Q9UBD9 (CLCF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	225 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 component	Secreted
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Domain	Signal
Molecular function	Cytokine
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B 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_component	CNTFR-CLCF1 complex Inferred from direct assay PubMed 11285233. Source: BHF-UCL CRLF-CLCF1 complex Inferred from direct assay PubMed 10966616. Source: BHF-UCL
Molecular_function	ciliary 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 27	27	Potential
	Chain	28 – 225	198	Cardiotrophin-like cytokine factor 1		PRO_0000015616
Amino acid modifications
	Glycosylation	29	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 10	10	Missing in isoform 2.		VSP_044269
	Natural variant	197	1	R → L in CISS2; incapacity to bind CNTFR alpha; heterozygous compound with a nonsense mutation. Ref.8		VAR_028354
Experimental info
	Sequence conflict	23	1	P → L in AAH66231. Ref.7
	Sequence conflict	218	1	L → P in AAH66231. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: E2DD4B6280833B55	FASTA	225	25,176
	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
	Isoform 2 [UniParc]. Checksum: 88FC4F7B4A454C1F	FASTA	215	24,087
	10 20 30 40 50 60 MLACLCTVLW HLPAVPALNR TGDPGPGPSI QKTYDLTRYL EHQLRSLAGT YLNYLGPPFN 70 80 90 100 110 120 EPDFNPPRLG AETLPRATVD LEVWRSLNDK LRLTQNYEAY SHLLCYLRGL NRQAATAELR 130 140 150 160 170 180 RSLAHFCTSL QGLLGSIAGV MAALGYPLPQ PLPGTEPTWT PGPAHSDFLQ KMDDFWLLKE 190 200 210 LQTWLWRSAK DFNRLKKKMQ PPAAAVTLHL GAHGF

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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

GeneReviews

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.
IPI	IPI00294405.
RefSeq	NP_001159684.1. NM_001166212.1. NP_037378.1. NM_013246.2.
UniGene	Hs.502977.
3D structure databases
ProteinModelPortal	Q9UBD9.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UBD9. 1 interaction.
STRING	9606.ENSP00000309338.
Polymorphism databases
DMDM	56404673.
Proteomic databases
PaxDb	Q9UBD9.
PeptideAtlas	Q9UBD9.
PRIDE	Q9UBD9.
Protocols and materials databases
DNASU	23529.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000312438; ENSP00000309338; ENSG00000175505. ENST00000528474; ENSP00000432553; ENSG00000175505. ENST00000533438; ENSP00000434122; ENSG00000175505.
GeneID	23529.
KEGG	hsa:23529.
UCSC	uc001okq.3. human.
Organism-specific databases
CTD	23529.
GeneCards	GC11M067131.
HGNC	HGNC:17412. CLCF1.
HPA	HPA042444.
MIM	607672. gene. 610313. phenotype.
neXtProt	NX_Q9UBD9.
Orphanet	157820. Cold-induced sweating syndrome.
PharmGKB	PA142672106.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG43976.
HOGENOM	HOG000111785.
HOVERGEN	HBG050737.
InParanoid	Q9UBD9.
KO	K05421.
OMA	AGDSWGM.
OrthoDB	EOG4HT8TG.
PhylomeDB	Q9UBD9.
Gene expression databases
ArrayExpress	Q9UBD9.
Bgee	Q9UBD9.
CleanEx	HS_CLC. HS_CLCF1.
Genevestigator	Q9UBD9.
GermOnline	ENSG00000175505. Homo sapiens.
Family and domain databases
Gene3D	1.20.1250.10. 1 hit.
InterPro	IPR009079. 4_helix_cytokine-like_core. IPR012351. 4_helix_cytokine_core. IPR010681. PRF. [Graphical view]
PANTHER	PTHR21353. PTHR21353. 1 hit.
Pfam	PF06875. PRF. 1 hit. [Graphical view]
SUPFAM	SSF47266. 4_helix_cytokine. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	23529.
NextBio	46000.
SOURCE	Search...

Entry information

Entry name

CLCF1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 99 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.