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Protein

E3 ubiquitin-protein ligase MARCH6

Gene

MARCH6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.

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

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000145495-MONOMER
BRENDAi2.3.2.B10 2681
ReactomeiR-HSA-901032 ER Quality Control Compartment (ERQC)
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase MARCH6 (EC:2.3.2.27)
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
RING-type E3 ubiquitin transferase MARCH6Curated
Gene namesi
Name:MARCH6
Synonyms:KIAA0597, RNF176, TEB4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000145495.14
HGNCiHGNC:30550 MARCH6
MIMi613297 gene
neXtProtiNX_O60337

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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
ProteomicsDBi49363

PTM databases

iPTMnetiO60337
PhosphoSitePlusiO60337

Expressioni

Tissue specificityi

Present in brain (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000145495 Expressed in 240 organ(s), highest expression level in cerebellar vermis
CleanExiHS_MARCH6
ExpressionAtlasiO60337 baseline and differential
GenevisibleiO60337 HS

Organism-specific databases

HPAiHPA040841
HPA063246

Interactioni

Subunit structurei

Interacts with DIO2.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
RGS2P41220-13EBI-2684600,EBI-16037474

GO - Molecular functioni

Protein-protein interaction databases

BioGridi115587, 24 interactors
DIPiDIP-56134N
IntActiO60337, 9 interactors
MINTiO60337
STRINGi9606.ENSP00000274140

Structurei

3D structure databases

ProteinModelPortaliO60337
SMRiO60337
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

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

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
GeneTreeiENSGT00930000150887
HOGENOMiHOG000286005
HOVERGENiHBG080753
InParanoidiO60337
KOiK10661
OMAiWLPIRIL
OrthoDBiEOG091G02GT
PhylomeDBiO60337
TreeFamiTF105777

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR011016 Znf_RING-CH
IPR013083 Znf_RING/FYVE/PHD
PfamiView protein in Pfam
PF12906 RINGv, 1 hit
SMARTiView protein in SMART
SM00744 RINGv, 1 hit
PROSITEiView protein in PROSITE
PS51292 ZF_RING_CH, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

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

This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0B4J206A0A0B4J206_HUMAN
E3 ubiquitin-protein ligase MARCH6
MARCH6
608Annotation score:
D6RHY7D6RHY7_HUMAN
E3 ubiquitin-protein ligase MARCH6
MARCH6
77Annotation score:

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 → L1 PublicationCorresponds to variant dbSNP:rs1062914Ensembl.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

Similar proteinsi

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
SMRiO60337
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115587, 24 interactors
DIPiDIP-56134N
IntActiO60337, 9 interactors
MINTiO60337
STRINGi9606.ENSP00000274140

PTM databases

iPTMnetiO60337
PhosphoSitePlusiO60337

Proteomic databases

EPDiO60337
MaxQBiO60337
PaxDbiO60337
PeptideAtlasiO60337
PRIDEiO60337
ProteomicsDBi49363

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
EuPathDBiHostDB:ENSG00000145495.14
GeneCardsiMARCH6
HGNCiHGNC:30550 MARCH6
HPAiHPA040841
HPA063246
MIMi613297 gene
neXtProtiNX_O60337
OpenTargetsiENSG00000145495
PharmGKBiPA134869368
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1609 Eukaryota
COG5183 LUCA
GeneTreeiENSGT00930000150887
HOGENOMiHOG000286005
HOVERGENiHBG080753
InParanoidiO60337
KOiK10661
OMAiWLPIRIL
OrthoDBiEOG091G02GT
PhylomeDBiO60337
TreeFamiTF105777

Enzyme and pathway databases

UniPathwayi
UPA00143

BioCyciMetaCyc:ENSG00000145495-MONOMER
BRENDAi2.3.2.B10 2681
ReactomeiR-HSA-901032 ER Quality Control Compartment (ERQC)

Miscellaneous databases

ChiTaRSiMARCH6 human
GeneWikiiMARCH6
GenomeRNAii10299
PROiPR:O60337
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000145495 Expressed in 240 organ(s), highest expression level in cerebellar vermis
CleanExiHS_MARCH6
ExpressionAtlasiO60337 baseline and differential
GenevisibleiO60337 HS

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR011016 Znf_RING-CH
IPR013083 Znf_RING/FYVE/PHD
PfamiView protein in Pfam
PF12906 RINGv, 1 hit
SMARTiView protein in SMART
SM00744 RINGv, 1 hit
PROSITEiView protein in PROSITE
PS51292 ZF_RING_CH, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMARH6_HUMAN
AccessioniPrimary (citable) accession number: O60337
Secondary accession number(s): A5PKZ4
, B4DKJ2, B4DT33, D3DTC8, O14670, Q86X77
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: February 6, 2007
Last modified: November 7, 2018
This is version 142 of the entry and version 2 of the sequence. See 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 entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  5. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
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