P10147 (CCL3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
C-C motif chemokine 3

Alternative name(s):
G0/G1 switch regulatory protein 19-1
Macrophage inflammatory protein 1-alpha
Short name=MIP-1-alpha
PAT 464.1
SIS-beta
Small-inducible cytokine A3
Tonsillar lymphocyte LD78 alpha protein

Cleaved into the following chain:

1. MIP-1-alpha(4-69)
   Alternative name(s):
   LD78-alpha(4-69)

Gene names

Name:	CCL3
Synonyms:	G0S19-1, MIP1A, SCYA3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	92 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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). Ref.8
Subunit structure	Self-associates. Also heterodimer of MIP-1-alpha(4-69) and MIP-1-beta(3-69). Ref.11
Subcellular location	Secreted.
Induction	By TPA or PHA (TPA = 12-O-tetradecanoyl phorbol-13 acetate (tumor promoter); PHA = phytohemagglutinin (T-cell mitogen)).
Post-translational modification	N-terminal processed form LD78-alpha(4-69) is produced by proteolytic cleavage after secretion from HTLV1-transformed T-cells.
Sequence similarities	Belongs to the intercrine beta (chemokine CC) family.

Ontologies

Keywords
Biological process	Chemotaxis Inflammatory response
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Cytokine
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	MAPK cascade Inferred from mutant phenotype PubMed 21147091. Source: UniProtKB T cell chemotaxis Inferred from direct assay PubMed 10706735. Source: UniProtKB astrocyte cell migration Inferred from sequence or structural similarity. Source: UniProtKB behavior Inferred from direct assay PubMed 20167378. Source: UniProtKB calcium-mediated signaling Inferred from direct assay PubMed 10072545PubMed 19523456. Source: UniProtKB cell-cell signaling Inferred from direct assay PubMed 10679098. Source: UniProtKB cellular response to interferon-gamma Inferred from expression pattern PubMed 9407497. Source: UniProtKB cellular response to interleukin-1 Inferred from expression pattern PubMed 9407497. Source: UniProtKB cellular response to organic cyclic compound Inferred from direct assay PubMed 21147091. Source: UniProtKB cellular response to tumor necrosis factor Inferred from expression pattern PubMed 9407497. Source: UniProtKB cytoskeleton organization Inferred from direct assay PubMed 10072545. Source: UniProtKB eosinophil chemotaxis Inferred from direct assay PubMed 10072545. Source: UniProtKB eosinophil degranulation Inferred from direct assay PubMed 10706735. Source: UniProtKB granulocyte chemotaxis Inferred from direct assay PubMed 10706735. Source: UniProtKB inflammatory response Inferred from direct assay PubMed 10679098PubMed 10706735PubMed 21147091. Source: UniProtKB lipopolysaccharide-mediated signaling pathway Inferred from direct assay PubMed 21147091. Source: UniProtKB macrophage chemotaxis Inferred from sequence or structural similarity. Source: UniProtKB monocyte chemotaxis Inferred from direct assay PubMed 10706735. Source: UniProtKB negative regulation by host of viral transcription Inferred from direct assay PubMed 10841574. Source: UniProtKB negative regulation of bone mineralization Inferred from direct assay PubMed 21403648. Source: UniProtKB negative regulation of gene expression Inferred from direct assay PubMed 21403648. Source: UniProtKB negative regulation of osteoclast differentiation Inferred from direct assay PubMed 21403648. Source: UniProtKB neutrophil chemotaxis Inferred from direct assay PubMed 10706735. Source: UniProtKB osteoblast differentiation Inferred from expression pattern PubMed 21403648. Source: UniProtKB positive regulation of ERK1 and ERK2 cascade Inferred from direct assay PubMed 21403648. Source: UniProtKB positive regulation of calcium ion transport Inferred from direct assay PubMed 15764707PubMed 8699119. Source: UniProtKB positive regulation of calcium-mediated signaling Inferred from mutant phenotype PubMed 10679098. Source: UniProtKB positive regulation of gene expression Inferred from direct assay PubMed 10706735. Source: UniProtKB positive regulation of inflammatory response Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of interleukin-1 beta secretion Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of natural killer cell chemotaxis Inferred from direct assay PubMed 7545673. Source: UniProtKB positive regulation of neuron apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of protein kinase B signaling cascade Inferred from expression pattern PubMed 21403648. Source: UniProtKB positive regulation of tumor necrosis factor production Inferred from sequence or structural similarity. Source: UniProtKB protein kinase B signaling cascade Inferred from mutant phenotype PubMed 21147091. Source: UniProtKB regulation of cell shape Inferred from direct assay PubMed 10072545. Source: UniProtKB regulation of sensory perception of pain Inferred from direct assay PubMed 15764707. Source: UniProtKB release of sequestered calcium ion into cytosol by sarcoplasmic reticulum Inferred from direct assay PubMed 19523456. Source: UniProtKB response to cholesterol Inferred from direct assay PubMed 19523456. Source: UniProtKB response to toxic substance Inferred from direct assay PubMed 10841574. Source: UniProtKB
Cellular_component	cytosol Inferred from direct assay PubMed 19523456. Source: UniProtKB extracellular space Inferred from direct assay PubMed 20167378PubMed 21403648. Source: UniProtKB
Molecular_function	calcium-dependent protein kinase C activity Inferred from direct assay PubMed 15764707. Source: UniProtKB chemoattractant activity Inferred from direct assay PubMed 10072545PubMed 10660125PubMed 10706735PubMed 15001559. Source: UniProtKB chemokine activity Inferred from direct assay PubMed 10072545PubMed 10660125. Source: UniProtKB phospholipase activator activity Inferred from direct assay PubMed 10734056. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 23

