GDF9_HUMAN
ID GDF9_HUMAN Reviewed; 454 AA.
AC O60383; Q4VAW5;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Growth/differentiation factor 9;
DE Short=GDF-9;
DE Flags: Precursor;
GN Name=GDF9;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=10443672; DOI=10.1210/jcem.84.8.5921;
RA Aaltonen J., Laitinen M.P., Vuojolainen K., Jaatinen R.,
RA Horelli-Kuitunen N., Seppae L., Louhio H., Tuuri T., Sjoeberg J.,
RA Buetzow R., Hovatta O., Dale L., Ritvos O.;
RT "Human growth differentiation factor 9 (GDF-9) and its novel homolog GDF-9B
RT are expressed in oocytes during early folliculogenesis.";
RL J. Clin. Endocrinol. Metab. 84:2744-2750(1999).
RN [4]
RP FUNCTION AS REGULATOR OF PROGESTERONE RELEASE, AND TISSUE SPECIFICITY.
RX PubMed=12050262; DOI=10.1210/jcem.87.6.8551;
RA Yamamoto N., Christenson L.K., McAllister J.M., Strauss J.F. III;
RT "Growth differentiation factor-9 inhibits 3'5'-adenosine monophosphate-
RT stimulated steroidogenesis in human granulosa and theca cells.";
RL J. Clin. Endocrinol. Metab. 87:2849-2856(2002).
RN [5]
RP ERRATUM OF PUBMED:12050262.
RA Yamamoto N., Christenson L.K., McAllister J.M., Strauss J.F. III;
RL J. Clin. Endocrinol. Metab. 87:4495-4495(2002).
RN [6]
RP PHOSPHORYLATION.
RX PubMed=18006624; DOI=10.1210/en.2007-1439;
RA McMahon H.E., Sharma S., Shimasaki S.;
RT "Phosphorylation of bone morphogenetic protein-15 and growth and
RT differentiation factor-9 plays a critical role in determining agonistic or
RT antagonistic functions.";
RL Endocrinology 149:812-817(2008).
RN [7]
RP FUNCTION IN GRANULOSA CELLS PROLIFERATION.
RX PubMed=19366876; DOI=10.1152/ajpendo.90929.2008;
RA Huang Q., Cheung A.P., Zhang Y., Huang H.F., Auersperg N., Leung P.C.;
RT "Effects of growth differentiation factor 9 on cell cycle regulators and
RT ERK42/44 in human granulosa cell proliferation.";
RL Am. J. Physiol. 296:E1344-E1353(2009).
RN [8]
RP PHOSPHORYLATION AT SER-325 BY CK, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=20067794; DOI=10.1016/j.febslet.2009.12.052;
RA Tibaldi E., Arrigoni G., Martinez H.M., Inagaki K., Shimasaki S.,
RA Pinna L.A.;
RT "Golgi apparatus casein kinase phosphorylates bioactive Ser-6 of bone
RT morphogenetic protein 15 and growth and differentiation factor 9.";
RL FEBS Lett. 584:801-805(2010).
RN [9]
RP FUNCTION AS REGULATOR OF STAR EXPRESSION AND PROGESTERONE RELEASE.
RX PubMed=20660033; DOI=10.1210/jc.2010-0477;
RA Shi F.T., Cheung A.P., Klausen C., Huang H.F., Leung P.C.;
RT "Growth differentiation factor 9 reverses activin A suppression of
RT steroidogenic acute regulatory protein expression and progesterone
RT production in human granulosa-lutein cells.";
RL J. Clin. Endocrinol. Metab. 95:E172-E180(2010).
RN [10]
RP FUNCTION IN PRIMORDIAL FOLLICLE DEVELOPMENT.
RX PubMed=21632818; DOI=10.1210/jc.2011-0410;
RA Kedem A., Fisch B., Garor R., Ben-Zaken A., Gizunterman T., Felz C.,
RA Ben-Haroush A., Kravarusic D., Abir R.;
RT "Growth differentiating factor 9 (GDF9) and bone morphogenetic protein 15
RT both activate development of human primordial follicles in vitro, with
RT seemingly more beneficial effects of GDF9.";
RL J. Clin. Endocrinol. Metab. 96:E1246-E1254(2011).
RN [11]
RP FUNCTION.
RX PubMed=21829661; DOI=10.1371/journal.pone.0022866;
RA Shi F.T., Cheung A.P., Huang H.F., Leung P.C.;
RT "Growth differentiation factor 9 (GDF9) suppresses follistatin and
RT follistatin-like 3 production in human granulosa-lutein cells.";
RL PLoS ONE 6:E22866-E22866(2011).
RN [12]
RP SPECIES-SPECIFIC OVULATION RATE DETERMINATION.
RX PubMed=21970812; DOI=10.1016/j.mce.2011.09.033;
RA Crawford J.L., McNatty K.P.;
RT "The ratio of growth differentiation factor 9: bone morphogenetic protein
RT 15 mRNA expression is tightly co-regulated and differs between species over
RT a wide range of ovulation rates.";
RL Mol. Cell. Endocrinol. 348:339-343(2012).
RN [13]
RP INVOLVEMENT IN POF14.
RX PubMed=29044499; DOI=10.1111/cge.13156;
RA Franca M.M., Funari M.F.A., Nishi M.Y., Narcizo A.M., Domenice S.,
RA Costa E.M.F., Lerario A.M., Mendonca B.B.;
RT "Identification of the first homozygous 1-bp deletion in GDF9 gene leading
RT to primary ovarian insufficiency by using targeted massively parallel
RT sequencing.";
RL Clin. Genet. 93:408-411(2018).
RN [14]
RP VARIANTS POF14 GLU-67 AND MET-216, AND INVOLVEMENT IN POF14.
RX PubMed=16278619; DOI=10.1097/01.gme.0000184424.96437.7a;
RA Dixit H., Rao L.K., Padmalatha V., Kanakavalli M., Deenadayal M., Gupta N.,
RA Chakravarty B., Singh L.;
RT "Mutational screening of the coding region of growth differentiation factor
RT 9 gene in Indian women with ovarian failure.";
RL Menopause 12:749-754(2005).
RN [15]
RP VARIANT POF14 TYR-186, AND INVOLVEMENT IN POF14.
RX PubMed=16645022; DOI=10.1530/eje.1.02135;
RA Laissue P., Christin-Maitre S., Touraine P., Kuttenn F., Ritvos O.,
RA Aittomaki K., Bourcigaux N., Jacquesson L., Bouchard P., Frydman R.,
RA Dewailly D., Reyss A.-C., Jeffery L., Bachelot A., Massin N., Fellous M.,
RA Veitia R.A.;
RT "Mutations and sequence variants in GDF9 and BMP15 in patients with
RT premature ovarian failure.";
RL Eur. J. Endocrinol. 154:739-744(2006).
RN [16]
RP VARIANT POF14 SER-103, VARIANTS ILE-121; LEU-374 AND CYS-454, AND POSSIBLE
RP INVOLVEMENT IN DIZYGOTIC TWINNING.
RX PubMed=16954162; DOI=10.1210/jc.2006-0970;
RA Palmer J.S., Zhao Z.Z., Hoekstra C., Hayward N.K., Webb P.M.,
RA Whiteman D.C., Martin N.G., Boomsma D.I., Duffy D.L., Montgomery G.W.;
RT "Novel variants in growth differentiation factor 9 in mothers of dizygotic
RT twins.";
RL J. Clin. Endocrinol. Metab. 91:4713-4716(2006).
RN [17]
RP VARIANT POF14 SER-103.
RX PubMed=17156781; DOI=10.1016/j.fertnstert.2006.05.079;
RA Kovanci E., Rohozinski J., Simpson J.L., Heard M.J., Bishop C.E.,
RA Carson S.A.;
RT "Growth differentiating factor-9 mutations may be associated with premature
RT ovarian failure.";
RL Fertil. Steril. 87:143-146(2007).
RN [18]
RP VARIANTS POF14 CYS-146; ALA-238 AND THR-428.
RX PubMed=17482612; DOI=10.1016/j.fertnstert.2007.01.021;
RA Zhao H., Qin Y., Kovanci E., Simpson J.L., Chen Z.J., Rajkovic A.;
RT "Analyses of GDF9 mutation in 100 Chinese women with premature ovarian
RT failure.";
RL Fertil. Steril. 88:1474-1476(2007).
RN [19]
RP VARIANT POF14 TYR-57.
RX PubMed=19438907; DOI=10.1111/j.1365-2265.2009.03613.x;
RA Wang B., Wen Q., Ni F., Zhou S., Wang J., Cao Y., Ma X.;
RT "Analyses of growth differentiation factor 9 (GDF9) and bone morphogenetic
RT protein 15 (BMP15) mutation in Chinese women with premature ovarian
RT failure.";
RL Clin. Endocrinol. (Oxf.) 72:135-136(2010).
CC -!- FUNCTION: Required for ovarian folliculogenesis. Promotes primordial
CC follicle development. Stimulates granulosa cell proliferation. Promotes
CC cell transition from G0/G1 to S and G2/M phases, through an increase of
CC CCND1 and CCNE1 expression, and RB1 phosphorylation. It regulates STAR
CC expression and cAMP-dependent progesterone release in granulosa and
CC thecal cells. Attenuates the suppressive effects of activin A on STAR
CC expression and progesterone production by increasing the expression of
CC inhibin B. It suppresses FST and FSTL3 production in granulosa-lutein
CC cells. {ECO:0000269|PubMed:12050262, ECO:0000269|PubMed:19366876,
CC ECO:0000269|PubMed:20660033, ECO:0000269|PubMed:21632818,
CC ECO:0000269|PubMed:21829661}.
CC -!- SUBUNIT: Homodimer or heterodimer (Potential). But, in contrast to
CC other members of this family, cannot be disulfide-linked (By
CC similarity). {ECO:0000250, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in ovarian granulosa cells. Present in
CC oocytes of primary follicles (at protein level).
CC {ECO:0000269|PubMed:10443672, ECO:0000269|PubMed:12050262}.
CC -!- PTM: Phosphorylated; phosphorylation is critical for GDF9 function. In
CC vitro, can be phosphorylated by CK at Ser-325.
CC {ECO:0000269|PubMed:18006624, ECO:0000269|PubMed:20067794}.
CC -!- DISEASE: Note=Altered GDF9 function may be involved in ovarian
CC disorders and contribute to the likelihood of dizygotic twinning.
CC {ECO:0000269|PubMed:16954162}.
CC -!- DISEASE: Premature ovarian failure 14 (POF14) [MIM:618014]: An ovarian
CC disorder defined as the cessation of ovarian function under the age of
CC 40 years. It is characterized by oligomenorrhea or amenorrhea, in the
CC presence of elevated levels of serum gonadotropins and low estradiol.
CC {ECO:0000269|PubMed:16278619, ECO:0000269|PubMed:16645022,
CC ECO:0000269|PubMed:16954162, ECO:0000269|PubMed:17156781,
CC ECO:0000269|PubMed:17482612, ECO:0000269|PubMed:19438907,
CC ECO:0000269|PubMed:29044499}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Ovarian physiology and fertility are controlled by
CC endocrine and paracrine signals. These act in a species-dependent
CC manner and determine the ovulation quota in different mammalian
CC species. While humans, and mammals such as the cow or red deer,
CC normally ovulate only one egg per cycle, other mammals such as mouse
CC and pig can ovulate in excess of ten per cycle. The mechanisms that
CC regulate the species-specific differences in the number of follicles
CC that go onto ovulate during each reproductive cycle are poorly
CC understood. According to PubMed:21970812, mRNA expression levels of
CC GDF9 and BMP15 are tightly coregulated within each species and
CC influence species-specific ovulation-rates.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
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DR EMBL; AC004500; AAC08450.1; -; Genomic_DNA.
DR EMBL; BC096228; AAH96228.1; -; mRNA.
DR EMBL; BC096229; AAH96229.1; -; mRNA.
DR EMBL; BC096230; AAH96230.1; -; mRNA.
DR EMBL; BC096231; AAH96231.1; -; mRNA.
