ID   CRLF2_MOUSE             Reviewed;         359 AA.
AC   Q8CII9; Q9CRJ6; Q9JIE7; Q9JIQ7; Q9JJH8; Q9JMD5;
DT   07-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT   07-NOV-2003, sequence version 2.
DT   22-JUL-2015, entry version 119.
DE   RecName: Full=Cytokine receptor-like factor 2;
DE   AltName: Full=Cytokine receptor-like molecule 2;
DE            Short=CRLM-2;
DE   AltName: Full=Thymic stromal lymphopoietin protein receptor;
DE            Short=TSLP receptor;
DE   AltName: Full=Type I cytokine receptor delta 1;
DE   Flags: Precursor;
GN   Name=Crlf2; Synonyms=Crlm2, Tpte2, Tslpr;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC   Muroidea; Muridae; Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Embryo;
RX   PubMed=10872831; DOI=10.1006/bbrc.2000.2764;
RA   Hiroyama T., Iwama A., Morita Y., Nakamura Y., Shibuya A.,
RA   Nakauchi H.;
RT   "Molecular cloning and characterization of CRLM-2, a novel type I
RT   cytokine receptor preferentially expressed in hematopoietic cells.";
RL   Biochem. Biophys. Res. Commun. 272:224-229(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND ALTERNATIVE SPLICING.
RC   TISSUE=Lymphocyte;
RX   PubMed=10733486;
RA   Fujio K., Nosaka T., Kojima T., Kawashima T., Yahata T.,
RA   Copeland N.G., Gilbert D.J., Jenkins N.A., Yamamoto K., Nishimura T.,
RA   Kitamura T.;
RT   "Molecular cloning of a novel type I cytokine receptor similar to the
RT   common gamma chain.";
RL   Blood 95:2204-2210(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION AS A RECEPTOR FOR
RP   TSLP.
RC   STRAIN=C57BL/6; TISSUE=Lymphocyte;
RX   PubMed=10974032; DOI=10.1084/jem.192.5.659;
RA   Park L.S., Martin U., Garka K., Gliniak B., Di Santo J.P., Muller W.,
RA   Largaespada D.A., Copeland N.G., Jenkins N.A., Farr A.G.,
RA   Ziegler S.F., Morrissey P.J., Paxton R., Sims J.E.;
RT   "Cloning of the murine thymic stromal lymphopoietin (TSLP) receptor.
RT   Formation Of a functional heteromeric complex requires interleukin 7
RT   receptor.";
RL   J. Exp. Med. 192:659-670(2000).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RX   PubMed=10881176; DOI=10.1038/76923;
RA   Pandey A., Ozaki K., Baumann H., Levin S.D., Puel A., Farr A.G.,
RA   Ziegler S.F., Leonard W.J., Lodish H.F.;
RT   "Cloning of a receptor subunit required for signaling by thymic
RT   stromal lymphopoietin.";
RL   Nat. Immunol. 1:59-64(2000).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC   STRAIN=C57BL/6J; TISSUE=Embryonic stem cell;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M.,
RA   Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
RA   Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
RA   Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
RA   Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
RA   Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
RA   di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
RA   Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
RA   Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
RA   Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
RA   Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
RA   Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
RA   Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
RA   Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
RA   Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
RA   Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
RA   Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
RA   Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
RA   Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
RA   Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B.,
RA   Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
RA   Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
RA   Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
RA   Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
RA   Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
RA   Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
RA   Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
RA   Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
RA   Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
RA   Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
RA   Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
RA   Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   STRAIN=FVB/N; TISSUE=Mammary gland;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 20-222 IN COMPLEX WITH IL7R
RP   AND TSLP, SUBUNIT, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-53.
RX   PubMed=24632570; DOI=10.1038/nsmb.2794;
RA   Verstraete K., van Schie L., Vyncke L., Bloch Y., Tavernier J.,
RA   Pauwels E., Peelman F., Savvides S.N.;
RT   "Structural basis of the proinflammatory signaling complex mediated by
RT   TSLP.";
RL   Nat. Struct. Mol. Biol. 21:375-382(2014).
CC   -!- FUNCTION: Receptor for thymic stromal lymphopoietin (TSLP). Forms
CC       a functional complex with TSLP and IL7R which is capable of
CC       stimulating cell proliferation through activation of STAT3 and
CC       STAT5. Also activates JAK2. Implicated in the development of the
CC       hematopoietic system. {ECO:0000269|PubMed:10974032}.
CC   -!- SUBUNIT: The TSLP receptor is a heterodimer of CRLF2 and IL7R.
CC       Binding of TSLP to CRLF2/TSLPR is a mechanistic prerequisite for
CC       recruitment of IL7R to the high-affinity ternary complex.
CC       {ECO:0000269|PubMed:24632570}.
CC   -!- SUBCELLULAR LOCATION: Isoform 1: Cell membrane; Single-pass type I
CC       membrane protein.
CC   -!- SUBCELLULAR LOCATION: Isoform 3: Cell membrane; Single-pass type I
CC       membrane protein.
