CKLF4_HUMAN
ID CKLF4_HUMAN Reviewed; 234 AA.
AC Q8IZR5; Q52M40; Q8IZR4; Q8IZV1;
DT 19-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=CKLF-like MARVEL transmembrane domain-containing protein 4;
DE AltName: Full=Chemokine-like factor superfamily member 4;
GN Name=CMTM4 {ECO:0000312|HGNC:HGNC:19175}; Synonyms=CKLFSF4;
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] (ISOFORMS 1 AND 3).
RC TISSUE=Kidney;
RA Ding P., Han W., Shi S., Yang T., Song Q., Zhang Y., Ma D.;
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC TISSUE=Spleen;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Liver;
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 [4]
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-194, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [6]
RP FUNCTION, INTERACTION WITH PD-L1/CD274 AND CMTM6, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
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: Acts as a backup for CMTM6 to regulate plasma membrane
CC expression of PD-L1/CD274, an immune inhibitory ligand critical for
CC immune tolerance to self and antitumor immunity. May protect PD-
CC L1/CD274 from being polyubiquitinated and targeted for degradation.
CC {ECO:0000269|PubMed:28813410}.
CC -!- SUBUNIT: Interacts with PD-L1/CD274 and CMTM6.
CC {ECO:0000269|PubMed:28813410}.
CC -!- INTERACTION:
CC Q8IZR5; Q9NZQ7: CD274; NbExp=3; IntAct=EBI-3925367, EBI-4314282;
CC Q8IZR5-2; P06727: APOA4; NbExp=3; IntAct=EBI-17278014, EBI-1222447;
CC Q8IZR5-2; Q8NI60: COQ8A; NbExp=3; IntAct=EBI-17278014, EBI-745535;
CC Q8IZR5-2; Q9BY27: DGCR6L; NbExp=3; IntAct=EBI-17278014, EBI-742953;
CC Q8IZR5-2; Q9NR28: DIABLO; NbExp=3; IntAct=EBI-17278014, EBI-517508;
CC Q8IZR5-2; C9JCN9: HSBP1L1; NbExp=3; IntAct=EBI-17278014, EBI-2685549;
CC Q8IZR5-2; Q504T8: MIDN; NbExp=3; IntAct=EBI-17278014, EBI-7153979;
CC Q8IZR5-2; Q96AL5: PBX3; NbExp=3; IntAct=EBI-17278014, EBI-741171;
CC Q8IZR5-2; P43378: PTPN9; NbExp=3; IntAct=EBI-17278014, EBI-742898;
CC Q8IZR5-2; Q9H0W8: SMG9; NbExp=3; IntAct=EBI-17278014, EBI-2872322;
CC Q8IZR5-2; Q13596: SNX1; NbExp=3; IntAct=EBI-17278014, EBI-2822329;
CC Q8IZR5-2; Q9NZD8: SPG21; NbExp=3; IntAct=EBI-17278014, EBI-742688;
CC Q8IZR5-2; Q99909: SSX3; NbExp=3; IntAct=EBI-17278014, EBI-10295431;
CC Q8IZR5-2; P49675: STAR; NbExp=3; IntAct=EBI-17278014, EBI-722932;
CC Q8IZR5-2; Q969Z0: TBRG4; NbExp=3; IntAct=EBI-17278014, EBI-702328;
CC Q8IZR5-2; Q15560: TCEA2; NbExp=3; IntAct=EBI-17278014, EBI-710310;
CC Q8IZR5-2; P49638: TTPA; NbExp=3; IntAct=EBI-17278014, EBI-10210710;
CC Q8IZR5-2; Q9BQ24: ZFYVE21; NbExp=3; IntAct=EBI-17278014, EBI-2849569;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8IZR5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IZR5-2; Sequence=VSP_008261;
CC Name=3;
CC IsoId=Q8IZR5-3; Sequence=VSP_008260, VSP_008261;
CC -!- TISSUE SPECIFICITY: Highly expressed in testis and prostate.
CC {ECO:0000269|PubMed:12782130}.
CC -!- SIMILARITY: Belongs to the chemokine-like factor family. {ECO:0000305}.
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DR EMBL; AF521889; AAN73845.1; -; mRNA.
DR EMBL; AF521890; AAN73846.1; -; mRNA.
DR EMBL; AF479814; AAN73436.1; -; mRNA.
DR EMBL; BC093679; AAH93679.1; -; mRNA.
DR CCDS; CCDS10817.1; -. [Q8IZR5-1]
DR CCDS; CCDS42170.1; -. [Q8IZR5-2]
DR RefSeq; NP_848933.1; NM_178818.2. [Q8IZR5-1]
DR RefSeq; NP_852662.1; NM_181521.2. [Q8IZR5-2]
DR RefSeq; XP_011521184.1; XM_011522882.1. [Q8IZR5-3]
DR AlphaFoldDB; Q8IZR5; -.
