CCD25_HUMAN
ID CCD25_HUMAN Reviewed; 208 AA.
AC Q86WR0; Q0P663; Q96SI2; Q9NV98;
DT 02-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Coiled-coil domain-containing protein 25 {ECO:0000305};
GN Name=CCDC25 {ECO:0000303|PubMed:32528174, ECO:0000312|HGNC:HGNC:25591};
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Retinoblastoma, Teratocarcinoma, and Trachea;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Retinoblastoma, and Uterus;
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-204, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-204, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP IDENTIFICATION BY MASS 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-204, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-23, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-204, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE 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 [11]
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-204, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-204, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [14]
RP FUNCTION, DNA-BINDING, SUBCELLULAR LOCATION, INTERACTION WITH ILK, AND
RP MUTAGENESIS OF 16-THR--GLY-20 AND 21-LYS--GLU-25.
RX PubMed=32528174; DOI=10.1038/s41586-020-2394-6;
RA Yang L., Liu Q., Zhang X., Liu X., Zhou B., Chen J., Huang D., Li J.,
RA Li H., Chen F., Liu J., Xing Y., Chen X., Su S., Song E.;
RT "DNA of neutrophil extracellular traps promotes cancer metastasis via
RT CCDC25.";
RL Nature 583:133-138(2020).
CC -!- FUNCTION: Transmembrane receptor that senses neutrophil extracellular
CC traps (NETs) and triggers the ILK-PARVB pathway to enhance cell
CC motility (PubMed:32528174). NETs are mainly composed of DNA fibers and
CC are released by neutrophils to bind pathogens during inflammation
CC (PubMed:32528174). Formation of NETs is also associated with cancer
CC metastasis, NET-DNA acting as a chemotactic factor to attract cancer
CC cells (PubMed:32528174). Specifically binds NETs on its extracellular
CC region, in particular the 8-OHdG-enriched DNA present in NETs, and
CC recruits ILK, initiating the ILK-PARVB cascade to induce cytoskeleton
CC rearrangement and directional migration of cells (PubMed:32528174). In
CC the context of cancer, promotes cancer metastasis by sensing NETs and
CC promoting migration of tumor cells (PubMed:32528174).
CC {ECO:0000269|PubMed:32528174}.
CC -!- SUBUNIT: Interacts (via cytoplasmic region) with ILK.
CC {ECO:0000269|PubMed:32528174}.
CC -!- INTERACTION:
CC Q86WR0; Q53SE7: FLJ13057; NbExp=3; IntAct=EBI-2690264, EBI-10172181;
CC Q86WR0; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-2690264, EBI-742388;
CC Q86WR0; P36406: TRIM23; NbExp=3; IntAct=EBI-2690264, EBI-740098;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:32528174};
CC Single-pass membrane protein {ECO:0000305|PubMed:32528174}.
CC Endomembrane system {ECO:0000269|PubMed:32528174}. Note=Localizes to
CC cytoplasmic membrane in tumor cells. {ECO:0000269|PubMed:32528174}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q86WR0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86WR0-2; Sequence=VSP_056046;
CC -!- SIMILARITY: Belongs to the CCDC25 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91857.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK001715; BAA91857.1; ALT_INIT; mRNA.
DR EMBL; AK027900; BAB55442.1; -; mRNA.
DR EMBL; AK292875; BAF85564.1; -; mRNA.
DR EMBL; AC013643; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC104997; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471080; EAW63539.1; -; Genomic_DNA.
DR EMBL; BC032588; AAH32588.1; -; mRNA.
DR EMBL; BC049197; AAH49197.2; -; mRNA.
DR EMBL; BC065295; AAH65295.1; -; mRNA.
DR CCDS; CCDS6062.2; -. [Q86WR0-1]
DR CCDS; CCDS78323.1; -. [Q86WR0-2]
DR RefSeq; NP_001291458.1; NM_001304529.1.
DR RefSeq; NP_001291459.1; NM_001304530.1.
DR RefSeq; NP_001291461.1; NM_001304532.1. [Q86WR0-2]
DR RefSeq; NP_060716.2; NM_018246.2. [Q86WR0-1]
DR RefSeq; XP_011542872.1; XM_011544570.2. [Q86WR0-2]
DR RefSeq; XP_011542873.1; XM_011544571.2. [Q86WR0-2]
DR AlphaFoldDB; Q86WR0; -.
DR SMR; Q86WR0; -.
DR BioGRID; 120537; 29.
DR IntAct; Q86WR0; 10.
DR MINT; Q86WR0; -.
DR STRING; 9606.ENSP00000348933; -.
DR GlyGen; Q86WR0; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q86WR0; -.
DR MetOSite; Q86WR0; -.
DR PhosphoSitePlus; Q86WR0; -.
