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O75462

- CRLF1_HUMAN

UniProt

O75462 - CRLF1_HUMAN

Protein

Cytokine receptor-like factor 1

Gene

CRLF1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 130 (01 Oct 2014)
      Sequence version 1 (01 Nov 1998)
      Previous versions | rss
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    Functioni

    Cytokine receptor subunit, possibly playing a regulatory role in the immune system and during fetal development. May be involved in nervous system development.

    GO - Molecular functioni

    1. cytokine binding Source: HGNC
    2. protein binding Source: BHF-UCL
    3. protein heterodimerization activity Source: BHF-UCL
    4. receptor activity Source: ProtInc

    GO - Biological processi

    1. negative regulation of motor neuron apoptotic process Source: Ensembl
    2. negative regulation of neuron apoptotic process Source: BHF-UCL
    3. positive regulation of cell proliferation Source: BHF-UCL
    4. positive regulation of tyrosine phosphorylation of Stat3 protein Source: BHF-UCL
    5. ureteric bud development Source: Ensembl

    Keywords - Molecular functioni

    Receptor

    Enzyme and pathway databases

    SignaLinkiO75462.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cytokine receptor-like factor 1
    Alternative name(s):
    Cytokine-like factor 1
    Short name:
    CLF-1
    ZcytoR5
    Gene namesi
    Name:CRLF1
    ORF Names:UNQ288/PRO327
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:2364. CRLF1.

    Subcellular locationi

    Secreted 1 Publication

    GO - Cellular componenti

    1. CRLF-CLCF1 complex Source: BHF-UCL
    2. extracellular space Source: ProtInc

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Involvement in diseasei

    Cold-induced sweating syndrome 1 (CISS1) [MIM:272430]: An autosomal recessive disorder characterized by profuse sweating induced by cool surroundings (temperatures of 7 to 18 degrees Celsius). Patients manifest, in the neonatal period, orofacial weakness with impaired sucking and swallowing, resulting in poor feeding. Affected infants show a tendency to startle, with contractions of the facial muscles in response to tactile stimuli or during crying, trismus, abundant salivation, and opisthotonus. These features are referred to as Crisponi syndrome and can result in early death in infancy. Patients who survive into childhood have hyperhidrosis, mainly of the upper body, in response to cold temperatures, and sweat very little with heat. Additional abnormalities include a high-arched palate, nasal voice, depressed nasal bridge, inability to fully extend the elbows and kyphoscoliosis.7 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti74 – 741L → P in CISS1. 1 Publication
    VAR_070817
    Natural varianti75 – 751Y → D in CISS1. 1 Publication
    VAR_070818
    Natural varianti76 – 761W → G in CISS1. 2 Publications
    VAR_033113
    Natural varianti81 – 811R → H in CISS1. 1 Publication
    VAR_017865
    Natural varianti113 – 1131N → I in CISS1; together with P-114. 1 Publication
    VAR_070819
    Natural varianti114 – 1141L → P in CISS1; together with I-113. 1 Publication
    VAR_070820
    Natural varianti138 – 1381P → L in CISS1. 1 Publication
    VAR_070821
    Natural varianti145 – 1451S → P in CISS1. 1 Publication
    VAR_070822
    Natural varianti216 – 2161R → C in CISS1. 1 Publication
    VAR_070823
    Natural varianti268 – 2681F → S in CISS1. 1 Publication
    VAR_070824
    Natural varianti284 – 2841W → C in CISS1. 1 Publication
    VAR_070825
    Natural varianti312 – 3121R → P in CISS1. 1 Publication
    VAR_070826
    Natural varianti340 – 3401R → C in CISS1. 1 Publication
    VAR_070827
    Natural varianti374 – 3741L → R in CISS1. 1 Publication
    VAR_017866

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi272430. phenotype.
    Orphaneti157820. Cold-induced sweating syndrome.
    1545. Crisponi syndrome.
    PharmGKBiPA26882.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 37371 PublicationAdd
    BLAST
    Chaini38 – 422385Cytokine receptor-like factor 1PRO_0000011039Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi92 – 921N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi104 – 1041N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi140 – 1401N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi143 ↔ 153By similarity
    Glycosylationi168 – 1681N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi184 ↔ 195By similarity
    Modified residuei219 – 2191PhosphoserineBy similarity
    Glycosylationi292 – 2921N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi382 – 3821N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein

    Proteomic databases

    MaxQBiO75462.
    PaxDbiO75462.
    PRIDEiO75462.

    PTM databases

    PhosphoSiteiO75462.

    Expressioni

    Tissue specificityi

    Highest levels of expression observed in spleen, thymus, lymph node, appendix, bone marrow, stomach, placenta, heart, thyroid and ovary. Strongly expressed also in fetal lung.1 Publication

    Inductioni

    Up-regulated in fibroblast primary cell cultures under stimulation by IFNG/IFN-gamma, TNF and IL6/interleukin-6.1 Publication

    Gene expression databases

    BgeeiO75462.
    CleanExiHS_CRLF1.
    GenevestigatoriO75462.

    Organism-specific databases

    HPAiHPA041493.
    HPA041793.

    Interactioni

    Subunit structurei

    Forms covalently linked di- and tetramers. Forms a heteromeric complex with cardiotrophin-like cytokine (CLC); the CRLF1/CLC complex is a ligand for the ciliary neurotrophic factor receptor (CNTFR).1 Publication

    Protein-protein interaction databases

    BioGridi114670. 1 interaction.
    STRINGi9606.ENSP00000376188.

    Structurei

    3D structure databases

    ProteinModelPortaliO75462.
    SMRiO75462. Positions 43-339.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini38 – 13194Ig-like C2-typeAdd
    BLAST
    Domaini137 – 23296Fibronectin type-III 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini237 – 341105Fibronectin type-III 2PROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi327 – 3315WSXWS motif

    Domaini

    The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.

    Sequence similaritiesi

    Contains 2 fibronectin type-III domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Immunoglobulin domain, Repeat, Signal

    Phylogenomic databases

    eggNOGiNOG43001.
    HOGENOMiHOG000111972.
    HOVERGENiHBG051119.
    InParanoidiO75462.
    OMAiKHAYGCS.
    OrthoDBiEOG7WX08H.
    PhylomeDBiO75462.
    TreeFamiTF106501.

    Family and domain databases

    Gene3Di2.60.40.10. 3 hits.
    InterProiIPR003961. Fibronectin_type3.
    IPR015152. Growth/epo_recpt_lig-bind.
    IPR013783. Ig-like_fold.
    [Graphical view]
    PfamiPF09067. EpoR_lig-bind. 1 hit.
    PF00041. fn3. 1 hit.
    [Graphical view]
    SMARTiSM00060. FN3. 2 hits.
    [Graphical view]
    SUPFAMiSSF49265. SSF49265. 2 hits.
    PROSITEiPS50853. FN3. 2 hits.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    O75462-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPAGRRGPAA QSARRPPPLL PLLLLLCVLG APRAGSGAHT AVISPQDPTL    50
    LIGSSLLATC SVHGDPPGAT AEGLYWTLNG RRLPPELSRV LNASTLALAL 100
    ANLNGSRQRS GDNLVCHARD GSILAGSCLY VGLPPEKPVN ISCWSKNMKD 150
    LTCRWTPGAH GETFLHTNYS LKYKLRWYGQ DNTCEEYHTV GPHSCHIPKD 200
    LALFTPYEIW VEATNRLGSA RSDVLTLDIL DVVTTDPPPD VHVSRVGGLE 250
    DQLSVRWVSP PALKDFLFQA KYQIRYRVED SVDWKVVDDV SNQTSCRLAG 300
    LKPGTVYFVQ VRCNPFGIYG SKKAGIWSEW SHPTAASTPR SERPGPGGGA 350
    CEPRGGEPSS GPVRRELKQF LGWLKKHAYC SNLSFRLYDQ WRAWMQKSHK 400
    TRNQDEGILP SGRRGTARGP AR 422
    Length:422
    Mass (Da):46,302
    Last modified:November 1, 1998 - v1
    Checksum:iAD9DEFCB01B84228
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti240 – 2401D → E in AAD54385. 1 PublicationCurated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti74 – 741L → P in CISS1. 1 Publication
    VAR_070817
    Natural varianti75 – 751Y → D in CISS1. 1 Publication
    VAR_070818
    Natural varianti76 – 761W → G in CISS1. 2 Publications
    VAR_033113
    Natural varianti81 – 811R → H in CISS1. 1 Publication
    VAR_017865
    Natural varianti113 – 1131N → I in CISS1; together with P-114. 1 Publication
    VAR_070819
    Natural varianti114 – 1141L → P in CISS1; together with I-113. 1 Publication
    VAR_070820
    Natural varianti138 – 1381P → L in CISS1. 1 Publication
    VAR_070821
    Natural varianti145 – 1451S → P in CISS1. 1 Publication
    VAR_070822
    Natural varianti176 – 1761R → K.
    Corresponds to variant rs11672248 [ dbSNP | Ensembl ].
    VAR_028355
    Natural varianti216 – 2161R → C in CISS1. 1 Publication
    VAR_070823
    Natural varianti268 – 2681F → S in CISS1. 1 Publication
    VAR_070824
    Natural varianti284 – 2841W → C in CISS1. 1 Publication
    VAR_070825
    Natural varianti312 – 3121R → P in CISS1. 1 Publication
    VAR_070826
    Natural varianti340 – 3401R → C in CISS1. 1 Publication
    VAR_070827
    Natural varianti374 – 3741L → R in CISS1. 1 Publication
    VAR_017866

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF059293 mRNA. Translation: AAC28335.1.
    AF073515 mRNA. Translation: AAD39681.1.
    AF178684 mRNA. Translation: AAD54385.1.
    AY358291 mRNA. Translation: AAQ88658.1.
    BC044634 mRNA. Translation: AAH44634.1.
    CCDSiCCDS32962.1.
    RefSeqiNP_004741.1. NM_004750.4.
    UniGeneiHs.114948.

    Genome annotation databases

    EnsembliENST00000392386; ENSP00000376188; ENSG00000006016.
    GeneIDi9244.
    KEGGihsa:9244.
    UCSCiuc010ebt.2. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF059293 mRNA. Translation: AAC28335.1 .
    AF073515 mRNA. Translation: AAD39681.1 .
    AF178684 mRNA. Translation: AAD54385.1 .
    AY358291 mRNA. Translation: AAQ88658.1 .
    BC044634 mRNA. Translation: AAH44634.1 .
    CCDSi CCDS32962.1.
    RefSeqi NP_004741.1. NM_004750.4.
    UniGenei Hs.114948.

    3D structure databases

    ProteinModelPortali O75462.
    SMRi O75462. Positions 43-339.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114670. 1 interaction.
    STRINGi 9606.ENSP00000376188.

    PTM databases

    PhosphoSitei O75462.

    Proteomic databases

    MaxQBi O75462.
    PaxDbi O75462.
    PRIDEi O75462.

    Protocols and materials databases

    DNASUi 9244.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000392386 ; ENSP00000376188 ; ENSG00000006016 .
    GeneIDi 9244.
    KEGGi hsa:9244.
    UCSCi uc010ebt.2. human.

    Organism-specific databases

    CTDi 9244.
    GeneCardsi GC19M018704.
    GeneReviewsi CRLF1.
    HGNCi HGNC:2364. CRLF1.
    HPAi HPA041493.
    HPA041793.
    MIMi 272430. phenotype.
    604237. gene.
    neXtProti NX_O75462.
    Orphaneti 157820. Cold-induced sweating syndrome.
    1545. Crisponi syndrome.
    PharmGKBi PA26882.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG43001.
    HOGENOMi HOG000111972.
    HOVERGENi HBG051119.
    InParanoidi O75462.
    OMAi KHAYGCS.
    OrthoDBi EOG7WX08H.
    PhylomeDBi O75462.
    TreeFami TF106501.

    Enzyme and pathway databases

    SignaLinki O75462.

    Miscellaneous databases

    GeneWikii CRLF1.
    GenomeRNAii 9244.
    NextBioi 34653.
    PROi O75462.
    SOURCEi Search...

    Gene expression databases

    Bgeei O75462.
    CleanExi HS_CRLF1.
    Genevestigatori O75462.

    Family and domain databases

    Gene3Di 2.60.40.10. 3 hits.
    InterProi IPR003961. Fibronectin_type3.
    IPR015152. Growth/epo_recpt_lig-bind.
    IPR013783. Ig-like_fold.
    [Graphical view ]
    Pfami PF09067. EpoR_lig-bind. 1 hit.
    PF00041. fn3. 1 hit.
    [Graphical view ]
    SMARTi SM00060. FN3. 2 hits.
    [Graphical view ]
    SUPFAMi SSF49265. SSF49265. 2 hits.
    PROSITEi PS50853. FN3. 2 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cytokine-like factor-1, a novel soluble protein, shares homology with members of the cytokine type I receptor family."
      Elson G.C.A., Graber P., Losberger C., Herren S., Gretener D., Menoud L.N., Wells T.N.C., Kosco-Vilbois M.H., Gauchat J.-F.
      J. Immunol. 161:1371-1379(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION.
      Tissue: Fetal lung.
    2. "Cloning and expression of a novel soluble protein containing hematopoietic cytokine receptor domains."
      Magrangeas F., Jacques Y., Minvielle S.
      Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. Lok S., Presnell S.R., Jelmberg A.C., Gilbert T., Whitmore T.E., Foster D.C., Adams R.L., Lehner J.M., O'Hara P.J.
      Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    5. "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].
      Tissue: Lymph.
    6. "Signal peptide prediction based on analysis of experimentally verified cleavage sites."
      Zhang Z., Henzel W.J.
      Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 38-52.
    7. Cited for: INTERACTION WITH CLC AND CNTFR.
    8. "Cold-induced sweating syndrome is caused by mutations in the CRLF1 gene."
      Knappskog P.M., Majewski J., Livneh A., Nilsen P.T.E., Bringsli J.S., Ott J., Boman H.
      Am. J. Hum. Genet. 72:375-383(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS CISS1 HIS-81 AND ARG-374.
    9. "Cold-induced sweating syndrome: a report of two cases and demonstration of genetic heterogeneity."
      Hahn A.F., Jones D.L., Knappskog P.M., Boman H., McLeod J.G.
      J. Neurol. Sci. 250:62-70(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CISS1 CYS-284.
    10. "Mutations in cytokine receptor-like factor 1 (CRLF1) account for both Crisponi and cold-induced sweating syndromes."
      Dagoneau N., Bellais S., Blanchet P., Sarda P., Al-Gazali L.I., Di Rocco M., Huber C., Djouadi F., Le Goff C., Munnich A., Cormier-Daire V.
      Am. J. Hum. Genet. 80:966-970(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CISS1 GLY-76.
    11. Cited for: VARIANT CISS1 GLY-76.
    12. "Differential secretion of the mutated protein is a major component affecting phenotypic severity in CRLF1-associated disorders."
      Herholz J., Meloni A., Marongiu M., Chiappe F., Deiana M., Herrero C.R., Zampino G., Hamamy H., Zalloum Y., Waaler P.E., Crisponi G., Crisponi L., Rutsch F.
      Eur. J. Hum. Genet. 19:525-533(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS CISS1 ASP-75; ILE-113 AND PRO-114.
    13. "Multiple small hyperintense lesions in the subcortical white matter on cranial MR images in two Turkish brothers with cold-induced sweating syndrome caused by a novel missense mutation in the CRLF1 gene."
      Tuysuz B., Kasapcopur O., Yalcinkaya C., Isik Hasiloglu Z., Knappskog P.M., Boman H.
      Brain Dev. 35:596-601(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CISS1 LEU-138.
    14. Cited for: VARIANTS CISS1 PRO-74; PRO-145; CYS-216; SER-268; PRO-312 AND CYS-340.

    Entry informationi

    Entry nameiCRLF1_HUMAN
    AccessioniPrimary (citable) accession number: O75462
    Secondary accession number(s): Q9UHH5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 1, 2004
    Last sequence update: November 1, 1998
    Last modified: October 1, 2014
    This is version 130 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny 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.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3