Protein:CXCL12 |
Protein Summary |
 Gene summary |
| Gene name: CXCL12 | ASpdb.0 ID: 6387 | Gene | Gene symbol | CXCL12 | Gene ID | 6387 |
| Gene name | C-X-C motif chemokine ligand 12 |
| Synonyms | IRH|PBSF|SCYB12|SDF1|TLSF|TPAR1 |
| Cytomap | 10q11.21 |
| Type of gene | protein-coding |
| Description | stromal cell-derived factor 1chemokine (C-X-C motif) ligand 12intercrine reduced in hepatomaspre-B cell growth-stimulating factor |
| Modification date | 20240407 |
| UniProtAcc | P48061 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | CXCL12 | GO:0005178 | integrin binding | 29301984 |
| Gene | CXCL12 | GO:0008009 | chemokine activity | 18308860 |
| Gene | CXCL12 | GO:0033622 | integrin activation | 29301984 |
| Gene | CXCL12 | GO:0045236 | CXCR chemokine receptor binding | 20388803 |
| Gene | CXCL12 | GO:0045785 | positive regulation of cell adhesion | 23620790 |
| Gene | CXCL12 | GO:0060326 | cell chemotaxis | 18308860 |
| Gene | CXCL12 | GO:0070098 | chemokine-mediated signaling pathway | 20388803 |
| Gene | CXCL12 | GO:0090026 | positive regulation of monocyte chemotaxis | 18802065 |
| Gene | CXCL12 | GO:1902230 | negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage | 20388803 |
| Gene | CXCL12 | GO:1903237 | negative regulation of leukocyte tethering or rolling | 18308860 |
| Gene | CXCL12 | GO:2000406 | positive regulation of T cell migration | 23620790 |
| Gene | CXCL12 | GO:2000669 | negative regulation of dendritic cell apoptotic process | 15059845 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P48061-1 | P48061-1_4uai_A.pdb | 4UAI | X-ray | 1.9 | A | 22 | 89 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P48061 | CXCL12 | P48061-1 | P48061-2 | 93 | 89 | 90 | 93 | Deletion | none | none | 89 | 89 |
| P48061 | CXCL12 | P48061-1 | P48061-3 | 93 | 119 | 90 | 93 | Substitution | RFKM | GRREEKVGKKEKIGKKKRQKKRKAAQKRKN | 90 | 119 |
| P48061 | CXCL12 | P48061-1 | P48061-4 | 93 | 140 | 89 | 93 | Substitution | KRFKM | NLISAAPAGKRVIAGARALHPSPPRACPTARALCEIRLWPPPEWSWPSPGDV | 89 | 140 |
| P48061 | CXCL12 | P48061-1 | P48061-5 | 93 | 90 | 89 | 93 | Substitution | KRFKM | NC | 89 | 90 |
| P48061 | CXCL12 | P48061-1 | P48061-6 | 93 | 100 | 90 | 93 | Substitution | RFKM | IWLYGNAETSR | 90 | 100 |
| P48061 | CXCL12 | P48061-1 | P48061-7 | 93 | 103 | 39 | 93 | Substitution | VARANVKHLKILNTPNCALQIVARLKNNNRQVCIDPKLKWIQEYLEKALNKRFKM | YCTCLIRVSFHGATPLTQGSWVLYSLSCAGGETGLREPGPMVSPRVESHQEGRLGVPGPVNLGKA | 39 | 103 |
| Multiple sequence alignment of our canonical and alternatively spliced CXCL12 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of CXCL12 |
| UniProt-id | ENSG | ENST | ENSP |
| P48061-1 | ENSG00000107562.18 | ENST00000374429.6 | ENSP00000363551.2 |
| P48061-2 | ENSG00000107562.18 | ENST00000343575.11 | ENSP00000339913.6 |
| P48061-3 | ENSG00000107562.18 | ENST00000374426.6 | ENSP00000363548.2 |
| P48061-4 | ENSG00000107562.18 | ENST00000395794.2 | ENSP00000379140.2 |
| P48061-7 | ENSG00000107562.18 | ENST00000395793.7 | ENSP00000379139.3 |
| UniProt-id | NM ID | NP ID |
| P48061-1 | NM_000609.6 | NP_000600.1 |
| P48061-2 | NM_199168.3 | NP_954637.1 |
| P48061-3 | NM_001033886.2 | NP_001029058.1 |
| P48061-4 | NM_001178134.1 | NP_001171605.1 |
| P48061-7 | NM_001277990.1 | NP_001264919.1 |
| Amino acid sequences of our canonical and alternatively spliced CXCL12 |
| accession_id | Protein sequence |
| P48061-1 | MNAKVVVVLVLVLTALCLSDGKPVSLSYRCPCRFFESHVARANVKHLKILNTPNCALQIVARLKNNNRQVCIDPKLKWIQEYLEKALNKR |
| P48061-2 | |
| P48061-3 | MNAKVVVVLVLVLTALCLSDGKPVSLSYRCPCRFFESHVARANVKHLKILNTPNCALQIVARLKNNNRQVCIDPKLKWIQEYLEKALNKG |
| P48061-4 | MNAKVVVVLVLVLTALCLSDGKPVSLSYRCPCRFFESHVARANVKHLKILNTPNCALQIVARLKNNNRQVCIDPKLKWIQEYLEKALNNL |
| P48061-5 | MNAKVVVVLVLVLTALCLSDGKPVSLSYRCPCRFFESHVARANVKHLKILNTPNCALQIVARLKNNNRQVCIDPKLKWIQEYLEKALNNC |
| P48061-6 | MNAKVVVVLVLVLTALCLSDGKPVSLSYRCPCRFFESHVARANVKHLKILNTPNCALQIVARLKNNNRQVCIDPKLKWIQEYLEKALNKI |
