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Q9UBD9 (CLCF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cardiotrophin-like cytokine factor 1
Alternative name(s):
B-cell-stimulating factor 3
Short name=BSF-3
Novel neurotrophin-1
Short name=NNT-1
Gene names
Name:CLCF1
Synonyms:BSF3, CLC, NNT1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length225 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Cytokine with B-cell stimulating capability. Binds to and activates the ILST/gp130 receptor. Ref.1 Ref.2

Subcellular location

Secreted By similarity.

Tissue specificity

Expressed predominantly in lymph nodes, spleen, peripheral blood lymphocytes, bone marrow, and fetal liver. Ref.1 Ref.2

Involvement in disease

Cold-induced sweating syndrome 2 (CISS2) [MIM:610313]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

Sequence similarities

Belongs to the IL-6 superfamily.

Ontologies

Keywords
   Cellular componentSecreted
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
   DomainSignal
   Molecular functionCytokine
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

JAK-STAT cascade

Inferred from sequence or structural similarity. Source: BHF-UCL

cytokine-mediated signaling pathway

Non-traceable author statement Ref.1. Source: UniProtKB

negative regulation of neuron apoptotic process

Inferred from direct assay PubMed 10966616PubMed 11285233. Source: BHF-UCL

positive regulation of B cell proliferation

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of astrocyte differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of immunoglobulin production

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of isotype switching to IgE isotypes

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of tyrosine phosphorylation of Stat3 protein

Inferred from direct assay PubMed 10966616PubMed 11285233. Source: BHF-UCL

   Cellular_componentCNTFR-CLCF1 complex

Inferred from direct assay PubMed 11285233. Source: BHF-UCL

CRLF-CLCF1 complex

Inferred from direct assay PubMed 10966616. Source: BHF-UCL

   Molecular_functionciliary neurotrophic factor receptor binding

Inferred from direct assay PubMed 11285233. Source: BHF-UCL

cytokine activity

Non-traceable author statement Ref.1. Source: UniProtKB

growth factor activity

Traceable author statement PubMed 14632778. Source: HGNC

protein heterodimerization activity

Inferred from direct assay PubMed 10966616. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UBD9-1)

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.
Isoform 2 (identifier: Q9UBD9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-10: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2727 Potential
Chain28 – 225198Cardiotrophin-like cytokine factor 1
PRO_0000015616

Amino acid modifications

Glycosylation291N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 1010Missing in isoform 2.
VSP_044269
Natural variant1971R → L in CISS2; incapacity to bind CNTFR alpha; heterozygous compound with a nonsense mutation. Ref.8
VAR_028354

Experimental info

Sequence conflict231P → L in AAH66231. Ref.7
Sequence conflict2181L → P in AAH66231. Ref.7

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: E2DD4B6280833B55

FASTA22525,176
        10         20         30         40         50         60 
MDLRAGDSWG MLACLCTVLW HLPAVPALNR TGDPGPGPSI QKTYDLTRYL EHQLRSLAGT 

        70         80         90        100        110        120 
YLNYLGPPFN EPDFNPPRLG AETLPRATVD LEVWRSLNDK LRLTQNYEAY SHLLCYLRGL 

       130        140        150        160        170        180 
NRQAATAELR RSLAHFCTSL QGLLGSIAGV MAALGYPLPQ PLPGTEPTWT PGPAHSDFLQ 

       190        200        210        220 
KMDDFWLLKE LQTWLWRSAK DFNRLKKKMQ PPAAAVTLHL GAHGF 

« Hide

Isoform 2 [UniParc].