DR BioMuta; CCDC25; -.
DR DMDM; 94707504; -.
DR EPD; Q86WR0; -.
DR jPOST; Q86WR0; -.
DR MassIVE; Q86WR0; -.
DR MaxQB; Q86WR0; -.
DR PaxDb; Q86WR0; -.
DR PeptideAtlas; Q86WR0; -.
DR PRIDE; Q86WR0; -.
DR ProteomicsDB; 58773; -.
DR ProteomicsDB; 70191; -. [Q86WR0-1]
DR Antibodypedia; 10313; 95 antibodies from 23 providers.
DR DNASU; 55246; -.
DR Ensembl; ENST00000356537.9; ENSP00000348933.4; ENSG00000147419.19. [Q86WR0-1]
DR Ensembl; ENST00000522915.5; ENSP00000428000.1; ENSG00000147419.19. [Q86WR0-2]
DR GeneID; 55246; -.
DR KEGG; hsa:55246; -.
DR MANE-Select; ENST00000356537.9; ENSP00000348933.4; NM_018246.3; NP_060716.2.
DR UCSC; uc003xgc.4; human. [Q86WR0-1]
DR CTD; 55246; -.
DR DisGeNET; 55246; -.
DR GeneCards; CCDC25; -.
DR HGNC; HGNC:25591; CCDC25.
DR HPA; ENSG00000147419; Low tissue specificity.
DR MIM; 619100; gene.
DR neXtProt; NX_Q86WR0; -.
DR OpenTargets; ENSG00000147419; -.
DR PharmGKB; PA142672183; -.
DR VEuPathDB; HostDB:ENSG00000147419; -.
DR eggNOG; KOG3272; Eukaryota.
DR GeneTree; ENSGT00390000004380; -.
DR HOGENOM; CLU_076656_0_1_1; -.
DR InParanoid; Q86WR0; -.
DR OMA; DVWFHVH; -.
DR OrthoDB; 1380409at2759; -.
DR PhylomeDB; Q86WR0; -.
DR TreeFam; TF300013; -.
DR PathwayCommons; Q86WR0; -.
DR SignaLink; Q86WR0; -.
DR BioGRID-ORCS; 55246; 19 hits in 1045 CRISPR screens.
DR ChiTaRS; CCDC25; human.
DR GeneWiki; Coiled-Coil_Domain_Containing_Protein_%E2%80%93_25; -.
DR GenomeRNAi; 55246; -.
DR Pharos; Q86WR0; Tbio.
DR PRO; PR:Q86WR0; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q86WR0; protein.
DR Bgee; ENSG00000147419; Expressed in oocyte and 198 other tissues.
DR ExpressionAtlas; Q86WR0; baseline and differential.
DR Genevisible; Q86WR0; HS.
DR GO; GO:0012505; C:endomembrane system; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:2000147; P:positive regulation of cell motility; IDA:UniProtKB.
DR InterPro; IPR039730; Jlp2/Ccd25.
DR InterPro; IPR008532; NFACT_RNA-bd.
DR PANTHER; PTHR13049; PTHR13049; 1.
DR Pfam; PF05670; NFACT-R_1; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cell membrane; Coiled coil; DNA-binding;
KW Membrane; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..208
FT /note="Coiled-coil domain-containing protein 25"
FT /id="PRO_0000233404"
FT TOPO_DOM 1..66
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:32528174"
FT TRANSMEM 67..83
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 84..208
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:32528174"
FT REGION 21..25
FT /note="DNA-binding"
FT /evidence="ECO:0000269|PubMed:32528174"
FT REGION 148..208
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 117..187
FT /evidence="ECO:0000255"
FT COMPBIAS 148..186
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 189..208
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 23
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 204
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..68
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_056046"
FT MUTAGEN 16..20
FT /note="TIYMG->AAAAA: Does not affect binding to neutrophil
FT extracellular traps (NETs)."
FT /evidence="ECO:0000269|PubMed:32528174"
FT MUTAGEN 21..25
FT /note="KDKYE->AAAAA: Abolished binding to neutrophil
FT extracellular traps (NETs)."
FT /evidence="ECO:0000269|PubMed:32528174"
SQ SEQUENCE 208 AA; 24479 MW; 8EA9E0FFD84494B6 CRC64;
MVFYFTSSSV NSSAYTIYMG KDKYENEDLI KHGWPEDIWF HVDKLSSAHV YLRLHKGENI
EDIPKEVLMD CAHLVKANSI QGCKMNNVNV VYTPWSNLKK TADMDVGQIG FHRQKDVKIV
TVEKKVNEIL NRLEKTKVER FPDLAAEKEC RDREERNEKK AQIQEMKKRE KEEMKKKREM
DELRSYSSLM KVENMSSNQD GNDSDEFM
