E3 ubiquitin-protein ligase MARCH6 - Homo sapiens (Human)

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O60337 (MARH6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 94. History...

Clusters with 100%, 90%, 50% identity |

Documents (6) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase MARCH6
EC=6.3.2.-

Alternative name(s):
Doa10 homolog
Membrane-associated RING finger protein 6
Membrane-associated RING-CH protein VI
Short name=MARCH-VI
Protein TEB-4
RING finger protein 176

Gene names

Name:	MARCH6
Synonyms:	KIAA0597, RNF176, TEB4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	910 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	E3 ubiquitin-protein ligase that promotes ubiquitination of DIO2, leading to its degradation. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates. May cooperate with UBE2G1. Ref.6 Ref.8
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with DIO2. Ref.8
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.6.
Tissue specificity	Present in brain (at protein level). Ref.6
Domain	The RING-CH-type zinc finger domain is required for E3 ligase activity.
Post-translational modification	Auto-ubiquitinated, which results in proteasomal degradation.
Sequence similarities	Contains 1 RING-CH-type zinc finger.
Sequence caution	The sequence AAB66840.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAB66840.1 differs from that shown. Reason: Frameshift at positions 381, 382, 383, 385, 391, 396 and 418. The sequence BAA25523.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein K48-linked ubiquitination Inferred from direct assay Ref.6. Source: UniProtKB
Cellular_component	integral to endoplasmic reticulum membrane Inferred from direct assay Ref.6. Source: UniProtKB
Molecular_function	ubiquitin-protein ligase activity Inferred from direct assay Ref.6. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 910

910

E3 ubiquitin-protein ligase MARCH6

PRO_0000274298

Regions

Topological domain

1 – 91

Cytoplasmic Potential

Transmembrane

92 – 112

Helical; Potential

Topological domain

113 – 142

Extracellular Potential

Transmembrane

143 – 163

Helical; Potential

Topological domain

164 – 283

120

Cytoplasmic Potential

Transmembrane

284 – 304

Helical; Potential

Topological domain

305 – 336

Extracellular Potential

Transmembrane

337 – 357

Helical; Potential

Topological domain

358 – 376

Cytoplasmic Potential

Transmembrane

377 – 397

Helical; Potential

Topological domain

398 – 421

Extracellular Potential

Transmembrane

422 – 442

Helical; Potential

Topological domain

443 – 480

Cytoplasmic Potential

Transmembrane

481 – 501

Helical; Potential

Topological domain

502 – 519

Extracellular Potential

Transmembrane

520 – 540

Helical; Potential

Topological domain

541 – 632

Cytoplasmic Potential

Transmembrane

633 – 653

Helical; Potential

Topological domain

654 – 678

Extracellular Potential

Transmembrane

679 – 699

Helical; Potential

Topological domain

700 – 721

Cytoplasmic Potential

Transmembrane

722 – 742

Helical; Potential

Topological domain

743 – 764

Extracellular Potential

Transmembrane

765 – 785

Helical; Potential

Topological domain

786 – 815

Cytoplasmic Potential

Transmembrane

816 – 836

Helical; Potential

Topological domain

837 – 848

Extracellular Potential

Transmembrane

849 – 869

Helical; Potential

Topological domain

870 – 910

Cytoplasmic Potential

Zinc finger

1 – 62

RING-CH-type

Natural variations

Natural variant

622

P → L. Ref.4
Corresponds to variant rs1062914 [ dbSNP | Ensembl ].

VAR_030251

Experimental info

Mutagenesis

C → A: Abolishes auto-ubiquitination. Ref.6

Sequence conflict

380

V → VG in AAB66840. Ref.4

Sequence conflict

384

G → GS in AAB66840. Ref.4

Sequence conflict

390

C → WW in AAB66840. Ref.4

Sequence conflict

395

D → G in AAB66840. Ref.4

Sequence conflict

399

L → LG in AAB66840. Ref.4

Sequence conflict

546

R → K in AAB66840. Ref.4

Sequences

Sequence

Length

Mass (Da)

Tools

O60337 [UniParc].

Last modified February 6, 2007. Version 2.
Checksum: C7A96FEA45B5CA8D
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FASTA

910

102,545

        10         20         30         40         50         60 
MDTAEEDICR VCRSEGTPEK PLYHPCVCTG SIKFIHQECL VQWLKHSRKE YCELCKHRFA 

        70         80         90        100        110        120 
FTPIYSPDMP SRLPIQDIFA GLVTSIGTAI RYWFHYTLVA FAWLGVVPLT ACRIYKCLFT 

       130        140        150        160        170        180 
GSVSSLLTLP LDMLSTENLL ADCLQGCFVV TCTLCAFISL VWLREQIVHG GAPIWLEHAA 

       190        200        210        220        230        240 
PPFNAAGHHQ NEAPAGGNGA ENVAADQPAN PPAENAVVGE NPDAQDDQAE EEEEDNEEED 

       250        260        270        280        290        300 
DAGVEDAADA NNGAQDDMNW NALEWDRAAE ELTWERMLGL DGSLVFLEHV FWVVSLNTLF 

       310        320        330        340        350        360 
ILVFAFCPYH IGHFSLVGLG FEEHVQASHF EGLITTIVGY ILLAITLIIC HGLATLVKFH 

       370        380        390        400        410        420 
RSRRLLGVCY IVVKVSLLVV VEIGVFPLIC GWWLDICSLE MFDATLKDRE LSFQSAPGTT 

       430        440        450        460        470        480 
MFLHWLVGMV YVFYFASFIL LLREVLRPGV LWFLRNLNDP DFNPVQEMIH LPIYRHLRRF 

