P55774 (CCL18_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
C-C motif chemokine 18

Alternative name(s):
Alternative macrophage activation-associated CC chemokine 1
Short name=AMAC-1
CC chemokine PARC
Dendritic cell chemokine 1
Short name=DC-CK1
Macrophage inflammatory protein 4
Short name=MIP-4
Pulmonary and activation-regulated chemokine
Small-inducible cytokine A18

Cleaved into the following 3 chains:

1. CCL18(1-68)
2. CCL18(3-69)
3. CCL18(4-69)

Gene names

Name:	CCL18
Synonyms:	AMAC1, DCCK1, MIP4, PARC, SCYA18

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	89 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	Chemotactic factor that attracts lymphocytes but not monocytes or granulocytes. May be involved in B-cell migration into B-cell follicles in lymph nodes. Attracts naive T-lymphocytes toward dendritic cells and activated macrophages in lymph nodes, has chemotactic activity for naive T-cells, CD4+ and CD8+ T-cells and thus may play a role in both humoral and cell-mediated immunity responses. Ref.13 Ref.14
Subcellular location	Secreted.
Tissue specificity	Expressed at high levels in lung, lymph nodes, placenta, bone marrow, dendritic cells present in germinal centers and T-cell areas of secondary lymphoid organs and macrophages derived from peripheral blood monocytes. Not expressed by peripheral blood monocytes and a monocyte-to-macrophage differentiation is a prerequisite for expression. Expressed in synovial fluids from patients with rheumatoid and septic arthritis and in ovarian carcinoma ascitic fluid. Ref.13
Induction	Specifically induced in macrophages by IL4/interleukin-4, IL13/interleukin-13, and IL10/interleukin-10. Expression is inhibited by IFNG/IFN-gamma while glucocorticoids exert a slightly positive synergistic effect in combination with IL4/interleukin-4. Strongly induced in several human cell lines, including monocytic U-937 cells, by phorbol myristate acetate (PMA). Induced in PBMC by staphylococcal enterotoxins SEA and SEB. Ref.13
Sequence similarities	Belongs to the intercrine beta (chemokine CC) family.
Mass spectrometry	Molecular mass is 7849.4 Da from positions 21 - 89. Determined by ESI. Ref.13 Molecular mass is 7652.1 Da from positions 23 - 89. Determined by ESI. Ref.13 Molecular mass is 7552.0 Da from positions 24 - 89. Determined by ESI. Ref.13

Ontologies

Keywords
Biological process	Chemotaxis Inflammatory response
Cellular component	Secreted
Domain	Signal
Molecular function	Cytokine
PTM	Disulfide bond
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell-cell signaling Traceable author statement Ref.2. Source: ProtInc chemotaxis Traceable author statement Ref.4. Source: ProtInc immune response Traceable author statement Ref.4. Source: ProtInc inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW response to biotic stimulus Traceable author statement Ref.2. Source: ProtInc signal transduction Traceable author statement Ref.2. Source: ProtInc
Cellular_component	extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	chemokine activity Traceable author statement Ref.4. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PITPNM3	Q9BZ71	4	EBI-711240,EBI-2815766

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	Ref.4
	Chain	21 – 89	69	C-C motif chemokine 18		PRO_0000005212
	Chain	21 – 88	68	CCL18(1-68)		PRO_0000041851
	Chain	23 – 89	67	CCL18(3-69)		PRO_0000041852
	Chain	24 – 89	66	CCL18(4-69)		PRO_0000041853
Amino acid modifications
	Disulfide bond	30 ↔ 54		By similarity
	Disulfide bond	31 ↔ 70		By similarity

