ID   CXL10_MOUSE             Reviewed;          98 AA.
AC   P17515;
DT   01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1990, sequence version 1.
DT   27-MAR-2024, entry version 197.
DE   RecName: Full=C-X-C motif chemokine 10;
DE   AltName: Full=10 kDa interferon gamma-induced protein;
DE            Short=Gamma-IP10;
DE            Short=IP-10;
DE   AltName: Full=C7;
DE   AltName: Full=Interferon-gamma induced protein CRG-2;
DE   AltName: Full=Small-inducible cytokine B10;
DE   Flags: Precursor;
GN   Name=Cxcl10; Synonyms=Crg2, Ifi10, Inp10, Scyb10;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=2189406; DOI=10.1016/0006-291x(90)91164-n;
RA   Ohmori Y., Hamilton T.A.;
RT   "A macrophage LPS-inducible early gene encodes the murine homologue of IP-
RT   10.";
RL   Biochem. Biophys. Res. Commun. 168:1261-1267(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2118520; DOI=10.1016/s0021-9258(18)77222-0;
RA   Vanguri P., Farber J.M.;
RT   "Identification of CRG-2. An interferon-inducible mRNA predicted to encode
RT   a murine monokine.";
RL   J. Biol. Chem. 265:15049-15057(1990).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=DBA/2J; TISSUE=Liver;
RX   PubMed=8454640; DOI=10.1016/s0021-9258(18)53303-2;
RA   Ohmori Y., Hamilton T.A.;
RT   "Cooperative interaction between interferon (IFN) stimulus response element
RT   and kappa B sequence motifs controls IFN gamma- and lipopolysaccharide-
RT   stimulated transcription from the murine IP-10 promoter.";
RL   J. Biol. Chem. 268:6677-6688(1993).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Thymus;
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   TISSUE SPECIFICITY.
RX   PubMed=8145049; DOI=10.1084/jem.179.4.1373;
RA   Gattass C.R., King L.B., Luster A.D., Ashwell J.D.;
RT   "Constitutive expression of interferon gamma-inducible protein 10 in
RT   lymphoid organs and inducible expression in T cells and thymocytes.";
RL   J. Exp. Med. 179:1373-1378(1994).
RN   [6]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=15456824; DOI=10.1523/jneurosci.2451-04.2004;
RA   Rappert A., Bechmann I., Pivneva T., Mahlo J., Biber K., Nolte C.,
RA   Kovac A.D., Gerard C., Boddeke H.W., Nitsch R., Kettenmann H.;
RT   "CXCR3-dependent microglial recruitment is essential for dendrite loss
RT   after brain lesion.";
RL   J. Neurosci. 24:8500-8509(2004).
RN   [7]
RP   FUNCTION.
RX   PubMed=18624292; DOI=10.1002/eji.200838155;
RA   Lindell D.M., Lane T.E., Lukacs N.W.;
RT   "CXCL10/CXCR3-mediated responses promote immunity to respiratory syncytial
RT   virus infection by augmenting dendritic cell and CD8(+) T cell efficacy.";
RL   Eur. J. Immunol. 38:2168-2179(2008).
RN   [8]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=19017990; DOI=10.4049/jimmunol.181.11.7985;
RA   Wuest T.R., Carr D.J.;
RT   "Dysregulation of CXCR3 signaling due to CXCL10 deficiency impairs the
RT   antiviral response to herpes simplex virus 1 infection.";
RL   J. Immunol. 181:7985-7993(2008).
RN   [9]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=28468883; DOI=10.1128/jvi.00278-17;
RA   Srivastava R., Khan A.A., Chilukuri S., Syed S.A., Tran T.T., Furness J.,
RA   Bahraoui E., BenMohamed L.;
RT   "CXCL10/CXCR3-Dependent Mobilization of Herpes Simplex Virus-Specific CD8+
RT   TEM and CD8+ TRM Cells within Infected Tissues Allows Efficient Protection
RT   against Recurrent Herpesvirus Infection and Disease.";
RL   J. Virol. 91:0-0(2017).
