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CCL4 Gene

protein-coding GIFtS: 63
GCID: GC17P034431

Chemokine (C-C Motif) Ligand 4

(Previous name: small inducible cytokine A4 (homologous to mouse Mip-1b))
(Previous symbols: LAG1, SCYA4)

See CCL4-related diseases
at

MalaCards

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
About This Section

This gene clusters with an RNA gene
Subcategory (RNA class): lncRNA

Quality score for the ORGUL clustered with this gene is 3

Aliases
Chemokine (C-C Motif) Ligand 4¹ ²		PAT 744² ³
SCYA4¹ ² ³ ⁵		T-Cell Activation Protein 2² ³
LAG1¹ ² ³		ACT2² ⁵
MIP1B² ³ ⁵		AT744.1² ⁵
Small Inducible Cytokine A4 (Homologous To Mouse Mip-1b)¹ ²		G-26²
Lymphocyte Activation Gene 1 Protein² ³		MIP1B1²
Macrophage Inflammatory Protein 1-Beta² ³		SCYA2²
HC21² ³		C-C Motif Chemokine 4²
LAG-1² ³		Secreted Protein G-26²
MIP-1-beta² ³		ACT-2³
MIP-1-beta(1-69)² ³		Protein H400³
SIS-gamma² ³		Small-Inducible Cytokine A4³
G-26 T-Lymphocyte-Secreted Protein² ³

External Ids:	HGNC: 10630¹	Entrez Gene: 6351²	Ensembl: ENSG00000129277⁷	OMIM: 182284⁵	UniProtKB: P13236³

ORGUL members:

Export aliases for CCL4 gene to outside databases

Previous GC identifers: GC17P034201 GC17P036466 GC17P034279 GC17P034576 GC17P031421 GC17P030617

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for CCL4 Gene:

The protein encoded by this gene is a mitogen-inducible monokine and is one of the major HIV-suppressive factors

produced by CD8+ T-cells. The encoded protein is secreted and has chemokinetic and inflammatory functions.

(provided by RefSeq, Dec 2012)

GeneCards Summary for CCL4 Gene:

CCL4 (chemokine (C-C motif) ligand 4) is a protein-coding gene. Diseases associated with CCL4 include malaria, and tuberculosis. GO annotations related to this gene include identical protein binding and chemokine activity. An important paralog of this gene is CCL15.

UniProtKB/Swiss-Prot: CCL4_HUMAN, P13236

Function: Monokine with inflammatory and chemokinetic properties. Binds to CCR5. One of the major HIV-suppressive

factors produced by CD8+ T-cells. Recombinant MIP-1-beta induces a dose-dependent inhibition of different strains

of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form MIP-1-beta(3-69) retains the

abilities to induce down-modulation of surface expression of the chemokine receptor CCR5 and to inhibit the

CCR5-mediated entry of HIV-1 in T-cells. MIP-1-beta(3-69) is also a ligand for CCR1 and CCR2 isoform B

Gene Wiki entry for CCL4 Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence at NCBI GenBank:

NC_000017.10 NC_018928.2 NT_010783.16 NT_187614.1 NT_187661.1

Regulatory elements:

Regulatory transcription factor binding sites in the CCL4 gene promoter:
CREB AML1a deltaCREB STAT3
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: CCL4 promoter sequence

Search Chromatin IP Primers for CCL4

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat CCL4

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 17q12 Ensembl cytogenetic band: 17q12 HGNC cytogenetic band: 17q21-q23

CCL4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CCL4 gene location

GeneLoc information about chromosome 17 GeneLoc Exon Structure

GeneLoc location for GC17P034431: view genomic region (about GC identifiers)

Start:	34,430,983 bp from pter	End:	34,433,014 bp from pter
Size:	2,032 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, antibodies-online, and/or GeneTex,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
About This Section

UniProtKB/Swiss-Prot: CCL4_HUMAN, P13236 (See protein sequence)

Recommended Name: C-C motif chemokine 4 precursor

Size: 92 amino acids; 10212 Da

Subunit: Homodimer and heterodimer of MIP-1-alpha(4-69) and MIP-1-beta(3-69)