Sequences

	Sequence		Length	Mass (Da)
	P55774 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: C287B94B9C0518E4	FASTA	89	9,849
	10 20 30 40 50 60 MKGLAAALLV LVCTMALCSC AQVGTNKELC CLVYTSWQIP QKFIVDYSET SPQCPKPGVI 70 80 LLTKRGRQIC ADPNKKWVQK YISDLKLNA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Macrophage inflammatory protein-3 and -4." Li H., Ruben S. Patent number US5504003, 02-APR-1996 Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"A novel human CC chemokine PARC that is most homologous to macrophage-inflammatory protein-1 alpha/LD78 alpha and chemotactic for T lymphocytes, but not for monocytes." Hieshima K., Imai T., Baba M., Shoudai K., Ishizuka K., Nakagawa T., Tsuruta J., Takeya M., Sakaki Y., Takatsuki K., Miura R., Opdenakker G., van Damme J., Yoshie O., Nomiyama H. J. Immunol. 159:1140-1149(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Aorta and Lung.
[3]	"Alternative macrophage activation-associated CC-chemokine-1, a novel structural homologue of macrophage inflammatory protein-1 alpha with a Th2-associated expression pattern." Kodelja V., Mueller C., Politz O., Hakij N., Orfanos C.E., Goerdt S. J. Immunol. 160:1411-1418(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"A dendritic-cell-derived C-C chemokine that preferentially attracts naive T cells." Adema G.J., Hartgers F., Verstraten R., de Vries E., Marland G., Menon S., Foster J., Xu Y., Nooyen P., McClanahan T., Bacon K.B., Figdor C.G. Nature 387:713-717(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF N-TERMINUS. Tissue: Dendritic cell.
[5]	"Chemokine PARC gene (SCYA18) generated by fusion of two MIP-1alpha/LD78alpha-like genes." Tasaki Y., Fukuda S., Iio M., Miura R., Imai T., Sugano S., Yoshie O., Hughes A.L., Nomiyama H. Genomics 55:353-357(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"Genomic organization and biological characterization of the novel human CC chemokine DC-CK-1/PARC/MIP-4/SCYA18." Guan P., Burghes A.H.M., Cunningham A., Lira P., Brissette W.H., Neote K., McColl S.R. Genomics 56:296-302(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], CHARACTERIZATION.
[7]	"The genomic locus for the AMAC-1 gene contains possible pseudo-exons within the first intron sequence." Politz O., Kodelja V., Guillot P., Orfanos C.E., Goerdt S. Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[9]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"Human protein factory for converting the transcriptome into an in vitro-expressed proteome." Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N. Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[11]	"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].
[12]	"The chemokine information source: identification and characterization of novel chemokines using the WorldWideWeb and expressed sequence tag databases." Wells T.N.C., Peitsch M.C. J. Leukoc. Biol. 61:545-550(1997) [PubMed] [Europe PMC] [Abstract] Cited for: DISCUSSION OF SEQUENCE.
[13]	"Selective induction of CCL18/PARC by staphylococcal enterotoxins in mononuclear cells and enhanced levels in septic and rheumatoid arthritis." Schutyser E., Struyf S., Wuyts A., Put W., Geboes K., Grillet B., Opdenakker G., Van Damme J. Eur. J. Immunol. 31:3755-3762(2001) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF CCL18(3-69) AND CCL18(4-69), PROTEOLYTIC PROCESSING OF N-TERMINAL, FUNCTION, MASS SPECTROMETRY, TISSUE SPECIFICITY, INDUCTION.
[14]	"Identification of biologically active chemokine isoforms from ascitic fluid and elevated levels of CCL18/pulmonary and activation-regulated chemokine in ovarian carcinoma." Schutyser E., Struyf S., Proost P., Opdenakker G., Laureys G., Verhasselt B., Peperstraete L., Van de Putte I., Saccani A., Allavena P., Mantovani A., Van Damme J. J. Biol. Chem. 277:24584-24593(2002) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF CCL18(1-68), PROTEOLYTIC PROCESSING OF C-TERMINAL, FUNCTION.
+	Additional computationally mapped references.

Web resources

Wikipedia

CCL18 entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB000221 mRNA. Translation: BAA21670.1. Y13710 mRNA. Translation: CAA74039.1. AB012113 Genomic DNA. Translation: BAA34368.1. AF082214, AF082212, AF082213 Genomic DNA. Translation: AAC32287.1. AF111198 Genomic DNA. Translation: AAD30390.1. CR407660 mRNA. Translation: CAG28588.1. AB451458 mRNA. Translation: BAG70272.1. CH471147 Genomic DNA. Translation: EAW80102.1. BC069700 mRNA. Translation: AAH69700.1. BC096124 mRNA. Translation: AAH96124.1. BC096125 mRNA. Translation: AAH96125.1. BC096126 mRNA. Translation: AAH96126.1. BC096127 mRNA. Translation: AAH96127.1.
IPI	IPI00026183.
RefSeq	NP_002979.1. NM_002988.2. XP_003960722.1. XM_003960673.1.
UniGene	Hs.143961.
3D structure databases
ProteinModelPortal	P55774.
ModBase	Search...
Protein-protein interaction databases
IntAct	P55774. 7 interactions.
MINT	MINT-1373449.
STRING	9606.ENSP00000004921.
Polymorphism databases
DMDM	2493666.
Proteomic databases
PaxDb	P55774.
PRIDE	P55774.
Protocols and materials databases
DNASU	6362.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000004921; ENSP00000004921; ENSG00000006074.
GeneID	101060271. 6362.
KEGG	hsa:101060271. hsa:6362.
UCSC	uc002hku.3. human.
Organism-specific databases
CTD	6362.
GeneCards	GC17P034391.
HGNC	HGNC:10616. CCL18.
MIM	603757. gene.
neXtProt	NX_P55774.
PharmGKB	PA35549.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG67988.
HOGENOM	HOG000036685.
InParanoid	P55774.
KO	K05514.
OMA	FIVDYSE.
OrthoDB	EOG48PMMR.
PhylomeDB	P55774.
Gene expression databases
Bgee	P55774.
CleanEx	HS_AMAC1. HS_CCL18.
Genevestigator	P55774.
GermOnline	ENSG00000006074. 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
NextBio	24720.
SOURCE	Search...

Entry information

Entry name

CCL18_HUMAN

Accession

Primary (citable) accession number: P55774
Secondary accession number(s): B5BUM2, Q53X71

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	May 1, 2013
This is version 113 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.