Checksum: 88FC4F7B4A454C1F
Show »

FASTA21524,087

References

« Hide 'large scale' references
[1]"Novel neurotrophin-1/B cell-stimulating factor-3: a cytokine of the IL-6 family."
Senaldi G., Varnum B.C., Sarmiento U., Starnes C., Lile J., Scully S., Guo J., Elliott G., McNinch J., Shaklee C.L., Freeman D., Manu F., Simonet W.S., Boone T., Chang M.-S.
Proc. Natl. Acad. Sci. U.S.A. 96:11458-11463(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY.
[2]"Computational EST database analysis identifies a novel member of the neuropoietic cytokine family."
Shi Y., Wang W., Yourey P.A., Gohari S., Zukauskas D., Zhang J., Ruben S., Alderson R.F.
Biochem. Biophys. Res. Commun. 262:132-138(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY.
[3]Hu X., Xu Y., Zhang B., Peng X., Yuan J., Qiang B.
Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
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. expand/collapse author list , 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.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Lung.
[5]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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).
Tissue: Kidney.
[8]"Inactivation of cardiotrophin-like cytokine, a second ligand for ciliary neurotrophic factor receptor, leads to cold-induced sweating syndrome in a patient."
Rousseau F., Gauchat J.-F., McLeod J.G., Chevalier S., Guillet C., Guilhot F., Cognet I., Froger J., Hahn A.F., Knappskog P.M., Gascan H., Boman H.
Proc. Natl. Acad. Sci. U.S.A. 103:10068-10073(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CISS2 LEU-197, CHARACTERIZATION OF VARIANT CISS2 LEU-197.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF176911 mRNA. Translation: AAF00991.1.
AF176912 Genomic DNA. Translation: AAF00992.1.
AF172854 mRNA. Translation: AAD54284.1.
AY049779 mRNA. Translation: AAL15436.1.
AK298052 mRNA. Translation: BAG60346.1.
AP003419 Genomic DNA. No translation available.
CH471076 Genomic DNA. Translation: EAW74601.1.
BC012939 mRNA. Translation: AAH12939.1.
BC066229 mRNA. Translation: AAH66229.1.
BC066230 mRNA. Translation: AAH66230.1.
BC066231 mRNA. Translation: AAH66231.1.
RefSeqNP_001159684.1. NM_001166212.1.
NP_037378.1. NM_013246.2.
XP_005273916.1. XM_005273859.1.
UniGeneHs.502977.

3D structure databases

ProteinModelPortalQ9UBD9.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117075. 4 interactions.
IntActQ9UBD9. 1 interaction.
STRING9606.ENSP00000309338.

Polymorphism databases

DMDM56404673.

Proteomic databases

PaxDbQ9UBD9.
PeptideAtlasQ9UBD9.
PRIDEQ9UBD9.

Protocols and materials databases

DNASU23529.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000312438; ENSP00000309338; ENSG00000175505. [Q9UBD9-1]
ENST00000528474; ENSP00000432553; ENSG00000175505. [Q9UBD9-2]
ENST00000533438; ENSP00000434122; ENSG00000175505. [Q9UBD9-2]
GeneID23529.
KEGGhsa:23529.
UCSCuc001okq.3. human. [Q9UBD9-1]

Organism-specific databases

CTD23529.
GeneCardsGC11M067131.
HGNCHGNC:17412. CLCF1.
HPAHPA042444.
MIM607672. gene.
610313. phenotype.
neXtProtNX_Q9UBD9.
Orphanet157820. Cold-induced sweating syndrome.
PharmGKBPA142672106.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG43976.
HOGENOMHOG000111785.
HOVERGENHBG050737.
InParanoidQ9UBD9.
KOK05421.
OMAAGDSWGM.
OrthoDBEOG7B05DT.
PhylomeDBQ9UBD9.
TreeFamTF333266.

Gene expression databases

BgeeQ9UBD9.
CleanExHS_CLC.
HS_CLCF1.
GenevestigatorQ9UBD9.

Family and domain databases

Gene3D1.20.1250.10. 1 hit.
InterProIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR010681. PRF.
[Graphical view]
PANTHERPTHR21353. PTHR21353. 1 hit.
PfamPF06875. PRF. 1 hit.
[Graphical view]
SUPFAMSSF47266. SSF47266. 1 hit.
ProtoNetSearch...

Other

GeneWikiCLCF1.
GenomeRNAi23529.
NextBio46000.
PROQ9UBD9.
SOURCESearch...

Entry information

Entry nameCLCF1_HUMAN
AccessionPrimary (citable) accession number: Q9UBD9
Secondary accession number(s): B4DNT4, Q6NZA4
Entry history
Integrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: May 1, 2000
Last modified: March 19, 2014
This is version 106 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM