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   24-JAN-2024, entry version 140.
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}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
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   SMR; Q8IZR5; -.
DR   BioGRID; 126972; 35.
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; 9606-ENSP00000333833; -.
DR   PeptideAtlas; Q8IZR5; -.
DR   ProteomicsDB; 71410; -. [Q8IZR5-1]
DR   ProteomicsDB; 71411; -. [Q8IZR5-2]
DR   ProteomicsDB; 71412; -. [Q8IZR5-3]
DR   Pumba; Q8IZR5; -.
DR   Antibodypedia; 15544; 170 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   AGR; HGNC:19175; -.
DR   CTD; 146223; -.
DR   DisGeNET; 146223; -.
DR   GeneCards; CMTM4; -.
DR   HGNC; HGNC:19175; CMTM4.
DR   HPA; ENSG00000183723; Low tissue specificity.
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; 5359001at2759; -.
DR   PhylomeDB; Q8IZR5; -.
DR   TreeFam; TF317387; -.
DR   PathwayCommons; Q8IZR5; -.
DR   SignaLink; Q8IZR5; -.
DR   BioGRID-ORCS; 146223; 15 hits in 1154 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 189 other cell types or tissues.
DR   ExpressionAtlas; Q8IZR5; baseline and differential.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR   InterPro; IPR008253; Marvel.
DR   PANTHER; PTHR22776:SF29; CKLF-LIKE MARVEL TRANSMEMBRANE DOMAIN-CONTAINING PROTEIN 4; 1.
DR   PANTHER; PTHR22776; MARVEL-CONTAINING POTENTIAL LIPID RAFT-ASSOCIATED PROTEIN; 1.
DR   Pfam; PF01284; MARVEL; 1.
DR   PROSITE; PS51225; MARVEL; 1.
DR   Genevisible; Q8IZR5; HS.
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
//