 Isoform 3: Cytoplasm › cytosol. Cell membrane Ref.1 Ref.5. Isoform 4: Cytoplasm › cytosol. Cell membrane Ref.1 Ref.5.
Domain	The RING finger is required for ubiquitin ligase activity By similarity.
Post-translational modification	Autoubiquitinated in vitro By similarity.
Sequence similarities	Contains 1 RING-type zinc finger.
Sequence caution	The sequence BAA25470.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cell membrane Cytoplasm Endosome Membrane Nucleus
Coding sequence diversity	Alternative splicing
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Lipoprotein Myristate Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	endosome to lysosome transport Inferred from mutant phenotype Ref.5. Source: UniProtKB negative regulation of G-protein coupled receptor protein signaling pathway Inferred from direct assay Ref.1. Source: UniProtKB negative regulation of cAMP-mediated signaling Inferred from direct assay Ref.1. Source: UniProtKB protein monoubiquitination Inferred from mutant phenotype Ref.5. Source: UniProtKB protein polyubiquitination Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell early endosome Inferred from direct assay Ref.5. Source: UniProtKB nucleus Inferred from direct assay Ref.5Ref.1. Source: UniProtKB plasma membrane Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	ubiquitin-protein ligase activity Inferred from direct assay Ref.5Ref.1. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O60291-1)

Also known as: (+)S;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O60291-2)

Also known as: (+)L;

The sequence of this isoform differs from the canonical sequence as follows:
     540-552: ALGPDSCSVGIDE → GRPTSMETAHGLATTSPTWPPLGGPSPDPSAAELTPL

Isoform 3 (identifier: O60291-3)

Also known as: (-)L;

The sequence of this isoform differs from the canonical sequence as follows:
     356-377: Missing.
     540-552: ALGPDSCSVGIDE → GRPTSMETAHGLATTSPTWPPLGGPSPDPSAAELTPL

Isoform 4 (identifier: O60291-4)

Also known as: (-)S;

