ID   MIS_BOVIN               Reviewed;         575 AA.
AC   P03972;
DT   23-OCT-1986, integrated into UniProtKB/Swiss-Prot.
DT   23-OCT-1986, sequence version 1.
DT   03-AUG-2022, entry version 119.
DE   RecName: Full=Muellerian-inhibiting factor;
DE   AltName: Full=Anti-Muellerian hormone;
DE            Short=AMH;
DE   AltName: Full=Muellerian-inhibiting substance {ECO:0000303|PubMed:3754790};
DE            Short=MIS {ECO:0000303|PubMed:3754790};
DE   Flags: Precursor;
GN   Name=AMH;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], PARTIAL PROTEIN SEQUENCE, TISSUE
RP   SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX   PubMed=3754790; DOI=10.1016/0092-8674(86)90783-x;
RA   Cate R.L., Mattaliano R.J., Hession C., Tizard R., Farber N.M., Cheung A.,
RA   Ninfa E.G., Frey A.Z., Gash D.J., Chow E.P., Fisher R.A., Bertonis J.M.,
RA   Torres G., Wallner B.P., Ramachandran K.L., Ragin R.C., Manganaro T.F.,
RA   McLaughlin D.T., Donahoe P.K.;
RT   "Isolation of the bovine and human genes for Mullerian inhibiting substance
RT   and expression of the human gene in animal cells.";
RL   Cell 45:685-698(1986).
CC   -!- FUNCTION: Plays an important role in several reproductive functions.
CC       Induces Muellerian duct regression during male fetal sexual
CC       differentiation and plays a role in Leydig cell differentiation and
CC       function (By similarity). In female acts as a negative regulator of the
CC       primordial to primary follicle transition and decreases FSH sensitivity
CC       of growing follicles. AMH signals by binding to a specific type-II
CC       receptor, AMHR2, that heterodimerizes with type-I receptors (ACVR1 and
CC       BMPR1A), and recruiting SMAD proteins that are translocated to the
CC       nucleus to regulate target gene expression (By similarity).
CC       {ECO:0000250|UniProtKB:P03971, ECO:0000250|UniProtKB:P27106}.
CC   -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000250|UniProtKB:P03971}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P03971}.
CC   -!- TISSUE SPECIFICITY: Expressed in fetal testis and adult ovaries.
CC       {ECO:0000269|PubMed:3754790}.
CC   -!- DEVELOPMENTAL STAGE: Expressed in testis at a high level immediately
CC       after birth, and decreases to a very low level by 3 months.
CC       {ECO:0000269|PubMed:3754790}.
CC   -!- PTM: Preproprotein is proteolytically processed to generate N- and C-
CC       terminal cleavage products that homodimerize and associate to form a
CC       biologically active non-covalent complex. Binding of the non-covalent
CC       complex to AMHR2 induces dissociation of the pro-region from the mature
CC       C-terminal dimer. The N-terminal portion of the protein, despite having
CC       no intrinsic activity, has the role of amplifying the activity of the
CC       C-terminus. {ECO:0000250|UniProtKB:P03971}.
CC   -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
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DR   EMBL; M13151; AAA98765.1; -; Genomic_DNA.
DR   PIR; A01398; WFBOM.
DR   RefSeq; NP_776315.1; NM_173890.1.
DR   AlphaFoldDB; P03972; -.
DR   SMR; P03972; -.
DR   STRING; 9913.ENSBTAP00000019912; -.
DR   PaxDb; P03972; -.
DR   PRIDE; P03972; -.
DR   GeneID; 280718; -.
DR   KEGG; bta:280718; -.
DR   CTD; 268; -.
DR   eggNOG; KOG3900; Eukaryota.
DR   InParanoid; P03972; -.
DR   OrthoDB; 516965at2759; -.
DR   Proteomes; UP000009136; Unplaced.
DR   GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR   GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR   GO; GO:0005114; F:type II transforming growth factor beta receptor binding; ISS:UniProtKB.
DR   GO; GO:0007506; P:gonadal mesoderm development; IEA:UniProtKB-KW.
DR   GO; GO:0033327; P:Leydig cell differentiation; ISS:UniProtKB.
DR   GO; GO:0001880; P:Mullerian duct regression; ISS:UniProtKB.
DR   GO; GO:2000355; P:negative regulation of ovarian follicle development; ISS:UniProtKB.
DR   GO; GO:0001541; P:ovarian follicle development; ISS:UniProtKB.
DR   GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; ISS:UniProtKB.
DR   Gene3D; 2.10.90.10; -; 1.
DR   InterPro; IPR006799; AMH_N.
DR   InterPro; IPR029034; Cystine-knot_cytokine.
DR   InterPro; IPR021203; Muellerian-inhibiting_factor.
DR   InterPro; IPR001839; TGF-b_C.
DR   InterPro; IPR017948; TGFb_CS.
DR   PANTHER; PTHR15009; PTHR15009; 1.
DR   Pfam; PF04709; AMH_N; 1.
DR   Pfam; PF00019; TGF_beta; 1.
DR   PIRSF; PIRSF037270; Muellerian-inhibiting_factor; 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   Differentiation; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW   Gonadal differentiation; Growth factor; Reference proteome; Secreted;
KW   Signal.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000255"
FT   PROPEP          25..466
FT                   /evidence="ECO:0000250|UniProtKB:P03971"
FT                   /id="PRO_0000033744"
FT   CHAIN           467..575
FT                   /note="Muellerian-inhibiting factor"
FT                   /id="PRO_0000033745"
FT   SITE            466..467
FT                   /note="Cleavage"
FT                   /evidence="ECO:0000250|UniProtKB:P03971"
FT   CARBOHYD        78
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        344
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        477..541
FT                   /evidence="ECO:0000250|UniProtKB:P03971"
FT   DISULFID        503..572
FT                   /evidence="ECO:0000250|UniProtKB:P03971"
FT   DISULFID        507..574
FT                   /evidence="ECO:0000250|UniProtKB:P03971"
FT   DISULFID        540
FT                   /note="Interchain"
FT                   /evidence="ECO:0000250|UniProtKB:P03971"
SQ   SEQUENCE   575 AA;  60624 MW;  892B89C11AC8B5A8 CRC64;
     MPGPSLSLAL VLSAMGALLR PGTPREEVFS TSALPREQAT GSGALIFQQA WDWPLSSLWL
     PGSPLDPLCL VTLHGSGNGS RAPLRVVGVL SSYEQAFLEA VRRTHWGLSD LTTFAVCPAG
     NGQPVLPHLQ RLQAWLGEPG GRWLVVLHLE EVTWEPTPLL RFQEPPPGGA SPPELALLVV
     YPGPGLEVTV TGAGLPGTQS LCLTADSDFL ALVVDHPEGA WRRPGLALTL RRRGNGALLS
     TAQLQALLFG ADSRCFTRKT PALLLLLPAR SSAPMPAHGR LDLVPFPQPR ASPEPEEAPP
     SADPFLETLT RLVRALAGPP ARASPPRLAL DPGALAGFPQ GQVNLSDPAA LERLLDGEEP
     LLLLLPPTAA TTGVPATPQG PKSPLWAAGL ARRVAAELQA VAAELRALPG LPPAAPPLLA
     RLLALCPGNP DSPGGPLRAL LLLKALQGLR AEWRGRERSG SARAQRSAGA AAADGPCALR
     ELSVDLRAER SVLIPETYQA NNCQGACGWP QSDRNPRYGN HVVLLLKMQA RGATLARPPC
     CVPTAYTGKL LISLSEERIS AHHVPNMVAT ECGCR