Caution: Was originally (PubMed:9521068) thought to be a ligand for CCR8

7 PDB 3D structures from and Proteopedia for CCL4 (see first 6):

1HUM (3D)

1HUN (3D)

1JE4 (3D)

2FFK (3D)

2FIN (3D)

2X6L (3D)

3TN2 (3D)

Secondary accessions: P22617 Q13704 Q3SXL8 Q6FGI8

Explore the universe of human proteins at neXtProt for CCL4: NX_P13236

Post-translational modifications:

N-terminal processed form MIP-1-beta(3-69) is produced by proteolytic cleavage after secretion from peripheral

blood lymphocytes¹

Modification sites at neXtProt

REFSEQ proteins: NP_002975.1

ENSEMBL proteins:

ENSP00000250151 ENSP00000378004

Reactome Protein details: P13236

CCL4 Human Recombinant Protein Products:

	Browse Purified and Recombinant Proteins at EMD Millipore
	R&D Systems Recombinant & Natural Proteins for CCL4 (CCL4/MIP-1 beta)
	Browse recombinant and purified proteins available from Enzo Life Sciences
	OriGene Purified Protein for CCL4 OriGene Protein Over-expression Lysate for CCL4 OriGene MassSpec for CCL4 OriGene Custom Protein Services for CCL4
	GenScript Purified and Recombinant Proteins for CCL4
	Novus Biologicals CCL4 Proteins Novus Biologicals CCL4 Lysates
	Sino Biological Recombinant Protein for CCL4 Browse Sino Biological Cell Lysates
	ProSpec Recombinant Protein for CCL4
	Browse Proteins at Cloud-Clone Corp.
	Search eBioscience for Proteins for CCL4
	GeneTex Proteins for CCL4: (see all 3) MIP-1 beta Recombinant Protein (Active) (GTX47972-PRO)
	antibodies-online proteins for CCL4 (58 products)
	antibodies-online peptides for CCL4

CCL4 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of CCL4
	R&D Systems Antibodies for CCL4 (CCL4/MIP-1 beta)
	OriGene Antibodies for CCL4 OriGene Custom Antibody Services for CCL4
	Novus Biologicals CCL4 Antibodies
	Abcam antibodies for CCL4 (P13236, Q8NHW4)
	Browse Antibodies at Cloud-Clone Corp.
	ThermoFisher Antibodies for CCL4
	antibodies-online antibodies for CCL4 (129 products)

CCL4 Assay Products:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Assay Services for CCL4
	R&D Systems Flow Cytometry Kits for CCL4 (CCL4/MIP-1 beta) (see all)
	GenScript Custom Assay Services for CCL4
	Browse Enzo Life Sciences for kits & assays
	Browse ELISAs at Cloud-Clone Corp. Browse CLIAs at Cloud-Clone Corp.
	Search eBioscience for ELISAs for CCL4
	antibodies-online kits for CCL4 (56 products)

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GenesLikeMe)
About This Section

HGNC Gene Families:

ENDOLIG: Endogenous ligands

CCL: Chemokine ligands

2 InterPro protein domains:

IPR000827 Chemokine_CC_CS

IPR001811 Chemokine_IL8-like_dom

Graphical View of Domain Structure for InterPro Entry P13236

ProtoNet protein and cluster: P13236

1 Blocks protein domain: IPB000827 Small chemokine

UniProtKB/Swiss-Prot: CCL4_HUMAN, P13236

Similarity: Belongs to the intercrine beta (chemokine CC) family

Find genes that share domains with CCL4 About GenesLikeMe

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene, Sets of similar genes according to GenesLikeMe)
About This Section

Molecular Function:

UniProtKB/Swiss-Prot Summary: CCL4_HUMAN, P13236

Function: Monokine with inflammatory and chemokinetic properties. Binds to CCR5. One of the major HIV-suppressive

factors produced by CD8+ T-cells. Recombinant MIP-1-beta induces a dose-dependent inhibition of different strains

of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form MIP-1-beta(3-69) retains the

abilities to induce down-modulation of surface expression of the chemokine receptor CCR5 and to inhibit the

CCR5-mediated entry of HIV-1 in T-cells. MIP-1-beta(3-69) is also a ligand for CCR1 and CCR2 isoform B