The sequence of this isoform differs from the canonical sequence as follows:
     356-377: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 552	552	E3 ubiquitin-protein ligase MGRN1		PRO_0000246687
Regions
	Zinc finger	278 – 317	40	RING-type
	Motif	406 – 409	4	Required for TSG101-binding
Amino acid modifications
	Modified residue	524	1	Phosphoserine Ref.6
	Lipidation	2	1	N-myristoyl glycine Ref.8
Natural variations
	Alternative sequence	356 – 377	22	Missing in isoform 3 and isoform 4.		VSP_036462
	Alternative sequence	540 – 552	13	ALGPD…VGIDE → GRPTSMETAHGLATTSPTWP PLGGPSPDPSAAELTPL in isoform 2 and isoform 3.		VSP_019853
Experimental info
	Mutagenesis	406 – 409	4	PSAP → ASAA: Loss of TSG101-binding and drastic reduction of TSG101-ubiquitination. Ref.5
	Sequence conflict	248	1	Y → H in ABO69623. Ref.1
	Sequence conflict	248	1	Y → H in ABO69624. Ref.1
	Sequence conflict	537	1	Y → H in ABO69623. Ref.1
	Sequence conflict	537	1	Y → H in ABO69624. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 ((+)S) [UniParc]. Last modified July 25, 2006. Version 2. Checksum: 1F923D25FB49DB4D	FASTA	552	60,753
	10 20 30 40 50 60 MGSILSRRIA GVEDIDIQAN SAYRYPPKSG NYFASHFFMG GEKFDTPHPE GYLFGENMDL 70 80 90 100 110 120 NFLGSRPVQF PYVTPAPHEP VKTLRSLVNI RKDSLRLVRY KDDADSPTED GDKPRVLYSL 130 140 150 160 170 180 EFTFDADARV AITIYCQASE EFLNGRAVYS PKSPSLQSET VHYKRGVSQQ FSLPSFKIDF 190 200 210 220 230 240 SEWKDDELNF DLDRGVFPVV IQAVVDEGDV VEVTGHAHVL LAAFEKHMDG SFSVKPLKQK 250 260 270 280 290 300 QIVDRVSYLL QEIYGIENKN NQETKPSDDE NSDNSNECVV CLSDLRDTLI LPCRHLCLCT 310 320 330 340 350 360 SCADTLRYQA NNCPICRLPF RALLQIRAVR KKPGALSPVS FSPVLAQSLE HDEHSCPFKK 370 380 390 400 410 420 SKPHPASLAS KKPKRETNSD SVPPGYEPIS LLEALNGLRA VSPAIPSAPL YEEITYSGIS 430 440 450 460 470 480 DGLSQASCPL AAIDHILDSS RQKGRPQSKA PDSTLRSPSS PIHEEDEEKL SEDVDAPPPL 490 500 510 520 530 540 GGAELALRES SSPESFITEE VDESSSPQQG TRAASIENVL QDSSPEHCGR GPPADIYLPA 550 LGPDSCSVGI DE
	Isoform 2 ((+)L) [UniParc]. Checksum: 220A9470E51853B9	FASTA	576	63,190
	10 20 30 40 50 60 MGSILSRRIA GVEDIDIQAN SAYRYPPKSG NYFASHFFMG GEKFDTPHPE GYLFGENMDL 70 80 90 100 110 120 NFLGSRPVQF PYVTPAPHEP VKTLRSLVNI RKDSLRLVRY KDDADSPTED GDKPRVLYSL 130 140 150 160 170 180 EFTFDADARV AITIYCQASE EFLNGRAVYS PKSPSLQSET VHYKRGVSQQ FSLPSFKIDF 190 200 210 220 230 240 SEWKDDELNF DLDRGVFPVV IQAVVDEGDV VEVTGHAHVL LAAFEKHMDG SFSVKPLKQK 250 260 270 280 290 300 QIVDRVSYLL QEIYGIENKN NQETKPSDDE NSDNSNECVV CLSDLRDTLI LPCRHLCLCT 310 320 330 340 350 360 SCADTLRYQA NNCPICRLPF RALLQIRAVR KKPGALSPVS FSPVLAQSLE HDEHSCPFKK 370 380 390 400 410 420 SKPHPASLAS KKPKRETNSD SVPPGYEPIS LLEALNGLRA VSPAIPSAPL YEEITYSGIS 430 440 450 460 470 480 DGLSQASCPL AAIDHILDSS RQKGRPQSKA PDSTLRSPSS PIHEEDEEKL SEDVDAPPPL 490 500 510 520 530 540 GGAELALRES SSPESFITEE VDESSSPQQG TRAASIENVL QDSSPEHCGR GPPADIYLPG 550 560 570 RPTSMETAHG LATTSPTWPP LGGPSPDPSA AELTPL
	Isoform 3 ((-)L) [UniParc]. Checksum: A7D83CB4E643D35E	FASTA	554	60,742
	10 20 30 40 50 60 MGSILSRRIA GVEDIDIQAN SAYRYPPKSG NYFASHFFMG GEKFDTPHPE GYLFGENMDL 70 80 90 100 110 120 NFLGSRPVQF PYVTPAPHEP VKTLRSLVNI RKDSLRLVRY KDDADSPTED GDKPRVLYSL 130 140 150 160 170 180 EFTFDADARV AITIYCQASE EFLNGRAVYS PKSPSLQSET VHYKRGVSQQ FSLPSFKIDF 190 200 210 220 230 240 SEWKDDELNF DLDRGVFPVV IQAVVDEGDV VEVTGHAHVL LAAFEKHMDG SFSVKPLKQK 250 260 270 280 290 300 QIVDRVSYLL QEIYGIENKN NQETKPSDDE NSDNSNECVV CLSDLRDTLI LPCRHLCLCT 310 320 330 340 350 360 SCADTLRYQA NNCPICRLPF RALLQIRAVR KKPGALSPVS FSPVLAQSLE HDEHSNSDSV 370 380 390 400 410 420 PPGYEPISLL EALNGLRAVS PAIPSAPLYE EITYSGISDG LSQASCPLAA IDHILDSSRQ 430 440 450 460 470 480 KGRPQSKAPD STLRSPSSPI HEEDEEKLSE DVDAPPPLGG AELALRESSS PESFITEEVD 490 500 510 520 530 540 ESSSPQQGTR AASIENVLQD SSPEHCGRGP PADIYLPGRP TSMETAHGLA TTSPTWPPLG 550 GPSPDPSAAE LTPL
	Isoform 4 ((-)S) [UniParc]. Checksum: ECFFB3444A87127A	FASTA	530	58,305
