CKLF6_HUMAN
ID CKLF6_HUMAN Reviewed; 183 AA.
AC Q9NX76; Q6IAC4;
DT 19-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=CKLF-like MARVEL transmembrane domain-containing protein 6 {ECO:0000303|PubMed:28813417};
DE AltName: Full=Chemokine-like factor superfamily member 6 {ECO:0000303|PubMed:12782130};
GN Name=CMTM6 {ECO:0000303|PubMed:28813417, ECO:0000312|HGNC:HGNC:19177};
GN Synonyms=CKLFSF6 {ECO:0000303|PubMed:12782130};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Prostate;
RX PubMed=12782130; DOI=10.1016/s0888-7543(03)00095-8;
RA Han W., Ding P., Xu M., Wang L., Rui M., Shi S., Liu Y., Zheng Y., Chen Y.,
RA Yang T., Ma D.;
RT "Identification of eight genes encoding chemokine-like factor superfamily
RT members 1-8 (CKLFSF1-8) by in silico cloning and experimental validation.";
RL Genomics 81:609-617(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 1-19; 23-33 AND 160-166, ACETYLATION AT MET-1, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Platelet;
RA Bienvenut W.V., Claeys D.;
RL Submitted (NOV-2005) to UniProtKB.
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-8, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-171, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PD-L1/CD274; CD58; ARG1;
RP ENO1 AND TMPO, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=28813417; DOI=10.1038/nature23643;
RA Burr M.L., Sparbier C.E., Chan Y.C., Williamson J.C., Woods K.,
RA Beavis P.A., Lam E.Y.N., Henderson M.A., Bell C.C., Stolzenburg S.,
RA Gilan O., Bloor S., Noori T., Morgens D.W., Bassik M.C., Neeson P.J.,
RA Behren A., Darcy P.K., Dawson S.J., Voskoboinik I., Trapani J.A., Cebon J.,
RA Lehner P.J., Dawson M.A.;
RT "CMTM6 maintains the expression of PD-L1 and regulates anti-tumour
RT immunity.";
RL Nature 549:101-105(2017).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PD-L1/CD274 AND CMTM4,
RP IDENTIFICATION BY MASS SPECTROMETRY, AND TOPOLOGY.
RX PubMed=28813410; DOI=10.1038/nature23669;
RA Mezzadra R., Sun C., Jae L.T., Gomez-Eerland R., de Vries E., Wu W.,
RA Logtenberg M.E.W., Slagter M., Rozeman E.A., Hofland I., Broeks A.,
RA Horlings H.M., Wessels L.F.A., Blank C.U., Xiao Y., Heck A.J.R., Borst J.,
RA Brummelkamp T.R., Schumacher T.N.M.;
RT "Identification of CMTM6 and CMTM4 as PD-L1 protein regulators.";
RL Nature 549:106-110(2017).
CC -!- FUNCTION: Master regulator of recycling and plasma membrane expression
CC of PD-L1/CD274, an immune inhibitory ligand critical for immune
CC tolerance to self and antitumor immunity. Associates with both
CC constitutive and IFNG-induced PD-L1/CD274 at recycling endosomes, where
CC it protects PD-L1/CD274 from being targeted for lysosomal degradation,
CC likely by preventing its STUB1-mediated ubiquitination. May stabilize
CC PD-L1/CD274 expression on antigen presenting cells and potentiates
CC inhibitory signaling by PDCD1/CD279, its receptor on T-cells,
CC ultimately triggering T-cell anergy. {ECO:0000269|PubMed:28813410,
CC ECO:0000269|PubMed:28813417}.
CC -!- SUBUNIT: Interacts with PD-L1/CD274 (via transmembrane domain); the
CC interaction is direct (PubMed:28813417, PubMed:28813410). Interacts
CC with CMTM4 (PubMed:28813410). Interacts with CD58, ARG1, ENO1 and TMPO
CC (PubMed:28813417). {ECO:0000269|PubMed:28813410,
CC ECO:0000269|PubMed:28813417}.
