O00421 (CCRL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
C-C chemokine receptor-like 2

Alternative name(s):
Chemokine receptor CCR11
Chemokine receptor X
Putative MCP-1 chemokine receptor

Gene names

Name:	CCRL2
Synonyms:	CCR11, CCR6, CKRX, CRAM, HCR

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	344 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 receptors. Plays a critical role for the development of Th2 responses.
Subcellular location	Cell membrane; Multi-pass membrane protein Ref.11 Ref.12.
Tissue specificity	Expressed abundantly in immunal tissues such as spleen, fetal liver, lymph node and bone marrow. Strong expression also in lung and heart. Expressed in almost all hematopoietic cells including monocytes, macrophages, PMNs, T-cells (both CD4+ and CD8+), monocyte-derived iDCs, NK cells, and CD34+ progenitor cells. B-cells expressed isoform 1 but not isoform 2. Up-regulated on synovial neutrophils of rheumatoid arthritis patients. Ref.1 Ref.9 Ref.10 Ref.11
Induction	Up-regulated by CCL5 on the pre-B-cell lines NALM-6 and G2. Ref.11
Domain	Lacks the conserved DRYLAIV motif in the second intracellular loop that is required for signaling of functional chemokine receptors.
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. 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
Coding sequence diversity	Alternative splicing Polymorphism
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 Traceable author statement Ref.1. Source: ProtInc inflammatory response Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	integral to plasma membrane Inferred from direct assay Ref.12. Source: UniProtKB
Molecular_function	chemokine receptor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: O00421-1)

Also known as: CRAM-B;

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 2 (identifier: O00421-2)

Also known as: CRAM-A;

