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O75462

- CRLF1_HUMAN

UniProt

O75462 - CRLF1_HUMAN

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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

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 heterodimerization activity Source: BHF-UCL
  3. 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
Complete GO annotation...

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
Complete GO annotation...

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.
GeneTreeiENSGT00530000063112.
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

        10         20         30         40         50
MPAGRRGPAA QSARRPPPLL PLLLLLCVLG APRAGSGAHT AVISPQDPTL
60 70 80 90 100
LIGSSLLATC SVHGDPPGAT AEGLYWTLNG RRLPPELSRV LNASTLALAL
110 120 130 140 150
ANLNGSRQRS GDNLVCHARD GSILAGSCLY VGLPPEKPVN ISCWSKNMKD
160 170 180 190 200
LTCRWTPGAH GETFLHTNYS LKYKLRWYGQ DNTCEEYHTV GPHSCHIPKD
210 220 230 240 250
LALFTPYEIW VEATNRLGSA RSDVLTLDIL DVVTTDPPPD VHVSRVGGLE
260 270 280 290 300
DQLSVRWVSP PALKDFLFQA KYQIRYRVED SVDWKVVDDV SNQTSCRLAG
310 320 330 340 350
LKPGTVYFVQ VRCNPFGIYG SKKAGIWSEW SHPTAASTPR SERPGPGGGA
360 370 380 390 400
CEPRGGEPSS GPVRRELKQF LGWLKKHAYC SNLSFRLYDQ WRAWMQKSHK
410 420
TRNQDEGILP SGRRGTARGP AR
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.
GeneTreei ENSGT00530000063112.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 131 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