DR CCDS; CCDS4162.1; -.
DR RefSeq; NP_001275753.1; NM_001288824.2.
DR RefSeq; NP_005251.1; NM_005260.5.
DR RefSeq; XP_011541610.1; XM_011543308.2.
DR AlphaFoldDB; O60383; -.
DR BioGRID; 108930; 58.
DR IntAct; O60383; 50.
DR MINT; O60383; -.
DR STRING; 9606.ENSP00000367942; -.
DR GlyGen; O60383; 6 sites.
DR iPTMnet; O60383; -.
DR PhosphoSitePlus; O60383; -.
DR BioMuta; GDF9; -.
DR MassIVE; O60383; -.
DR PaxDb; O60383; -.
DR PeptideAtlas; O60383; -.
DR PRIDE; O60383; -.
DR ProteomicsDB; 49386; -.
DR Antibodypedia; 26178; 566 antibodies from 31 providers.
DR DNASU; 2661; -.
DR Ensembl; ENST00000378673.2; ENSP00000367942.2; ENSG00000164404.9.
DR Ensembl; ENST00000464378.2; ENSP00000509893.1; ENSG00000164404.9.
DR Ensembl; ENST00000687138.1; ENSP00000510441.1; ENSG00000164404.9.
DR GeneID; 2661; -.
DR KEGG; hsa:2661; -.
DR MANE-Select; ENST00000687138.1; ENSP00000510441.1; NM_005260.7; NP_005251.1.
DR UCSC; uc003kxz.3; human.
DR CTD; 2661; -.
DR DisGeNET; 2661; -.
DR GeneCards; GDF9; -.
DR HGNC; HGNC:4224; GDF9.
DR HPA; ENSG00000164404; Tissue enhanced (testis).
DR MalaCards; GDF9; -.
DR MIM; 601918; gene.
DR MIM; 618014; phenotype.
DR neXtProt; NX_O60383; -.
DR OpenTargets; ENSG00000164404; -.
DR Orphanet; 619; NON RARE IN EUROPE: Primary ovarian failure.
DR PharmGKB; PA28639; -.
DR VEuPathDB; HostDB:ENSG00000164404; -.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000159784; -.
DR InParanoid; O60383; -.
DR OMA; CAQHKQA; -.
DR OrthoDB; 724783at2759; -.
DR PhylomeDB; O60383; -.
DR TreeFam; TF351788; -.
DR PathwayCommons; O60383; -.
DR SignaLink; O60383; -.
DR BioGRID-ORCS; 2661; 7 hits in 1067 CRISPR screens.
DR ChiTaRS; GDF9; human.
DR GeneWiki; Growth_differentiation_factor-9; -.
DR GenomeRNAi; 2661; -.
DR Pharos; O60383; Tbio.
DR PRO; PR:O60383; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; O60383; protein.
DR Bgee; ENSG00000164404; Expressed in oocyte and 100 other tissues.
DR ExpressionAtlas; O60383; baseline and differential.
DR Genevisible; O60383; 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; TAS:ProtInc.
DR GO; GO:0070698; F:type I activin receptor binding; IBA:GO_Central.
DR GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0007292; P:female gamete generation; TAS:ProtInc.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IBA:GO_Central.
DR GO; GO:2000870; P:regulation of progesterone secretion; IDA:UniProtKB.
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; IPR015617; Growth_differentiation_fac-9.
DR InterPro; IPR001839; TGF-b_C.
DR InterPro; IPR015615; TGF-beta-rel.
DR InterPro; IPR017948; TGFb_CS.
DR PANTHER; PTHR11848; PTHR11848; 1.
DR PANTHER; PTHR11848:SF19; PTHR11848:SF19; 1.
DR Pfam; PF00019; TGF_beta; 1.
