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C-C motif chemokine 3 (G0/G1 switch regulatory protein 19-1) (Macrophage inflammatory protein 1-alpha) (MIP-1-alpha) (PAT 464.1) (SIS-beta) (Small-inducible cytokine A3) (Tonsillar lymphocyte LD78 alpha protein) [Cleaved into: MIP-1-alpha(4-69) (LD78-alpha(4-69))]

 CCL3_HUMAN              Reviewed;          92 AA.
P10147;
01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
01-JUL-1989, sequence version 1.
25-OCT-2017, entry version 185.
RecName: Full=C-C motif chemokine 3;
AltName: Full=G0/G1 switch regulatory protein 19-1;
AltName: Full=Macrophage inflammatory protein 1-alpha;
Short=MIP-1-alpha;
AltName: Full=PAT 464.1;
AltName: Full=SIS-beta;
AltName: Full=Small-inducible cytokine A3;
AltName: Full=Tonsillar lymphocyte LD78 alpha protein;
Contains:
RecName: Full=MIP-1-alpha(4-69);
AltName: Full=LD78-alpha(4-69);
Flags: Precursor;
Name=CCL3; Synonyms=G0S19-1, MIP1A, SCYA3;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
TISSUE=Lymphocyte;
PubMed=3086300;
Obaru K., Fukuda M., Maeda S., Shimada K.;
"A cDNA clone used to study mRNA inducible in human tonsillar
lymphocytes by a tumor promoter.";
J. Biochem. 99:885-894(1986).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=T-cell;
PubMed=2521882;
Zipfel P.F., Balke J., Irving S.G., Kelly K., Siebenlist U.;
"Mitogenic activation of human T cells induces two closely related
genes which share structural similarities with a new family of
secreted factors.";
J. Immunol. 142:1582-1590(1989).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
TISSUE=Lymphocyte;
PubMed=2271120; DOI=10.1089/dna.1990.9.589;
Blum S., Forsdyke R.E., Forsdyke D.R.;
"Three human homologs of a murine gene encoding an inhibitor of stem
cell proliferation.";
DNA Cell Biol. 9:589-602(1990).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
TISSUE=Lymphocyte;
PubMed=1694014; DOI=10.1128/MCB.10.7.3646;
Nakao M., Nomiyama H., Shimada K.;
"Structures of human genes coding for cytokine LD78 and their
expression.";
Mol. Cell. Biol. 10:3646-3658(1990).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Natural killer cell;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
NUCLEOTIDE SEQUENCE [MRNA] OF 23-92.
TISSUE=Leukocyte;
Jang J.S., Kim B.E.;
Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
[7]
PROTEIN SEQUENCE OF 24-92, AND MUTAGENESIS OF ASP-49.
PubMed=8541527;
Hunter M.G., Bawden L., Brotherton D., Craig S., Cribbes S.,
Czaplewski L.G., Dexter T.M., Drummond A.H., Gearing A.H.,
Heyworth C.M., Lord B.I., Mccourt M., Varley P.G., Wood L.M.,
Edwards R.M., Lewis P.J.;
"BB-10010: an active variant of human macrophage inflammatory protein-
1 alpha with improved pharmaceutical properties.";
Blood 86:4400-4408(1995).
[8]
PROTEIN SEQUENCE OF 27-40 AND 71-83, AND FUNCTION.
PubMed=8525373; DOI=10.1126/science.270.5243.1811;
Cocchi F., DeVico A.L., Garzino-Demo A., Arya S.K., Gallo R.C.,
Lusso P.;
"Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major
HIV-suppressive factors produced by CD8+ T cells.";
Science 270:1811-1815(1995).
[9]
PROTEIN SEQUENCE OF 27-51, AND IDENTIFICATION OF LD78-ALPHA(4-69).
PubMed=7537510; DOI=10.1089/aid.1995.11.155;
Bertini R., Luini W., Sozzani S., Bottazzi B., Ruggiero P.,
Boraschi D., Saggioro D., Chieco-Bianchi L., Proost P., van Damme J.,
Mantovani A.;
"Identification of MIP-1 alpha/LD78 as a monocyte chemoattractant
released by the HTLV-I-transformed cell line MT4.";
AIDS Res. Hum. Retroviruses 11:155-160(1995).
[10]
GAG BINDING SITES ARG-40; ARG-68 AND ARG-70, AND MUTAGENESIS OF
ARG-40; ARG-68 AND ARG-70.