| P48061-7 | MNAKVVVVLVLVLTALCLSDGKPVSLSYRCPCRFFESHYCTCLIRVSFHGATPLTQGSWVLYSLSCAGGETGLREPGPMVSPRVESHQEG |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| CXCL12 (go to UniProt):P48061 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P48061 | Region | 39 | 41 | Note=Receptor binding | Type=Substitution;Start=39;End=93 |
| P48061 | Region | 48 | 50 | Note=Receptor binding | Type=Substitution;Start=39;End=93 |
| P48061 | Region | 60 | 70 | Note=Receptor binding | Type=Substitution;Start=39;End=93 |
Gene Isoform Structures and Expression Levels for CXCL12 |
| Gene structures of our canonical and alternative spliced genes of CXCL12 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P48061-1 |
| 3D view using mol* of P48061-2 |
| 3D view using mol* of P48061-3 |
| 3D view using mol* of P48061-4 |
| 3D view using mol* of P48061-5 |
| 3D view using mol* of P48061-6 |
| 3D view using mol* of P48061-7 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P48061-1 |
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| pLDDT distribution across the protein length of P48061-2 |
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| pLDDT distribution across the protein length of P48061-3 |
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| pLDDT distribution across the protein length of P48061-4 |
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| pLDDT distribution across the protein length of P48061-5 |
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| pLDDT distribution across the protein length of P48061-6 |
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| pLDDT distribution across the protein length of P48061-7 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P48061-1 |
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| Ramachandran plot of P48061-3 |
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| Ramachandran plot of P48061-4 |
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| Ramachandran plot of P48061-5 |
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| Ramachandran plot of P48061-6 |
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| Ramachandran plot of P48061-7 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P48061-1 | 0.544 | 23 | 0.469 | 72.03 | 0.744 | 0.578 | 0.765 | 0.024 | 1.009 | 0.023 | 0.952 | 27,28,29,30,31,52,53,54,55
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| P48061-2 | 0.488 | 13 | 0.147 | 23.667 | 0.618 | 0.633 | 0.874 | 0 | 1.754 | 0 | 0.254 | 46,47,48,60,61,62,69
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| P48061-3 | 0.476 | 9 | 0.416 | 39.445 | 0.827 | 0.563 | 0.811 | 0.723 | 0.625 | 1.157 | 3.425 | 26,27,28,29,52,53,54,55
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| P48061-4 | 1.025 | 140 | 1.071 | 334.425 | 0.522 | 0.68 | 0.945 | 0.877 | 0.849 | 1.032 | 0.836 | 41,42,44,45,46,47,48,49,59,64,78,79,82,83,85,86,87 ,89,90,132,133,134,135,136,137 |
| P48061-5 | 0.464 | 18 | 0.352 | 38.073 | 0.769 | 0.528 | 0.7 | 0.104 | 1.115 | 0.093 | 0.219 | 31,32,33,34,36,68,69,70,71
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| P48061-6 | 0.573 | 17 | 0.53 | 45.962 | 0.721 | 0.593 | 0.848 | 1.177 | 0.653 | 1.802 | 3.214 | 26,27,28,29,30,31,52,53,55
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| P48061-7 | 0.428 | 14 | 0.365 | 0.686 | 0.77 | 0.463 | 0.603 | 0.23 | 0.811 | 0.284 | 0.145 | 40,42,64,65,66,67
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Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P48061-1_P48061-1_4uai_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P48061-1_4uai_A_P48061-2.pdb |
| 3D view using mol* of P48061-1_4uai_A_P48061-3.pdb |
| 3D view using mol* of P48061-1_4uai_A_P48061-4.pdb |
| 3D view using mol* of P48061-1_4uai_A_P48061-5.pdb |
| 3D view using mol* of P48061-1_4uai_A_P48061-6.pdb |
| 3D view using mol* of P48061-1_4uai_A_P48061-7.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P48061-1_P48061-2.pdb |
| 3D view using mol* of P48061-1_P48061-3.pdb |
| 3D view using mol* of P48061-1_P48061-4.pdb |
| 3D view using mol* of P48061-1_P48061-5.pdb |
| 3D view using mol* of P48061-1_P48061-6.pdb |
| 3D view using mol* of P48061-1_P48061-7.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P48061-1_vs_P48061-2.png |
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| ./stats/secondary_structure/figure/P48061-1_vs_P48061-3.png |
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| ./stats/secondary_structure/figure/P48061-1_vs_P48061-4.png |
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| ./stats/secondary_structure/figure/P48061-1_vs_P48061-5.png |
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| ./stats/secondary_structure/figure/P48061-1_vs_P48061-6.png |
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| ./stats/secondary_structure/figure/P48061-1_vs_P48061-7.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P48061-1_vs_P48061-2.png |
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| ./stats/relative_asa/P48061-1_vs_P48061-3.png |
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| ./stats/relative_asa/P48061-1_vs_P48061-4.png |
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| ./stats/relative_asa/P48061-1_vs_P48061-5.png |
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| ./stats/relative_asa/P48061-1_vs_P48061-6.png |
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| ./stats/relative_asa/P48061-1_vs_P48061-7.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to CXCL12 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P48061 | CXCL12 | DB06822 | Tinzaparin | approved | binder |
| P48061 | CXCL12 | DB05934 | CTCE-0214 | investigational |
Related Diseases to CXCL12 |
| Previous studies relating to the alternative splicing of CXCL12 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| CXCL12 | 12782716 | An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4. | The chemokines CXCL9/Mig, CXCL10/IP-10, and CXCL11/I-TAC regulate lymphocyte chemotaxis, mediate vascular pericyte proliferation, and act as angiostatic agents, thus inhibiting tumor growth. These multiple activities are apparently mediated by a unique G protein-coupled receptor, termed CXCR3. The chemokine CXCL4/PF4 shares several activities with CXCL9, CXCL10, and CXCL11, including a powerful angiostatic effect, but its specific receptor is still unknown. Here, we describe a distinct, previously unrecognized receptor named CXCR3-B, derived from an alternative splicing of the CXCR3 gene that mediates the angiostatic activity of CXCR3 ligands and also acts as functional receptor for CXCL4. Human microvascular endothelial cell line-1 (HMEC-1), transfected with either the known CXCR3 (renamed CXCR3-A) or CXCR3-B, bound CXCL9, CXCL10, and CXCL11, whereas CXCL4 showed high affinity only for CXCR3-B. Overexpression of CXCR3-A induced an increase of survival, whereas overexpression of CXCR3-B dramatically reduced DNA synthesis and up-regulated apoptotic HMEC-1 death through activation of distinct signal transduction pathways. Remarkably, primary cultures of human microvascular endothelial cells, whose growth is inhibited by CXCL9, CXCL10, CXCL11, and CXCL4, expressed CXCR3-B, but not CXCR3-A. Finally, monoclonal antibodies raised to selectively recognize CXCR3-B reacted with endothelial cells from neoplastic tissues, providing evidence that CXCR3-B is also expressed in vivo and may account for the angiostatic effects of CXC chemokines. | D009369 | Neoplasms |
| CXCL12 | 21953583 | CXCL12γ isoform is expressed on endothelial and dendritic cells in rheumatoid arthritis synovium and regulates T cell activation. | CXCL12γ is an alternative splicing isoform of CXCL12 with enhanced affinity for heparan sulfate (HS) proteoglycans. This study was undertaken to investigate the distribution and potential function of CXCL12γ in rheumatoid arthritis (RA) synovium and normal lymphoid tissue, where its immobilization to HS may be relevant in pathologic or homeostatic immune cell migration and activation. | D001172 | Arthritis, Rheumatoid |
Clinically important variants in CXCL12 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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