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Protein

E3 ubiquitin-protein ligase MARCH1

Gene

MARCH1

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 mediates ubiquitination of TFRC, CD86, FAS and MHC class II proteins, such as HLA-DR alpha and beta, and promotes their subsequent endocytosis and sorting to lysosomes via multivesicular bodies. By constitutively ubiquitinating MHC class II proteins in immature dendritic cells, down-regulates their cell surface localization thus sequestering them in the intracellular endosomal system.4 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 fingeri72 – 133RING-CH-typePROSITE-ProRule annotationAdd BLAST62

GO - Molecular functioni

  • ligase activity Source: UniProtKB-KW
  • MHC protein binding Source: UniProtKB
  • ubiquitin protein ligase activity Source: Ensembl
  • ubiquitin-protein transferase activity Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • antigen processing and presentation of peptide antigen via MHC class II Source: UniProtKB
  • immune response Source: UniProtKB
  • protein polyubiquitination Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Immunity, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase MARCH1 (EC:6.3.2.-)
Alternative name(s):
Membrane-associated RING finger protein 1
Membrane-associated RING-CH protein I
Short name:
MARCH-I
RING finger protein 171
Gene namesi
Name:MARCH1
Synonyms:RNF171
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:26077. MARCH1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei155 – 175HelicalSequence analysisAdd BLAST21
Transmembranei197 – 217HelicalSequence analysisAdd BLAST21

GO - Cellular componenti

  • cytoplasmic vesicle membrane Source: UniProtKB-SubCell
  • early endosome membrane Source: UniProtKB
  • endoplasmic reticulum membrane Source: UniProtKB
  • endosome Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • late endosome membrane Source: UniProtKB
  • lysosomal membrane Source: UniProtKB
  • lysosome Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • trans-Golgi network membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Endosome, Golgi apparatus, Lysosome, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi55016.
OpenTargetsiENSG00000145416.
PharmGKBiPA134986392.

Polymorphism and mutation databases

BioMutaiMARCH1.
DMDMi74762613.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002743651 – 289E3 ubiquitin-protein ligase MARCH1Add BLAST289

Post-translational modificationi

Has a short half-life. Instability/short half-life permits rapid changes that allow efficient induction of antigen presentation once antigen presenting cells, APCs, receive maturation signals. Small changes in protein levels significantly alter the cell surface display of MHC class II proteins (By similarity).By similarity

Proteomic databases

EPDiQ8TCQ1.
PaxDbiQ8TCQ1.
PeptideAtlasiQ8TCQ1.
PRIDEiQ8TCQ1.

PTM databases

iPTMnetiQ8TCQ1.
PhosphoSitePlusiQ8TCQ1.

Expressioni

Tissue specificityi

Expressed in antigen presenting cells, APCs, located in lymph nodes and spleen. Also expressed in lung. Expression is high in follicular B-cells, moderate in dendritic cells and low in splenic T-cells.2 Publications

Developmental stagei

During maturation of dendritic cells, expression is down-regulated and stabilizes MHC class II proteins accumulate at the plasma membrane.

Inductioni

By IL10/interleukin-10.1 Publication

Gene expression databases

BgeeiENSG00000145416.
CleanExiHS_MARCH1.
ExpressionAtlasiQ8TCQ1. baseline and differential.
GenevisibleiQ8TCQ1. HS.

Organism-specific databases

HPAiHPA014600.

Interactioni

GO - Molecular functioni

  • MHC protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi120348. 10 interactors.
STRINGi9606.ENSP00000274056.

Structurei

3D structure databases

ProteinModelPortaliQ8TCQ1.
SMRiQ8TCQ1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 66Responsible for low stabilityBy similarityAdd BLAST66
Regioni222 – 279Responsible for down-regulation of CD86 and MHC class II cell surface expressionBy similarityAdd BLAST58

Domaini

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

Sequence similaritiesi

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

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.
GeneTreeiENSGT00730000110355.
HOGENOMiHOG000113483.
HOVERGENiHBG081957.
InParanoidiQ8TCQ1.
KOiK10656.
OMAiERRKICC.
PhylomeDBiQ8TCQ1.
TreeFamiTF319557.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR033275. MARCH-like.
IPR011016. Znf_RING-CH.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PANTHERiPTHR23012. PTHR23012. 1 hit.
PfamiPF12906. RINGv. 1 hit.
[Graphical view]
SMARTiSM00744. RINGv. 1 hit.
[Graphical view]
PROSITEiPS51292. ZF_RING_CH. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q8TCQ1-1) [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
MLGWCEAIAR NPHRIPNNTR TPEISGDLAD ASQTSTLNEK SPGRSASRSS
60 70 80 90 100
NISKASSPTT GTAPRSQSRL SVCPSTQDIC RICHCEGDEE SPLITPCRCT
110 120 130 140 150
GTLRFVHQSC LHQWIKSSDT RCCELCKYDF IMETKLKPLR KWEKLQMTTS
160 170 180 190 200
ERRKIFCSVT FHVIAITCVV WSLYVLIDRT AEEIKQGNDN GVLEWPFWTK
210 220 230 240 250
LVVVAIGFTG GLVFMYVQCK VYVQLWRRLK AYNRVIFVQN CPDTAKKLEK
260 270 280
NFSCNVNTDI KDAVVVPVPQ TGANSLPSAE GGPPEVVSV
Length:289
Mass (Da):32,308
Last modified:June 1, 2002 - v1
Checksum:i923E1809AB3D7087
GO
Isoform 2 (identifier: Q8TCQ1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-18: Missing.
     19-54: TRTPEISGDLADASQTSTLNEKSPGRSASRSSNISK → MTSSHVCCNFLNMWKKSKISTMYYLNQDAKLSNLFLQ