Induction: By mitogens

Gene Ontology (GO): Selected molecular function terms (see all 6): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005125	cytokine activity	TAS	2462251
GO:0005515	protein binding	IPI	--
GO:0008009	chemokine activity	IEA	--
GO:0031726	CCR1 chemokine receptor binding	IPI	7545673
GO:0031730	CCR5 chemokine receptor binding	IPI	10679098

Find genes that share ontologies with CCL4 About GenesLikeMe

Animal Models:

genOway: Develop your customized and physiologically relevant rodent model for CCL4

miRNA Products:		miRTarBase miRNAs that target CCL4: hsa-mir-195-5p (MIRT004669)

		Block miRNA regulation of human, mouse, rat CCL4 using miScript Target Protectors
		3 qRT-PCR Assays for microRNAs that regulate CCL4:
		hsa-miR-125a-3p hsa-miR-3919 hsa-miR-570
		SwitchGear 3'UTR luciferase reporter plasmid: CCL4 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for CCL4
		Predesigned siRNA for gene silencing in human, mouse, rat CCL4

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for CCL4

Clone Products:		OriGene clones in human, mouse for CCL4 (see all 6) OriGene ORF clones in mouse, rat for CCL4 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: CCL4 (NM_002984)
		Sino Biological Human cDNA Clone for CCL4
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for CCL4
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat CCL4
		Addgene plasmids for CCL4

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for CCL4
		Browse ESI BIO Cell Lines and PureStem Progenitors for CCL4

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CCL4

(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene, Sets of similar genes according to GenesLikeMe)
About This Section

Subcellular locations from UniProtKB/Swiss-Prot

CCL4_HUMAN, P13236: Secreted

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
extracellular	5
nucleus	2
cytoskeleton	1
cytosol	1
plasma membrane	1
vacuole	1

About this image

Gene Ontology (GO): 2 cellular component terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005576	extracellular region	TAS	--
GO:0005615	extracellular space	IEA	--

Find genes that share ontologies with CCL4 About GenesLikeMe

(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GenesLikeMe, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene, Sets of similar genes according to GenesLikeMe)
About This Section

SuperPaths for CCL4 About (see all 18)

See pathways by source

Powered
by

SuperPath

Selected contained pathways About (see all per SuperPath)

PEDF Induced Signaling

MIF Regulation of Innate Immune Cells	0.94	NFAT Signaling and Lymphocyte Interactions	0.57
MIF Mediated Glucocorticoid Regulation	0.94	PGC1Alpha Pathway	0.51
PEDF Induced Signaling	0.73	STAT3 Pathway	0.47
all-trans-Retinoic Acid Signaling in Brain	0.71	Endothelin-1 Signaling Pathway	0.46

Toll-like receptor signaling pathway

	Toll-like receptor signaling pathway	0.94			Regulation of toll-like receptor signaling pathway	0.93
	Toll-like receptor signaling pathway	0.94

Chemokine Superfamily: Human/Mouse Ligand-Receptor Interactions

Chemokine receptors bind chemokines

0.81

Chemokine Superfamily: Human/Mouse Ligand-Receptor Interactions

0.81

Chemokine Signaling

Chemokine Signaling

0.33

Chemokine signaling pathway

0.33

TGF-Beta Pathway

TGF-Beta Pathway	0.60	JNK Pathway	0.51
MAPK Family Pathway	0.60	Regulation of eIF4 and p70S6K	0.43
JAK-STAT Pathway	0.57	SOCS Pathway	0.40

Find genes that share SuperPaths with CCL4 About GenesLikeMe

Pathways by source See SuperPaths
Show all pathways

2 R&D Systems Pathways for CCL4

	Chemokine Superfamily: Human/Mouse Ligand-Receptor Interactions
	IL-15 Signaling and its Primary Biological Effects in Different Immune Cell Types

Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for CCL4 (see all 28)

	Endothelin-1 Signaling Pathway
	Molecular Mechanisms of Cancer
	Antioxidant Action of Vitamin-C
	NFAT Signaling and Lymphocyte Interactions
	JNK Pathway

