Q16627 (CCL14_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
C-C motif chemokine 14

Alternative name(s):
Chemokine CC-1/CC-3
Short name=HCC-1/HCC-3
HCC-1(1-74)
NCC-2
Small-inducible cytokine A14

Cleaved into the following 3 chains:

1. HCC-1(3-74)
2. HCC-1(4-74)
3. HCC-1(9-74)

Gene names

Name:	CCL14
Synonyms:	NCC2, SCYA14

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	93 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	Has weak activities on human monocytes and acts via receptors that also recognize MIP-1 alpha. It induced intracellular Ca2+ changes and enzyme release, but no chemotaxis, at concentrations of 100-1,000 nM, and was inactive on T-lymphocytes, neutrophils, and eosinophil leukocytes. Enhances the proliferation of CD34 myeloid progenitor cells. The processed form HCC-1(9-74) is a chemotactic factor that attracts monocytes eosinophils, and T-cells and is a ligand for CCR1, CCR3 and CCR5. Ref.7
Subcellular location	Secreted.
Tissue specificity	Expressed constitutively in several normal tissues: spleen, liver, skeletal and heart muscle, gut, and bone marrow, present at high concentrations (1-80 nM) in plasma. Ref.2
Post-translational modification	The N-terminal processed forms HCC-1(3-74), HCC-1(4-74) and HCC-1(9-74) are produced in small amounts by proteolytic cleavage after secretion in blood. HCC-1(1-74), but not HCC-1(3-74) and HCC-1(4-74), is partially O-glycosylated; the O-linked glycan consists of one Gal-GalNAc disaccharide, further modified by two N-acetylneuraminic acids. Ref.6
Sequence similarities	Belongs to the intercrine beta (chemokine CC) family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Molecular function	Cytokine
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular calcium ion homeostasis Traceable author statement Ref.1. Source: ProtInc immune response Inferred from electronic annotation. Source: InterPro positive regulation of cell proliferation Traceable author statement Ref.1. Source: ProtInc
Cellular_component	extracellular space Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform HCC-1 (identifier: Q16627-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform HCC-3 (identifier: Q16627-2)

The sequence of this isoform differs from the canonical sequence as follows:
     27-27: R → QTGGKPKVVKIQLKLVG

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

Ref.1 Ref.6 Ref.7

Chain

20 – 93

74

C-C motif chemokine 14

PRO_0000005204

Chain

22 – 93

72

HCC-1(3-74)

PRO_0000005205

Chain

23 – 93

71

HCC-1(4-74)

PRO_0000005206

Chain

28 – 93

66

HCC-1(9-74)

PRO_0000005207

Amino acid modifications

Glycosylation

26

1

O-linked (GalNAc...); partial Ref.6

Disulfide bond

35 ↔ 59

Disulfide bond

36 ↔ 75

Natural variations

Alternative sequence

27

1

R → QTGGKPKVVKIQLKLVG in isoform HCC-3.

VSP_001060

Natural variant

61

1

K → E.
Corresponds to variant rs16971802 [ dbSNP | Ensembl ].

VAR_048707

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

93

Helix Strand Turn

Details...

Beta strand

33 – 35

3

Helix

46 – 48

3

Beta strand

49 – 54

6

Beta strand

59 – 61

3

Beta strand

64 – 68

5

Beta strand

73 – 76

4

Helix

81 – 90

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform HCC-1 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: DDDB899DC9148836	FASTA	93	10,678
	10 20 30 40 50 60 MKISVAAIPF FLLITIALGT KTESSSRGPY HPSECCFTYT TYKIPRQRIM DYYETNSQCS 70 80 90 KPGIVFITKR GHSVCTNPSD KWVQDYIKDM KEN
	Isoform HCC-3 [UniParc]. Checksum: 73591D5CFF6D3C28	FASTA	109	12,297
	10 20 30 40 50 60 MKISVAAIPF FLLITIALGT KTESSSQTGG KPKVVKIQLK LVGGPYHPSE CCFTYTTYKI 70 80 90 100 PRQRIMDYYE TNSQCSKPGI VFITKRGHSV CTNPSDKWVQ DYIKDMKEN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"HCC-1, a novel chemokine from human plasma." Schulz-Knappe P., Maegert H.-J., Dewald B., Meyer M., Cetin Y., Kubbies M., Tomeczkowski J., Kirchhoff K., Raida M., Adermann K., Kist A., Reinecke M., Sillard R., Pardigol A., Uguccioni M., Baggiolini M., Forssmann W.-G. J. Exp. Med. 183:295-299(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM HCC-1), PROTEIN SEQUENCE OF 20-93. Tissue: Bone marrow.
[2]	"HCC-2, a human chemokine: gene structure, expression pattern, and biological activity." Pardigol A., Forssmann U., Zucht H.-D., Loetscher P., Schulz-Knappe P., Baggiolini M., Forssmann W.-G., Maegert H.-J. Proc. Natl. Acad. Sci. U.S.A. 95:6308-6313(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS HCC-1 AND HCC-3), TISSUE SPECIFICITY. Tissue: Liver.
[3]	"Organization of the chemokine gene cluster on human chromosome 17q11.2 containing the genes for CC chemokine MPIF-1, HCC-2, LEC, and RANTES." Nomiyama H., Fukuda S., Iio M., Tanase S., Miura R., Yoshie O. J. Interferon Cytokine Res. 19:227-234(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	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].
[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] (ISOFORM HCC-1). Tissue: Pancreas and Spleen.
[6]	"Posttranslationally processed forms of the human chemokine HCC-1." Richter R., Schulz-Knappe P., John H., Forssmann W.-G. Biochemistry 39:10799-10805(2000) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-32, IDENTIFICATION OF HCC-1(3-74) AND HCC-1(4-74), MASS SPECTROMETRY, GLYCOSYLATION AT SER-26.
[7]	"Natural proteolytic processing of hemofiltrate CC chemokine 1 generates a potent CC chemokine receptor (CCR)1 and CCR5 agonist with anti-HIV properties." Detheux M., Staendker L., Vakili J., Muench J., Forssmann U., Adermann K., Poehlmann S., Vassart G., Kirchhoff F., Parmentier M., Forssmann W.-G. J. Exp. Med. 192:1501-1508(2000) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-48, IDENTIFICATION OF HCC-1(9-74), MASS SPECTROMETRY, FUNCTION.
[8]	"Structural and functional characterization of CC chemokine CCL14." Blain K.Y., Kwiatkowski W., Zhao Q., La Fleur D., Naik C., Chun T.-W., Tsareva T., Kanakaraj P., Laird M.W., Shah R., George L., Sanyal I., Moore P.A., Demeler B., Choe S. Biochemistry 46:10008-10015(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS) OF 28-93.
+	Additional computationally mapped references.

Web resources

Wikipedia

CCL14 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z49270 mRNA. Translation: CAA89264.1.
Z70292 mRNA. Translation: CAA94307.1.
Z70293 mRNA. Translation: CAA94309.1.
Z49269 Genomic DNA. Translation: CAA89263.1.
AF088219 Genomic DNA. Translation: AAC63329.1.
AF088219 Genomic DNA. Translation: AAF23982.1.
CH471147 Genomic DNA. Translation: EAW80105.1.
CH471147 Genomic DNA. Translation: EAW80106.1.
CH471147 Genomic DNA. Translation: EAW80107.1.
CH471147 Genomic DNA. Translation: EAW80108.1.
BC038289 mRNA. Translation: AAH38289.1.
BC045165 mRNA. Translation: AAH45165.1.

IPI

IPI00003375.
IPI00215742.

RefSeq

NP_116738.1. NM_032962.4.
NP_116739.1. NM_032963.3.

UniGene

Hs.272493.
Hs.740501.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2Q8R	X-ray	1.82	E/F/G/H	28-93	[»]
2Q8T	X-ray	2.23	A/B/C/D	20-93	[»]

ProteinModelPortal

Q16627.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5861N.

IntAct

Q16627. 4 interactions.

STRING

9606.ENSP00000409197.

PTM databases

PhosphoSite

Q16627.

Polymorphism databases

DMDM

2493670.

Proteomic databases

PaxDb

Q16627.

PRIDE

Q16627.

Protocols and materials databases

DNASU

6358.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000394509; ENSP00000378017; ENSG00000213494.
ENST00000435911; ENSP00000409197; ENSG00000213494.
ENST00000536149; ENSP00000441771; ENSG00000213494.

GeneID

6358.

KEGG

hsa:6358.

UCSC

uc010wcq.1. human.
uc010wcr.1. human.

Organism-specific databases

CTD

6358.

GeneCards

GC17M034311.

H-InvDB

HIX0039168.

HGNC

HGNC:10612. CCL14.

HPA

CAB004423.
HPA030268.

MIM

601392. gene.

neXtProt

NX_Q16627.

PharmGKB

PA35545.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG84308.

HOGENOM

HOG000036685.

HOVERGEN

HBG017871.

InParanoid

Q16627.

KO

K05514.

OMA

QDYIKDM.

OrthoDB

EOG4JQ403.

Gene expression databases

Bgee

Q16627.

CleanEx

HS_CCL14.

Genevestigator

Q16627.

GermOnline

ENSG00000161574. 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

Q16627.

GenomeRNAi

6358.

NextBio

24696.

SOURCE

Search...

Entry information

Entry name

CCL14_HUMAN

Accession

Primary (citable) accession number: Q16627
Secondary accession number(s): E1P649, E1P650, Q13954

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	May 1, 2013
This is version 119 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.