Tbio CXCL12 Stromal cell-derived factor 1

Protein Summary

Description

Chemoattractant active on T-lymphocytes and monocytes but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions and chemotaxis. SDF-1-beta(3-72) and SDF-1-alpha(3-67) show a reduced chemotactic activity. Binding to cell surface proteoglycans seems to inhibit formation of SDF-1-alpha(3-67) and thus to preserve activity on local sites. Also binds to atypical chemokine receptor ACKR3, which activates the beta-arrestin pathway and acts as a scavenger receptor for SDF-1. Binds to the allosteric site (site 2) of integrins and activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1 in a CXCR4-independent manner (PubMed:29301984). Acts as a positive regulator of monocyte migration and a negative regulator of monocyte adhesion via the LYN kinase. Stimulates migration of monocytes and T-lymphocytes through its receptors, CXCR4 and ACKR3, and decreases monocyte adherence to surfaces coated with ICAM-1, a ligand for beta-2 integrins. SDF1A/CXCR4 signaling axis inhibits beta-2 integrin LFA-1 mediated adhesion of monocytes to ICAM-1 through LYN kinase. Inhibits CXCR4-mediated infection by T-cell line-adapted HIV-1. Plays a protective role after myocardial infarction. Induces down-regulation and internalization of ACKR3 expressed in various cells. Has several critical functions during embryonic development; required for B-cell lymphopoiesis, myelopoiesis in bone marrow and heart ventricular septum formation. Stimulates the proliferation of bone marrow-derived B-cell progenitors in the presence of IL7 as well as growth of stromal cell-dependent pre-B-cells (By similarity). This antimicrobial gene encodes a stromal cell-derived alpha chemokine member of the intercrine family. The encoded protein functions as the ligand for the G-protein coupled receptor, chemokine (C-X-C motif) receptor 4, and plays a role in many diverse cellular functions, including embryogenesis, immune surveillance, inflammation response, tissue homeostasis, and tumor growth and metastasis. Mutations in this gene are associated with resistance to human immunodeficiency virus type 1 infections. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

Uniprot Accession IDs

• P48061
• B2R4G0
• E7EVL0
• H7BYN8
• Q2L985
• Q2L986
• Q2L988
• Q5IT36
• Q6ICW0
• Q9H554
• SDF-1

Gene Name

• CXCL12

Ensembl ID

• ENST00000343575
• ENSP00000339913
• ENSG00000107562
• ENST00000374426
• ENSP00000363548
• ENST00000374429
• ENSP00000363551
• ENST00000395793
• ENSP00000379139
• ENST00000395794
• ENSP00000379140
• ENST00000395795
• ENSP00000379141

Symbol

• SDF1
• SDF1A
• SDF1B
• IRH
• PBSF
• SDF1
• TLSF
• TPAR1
• SCYB12

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
biological term	1
PubMedID	1
disease perturbation	0.9
disease	0.88

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 3327.09   (req: < 5)

Gene RIFs: 1048   (req: <= 3)

Antibodies: 788   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 3327.09   (req: >= 5)

Gene RIFs: 1048   (req: > 3)

Antibodies: 788   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 49

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Data Bank (20)

1 – 5 of 20

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (36)

Reactome (17)

KEGG (11)

PathwayCommons (4)

WikiPathways (4)

Axon guidance (R-HSA-422475)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Axon guidance	533 targets	R-HSA-422475
Reactome	Chemokine receptors bind chemokines	48 targets	R-HSA-380108
Reactome	Class A/1 (Rhodopsin-like receptors)	323 targets	R-HSA-373076
Reactome	Developmental Biology	1055 targets	R-HSA-1266738
Reactome	ESR-mediated signaling	189 targets	R-HSA-8939211

Name	Explore in Pharos	Explore in Source
Axon guidance	533 targets	R-HSA-422475
Chemokine receptors bind chemokines	48 targets	R-HSA-380108
Class A/1 (Rhodopsin-like receptors)	323 targets	R-HSA-373076
Developmental Biology	1055 targets	R-HSA-1266738
ESR-mediated signaling	189 targets	R-HSA-8939211

Gene Ontology Terms (54)

Functions (6)

Components (5)

Processes (43)

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10

1 – 6 of 6

GO Term	Evidence	Assigned by
chemokine activity	Inferred from Direct Assay (IDA)	UniProtKB
CXCR chemokine receptor binding	Inferred from Direct Assay (IDA)	BHF-UCL
integrin binding	Inferred from Direct Assay (IDA)	UniProtKB
chemokine receptor binding	Inferred from Mutant Phenotype (IMP)	UniProtKB
signaling receptor binding	Traceable Author Statement (TAS)	ProtInc
growth factor activity	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Protein-Protein Interactions (581)

Explore Interacting Targets

1 – 10 of 581

• See Interactions on String-DB

CXCR4

Tclin

Family: GPCR

Novelty: 0.00033459

Score: 0.998

Data Source: Reactome,STRINGDB

ACKR3

Tchem

Family: GPCR

Novelty: 0.00876425

Score: 0.995

Data Source: Reactome,STRINGDB

CCL25

Tbio

Novelty: 0.01203102

Score: 0.988

Data Source: STRINGDB

CCL21

Tbio

Novelty: 0.0007729

Score: 0.983

Data Source: STRINGDB

CCL20

Tbio

Novelty: 0.00082571

Score: 0.983

Data Source: STRINGDB

CCR4

Tclin

Family: GPCR

Novelty: 0.01606117

Score: 0.982

Data Source: STRINGDB

CCL5

Tchem

Novelty: 0.00039604

Score: 0.981

Data Source: STRINGDB

CXCL13

Tbio

Novelty: 0.00156696

Score: 0.976

Data Source: STRINGDB

CXCL10

Tchem

Novelty: 0.00051044

Score: 0.976

Data Source: STRINGDB

CCL19

Tbio

Novelty: 0.00235957

Score: 0.976

Data Source: STRINGDB

Publication Statistics

PubMed Score  3327.09

PubMed score by year

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PubTator Score  2101.61

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

3D-structure
Alternative splicing
Chemotaxis
Complete proteome
Cytokine
Disulfide bond
Growth factor
Host-virus interaction
Reference proteome
Secreted

GWAS Trait Find Similar Targets

coronary artery disease
coronary heart disease
myocardial infarction
particulate matter air pollution measurement
QT interval
response to reverse transcriptase inhibitor

MGI Phenotype Find Similar Targets

cardiovascular system phenotype
cellular phenotype
endocrine/exocrine gland phenotype
hematopoietic system phenotype
immune system phenotype
liver/biliary system phenotype
mortality/aging
muscle phenotype
nervous system phenotype
reproductive system phenotype