23

Ref.7

Chain

24 – 92

69

C-C motif chemokine 3

PRO_0000005156

Chain

27 – 92

66

MIP-1-alpha(4-69)

PRO_0000005157

Sites

Site

40

1

Involved in GAG binding

Site

68

1

Involved in GAG binding

Site

70

1

Involved in GAG binding

Amino acid modifications

Disulfide bond

33 ↔ 57

By similarity

Disulfide bond

34 ↔ 73

By similarity

Natural variations

Natural variant

78

1

E → D.
Corresponds to variant rs34171309 [ dbSNP | Ensembl ].

VAR_048701

Experimental info

Mutagenesis

40

1

R → A: Slightly reduces heparin binding. Ref.10

Mutagenesis

49

1

D → A: Reduces self-association; in BB-10010: Improved pharmaceutical properties. Ref.7 Ref.13

Mutagenesis

68

1

R → A: Strongly reduces heparin binding. Ref.10

Mutagenesis

70

1

R → A: Reduces heparin binding. Ref.10

Mutagenesis

89

1

E → A: Reduces self-association. Ref.13

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

92

Helix Strand Turn

Details...

Helix

26 – 28

3

Beta strand

31 – 33

3

Helix

44 – 46

3

Beta strand

47 – 52

6

Beta strand

57 – 59

3

Beta strand

62 – 66

5

Beta strand

71 – 74

4

Helix

79 – 87

9

Sequences

	Sequence		Length	Mass (Da)
	P10147 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: 517865D5D6776CA8	FASTA	92	10,085
	10 20 30 40 50 60 MQVSTAALAV LLCTMALCNQ FSASLAADTP TACCFSYTSR QIPQNFIADY FETSSQCSKP 70 80 90 GVIFLTKRSR QVCADPSEEW VQKYVSDLEL SA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A cDNA clone used to study mRNA inducible in human tonsillar lymphocytes by a tumor promoter." Obaru K., Fukuda M., Maeda S., Shimada K. J. Biochem. 99:885-894(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. Tissue: Lymphocyte.
[2]	"Mitogenic activation of human T cells induces two closely related genes which share structural similarities with a new family of secreted factors." Zipfel P.F., Balke J., Irving S.G., Kelly K., Siebenlist U. J. Immunol. 142:1582-1590(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: T-cell.
[3]	"Three human homologs of a murine gene encoding an inhibitor of stem cell proliferation." Blum S., Forsdyke R.E., Forsdyke D.R. DNA Cell Biol. 9:589-602(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. Tissue: Lymphocyte.
[4]	"Structures of human genes coding for cytokine LD78 and their expression." Nakao M., Nomiyama H., Shimada K. Mol. Cell. Biol. 10:3646-3658(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Lymphocyte.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Natural killer cell.
[6]	Jang J.S., Kim B.E. Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 23-92. Tissue: Leukocyte.
[7]	"BB-10010: an active variant of human macrophage inflammatory protein-1 alpha with improved pharmaceutical properties." 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. Blood 86:4400-4408(1995) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 24-92, MUTAGENESIS OF ASP-49.
[8]	"Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells." Cocchi F., DeVico A.L., Garzino-Demo A., Arya S.K., Gallo R.C., Lusso P. Science 270:1811-1815(1995) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-40 AND 71-83, FUNCTION.
[9]	"Identification of MIP-1 alpha/LD78 as a monocyte chemoattractant released by the HTLV-I-transformed cell line MT4." Bertini R., Luini W., Sozzani S., Bottazzi B., Ruggiero P., Boraschi D., Saggioro D., Chieco-Bianchi L., Proost P., van Damme J., Mantovani A. AIDS Res. Hum. Retroviruses 11:155-160(1995) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-51, IDENTIFICATION OF LD78-ALPHA(4-69).
[10]	"Identification of a glycosaminoglycan-binding site in chemokine macrophage inflammatory protein-1alpha." Koopmann W., Krangel M.S. J. Biol. Chem. 272:10103-10109(1997) [PubMed] [Europe PMC] [Abstract] Cited for: GAG BINDING SITES ARG-40; ARG-68 AND ARG-70, MUTAGENESIS OF ARG-40; ARG-68 AND ARG-70.
[11]	"Natural truncation of the chemokine MIP-1beta/CCL4 affects receptor specificity but not anti-HIV-1 activity." Guan E., Wang J., Roderiquez G., Norcross M.A. J. Biol. Chem. 277:32348-32352(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT, INTERACTION WITH MIP-1-BETA(3-69).
[12]	"Macrophage inflammatory protein-1." Menten P., Wuyts A., Van Damme J. Cytokine Growth Factor Rev. 13:455-481(2002) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[13]	"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." 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. J. Biol. Chem. 274:16077-16084(1999) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 24-92, MUTAGENESIS OF ASP-49 AND GLU-89.
+	Additional computationally mapped references.