1 GeneGo (Thomson Reuters) Pathway for CCL4

Apoptosis and survival APRIL and BAFF signaling

3 BioSystems Pathways for CCL4

	Toll-like receptor signaling pathway
	IL12-mediated signaling events
	Regulation of toll-like receptor signaling pathway

1 Reactome Pathway for CCL4

Chemokine receptors bind chemokines

Selected Kegg Pathways (Kegg details for CCL4) (see all 6):

	Cytokine-cytokine receptor interaction
	Chemokine signaling pathway
	NF-kappa B signaling pathway
	Toll-like receptor signaling pathway
	Cytosolic DNA-sensing pathway

Pathway & Disease-focused RT² Profiler PCR Arrays including CCL4 (see all 14):

HIV Host Response in human mouse rat

G-Protein-Coupled Receptor Signaling PathwayFinder in human mouse rat

Antiviral Response in human mouse rat

Inflammatory Response & Autoimmunity in human mouse rat

T-cell & B-cell Activation in human mouse rat

Interactions:

GeneGlobe Interaction Network for CCL4

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

Selected Interacting proteins for CCL4 (P13236^{1, 2, 3} ENSP00000250151⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 30)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
CCR5	P51681¹^,³, ENSP00000292303⁴	EBI-6625160,EBI-489374 I2D: score=3 STRING: ENSP00000292303
IDE	P14735²^,³, ENSP00000265986⁴	MINT-8087616 I2D: score=1 STRING: ENSP00000265986
CCR1	P32246³, ENSP00000296140⁴	I2D: score=5 STRING: ENSP00000296140
ACKR2	O00590³, ENSP00000273145⁴	I2D: score=4 STRING: ENSP00000273145
CCL3	P10147³, ENSP00000225245⁴	I2D: score=3 STRING: ENSP00000225245

About this table

Gene Ontology (GO): Selected biological process terms (see all 15): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006928	cellular component movement	TAS	9759849
GO:0006935	chemotaxis	--	--
GO:0006954	inflammatory response	IEA	--
GO:0006955	immune response	IEA	--
GO:0007155	cell adhesion	TAS	10929056

Find genes that share ontologies with CCL4 About GenesLikeMe

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, Sets of similar genes according to GenesLikeMe)
About This Section

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse compounds at ApexBio

Browse Tocris compounds for CCL4

Selected Novoseek inferred chemical compound relationships for CCL4 gene (see all 67) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
rantes	97	722	10888363 (7), 11861332 (6), 9746565 (6), 16924394 (5) (see all 99)
ccl3	90.8	130	12960284 (3), 15585374 (3), 16773571 (3), 19074730 (3) (see all 74)
ccl4	84.6	232	14761932 (7), 15240137 (6), 15843566 (4), 14673550 (4) (see all 99)
mip 1alpha	84.3	23	16518599 (5), 18403790 (4), 11097208 (2), 9343222 (1) (see all 12)
groalpha	78.1	15	10437780 (2), 16542377 (2), 10419917 (1), 17228323 (1) (see all 13)
tarc	76.6	17	10540332 (3), 9521068 (2), 15941911 (1), 9153236 (1) (see all 12)
grogamma	71	3	10467937 (2), 11808935 (1)
larc	68.8	9	18492658 (3), 9153236 (1), 9169480 (1), 10449163 (1) (see all 7)
mcp 1	59.6	5	10559777 (2), 15660413 (1), 17993576 (1), 11683586 (1)
mdms	58.3	7	16857988 (1), 9870313 (1), 10082122 (1), 11839143 (1)

Find genes that share compounds with CCL4 About GenesLikeMe

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
About This Section

REFSEQ mRNAs for CCL4 gene:

NM_002984.2

Unigene Cluster for CCL4:

Chemokine (C-C motif) ligand 4

Hs.75703 [show with all ESTs]

Unigene Representative Sequence: CD521853

3 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000250151(uc002hkw.1) ENST00000394495(uc002hkx.1) ENST00000591883

miRNA Products:		Block miRNA regulation of human, mouse, rat CCL4 using miScript Target Protectors
		3 qRT-PCR Assays for microRNAs that regulate CCL4:
		hsa-miR-125a-3p hsa-miR-3919 hsa-miR-570
		SwitchGear 3'UTR luciferase reporter plasmid: CCL4 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for CCL4
		Predesigned siRNA for gene silencing in human, mouse, rat CCL4

