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Protein

E3 ubiquitin-protein ligase MARCH8

Gene

MARCH8

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

Functioni

E3 ubiquitin-protein ligase that mediates ubiquitination of CD86 and MHC class II proteins, such as HLA-DR alpha and beta, and promotes their subsequent endocytosis and sorting to lysosomes via multivesicular bodies. May also promote ubiquitination and endocytosis of TFRC and FAS.5 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 fingeri72 – 133RING-CH-typePROSITE-ProRule annotationAdd BLAST62

GO - Molecular functioni

  • ubiquitin-protein transferase activity Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • protein polyubiquitination Source: UniProtKB

Keywordsi

Molecular functionTransferase
Biological processAdaptive immunity, Immunity, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase MARCH8 (EC:2.3.2.27)
Alternative name(s):
Cellular modulator of immune recognition
Short name:
c-MIR
Membrane-associated RING finger protein 8
Membrane-associated RING-CH protein VIII
Short name:
MARCH-VIII
RING finger protein 178
RING-type E3 ubiquitin transferase MARCH8Curated
Gene namesi
Name:MARCH8
Synonyms:MIR, RNF178
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000165406.15
HGNCiHGNC:23356 MARCH8
MIMi613335 gene
neXtProtiNX_Q5T0T0

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
Transmembranei157 – 177HelicalSequence analysisAdd BLAST21
Transmembranei197 – 217HelicalSequence analysisAdd BLAST21

Keywords - Cellular componenti

Cytoplasmic vesicle, Endosome, Lysosome, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi220972
OpenTargetsiENSG00000165406
PharmGKBiPA37370

Polymorphism and mutation databases

BioMutaiMARK8
DMDMi74744352

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002743701 – 291E3 ubiquitin-protein ligase MARCH8Add BLAST291

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei253PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ5T0T0
PaxDbiQ5T0T0
PeptideAtlasiQ5T0T0
PRIDEiQ5T0T0
ProteomicsDBi64200

PTM databases

iPTMnetiQ5T0T0
PhosphoSitePlusiQ5T0T0

Expressioni

Tissue specificityi

Broadly expressed. Present in immature dendritic cells (at protein level).2 Publications

Gene expression databases

BgeeiENSG00000165406
CleanExiHS_MARCH8
ExpressionAtlasiQ5T0T0 baseline and differential
GenevisibleiQ5T0T0 HS

Organism-specific databases

HPAiHPA014597

Interactioni

Subunit structurei

Interacts with CD86.1 Publication

Protein-protein interaction databases

BioGridi128666, 10 interactors
IntActiQ5T0T0, 1 interactor
STRINGi9606.ENSP00000317087

Structurei

Secondary structure

1291
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi81 – 83Combined sources3
Beta strandi89 – 91Combined sources3
Beta strandi96 – 98Combined sources3
Beta strandi101 – 103Combined sources3
Helixi110 – 118Combined sources9
Beta strandi124 – 126Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2D8SNMR-A70-136[»]
ProteinModelPortaliQ5T0T0
SMRiQ5T0T0
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ5T0T0

Family & Domainsi

Domaini

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri72 – 133RING-CH-typePROSITE-ProRule annotationAdd BLAST62

Keywords - Domaini

Transmembrane, Transmembrane helix, Zinc-finger

Phylogenomic databases

eggNOGiKOG1609 Eukaryota
COG5183 LUCA
GeneTreeiENSGT00920000148985
HOGENOMiHOG000113483
HOVERGENiHBG081957
InParanoidiQ5T0T0
KOiK10656
OMAiSGDTCRI
OrthoDBiEOG091G0WJX
PhylomeDBiQ5T0T0
TreeFamiTF319557

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR033275 MARCH-like
IPR011016 Znf_RING-CH
IPR013083 Znf_RING/FYVE/PHD
PANTHERiPTHR23012 PTHR23012, 1 hit
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 (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q5T0T0-1) [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
MSMPLHQISA IPSQDAISAR VYRSKTKEKE REEQNEKTLG HFMSHSSNIS
60 70 80 90 100
KAGSPPSASA PAPVSSFSRT SITPSSQDIC RICHCEGDDE SPLITPCHCT
110 120 130 140 150
GSLHFVHQAC LQQWIKSSDT RCCELCKYEF IMETKLKPLR KWEKLQMTSS
160 170 180 190 200
ERRKIMCSVT FHVIAITCVV WSLYVLIDRT AEEIKQGQAT GILEWPFWTK
210 220 230 240 250
LVVVAIGFTG GLLFMYVQCK VYVQLWKRLK AYNRVIYVQN CPETSKKNIF
260 270 280 290
EKSPLTEPNF ENKHGYGICH SDTNSSCCTE PEDTGAEIIH V
Length:291
Mass (Da):32,965
Last modified:April 12, 2005 - v1
Checksum:iF45D9BFAA3889BB3
GO
Isoform 2 (identifier: Q5T0T0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     79-79: I → ICSSSAVFSE...ISPVSTSGDV

Note: No experimental confirmation available. Gene prediction based on EST data.
Show »
Length:573
Mass (Da):63,319
Checksum:i8B7E5DF14206565E
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03026692P → S. Corresponds to variant dbSNP:rs3764990Ensembl.1
Natural variantiVAR_030267266Y → H1 PublicationCorresponds to variant dbSNP:rs7908745Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05569779I → ICSSSAVFSECCHHSSVQSA VVSKAPHCQSSLTQGLTVTV ICKDTLQASKRNSFGSEWAQ ALKPAKNTKARRTLKFSRSL NDVGEKAQDTSESFAYVERT CSEGKLILPQDTCLRTNRFH HKEKRTLNHKPLGNSKHSCV SCLSAGRSTASEVEAGKGGR PGLLLEEKADGEATSRSRQL LQYLFSLSHGLSASSLHRFH ELESCAARLHTAKSSSGLAG SMGFCSDEMGDDDVFEDSTS AKLKSRVLRAPLCSTEKDSD LDCPSPFSEKLPPISPVSTS GDV in isoform 2. Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK313340 mRNA Translation: BAG36144.1
AL445201 Genomic DNA No translation available.
AL512595 Genomic DNA No translation available.
AL731567 Genomic DNA No translation available.
CH471160 Genomic DNA Translation: EAW86647.1
CH471160 Genomic DNA Translation: EAW86648.1
BC025394 mRNA Translation: AAH25394.1
BC066988 mRNA Translation: AAH66988.1
CCDSiCCDS60519.1 [Q5T0T0-2]
CCDS7213.1 [Q5T0T0-1]
RefSeqiNP_001002266.1, NM_001002266.2 [Q5T0T0-1]
NP_001269795.1, NM_001282866.1 [Q5T0T0-2]
NP_659458.2, NM_145021.5 [Q5T0T0-1]
XP_005271861.1, XM_005271804.2 [Q5T0T0-2]
XP_006717767.1, XM_006717704.2 [Q5T0T0-2]
XP_011537794.1, XM_011539492.2 [Q5T0T0-2]
XP_011537795.1, XM_011539493.2 [Q5T0T0-2]
XP_011537796.1, XM_011539494.2 [Q5T0T0-2]
XP_011537797.1, XM_011539495.1 [Q5T0T0-1]
XP_016871383.1, XM_017015894.1 [Q5T0T0-1]
UniGeneiHs.499489

Genome annotation databases

EnsembliENST00000319836; ENSP00000317087; ENSG00000165406 [Q5T0T0-1]
ENST00000395769; ENSP00000379116; ENSG00000165406 [Q5T0T0-1]
ENST00000395771; ENSP00000379118; ENSG00000278545
ENST00000453424; ENSP00000411848; ENSG00000165406 [Q5T0T0-2]
GeneIDi220972
KEGGihsa:220972
UCSCiuc001jcf.5 human [Q5T0T0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiMARH8_HUMAN
AccessioniPrimary (citable) accession number: Q5T0T0
Secondary accession number(s): B2R8E7
, H0Y7C6, Q5T0S8, Q8TC72
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: April 12, 2005
Last modified: June 20, 2018
This is version 119 of the entry and version 1 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

3D-structure, Complete proteome, Reference proteome

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