RN   [10]
RP   FUNCTION.
RX   PubMed=28623423; DOI=10.1007/s10456-017-9561-x;
RA   Gao N., Liu X., Wu J., Li J., Dong C., Wu X., Xiao X., Yu F.X.;
RT   "CXCL10 suppression of hem- and lymph-angiogenesis in inflamed corneas
RT   through MMP13.";
RL   Angiogenesis 20:505-518(2017).
RN   [11]
RP   X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 23-89, DISULFIDE BONDS, AND
RP   SUBUNIT.
RX   PubMed=18560148; DOI=10.1107/s0907444908007026;
RA   Jabeen T., Leonard P., Jamaluddin H., Acharya K.R.;
RT   "Structure of mouse IP-10, a chemokine.";
RL   Acta Crystallogr. D 64:611-619(2008).
CC   -!- FUNCTION: Pro-inflammatory cytokine that is involved in a wide variety
CC       of processes such as chemotaxis, differentiation, and activation of
CC       peripheral immune cells, regulation of cell growth, apoptosis and
CC       modulation of angiostatic effects (By similarity) (PubMed:28623423).
CC       Plays thereby an important role during viral infections by stimulating
CC       the activation and migration of immune cells to the infected sites
CC       (PubMed:18624292, PubMed:19017990, PubMed:28468883). Mechanistically,
CC       binding of CXCL10 to the CXCR3 receptor activates G protein-mediated
CC       signaling and results in downstream activation of phospholipase C-
CC       dependent pathway, an increase in intracellular calcium production and
CC       actin reorganization. In turn, recruitment of activated Th1 lymphocytes
CC       occurs at sites of inflammation (By similarity). Activation of the
CC       CXCL10/CXCR3 axis also plays an important role in neurons in response
CC       to brain injury for activating microglia, the resident macrophage
CC       population of the central nervous system, and directing them to the
CC       lesion site. This recruitment is an essential element for neuronal
CC       reorganization (PubMed:15456824). {ECO:0000250|UniProtKB:P02778,
CC       ECO:0000269|PubMed:15456824, ECO:0000269|PubMed:18624292,
CC       ECO:0000269|PubMed:19017990, ECO:0000269|PubMed:28468883,
CC       ECO:0000269|PubMed:28623423}.
CC   -!- SUBUNIT: Monomer, dimer, and tetramer (PubMed:18560148). Interacts with
CC       CXCR3 (via N-terminus) (By similarity). {ECO:0000250|UniProtKB:P02778,
CC       ECO:0000269|PubMed:18560148}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P02778}.
CC   -!- TISSUE SPECIFICITY: Expressed in the spleen, thymus, lymph nodes and
CC       liver (PubMed:8145049). Expressed in astrocytes, microglia, and neurons
CC       (PubMed:15456824). {ECO:0000269|PubMed:15456824,
CC       ECO:0000269|PubMed:8145049}.
CC   -!- INDUCTION: By interferon gamma.
CC   -!- DISRUPTION PHENOTYPE: CXCL10-deficient mice possess a significantly
CC       reduced or delayed infiltration of NK and HSV-1-specific CD8+ T cells
CC       into herpes virus-infected tissue. In consequence, the antiviral
CC       response is delayed. {ECO:0000269|PubMed:19017990,
CC       ECO:0000269|PubMed:28468883}.
CC   -!- SIMILARITY: Belongs to the intercrine alpha (chemokine CxC) family.
CC       {ECO:0000305}.
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DR   EMBL; M33266; AAA02968.1; -; mRNA.
DR   EMBL; M86829; AAA21489.1; -; mRNA.
DR   EMBL; L07417; AAA75249.1; -; Genomic_DNA.
DR   EMBL; BC030067; AAH30067.1; -; mRNA.
DR   CCDS; CCDS39153.1; -.
DR   PIR; A45492; A45492.
