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Protein

E3 ubiquitin-protein ligase MARCH6

Gene

MARCH6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 UBE2G1.2 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri1 – 62RING-CH-typePROSITE-ProRule annotationAdd BLAST62

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • ligase activity Source: UniProtKB-KW
  • ubiquitin conjugating enzyme binding Source: UniProtKB
  • ubiquitin protein ligase activity involved in ERAD pathway Source: ParkinsonsUK-UCL
  • ubiquitin-protein transferase activity Source: UniProtKB
  • ubiquitin-specific protease binding Source: ParkinsonsUK-UCL
  • zinc ion binding Source: InterPro

GO - Biological processi

  • ERAD pathway Source: ParkinsonsUK-UCL
  • ER-associated ubiquitin-dependent protein catabolic process Source: GO_Central
  • proteasomal protein catabolic process Source: ParkinsonsUK-UCL
  • protein K48-linked ubiquitination Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi2.3.2.B10. 2681.
ReactomeiR-HSA-901032. ER Quality Control Compartment (ERQC).
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
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 namesi
Name:MARCH6
Synonyms:KIAA0597, RNF176, TEB4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:30550. MARCH6.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 91CytoplasmicSequence analysisAdd BLAST91
Transmembranei92 – 112HelicalSequence analysisAdd BLAST21
Topological domaini113 – 142ExtracellularSequence analysisAdd BLAST30
Transmembranei143 – 163HelicalSequence analysisAdd BLAST21
Topological domaini164 – 283CytoplasmicSequence analysisAdd BLAST120
Transmembranei284 – 304HelicalSequence analysisAdd BLAST21
Topological domaini305 – 336ExtracellularSequence analysisAdd BLAST32
Transmembranei337 – 357HelicalSequence analysisAdd BLAST21
Topological domaini358 – 376CytoplasmicSequence analysisAdd BLAST19
Transmembranei377 – 397HelicalSequence analysisAdd BLAST21
Topological domaini398 – 421ExtracellularSequence analysisAdd BLAST24
Transmembranei422 – 442HelicalSequence analysisAdd BLAST21
Topological domaini443 – 480CytoplasmicSequence analysisAdd BLAST38
Transmembranei481 – 501HelicalSequence analysisAdd BLAST21
Topological domaini502 – 519ExtracellularSequence analysisAdd BLAST18
Transmembranei520 – 540HelicalSequence analysisAdd BLAST21
Topological domaini541 – 632CytoplasmicSequence analysisAdd BLAST92
Transmembranei633 – 653HelicalSequence analysisAdd BLAST21
Topological domaini654 – 678ExtracellularSequence analysisAdd BLAST25
Transmembranei679 – 699HelicalSequence analysisAdd BLAST21
Topological domaini700 – 721CytoplasmicSequence analysisAdd BLAST22
Transmembranei722 – 742HelicalSequence analysisAdd BLAST21
Topological domaini743 – 764ExtracellularSequence analysisAdd BLAST22
Transmembranei765 – 785HelicalSequence analysisAdd BLAST21
Topological domaini786 – 815CytoplasmicSequence analysisAdd BLAST30
Transmembranei816 – 836HelicalSequence analysisAdd BLAST21
Topological domaini837 – 848ExtracellularSequence analysisAdd BLAST12
Transmembranei849 – 869HelicalSequence analysisAdd BLAST21
Topological domaini870 – 910CytoplasmicSequence analysisAdd BLAST41

GO - Cellular componenti

  • ER ubiquitin ligase complex Source: ParkinsonsUK-UCL
  • integral component of endoplasmic reticulum membrane Source: UniProtKB
  • integral component of membrane Source: ParkinsonsUK-UCL
  • membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi9C → A: Abolishes auto-ubiquitination. 1 Publication1

Organism-specific databases

DisGeNETi10299.
OpenTargetsiENSG00000145495.
PharmGKBiPA134869368.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002742981 – 910E3 ubiquitin-protein ligase MARCH6Add BLAST910

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1

Post-translational modificationi

Auto-ubiquitinated, which results in proteasomal degradation.1 Publication

Keywords - PTMi

Acetylation, Ubl conjugation

Proteomic databases

EPDiO60337.
MaxQBiO60337.
PaxDbiO60337.
PeptideAtlasiO60337.
PRIDEiO60337.

PTM databases

iPTMnetiO60337.
PhosphoSitePlusiO60337.

Expressioni

Tissue specificityi

Present in brain (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000145495.
CleanExiHS_MARCH6.
ExpressionAtlasiO60337. baseline and differential.
GenevisibleiO60337. HS.

Organism-specific databases

HPAiHPA063246.

