O35457 (CCRL2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
C-C chemokine receptor-like 2

Alternative name(s):
Chemokine receptor CCR11
G-protein coupled beta chemokine receptor
Lipopolysaccharide-inducible C-C chemokine receptor
Short name=L-CCR

Gene names

Name:	Ccrl2
Synonyms:	Ccr11, Lccr

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	360 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for CCL19 and chemerin/RARRES2. Does not appear to be a signaling receptor, but may have a role in modulating chemokine-triggered immune responses by capturing and internalizing CCL19 or by presenting RARRES2 ligand to CMKLR1, a functional signaling receptor. Plays a critical role for the development of Th2 responses By similarity. Ref.7 Ref.10 Ref.11
Subcellular location	Cell membrane; Multi-pass membrane protein By similarity.
Tissue specificity	Expressed in macrophages, astrocytes, in glial cells. Constitutively expressed by mast cells. Detected in bronchial epithelium in OVA-induced airway inflammation. Up-regulated during dendritic cell (DC) maturation. Ref.1 Ref.2 Ref.8 Ref.9 Ref.11
Induction	By bacterial lipopolysaccharide in astrocytes. Ref.2
Domain	Lacks the conserved DRYLAIV motif in the second intracellular loop that is required for signaling of functional chemokine receptors By similarity.
Disruption phenotype	No visible phenotype. Deficient-mice have normal numbers of mast cells in all tissues analyzed. Wild-type and deficient mice develop marked local inflammation when sensitized with a high dose of DNP-specific IgE, however deficient mice have significantly reduced IgE-dependent passive cutaneous anaphylaxis (PCA) reactions when lower sensitizing dose is used. Deficient-mice show normal recruitment of circulating DC into the lung, but a defective trafficking of antigen-loaded lung DC to mediastinal lymph nodes. This defect was associated to a reduction in lymph node cellularity and reduced priming of T-helper cell 2 response. Ref.10 Ref.11
Miscellaneous	It was initially reported that CCRL2 responds functionally to CCL2, CCL5, CCL7, and CCL8 via intracellular calcium mobilization and transwell chemotaxis although no evidence for a direct ligand-receptor interaction was provided in this report (Ref.8). These results are now controversial and other studies failed to confirm CCRL2 recognition and transwell chemotaxis of these chemokines or a series of other CC- and CXC-chemokines using CCRL2-transfected cells (Ref.10).
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	chemotaxis Inferred from electronic annotation. Source: InterPro inflammatory response Inferred from direct assay Ref.10. Source: UniProtKB
Cellular_component	integral to plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	C-C chemokine receptor activity Inferred from sequence or structural similarity Ref.1. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 360	360	C-C chemokine receptor-like 2		PRO_0000236800
Regions
	Topological domain	1 – 42	42	Extracellular Potential
	Transmembrane	43 – 63	21	Helical; Name=1; Potential
	Topological domain	64 – 73	10	Cytoplasmic Potential
	Transmembrane	74 – 94	21	Helical; Name=2; Potential
	Topological domain	95 – 109	15	Extracellular Potential
	Transmembrane	110 – 130	21	Helical; Name=3; Potential
	Topological domain	131 – 141	11	Cytoplasmic Potential
	Transmembrane	142 – 162	21	Helical; Name=4; Potential
	Topological domain	163 – 202	40	Extracellular Potential
	Transmembrane	203 – 223	21	Helical; Name=5; Potential
	Topological domain	224 – 243	20	Cytoplasmic Potential
	Transmembrane	244 – 264	21	Helical; Name=6; Potential
	Topological domain	265 – 285	21	Extracellular Potential
	Transmembrane	286 – 307	22	Helical; Name=7; Potential
	Topological domain	308 – 360	53	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	3	1	N-linked (GlcNAc...) Potential
	Glycosylation	105	1	N-linked (GlcNAc...) Potential
	Disulfide bond	108 ↔ 185		By similarity
Experimental info
	Sequence conflict	37	1	P → S in BAE26775. Ref.4
	Sequence conflict	39	1	Q → R in CAC79612. Ref.2
	Sequence conflict	157	1	I → V in AAB86479. Ref.3
	Sequence conflict	215	1	F → L in CAC79612. Ref.2
	Sequence conflict	292	1	V → A in CAC79612. Ref.2
	Sequence conflict	334	1	Y → S in AAB86479. Ref.3
	Sequence conflict	341	1	E → K in AAB86479. Ref.3
	Sequence conflict	359	1	I → K in CAJ18456. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	O35457 [UniParc]. Last modified May 30, 2006. Version 2. Checksum: E0DBF990A8595E3B	FASTA	360	40,745
	10 20 30 40 50 60 MDNYTVAPDD EYDVLILDDY LDNSGPDQVP APEFLSPQQV LQFCCAVFAV GLLDNVLAVF 70 80 90 100 110 120 ILVKYKGLKN LGNIYFLNLA LSNLCFLLPL PFWAHTAAHG ESPGNGTCKV LVGLHSSGLY 130 140 150 160 170 180 SEVFSNILLL VQGYRVFSQG RLASIFTTVS CGIVACILAW AMATALSLPE SVFYEPRMER 190 200 210 220 230 240 QKHKCAFGKP HFLPIEAPLW KYVLTSKMII LVLAFPLLVF IICCRQLRRR QSFRERQYDL 250 260 270 280 290 300 HKPALVITGV FLLMWAPYNT VLFLSAFQEH LSLQDEKSSY HLDASVQVTQ LVATTHCCVN 310 320 330 340 350 360 PLLYLLLDRK AFMRYLRSLF PRCNDIPYQS SGGYQQAPPR EGHGRPIELY SNLHQRQDII