DR   RefSeq; NP_067249.1; NM_021274.2.
DR   PDB; 2R3Z; X-ray; 2.50 A; A/B/C/D=23-89.
DR   PDBsum; 2R3Z; -.
DR   AlphaFoldDB; P17515; -.
DR   SMR; P17515; -.
DR   STRING; 10090.ENSMUSP00000047646; -.
DR   PhosphoSitePlus; P17515; -.
DR   PaxDb; 10090-ENSMUSP00000047646; -.
DR   ProteomicsDB; 284079; -.
DR   Antibodypedia; 6335; 984 antibodies from 41 providers.
DR   DNASU; 15945; -.
DR   Ensembl; ENSMUST00000038816.13; ENSMUSP00000047646.7; ENSMUSG00000034855.14.
DR   GeneID; 15945; -.
DR   KEGG; mmu:15945; -.
DR   UCSC; uc008ycz.2; mouse.
DR   AGR; MGI:1352450; -.
DR   CTD; 3627; -.
DR   MGI; MGI:1352450; Cxcl10.
DR   VEuPathDB; HostDB:ENSMUSG00000034855; -.
DR   eggNOG; ENOG502S7MM; Eukaryota.
DR   GeneTree; ENSGT00940000161759; -.
DR   InParanoid; P17515; -.
DR   OMA; VRCTCIK; -.
DR   OrthoDB; 4264143at2759; -.
DR   PhylomeDB; P17515; -.
DR   TreeFam; TF333433; -.
DR   Reactome; R-MMU-380108; Chemokine receptors bind chemokines.
DR   Reactome; R-MMU-418594; G alpha (i) signalling events.
DR   BioGRID-ORCS; 15945; 2 hits in 82 CRISPR screens.
DR   EvolutionaryTrace; P17515; -.
DR   PRO; PR:P17515; -.
DR   Proteomes; UP000000589; Chromosome 5.
DR   RNAct; P17515; Protein.
DR   Bgee; ENSMUSG00000034855; Expressed in mesenteric lymph node and 84 other cell types or tissues.
DR   ExpressionAtlas; P17515; baseline and differential.
DR   GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR   GO; GO:0005576; C:extracellular region; ISO:MGI.
DR   GO; GO:0005615; C:extracellular space; IDA:MGI.
DR   GO; GO:0042056; F:chemoattractant activity; ISO:MGI.
DR   GO; GO:0008009; F:chemokine activity; ISS:UniProtKB.
DR   GO; GO:0045236; F:CXCR chemokine receptor binding; IBA:GO_Central.
DR   GO; GO:0048248; F:CXCR3 chemokine receptor binding; ISS:UniProtKB.
DR   GO; GO:0008201; F:heparin binding; ISO:MGI.
DR   GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; ISO:MGI.
DR   GO; GO:0140374; P:antiviral innate immune response; IEA:Ensembl.
DR   GO; GO:0097398; P:cellular response to interleukin-17; IDA:MGI.
DR   GO; GO:0071222; P:cellular response to lipopolysaccharide; ISO:MGI.
DR   GO; GO:0098586; P:cellular response to virus; IEA:Ensembl.
DR   GO; GO:0070098; P:chemokine-mediated signaling pathway; ISO:MGI.
DR   GO; GO:0006935; P:chemotaxis; ISS:UniProtKB.
DR   GO; GO:0051607; P:defense response to virus; IDA:MGI.
DR   GO; GO:0042118; P:endothelial cell activation; ISO:MGI.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:0006955; P:immune response; ISO:MGI.
DR   GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR   GO; GO:0031640; P:killing of cells of another organism; ISO:MGI.
DR   GO; GO:0016525; P:negative regulation of angiogenesis; ISO:MGI.
DR   GO; GO:0045662; P:negative regulation of myoblast differentiation; IMP:MGI.
DR   GO; GO:1901740; P:negative regulation of myoblast fusion; IMP:MGI.
DR   GO; GO:0030593; P:neutrophil chemotaxis; IBA:GO_Central.