	10 20 30 40 50 60 MGSILSRRIA GVEDIDIQAN SAYRYPPKSG NYFASHFFMG GEKFDTPHPE GYLFGENMDL 70 80 90 100 110 120 NFLGSRPVQF PYVTPAPHEP VKTLRSLVNI RKDSLRLVRY KDDADSPTED GDKPRVLYSL 130 140 150 160 170 180 EFTFDADARV AITIYCQASE EFLNGRAVYS PKSPSLQSET VHYKRGVSQQ FSLPSFKIDF 190 200 210 220 230 240 SEWKDDELNF DLDRGVFPVV IQAVVDEGDV VEVTGHAHVL LAAFEKHMDG SFSVKPLKQK 250 260 270 280 290 300 QIVDRVSYLL QEIYGIENKN NQETKPSDDE NSDNSNECVV CLSDLRDTLI LPCRHLCLCT 310 320 330 340 350 360 SCADTLRYQA NNCPICRLPF RALLQIRAVR KKPGALSPVS FSPVLAQSLE HDEHSNSDSV 370 380 390 400 410 420 PPGYEPISLL EALNGLRAVS PAIPSAPLYE EITYSGISDG LSQASCPLAA IDHILDSSRQ 430 440 450 460 470 480 KGRPQSKAPD STLRSPSSPI HEEDEEKLSE DVDAPPPLGG AELALRESSS PESFITEEVD 490 500 510 520 530 ESSSPQQGTR AASIENVLQD SSPEHCGRGP PADIYLPALG PDSCSVGIDE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mahogunin ring finger-1 (MGRN1) E3 ubiquitin ligase inhibits signaling from melanocortin receptor by competition with Galphas." Perez-Oliva A.B., Olivares C., Jimenez-Cervantes C., Garcia-Borron J.C. J. Biol. Chem. 284:31714-31725(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), FUNCTION, INTERACTION WITH MC1R AND MC4R, SUBCELLULAR LOCATION.
[2]	"Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:31-39(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[3]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Leukocyte.
[5]	"Spongiform neurodegeneration-associated E3 ligase Mahogunin ubiquitylates TSG101 and regulates endosomal trafficking." Kim B.Y., Olzmann J.A., Barsh G.S., Chin L.S., Li L. Mol. Biol. Cell 18:1129-1142(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH TSG101, MUTAGENESIS OF 406-PRO--PRO-409, SUBCELLULAR LOCATION.
[6]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-524, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"Abnormal regulation of TSG101 in mice with spongiform neurodegeneration." Jiao J., Sun K., Walker W.P., Bagher P., Cota C.D., Gunn T.M. Biochim. Biophys. Acta 1792:1027-1035(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH TSG101.
[8]	"Strategy for comprehensive identification of human N-myristoylated proteins using an insect cell-free protein synthesis system." Suzuki T., Moriya K., Nagatoshi K., Ota Y., Ezure T., Ando E., Tsunasawa S., Utsumi T. Proteomics 10:1780-1793(2010) [PubMed] [Europe PMC] [Abstract] Cited for: MYRISTOYLATION AT GLY-2.
[9]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	EF471397 mRNA. Translation: ABO69623.2. EF471398 mRNA. Translation: ABO69624.2. AB011116 mRNA. Translation: BAA25470.1. Different initiation. AC023830 Genomic DNA. No translation available. BC050389 mRNA. Translation: AAH50389.1.
IPI	IPI00297251. IPI00643212. IPI00915351. IPI00915359.
RefSeq	NP_001135761.2. NM_001142289.2. NP_001135762.1. NM_001142290.2. NP_001135763.2. NM_001142291.2. NP_056061.1. NM_015246.3.
UniGene	Hs.526494.
3D structure databases
ProteinModelPortal	O60291.
ModBase	Search...
Protein-protein interaction databases
IntAct	O60291. 12 interactions.
STRING	9606.ENSP00000262370.
Proteomic databases
PaxDb	O60291.
PRIDE	O60291.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000262370; ENSP00000262370; ENSG00000102858. ENST00000399577; ENSP00000382487; ENSG00000102858. ENST00000586183; ENSP00000465860; ENSG00000102858. ENST00000588994; ENSP00000468819; ENSG00000102858.
GeneID	23295.
KEGG	hsa:23295.
UCSC	uc002cwz.3. human. uc002cxa.3. human. uc010uxo.2. human. uc010uxp.2. human.
Organism-specific databases
CTD	23295.
GeneCards	GC16P004641.
H-InvDB	HIX0012786.
HGNC	HGNC:20254. MGRN1.
HPA	HPA007653.
MIM	607559. gene.
neXtProt	NX_O60291.
PharmGKB	PA134941221.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG332026.
HOGENOM	HOG000231196.
HOVERGEN	HBG061762.
KO	K10604.
OMA	NGMAVYS.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
UniPathway	UPA00143.
Gene expression databases
ArrayExpress	O60291.
Bgee	O60291.
CleanEx	HS_MGRN1.
Genevestigator	O60291.
GermOnline	ENSG00000102858. Homo sapiens.
Family and domain databases
Gene3D	3.30.40.10. 1 hit.
InterPro	IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. [Graphical view]
SMART	SM00184. RING. 1 hit. [Graphical view]
PROSITE	PS00518. ZF_RING_1. False negative. PS50089. ZF_RING_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	MGRN1. human.
GenomeRNAi	23295.
NextBio	45124.
SOURCE	Search...

Entry information

Entry name

MGRN1_HUMAN

Accession

Primary (citable) accession number: O60291
Secondary accession number(s): A4URL3, A4URL4, Q86W76

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 25, 2006
Last sequence update:	July 25, 2006
Last modified:	May 1, 2013
This is version 95 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.