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O75462 (CRLF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 129. 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·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length422 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3737 Ref.6
Chain38 – 422385Cytokine receptor-like factor 1
PRO_0000011039

Regions

Domain38 – 13194Ig-like C2-type
Domain137 – 23296Fibronectin type-III 1
Domain237 – 341105Fibronectin type-III 2
Motif327 – 3315WSXWS motif

Amino acid modifications

Modified residue2191Phosphoserine By similarity
Glycosylation921N-linked (GlcNAc...) Potential
Glycosylation1041N-linked (GlcNAc...) Potential
Glycosylation1401N-linked (GlcNAc...) Potential
Glycosylation1681N-linked (GlcNAc...) Potential
Glycosylation2921N-linked (GlcNAc...) Potential
Glycosylation3821N-linked (GlcNAc...) Potential
Disulfide bond143 ↔ 153 By similarity
Disulfide bond184 ↔ 195 By similarity

Natural variations

Natural variant741L → P in CISS1. Ref.14
VAR_070817
Natural variant751Y → D in CISS1. Ref.12
VAR_070818
Natural variant761W → G in CISS1. Ref.10 Ref.11
VAR_033113
Natural variant811R → H in CISS1. Ref.8
VAR_017865
Natural variant1131N → I in CISS1; together with P-114. Ref.12
VAR_070819
Natural variant1141L → P in CISS1; together with I-113. Ref.12
VAR_070820
Natural variant1381P → L in CISS1. Ref.13
VAR_070821
Natural variant1451S → P in CISS1. Ref.14
VAR_070822
Natural variant1761R → K.
Corresponds to variant rs11672248 [ dbSNP | Ensembl ].
VAR_028355
Natural variant2161R → C in CISS1. Ref.14
VAR_070823
Natural variant2681F → S in CISS1. Ref.14
VAR_070824
Natural variant2841W → C in CISS1. Ref.9
VAR_070825
Natural variant3121R → P in CISS1. Ref.14
VAR_070826
Natural variant3401R → C in CISS1. Ref.14
VAR_070827
Natural variant3741L → R in CISS1. Ref.8
VAR_017866

Experimental info

Sequence conflict2401D → E in AAD54385. Ref.3

Sequences

Sequence LengthMass (Da)Tools
O75462 [UniParc].

Last modified November 1, 1998. Version 1.
Checksum: AD9DEFCB01B84228

FASTA42246,302
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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]"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]"Crisponi syndrome is caused by mutations in the CRLF1 gene and is allelic to cold-induced sweating syndrome type 1."
Crisponi L., Crisponi G., Meloni A., Toliat M.R., Nurnberg G., Usala G., Uda M., Masala M., Hohne W., Becker C., Marongiu M., Chiappe F., Kleta R., Rauch A., Wollnik B., Strasser F., Reese T., Jakobs C. expand/collapse author list , Kurlemann G., Cao A., Nurnberg P., Rutsch F.
Am. J. Hum. Genet. 80:971-981(2007) [PubMed] [Europe PMC] [Abstract]
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]"Expanding the mutational spectrum of CRLF1 in Crisponi/CISS1 syndrome."
Piras R., Chiappe F., Torraca I.L., Buers I., Usala G., Angius A., Akin M.A., Basel-Vanagaite L., Benedicenti F., Chiodin E., El Assy O., Feingold-Zadok M., Guibert J., Kamien B., Kasapkara C.S., Kilic E., Boduroglu K., Kurtoglu S. expand/collapse author list , Manzur A.Y., Onal E.E., Paderi E., Roche C.H., Tumer L., Unal S., Utine G.E., Zanda G., Zankl A., Zampino G., Crisponi G., Crisponi L., Rutsch F.
Hum. Mutat. 35:424-433(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CISS1 PRO-74; PRO-145; CYS-216; SER-268; PRO-312 AND CYS-340.
+Additional computationally mapped references.

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.
CCDSCCDS32962.1.
RefSeqNP_004741.1. NM_004750.4.
UniGeneHs.114948.

3D structure databases

ProteinModelPortalO75462.
SMRO75462. Positions 43-339.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114670. 1 interaction.
STRING9606.ENSP00000376188.

PTM databases

PhosphoSiteO75462.

Proteomic databases

MaxQBO75462.
PaxDbO75462.
PRIDEO75462.

Protocols and materials databases

DNASU9244.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000392386; ENSP00000376188; ENSG00000006016.
GeneID9244.
KEGGhsa:9244.
UCSCuc010ebt.2. human.

Organism-specific databases

CTD9244.
GeneCardsGC19M018704.
GeneReviewsCRLF1.
HGNCHGNC:2364. CRLF1.
HPAHPA041493.
HPA041793.
MIM272430. phenotype.
604237. gene.
neXtProtNX_O75462.
Orphanet157820. Cold-induced sweating syndrome.
1545. Crisponi syndrome.
PharmGKBPA26882.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG43001.
HOGENOMHOG000111972.
HOVERGENHBG051119.
InParanoidO75462.
OMAKHAYGCS.
OrthoDBEOG7WX08H.
PhylomeDBO75462.
TreeFamTF106501.

Enzyme and pathway databases

SignaLinkO75462.

Gene expression databases

BgeeO75462.
CleanExHS_CRLF1.
GenevestigatorO75462.

Family and domain databases

Gene3D2.60.40.10. 3 hits.
InterProIPR003961. Fibronectin_type3.
IPR015152. Growth/epo_recpt_lig-bind.
IPR013783. Ig-like_fold.
[Graphical view]
PfamPF09067. EpoR_lig-bind. 1 hit.
PF00041. fn3. 1 hit.
[Graphical view]
SMARTSM00060. FN3. 2 hits.
[Graphical view]
SUPFAMSSF49265. SSF49265. 2 hits.
PROSITEPS50853. FN3. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCRLF1.
GenomeRNAi9244.
NextBio34653.
PROO75462.
SOURCESearch...

Entry information

Entry nameCRLF1_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 129 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 19

Human chromosome 19: entries, gene names and cross-references to MIM