Interactioni

Subunit structurei

Interacts with DIO2.1 Publication

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • ubiquitin conjugating enzyme binding Source: UniProtKB
  • ubiquitin-specific protease binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi115587. 20 interactors.
DIPiDIP-56134N.
IntActiO60337. 8 interactors.
STRINGi9606.ENSP00000274140.

Structurei

3D structure databases

ProteinModelPortaliO60337.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

The RING-CH-type zinc finger domain is required for E3 ligase activity.

Sequence similaritiesi

Contains 1 RING-CH-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri1 – 62RING-CH-typePROSITE-ProRule annotationAdd BLAST62

Keywords - Domaini

Transmembrane, Transmembrane helix, Zinc-finger

Phylogenomic databases

eggNOGiKOG1609. Eukaryota.
COG5183. LUCA.
GeneTreeiENSGT00730000110355.
HOGENOMiHOG000286005.
HOVERGENiHBG080753.
InParanoidiO60337.
KOiK10661.
OMAiGGYLCWI.
OrthoDBiEOG091G02GT.
PhylomeDBiO60337.
TreeFamiTF105777.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR011016. Znf_RING-CH.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF12906. RINGv. 1 hit.
[Graphical view]
SMARTiSM00744. RINGv. 1 hit.
[Graphical view]
PROSITEiPS51292. ZF_RING_CH. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O60337-4) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MDTAEEDICR VCRSEGTPEK PLYHPCVCTG SIKFIHQECL VQWLKHSRKE
60 70 80 90 100
YCELCKHRFA FTPIYSPDMP SRLPIQDIFA GLVTSIGTAI RYWFHYTLVA
110 120 130 140 150
FAWLGVVPLT ACRIYKCLFT GSVSSLLTLP LDMLSTENLL ADCLQGCFVV
160 170 180 190 200
TCTLCAFISL VWLREQIVHG GAPIWLEHAA PPFNAAGHHQ NEAPAGGNGA
210 220 230 240 250
ENVAADQPAN PPAENAVVGE NPDAQDDQAE EEEEDNEEED DAGVEDAADA
260 270 280 290 300
NNGAQDDMNW NALEWDRAAE ELTWERMLGL DGSLVFLEHV FWVVSLNTLF
310 320 330 340 350
ILVFAFCPYH IGHFSLVGLG FEEHVQASHF EGLITTIVGY ILLAITLIIC
360 370 380 390 400
HGLATLVKFH RSRRLLGVCY IVVKVSLLVV VEIGVFPLIC GWWLDICSLE
410 420 430 440 450
MFDATLKDRE LSFQSAPGTT MFLHWLVGMV YVFYFASFIL LLREVLRPGV
460 470 480 490 500
LWFLRNLNDP DFNPVQEMIH LPIYRHLRRF ILSVIVFGSI VLLMLWLPIR
510 520 530 540 550
IIKSVLPNFL PYNVMLYSDA PVSELSLELL LLQVVLPALL EQGHTRQWLK
560 570 580 590 600
GLVRAWTVTA GYLLDLHSYL LGDQEENENS ANQQVNNNQH ARNNNAIPVV
610 620 630 640 650
GEGLHAAHQA ILQQGGPVGF QPYRRPLNFP LRIFLLIVFM CITLLIASLI
660 670 680 690 700
CLTLPVFAGR WLMSFWTGTA KIHELYTAAC GLYVCWLTIR AVTVMVAWMP
710 720 730 740 750
QGRRVIFQKV KEWSLMIMKT LIVAVLLAGV VPLLLGLLFE LVIVAPLRVP
760 770 780 790 800
LDQTPLFYPW QDWALGVLHA KIIAAITLMG PQWWLKTVIE QVYANGIRNI
810 820 830 840 850
DLHYIVRKLA APVISVLLLS LCVPYVIASG VVPLLGVTAE MQNLVHRRIY
860 870 880 890 900
PFLLMVVVLM AILSFQVRQF KRLYEHIKND KYLVGQRLVN YERKSGKQGS
910
SPPPPQSSQE
Length:910
Mass (Da):102,545
Last modified:February 6, 2007 - v2
Checksum:iC7A96FEA45B5CA8D
GO
Isoform 2 (identifier: O60337-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     64-112: IYSPDMPSRLPIQDIFAGLVTSIGTAIRYWFHYTLVAFAWLGVVPLTAC → S

Show »
Length:862
Mass (Da):97,178
Checksum:iE05382BAE7E49AF3
GO
Isoform 3 (identifier: O60337-6) [UniParc]FASTAAdd to basket