CC -!- INTERACTION:
CC Q9NX76; Q6Q788: APOA5; NbExp=3; IntAct=EBI-1054315, EBI-3936819;
CC Q9NX76; Q96DR5: BPIFA2; NbExp=3; IntAct=EBI-1054315, EBI-10284754;
CC Q9NX76; O95971: CD160; NbExp=3; IntAct=EBI-1054315, EBI-4314390;
CC Q9NX76; Q9NZQ7: CD274; NbExp=14; IntAct=EBI-1054315, EBI-4314282;
CC Q9NX76; P25942: CD40; NbExp=3; IntAct=EBI-1054315, EBI-525714;
CC Q9NX76; Q9H5X1: CIAO2A; NbExp=3; IntAct=EBI-1054315, EBI-752069;
CC Q9NX76; Q8NI60: COQ8A; NbExp=3; IntAct=EBI-1054315, EBI-745535;
CC Q9NX76; Q5VYK3: ECPAS; NbExp=3; IntAct=EBI-1054315, EBI-521451;
CC Q9NX76; Q08426: EHHADH; NbExp=3; IntAct=EBI-1054315, EBI-2339219;
CC Q9NX76; Q9NQG6: MIEF1; NbExp=3; IntAct=EBI-1054315, EBI-740987;
CC Q9NX76; Q8N0V3: RBFA; NbExp=3; IntAct=EBI-1054315, EBI-3232108;
CC Q9NX76; P38159: RBMX; NbExp=3; IntAct=EBI-1054315, EBI-743526;
CC Q9NX76; Q9BVN2: RUSC1; NbExp=3; IntAct=EBI-1054315, EBI-6257312;
CC Q9NX76; P08579: SNRPB2; NbExp=3; IntAct=EBI-1054315, EBI-1053651;
CC Q9NX76; Q9NZD8: SPG21; NbExp=3; IntAct=EBI-1054315, EBI-742688;
CC Q9NX76; Q15560: TCEA2; NbExp=3; IntAct=EBI-1054315, EBI-710310;
CC Q9NX76; Q6PL24: TMED8; NbExp=3; IntAct=EBI-1054315, EBI-11603430;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:28813410,
CC ECO:0000269|PubMed:28813417}; Multi-pass membrane protein
CC {ECO:0000255}. Early endosome membrane {ECO:0000269|PubMed:28813417};
CC Multi-pass membrane protein {ECO:0000255}. Recycling endosome membrane
CC {ECO:0000269|PubMed:28813417}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Co-localizes with PD-L1/CD274 in the plasma
CC membrane and in recycling endosomes. {ECO:0000269|PubMed:28813417}.
CC -!- TISSUE SPECIFICITY: Expressed in the leukocytes, placenta and testis.
CC {ECO:0000269|PubMed:12782130}.
CC -!- SIMILARITY: Belongs to the chemokine-like factor family. {ECO:0000305}.
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DR EMBL; AF479261; AAN73039.1; -; mRNA.
DR EMBL; AK000403; BAA91141.1; -; mRNA.
DR EMBL; CR457231; CAG33512.1; -; mRNA.
DR EMBL; CH471055; EAW64429.1; -; Genomic_DNA.
DR EMBL; BC002797; AAH02797.1; -; mRNA.
DR CCDS; CCDS2653.1; -.
DR RefSeq; NP_060271.1; NM_017801.2.
DR AlphaFoldDB; Q9NX76; -.
DR BioGRID; 120259; 106.
DR IntAct; Q9NX76; 29.
DR MINT; Q9NX76; -.
DR STRING; 9606.ENSP00000205636; -.
DR iPTMnet; Q9NX76; -.
DR PhosphoSitePlus; Q9NX76; -.
DR SwissPalm; Q9NX76; -.
DR BioMuta; CMTM6; -.
DR DMDM; 34922183; -.
DR EPD; Q9NX76; -.
DR jPOST; Q9NX76; -.
DR MassIVE; Q9NX76; -.
DR MaxQB; Q9NX76; -.
DR PaxDb; Q9NX76; -.
DR PeptideAtlas; Q9NX76; -.
DR PRIDE; Q9NX76; -.
DR ProteomicsDB; 83052; -.
DR TopDownProteomics; Q9NX76; -.
DR Antibodypedia; 27750; 131 antibodies from 23 providers.
DR DNASU; 54918; -.
DR Ensembl; ENST00000205636.4; ENSP00000205636.3; ENSG00000091317.8.
DR GeneID; 54918; -.
DR KEGG; hsa:54918; -.
DR MANE-Select; ENST00000205636.4; ENSP00000205636.3; NM_017801.3; NP_060271.1.
DR UCSC; uc003cfa.2; human.
DR CTD; 54918; -.
DR DisGeNET; 54918; -.
DR GeneCards; CMTM6; -.
DR HGNC; HGNC:19177; CMTM6.
DR HPA; ENSG00000091317; Low tissue specificity.
DR MIM; 607889; gene.
DR neXtProt; NX_Q9NX76; -.
DR OpenTargets; ENSG00000091317; -.
DR PharmGKB; PA38816; -.
DR VEuPathDB; HostDB:ENSG00000091317; -.
DR eggNOG; KOG4788; Eukaryota.
DR GeneTree; ENSGT00940000157911; -.
DR HOGENOM; CLU_104458_1_0_1; -.
DR InParanoid; Q9NX76; -.
DR OMA; FIWKRRE; -.
DR OrthoDB; 1400503at2759; -.
DR PhylomeDB; Q9NX76; -.
DR TreeFam; TF317387; -.
DR PathwayCommons; Q9NX76; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; Q9NX76; -.
DR BioGRID-ORCS; 54918; 17 hits in 1081 CRISPR screens.
DR ChiTaRS; CMTM6; human.
DR GenomeRNAi; 54918; -.
DR Pharos; Q9NX76; Tbio.
DR PRO; PR:Q9NX76; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9NX76; protein.
DR Bgee; ENSG00000091317; Expressed in bronchial epithelial cell and 207 other tissues.
DR Genevisible; Q9NX76; HS.
DR GO; GO:0035577; C:azurophil granule membrane; TAS:Reactome.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; IDA:UniProtKB.
DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome.
DR GO; GO:0032456; P:endocytic recycling; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IMP:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; IMP:UniProtKB.
DR InterPro; IPR008253; Marvel.
DR Pfam; PF01284; MARVEL; 1.
DR PROSITE; PS51225; MARVEL; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cell membrane; Direct protein sequencing; Endosome; Membrane;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..183
FT /note="CKLF-like MARVEL transmembrane domain-containing
FT protein 6"
FT /id="PRO_0000186107"
FT TOPO_DOM 1..39
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:28813410"
FT TRANSMEM 40..60
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 61..67
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:28813410"
FT TRANSMEM 68..88
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 89..106
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:28813410"
FT TRANSMEM 107..127
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 128..134
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:28813410"
FT TRANSMEM 135..155
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 156..183
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:28813410"
FT DOMAIN 33..160
FT /note="MARVEL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00581"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 8
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 171
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 91
FT /note="T -> A (in dbSNP:rs35574803)"
FT /id="VAR_061998"
SQ SEQUENCE 183 AA; 20419 MW; 43DAEB652A6B50B4 CRC64;
MENGAVYSPT TEEDPGPARG PRSGLAAYFF MGRLPLLRRV LKGLQLLLSL LAFICEEVVS
QCTLCGGLYF FEFVSCSAFL LSLLILIVYC TPFYERVDTT KVKSSDFYIT LGTGCVFLLA
SIIFVSTHDR TSAEIAAIVF GFIASFMFLL DFITMLYEKR QESQLRKPEN TTRAEALTEP
LNA
