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Protein

CKLF-like MARVEL transmembrane domain-containing protein 6

Gene

CMTM6

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

Functioni

Master regulator of recycling and plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity. Associates with both constitutive and IFNG-induced PD-L1/CD274 at recycling endosomes, where it protects PD-L1/CD274 from being targeted for lysosomal degradation, likely by preventing its STUB1-mediated ubiquitination. May stabilize PD-L1/CD274 expression on antigen presenting cells and potentiates inhibitory signaling by PDCD1/CD279, its receptor on T-cells, ultimately triggering T-cell anergy.2 Publications

GO - Molecular functioni

GO - Biological processi

  • chemotaxis Source: UniProtKB-KW
  • endocytic recycling Source: UniProtKB
  • neutrophil degranulation Source: Reactome
  • protein transport Source: UniProtKB
  • regulation of protein stability Source: UniProtKB

Keywordsi

Biological processTransport

Enzyme and pathway databases

ReactomeiR-HSA-6798695 Neutrophil degranulation

Names & Taxonomyi

Protein namesi
Recommended name:
CKLF-like MARVEL transmembrane domain-containing protein 61 Publication
Alternative name(s):
Chemokine-like factor superfamily member 61 Publication
Gene namesi
Name:CMTM61 PublicationImported
Synonyms:CKLFSF61 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000091317.7
HGNCiHGNC:19177 CMTM6
MIMi607889 gene
neXtProtiNX_Q9NX76

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 – 39Cytoplasmic1 PublicationAdd BLAST39
Transmembranei40 – 60HelicalSequence analysisAdd BLAST21
Topological domaini61 – 67Extracellular1 Publication7
Transmembranei68 – 88HelicalSequence analysisAdd BLAST21
Topological domaini89 – 106Cytoplasmic1 PublicationAdd BLAST18
Transmembranei107 – 127HelicalSequence analysisAdd BLAST21
Topological domaini128 – 134Extracellular1 Publication7
Transmembranei135 – 155HelicalSequence analysisAdd BLAST21
Topological domaini156 – 183Cytoplasmic1 PublicationAdd BLAST28

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Organism-specific databases

OpenTargetsiENSG00000091317
PharmGKBiPA38816

Polymorphism and mutation databases

BioMutaiCMTM6
DMDMi34922183

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001861071 – 183CKLF-like MARVEL transmembrane domain-containing protein 6Add BLAST183

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1 Publication1
Modified residuei8PhosphoserineCombined sources1
Modified residuei171PhosphothreonineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9NX76
MaxQBiQ9NX76
PaxDbiQ9NX76
PeptideAtlasiQ9NX76
PRIDEiQ9NX76
TopDownProteomicsiQ9NX76

PTM databases

iPTMnetiQ9NX76
PhosphoSitePlusiQ9NX76
SwissPalmiQ9NX76

Expressioni

Tissue specificityi

Expressed in the leukocytes, placenta and testis.1 Publication

Gene expression databases

BgeeiENSG00000091317
CleanExiHS_CMTM6
GenevisibleiQ9NX76 HS

Organism-specific databases

HPAiHPA026980

Interactioni

Subunit structurei

Interacts with PD-L1/CD274 (via transmembrane domain); the interaction is direct (PubMed:28813417, PubMed:28813410). Interacts with CMTM4 (PubMed:28813410). Interacts with CD58, ARG1, ENO1 and TMPO (PubMed:28813417).2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CD274Q9NZQ711EBI-1054315,EBI-4314282

GO - Molecular functioni

Protein-protein interaction databases

BioGridi120259, 20 interactors
IntActiQ9NX76, 11 interactors
MINTiQ9NX76
STRINGi9606.ENSP00000205636

Structurei

3D structure databases

ProteinModelPortaliQ9NX76
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini33 – 160MARVELPROSITE-ProRule annotationAdd BLAST128

Sequence similaritiesi

Belongs to the chemokine-like factor family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4788 Eukaryota
ENOG4111IAF LUCA
GeneTreeiENSGT00530000063578
HOGENOMiHOG000261609
HOVERGENiHBG050980
InParanoidiQ9NX76
OMAiHDRTSAE
OrthoDBiEOG091G0KPO
PhylomeDBiQ9NX76
TreeFamiTF317387

Family and domain databases

InterProiView protein in InterPro
IPR008253 Marvel
PfamiView protein in Pfam
PF01284 MARVEL, 1 hit
PROSITEiView protein in PROSITE
PS51225 MARVEL, 1 hit

Sequencei

Sequence statusi: Complete.

Q9NX76-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MENGAVYSPT TEEDPGPARG PRSGLAAYFF MGRLPLLRRV LKGLQLLLSL
60 70 80 90 100
LAFICEEVVS QCTLCGGLYF FEFVSCSAFL LSLLILIVYC TPFYERVDTT
110 120 130 140 150
KVKSSDFYIT LGTGCVFLLA SIIFVSTHDR TSAEIAAIVF GFIASFMFLL
160 170 180
DFITMLYEKR QESQLRKPEN TTRAEALTEP LNA
Length:183
Mass (Da):20,419
Last modified:October 1, 2000 - v1
Checksum:i43DAEB652A6B50B4
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06199891T → A. Corresponds to variant dbSNP:rs35574803Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF479261 mRNA Translation: AAN73039.1
AK000403 mRNA Translation: BAA91141.1
CR457231 mRNA Translation: CAG33512.1
CH471055 Genomic DNA Translation: EAW64429.1
BC002797 mRNA Translation: AAH02797.1
CCDSiCCDS2653.1
RefSeqiNP_060271.1, NM_017801.2
UniGeneiHs.380627
Hs.731820

Genome annotation databases

EnsembliENST00000205636; ENSP00000205636; ENSG00000091317
GeneIDi54918
KEGGihsa:54918
UCSCiuc003cfa.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCKLF6_HUMAN
AccessioniPrimary (citable) accession number: Q9NX76
Secondary accession number(s): Q6IAC4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: October 1, 2000
Last modified: May 23, 2018
This is version 128 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

Complete proteome, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health