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel lipopolysaccharide inducible C-C chemokine receptor related gene in murine macrophages." Shimada T., Matsumoto M., Tatsumi Y., Kanamaru A., Akira S. FEBS Lett. 425:490-494(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[2]	"LPS-induced expression of a novel chemokine receptor (L-CCR) in mouse glial cells in vitro and in vivo." Zuurman M.W., Heeroma J., Brouwer N., Boddeke H.W., Biber K.P.H. Glia 41:327-336(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION, TISSUE SPECIFICITY. Strain: CD-1.
[3]	"RANTES and eotaxin stimulate chemotaxis, chemokine/cytokine synthesis, and receptor modulation in murine astroctyes." Luo Y., Berman M.A., Fischer F.R., Abromson-Leeman S.R., Kuziel W.A., Gerard C., Dorf M.E. Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: 129/Sv and C57BL/10.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Placenta.
[5]	"Cloning of mouse full open reading frames in Gateway(R) system entry vector (pDONR201)." Ebert L., Muenstermann E., Schatten R., Henze S., Bohn E., Mollenhauer J., Wiemann S., Schick M., Korn B. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"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]. Strain: C57BL/6J. Tissue: Mammary gland.
[7]	"Expression of L-CCR in HEK 293 cells reveals functional responses to CCL2, CCL5, CCL7, and CCL8." Biber K., Zuurman M.W., Homan H., Boddeke H.W.G.M. J. Leukoc. Biol. 74:243-251(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Induction of glial L-CCR mRNA expression in spinal cord and brain in experimental autoimmune encephalomyelitis." Brouwer N., Zuurman M.W., Wei T., Ransohoff R.M., Boddeke H.W., Biber K. Glia 46:84-94(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[9]	"Localization and enhanced mRNA expression of the orphan chemokine receptor L-CCR in the lung in a murine model of ovalbumin-induced airway inflammation." Oostendorp J., Hylkema M.N., Luinge M., Geerlings M., Meurs H., Timens W., Zaagsma J., Postma D.S., Boddeke H.W., Biber K. J. Histochem. Cytochem. 52:401-410(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[10]	"Mast cell-expressed orphan receptor CCRL2 binds chemerin and is required for optimal induction of IgE-mediated passive cutaneous anaphylaxis." Zabel B.A., Nakae S., Zuniga L., Kim J.Y., Ohyama T., Alt C., Pan J., Suto H., Soler D., Allen S.J., Handel T.M., Song C.H., Galli S.J., Butcher E.C. J. Exp. Med. 205:2207-2220(2008) [PubMed] [Europe PMC] [Abstract] Cited for: LIGAND-BINDING, DISRUPTION PHENOTYPE, FUNCTION, LACK OF RESPOND TO CCL2; CCL5; CCL7 AND CCL8.
[11]	"Nonredundant role of CCRL2 in lung dendritic cell trafficking." Otero K., Vecchi A., Hirsch E., Kearley J., Vermi W., Del Prete A., Gonzalvo-Feo S., Garlanda C., Azzolino O., Salogni L., Lloyd C.M., Facchetti F., Mantovani A., Sozzani S. Blood 116:2942-2949(2010) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB009384 mRNA. Translation: BAA25879.1. AJ318863 mRNA. Translation: CAC79612.1. AF316576 mRNA. Translation: AAG30950.1. AF030185 mRNA. Translation: AAB86479.1. AK007808 mRNA. Translation: BAB25273.1. AK145946 mRNA. Translation: BAE26775.1. AK151856 mRNA. Translation: BAE30745.1. CT010248 mRNA. Translation: CAJ18456.1. BC038631 mRNA. Translation: AAH38631.1.
IPI	IPI00453759.
RefSeq	NP_059494.2. NM_017466.4.
UniGene	Mm.7336.
3D structure databases
ProteinModelPortal	O35457.
SMR	O35457. Positions 46-308.
ModBase	Search...
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	O35457.
Proteomic databases
PRIDE	O35457.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000111888; ENSMUSP00000107519; ENSMUSG00000043953.
GeneID	54199.
KEGG	mmu:54199.
UCSC	uc009rvk.1. mouse.
Organism-specific databases
CTD	9034.
MGI	MGI:1920904. Ccrl2.
Phylogenomic databases
eggNOG	NOG149863.
GeneTree	ENSGT00700000104407.
HOGENOM	HOG000234122.
HOVERGEN	HBG106917.
InParanoid	O35457.
KO	K08373.
OMA	FLLMWAP.
OrthoDB	EOG45B1G8.
Gene expression databases
Bgee	O35457.
CleanEx	MM_CCRL2.
Genevestigator	O35457.
GermOnline	ENSMUSG00000043953. Mus musculus.
Family and domain databases
InterPro	IPR000355. Chemokine_rcpt. IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00657. CCCHEMOKINER. PR00237. GPCRRHODOPSN.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. False negative. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	311054.
SOURCE	Search...

Entry information

Entry name

CCRL2_MOUSE

Accession

Primary (citable) accession number: O35457
Secondary accession number(s): O70171 , Q3UKM6, Q4FK04, Q91YD7

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2006
Last sequence update:	May 30, 2006
Last modified:	May 1, 2013
This is version 87 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program