       490        500        510        520        530        540 
ILSVIVFGSI VLLMLWLPIR IIKSVLPNFL PYNVMLYSDA PVSELSLELL LLQVVLPALL 

       550        560        570        580        590        600 
EQGHTRQWLK GLVRAWTVTA GYLLDLHSYL LGDQEENENS ANQQVNNNQH ARNNNAIPVV 

       610        620        630        640        650        660 
GEGLHAAHQA ILQQGGPVGF QPYRRPLNFP LRIFLLIVFM CITLLIASLI CLTLPVFAGR 

       670        680        690        700        710        720 
WLMSFWTGTA KIHELYTAAC GLYVCWLTIR AVTVMVAWMP QGRRVIFQKV KEWSLMIMKT 

       730        740        750        760        770        780 
LIVAVLLAGV VPLLLGLLFE LVIVAPLRVP LDQTPLFYPW QDWALGVLHA KIIAAITLMG 

       790        800        810        820        830        840 
PQWWLKTVIE QVYANGIRNI DLHYIVRKLA APVISVLLLS LCVPYVIASG VVPLLGVTAE 

       850        860        870        880        890        900 
MQNLVHRRIY PFLLMVVVLM AILSFQVRQF KRLYEHIKND KYLVGQRLVN YERKSGKQGS 

       910 
SPPPPQSSQE

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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]. Tissue: Brain.
[2]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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]. Tissue: Pancreas.
[4]	"High resolution physical and transcription maps of the Cri-du-chat critical region." Simmons A.D., Lovett M.L. Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 379-910, VARIANT LEU-622.
[5]	"A conserved ubiquitin ligase of the nuclear envelope/endoplasmic reticulum that functions in both ER-associated and Matalpha2 repressor degradation." Swanson R., Locher M., Hochstrasser M. Genes Dev. 15:2660-2674(2001) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION.
[6]	"TEB4 is a C4HC3 RING finger-containing ubiquitin ligase of the endoplasmic reticulum." Hassink G., Kikkert M., van Voorden S., Lee S.-J., Spaapen R., van Laar T., Coleman C.S., Bartee E., Frueh K., Chau V., Wiertz E. Biochem. J. 388:647-655(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, UBIQUITINATION, MUTAGENESIS OF CYS-9.
[7]	"Membrane topology of the yeast endoplasmic reticulum-localized ubiquitin ligase Doa10 and comparison with its human ortholog TEB4 (MARCH-VI)." Kreft S.G., Wang L., Hochstrasser M. J. Biol. Chem. 281:4646-4653(2006) [PubMed] [Europe PMC] [Abstract] Cited for: TOPOLOGY.
[8]	"The E3 ubiquitin ligase TEB4 mediates degradation of type 2 iodothyronine deiodinase." Zavacki A.M., Arrojo E Drigo R., Freitas B.C., Chung M., Harney J.W., Egri P., Wittmann G., Fekete C., Gereben B., Bianco A.C. Mol. Cell. Biol. 29:5339-5347(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS AN E3 UBIQUITIN LIGASE FOR DIO2, INTERACTION WITH DIO2.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB011169 mRNA. Translation: BAA25523.1. Different initiation. CH471102 Genomic DNA. Translation: EAX08065.1. CH471102 Genomic DNA. Translation: EAX08066.1. BC046148 mRNA. Translation: AAH46148.1. BC136461 mRNA. Translation: AAI36462.1. BC136462 mRNA. Translation: AAI36463.1. BC142679 mRNA. Translation: AAI42680.1. BC142694 mRNA. Translation: AAI42695.1. AF009301 mRNA. Translation: AAB66840.1. Sequence problems.
IPI	IPI00105518.
PIR	T00268.
RefSeq	NP_005876.2. NM_005885.3.
UniGene	Hs.432862.
3D structure databases
ProteinModelPortal	O60337.
ModBase	Search...
Protein-protein interaction databases
IntAct	O60337. 1 interaction.
STRING	9606.ENSP00000274140.
PTM databases
PhosphoSite	O60337.
Proteomic databases
PaxDb	O60337.
PRIDE	O60337.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000274140; ENSP00000274140; ENSG00000145495.
GeneID	10299.
KEGG	hsa:10299.
UCSC	uc003jet.1. human.
Organism-specific databases
CTD	10299.
GeneCards	GC05P010353.
HGNC	HGNC:30550. MARCH6.
MIM	613297. gene.
neXtProt	NX_O60337.
PharmGKB	PA134869368.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5183.
HOGENOM	HOG000286005.
HOVERGEN	HBG080753.
InParanoid	O60337.
KO	K10661.
OMA	DNLLADC.
OrthoDB	EOG4WM4T3.
Enzyme and pathway databases
UniPathway	UPA00143.
Gene expression databases
ArrayExpress	O60337.
Bgee	O60337.
CleanEx	HS_MARCH6.
Genevestigator	O60337.
Family and domain databases
Gene3D	3.30.40.10. 1 hit.
InterPro	IPR011016. Znf_RING-CH. IPR013083. Znf_RING/FYVE/PHD. [Graphical view]
Pfam	PF12906. RINGv. 1 hit. [Graphical view]
SMART	SM00744. RINGv. 1 hit. [Graphical view]
PROSITE	PS51292. ZF_RING_CH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	MARCH6. human.
GenomeRNAi	10299.
NextBio	39040.
SOURCE	Search...

Entry information

Entry name

MARH6_HUMAN

Accession

Primary (citable) accession number: O60337
Secondary accession number(s): A5PKZ4

Q86X77

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 6, 2007
Last sequence update:	February 6, 2007
Last modified:	May 1, 2013
This is version 94 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.

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List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents