O00292 (LFTY2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	LEFTY2
Synonyms:	EBAF, LEFTA, LEFTYA, TGFB4
ORF Names:	PSEC0024

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	366 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	Required for left-right (L-R) asymmetry determination of organ systems in mammals. May play a role in endometrial bleeding.
Subcellular location	Secreted.
Tissue specificity	Mesenchymal cells of the endometrial stroma.
Developmental stage	Transiently expressed before and during menstrual bleeding.
Post-translational modification	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.
Involvement in disease	Left-right axis malformations (LRAM) [MIM:601877]: The defect includes left pulmonary isomerism, with cardiac anomalies characterized by complete atrioventricular canal defect and hypoplastic left ventricle, and interrupted inferior vena cava. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2
Sequence similarities	Belongs to the TGF-beta family.
Sequence caution	The sequence AAB53269.1 differs from that shown. Reason: Authors have revised their sequence, but have not submitted the revised DNA sequence.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Heterotaxy
Domain	Signal
Molecular function	Cytokine Developmental protein Growth factor
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell growth Inferred from electronic annotation. Source: InterPro multicellular organismal development Traceable author statement Ref.2. Source: ProtInc platelet activation Traceable author statement. Source: Reactome platelet degranulation Traceable author statement. Source: Reactome transforming growth factor beta receptor signaling pathway Traceable author statement Ref.1. Source: ProtInc
Cellular_component	extracellular region Traceable author statement. Source: Reactome extracellular space Inferred from electronic annotation. Source: UniProtKB-KW platelet alpha granule lumen Traceable author statement. Source: Reactome
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O00292-1)

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.

Isoform 2 (identifier: O00292-2)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Propeptide	22 – 76	55	Or 135 Potential		PRO_0000033806
	Chain	77 – 366	290	Left-right determination factor 2		PRO_0000033807
Amino acid modifications
	Glycosylation	158	1	N-linked (GlcNAc...) Potential
	Disulfide bond	251 ↔ 264		By similarity
	Disulfide bond	263 ↔ 316		By similarity
	Disulfide bond	293 ↔ 351		By similarity
	Disulfide bond	297 ↔ 353		By similarity
Natural variations
	Alternative sequence	94 – 127	34	Missing in isoform 2.		VSP_045264
	Natural variant	92	1	S → L. Corresponds to variant rs366439 [ dbSNP | Ensembl ].		VAR_021980
	Natural variant	286	1	P → L. Corresponds to variant rs2295418 [ dbSNP | Ensembl ].		VAR_021981
	Natural variant	342	1	S → N in LRAM. Ref.2		VAR_010385
Experimental info
	Sequence conflict	132	1	R → G in BAG65344. Ref.3
	Sequence conflict	183	1	A → P in BAC11556. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 21, 2001. Version 2. Checksum: 63A416CAE30F7A39	FASTA	366	40,920
	10 20 30 40 50 60 MWPLWLCWAL WVLPLAGPGA ALTEEQLLGS LLRQLQLSEV PVLDRADMEK LVIPAHVRAQ 70 80 90 100 110 120 YVVLLRRSHG DRSRGKRFSQ SFREVAGRFL ASEASTHLLV FGMEQRLPPN SELVQAVLRL 130 140 150 160 170 180 FQEPVPKAAL HRHGRLSPRS AQARVTVEWL RVRDDGSNRT SLIDSRLVSV HESGWKAFDV 190 200 210 220 230 240 TEAVNFWQQL SRPRQPLLLQ VSVQREHLGP LASGAHKLVR FASQGAPAGL GEPQLELHTL 250 260 270 280 290 300 DLRDYGAQGD CDPEAPMTEG TRCCRQEMYI DLQGMKWAKN WVLEPPGFLA YECVGTCQQP 310 320 330 340 350 360 PEALAFNWPF LGPRQCIASE TASLPMIVSI KEGGRTRPQV VSLPNMRVQK CSCASDGALV PRRLQP
	Isoform 2 [UniParc]. Checksum: 1E838AE7C0D31017	FASTA	332	37,093
	10 20 30 40 50 60 MWPLWLCWAL WVLPLAGPGA ALTEEQLLGS LLRQLQLSEV PVLDRADMEK LVIPAHVRAQ 70 80 90 100 110 120 YVVLLRRSHG DRSRGKRFSQ SFREVAGRFL ASEAALHRHG RLSPRSAQAR VTVEWLRVRD 130 140 150 160 170 180 DGSNRTSLID SRLVSVHESG WKAFDVTEAV NFWQQLSRPR QPLLLQVSVQ REHLGPLASG 190 200 210 220 230 240 AHKLVRFASQ GAPAGLGEPQ LELHTLDLRD YGAQGDCDPE APMTEGTRCC RQEMYIDLQG 250 260 270 280 290 300 MKWAKNWVLE PPGFLAYECV GTCQQPPEAL AFNWPFLGPR QCIASETASL PMIVSIKEGG 310 320 330 RTRPQVVSLP NMRVQKCSCA SDGALVPRRL QP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Detection of ebaf, a novel human gene of the transforming growth factor beta superfamily association of gene expression with endometrial bleeding." Kothapalli R., Buyuksal I., Wu S.-Q., Chegini N., Tabibzadeh S. J. Clin. Invest. 99:2342-2350(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Placenta.
[2]	"Characterization and mutation analysis of human LEFTY A and LEFTY B, homologues of murine genes implicated in left-right axis development." Kosaki K., Bassi M.T., Kosaki R., Lewin M., Belmont J., Schauer G., Casey B. Am. J. Hum. Genet. 64:712-721(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LRAM ASN-342. Tissue: Placenta.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Uterus.
[4]	"Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries." Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y. , Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., Isogai T. DNA Res. 12:117-126(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Teratocarcinoma.
[5]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORM 1). Tissue: Ovary.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	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. Translation: CAI21804.1. BC035718 mRNA. Translation: AAH35718.1.
IPI	IPI00010893. IPI00910132.
RefSeq	NP_001165896.1. NM_001172425.1. NP_003231.2. NM_003240.3.
UniGene	Hs.520187.
3D structure databases
ProteinModelPortal	O00292.
SMR	O00292. Positions 261-354.
ModBase	Search...
Protein-protein interaction databases
IntAct	O00292. 1 interaction.
STRING	9606.ENSP00000355785.
Proteomic databases
PaxDb	O00292.
PRIDE	O00292.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000366820; ENSP00000355785; ENSG00000143768. ENST00000420304; ENSP00000388009; ENSG00000143768.
GeneID	7044.
KEGG	hsa:7044.
UCSC	uc001hpt.2. human. uc010pvk.2. human.
Organism-specific databases
CTD	7044.
GeneCards	GC01M226126.
HGNC	HGNC:3122. LEFTY2.
HPA	CAB025801.
MIM	601877. gene+phenotype.
neXtProt	NX_O00292.
Orphanet	157769. Situs ambiguus.
PharmGKB	PA27580.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG266606.
HOGENOM	HOG000113317.
HOVERGEN	HBG074429.
InParanoid	O00292.
KO	K04668.
OMA	QAFRCTG.
OrthoDB	EOG4HHP2N.
PhylomeDB	O00292.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology. REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	O00292.
Bgee	O00292.
CleanEx	HS_LEFTY2.
Genevestigator	O00292.
GermOnline	ENSG00000143768. Homo sapiens.
Family and domain databases
InterPro	IPR003942. LRDF. IPR001839. TGF-b_C. IPR001111. TGF-b_N. IPR015615. TGF-beta-rel. IPR017948. TGFb_CS. [Graphical view]
PANTHER	PTHR11848. PTHR11848. 1 hit.
Pfam	PF00019. TGF_beta. 1 hit. PF00688. TGFb_propeptide. 1 hit. [Graphical view]
PIRSF	PIRSF037402. TGFb4. 1 hit.
PRINTS	PR01427. TGFBETA4.
SMART	SM00204. TGFB. 1 hit. [Graphical view]
PROSITE	PS00250. TGF_BETA_1. 1 hit. PS51362. TGF_BETA_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	7044.
NextBio	27525.
SOURCE	Search...

Entry information

Entry name

LFTY2_HUMAN

Accession

Primary (citable) accession number: O00292
Secondary accession number(s): B3KNH4 , B4E332, E9PDM4, O75611, Q5TE89, Q8NBQ9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	February 21, 2001
Last modified:	May 29, 2013
This is version 136 of the entry and version 2 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.