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Cytokine receptor-like factor 2 (Cytokine receptor-like 2) (IL-XR) (Thymic stromal lymphopoietin protein receptor) (TSLP receptor)

 CRLF2_HUMAN             Reviewed;         371 AA.
Q9HC73; J3QKD1; Q5G7M1; Q9H5R3;
07-NOV-2003, integrated into UniProtKB/Swiss-Prot.
01-MAR-2001, sequence version 1.
07-NOV-2018, entry version 152.
RecName: Full=Cytokine receptor-like factor 2;
AltName: Full=Cytokine receptor-like 2;
AltName: Full=IL-XR;
AltName: Full=Thymic stromal lymphopoietin protein receptor;
Short=TSLP receptor;
Flags: Precursor;
Name=CRLF2; Synonyms=CRL2, ILXR, TSLPR;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
TISSUE=Dendritic cell;
PubMed=11237741; DOI=10.1006/bbrc.2001.4432;
Zhang W., Wang J., Wang Q., Chen G., Zhang J., Chen T., Wan T.,
Zhang Y., Cao X.;
"Identification of a novel type I cytokine receptor CRL2
preferentially expressed by human dendritic cells and activated
monocytes.";
Biochem. Biophys. Res. Commun. 281:878-883(2001).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
TISSUE=T-cell;
PubMed=11474172;
Tonozuka Y., Fujio K., Sugiyama T., Nosaka T., Hirai M., Kitamura T.;
"Molecular cloning of a human novel type I cytokine receptor related
to delta1/TSLPR.";
Cytogenet. Cell Genet. 93:23-25(2001).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION AS A RECEPTOR FOR
TSLP.
PubMed=11418668; DOI=10.4049/jimmunol.167.1.336;
Reche P.A., Soumelis V., Gorman D.M., Clifford T., Liu M.-R.,
Travis M., Zurawski S.M., Johnston J., Liu Y.-J., Spits H.,
de Waal Malefyt R., Kastelein R.A., Bazan J.F.;
"Human thymic stromal lymphopoietin preferentially stimulates myeloid
cells.";
J. Immunol. 167:336-343(2001).
[4]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
Li T., Yu X., Cao J., Wang S., Li X., Cui Q., Chen J., Zhang S.,
Chang Z., Fu X., Liu L.;
"Human thymic stromal lymphopoietin receptor presents three splicing
variants in selected tumor cells and functionally cooperates with IL-2
receptor beta to activate mitogenic signals.";
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
TISSUE=Lung;
PubMed=14702039; DOI=10.1038/ng1285;
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.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15772651; DOI=10.1038/nature03440;
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
"The DNA sequence of the human X chromosome.";
Nature 434:325-337(2005).
-!- FUNCTION: Receptor for thymic stromal lymphopoietin (TSLP). Forms
a functional complex with TSLP and IL7R which is capable of
stimulating cell proliferation through activation of STAT3 and
STAT5. Also activates JAK2 (By similarity). Implicated in the
development of the hematopoietic system. {ECO:0000250,
ECO:0000269|PubMed:11418668}.
-!- SUBUNIT: Heterodimer of CRLF2 and IL7R.
-!- SUBCELLULAR LOCATION: Isoform 1: Cell membrane {ECO:0000305};
Single-pass type I membrane protein {ECO:0000305}.
-!- SUBCELLULAR LOCATION: Isoform 2: Secreted {ECO:0000305}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=3;
Name=1;
IsoId=Q9HC73-1; Sequence=Displayed;
Name=2;
IsoId=Q9HC73-2; Sequence=VSP_008786, VSP_008787;
Note=No experimental confirmation available.;
Name=3;
IsoId=Q9HC73-3; Sequence=VSP_057463;
-!- TISSUE SPECIFICITY: Expressed in heart, skeletal muscle, kidney
and adult and fetal liver. Primarily expressed in dendrites and
monocytes. Weakly expressed in T-cells.
-!- INDUCTION: Up-regulated in activated peripheral monocytes and THP-
1 cells.
-!- DOMAIN: The WSXWS motif appears to be necessary for proper protein
folding and thereby efficient intracellular transport and cell-
surface receptor binding.
-!- DOMAIN: The box 1 motif is important for association with JAKs.
-!- MISCELLANEOUS: The gene coding for this protein is located in the
pseudoautosomal region 1 (PAR1) of X and Y chromosomes.
-!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 5
subfamily. {ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; AF142570; AAG27923.1; -; mRNA.
EMBL; AB052639; BAB60717.1; -; mRNA.
EMBL; AF338733; AAK60618.1; -; mRNA.
EMBL; AY775789; AAW66851.1; -; mRNA.
EMBL; AK026800; BAB15557.1; -; mRNA.
EMBL; AC188046; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BX908382; -; NOT_ANNOTATED_CDS; Genomic_DNA.
CCDS; CCDS75944.1; -. [Q9HC73-3]
CCDS; CCDS75945.1; -. [Q9HC73-1]
RefSeq; NP_001012288.2; NM_001012288.2. [Q9HC73-3]
RefSeq; NP_071431.2; NM_022148.3. [Q9HC73-1]
UniGene; Hs.287729; -.
PDB; 5J11; X-ray; 2.56 A; C=1-221.
PDB; 5J12; X-ray; 3.55 A; C=1-221.
PDBsum; 5J11; -.
PDBsum; 5J12; -.
ProteinModelPortal; Q9HC73; -.
SMR; Q9HC73; -.
STRING; 9606.ENSP00000370979; -.
iPTMnet; Q9HC73; -.
PhosphoSitePlus; Q9HC73; -.
BioMuta; CRLF2; -.
DMDM; 38257768; -.
PaxDb; Q9HC73; -.
PeptideAtlas; Q9HC73; -.
PRIDE; Q9HC73; -.
ProteomicsDB; 81644; -.
ProteomicsDB; 81645; -. [Q9HC73-2]
DNASU; 64109; -.
Ensembl; ENST00000381566; ENSP00000370978; ENSG00000205755. [Q9HC73-1]
Ensembl; ENST00000381567; ENSP00000370979; ENSG00000205755. [Q9HC73-3]
Ensembl; ENST00000400841; ENSP00000383641; ENSG00000205755. [Q9HC73-1]
GeneID; 64109; -.
KEGG; hsa:64109; -.
UCSC; uc004cpl.4; human.
UCSC; uc022brs.3; human. [Q9HC73-1]
CTD; 64109; -.
DisGeNET; 64109; -.
EuPathDB; HostDB:ENSG00000205755.11; -.
GeneCards; CRLF2; -.
HGNC; HGNC:14281; CRLF2.
MalaCards; CRLF2; -.
MIM; 300357; gene.
MIM; 400023; gene.
neXtProt; NX_Q9HC73; -.
OpenTargets; ENSG00000205755; -.
PharmGKB; PA26883; -.
eggNOG; ENOG410IKHC; Eukaryota.
eggNOG; ENOG41116BS; LUCA.
GeneTree; ENSGT00510000049974; -.
HOGENOM; HOG000172557; -.
HOVERGEN; HBG097013; -.
InParanoid; Q9HC73; -.
KO; K05078; -.
OMA; EKCYFFR; -.
OrthoDB; EOG091G09QC; -.
PhylomeDB; Q9HC73; -.
TreeFam; TF342693; -.
Reactome; R-HSA-1266695; Interleukin-7 signaling.
SignaLink; Q9HC73; -.
SIGNOR; Q9HC73; -.
ChiTaRS; CRLF2; human.
GenomeRNAi; 64109; -.
PRO; PR:Q9HC73; -.
Proteomes; UP000005640; Chromosome X.
Bgee; ENSG00000205755; Expressed in 32 organ(s), highest expression level in leukocyte.
CleanEx; HS_CRLF2; -.
ExpressionAtlas; Q9HC73; baseline and differential.
Genevisible; Q9HC73; HS.
GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0005886; C:plasma membrane; TAS:Reactome.
GO; GO:0043235; C:receptor complex; IBA:GO_Central.
GO; GO:0019955; F:cytokine binding; IBA:GO_Central.
GO; GO:0004896; F:cytokine receptor activity; IDA:UniProtKB.
GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:UniProtKB.
GO; GO:0038111; P:interleukin-7-mediated signaling pathway; TAS:Reactome.
GO; GO:0008284; P:positive regulation of cell proliferation; IDA:UniProtKB.
GO; GO:2000664; P:positive regulation of interleukin-5 secretion; IMP:UniProtKB.
GO; GO:0033005; P:positive regulation of mast cell activation; IMP:UniProtKB.
GO; GO:1904894; P:positive regulation of STAT cascade; IDA:UniProtKB.
CDD; cd00063; FN3; 1.
Gene3D; 2.60.40.10; -; 2.
InterPro; IPR003961; FN3_dom.
InterPro; IPR036116; FN3_sf.
InterPro; IPR013783; Ig-like_fold.