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MIYTRFLKGSLKM

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 344	344	C-C chemokine receptor-like 2		PRO_0000236798
Regions
	Topological domain	1 – 43	43	Extracellular Potential
	Transmembrane	44 – 64	21	Helical; Name=1; Potential
	Topological domain	65 – 74	10	Cytoplasmic Potential
	Transmembrane	75 – 95	21	Helical; Name=2; Potential
	Topological domain	96 – 104	9	Extracellular Potential
	Transmembrane	105 – 125	21	Helical; Name=3; Potential
	Topological domain	126 – 144	19	Cytoplasmic Potential
	Transmembrane	145 – 165	21	Helical; Name=4; Potential
	Topological domain	166 – 198	33	Extracellular Potential
	Transmembrane	199 – 219	21	Helical; Name=5; Potential
	Topological domain	220 – 238	19	Cytoplasmic Potential
	Transmembrane	239 – 259	21	Helical; Name=6; Potential
	Topological domain	260 – 286	27	Extracellular Potential
	Transmembrane	287 – 307	21	Helical; Name=7; Potential
	Topological domain	308 – 344	37	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	3	1	N-linked (GlcNAc...) Potential
	Disulfide bond	103 ↔ 181		By similarity
Natural variations
	Alternative sequence	1	1	M → MIYTRFLKGSLKM in isoform 2.		VSP_018584
	Natural variant	4	1	Y → C. Corresponds to variant rs11574443 [ dbSNP | Ensembl ].		VAR_049385
	Natural variant	167	1	F → Y. Ref.1 Ref.2 Ref.6 Ref.7 Ref.8 Corresponds to variant rs3204849 [ dbSNP | Ensembl ].		VAR_026488
	Natural variant	168	1	V → M. Ref.8 Corresponds to variant rs6441977 [ dbSNP | Ensembl ].		VAR_026489
	Natural variant	243	1	I → V. Ref.3 Corresponds to variant rs3204850 [ dbSNP | Ensembl ].		VAR_026490
Experimental info
	Sequence conflict	45	1	C → S in BAG59270. Ref.5
	Sequence conflict	135	1	K → R in BAG59270. Ref.5
	Sequence conflict	158	1	T → Q in CAC82985. Ref.4
	Sequence conflict	334	1	S → P in BAG59270. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (CRAM-B) [UniParc]. Last modified May 30, 2006. Version 2. Checksum: D8BBF3A0EE5BB14C	FASTA	344	39,513
	10 20 30 40 50 60 MANYTLAPED EYDVLIEGEL ESDEAEQCDK YDAQALSAQL VPSLCSAVFV IGVLDNLLVV 70 80 90 100 110 120 LILVKYKGLK RVENIYLLNL AVSNLCFLLT LPFWAHAGGD PMCKILIGLY FVGLYSETFF 130 140 150 160 170 180 NCLLTVQRYL VFLHKGNFFS ARRRVPCGII TSVLAWVTAI LATLPEFVVY KPQMEDQKYK 190 200 210 220 230 240 CAFSRTPFLP ADETFWKHFL TLKMNISVLV LPLFIFTFLY VQMRKTLRFR EQRYSLFKLV 250 260 270 280 290 300 FAIMVVFLLM WAPYNIAFFL STFKEHFSLS DCKSSYNLDK SVHITKLIAT THCCINPLLY 310 320 330 340 AFLDGTFSKY LCRCFHLRSN TPLQPRGQSA QGTSREEPDH STEV
	Isoform 2 (CRAM-A) [UniParc]. Checksum: 83883A727B797D00	FASTA	356	40,952
	10 20 30 40 50 60 MIYTRFLKGS LKMANYTLAP EDEYDVLIEG ELESDEAEQC DKYDAQALSA QLVPSLCSAV 70 80 90 100 110 120 FVIGVLDNLL VVLILVKYKG LKRVENIYLL NLAVSNLCFL LTLPFWAHAG GDPMCKILIG 130 140 150 160 170 180 LYFVGLYSET FFNCLLTVQR YLVFLHKGNF FSARRRVPCG IITSVLAWVT AILATLPEFV 190 200 210 220 230 240 VYKPQMEDQK YKCAFSRTPF LPADETFWKH FLTLKMNISV LVLPLFIFTF LYVQMRKTLR 250 260 270 280 290 300 FREQRYSLFK LVFAIMVVFL LMWAPYNIAF FLSTFKEHFS LSDCKSSYNL DKSVHITKLI 310 320 330 340 350 ATTHCCINPL LYAFLDGTFS KYLCRCFHLR SNTPLQPRGQ SAQGTSREEP DHSTEV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of a novel human chemokine receptor." Fan P., Kyaw H., Su K., Zeng Z., Augustus M., Carter K.C., Li Y. Biochem. Biophys. Res. Commun. 243:264-268(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANT TYR-167.
[2]	"Haplotype analysis of a gene cluster containing CCR5 and a new member of chemokine receptor gene family." Ansari-Lari M.A., Liu X.-M., Gorrell J.H., Gibbs R.A. Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT TYR-167. Tissue: Leukocyte.
[3]	"CRAM: a novel human chemokine receptor-like gene expressed in activated monocytes." Gish K., McClanahan T.K., Moore K.W. Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT VAL-243. Tissue: Monocyte.
[4]	"Cloning and characterisation of a new MCP-1 chemokine receptor CCR11." Biber K.P.H. Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Microglia.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Umbilical cord blood.
[6]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." Kopatz S.A., Aronstam R.S., Sharma S.V. Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT TYR-167. Tissue: Lung.
[7]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT TYR-167.
[8]	"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 1), VARIANTS TYR-167 AND MET-168. Tissue: Brain, Lung, Pancreas, Spleen and Testis.
[9]	"Distribution and regulation of expression of the putative human chemokine receptor HCR in leukocyte populations." Migeotte I., Franssen J.D., Goriely S., Willems F., Parmentier M. Eur. J. Immunol. 32:494-501(2002) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[10]	"Up-regulated expression and activation of the orphan chemokine receptor, CCRL2, in rheumatoid arthritis." Galligan C.L., Matsuyama W., Matsukawa A., Mizuta H., Hodge D.R., Howard O.M., Yoshimura T. Arthritis Rheum. 50:1806-1814(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, LACK OF RESPOND BY CCL2.
[11]	"Human B cells express the orphan chemokine receptor CRAM-A/B in a maturation-stage-dependent and CCL5-modulated manner." Hartmann T.N., Leick M., Ewers S., Diefenbacher A., Schraufstatter I., Honczarenko M., Burger M. Immunology 125:252-262(2008) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INDUCTION.
[12]	"CCL19 is a specific ligand of the constitutively recycling atypical human chemokine receptor CRAM-B." Leick M., Catusse J., Follo M., Nibbs R.J., Hartmann T.N., Veelken H., Burger M. Immunology 129:536-546(2010) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, LIGAND-BINDING.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U97123 mRNA. Translation: AAC39595.1. AF014958 mRNA. Translation: AAB82106.1. AF015524 mRNA. Translation: AAC34601.1. AF015525 mRNA. Translation: AAC34602.1. AJ344142 mRNA. Translation: CAC82985.1. AK296673 mRNA. Translation: BAG59270.1. AY337001 mRNA. Translation: AAQ76789.1. U95626 Genomic DNA. Translation: AAB57794.1. BC025717 mRNA. Translation: AAH25717.1. BC071682 mRNA. Translation: AAH71682.1. BC096075 mRNA. Translation: AAH96075.1. BC096076 mRNA. Translation: AAH96076.1. BC099623 mRNA. Translation: AAH99623.1.
IPI	IPI00018247. IPI00759535.
PIR	JC5942.
RefSeq	NP_001124382.1. NM_001130910.1. NP_003956.2. NM_003965.4.
UniGene	Hs.535713.
3D structure databases
ProteinModelPortal	O00421.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000349967.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	O00421.
Proteomic databases
PaxDb	O00421.
PRIDE	O00421.
Protocols and materials databases
DNASU	9034.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000357392; ENSP00000349967; ENSG00000121797. ENST00000399036; ENSP00000381994; ENSG00000121797. ENST00000400880; ENSP00000383677; ENSG00000121797. ENST00000400882; ENSP00000383678; ENSG00000121797.
GeneID	9034.
KEGG	hsa:9034.
UCSC	uc003cpp.4. human. uc010hjg.3. human.
Organism-specific databases
CTD	9034.
GeneCards	GC03P046448.
HGNC	HGNC:1612. CCRL2.
HPA	HPA043238.
MIM	608379. gene.
neXtProt	NX_O00421.
PharmGKB	PA26175.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG149863.
HOVERGEN	HBG106917.
InParanoid	O00421.
KO	K08373.
OMA	FLLMWAP.
OrthoDB	EOG45B1G8.
Gene expression databases
ArrayExpress	O00421.
Bgee	O00421.
CleanEx	HS_CCR6. HS_CCRL2.
Genevestigator	O00421.
GermOnline	ENSG00000121797. Homo sapiens.
Family and domain databases
InterPro	IPR000355. Chemokine_rcpt. IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. [Graphical view]
PANTHER	PTHR24227. PTHR24227. 1 hit.
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
GenomeRNAi	9034.
NextBio	33847.
SOURCE	Search...

Entry information

Entry name

CCRL2_HUMAN

Accession

Primary (citable) accession number: O00421
Secondary accession number(s): B4DKQ8 , O75307, Q4VBB0, Q6IPX0, Q7KYQ9, Q96KP5, Q9UPG0

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2006
Last sequence update:	May 30, 2006
Last modified:	May 29, 2013
This is version 104 of the entry and version 2 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.