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O35457

- CCRL2_MOUSE

UniProt

O35457 - CCRL2_MOUSE

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Protein

C-C chemokine receptor-like 2

Gene

Ccrl2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli

Functioni

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).By similarity

GO - Molecular functioni

  1. C-C chemokine receptor activity Source: MGI
  2. chemokine receptor binding Source: UniProtKB

GO - Biological processi

  1. chemokine-mediated signaling pathway Source: GOC
  2. chemotaxis Source: InterPro
  3. inflammatory response Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Names & Taxonomyi

Protein namesi
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 namesi
Name:Ccrl2
Synonyms:Ccr11, Lccr
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 9

Organism-specific databases

MGIiMGI:1920904. Ccrl2.

Subcellular locationi

Cell membrane By similarity; Multi-pass membrane protein By similarity

GO - Cellular componenti

  1. integral component of plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

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.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 360360C-C chemokine receptor-like 2PRO_0000236800Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi3 – 31N-linked (GlcNAc...)Sequence Analysis
Glycosylationi105 – 1051N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi108 ↔ 185PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PRIDEiO35457.

PTM databases

PhosphoSiteiO35457.

Expressioni

Tissue specificityi

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.5 Publications

Inductioni

By bacterial lipopolysaccharide in astrocytes.1 Publication

Gene expression databases

BgeeiO35457.
CleanExiMM_CCRL2.
GenevestigatoriO35457.

Structurei

3D structure databases

ProteinModelPortaliO35457.
SMRiO35457. Positions 47-320.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 4242ExtracellularSequence AnalysisAdd
BLAST
Topological domaini64 – 7310CytoplasmicSequence Analysis
Topological domaini95 – 10915ExtracellularSequence AnalysisAdd
BLAST
Topological domaini131 – 14111CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini163 – 20240ExtracellularSequence AnalysisAdd
BLAST
Topological domaini224 – 24320CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini265 – 28521ExtracellularSequence AnalysisAdd
BLAST
Topological domaini308 – 36053CytoplasmicSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei43 – 6321Helical; Name=1Sequence AnalysisAdd
BLAST
Transmembranei74 – 9421Helical; Name=2Sequence AnalysisAdd
BLAST
Transmembranei110 – 13021Helical; Name=3Sequence AnalysisAdd
BLAST
Transmembranei142 – 16221Helical; Name=4Sequence AnalysisAdd
BLAST
Transmembranei203 – 22321Helical; Name=5Sequence AnalysisAdd
BLAST
Transmembranei244 – 26421Helical; Name=6Sequence AnalysisAdd
BLAST
Transmembranei286 – 30722Helical; Name=7Sequence AnalysisAdd
BLAST

Family & Domainsi

Domaini

Lacks the conserved DRYLAIV motif in the second intracellular loop that is required for signaling of functional chemokine receptors.By similarity

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG149863.
GeneTreeiENSGT00760000118785.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiO35457.
KOiK08373.
OMAiFLLMWAP.
OrthoDBiEOG77HDFH.
PhylomeDBiO35457.
TreeFamiTF330966.

Family and domain databases

Gene3Di1.20.1070.10. 1 hit.
InterProiIPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24227. PTHR24227. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00657. CCCHEMOKINER.
PR00237. GPCRRHODOPSN.
PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O35457-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MDNYTVAPDD EYDVLILDDY LDNSGPDQVP APEFLSPQQV LQFCCAVFAV
60 70 80 90 100
GLLDNVLAVF ILVKYKGLKN LGNIYFLNLA LSNLCFLLPL PFWAHTAAHG
110 120 130 140 150
ESPGNGTCKV LVGLHSSGLY SEVFSNILLL VQGYRVFSQG RLASIFTTVS
160 170 180 190 200
CGIVACILAW AMATALSLPE SVFYEPRMER QKHKCAFGKP HFLPIEAPLW
210 220 230 240 250
KYVLTSKMII LVLAFPLLVF IICCRQLRRR QSFRERQYDL HKPALVITGV
260 270 280 290 300
FLLMWAPYNT VLFLSAFQEH LSLQDEKSSY HLDASVQVTQ LVATTHCCVN
310 320 330 340 350
PLLYLLLDRK AFMRYLRSLF PRCNDIPYQS SGGYQQAPPR EGHGRPIELY
360
SNLHQRQDII
Length:360
Mass (Da):40,745
Last modified:May 30, 2006 - v2
Checksum:iE0DBF990A8595E3B
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti37 – 371P → S in BAE26775. (PubMed:16141072)Curated
Sequence conflicti39 – 391Q → R in CAC79612. (PubMed:12555200)Curated
Sequence conflicti157 – 1571I → V in AAB86479. 1 PublicationCurated
Sequence conflicti215 – 2151F → L in CAC79612. (PubMed:12555200)Curated
Sequence conflicti292 – 2921V → A in CAC79612. (PubMed:12555200)Curated
Sequence conflicti334 – 3341Y → S in AAB86479. 1 PublicationCurated
Sequence conflicti341 – 3411E → K in AAB86479. 1 PublicationCurated
Sequence conflicti359 – 3591I → K in CAJ18456. 1 PublicationCurated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS23582.1.
RefSeqiNP_059494.2. NM_017466.4.
XP_006512248.1. XM_006512185.1.
XP_006512249.1. XM_006512186.1.
UniGeneiMm.7336.

Genome annotation databases

EnsembliENSMUST00000111888; ENSMUSP00000107519; ENSMUSG00000043953.
GeneIDi54199.
KEGGimmu:54199.
UCSCiuc009rvk.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS23582.1.
RefSeqi NP_059494.2. NM_017466.4.
XP_006512248.1. XM_006512185.1.
XP_006512249.1. XM_006512186.1.
UniGenei Mm.7336.

3D structure databases

ProteinModelPortali O35457.
SMRi O35457. Positions 47-320.
ModBasei Search...
MobiDBi Search...

Chemistry

GuidetoPHARMACOLOGYi 78.

Protein family/group databases

GPCRDBi Search...

PTM databases

PhosphoSitei O35457.

Proteomic databases

PRIDEi O35457.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000111888 ; ENSMUSP00000107519 ; ENSMUSG00000043953 .
GeneIDi 54199.
KEGGi mmu:54199.
UCSCi uc009rvk.1. mouse.

Organism-specific databases

CTDi 9034.
MGIi MGI:1920904. Ccrl2.

Phylogenomic databases

eggNOGi NOG149863.
GeneTreei ENSGT00760000118785.
HOGENOMi HOG000234122.
HOVERGENi HBG106917.
InParanoidi O35457.
KOi K08373.
OMAi FLLMWAP.
OrthoDBi EOG77HDFH.
PhylomeDBi O35457.
TreeFami TF330966.

Miscellaneous databases

NextBioi 311054.
PROi O35457.
SOURCEi Search...

Gene expression databases

Bgeei O35457.
CleanExi MM_CCRL2.
Genevestigatori O35457.

Family and domain databases

Gene3Di 1.20.1070.10. 1 hit.
InterProi IPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view ]
PANTHERi PTHR24227. PTHR24227. 1 hit.
Pfami PF00001. 7tm_1. 1 hit.
[Graphical view ]
PRINTSi PR00657. CCCHEMOKINER.
PR00237. GPCRRHODOPSN.
PROSITEi PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, FUNCTION.

Entry informationi

Entry nameiCCRL2_MOUSE
AccessioniPrimary (citable) accession number: O35457
Secondary accession number(s): O70171
, Q3UKM6, Q4FK04, Q91YD7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: May 30, 2006
Last modified: October 29, 2014
This is version 99 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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 (PubMed:14999816). 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 (PubMed:18794339).2 Publications

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3