Clone Products:		OriGene clones in human, mouse for CCL4 (see all 6) OriGene ORF clones in mouse, rat for CCL4 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: CCL4 (NM_002984)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for CCL4
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat CCL4
		Addgene plasmids for CCL4

Primer Products:		OriGene qPCR primer pairs and template standards for CCL4 OriGene qSTAR qPCR primer pairs in human, mouse for CCL4
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat CCL4
		QuantiTect SYBR Green Assays in human, mouse, rat CCL4
		QuantiFast Probe-based Assays in human, mouse, rat CCL4

Additional mRNA sequence:

AY312578.1 AY766446.1 AY766448.1 BC104226.1 BC104227.1 BC107433.1 CR542119.1 J04130.1

M23502.1 M25316.1 M57503.1 X16166.1 X53683.1

12 DOTS entries:

DT.100044914 DT.100044255 DT.97766642 DT.100890234 DT.86854556 DT.100890235 DT.100762795 DT.120948312

DT.95267994 DT.95267995 DT.120948253 DT.453194

Selected AceView cDNA sequences (see all 177):

AA362350 T29074 AA362359 BE326709 AI341064 CR610625 AI359523 AI862912

AA362287 AI343539 BM543715 AY312578 BU753465 AW059871 CD638976 BV203915

CA748764 CD522340 BV203909 BQ007461 CD521723 AI950224 CD521196 CD522904

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GenesLikeMe, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

CCL4 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: GATAACACAT

About this image

CCL4 expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database
selected tissues (see all 7) fully expand


Bone (Muscoskeletal System) fully expand to see all 4 entries
Bone Marrow
Bone marrow-derived mesenchymal stem cells (Stempeucel)

Blood (Hematopoietic System) fully expand to see all 2 entries
Natural Killer Cells Peripheral Blood

Ovary (Reproductive System)
Secondary follicles

Mesenchymal Stem Cells
Bone marrow-derived mesenchymal stem cells (Stempeucel)

Lateral Plate Mesoderm (Gastrulation Derivatives)
Hematopoietic Stem Cells Aorta-Gonad-Mesonephros

CCL4 Protein expression data from MOPED¹, PaxDb² and MaxQB³:

--

SOURCE GeneReport for Unigene cluster: Hs.75703

Pathway & Disease-focused RT² Profiler PCR Arrays including CCL4 (see all 14):

HIV Host Response in human mouse rat

G-Protein-Coupled Receptor Signaling PathwayFinder in human mouse rat

Antiviral Response in human mouse rat

Inflammatory Response & Autoimmunity in human mouse rat

T-cell & B-cell Activation in human mouse rat

Primer Products:		OriGene qPCR primer pairs and template standards for CCL4 OriGene qSTAR qPCR primer pairs in human, mouse for CCL4
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat CCL4
		QuantiTect SYBR Green Assays in human, mouse, rat CCL4
		QuantiFast Probe-based Assays in human, mouse, rat CCL4

In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CCL4

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of chordates.

Orthologs for CCL4 gene from Selected species (see all 9) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Ccl4^{1 , 5}	chemokine (C-C motif) ligand 4^{1, 5}	81.88(n)¹ 76.09(a)¹		11 (51.09 cM)⁵ 20303¹ NM_013652.2¹ NP_038680.1¹ 83662584⁵
chicken (Gallus gallus)	Aves	CCL4¹	chemokine (C-C motif) ligand 4	59.93(n) 50.56(a)		395468 NM_204720.1 NP_990051.1
zebrafish (Danio rerio)	Actinopterygii	ZGC:193706⁶	chemokine CCL-C25y-like (LOC100000034), mRNA	33(a)	1 → many	25(25902180-25904281) ENSDARG00000070378

ENSEMBL Gene Tree for CCL4 (if available)
TreeFam Gene Tree for CCL4 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68,Sets of similar genes according to GenesLikeMe)
About This Section