DR BioGRID; 126972; 34.
DR IntAct; Q8IZR5; 30.
DR STRING; 9606.ENSP00000333833; -.
DR TCDB; 1.A.64.4.4; the plasmolipin (plasmolipin) family.
DR iPTMnet; Q8IZR5; -.
DR PhosphoSitePlus; Q8IZR5; -.
DR SwissPalm; Q8IZR5; -.
DR BioMuta; CMTM4; -.
DR DMDM; 34921813; -.
DR EPD; Q8IZR5; -.
DR jPOST; Q8IZR5; -.
DR MassIVE; Q8IZR5; -.
DR MaxQB; Q8IZR5; -.
DR PaxDb; Q8IZR5; -.
DR PeptideAtlas; Q8IZR5; -.
DR PRIDE; Q8IZR5; -.
DR ProteomicsDB; 71410; -. [Q8IZR5-1]
DR ProteomicsDB; 71411; -. [Q8IZR5-2]
DR ProteomicsDB; 71412; -. [Q8IZR5-3]
DR Antibodypedia; 15544; 145 antibodies from 26 providers.
DR DNASU; 146223; -.
DR Ensembl; ENST00000330687.8; ENSP00000333833.4; ENSG00000183723.13. [Q8IZR5-1]
DR Ensembl; ENST00000394106.7; ENSP00000377666.2; ENSG00000183723.13. [Q8IZR5-2]
DR Ensembl; ENST00000563952.1; ENSP00000456380.1; ENSG00000183723.13. [Q8IZR5-3]
DR GeneID; 146223; -.
DR KEGG; hsa:146223; -.
DR MANE-Select; ENST00000394106.7; ENSP00000377666.2; NM_181521.3; NP_852662.1. [Q8IZR5-2]
DR UCSC; uc002epz.3; human. [Q8IZR5-1]
DR CTD; 146223; -.
DR DisGeNET; 146223; -.
DR GeneCards; CMTM4; -.
DR HGNC; HGNC:19175; CMTM4.
DR HPA; ENSG00000183723; Tissue enhanced (brain).
DR MIM; 607887; gene.
DR neXtProt; NX_Q8IZR5; -.
DR OpenTargets; ENSG00000183723; -.
DR PharmGKB; PA38814; -.
DR VEuPathDB; HostDB:ENSG00000183723; -.
DR eggNOG; KOG4788; Eukaryota.
DR GeneTree; ENSGT00940000159573; -.
DR HOGENOM; CLU_104458_0_0_1; -.
DR InParanoid; Q8IZR5; -.
DR OMA; SFICIET; -.
DR OrthoDB; 1400503at2759; -.
DR PhylomeDB; Q8IZR5; -.
DR TreeFam; TF317387; -.
DR PathwayCommons; Q8IZR5; -.
DR SignaLink; Q8IZR5; -.
DR BioGRID-ORCS; 146223; 15 hits in 1076 CRISPR screens.
DR ChiTaRS; CMTM4; human.
DR GenomeRNAi; 146223; -.
DR Pharos; Q8IZR5; Tbio.
DR PRO; PR:Q8IZR5; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q8IZR5; protein.
DR Bgee; ENSG00000183723; Expressed in secondary oocyte and 187 other tissues.
DR ExpressionAtlas; Q8IZR5; baseline and differential.
DR Genevisible; Q8IZR5; HS.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR InterPro; IPR008253; Marvel.
DR Pfam; PF01284; MARVEL; 1.
DR PROSITE; PS51225; MARVEL; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Membrane; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..234
FT /note="CKLF-like MARVEL transmembrane domain-containing
FT protein 4"
FT /id="PRO_0000186103"
FT TRANSMEM 59..79
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 85..105
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 123..143
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 151..171
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 49..176
FT /note="MARVEL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00581"
FT REGION 1..38
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 14..35
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 194
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 34..62
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_008260"
FT VAR_SEQ 209..234
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:12782130,
FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.1"
FT /id="VSP_008261"
SQ SEQUENCE 234 AA; 25828 MW; 629B5CCEE873C895 CRC64;
MRSGEELDGF EGEASSTSMI SGASSPYQPT TEPVSQRRGL AGLRCDPDYL RGALGRLKVA
QVILALIAFI CIETIMACSP CEGLYFFEFV SCSAFVVTGV LLIMFSLNLH MRIPQINWNL
TDLVNTGLSA FLFFIASIVL AALNHRAGAE IAAVIFGFLA TAAYAVNTFL AVQKWRVSVR
QQSTNDYIRA RTESRDVDSR PEIQRLDTFS YSTNVTVRKK SPTNLLSLNH WQLA