SUPFAM; SSF49265; SSF49265; 2.
PROSITE; PS50853; FN3; 1.
1: Evidence at protein level;
3D-structure; Alternative splicing; Cell membrane; Complete proteome;
Disulfide bond; Glycoprotein; Membrane; Receptor; Reference proteome;
Secreted; Signal; Transmembrane; Transmembrane helix.
SIGNAL 1 22 {ECO:0000255}.
CHAIN 23 371 Cytokine receptor-like factor 2.
/FTId=PRO_0000011041.
TOPO_DOM 23 231 Extracellular. {ECO:0000255}.
TRANSMEM 232 252 Helical. {ECO:0000255}.
TOPO_DOM 253 371 Cytoplasmic. {ECO:0000255}.
DOMAIN 118 211 Fibronectin type-III.
{ECO:0000255|PROSITE-ProRule:PRU00316}.
MOTIF 200 204 WSXWS motif.
MOTIF 261 269 Box 1 motif.
CARBOHYD 47 47 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 55 55 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 101 101 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 169 169 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 71 84 {ECO:0000250|UniProtKB:Q8CII9}.
DISULFID 180 218 {ECO:0000250|UniProtKB:Q8CII9}.
VAR_SEQ 1 112 Missing (in isoform 3).
{ECO:0000303|Ref.4}.
/FTId=VSP_057463.
VAR_SEQ 162 233 SKQENTCNVTIEGLDAEKCYSFWVRVKAMEDVYGPDTYPSD
WSEVTCWQRGEIRDACAETPTPPKPKLSKFI -> TQSRSV
TQAGVQWCDLCLLQPSPPRFKRFSCLSLPSSWDYRHPPPRL
ANFCIISRDGVSPCWPGWSRTCDLR (in isoform 2).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_008786.
VAR_SEQ 234 371 Missing (in isoform 2).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_008787.
CONFLICT 27 27 Missing (in Ref. 5; BAB15557).
{ECO:0000305}.
CONFLICT 258 258 K -> R (in Ref. 4; AAW66851).
CONFLICT 305 305 E -> G (in Ref. 4; AAW66851).
CONFLICT 358 358 G -> D (in Ref. 4; AAW66851).
STRAND 31 37 {ECO:0000244|PDB:5J11}.
TURN 38 40 {ECO:0000244|PDB:5J11}.
STRAND 41 47 {ECO:0000244|PDB:5J11}.
HELIX 49 51 {ECO:0000244|PDB:5J11}.
STRAND 57 63 {ECO:0000244|PDB:5J11}.
STRAND 72 77 {ECO:0000244|PDB:5J11}.
STRAND 80 87 {ECO:0000244|PDB:5J11}.
STRAND 94 101 {ECO:0000244|PDB:5J11}.
STRAND 104 112 {ECO:0000244|PDB:5J11}.
HELIX 113 116 {ECO:0000244|PDB:5J11}.
STRAND 126 129 {ECO:0000244|PDB:5J11}.
STRAND 131 137 {ECO:0000244|PDB:5J11}.
STRAND 145 153 {ECO:0000244|PDB:5J11}.
STRAND 161 174 {ECO:0000244|PDB:5J11}.
STRAND 181 189 {ECO:0000244|PDB:5J11}.
HELIX 191 194 {ECO:0000244|PDB:5J11}.
STRAND 207 210 {ECO:0000244|PDB:5J11}.
STRAND 213 216 {ECO:0000244|PDB:5J11}.
SEQUENCE 371 AA; 42013 MW; DEA53814758B69E4 CRC64;
MGRLVLLWGA AVFLLGGWMA LGQGGAAEGV QIQIIYFNLE TVQVTWNASK YSRTNLTFHY
RFNGDEAYDQ CTNYLLQEGH TSGCLLDAEQ RDDILYFSIR NGTHPVFTAS RWMVYYLKPS
SPKHVRFSWH QDAVTVTCSD LSYGDLLYEV QYRSPFDTEW QSKQENTCNV TIEGLDAEKC
YSFWVRVKAM EDVYGPDTYP SDWSEVTCWQ RGEIRDACAE TPTPPKPKLS KFILISSLAI
LLMVSLLLLS LWKLWRVKKF LIPSVPDPKS IFPGLFEIHQ GNFQEWITDT QNVAHLHKMA
GAEQESGPEE PLVVQLAKTE AESPRMLDPQ TEEKEASGGS LQLPHQPLQG GDVVTIGGFT
FVMNDRSYVA L


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