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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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	G-protein coupled receptor signaling pathway Traceable author statement. Source: ProtInc cell-cell signaling Traceable author statement. Source: ProtInc cellular calcium ion homeostasis Traceable author statement. Source: ProtInc cellular component movement Traceable author statement. Source: ProtInc cytoskeleton organization Traceable author statement. Source: ProtInc exocytosis Traceable author statement. Source: ProtInc immune response Inferred from electronic annotation. Source: InterPro inflammatory response Traceable author statement. Source: ProtInc regulation of viral genome replication Traceable author statement. Source: ProtInc
Cellular component	extracellular space Inferred from electronic annotation. Source: UniProtKB-KW soluble fraction Traceable author statement. Source: ProtInc
Molecular function	chemoattractant activity Inferred from direct assay. Source: UniProtKB chemokine activity Traceable author statement. Source: ProtInc
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...

Turn

44 – 46

3

Beta strand

49 – 51

3

Turn

55 – 58

4

Beta strand

63 – 65

3

Helix

79 – 84

6

Turn

85 – 88

4

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: 3086300] [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: 2521882] [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: 2271120] [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: 1694014] [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: 15489334] [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: 8541527] [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: 8525373] [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: 7537510] [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: 9092555] [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: 12070155] [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: 12401480] [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: 10347159] [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.

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	[»]

ProteinModelPortal

P10147.

SMR

P10147. Positions 26-91.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5837N.

STRING

P10147.

Polymorphism databases

DMDM

127078.

Proteomic databases

PRIDE

P10147.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000225245; ENSP00000225245; ENSG00000006075.

GeneID

6348.

KEGG

hsa:6348.

UCSC

uc002hkv.1. human.

Organism-specific databases

CTD

6348.

GeneCards

GC17M034415.

H-InvDB

HIX0039045.

HGNC

HGNC:10627. CCL3.

MIM

182283. gene.

neXtProt

NX_P10147.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG505826.

HOVERGEN

HBG017871.

InParanoid

P10147.

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.

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]

KO

K05408.

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

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:	January 25, 2012
This is version 134 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.