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

Show »
Length:805
Mass (Da):90,413
Checksum:i1DC90D272E92EDD9
GO

Sequence cautioni

The sequence AAB66840 differs from that shown. Reason: Frameshift at positions 381, 382, 383, 385, 391, 396 and 418.Curated
The sequence AAB66840 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAA25523 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti380V → VG in AAB66840 (Ref. 6) Curated1
Sequence conflicti384G → GS in AAB66840 (Ref. 6) Curated1
Sequence conflicti390C → WW in AAB66840 (Ref. 6) Curated1
Sequence conflicti395D → G in AAB66840 (Ref. 6) Curated1
Sequence conflicti399L → LG in AAB66840 (Ref. 6) Curated1
Sequence conflicti546R → K in AAB66840 (Ref. 6) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_030251622P → L.1 PublicationCorresponds to variant rs1062914dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0470357 – 112DICRV…PLTAC → G in isoform 3. 1 PublicationAdd BLAST106
Alternative sequenceiVSP_04703664 – 112IYSPD…PLTAC → S in isoform 2. 1 PublicationAdd BLAST49

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS34135.1. [O60337-4]
CCDS59487.1. [O60337-5]
CCDS59488.1. [O60337-6]
PIRiT00268.
RefSeqiNP_001257589.1. NM_001270660.1. [O60337-5]
NP_001257590.1. NM_001270661.1. [O60337-6]
NP_005876.2. NM_005885.3. [O60337-4]
UniGeneiHs.432862.

Genome annotation databases

EnsembliENST00000274140; ENSP00000274140; ENSG00000145495. [O60337-4]
ENST00000449913; ENSP00000414643; ENSG00000145495. [O60337-5]
ENST00000503788; ENSP00000425930; ENSG00000145495. [O60337-6]
GeneIDi10299.
KEGGihsa:10299.
UCSCiuc003jet.3. human. [O60337-4]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS34135.1. [O60337-4]
CCDS59487.1. [O60337-5]
CCDS59488.1. [O60337-6]
PIRiT00268.
RefSeqiNP_001257589.1. NM_001270660.1. [O60337-5]
NP_001257590.1. NM_001270661.1. [O60337-6]
NP_005876.2. NM_005885.3. [O60337-4]
UniGeneiHs.432862.

3D structure databases

ProteinModelPortaliO60337.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115587. 20 interactors.
DIPiDIP-56134N.
IntActiO60337. 8 interactors.
STRINGi9606.ENSP00000274140.

PTM databases

iPTMnetiO60337.
PhosphoSitePlusiO60337.

Proteomic databases

EPDiO60337.
MaxQBiO60337.
PaxDbiO60337.
PeptideAtlasiO60337.
PRIDEiO60337.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000274140; ENSP00000274140; ENSG00000145495. [O60337-4]
ENST00000449913; ENSP00000414643; ENSG00000145495. [O60337-5]
ENST00000503788; ENSP00000425930; ENSG00000145495. [O60337-6]
GeneIDi10299.
KEGGihsa:10299.
UCSCiuc003jet.3. human. [O60337-4]

Organism-specific databases

CTDi10299.
DisGeNETi10299.
GeneCardsiMARCH6.
HGNCiHGNC:30550. MARCH6.
HPAiHPA063246.
MIMi613297. gene.
neXtProtiNX_O60337.
OpenTargetsiENSG00000145495.
PharmGKBiPA134869368.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1609. Eukaryota.
COG5183. LUCA.
GeneTreeiENSGT00730000110355.
HOGENOMiHOG000286005.
HOVERGENiHBG080753.
InParanoidiO60337.
KOiK10661.
OMAiGGYLCWI.
OrthoDBiEOG091G02GT.
PhylomeDBiO60337.
TreeFamiTF105777.

Enzyme and pathway databases

UniPathwayiUPA00143.
BRENDAi2.3.2.B10. 2681.
ReactomeiR-HSA-901032. ER Quality Control Compartment (ERQC).

Miscellaneous databases

ChiTaRSiMARCH6. human.
GeneWikiiMARCH6.
GenomeRNAii10299.
PROiO60337.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000145495.
CleanExiHS_MARCH6.
ExpressionAtlasiO60337. baseline and differential.
GenevisibleiO60337. HS.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR011016. Znf_RING-CH.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF12906. RINGv. 1 hit.
[Graphical view]
SMARTiSM00744. RINGv. 1 hit.
[Graphical view]
PROSITEiPS51292. ZF_RING_CH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMARH6_HUMAN
AccessioniPrimary (citable) accession number: O60337
Secondary accession number(s): A5PKZ4
, B4DKJ2, B4DT33, D3DTC8, O14670, Q86X77
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: February 6, 2007
Last modified: November 30, 2016
This is version 127 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.