CC   -!- SUBCELLULAR LOCATION: Isoform 2: Secreted.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=4;
CC         Comment=Additional isoforms seem to exist.;
CC       Name=1;
CC         IsoId=Q8CII9-1; Sequence=Displayed;
CC       Name=2; Synonyms=Soluble CRLM-2;
CC         IsoId=Q8CII9-2; Sequence=VSP_008788, VSP_008789;
CC       Name=3;
CC         IsoId=Q8CII9-3; Sequence=VSP_008790;
CC         Note=No experimental confirmation available.;
CC       Name=4;
CC         IsoId=Q8CII9-4; Sequence=VSP_018990, VSP_018991;
CC         Note=No experimental confirmation available.;
CC   -!- TISSUE SPECIFICITY: High level of expression in liver, lung and
CC       testis. Also expressed in heart, brain, spleen, thymus and bone
CC       marrow. Highly expressed in progenitors and myeloid cells. Isoform
CC       2 is expressed in primary hemotopoietic cells.
CC   -!- INDUCTION: Up-regulated in the myeloid 32D cell line by
CC       granulocyte colony-stimulating factor (G-CSF).
CC   -!- DOMAIN: The WSXWS motif appears to be necessary for proper protein
CC       folding and thereby efficient intracellular transport and cell-
CC       surface receptor binding.
CC   -!- DOMAIN: The box 1 motif is required for JAK interaction and/or
CC       activation.
CC   -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 5
CC       subfamily. {ECO:0000305}.
CC   -!- SIMILARITY: Contains 1 fibronectin type-III domain.
CC       {ECO:0000255|PROSITE-ProRule:PRU00316}.
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DR   EMBL; AB039945; BAA92684.1; -; mRNA.
DR   EMBL; AB031333; BAA92159.1; -; mRNA.
DR   EMBL; AF232936; AAF81676.1; -; mRNA.
DR   EMBL; AF201963; AAF82189.1; -; mRNA.
DR   EMBL; AK010291; BAB26827.2; -; mRNA.
DR   EMBL; BC023788; AAH23788.1; -; mRNA.
DR   CCDS; CCDS19521.1; -. [Q8CII9-1]
DR   PIR; JC7280; JC7280.
DR   RefSeq; NP_001158207.1; NM_001164735.1.
DR   RefSeq; NP_057924.3; NM_016715.4.
DR   UniGene; Mm.35771; -.
DR   PDB; 4NN5; X-ray; 1.90 A; C=20-222.
DR   PDB; 4NN6; X-ray; 2.54 A; C=20-222.
DR   PDB; 4NN7; X-ray; 3.78 A; C=20-222.
DR   PDBsum; 4NN5; -.
DR   PDBsum; 4NN6; -.
DR   PDBsum; 4NN7; -.
DR   ProteinModelPortal; Q8CII9; -.
DR   SMR; Q8CII9; 28-206.
DR   BioGrid; 208364; 1.
DR   DIP; DIP-59471N; -.
DR   STRING; 10090.ENSMUSP00000036326; -.
DR   PhosphoSite; Q8CII9; -.
DR   PaxDb; Q8CII9; -.
DR   PRIDE; Q8CII9; -.
DR   GeneID; 57914; -.
DR   KEGG; mmu:57914; -.
DR   UCSC; uc008ypg.2; mouse. [Q8CII9-1]
DR   CTD; 64109; -.
DR   MGI; MGI:1889506; Crlf2.
DR   eggNOG; NOG74051; -.
DR   HOGENOM; HOG000185192; -.
DR   HOVERGEN; HBG051120; -.
DR   InParanoid; Q8CII9; -.
DR   KO; K05078; -.
DR   OrthoDB; EOG71K63B; -.
DR   PhylomeDB; Q8CII9; -.
DR   TreeFam; TF342693; -.
DR   NextBio; 314093; -.
DR   PRO; PR:Q8CII9; -.
DR   Proteomes; UP000000589; Unplaced.
DR   Bgee; Q8CII9; -.
DR   CleanEx; MM_CRLF2; -.
DR   Genevisible; Q8CII9; MM.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0002380; P:immunoglobulin secretion involved in immune response; IDA:MGI.
DR   GO; GO:0006954; P:inflammatory response; IMP:MGI.
DR   GO; GO:0035745; P:T-helper 2 cell cytokine production; IDA:MGI.
DR   Gene3D; 2.60.40.10; -; 1.
DR   InterPro; IPR003961; FN3_dom.
DR   InterPro; IPR013783; Ig-like_fold.
DR   Pfam; PF00041; fn3; 1.
DR   SMART; SM00060; FN3; 1.
DR   SUPFAM; SSF49265; SSF49265; 2.
DR   PROSITE; PS50853; FN3; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cell membrane; Complete proteome;
KW   Disulfide bond; Glycoprotein; Membrane; Receptor; Reference proteome;
KW   Secreted; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL        1     19       {ECO:0000255}.
FT   CHAIN        20    359       Cytokine receptor-like factor 2.
FT                                /FTId=PRO_0000011042.
FT   TOPO_DOM     20    232       Extracellular. {ECO:0000255}.
FT   TRANSMEM    233    253       Helical. {ECO:0000255}.
FT   TOPO_DOM    254    359       Cytoplasmic. {ECO:0000255}.
FT   DOMAIN      119    213       Fibronectin type-III.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00316}.
FT   MOTIF       201    205       WSXWS motif.
FT   MOTIF       262    270       Box 1 motif.
FT   CARBOHYD     53     53       N-linked (GlcNAc...).
FT                                {ECO:0000269|PubMed:24632570}.
FT   CARBOHYD    122    122       N-linked (GlcNAc...). {ECO:0000255}.
FT   DISULFID     68     82       {ECO:0000269|PubMed:24632570}.
FT   DISULFID    168    169       {ECO:0000269|PubMed:24632570}.
FT   DISULFID    181    219       {ECO:0000269|PubMed:24632570}.
FT   VAR_SEQ       1    233       Missing (in isoform 4).
FT                                {ECO:0000303|PubMed:16141072}.
FT                                /FTId=VSP_018990.
FT   VAR_SEQ     217    217       A -> G (in isoform 2).
FT                                {ECO:0000303|PubMed:10872831}.
FT                                /FTId=VSP_008788.
FT   VAR_SEQ     217    217       A -> AGDPCAAHLPPL (in isoform 3).
FT                                {ECO:0000303|PubMed:10881176}.
FT                                /FTId=VSP_008790.
FT   VAR_SEQ     218    359       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:10872831}.
FT                                /FTId=VSP_008789.
FT   VAR_SEQ     234    234       L -> M (in isoform 4).
FT                                {ECO:0000303|PubMed:16141072}.
FT                                /FTId=VSP_018991.
FT   CONFLICT     15     15       A -> T (in Ref. 2; BAA92159).
FT                                {ECO:0000305}.
FT   CONFLICT     51     51       G -> S (in Ref. 4; AAF82189 and 6;
FT                                AAH23788). {ECO:0000305}.
FT   CONFLICT     87     87       A -> G (in Ref. 3; AAF81676).
FT                                {ECO:0000305}.
FT   CONFLICT    179    179       A -> V (in Ref. 1; BAA92684 and 3;
FT                                AAF81676). {ECO:0000305}.
FT   CONFLICT    309    309       P -> T (in Ref. 1; BAA92684, 3; AAF81676
FT                                and 5; BAB26827). {ECO:0000305}.
FT   CONFLICT    355    355       G -> R (in Ref. 5; BAB26827).
FT                                {ECO:0000305}.
FT   STRAND       30     34       {ECO:0000244|PDB:4NN5}.
FT   TURN         35     37       {ECO:0000244|PDB:4NN5}.
FT   STRAND       38     42       {ECO:0000244|PDB:4NN5}.
FT   STRAND       55     60       {ECO:0000244|PDB:4NN5}.
FT   STRAND       69     73       {ECO:0000244|PDB:4NN5}.
FT   STRAND       79     85       {ECO:0000244|PDB:4NN5}.
FT   STRAND       88     90       {ECO:0000244|PDB:4NN5}.
FT   STRAND       92     97       {ECO:0000244|PDB:4NN5}.
FT   STRAND      103    109       {ECO:0000244|PDB:4NN5}.
FT   HELIX       111    114       {ECO:0000244|PDB:4NN5}.
FT   STRAND      124    127       {ECO:0000244|PDB:4NN5}.
FT   STRAND      133    136       {ECO:0000244|PDB:4NN5}.
FT   STRAND      141    143       {ECO:0000244|PDB:4NN5}.
FT   STRAND      145    153       {ECO:0000244|PDB:4NN5}.
FT   STRAND      162    167       {ECO:0000244|PDB:4NN5}.
FT   STRAND      170    173       {ECO:0000244|PDB:4NN5}.
FT   STRAND      180    190       {ECO:0000244|PDB:4NN5}.
FT   HELIX       192    195       {ECO:0000244|PDB:4NN5}.
FT   STRAND      208    214       {ECO:0000244|PDB:4NN5}.
FT   HELIX       216    218       {ECO:0000244|PDB:4NN5}.
SQ   SEQUENCE   359 AA;  37762 MW;  F9C521C54B4AC9DD CRC64;
     MAWALAVILL PRLLAAAAAA AAVTSRGDVT VVCHDLETVE VTWGSGPDHH GANLSLEFRY
     GTGALQPCPR YFLSGAGVTS GCILPAARAG LLELALRDGG GAMVFKARQR ASAWLKPRPP
     WNVTLLWTPD GDVTVSWPAH SYLGLDYEVQ HRESNDDEDA WQTTSGPCCD LTVGGLDPAR
     CYDFRVRASP RAAHYGLEAQ PSEWTAVTRL SGAASAASCT ASPAPSPALA PPLLPLGCGL
     AALLTLSLLL AALRLRRVKD ALLPCVPDPS GSFPGLFEKH HGNFQAWIAD AQATAPPART
     EEEDDLIHPK AKRVEPEDGT SLCTVPRPPS FEPRGPGGGA MVSVGGATFM VGDSGYMTL
//