Paralogs for CCL4 gene

CCL15² CCL16² CCL14² CCL4L1² CCL3L1² CCL4L2² CCL26² CCL3²

CCL5² CCL23² CCL3L3² CCL18² CCL15-CCL14²

Selected SIMAP similar genes for CCL4 using alignment to 3 protein entries: CCL4_HUMAN (see all proteins) (see all similar genes):

CCL4L2 LOC728835 CCL4L1 CCL3L1 CCL3 CCL14

CCL5 CCL3L3 CCL11 CCL18 CCL7 MCP-3

CCL2 CCL16 CCL26 CCL8 CCL13 CCL22

Find genes that share paralogs with CCL4 About GenesLikeMe

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
About This Section

SNP ID	Clinical significance	Chr 17 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data				Transcription Related Data				Allele Frequencies
			--	--	--		--	--
rs1719152^1,2,4	--	--	see VAR_059211	2		mis⁴		0	--	--	--	--
rs9635771^1,2,4	--	--	see VAR_048702	2		mis⁴		0	--	--	--	--
rs1130750^1,2,4	--	--	see VAR_048703	2		mis⁴		0	--	--	--	--

HapMap Linkage Disequilibrium report for CCL4 (34430983 - 34433014 bp)

Structural Variations
Database of Genomic Variants (DGV) Selected variations for CCL4 (see all 29): About this table

Variant ID	Type	Subtype	PubMed ID
esv2664544	CNV	Deletion	23128226
esv2715876	CNV	Deletion	23290073
esv2670934	CNV	Deletion	23128226
nsv471396	CNV	Duplication	19718026
nsv833427	CNV	Loss	17160897
esv33107	CNV	Loss	17666407
dgv178n21	CNV	Loss	19592680
dgv122e55	CNV	Gain	17911159
dgv522n67	CNV	Gain	20364138
dgv3144n71	CNV	Gain	21882294

Site Specific Mutation Identification with PCR Assays

Search QIAGEN SeqTarget long-range PCR primers for resequencing CCL4

DNA2.0 Custom Variant and Variant Library Synthesis for CCL4

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB, Sets of similar genes according to GenesLikeMe)
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OMIM gene information: 182284 OMIM disorders: --

12 diseases for CCL4:
About MalaCards

malaria tuberculosis stachybotrys chartarum relapsing polychondritis

alexithymia meconium aspiration syndrome hiv-1 periapical granuloma

idiopathic pulmonary alveolar proteinosis retinal vasculitis erdheim-chester disease measles

1 inferred disease relationship from the University of Copenhagen DISEASES database for CCL4:

Human immunodeficiency virus infectious disease

Find genes that share disorders with CCL4 About GenesLikeMe

Selected Novoseek inferred disease relationships for CCL4 gene (see all 74) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
necrosis	67.3	152	14726627 (2), 14586377 (2), 18622277 (2), 10496934 (2) (see all 99)
immunodeficiency	66.9	34	10979927 (2), 9343222 (1), 9359702 (1), 12427015 (1) (see all 29)
inflammation	63.1	15	9841832 (2), 11097208 (1), 12548712 (1), 14761932 (1) (see all 13)
hiv infections	61.4	17	9732062 (2), 9649315 (1), 10461827 (1), 11120614 (1) (see all 14)
virus infection	43.2	8	10501489 (1), 19155475 (1), 17547763 (1), 19846870 (1) (see all 8)
tumors	43.2	132	15126779 (5), 14586377 (2), 18622277 (2), 12473593 (2) (see all 99)
periapical granuloma	39.6	2	11683586 (2)
aids	37.6	17	9466518 (3), 9420304 (2), 10618285 (1), 16773571 (1) (see all 10)
fibrosis idiopathic pulmonary	32.6	5	11031344 (1), 10384061 (1), 19046553 (1)
viremia	27.5	1	18234797 (1)

Genetic Association Database (GAD): CCL4
Human Genome Epidemiology (HuGE) Navigator: CCL4 (17 documents)

Export disorders for CCL4 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for CCL4 gene, integrated from 10 sources (see all 951):
(articles sorted by number of sources associating them with CCL4)

CCL3L1 and CCL4L1: variable gene copy number in adolescents with and without human immunodeficiency virus type 1 (HIV-1) infection. (PubMed id 17330138)^{1, 4, 9} Shao W.... Kaslow R.A. (Genes Immun. 2007)
Multiple products derived from two CCL4 loci: high incidence of a new polymorphism in HIV+ patients. (PubMed id 15843566)^{1, 2, 9} Colobran R.... Juan M. (J. Immunol. 2005)
Macrophage inflammatory protein-1. (PubMed id 12401480)^{1, 2, 9} Menten P.... Van Damme J. (Cytokine Growth Factor Rev. 2002)
Identification of the CC chemokines TARC and macrophage inflammatory protein-1 beta as novel functional ligands for the CCR8 receptor. (PubMed id 9521068)^{1, 2, 9} Bernardini G....Napolitano M. (Eur. J. Immunol. 1998)
The assignment of chemokine-chemokine receptor pairs: TARC and MIP-1 beta are not ligands for human CC-chemokine receptor 8. (PubMed id 10540332)^{1, 2, 9} Garlisi C.G....Umland S.P. (Eur. J. Immunol. 1999)
Polymorphisms in innate immunity genes and patients response to dendritic cell-based HIV immuno-treatment. (PubMed id 20056178)^{1, 4} Segat L....Crovella S. (Vaccine 2010)
Interleukin-9 polymorphism in infants with respiratory syncytial virus infection: an opposite effect in boys and girls. (PubMed id 20503287)^{1, 4} Schuurhof A....Janssen R. (Pediatr. Pulmonol. 2010)
Genetic susceptibility to respiratory syncytial virus bronchiolitis in preterm children is associated with airway remodeling genes and innate immune genes. (PubMed id 19258923)^{1, 4} Siezen C.L....Janssen R. (Pediatr. Infect. Dis. J. 2009)
Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes. (PubMed id 17703412)^{1, 4} Janssen R....Hoebee B. (J. Infect. Dis. 2007)
DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. (PubMed id 16625196)^{1, 2} Zody M.C.... Nusbaum C. (Nature 2006)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 6351	HGNC: 10630	AceView: CCL4	Ensembl:ENSG00000129277	euGenes: HUgn6351
ECgene: CCL4	Kegg: 6351	H-InvDB: CCL4

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for CCL4	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for CCL4	Genetics and Cytogenetics in Oncology and Haematology
Wikipedia	http://en.wikipedia.org/wiki/Macrophage_Inflammatory_Protein

Intellectual Property for CCL4 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for CCL4 gene:
Search GeneIP for patents involving CCL4

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, eBioscience, antibodies-online, GeneTex, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
Advanced Cell Diagnostics, Animal models from genOway)
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	Regulatory tfbs in CCL4 promoter

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Selected GeneTex proteins for CCL4: MIP-1 beta Recombinant Protein (Active) (GTX47972-PRO)

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CCL4 Gene

Chemokine (C-C Motif) Ligand 4

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CCL4 (Gene Symbol)
Chemokine (C-C Motif) Ligand 4
SCYA4
LAG1
MIP1B
Small Inducible Cytokine A4 (Homologous To Mouse Mip-1b)
Lymphocyte Activation Gene 1 Protein
Macrophage Inflammatory Protein 1-Beta
HC21
LAG-1
MIP-1-beta
MIP-1-beta(1-69)
SIS-gamma
G-26 T-Lymphocyte-Secreted Protein
PAT 744
T-Cell Activation Protein 2
ACT2
AT744.1
G-26
MIP1B1
SCYA2
C-C Motif Chemokine 4
Secreted Protein G-26
ACT-2
Protein H400
Small-Inducible Cytokine A4

Vertical Transmission
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Atherosclerosis
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Edema
Toxic Shock Syndrome
Asthma
AIDS
Cancer
Uveitis
Lymphoma
Lyme Disease
Meningitis
Bronchoalveolar Lavage Fluid
Osteolysis
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BONE LESION
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Malaria Falciparum
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osteolytic
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FIBROSIS IDIOPATHIC PULMONARY
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CCL4 Gene

Chemokine (C-C Motif) Ligand 4

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