DR   GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR   GO; GO:0002690; P:positive regulation of leukocyte chemotaxis; ISO:MGI.
DR   GO; GO:0090026; P:positive regulation of monocyte chemotaxis; ISO:MGI.
DR   GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; ISS:UniProtKB.
DR   GO; GO:2000406; P:positive regulation of T cell migration; ISO:MGI.
DR   GO; GO:0042981; P:regulation of apoptotic process; ISO:MGI.
DR   GO; GO:0042127; P:regulation of cell population proliferation; ISS:UniProtKB.
DR   GO; GO:1901509; P:regulation of endothelial tube morphogenesis; ISO:MGI.
DR   GO; GO:0010819; P:regulation of T cell chemotaxis; ISO:MGI.
DR   GO; GO:0009617; P:response to bacterium; IEP:MGI.
DR   GO; GO:0010818; P:T cell chemotaxis; ISO:MGI.
DR   CDD; cd00273; Chemokine_CXC; 1.
DR   Gene3D; 2.40.50.40; -; 1.
DR   InterPro; IPR039809; Chemokine_b/g/d.
DR   InterPro; IPR001089; Chemokine_CXC.
DR   InterPro; IPR018048; Chemokine_CXC_CS.
DR   InterPro; IPR001811; Chemokine_IL8-like_dom.
DR   InterPro; IPR033899; CXC_Chemokine_domain.
DR   InterPro; IPR036048; Interleukin_8-like_sf.
DR   PANTHER; PTHR12015:SF202; C-X-C MOTIF CHEMOKINE 10; 1.
DR   PANTHER; PTHR12015; SMALL INDUCIBLE CYTOKINE A; 1.
DR   Pfam; PF00048; IL8; 1.
DR   PRINTS; PR00436; INTERLEUKIN8.
DR   PRINTS; PR00437; SMALLCYTKCXC.
DR   SMART; SM00199; SCY; 1.
DR   SUPFAM; SSF54117; Interleukin 8-like chemokines; 1.
DR   PROSITE; PS00471; SMALL_CYTOKINES_CXC; 1.
DR   Genevisible; P17515; MM.
PE   1: Evidence at protein level;
KW   3D-structure; Chemotaxis; Citrullination; Cytokine; Disulfide bond;
KW   Inflammatory response; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   CHAIN           22..98
FT                   /note="C-X-C motif chemokine 10"
FT                   /id="PRO_0000005104"
FT   MOD_RES         26
FT                   /note="Citrulline"
FT                   /evidence="ECO:0000250|UniProtKB:P02778"
FT   DISULFID        30..57
FT                   /evidence="ECO:0000269|PubMed:18560148"
FT   DISULFID        32..74
FT                   /evidence="ECO:0000269|PubMed:18560148"
FT   STRAND          26..31
FT                   /evidence="ECO:0007829|PDB:2R3Z"
FT   STRAND          42..44
FT                   /evidence="ECO:0007829|PDB:2R3Z"
FT   STRAND          47..51
FT                   /evidence="ECO:0007829|PDB:2R3Z"
FT   STRAND          55..59
FT                   /evidence="ECO:0007829|PDB:2R3Z"
FT   STRAND          61..65
FT                   /evidence="ECO:0007829|PDB:2R3Z"
FT   TURN            67..69
FT                   /evidence="ECO:0007829|PDB:2R3Z"
FT   STRAND          72..75
FT                   /evidence="ECO:0007829|PDB:2R3Z"
FT   HELIX           80..86
FT                   /evidence="ECO:0007829|PDB:2R3Z"
SQ   SEQUENCE   98 AA;  10789 MW;  42B0E6A0CC56FE36 CRC64;
     MNPSAAVIFC LILLGLSGTQ GIPLARTVRC NCIHIDDGPV RMRAIGKLEI IPASLSCPRV
     EIIATMKKND EQRCLNPESK TIKNLMKAFS QKRSKRAP
//