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Protein

Left-right determination factor 2

Gene

LEFTY2

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

Functioni

Required for left-right (L-R) asymmetry determination of organ systems in mammals. May play a role in endometrial bleeding.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCytokine, Developmental protein, Growth factor

Enzyme and pathway databases

ReactomeiR-HSA-114608. Platelet degranulation.
R-HSA-1181150. Signaling by NODAL.
R-HSA-1433617. Regulation of signaling by NODAL.

Names & Taxonomyi

Protein namesi
Recommended name:
Left-right determination factor 2
Alternative name(s):
Endometrial bleeding-associated factor
Left-right determination factor A
Protein lefty-2
Protein lefty-A
Transforming growth factor beta-4
Short name:
TGF-beta-4
Gene namesi
Name:LEFTY2
Synonyms:EBAF, LEFTA, LEFTYA, TGFB4
ORF Names:PSEC0024
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000143768.11.
HGNCiHGNC:3122. LEFTY2.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Left-right axis malformations (LRAM)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionThe defect includes left pulmonary isomerism, with cardiac anomalies characterized by complete atrioventricular canal defect and hypoplastic left ventricle, and interrupted inferior vena cava.
See also OMIM:601877
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_010385342S → N in LRAM. 1 PublicationCorresponds to variant dbSNP:rs121909126Ensembl.1

Keywords - Diseasei

Disease mutation, Heterotaxy

Organism-specific databases

DisGeNETi7044.
MalaCardsiLEFTY2.
MIMi601877. gene+phenotype.
OpenTargetsiENSG00000143768.
Orphaneti157769. Situs ambiguus.
PharmGKBiPA27580.

Polymorphism and mutation databases

BioMutaiLEFTY2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
PropeptideiPRO_000003380622 – 76Or 135Sequence analysisAdd BLAST55
ChainiPRO_000003380777 – 366Left-right determination factor 2Add BLAST290

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi158N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi251 ↔ 264By similarity
Disulfide bondi263 ↔ 316By similarity
Disulfide bondi293 ↔ 351By similarity
Disulfide bondi297 ↔ 353By similarity

Post-translational modificationi

The processing of the protein may also occur at the second R-X-X-R site located at AA 132-135. Processing appears to be regulated in a cell-type specific manner.

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiO00292.
PaxDbiO00292.
PeptideAtlasiO00292.
PRIDEiO00292.

PTM databases

iPTMnetiO00292.
PhosphoSitePlusiO00292.

Expressioni

Tissue specificityi

Mesenchymal cells of the endometrial stroma.

Developmental stagei

Transiently expressed before and during menstrual bleeding.

Gene expression databases

BgeeiENSG00000143768.
CleanExiHS_LEFTY2.
ExpressionAtlasiO00292. baseline and differential.
GenevisibleiO00292. HS.

Organism-specific databases

HPAiCAB025801.
HPA047883.
HPA056210.

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112902. 3 interactors.
IntActiO00292. 2 interactors.
STRINGi9606.ENSP00000355785.

Structurei

3D structure databases

ProteinModelPortaliO00292.
SMRiO00292.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the TGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3900. Eukaryota.
ENOG410XT8Z. LUCA.
GeneTreeiENSGT00390000010056.
HOGENOMiHOG000113317.
HOVERGENiHBG074429.
InParanoidiO00292.
KOiK04668.
OMAiETGWKSF.
PhylomeDBiO00292.
TreeFamiTF106462.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiView protein in InterPro
IPR029034. Cystine-knot_cytokine.
IPR003942. LRDF.
IPR001839. TGF-b_C.
IPR001111. TGF-b_propeptide.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
PANTHERiPTHR11848. PTHR11848. 1 hit.
PfamiView protein in Pfam
PF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
PIRSFiPIRSF037402. TGFb4. 1 hit.
PRINTSiPR01427. TGFBETA4.
SMARTiView protein in SMART
SM00204. TGFB. 1 hit.
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiView protein in PROSITE
PS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.

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: O00292-1) [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
MWPLWLCWAL WVLPLAGPGA ALTEEQLLGS LLRQLQLSEV PVLDRADMEK
60 70 80 90 100
LVIPAHVRAQ YVVLLRRSHG DRSRGKRFSQ SFREVAGRFL ASEASTHLLV
110 120 130 140 150
FGMEQRLPPN SELVQAVLRL FQEPVPKAAL HRHGRLSPRS AQARVTVEWL
160 170 180 190 200
RVRDDGSNRT SLIDSRLVSV HESGWKAFDV TEAVNFWQQL SRPRQPLLLQ
210 220 230 240 250
VSVQREHLGP LASGAHKLVR FASQGAPAGL GEPQLELHTL DLRDYGAQGD
260 270 280 290 300
CDPEAPMTEG TRCCRQEMYI DLQGMKWAKN WVLEPPGFLA YECVGTCQQP
310 320 330 340 350
PEALAFNWPF LGPRQCIASE TASLPMIVSI KEGGRTRPQV VSLPNMRVQK
360
CSCASDGALV PRRLQP
Length:366
Mass (Da):40,920
Last modified:February 21, 2001 - v2
Checksum:i63A416CAE30F7A39
GO
Isoform 2 (identifier: O00292-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     94-127: Missing.

Note: No experimental confirmation available.
Show »
Length:332
Mass (Da):37,093
Checksum:i1E838AE7C0D31017
GO

Sequence cautioni

The sequence AAB53269 differs from that shown. Authors have revised their sequence, but have not submitted the revised DNA sequence.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti132R → G in BAG65344 (PubMed:14702039).Curated1
Sequence conflicti183A → P in BAC11556 (PubMed:16303743).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02198092S → L. Corresponds to variant dbSNP:rs366439Ensembl.1
Natural variantiVAR_021981286P → L. Corresponds to variant dbSNP:rs2295418Ensembl.1
Natural variantiVAR_010385342S → N in LRAM. 1 PublicationCorresponds to variant dbSNP:rs121909126Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04526494 – 127Missing in isoform 2. 1 PublicationAdd BLAST34

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U81523 mRNA. Translation: AAB53269.1. Sequence problems.
AF081511
, AF081508, AF081509, AF081510 Genomic DNA. Translation: AAC32600.1.
AF081513 mRNA. Translation: AAD48145.1.
AK027520 mRNA. Translation: BAG51336.1.
AK075344 mRNA. Translation: BAC11556.1.
AK304549 mRNA. Translation: BAG65344.1.
AL117348 Genomic DNA. No translation available.
BC035718 mRNA. Translation: AAH35718.1.
CCDSiCCDS1549.1. [O00292-1]
CCDS53479.1. [O00292-2]
RefSeqiNP_001165896.1. NM_001172425.2. [O00292-2]
NP_003231.2. NM_003240.4. [O00292-1]
UniGeneiHs.520187.

Genome annotation databases

EnsembliENST00000366820; ENSP00000355785; ENSG00000143768. [O00292-1]
ENST00000420304; ENSP00000388009; ENSG00000143768. [O00292-2]
GeneIDi7044.
KEGGihsa:7044.
UCSCiuc001hpt.3. human. [O00292-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiLFTY2_HUMAN
AccessioniPrimary (citable) accession number: O00292
Secondary accession number(s): B3KNH4
, B4E332, E9PDM4, O75611, Q5TE89, Q8NBQ9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: February 21, 2001
Last modified: September 27, 2017
This is version 175 of the entry and version 2 of the sequence. See 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, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: 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