LFTY1_HUMAN
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 03-AUG-2022, entry version 176.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 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., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS SER-92 AND 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 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., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., 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., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., 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., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Required for left-right axis determination as a regulator of
CC LEFTY2 and NODAL.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- PTM: The processing of the protein may also occur at the second R-X-X-R
CC site located at AA 132-135. Processing appears to be regulated in a
CC 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 AlphaFoldDB; O75610; -.
DR BioGRID; 115881; 7.
DR IntAct; O75610; 2.
DR STRING; 9606.ENSP00000272134; -.
DR GlyGen; O75610; 1 site.
DR iPTMnet; O75610; -.
DR PhosphoSitePlus; O75610; -.
DR BioMuta; LEFTY1; -.
DR EPD; O75610; -.
DR jPOST; O75610; -.
DR MassIVE; O75610; -.
DR PaxDb; O75610; -.
DR PeptideAtlas; O75610; -.
DR PRIDE; O75610; -.
DR ProteomicsDB; 50119; -.
DR Antibodypedia; 34775; 360 antibodies from 27 providers.
DR DNASU; 10637; -.
DR Ensembl; ENST00000272134.5; ENSP00000272134.5; ENSG00000243709.1.
DR GeneID; 10637; -.
DR KEGG; hsa:10637; -.
DR MANE-Select; ENST00000272134.5; ENSP00000272134.5; NM_020997.4; NP_066277.1.
DR UCSC; uc001hpo.3; human.
DR CTD; 10637; -.
DR DisGeNET; 10637; -.
DR GeneCards; LEFTY1; -.
DR HGNC; HGNC:6552; LEFTY1.
DR HPA; ENSG00000243709; Group enriched (intestine, pancreas).
DR MIM; 603037; gene.
DR neXtProt; NX_O75610; -.
DR OpenTargets; ENSG00000243709; -.
DR PharmGKB; PA30332; -.
DR VEuPathDB; HostDB:ENSG00000243709; -.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00390000010056; -.
DR HOGENOM; CLU_064098_0_0_1; -.
DR InParanoid; O75610; -.
DR OMA; AGSEVMM; -.
DR OrthoDB; 751948at2759; -.
DR PhylomeDB; O75610; -.
DR TreeFam; TF106462; -.
DR PathwayCommons; O75610; -.
DR Reactome; R-HSA-1181150; Signaling by NODAL.
DR Reactome; R-HSA-1433617; Regulation of signaling by NODAL.
DR SignaLink; O75610; -.
DR SIGNOR; O75610; -.
DR BioGRID-ORCS; 10637; 10 hits in 1061 CRISPR screens.
DR ChiTaRS; LEFTY1; human.
DR GenomeRNAi; 10637; -.
DR Pharos; O75610; Tbio.
DR PRO; PR:O75610; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O75610; protein.
DR Bgee; ENSG00000243709; Expressed in mucosa of transverse colon and 90 other tissues.
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; IEA:InterPro.
DR GO; GO:0030509; P:BMP signaling pathway; 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: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 Cytokine; Developmental protein; Disulfide bond; Glycoprotein;
KW Growth factor; Reference proteome; Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..76
FT /note="Or 135"
FT /evidence="ECO:0000255"
FT /id="PRO_0000033810"
FT CHAIN 77..366
FT /note="Left-right determination factor 1"
FT /id="PRO_0000033811"
FT CARBOHYD 158
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 251..264
FT /evidence="ECO:0000250"
FT DISULFID 263..316
FT /evidence="ECO:0000250"
FT DISULFID 293..351
FT /evidence="ECO:0000250"
FT DISULFID 297..353
FT /evidence="ECO:0000250"
FT VARIANT 57
FT /note="V -> M (in dbSNP:rs35273824)"
FT /id="VAR_052567"
FT VARIANT 92
FT /note="L -> S (in dbSNP:rs145431393)"
FT /evidence="ECO:0000269|PubMed:14702039, ECO:0000269|Ref.4"
FT /id="VAR_070888"
FT VARIANT 142
FT /note="R -> Q (in dbSNP:rs191758097)"
FT /evidence="ECO:0000269|PubMed:14702039, ECO:0000269|Ref.4"
FT /id="VAR_070889"
FT VARIANT 322
FT /note="D -> A (in dbSNP:rs360057)"
FT /id="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