PubMed=9092555; DOI=10.1074/jbc.272.15.10103;
Koopmann W., Krangel M.S.;
"Identification of a glycosaminoglycan-binding site in chemokine
macrophage inflammatory protein-1alpha.";
J. Biol. Chem. 272:10103-10109(1997).
[11]
SUBUNIT, AND INTERACTION WITH MIP-1-BETA(3-69).
PubMed=12070155; DOI=10.1074/jbc.M203077200;
Guan E., Wang J., Roderiquez G., Norcross M.A.;
"Natural truncation of the chemokine MIP-1beta/CCL4 affects receptor
specificity but not anti-HIV-1 activity.";
J. Biol. Chem. 277:32348-32352(2002).
[12]
REVIEW.
PubMed=12401480; DOI=10.1016/S1359-6101(02)00045-X;
Menten P., Wuyts A., Van Damme J.;
"Macrophage inflammatory protein-1.";
Cytokine Growth Factor Rev. 13:455-481(2002).
[13]
STRUCTURE BY NMR OF 24-92, AND MUTAGENESIS OF ASP-49 AND GLU-89.
PubMed=10347159; DOI=10.1074/jbc.274.23.16077;
Czaplewski L.G., McKeating J., Craven C.J., Higgins L.D., Appay V.,
Brown A., Dudgeon T., Howard L.A., Meyers T., Owen J., Palan S.R.,
Tan P., Wilson G., Woods N.R., Heyworth C.M., Lord B.I.,
Brotherton D., Christison R., Craig S., Cribbes S., Edwards R.M.,
Evans S.J., Gilbert R., Morgan P., Eliot Randle E., Schofield N.,
Varley P.G., Fisher J., Jonathan P., Waltho J.P., Hunter M.G.;
"Identification of amino acid residues critical for aggregation of
human CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-
1beta, and RANTES. Characterization of active disaggregated chemokine
variants.";
J. Biol. Chem. 274:16077-16084(1999).
-!- FUNCTION: Monokine with inflammatory and chemokinetic properties.
Binds to CCR1, CCR4 and CCR5. One of the major HIV-suppressive
factors produced by CD8+ T-cells. Recombinant MIP-1-alpha induces
a dose-dependent inhibition of different strains of HIV-1, HIV-2,
and simian immunodeficiency virus (SIV).
{ECO:0000269|PubMed:8525373}.
-!- SUBUNIT: Self-associates. Also heterodimer of MIP-1-alpha(4-69)
and MIP-1-beta(3-69). {ECO:0000269|PubMed:12070155}.
-!- INTERACTION:
Self; NbExp=3; IntAct=EBI-8459634, EBI-8459634;
Q2F862:- (xeno); NbExp=2; IntAct=EBI-8459634, EBI-16161937;
P14735:IDE; NbExp=3; IntAct=EBI-8459634, EBI-2556886;
-!- SUBCELLULAR LOCATION: Secreted.
-!- INDUCTION: By TPA or PHA (TPA = 12-O-tetradecanoyl phorbol-13
acetate (tumor promoter); PHA = phytohemagglutinin (T-cell
mitogen)).
-!- PTM: N-terminal processed form LD78-alpha(4-69) is produced by
proteolytic cleavage after secretion from HTLV1-transformed T-
cells.
-!- SIMILARITY: Belongs to the intercrine beta (chemokine CC) family.
{ECO:0000305}.
-!- WEB RESOURCE: Name=Wikipedia; Note=Macrophage inflammatory protein
entry;
URL="https://en.wikipedia.org/wiki/Macrophage_Inflammatory_Protein";
-----------------------------------------------------------------------
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EMBL; D00044; BAA00029.1; -; mRNA.
EMBL; X03754; CAA27388.1; -; mRNA.
EMBL; X04018; CAA27643.1; ALT_SEQ; Genomic_DNA.
EMBL; M25315; AAA57255.1; -; mRNA.
EMBL; M23452; AAA36316.1; -; mRNA.
EMBL; M23178; AAA35858.1; -; Genomic_DNA.
EMBL; D90144; BAA14172.1; -; Genomic_DNA.
EMBL; BC071834; AAH71834.1; -; mRNA.
EMBL; AF043339; AAC03539.1; -; mRNA.
CCDS; CCDS11307.1; -.
PIR; A35673; A30574.
RefSeq; NP_002974.1; NM_002983.2.
UniGene; Hs.514107; -.
PDB; 1B50; NMR; -; A/B=24-92.
PDB; 1B53; NMR; -; A/B=24-92.
PDB; 2X69; X-ray; 2.65 A; A/B/C/D/E=23-92.
PDB; 2X6G; X-ray; 2.18 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R=23-92.
PDB; 3FPU; X-ray; 1.76 A; B=24-92.
PDB; 3H44; X-ray; 3.00 A; C/D=23-92.
PDB; 3KBX; X-ray; 2.65 A; A/B/C/D/E=23-92.
PDB; 4RA8; X-ray; 2.60 A; A/B/C/D/E=23-91.
PDB; 4ZKB; X-ray; 2.90 A; B=24-92.
PDB; 5COR; X-ray; 2.55 A; A/B/C/D/E/F/G/H/I/J=23-92.
PDB; 5D65; X-ray; 3.10 A; A/B/C/D/E=23-92.
PDBsum; 1B50; -.
PDBsum; 1B53; -.
PDBsum; 2X69; -.
PDBsum; 2X6G; -.
PDBsum; 3FPU; -.
PDBsum; 3H44; -.
PDBsum; 3KBX; -.
PDBsum; 4RA8; -.
PDBsum; 4ZKB; -.
PDBsum; 5COR; -.
PDBsum; 5D65; -.
ProteinModelPortal; P10147; -.
SMR; P10147; -.
BioGrid; 112252; 5.
DIP; DIP-5837N; -.
IntAct; P10147; 4.
MINT; MINT-103148; -.
STRING; 9606.ENSP00000225245; -.
DrugBank; DB05364; ROX-888.
BioMuta; CCL3; -.
DMDM; 127078; -.
PaxDb; P10147; -.
PeptideAtlas; P10147; -.
PRIDE; P10147; -.
Ensembl; ENST00000613396; ENSP00000480753; ENSG00000278567.
Ensembl; ENST00000613922; ENSP00000477908; ENSG00000277632.
Ensembl; ENST00000616221; ENSP00000483712; ENSG00000274221.
GeneID; 6348; -.
KEGG; hsa:6348; -.
UCSC; uc002hkv.5; human.
CTD; 6348; -.
DisGeNET; 6348; -.
EuPathDB; HostDB:ENSG00000277632.1; -.
GeneCards; CCL3; -.
HGNC; HGNC:10627; CCL3.
MalaCards; CCL3; -.
MIM; 182283; gene.
neXtProt; NX_P10147; -.
OpenTargets; ENSG00000277632; -.
PharmGKB; PA35559; -.
eggNOG; ENOG410J4I9; Eukaryota.
eggNOG; ENOG410YXJU; LUCA.
GeneTree; ENSGT00900000140870; -.
HOGENOM; HOG000036685; -.
HOVERGEN; HBG017871; -.
InParanoid; P10147; -.
KO; K05408; -.
OMA; NTPTACC; -.
OrthoDB; EOG091G14Y2; -.
PhylomeDB; P10147; -.
TreeFam; TF334888; -.
Reactome; R-HSA-6783783; Interleukin-10 signaling.
SIGNOR; P10147; -.
EvolutionaryTrace; P10147; -.
GeneWiki; CCL3; -.
GenomeRNAi; 6348; -.
PRO; PR:P10147; -.
Proteomes; UP000005640; Chromosome 17.
Bgee; ENSG00000277632; -.
CleanEx; HS_CCL3; -.
ExpressionAtlas; P10147; baseline and differential.
Genevisible; P10147; HS.
GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
GO; GO:0005829; C:cytosol; IDA:UniProtKB.
GO; GO:0005576; C:extracellular region; IDA:BHF-UCL.
GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
GO; GO:0005622; C:intracellular; IDA:UniProtKB.
GO; GO:0004698; F:calcium-dependent protein kinase C activity; IDA:UniProtKB.
GO; GO:0031726; F:CCR1 chemokine receptor binding; IPI:UniProtKB.
GO; GO:0031730; F:CCR5 chemokine receptor binding; IPI:UniProtKB.
GO; GO:0042056; F:chemoattractant activity; IDA:UniProtKB.
GO; GO:0008009; F:chemokine activity; IDA:UniProtKB.
GO; GO:0042802; F:identical protein binding; IPI:IntAct.
GO; GO:0016301; F:kinase activity; IDA:UniProtKB.
GO; GO:0016004; F:phospholipase activator activity; IDA:UniProtKB.
GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
GO; GO:0043615; P:astrocyte cell migration; ISS:UniProtKB.
GO; GO:0007610; P:behavior; IDA:UniProtKB.
GO; GO:0006816; P:calcium ion transport; IDA:UniProtKB.
GO; GO:0019722; P:calcium-mediated signaling; IDA:UniProtKB.
GO; GO:0001775; P:cell activation; IDA:UniProtKB.
GO; GO:0007267; P:cell-cell signaling; IDA:UniProtKB.
GO; GO:0006874; P:cellular calcium ion homeostasis; IDA:UniProtKB.
GO; GO:0071346; P:cellular response to interferon-gamma; IEP:UniProtKB.
GO; GO:0071347; P:cellular response to interleukin-1; IEP:UniProtKB.
GO; GO:0071407; P:cellular response to organic cyclic compound; IDA:UniProtKB.
GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:UniProtKB.
GO; GO:0070098; P:chemokine-mediated signaling pathway; IBA:GO_Central.
GO; GO:0006935; P:chemotaxis; IDA:UniProtKB.
GO; GO:0007010; P:cytoskeleton organization; IDA:UniProtKB.
GO; GO:0048245; P:eosinophil chemotaxis; IDA:UniProtKB.
GO; GO:0043308; P:eosinophil degranulation; IDA:UniProtKB.
GO; GO:0006887; P:exocytosis; IDA:UniProtKB.
GO; GO:0007186; P:G-protein coupled receptor signaling pathway; IBA:GO_Central.
GO; GO:0071621; P:granulocyte chemotaxis; IDA:UniProtKB.
GO; GO:0006954; P:inflammatory response; IDA:UniProtKB.
GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IDA:UniProtKB.
GO; GO:0048247; P:lymphocyte chemotaxis; IDA:UniProtKB.
GO; GO:0048246; P:macrophage chemotaxis; ISS:UniProtKB.
GO; GO:0000165; P:MAPK cascade; IMP:UniProtKB.
GO; GO:0002548; P:monocyte chemotaxis; IDA:UniProtKB.
GO; GO:0043922; P:negative regulation by host of viral transcription; IDA:UniProtKB.
GO; GO:0030502; P:negative regulation of bone mineralization; IDA:UniProtKB.
GO; GO:0010629; P:negative regulation of gene expression; IDA:UniProtKB.
GO; GO:0045671; P:negative regulation of osteoclast differentiation; IDA:UniProtKB.
GO; GO:0030593; P:neutrophil chemotaxis; IDA:UniProtKB.
GO; GO:0001649; P:osteoblast differentiation; IEP:UniProtKB.
GO; GO:0090280; P:positive regulation of calcium ion import; TAS:BHF-UCL.
GO; GO:0051928; P:positive regulation of calcium ion transport; IDA:UniProtKB.
GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IMP:UniProtKB.
GO; GO:0030335; P:positive regulation of cell migration; IDA:UniProtKB.
GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
GO; GO:0043547; P:positive regulation of GTPase activity; IBA:GO_Central.
GO; GO:0050729; P:positive regulation of inflammatory response; ISS:UniProtKB.
GO; GO:0050718; P:positive regulation of interleukin-1 beta secretion; ISS:UniProtKB.
GO; GO:2000503; P:positive regulation of natural killer cell chemotaxis; IDA:UniProtKB.
GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISS:UniProtKB.
GO; GO:0051897; P:positive regulation of protein kinase B signaling; IEP:UniProtKB.
GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:UniProtKB.
GO; GO:0043491; P:protein kinase B signaling; IMP:UniProtKB.
GO; GO:0008360; P:regulation of cell shape; IDA:UniProtKB.
GO; GO:0051930; P:regulation of sensory perception of pain; IDA:UniProtKB.
GO; GO:0014808; P:release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; IDA:UniProtKB.
GO; GO:0070723; P:response to cholesterol; IDA:UniProtKB.
GO; GO:0009636; P:response to toxic substance; IDA:UniProtKB.
GO; GO:0023052; P:signaling; IEP:UniProtKB.
GO; GO:0010818; P:T cell chemotaxis; IDA:UniProtKB.
InterPro; IPR000827; Chemokine_CC_CS.
InterPro; IPR001811; Chemokine_IL8-like_dom.
InterPro; IPR036048; Interleukin_8-like_sf.
Pfam; PF00048; IL8; 1.
SMART; SM00199; SCY; 1.
SUPFAM; SSF54117; SSF54117; 1.
PROSITE; PS00472; SMALL_CYTOKINES_CC; 1.
1: Evidence at protein level;
3D-structure; Chemotaxis; Complete proteome; Cytokine;
Direct protein sequencing; Disulfide bond; Inflammatory response;
Polymorphism; Reference proteome; Secreted; Signal.
SIGNAL 1 23 {ECO:0000269|PubMed:8541527}.
CHAIN 24 92 C-C motif chemokine 3.
/FTId=PRO_0000005156.
CHAIN 27 92 MIP-1-alpha(4-69).
/FTId=PRO_0000005157.
SITE 40 40 Involved in GAG binding.
SITE 68 68 Involved in GAG binding.
SITE 70 70 Involved in GAG binding.
DISULFID 33 57 {ECO:0000250}.
DISULFID 34 73 {ECO:0000250}.
VARIANT 78 78 E -> D (in dbSNP:rs34171309).
/FTId=VAR_048701.
MUTAGEN 40 40 R->A: Slightly reduces heparin binding.
{ECO:0000269|PubMed:9092555}.
MUTAGEN 49 49 D->A: Reduces self-association; in BB-
10010: Improved pharmaceutical
properties. {ECO:0000269|PubMed:10347159,
ECO:0000269|PubMed:8541527}.
MUTAGEN 68 68 R->A: Strongly reduces heparin binding.
{ECO:0000269|PubMed:9092555}.
MUTAGEN 70 70 R->A: Reduces heparin binding.
{ECO:0000269|PubMed:9092555}.
MUTAGEN 89 89 E->A: Reduces self-association.
{ECO:0000269|PubMed:10347159}.
HELIX 26 28 {ECO:0000244|PDB:3FPU}.
STRAND 31 33 {ECO:0000244|PDB:2X6G}.
HELIX 44 46 {ECO:0000244|PDB:3FPU}.
STRAND 47 52 {ECO:0000244|PDB:3FPU}.
STRAND 57 59 {ECO:0000244|PDB:3FPU}.
STRAND 62 66 {ECO:0000244|PDB:3FPU}.
STRAND 71 74 {ECO:0000244|PDB:3FPU}.
STRAND 76 78 {ECO:0000244|PDB:4ZKB}.
HELIX 79 87 {ECO:0000244|PDB:3FPU}.
SEQUENCE 92 AA; 10085 MW; 517865D5D6776CA8 CRC64;
MQVSTAALAV LLCTMALCNQ FSASLAADTP TACCFSYTSR QIPQNFIADY FETSSQCSKP
GVIFLTKRSR QVCADPSEEW VQKYVSDLEL SA


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E0092m ELISA C-C motif chemokine 3,Ccl3,Heparin-binding chemotaxis protein,L2G25B,Macrophage inflammatory protein 1-alpha,Mip1a,MIP-1-alpha,Mouse,Mus musculus,Scya3,SIS-alpha,Small-inducible cytokine A3,TY-5 96T
U0092m CLIA C-C motif chemokine 3,Ccl3,Heparin-binding chemotaxis protein,L2G25B,Macrophage inflammatory protein 1-alpha,Mip1a,MIP-1-alpha,Mouse,Mus musculus,Scya3,SIS-alpha,Small-inducible cytokine A3,TY-5 96T
18-783-75647 RABBIT ANTI HUMAN MIP-3 ALPHA - CCL20; Small-inducible cytokine A20; Macrophage inflammatory protein 3 alpha; MIP-3-alpha; Liver and activation-regulated chemokine; CC chemokine LARC; Beta chemokine e 0.1 mg
18-783-78922 RABBIT ANTI HUMAN MIP-3 ALPHA Biotin - CCL20; Small-inducible cytokine A20; Macrophage inflammatory protein 3 alpha; MIP-3-alpha; Liver and activation-regulated chemokine; CC chemokine LARC; Beta chem 0.05 mg
E0092b ELISA Bos taurus,Bovine,C-C motif chemokine 3,CCL3,Macrophage inflammatory protein 1-alpha,MIP-1-alpha,SCYA3,Small-inducible cytokine A3 96T
E0092b ELISA kit Bos taurus,Bovine,C-C motif chemokine 3,CCL3,Macrophage inflammatory protein 1-alpha,MIP-1-alpha,SCYA3,Small-inducible cytokine A3 96T
U0092b CLIA Bos taurus,Bovine,C-C motif chemokine 3,CCL3,Macrophage inflammatory protein 1-alpha,MIP-1-alpha,SCYA3,Small-inducible cytokine A3 96T
U0095b CLIA Bos taurus,Bovine,C-C motif chemokine 20,CCL20,Macrophage inflammatory protein 3 alpha,MIP3A,MIP-3-alpha,SCYA20,Small-inducible cytokine A20 96T


 

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