O75462 (CRLF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cytokine receptor-like factor 1

Alternative name(s):
Cytokine-like factor 1
Short name=CLF-1
ZcytoR5

Gene names

Name:	CRLF1
ORF Names:	UNQ288/PRO327

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	422 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 receptor subunit, possibly playing a regulatory role in the immune system and during fetal development. May be involved in nervous system development.
Subunit structure	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). Ref.1
Subcellular location	Secreted Ref.1.
Tissue specificity	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. Ref.1
Induction	Up-regulated in fibroblast primary cell cultures under stimulation by IFNG/IFN-gamma, TNF and IL6/interleukin-6. Ref.1
Domain	The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
Involvement in disease	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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9
Sequence similarities	Belongs to the type I cytokine receptor family. Type 3 subfamily. Contains 2 fibronectin type-III domains. Contains 1 Ig-like C2-type (immunoglobulin-like) domain.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Immunoglobulin domain Repeat Signal
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of motor neuron apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of neuron apoptotic process Inferred from direct assay Ref.7. Source: BHF-UCL positive regulation of cell proliferation Inferred from direct assay Ref.7. Source: BHF-UCL positive regulation of tyrosine phosphorylation of Stat3 protein Inferred from direct assay Ref.7. Source: BHF-UCL ureteric bud development Inferred from electronic annotation. Source: Compara
Cellular_component	CRLF-CLCF1 complex Inferred from direct assay Ref.7. Source: BHF-UCL cytoplasm Inferred from direct assay. Source: HPA plasma membrane Inferred from direct assay. Source: HPA
Molecular_function	protein heterodimerization activity Inferred from direct assay Ref.7. Source: BHF-UCL receptor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 37	37	Ref.6
	Chain	38 – 422	385	Cytokine receptor-like factor 1		PRO_0000011039
Regions
	Domain	38 – 131	94	Ig-like C2-type
	Domain	134 – 229	96	Fibronectin type-III 1
	Domain	234 – 334	101	Fibronectin type-III 2
	Motif	327 – 331	5	WSXWS motif
Amino acid modifications
	Modified residue	219	1	Phosphoserine By similarity
	Glycosylation	92	1	N-linked (GlcNAc...) Potential
	Glycosylation	104	1	N-linked (GlcNAc...) Potential
	Glycosylation	140	1	N-linked (GlcNAc...) Potential
	Glycosylation	168	1	N-linked (GlcNAc...) Potential
	Glycosylation	292	1	N-linked (GlcNAc...) Potential
	Glycosylation	382	1	N-linked (GlcNAc...) Potential
	Disulfide bond	143 ↔ 153		By similarity
	Disulfide bond	184 ↔ 195		By similarity
Natural variations
	Natural variant	76	1	W → G in CISS1. Ref.9		VAR_033113
	Natural variant	81	1	R → H in CISS1. Ref.8		VAR_017865
	Natural variant	176	1	R → K. Corresponds to variant rs11672248 [ dbSNP | Ensembl ].		VAR_028355
	Natural variant	374	1	L → R in CISS1. Ref.8		VAR_017866
Experimental info
	Sequence conflict	240	1	D → E in AAD54385. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	O75462 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: AD9DEFCB01B84228	FASTA	422	46,302
	10 20 30 40 50 60 MPAGRRGPAA QSARRPPPLL PLLLLLCVLG APRAGSGAHT AVISPQDPTL LIGSSLLATC 70 80 90 100 110 120 SVHGDPPGAT AEGLYWTLNG RRLPPELSRV LNASTLALAL ANLNGSRQRS GDNLVCHARD 130 140 150 160 170 180 GSILAGSCLY VGLPPEKPVN ISCWSKNMKD LTCRWTPGAH GETFLHTNYS LKYKLRWYGQ 190 200 210 220 230 240 DNTCEEYHTV GPHSCHIPKD LALFTPYEIW VEATNRLGSA RSDVLTLDIL DVVTTDPPPD 250 260 270 280 290 300 VHVSRVGGLE DQLSVRWVSP PALKDFLFQA KYQIRYRVED SVDWKVVDDV SNQTSCRLAG 310 320 330 340 350 360 LKPGTVYFVQ VRCNPFGIYG SKKAGIWSEW SHPTAASTPR SERPGPGGGA CEPRGGEPSS 370 380 390 400 410 420 GPVRRELKQF LGWLKKHAYC SNLSFRLYDQ WRAWMQKSHK TRNQDEGILP SGRRGTARGP AR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] 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]	"CLF associates with CLC to form a functional heteromeric ligand for the CNTF receptor complex." Elson G.C.A., Lelievre E., Guillet C., Chevalier S., Plun-Favreau H., Froger J., Suard I., de Coignac A.B., Delneste Y., Bonnefoy J.-Y., Gauchat J.-F., Gascan H. Nat. Neurosci. 3:867-872(2000) [PubMed] [Europe PMC] [Abstract] 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]	"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.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00289561.
RefSeq	NP_004741.1. NM_004750.4.
UniGene	Hs.114948.
3D structure databases
ProteinModelPortal	O75462.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000376188.
PTM databases
PhosphoSite	O75462.
Proteomic databases
PaxDb	O75462.
PRIDE	O75462.
Protocols and materials databases
DNASU	9244.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000392386; ENSP00000376188; ENSG00000006016.
GeneID	9244.
KEGG	hsa:9244.
UCSC	uc010ebt.2. human.
Organism-specific databases
CTD	9244.
GeneCards	GC19M018704.
HGNC	HGNC:2364. CRLF1.
HPA	HPA041493. HPA041793.
MIM	272430. phenotype. 604237. gene.
neXtProt	NX_O75462.
Orphanet	157820. Cold-induced sweating syndrome. 1545. Crisponi syndrome.
PharmGKB	PA26882.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG43001.
HOGENOM	HOG000111972.
HOVERGEN	HBG051119.
InParanoid	O75462.
OMA	WTPGAHG.
OrthoDB	EOG4BVRTT.
PhylomeDB	O75462.
Enzyme and pathway databases
SignaLink	O75462.
Gene expression databases
Bgee	O75462.
CleanEx	HS_CRLF1.
Genevestigator	O75462.
GermOnline	ENSG00000006016. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.10. 3 hits.
InterPro	IPR003961. Fibronectin_type3. IPR015152. Growth/epo_recpt_lig-bind. IPR013783. Ig-like_fold. [Graphical view]
Pfam	PF09067. EpoR_lig-bind. 1 hit. PF00041. fn3. 1 hit. [Graphical view]
SMART	SM00060. FN3. 2 hits. [Graphical view]
SUPFAM	SSF49265. FN_III-like. 2 hits.
PROSITE	PS50853. FN3. 2 hits. PS50835. IG_LIKE. False negative. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	9244.
NextBio	34653.
SOURCE	Search...

Entry information

Entry name

CRLF1_HUMAN

Accession

Primary (citable) accession number: O75462
Secondary accession number(s): Q9UHH5

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 2004
Last sequence update:	November 1, 1998
Last modified:	May 29, 2013
This is version 118 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.