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Protein

Leukemia inhibitory factor

Gene

LIF

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

LIF has the capacity to induce terminal differentiation in leukemic cells. Its activities include the induction of hematopoietic differentiation in normal and myeloid leukemia cells, the induction of neuronal cell differentiation, and the stimulation of acute-phase protein synthesis in hepatocytes.

GO - Molecular functioni

  • cytokine activity Source: MGI
  • growth factor activity Source: BHF-UCL
  • leukemia inhibitory factor receptor binding Source: BHF-UCL
  • receptor binding Source: BHF-UCL
  • transcription factor activity, RNA polymerase II transcription factor recruiting Source: BHF-UCL

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Growth factor

Enzyme and pathway databases

BioCyciZFISH:ENSG00000128342-MONOMER.
ReactomeiR-HSA-6788467. IL-6-type cytokine receptor ligand interactions.
SignaLinkiP15018.
SIGNORiP15018.

Names & Taxonomyi

Protein namesi
Recommended name:
Leukemia inhibitory factor
Short name:
LIF
Alternative name(s):
Differentiation-stimulating factor
Short name:
D factor
Melanoma-derived LPL inhibitor
Short name:
MLPLI
INN: Emfilermin
Gene namesi
Name:LIF
Synonyms:HILDA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

HGNCiHGNC:6596. LIF.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • extracellular region Source: Reactome
  • extracellular space Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Pharmaceutical usei

In phase II clinical trial. The drug is being developed by Amrad to assist embryo implantation in women who have failed to become pregnant despite assisted reproductive technologies (ART).

Organism-specific databases

DisGeNETi3976.
OpenTargetsiENSG00000128342.
PharmGKBiPA30370.

Polymorphism and mutation databases

BioMutaiLIF.
DMDMi126279.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 221 PublicationAdd BLAST22
ChainiPRO_000001771523 – 202Leukemia inhibitory factorAdd BLAST180

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi31N-linked (GlcNAc...)1 Publication1
Disulfide bondi34 ↔ 1561 Publication
Disulfide bondi40 ↔ 1531 Publication
Glycosylationi56N-linked (GlcNAc...)1 Publication1
Disulfide bondi82 ↔ 1851 Publication
Glycosylationi85N-linked (GlcNAc...)1 Publication1
Glycosylationi95N-linked (GlcNAc...)1 Publication1
Glycosylationi118N-linked (GlcNAc...)1 Publication1
Glycosylationi138N-linked (GlcNAc...)1 Publication1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP15018.
PeptideAtlasiP15018.
PRIDEiP15018.

Miscellaneous databases

PMAP-CutDBP15018.

Expressioni

Gene expression databases

BgeeiENSG00000128342.
CleanExiHS_LIF.
GenevisibleiP15018. HS.

Organism-specific databases

HPAiCAB025985.
HPA018844.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
IL6STP401892EBI-1037189,EBI-1030834

GO - Molecular functioni

  • cytokine activity Source: MGI
  • growth factor activity Source: BHF-UCL
  • leukemia inhibitory factor receptor binding Source: BHF-UCL
  • receptor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi110164. 1 interactor.
DIPiDIP-5769N.
IntActiP15018. 5 interactors.
MINTiMINT-1352030.
STRINGi9606.ENSP00000249075.

Structurei

Secondary structure

1202
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi44 – 70Combined sources27
Turni72 – 77Combined sources6
Helixi78 – 81Combined sources4
Beta strandi82 – 84Combined sources3
Beta strandi94 – 96Combined sources3
Helixi98 – 126Combined sources29
Helixi131 – 157Combined sources27
Helixi177 – 199Combined sources23

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1EMRX-ray3.50A44-202[»]
1PVHX-ray2.50B/D34-202[»]
2Q7NX-ray4.00B/D23-202[»]
ProteinModelPortaliP15018.
SMRiP15018.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP15018.

Family & Domainsi

Sequence similaritiesi

Belongs to the LIF/OSM family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410ITBQ. Eukaryota.
ENOG410YVPP. LUCA.
GeneTreeiENSGT00390000000059.
HOGENOMiHOG000059647.
HOVERGENiHBG006267.
InParanoidiP15018.
KOiK05419.
OMAiKYHVAHV.
OrthoDBiEOG091G0HWD.
PhylomeDBiP15018.
TreeFamiTF336245.

Family and domain databases

Gene3Di1.20.1250.10. 1 hit.
InterProiIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR003624. Leukemia_IF.
IPR001581. Leukemia_IF/oncostatin.
IPR019827. Leukemia_IF/oncostatin_CS.
[Graphical view]
PANTHERiPTHR10633. PTHR10633. 1 hit.
PfamiPF01291. LIF_OSM. 1 hit.
[Graphical view]
PRINTSiPR01883. LEUKAEMIAIF.
SMARTiSM00080. LIF_OSM. 1 hit.
[Graphical view]
SUPFAMiSSF47266. SSF47266. 1 hit.
PROSITEiPS00590. LIF_OSM. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P15018-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MKVLAAGVVP LLLVLHWKHG AGSPLPITPV NATCAIRHPC HNNLMNQIRS
60 70 80 90 100
QLAQLNGSAN ALFILYYTAQ GEPFPNNLDK LCGPNVTDFP PFHANGTEKA
110 120 130 140 150
KLVELYRIVV YLGTSLGNIT RDQKILNPSA LSLHSKLNAT ADILRGLLSN
160 170 180 190 200
VLCRLCSKYH VGHVDVTYGP DTSGKDVFQK KKLGCQLLGK YKQIIAVLAQ

AF
Length:202
Mass (Da):22,008
Last modified:April 1, 1990 - v1
Checksum:i634CD10BFF67A217
GO
Isoform 2 (identifier: P15018-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     7-88: GVVPLLLVLH...DKLCGPNVTD → VHSPGGAVPQ...RHRRHPARPP
     89-202: Missing.

Note: No experimental confirmation available.
Show »
Length:88
Mass (Da):9,563
Checksum:iC27010E1B89B18E5
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0455517 – 88GVVPL…PNVTD → VHSPGGAVPQQPGQAMWPQR DGLPALPRQRHGEGQAGGAV PHSRVPWHLPGQHHPGPEDP QPQCPQPPQQAQRHRRHPAR PP in isoform 2. 1 PublicationAdd BLAST82
Alternative sequenceiVSP_04555289 – 202Missing in isoform 2. 1 PublicationAdd BLAST114

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X13967 mRNA. Translation: CAA32147.1.
M27053, M27052 Genomic DNA. Translation: AAA53188.1.
AC004264 Genomic DNA. Translation: AAC05174.1.
M63420 Genomic DNA. Translation: AAA51699.1.
CN409468 mRNA. No translation available.
AK315310 mRNA. Translation: BAG37714.1.
CH471095 Genomic DNA. Translation: EAW59863.1.
BC069540 mRNA. Translation: AAH69540.1.
BC093733 mRNA. Translation: AAH93733.1.
BC093735 mRNA. Translation: AAH93735.1.
J03261 Genomic DNA. Translation: AAA59517.1.
CCDSiCCDS13872.1. [P15018-1]
CCDS58799.1. [P15018-2]
PIRiB36282.
RefSeqiNP_001244064.1. NM_001257135.1. [P15018-2]
NP_002300.1. NM_002309.4. [P15018-1]
UniGeneiHs.2250.

Genome annotation databases

EnsembliENST00000249075; ENSP00000249075; ENSG00000128342. [P15018-1]
ENST00000403987; ENSP00000384450; ENSG00000128342. [P15018-2]
GeneIDi3976.
KEGGihsa:3976.
UCSCiuc003agz.3. human. [P15018-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Wikipedia

Leukemia inhibitory factor entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X13967 mRNA. Translation: CAA32147.1.
M27053, M27052 Genomic DNA. Translation: AAA53188.1.
AC004264 Genomic DNA. Translation: AAC05174.1.
M63420 Genomic DNA. Translation: AAA51699.1.
CN409468 mRNA. No translation available.
AK315310 mRNA. Translation: BAG37714.1.
CH471095 Genomic DNA. Translation: EAW59863.1.
BC069540 mRNA. Translation: AAH69540.1.
BC093733 mRNA. Translation: AAH93733.1.
BC093735 mRNA. Translation: AAH93735.1.
J03261 Genomic DNA. Translation: AAA59517.1.
CCDSiCCDS13872.1. [P15018-1]
CCDS58799.1. [P15018-2]
PIRiB36282.
RefSeqiNP_001244064.1. NM_001257135.1. [P15018-2]
NP_002300.1. NM_002309.4. [P15018-1]
UniGeneiHs.2250.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1EMRX-ray3.50A44-202[»]
1PVHX-ray2.50B/D34-202[»]
2Q7NX-ray4.00B/D23-202[»]
ProteinModelPortaliP15018.
SMRiP15018.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110164. 1 interactor.
DIPiDIP-5769N.
IntActiP15018. 5 interactors.
MINTiMINT-1352030.
STRINGi9606.ENSP00000249075.

Polymorphism and mutation databases

BioMutaiLIF.
DMDMi126279.

Proteomic databases

PaxDbiP15018.
PeptideAtlasiP15018.
PRIDEiP15018.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000249075; ENSP00000249075; ENSG00000128342. [P15018-1]
ENST00000403987; ENSP00000384450; ENSG00000128342. [P15018-2]
GeneIDi3976.
KEGGihsa:3976.
UCSCiuc003agz.3. human. [P15018-1]

Organism-specific databases

CTDi3976.
DisGeNETi3976.
GeneCardsiLIF.
HGNCiHGNC:6596. LIF.
HPAiCAB025985.
HPA018844.
MIMi159540. gene.
neXtProtiNX_P15018.
OpenTargetsiENSG00000128342.
PharmGKBiPA30370.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410ITBQ. Eukaryota.
ENOG410YVPP. LUCA.
GeneTreeiENSGT00390000000059.
HOGENOMiHOG000059647.
HOVERGENiHBG006267.
InParanoidiP15018.
KOiK05419.
OMAiKYHVAHV.
OrthoDBiEOG091G0HWD.
PhylomeDBiP15018.
TreeFamiTF336245.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000128342-MONOMER.
ReactomeiR-HSA-6788467. IL-6-type cytokine receptor ligand interactions.
SignaLinkiP15018.
SIGNORiP15018.

Miscellaneous databases

EvolutionaryTraceiP15018.
GeneWikiiLeukemia_inhibitory_factor.
GenomeRNAii3976.
PMAP-CutDBP15018.
PROiP15018.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000128342.
CleanExiHS_LIF.
GenevisibleiP15018. HS.

Family and domain databases

Gene3Di1.20.1250.10. 1 hit.
InterProiIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR003624. Leukemia_IF.
IPR001581. Leukemia_IF/oncostatin.
IPR019827. Leukemia_IF/oncostatin_CS.
[Graphical view]
PANTHERiPTHR10633. PTHR10633. 1 hit.
PfamiPF01291. LIF_OSM. 1 hit.
[Graphical view]
PRINTSiPR01883. LEUKAEMIAIF.
SMARTiSM00080. LIF_OSM. 1 hit.
[Graphical view]
SUPFAMiSSF47266. SSF47266. 1 hit.
PROSITEiPS00590. LIF_OSM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLIF_HUMAN
AccessioniPrimary (citable) accession number: P15018
Secondary accession number(s): B2RCW7, B5MC23, Q52LZ2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: November 30, 2016
This is version 174 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

3D-structure, Complete proteome, Direct protein sequencing, Pharmaceutical, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.