CRLF2_MOUSE
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 25-MAY-2022, entry version 150.
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; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC 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., Nakauchi H.;
RT "Molecular cloning and characterization of CRLM-2, a novel type I cytokine
RT 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., Copeland N.G.,
RA Gilbert D.J., Jenkins N.A., Yamamoto K., Nishimura T., 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/6J; 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., Ziegler S.F.,
RA 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 stromal
RT 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., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., 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., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., 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 project:
RT 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 AND
RP 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., Pauwels E.,
RA 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 a
CC functional complex with TSLP and IL7R which is capable of stimulating
CC cell proliferation through activation of STAT3 and STAT5. Also
CC activates JAK2. Implicated in the development of the hematopoietic
CC system. {ECO:0000269|PubMed:10974032}.
CC -!- SUBUNIT: The TSLP receptor is a heterodimer of CRLF2 and IL7R. Binding
CC of TSLP to CRLF2/TSLPR is a mechanistic prerequisite for recruitment of
CC IL7R to the high-affinity ternary complex.
CC {ECO:0000269|PubMed:24632570}.
CC -!- INTERACTION:
CC Q8CII9; Q9JIE6: Tslp; NbExp=9; IntAct=EBI-15887886, EBI-16096402;
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 Name=4;
CC IsoId=Q8CII9-4; Sequence=VSP_018990, VSP_018991;
CC -!- TISSUE SPECIFICITY: High level of expression in liver, lung and testis.
CC Also expressed in heart, brain, spleen, thymus and bone marrow. Highly
CC expressed in progenitors and myeloid cells. Isoform 2 is expressed in
CC primary hemotopoietic cells.
CC -!- INDUCTION: Up-regulated in the myeloid 32D cell line by granulocyte
CC 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-surface
CC 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}.
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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 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 AlphaFoldDB; Q8CII9; -.
DR SMR; Q8CII9; -.
DR BioGRID; 208364; 1.
DR DIP; DIP-59471N; -.
DR IntAct; Q8CII9; 3.
DR STRING; 10090.ENSMUSP00000036326; -.
DR GlyGen; Q8CII9; 2 sites.
DR iPTMnet; Q8CII9; -.
DR PhosphoSitePlus; Q8CII9; -.
DR EPD; Q8CII9; -.
DR PaxDb; Q8CII9; -.
DR PRIDE; Q8CII9; -.
DR ProteomicsDB; 284018; -. [Q8CII9-1]
DR ProteomicsDB; 284019; -. [Q8CII9-2]
DR ProteomicsDB; 284020; -. [Q8CII9-3]
DR ProteomicsDB; 284021; -. [Q8CII9-4]
DR DNASU; 57914; -.
DR GeneID; 57914; -.
DR KEGG; mmu:57914; -.
DR UCSC; uc008ypg.2; mouse. [Q8CII9-1]
DR CTD; 64109; -.
DR MGI; MGI:1889506; Crlf2.
DR eggNOG; ENOG502RYG2; Eukaryota.
DR InParanoid; Q8CII9; -.
DR OrthoDB; 1414804at2759; -.
DR PhylomeDB; Q8CII9; -.
DR TreeFam; TF342693; -.
DR BioGRID-ORCS; 57914; 0 hits in 73 CRISPR screens.
DR PRO; PR:Q8CII9; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q8CII9; protein.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
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:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005125; F:cytokine activity; ISO:MGI.
DR GO; GO:0019955; F:cytokine binding; IBA:GO_Central.
DR GO; GO:0004896; F:cytokine receptor activity; ISO:MGI.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; ISO:MGI.
DR GO; GO:0006954; P:inflammatory response; IMP:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0032754; P:positive regulation of interleukin-5 production; ISO:MGI.
DR GO; GO:0033005; P:positive regulation of mast cell activation; ISO:MGI.
DR GO; GO:1904894; P:positive regulation of receptor signaling pathway via STAT; ISO:MGI.
DR CDD; cd00063; FN3; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
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; Disulfide bond;
KW Glycoprotein; Membrane; Receptor; Reference proteome; Secreted; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..359
FT /note="Cytokine receptor-like factor 2"
FT /id="PRO_0000011042"
FT TOPO_DOM 20..232
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 233..253
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 254..359
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 119..213
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 312..336
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 201..205
FT /note="WSXWS motif"
FT MOTIF 262..270
FT /note="Box 1 motif"
FT CARBOHYD 53
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:24632570"
FT CARBOHYD 122
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 68..82
FT /evidence="ECO:0000269|PubMed:24632570"
FT DISULFID 168..169
FT /evidence="ECO:0000269|PubMed:24632570"
FT DISULFID 181..219
FT /evidence="ECO:0000269|PubMed:24632570"
FT VAR_SEQ 1..233
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_018990"
FT VAR_SEQ 217
FT /note="A -> G (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10872831"
FT /id="VSP_008788"
FT VAR_SEQ 217
FT /note="A -> AGDPCAAHLPPL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10881176"
FT /id="VSP_008790"
FT VAR_SEQ 218..359
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10872831"
FT /id="VSP_008789"
FT VAR_SEQ 234
FT /note="L -> M (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_018991"
FT CONFLICT 15
FT /note="A -> T (in Ref. 2; BAA92159)"
FT /evidence="ECO:0000305"
FT CONFLICT 51
FT /note="G -> S (in Ref. 4; AAF82189 and 6; AAH23788)"
FT /evidence="ECO:0000305"
FT CONFLICT 87
FT /note="A -> G (in Ref. 3; AAF81676)"
FT /evidence="ECO:0000305"
FT CONFLICT 179
FT /note="A -> V (in Ref. 1; BAA92684 and 3; AAF81676)"
FT /evidence="ECO:0000305"
FT CONFLICT 309
FT /note="P -> T (in Ref. 1; BAA92684, 3; AAF81676 and 5;
FT BAB26827)"
FT /evidence="ECO:0000305"
FT CONFLICT 355
FT /note="G -> R (in Ref. 5; BAB26827)"
FT /evidence="ECO:0000305"
FT STRAND 30..34
FT /evidence="ECO:0007829|PDB:4NN5"
FT TURN 35..37
FT /evidence="ECO:0007829|PDB:4NN5"
FT STRAND 38..42
FT /evidence="ECO:0007829|PDB:4NN5"
FT STRAND 55..60
FT /evidence="ECO:0007829|PDB:4NN5"
FT STRAND 69..73
FT /evidence="ECO:0007829|PDB:4NN5"
FT STRAND 79..85
FT /evidence="ECO:0007829|PDB:4NN5"
FT STRAND 88..90
FT /evidence="ECO:0007829|PDB:4NN5"
FT STRAND 92..97
FT /evidence="ECO:0007829|PDB:4NN5"
FT STRAND 103..109
FT /evidence="ECO:0007829|PDB:4NN5"
FT HELIX 111..114
FT /evidence="ECO:0007829|PDB:4NN5"
FT STRAND 124..127
FT /evidence="ECO:0007829|PDB:4NN5"
FT STRAND 133..136
FT /evidence="ECO:0007829|PDB:4NN5"
FT STRAND 141..143
FT /evidence="ECO:0007829|PDB:4NN5"
FT STRAND 145..153
FT /evidence="ECO:0007829|PDB:4NN5"
FT STRAND 162..167
FT /evidence="ECO:0007829|PDB:4NN5"
FT STRAND 170..173
FT /evidence="ECO:0007829|PDB:4NN5"
FT STRAND 180..190
FT /evidence="ECO:0007829|PDB:4NN5"
FT HELIX 192..195
FT /evidence="ECO:0007829|PDB:4NN5"
FT STRAND 208..214
FT /evidence="ECO:0007829|PDB:4NN5"
FT HELIX 216..218
FT /evidence="ECO:0007829|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