Web resources

Wikipedia

Macrophage inflammatory protein entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D00044 mRNA. Translation: BAA00029.1.
X03754 mRNA. Translation: CAA27388.1.
X04018 Genomic DNA. Translation: CAA27643.1. Sequence problems.
M25315 mRNA. Translation: AAA57255.1.
M23452 mRNA. Translation: AAA36316.1.
M23178 Genomic DNA. Translation: AAA35858.1.
D90144 Genomic DNA. Translation: BAA14172.1.
BC071834 mRNA. Translation: AAH71834.1.
AF043339 mRNA. Translation: AAC03539.1.

IPI

IPI00019426.

PIR

A30574. A35673.

RefSeq

NP_002974.1. NM_002983.2.
XP_003960721.1. XM_003960672.1.

UniGene

Hs.514107.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1B50	NMR	-	A/B	24-92	[»]
1B53	NMR	-	A/B	24-92	[»]
2X69	X-ray	2.65	A/B/C/D/E	23-92	[»]
2X6G	X-ray	2.18	A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R	23-92	[»]
3FPU	X-ray	1.76	B	24-92	[»]
3H44	X-ray	3.00	C/D	23-92	[»]
3KBX	X-ray	2.65	A/B/C/D/E	23-92	[»]
3TN1	X-ray	2.60	A/B/C/D/E	25-91	[»]

ProteinModelPortal

P10147.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5837N.

MINT

MINT-103148.

STRING

9606.ENSP00000225245.

Polymorphism databases

DMDM

127078.

Proteomic databases

PaxDb

P10147.

PRIDE

P10147.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000225245; ENSP00000225245; ENSG00000006075.

GeneID

101060267.
6348.

KEGG

hsa:101060267.
hsa:6348.

UCSC

uc002hkv.3. human.

Organism-specific databases

CTD

6348.

GeneCards

GC17M034415.

HGNC

HGNC:10627. CCL3.

MIM

182283. gene.

neXtProt

NX_P10147.

PharmGKB

PA35559.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG42742.

HOGENOM

HOG000036685.

HOVERGEN

HBG017871.

InParanoid

P10147.

KO

K05408.

OMA

PREAWVQ.

OrthoDB

EOG42Z4RR.

PhylomeDB

P10147.

Enzyme and pathway databases

Pathway_Interaction_DB

il12_2pathway. IL12-mediated signaling events.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P10147.

Bgee

P10147.

CleanEx

HS_CCL3.

Genevestigator

P10147.

GermOnline

ENSG00000006075. Homo sapiens.

Family and domain databases

InterPro

IPR000827. Chemokine_CC_CS.
IPR001811. Chemokine_IL8-like_dom.
[Graphical view]

Pfam

PF00048. IL8. 1 hit.
[Graphical view]

SMART

SM00199. SCY. 1 hit.
[Graphical view]

SUPFAM

SSF54117. Chemokine_IL8. 1 hit.

PROSITE

PS00472. SMALL_CYTOKINES_CC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P10147.

NextBio

24664.

SOURCE

Search...

Entry information

Entry name

CCL3_HUMAN

Accession

Primary (citable) accession number: P10147

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	May 29, 2013
This is version 149 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.