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 1: Evidence at protein level;
KW Cleavage on pair of basic residues; Cytokine; Disulfide bond; Glycoprotein;
KW Growth factor; Phosphoprotein; Premature ovarian failure;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PROPEP 25..319
FT /evidence="ECO:0000255"
FT /id="PRO_0000033980"
FT CHAIN 320..454
FT /note="Growth/differentiation factor 9"
FT /id="PRO_0000033981"
FT REGION 303..330
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 307..325
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 325
FT /note="Phosphoserine; by CK"
FT /evidence="ECO:0000305|PubMed:20067794"
FT CARBOHYD 106
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 163
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 236
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 255
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 268
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 338
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 353..419
FT /evidence="ECO:0000250"
FT DISULFID 382..451
FT /evidence="ECO:0000250"
FT DISULFID 386..453
FT /evidence="ECO:0000250"
FT VARIANT 57
FT /note="D -> Y (in POF14; unknown pathological significance;
FT dbSNP:rs138136756)"
FT /evidence="ECO:0000269|PubMed:19438907"
FT /id="VAR_066934"
FT VARIANT 67
FT /note="K -> E (in POF14; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:16278619"
FT /id="VAR_058945"
FT VARIANT 103
FT /note="P -> S (in POF14; unknown pathological significance;
FT also found at higher frequency in mothers of dizygotic
FT twins than in controls; dbSNP:rs61754583)"
FT /evidence="ECO:0000269|PubMed:16954162,
FT ECO:0000269|PubMed:17156781"
FT /id="VAR_066935"
FT VARIANT 121
FT /note="T -> I (found at higher frequency in mothers of
FT dizygotic twins than in controls; dbSNP:rs149821575)"
FT /evidence="ECO:0000269|PubMed:16954162"
FT /id="VAR_066936"
FT VARIANT 146
FT /note="R -> C (in POF14; unknown pathological significance;
FT dbSNP:rs76349024)"
FT /evidence="ECO:0000269|PubMed:17482612"
FT /id="VAR_066937"
FT VARIANT 186
FT /note="S -> Y (in POF14; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:16645022"
FT /id="VAR_058946"
FT VARIANT 216
FT /note="V -> M (in POF14; unknown pathological significance;
FT dbSNP:rs1205723048)"
FT /evidence="ECO:0000269|PubMed:16278619"
FT /id="VAR_058947"
FT VARIANT 238
FT /note="T -> A (in POF14; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:17482612"
FT /id="VAR_066938"
FT VARIANT 374
FT /note="P -> L (found at higher frequency in mothers of
FT dizygotic twins than in controls; dbSNP:rs373477788)"
FT /evidence="ECO:0000269|PubMed:16954162"
FT /id="VAR_066939"
FT VARIANT 428
FT /note="S -> T (in POF14; unknown pathological significance;
FT dbSNP:rs118080183)"
FT /evidence="ECO:0000269|PubMed:17482612"
FT /id="VAR_066940"
FT VARIANT 454
FT /note="R -> C (found at higher frequency in mothers of
FT dizygotic twins than in controls; dbSNP:rs61754582)"
FT /evidence="ECO:0000269|PubMed:16954162"
FT /id="VAR_066941"
SQ SEQUENCE 454 AA; 51444 MW; 94EA366E90CDBC27 CRC64;
MARPNKFLLW FCCFAWLCFP ISLGSQASGG EAQIAASAEL ESGAMPWSLL QHIDERDRAG
LLPALFKVLS VGRGGSPRLQ PDSRALHYMK KLYKTYATKE GIPKSNRSHL YNTVRLFTPC
TRHKQAPGDQ VTGILPSVEL LFNLDRITTV EHLLKSVLLY NINNSVSFSS AVKCVCNLMI
KEPKSSSRTL GRAPYSFTFN SQFEFGKKHK WIQIDVTSLL QPLVASNKRS IHMSINFTCM
KDQLEHPSAQ NGLFNMTLVS PSLILYLNDT SAQAYHSWYS LHYKRRPSQG PDQERSLSAY
PVGEEAAEDG RSSHHRHRRG QETVSSELKK PLGPASFNLS EYFRQFLLPQ NECELHDFRL
SFSQLKWDNW IVAPHRYNPR YCKGDCPRAV GHRYGSPVHT MVQNIIYEKL DSSVPRPSCV
PAKYSPLSVL TIEPDGSIAY KEYEDMIATK CTCR