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O60337 (MARH6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length910 AA.
Sequence statusComplete.
Protein existenceEvidence 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.8 Ref.10

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Interacts with DIO2. Ref.10

Subcellular location

Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.8.

Tissue specificity

Present in brain (at protein level). Ref.8

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.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O60337-4)

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: O60337-5)

The sequence of this isoform differs from the canonical sequence as follows:
     64-112: IYSPDMPSRLPIQDIFAGLVTSIGTAIRYWFHYTLVAFAWLGVVPLTAC → S
Isoform 3 (identifier: O60337-6)

The sequence of this isoform differs from the canonical sequence as follows:
     7-112: DICRVCRSEG...WLGVVPLTAC → G

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 910910E3 ubiquitin-protein ligase MARCH6
PRO_0000274298

Regions

Topological domain1 – 9191Cytoplasmic Potential
Transmembrane92 – 11221Helical; Potential
Topological domain113 – 14230Extracellular Potential
Transmembrane143 – 16321Helical; Potential
Topological domain164 – 283120Cytoplasmic Potential
Transmembrane284 – 30421Helical; Potential
Topological domain305 – 33632Extracellular Potential
Transmembrane337 – 35721Helical; Potential
Topological domain358 – 37619Cytoplasmic Potential
Transmembrane377 – 39721Helical; Potential
Topological domain398 – 42124Extracellular Potential
Transmembrane422 – 44221Helical; Potential
Topological domain443 – 48038Cytoplasmic Potential
Transmembrane481 – 50121Helical; Potential
Topological domain502 – 51918Extracellular Potential
Transmembrane520 – 54021Helical; Potential
Topological domain541 – 63292Cytoplasmic Potential
Transmembrane633 – 65321Helical; Potential
Topological domain654 – 67825Extracellular Potential
Transmembrane679 – 69921Helical; Potential
Topological domain700 – 72122Cytoplasmic Potential
Transmembrane722 – 74221Helical; Potential
Topological domain743 – 76422Extracellular Potential
Transmembrane765 – 78521Helical; Potential
Topological domain786 – 81530Cytoplasmic Potential
Transmembrane816 – 83621Helical; Potential
Topological domain837 – 84812Extracellular Potential
Transmembrane849 – 86921Helical; Potential
Topological domain870 – 91041Cytoplasmic Potential
Zinc finger1 – 6262RING-CH-type

Amino acid modifications

Modified residue11N-acetylmethionine Ref.11

Natural variations

Alternative sequence7 – 112106DICRV…PLTAC → G in isoform 3.
VSP_047035
Alternative sequence64 – 11249IYSPD…PLTAC → S in isoform 2.
VSP_047036
Natural variant6221P → L. Ref.6
Corresponds to variant rs1062914 [ dbSNP | Ensembl ].
VAR_030251

Experimental info

Mutagenesis91C → A: Abolishes auto-ubiquitination. Ref.8
Sequence conflict3801V → VG in AAB66840. Ref.6
Sequence conflict3841G → GS in AAB66840. Ref.6
Sequence conflict3901C → WW in AAB66840. Ref.6
Sequence conflict3951D → G in AAB66840. Ref.6
Sequence conflict3991L → LG in AAB66840. Ref.6
Sequence conflict5461R → K in AAB66840. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

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

FASTA910102,545
        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

Isoform 2 [UniParc].

Checksum: E05382BAE7E49AF3
Show »

FASTA86297,178
Isoform 3 [UniParc].

Checksum: 1DC90D272E92EDD9
Show »

FASTA80590,413

References

« Hide '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] (ISOFORM 1).
Tissue: Brain.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
[3]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]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. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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 1).
Tissue: Pancreas.
[6]"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 (ISOFORM 1), VARIANT LEU-622.
[7]"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.
[8]"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.
[9]"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.
[10]"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.
[11]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB011169 mRNA. Translation: BAA25523.1. Different initiation.
AK296585 mRNA. Translation: BAG59204.1.
AK300034 mRNA. Translation: BAG61845.1.
AC012640 Genomic DNA. No translation available.
AC092336 Genomic DNA. No translation available.
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.
PIRT00268.
RefSeqNP_001257589.1. NM_001270660.1.
NP_001257590.1. NM_001270661.1.
NP_005876.2. NM_005885.3.
UniGeneHs.432862.

3D structure databases

ProteinModelPortalO60337.
SMRO60337. Positions 4-59.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115587. 3 interactions.
IntActO60337. 1 interaction.
STRING9606.ENSP00000274140.

PTM databases

PhosphoSiteO60337.

Proteomic databases

PaxDbO60337.
PRIDEO60337.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000274140; ENSP00000274140; ENSG00000145495. [O60337-4]
ENST00000449913; ENSP00000414643; ENSG00000145495. [O60337-5]
ENST00000503788; ENSP00000425930; ENSG00000145495. [O60337-6]
GeneID10299.
KEGGhsa:10299.
UCSCuc003jet.2. human. [O60337-4]

Organism-specific databases

CTD10299.
GeneCardsGC05P010353.
HGNCHGNC:30550. MARCH6.
MIM613297. gene.
neXtProtNX_O60337.
PharmGKBPA134869368.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5183.
HOGENOMHOG000286005.
HOVERGENHBG080753.
InParanoidO60337.
KOK10661.
OMADNLLADC.
OrthoDBEOG7J4464.
PhylomeDBO60337.
TreeFamTF105777.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

ArrayExpressO60337.
BgeeO60337.
CleanExHS_MARCH6.
GenevestigatorO60337.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
InterProIPR011016. Znf_RING-CH.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamPF12906. RINGv. 1 hit.
[Graphical view]
SMARTSM00744. RINGv. 1 hit.
[Graphical view]
PROSITEPS51292. ZF_RING_CH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMARCH6. human.
GeneWikiMARCH6.
GenomeRNAi10299.
NextBio35472800.
PROO60337.
SOURCESearch...

Entry information

Entry nameMARH6_HUMAN
AccessionPrimary (citable) accession number: O60337
Secondary accession number(s): A5PKZ4 expand/collapse secondary AC list , B4DKJ2, B4DT33, D3DTC8, O14670, Q86X77
Entry history
Integrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: February 6, 2007
Last modified: April 16, 2014
This is version 103 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM