ID   LFTY1_HUMAN             Reviewed;         366 AA.
AC   O75610; B2R7U0; Q53H67; Q5TE94;
DT   21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1998, sequence version 1.
DT   13-FEB-2019, entry version 160.
DE   RecName: Full=Left-right determination factor 1;
DE   AltName: Full=Left-right determination factor B;
DE   AltName: Full=Protein lefty-1;
DE   AltName: Full=Protein lefty-B;
DE   Flags: Precursor;
GN   Name=LEFTY1; Synonyms=LEFTB, LEFTYB; ORFNames=UNQ278/PRO317;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC   TISSUE=Teratocarcinoma;
RX   PubMed=10053005; DOI=10.1086/302289;
RA   Kosaki K., Bassi M.T., Kosaki R., Lewin M., Belmont J., Schauer G.,
RA   Casey B.;
RT   "Characterization and mutation analysis of human LEFTY A and LEFTY B,
RT   homologues of murine genes implicated in left-right axis
RT   development.";
RL   Am. J. Hum. Genet. 64:712-721(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=12975309; DOI=10.1101/gr.1293003;
RA   Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA   Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA   Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S.,
RA   Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
RA   Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
RA   Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
RA   Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
RA   Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
RA   Wood W.I., Godowski P.J., Gray A.M.;
RT   "The secreted protein discovery initiative (SPDI), a large-scale
RT   effort to identify novel human secreted and transmembrane proteins: a
RT   bioinformatics assessment.";
RL   Genome Res. 13:2265-2270(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS SER-92 AND
RP   GLN-142.
RC   TISSUE=Colon;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS SER-92 AND
RP   GLN-142.
RC   TISSUE=Colon;
RA   Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA   Tanaka A., Yokoyama S.;
RL   Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA   Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA   Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA   McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA   Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA   Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA   Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA   Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA   Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA   Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA   Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA   Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA   Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA   Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA   Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA   Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA   Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA   Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA   Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA   Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA   Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA   Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA   Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA   Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA   Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Pancreas, and Spleen;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
CC   -!- FUNCTION: Required for left-right axis determination as a
CC       regulator of LEFTY2 and NODAL.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- PTM: The processing of the protein may also occur at the second R-
CC       X-X-R site located at AA 132-135. Processing appears to be
CC       regulated in a cell-type specific manner.
CC   -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
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DR   EMBL; AF081507; AAC33967.1; -; Genomic_DNA.
DR   EMBL; AF081504; AAC33967.1; JOINED; Genomic_DNA.
DR   EMBL; AF081505; AAC33967.1; JOINED; Genomic_DNA.
DR   EMBL; AF081506; AAC33967.1; JOINED; Genomic_DNA.
DR   EMBL; AF081512; AAD48144.1; -; mRNA.
DR   EMBL; AY358873; AAQ89232.1; -; mRNA.
DR   EMBL; AK313115; BAG35937.1; -; mRNA.
DR   EMBL; AK222714; BAD96434.1; -; mRNA.
DR   EMBL; AL117348; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC027883; AAH27883.1; -; mRNA.
DR   CCDS; CCDS1548.1; -.
DR   RefSeq; NP_066277.1; NM_020997.3.
DR   UniGene; Hs.656214; -.
DR   ProteinModelPortal; O75610; -.
DR   SMR; O75610; -.
DR   BioGrid; 115881; 2.
DR   STRING; 9606.ENSP00000272134; -.
DR   iPTMnet; O75610; -.
DR   PhosphoSitePlus; O75610; -.
DR   BioMuta; LEFTY1; -.
DR   EPD; O75610; -.
DR   jPOST; O75610; -.
DR   PaxDb; O75610; -.
DR   PeptideAtlas; O75610; -.
DR   PRIDE; O75610; -.
DR   ProteomicsDB; 50119; -.
DR   DNASU; 10637; -.
DR   Ensembl; ENST00000272134; ENSP00000272134; ENSG00000243709.
DR   GeneID; 10637; -.
DR   KEGG; hsa:10637; -.
DR   UCSC; uc001hpo.3; human.
DR   CTD; 10637; -.
DR   DisGeNET; 10637; -.
DR   EuPathDB; HostDB:ENSG00000243709.1; -.
DR   GeneCards; LEFTY1; -.
DR   HGNC; HGNC:6552; LEFTY1.
DR   HPA; HPA047883; -.
DR   HPA; HPA056210; -.
DR   MIM; 603037; gene.
DR   neXtProt; NX_O75610; -.
DR   OpenTargets; ENSG00000243709; -.
DR   PharmGKB; PA30332; -.
DR   eggNOG; KOG3900; Eukaryota.
DR   eggNOG; ENOG410XT8Z; LUCA.
DR   GeneTree; ENSGT00390000010056; -.
DR   HOGENOM; HOG000113317; -.
DR   HOVERGEN; HBG074429; -.
DR   InParanoid; O75610; -.
DR   KO; K04668; -.
DR   OMA; MAIPTHV; -.
DR   OrthoDB; 751948at2759; -.
DR   PhylomeDB; O75610; -.
DR   TreeFam; TF106462; -.
DR   Reactome; R-HSA-1181150; Signaling by NODAL.
DR   Reactome; R-HSA-1433617; Regulation of signaling by NODAL.
DR   SIGNOR; O75610; -.
DR   ChiTaRS; LEFTY1; human.
DR   GenomeRNAi; 10637; -.
DR   PMAP-CutDB; O75610; -.
DR   PRO; PR:O75610; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   Bgee; ENSG00000243709; Expressed in 81 organ(s), highest expression level in transverse colon.
DR   ExpressionAtlas; O75610; baseline and differential.
DR   Genevisible; O75610; HS.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR   GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR   GO; GO:0005160; F:transforming growth factor beta receptor binding; IBA:GO_Central.
DR   GO; GO:0048468; P:cell development; IBA:GO_Central.
DR   GO; GO:0007368; P:determination of left/right symmetry; ISS:BHF-UCL.
DR   GO; GO:0003007; P:heart morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:BHF-UCL.
DR   GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IBA:GO_Central.
DR   GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central.
DR   GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
DR   GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR   GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:ProtInc.
DR   Gene3D; 2.10.90.10; -; 1.
DR   InterPro; IPR029034; Cystine-knot_cytokine.
DR   InterPro; IPR003942; LRDF.
DR   InterPro; IPR001839; TGF-b_C.
DR   InterPro; IPR001111; TGF-b_propeptide.
DR   InterPro; IPR015615; TGF-beta-rel.
DR   InterPro; IPR017948; TGFb_CS.
DR   PANTHER; PTHR11848; PTHR11848; 1.
DR   Pfam; PF00019; TGF_beta; 1.
DR   Pfam; PF00688; TGFb_propeptide; 1.
DR   PIRSF; PIRSF037402; TGFb4; 1.
DR   PRINTS; PR01427; TGFBETA4.
DR   SMART; SM00204; TGFB; 1.
DR   SUPFAM; SSF57501; SSF57501; 1.
DR   PROSITE; PS00250; TGF_BETA_1; 1.
DR   PROSITE; PS51362; TGF_BETA_2; 1.
PE   2: Evidence at transcript level;
KW   Complete proteome; Cytokine; Developmental protein; Disulfide bond;
KW   Glycoprotein; Growth factor; Polymorphism; Reference proteome;
KW   Secreted; Signal.
FT   SIGNAL        1     21       {ECO:0000255}.
FT   PROPEP       22     76       Or 135. {ECO:0000255}.
FT                                /FTId=PRO_0000033810.
FT   CHAIN        77    366       Left-right determination factor 1.
FT                                /FTId=PRO_0000033811.
FT   CARBOHYD    158    158       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID    251    264       {ECO:0000250}.
FT   DISULFID    263    316       {ECO:0000250}.
FT   DISULFID    293    351       {ECO:0000250}.
FT   DISULFID    297    353       {ECO:0000250}.
FT   VARIANT      57     57       V -> M (in dbSNP:rs35273824).
FT                                /FTId=VAR_052567.
FT   VARIANT      92     92       L -> S (in dbSNP:rs145431393).
FT                                {ECO:0000269|PubMed:14702039,
FT                                ECO:0000269|Ref.4}.
FT                                /FTId=VAR_070888.
FT   VARIANT     142    142       R -> Q (in dbSNP:rs191758097).
FT                                {ECO:0000269|PubMed:14702039,
FT                                ECO:0000269|Ref.4}.
FT                                /FTId=VAR_070889.
FT   VARIANT     322    322       D -> A (in dbSNP:rs360057).
FT                                /FTId=VAR_024231.
SQ   SEQUENCE   366 AA;  40880 MW;  BCF900C71ED9AA2A CRC64;
     MQPLWLCWAL WVLPLASPGA ALTGEQLLGS LLRQLQLKEV PTLDRADMEE LVIPTHVRAQ
     YVALLQRSHG DRSRGKRFSQ SFREVAGRFL ALEASTHLLV FGMEQRLPPN SELVQAVLRL
     FQEPVPKAAL HRHGRLSPRS ARARVTVEWL RVRDDGSNRT SLIDSRLVSV HESGWKAFDV
     TEAVNFWQQL SRPRQPLLLQ VSVQREHLGP LASGAHKLVR FASQGAPAGL GEPQLELHTL
     DLGDYGAQGD CDPEAPMTEG TRCCRQEMYI DLQGMKWAEN WVLEPPGFLA YECVGTCRQP
     PEALAFKWPF LGPRQCIASE TDSLPMIVSI KEGGRTRPQV VSLPNMRVQK CSCASDGALV
     PRRLQP
//