Show »
Length:272
Mass (Da):30,873
Checksum:iF329A16B3E9AB510
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0227241 – 18Missing in isoform 2. 1 PublicationAdd BLAST18
Alternative sequenceiVSP_02272519 – 54TRTPE…SNISK → MTSSHVCCNFLNMWKKSKIS TMYYLNQDAKLSNLFLQ in isoform 2. 1 PublicationAdd BLAST36

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK000675 mRNA. Translation: BAA91319.1.
AL713759 mRNA. Translation: CAD28529.1.
CH471056 Genomic DNA. Translation: EAX04835.1.
CCDSiCCDS3806.1. [Q8TCQ1-2]
CCDS54814.1. [Q8TCQ1-1]
RefSeqiNP_001159845.1. NM_001166373.1. [Q8TCQ1-1]
NP_060393.1. NM_017923.3. [Q8TCQ1-2]
XP_016863823.1. XM_017008334.1. [Q8TCQ1-1]
UniGeneiHs.592804.
Hs.608487.

Genome annotation databases

EnsembliENST00000274056; ENSP00000274056; ENSG00000145416. [Q8TCQ1-1]
ENST00000339875; ENSP00000345676; ENSG00000145416. [Q8TCQ1-2]
ENST00000503008; ENSP00000427223; ENSG00000145416. [Q8TCQ1-1]
GeneIDi55016.
KEGGihsa:55016.
UCSCiuc003iqr.3. human. [Q8TCQ1-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK000675 mRNA. Translation: BAA91319.1.
AL713759 mRNA. Translation: CAD28529.1.
CH471056 Genomic DNA. Translation: EAX04835.1.
CCDSiCCDS3806.1. [Q8TCQ1-2]
CCDS54814.1. [Q8TCQ1-1]
RefSeqiNP_001159845.1. NM_001166373.1. [Q8TCQ1-1]
NP_060393.1. NM_017923.3. [Q8TCQ1-2]
XP_016863823.1. XM_017008334.1. [Q8TCQ1-1]
UniGeneiHs.592804.
Hs.608487.

3D structure databases

ProteinModelPortaliQ8TCQ1.
SMRiQ8TCQ1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120348. 10 interactors.
STRINGi9606.ENSP00000274056.

PTM databases

iPTMnetiQ8TCQ1.
PhosphoSitePlusiQ8TCQ1.

Polymorphism and mutation databases

BioMutaiMARCH1.
DMDMi74762613.

Proteomic databases

EPDiQ8TCQ1.
PaxDbiQ8TCQ1.
PeptideAtlasiQ8TCQ1.
PRIDEiQ8TCQ1.

Protocols and materials databases

DNASUi55016.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000274056; ENSP00000274056; ENSG00000145416. [Q8TCQ1-1]
ENST00000339875; ENSP00000345676; ENSG00000145416. [Q8TCQ1-2]
ENST00000503008; ENSP00000427223; ENSG00000145416. [Q8TCQ1-1]
GeneIDi55016.
KEGGihsa:55016.
UCSCiuc003iqr.3. human. [Q8TCQ1-1]

Organism-specific databases

CTDi55016.
DisGeNETi55016.
GeneCardsiMARCH1.
HGNCiHGNC:26077. MARCH1.
HPAiHPA014600.
MIMi613331. gene.
neXtProtiNX_Q8TCQ1.
OpenTargetsiENSG00000145416.
PharmGKBiPA134986392.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1609. Eukaryota.
COG5183. LUCA.
GeneTreeiENSGT00730000110355.
HOGENOMiHOG000113483.
HOVERGENiHBG081957.
InParanoidiQ8TCQ1.
KOiK10656.
OMAiERRKICC.
PhylomeDBiQ8TCQ1.
TreeFamiTF319557.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

ChiTaRSiMARCH1. human.
GenomeRNAii55016.
PROiQ8TCQ1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000145416.
CleanExiHS_MARCH1.
ExpressionAtlasiQ8TCQ1. baseline and differential.
GenevisibleiQ8TCQ1. HS.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR033275. MARCH-like.
IPR011016. Znf_RING-CH.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PANTHERiPTHR23012. PTHR23012. 1 hit.
PfamiPF12906. RINGv. 1 hit.
[Graphical view]
SMARTiSM00744. RINGv. 1 hit.
[Graphical view]
PROSITEiPS51292. ZF_RING_CH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMARH1_HUMAN
AccessioniPrimary (citable) accession number: Q8TCQ1
Secondary accession number(s): D3DP29, Q9NWR0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: June 1, 2002
Last modified: November 2, 2016
This is version 124 of the entry and version 1 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 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. 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.