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Protein

Cytokine receptor-like factor 2

Gene

Crlf2

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

Functioni

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. Implicated in the development of the hematopoietic system.1 Publication

GO - Biological processi

  • immunoglobulin secretion involved in immune response Source: MGI
  • inflammatory response Source: MGI
  • T-helper 2 cell cytokine production Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Names & Taxonomyi

Protein namesi
Recommended name:
Cytokine receptor-like factor 2
Alternative name(s):
Cytokine receptor-like molecule 2
Short name:
CRLM-2
Thymic stromal lymphopoietin protein receptor
Short name:
TSLP receptor
Type I cytokine receptor delta 1
Gene namesi
Name:Crlf2
Synonyms:Crlm2, Tpte2, Tslpr
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1889506. Crlf2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini20 – 232213ExtracellularSequence AnalysisAdd
BLAST
Transmembranei233 – 25321HelicalSequence AnalysisAdd
BLAST
Topological domaini254 – 359106CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919Sequence AnalysisAdd
BLAST
Chaini20 – 359340Cytokine receptor-like factor 2PRO_0000011042Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi53 – 531N-linked (GlcNAc...)1 Publication
Disulfide bondi68 ↔ 821 Publication
Glycosylationi122 – 1221N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi168 ↔ 1691 Publication
Disulfide bondi181 ↔ 2191 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ8CII9.
PRIDEiQ8CII9.

PTM databases

PhosphoSiteiQ8CII9.

Expressioni

Tissue specificityi

High level of expression in liver, lung and testis. Also expressed in heart, brain, spleen, thymus and bone marrow. Highly expressed in progenitors and myeloid cells. Isoform 2 is expressed in primary hemotopoietic cells.

Inductioni

Up-regulated in the myeloid 32D cell line by granulocyte colony-stimulating factor (G-CSF).

Gene expression databases

BgeeiQ8CII9.
CleanExiMM_CRLF2.
GenevisibleiQ8CII9. MM.

Interactioni

Subunit structurei

The TSLP receptor is a heterodimer of CRLF2 and IL7R. Binding of TSLP to CRLF2/TSLPR is a mechanistic prerequisite for recruitment of IL7R to the high-affinity ternary complex.1 Publication

Protein-protein interaction databases

BioGridi208364. 1 interaction.
DIPiDIP-59471N.
STRINGi10090.ENSMUSP00000036326.

Structurei

Secondary structure

1
359
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi30 – 345Combined sources
Turni35 – 373Combined sources
Beta strandi38 – 425Combined sources
Beta strandi55 – 606Combined sources
Beta strandi69 – 735Combined sources
Beta strandi79 – 857Combined sources
Beta strandi88 – 903Combined sources
Beta strandi92 – 976Combined sources
Beta strandi103 – 1097Combined sources
Helixi111 – 1144Combined sources
Beta strandi124 – 1274Combined sources
Beta strandi133 – 1364Combined sources
Beta strandi141 – 1433Combined sources
Beta strandi145 – 1539Combined sources
Beta strandi162 – 1676Combined sources
Beta strandi170 – 1734Combined sources
Beta strandi180 – 19011Combined sources
Helixi192 – 1954Combined sources
Beta strandi208 – 2147Combined sources
Helixi216 – 2183Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4NN5X-ray1.90C20-222[»]
4NN6X-ray2.54C20-222[»]
4NN7X-ray3.78C20-222[»]
ProteinModelPortaliQ8CII9.
SMRiQ8CII9. Positions 28-206.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini119 – 21395Fibronectin type-IIIPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi201 – 2055WSXWS motif
Motifi262 – 2709Box 1 motif

Domaini

The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
The box 1 motif is required for JAK interaction and/or activation.

Sequence similaritiesi

Contains 1 fibronectin type-III domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG74051.
HOGENOMiHOG000185192.
HOVERGENiHBG051120.
InParanoidiQ8CII9.
KOiK05078.
OrthoDBiEOG71K63B.
PhylomeDBiQ8CII9.
TreeFamiTF342693.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR003961. FN3_dom.
IPR013783. Ig-like_fold.
[Graphical view]
PfamiPF00041. fn3. 1 hit.
[Graphical view]
SMARTiSM00060. FN3. 1 hit.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 2 hits.
PROSITEiPS50853. FN3. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: Q8CII9-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAWALAVILL PRLLAAAAAA AAVTSRGDVT VVCHDLETVE VTWGSGPDHH
60 70 80 90 100
GANLSLEFRY GTGALQPCPR YFLSGAGVTS GCILPAARAG LLELALRDGG
110 120 130 140 150
GAMVFKARQR ASAWLKPRPP WNVTLLWTPD GDVTVSWPAH SYLGLDYEVQ
160 170 180 190 200
HRESNDDEDA WQTTSGPCCD LTVGGLDPAR CYDFRVRASP RAAHYGLEAQ
210 220 230 240 250
PSEWTAVTRL SGAASAASCT ASPAPSPALA PPLLPLGCGL AALLTLSLLL
260 270 280 290 300
AALRLRRVKD ALLPCVPDPS GSFPGLFEKH HGNFQAWIAD AQATAPPART
310 320 330 340 350
EEEDDLIHPK AKRVEPEDGT SLCTVPRPPS FEPRGPGGGA MVSVGGATFM

VGDSGYMTL
Length:359
Mass (Da):37,762
Last modified:November 7, 2003 - v2
Checksum:iF9C521C54B4AC9DD
GO
Isoform 2 (identifier: Q8CII9-2) [UniParc]FASTAAdd to basket

Also known as: Soluble CRLM-2

The sequence of this isoform differs from the canonical sequence as follows:
     217-217: A → G
     218-359: Missing.

Show »
Length:217
Mass (Da):23,086
Checksum:iD4382C3273C1B8CA
GO
Isoform 3 (identifier: Q8CII9-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     217-217: A → AGDPCAAHLPPL

Note: No experimental confirmation available.
Show »
Length:370
Mass (Da):38,834
Checksum:i1063D4172A8BE320
GO
Isoform 4 (identifier: Q8CII9-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-233: Missing.
     234-234: L → M

Note: No experimental confirmation available.
Show »
Length:126
Mass (Da):13,236
Checksum:iBD387A6F9B4CEDF7
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti15 – 151A → T in BAA92159 (PubMed:10733486).Curated
Sequence conflicti51 – 511G → S in AAF82189 (PubMed:10881176).Curated
Sequence conflicti51 – 511G → S in AAH23788 (PubMed:15489334).Curated
Sequence conflicti87 – 871A → G in AAF81676 (PubMed:10974032).Curated
Sequence conflicti179 – 1791A → V in BAA92684 (PubMed:10872831).Curated
Sequence conflicti179 – 1791A → V in AAF81676 (PubMed:10974032).Curated
Sequence conflicti309 – 3091P → T in BAA92684 (PubMed:10872831).Curated
Sequence conflicti309 – 3091P → T in AAF81676 (PubMed:10974032).Curated
Sequence conflicti309 – 3091P → T in BAB26827 (PubMed:16141072).Curated
Sequence conflicti355 – 3551G → R in BAB26827 (PubMed:16141072).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 233233Missing in isoform 4. 1 PublicationVSP_018990Add
BLAST
Alternative sequencei217 – 2171A → G in isoform 2. 1 PublicationVSP_008788
Alternative sequencei217 – 2171A → AGDPCAAHLPPL in isoform 3. 1 PublicationVSP_008790
Alternative sequencei218 – 359142Missing in isoform 2. 1 PublicationVSP_008789Add
BLAST
Alternative sequencei234 – 2341L → M in isoform 4. 1 PublicationVSP_018991

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB039945 mRNA. Translation: BAA92684.1.
AB031333 mRNA. Translation: BAA92159.1.
AF232936 mRNA. Translation: AAF81676.1.
AF201963 mRNA. Translation: AAF82189.1.
AK010291 mRNA. Translation: BAB26827.2.
BC023788 mRNA. Translation: AAH23788.1.
CCDSiCCDS19521.1. [Q8CII9-1]
PIRiJC7280.
RefSeqiNP_001158207.1. NM_001164735.1.
NP_057924.3. NM_016715.4.
UniGeneiMm.35771.

Genome annotation databases

GeneIDi57914.
KEGGimmu:57914.
UCSCiuc008ypg.2. mouse. [Q8CII9-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB039945 mRNA. Translation: BAA92684.1.
AB031333 mRNA. Translation: BAA92159.1.
AF232936 mRNA. Translation: AAF81676.1.
AF201963 mRNA. Translation: AAF82189.1.
AK010291 mRNA. Translation: BAB26827.2.
BC023788 mRNA. Translation: AAH23788.1.
CCDSiCCDS19521.1. [Q8CII9-1]
PIRiJC7280.
RefSeqiNP_001158207.1. NM_001164735.1.
NP_057924.3. NM_016715.4.
UniGeneiMm.35771.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4NN5X-ray1.90C20-222[»]
4NN6X-ray2.54C20-222[»]
4NN7X-ray3.78C20-222[»]
ProteinModelPortaliQ8CII9.
SMRiQ8CII9. Positions 28-206.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi208364. 1 interaction.
DIPiDIP-59471N.
STRINGi10090.ENSMUSP00000036326.

PTM databases

PhosphoSiteiQ8CII9.

Proteomic databases

PaxDbiQ8CII9.
PRIDEiQ8CII9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi57914.
KEGGimmu:57914.
UCSCiuc008ypg.2. mouse. [Q8CII9-1]

Organism-specific databases

CTDi64109.
MGIiMGI:1889506. Crlf2.

Phylogenomic databases

eggNOGiNOG74051.
HOGENOMiHOG000185192.
HOVERGENiHBG051120.
InParanoidiQ8CII9.
KOiK05078.
OrthoDBiEOG71K63B.
PhylomeDBiQ8CII9.
TreeFamiTF342693.

Miscellaneous databases

NextBioi314093.
PROiQ8CII9.
SOURCEiSearch...

Gene expression databases

BgeeiQ8CII9.
CleanExiMM_CRLF2.
GenevisibleiQ8CII9. MM.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR003961. FN3_dom.
IPR013783. Ig-like_fold.
[Graphical view]
PfamiPF00041. fn3. 1 hit.
[Graphical view]
SMARTiSM00060. FN3. 1 hit.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 2 hits.
PROSITEiPS50853. FN3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning and characterization of CRLM-2, a novel type I cytokine receptor preferentially expressed in hematopoietic cells."
    Hiroyama T., Iwama A., Morita Y., Nakamura Y., Shibuya A., Nakauchi H.
    Biochem. Biophys. Res. Commun. 272:224-229(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
    Tissue: Embryo.
  2. "Molecular cloning of a novel type I cytokine receptor similar to the common gamma chain."
    Fujio K., Nosaka T., Kojima T., Kawashima T., Yahata T., Copeland N.G., Gilbert D.J., Jenkins N.A., Yamamoto K., Nishimura T., Kitamura T.
    Blood 95:2204-2210(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING.
    Tissue: Lymphocyte.
  3. "Cloning of the murine thymic stromal lymphopoietin (TSLP) receptor. Formation Of a functional heteromeric complex requires interleukin 7 receptor."
    Park L.S., Martin U., Garka K., Gliniak B., Di Santo J.P., Muller W., Largaespada D.A., Copeland N.G., Jenkins N.A., Farr A.G., Ziegler S.F., Morrissey P.J., Paxton R., Sims J.E.
    J. Exp. Med. 192:659-670(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION AS A RECEPTOR FOR TSLP.
    Strain: C57BL/6.
    Tissue: Lymphocyte.
  4. "Cloning of a receptor subunit required for signaling by thymic stromal lymphopoietin."
    Pandey A., Ozaki K., Baumann H., Levin S.D., Puel A., Farr A.G., Ziegler S.F., Leonard W.J., Lodish H.F.
    Nat. Immunol. 1:59-64(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
  5. "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] (ISOFORM 4).
    Strain: C57BL/6J.
    Tissue: Embryonic stem cell.
  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] (ISOFORM 1).
    Strain: FVB/N.
    Tissue: Mammary gland.
  7. Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 20-222 IN COMPLEX WITH IL7R AND TSLP, SUBUNIT, DISULFIDE BONDS, GLYCOSYLATION AT ASN-53.

Entry informationi

Entry nameiCRLF2_MOUSE
AccessioniPrimary (citable) accession number: Q8CII9
Secondary accession number(s): Q9CRJ6
, Q9JIE7, Q9JIQ7, Q9JJH8, Q9JMD5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 7, 2003
Last sequence update: November 7, 2003
Last modified: July 22, 2015
This is version 119 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.