MIS_RAT
ID MIS_RAT Reviewed; 553 AA.
AC P49000;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Muellerian-inhibiting factor;
DE AltName: Full=Anti-Muellerian hormone;
DE Short=AMH;
DE AltName: Full=Muellerian-inhibiting substance;
DE Short=MIS;
DE Flags: Precursor;
GN Name=Amh;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1572639; DOI=10.1016/0888-7543(92)90291-y;
RA Haqq C., Lee M.M., Tizard R., Wysk M., Demarinis J., Donahoe P.K.,
RA Cate R.L.;
RT "Isolation of the rat gene for Mullerian inhibiting substance.";
RL Genomics 12:665-669(1992).
RN [2]
RP TISSUE SPECIFICITY.
RX PubMed=7588229; DOI=10.1210/endo.136.11.7588229;
RA Baarends W.M., Uilenbroek J.T., Kramer P., Hoogerbrugge J.W.,
RA van Leeuwen E.C., Themmen A.P., Grootegoed J.A.;
RT "Anti-muellerian hormone and anti-muellerian hormone type II receptor
RT messenger ribonucleic acid expression in rat ovaries during postnatal
RT development, the estrous cycle, and gonadotropin-induced follicle growth.";
RL Endocrinology 136:4951-4962(1995).
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: Mainly expressed in granulosa cells from preantral
CC and small antral follicles. {ECO:0000269|PubMed:7588229}.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; S98336; AAB22104.1; -; Genomic_DNA.
DR PIR; A42499; A42499.
DR RefSeq; NP_037034.1; NM_012902.1.
DR AlphaFoldDB; P49000; -.
DR SMR; P49000; -.
DR STRING; 10116.ENSRNOP00000026220; -.
DR CarbonylDB; P49000; -.
DR GlyGen; P49000; 2 sites.
DR PaxDb; P49000; -.
DR Ensembl; ENSRNOT00000026220; ENSRNOP00000026220; ENSRNOG00000019377.
DR GeneID; 25378; -.
DR KEGG; rno:25378; -.
DR UCSC; RGD:2108; rat.
DR CTD; 268; -.
DR RGD; 2108; Amh.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00390000006337; -.
DR HOGENOM; CLU_025681_1_0_1; -.
DR InParanoid; P49000; -.
DR OMA; DPAPLHD; -.
DR OrthoDB; 516965at2759; -.
DR PhylomeDB; P49000; -.
DR TreeFam; TF335595; -.
DR Reactome; R-RNO-201451; Signaling by BMP.
DR PRO; PR:P49000; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000019377; Expressed in ovary and 4 other tissues.
DR Genevisible; P49000; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0005102; F:signaling receptor binding; ISO:RGD.
DR GO; GO:0005160; F:transforming growth factor beta receptor binding; IDA:MGI.
DR GO; GO:0005114; F:type II transforming growth factor beta receptor binding; ISS:UniProtKB.
DR GO; GO:0007568; P:aging; IEP:RGD.
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; IDA:RGD.
DR GO; GO:0001541; P:ovarian follicle development; ISO:RGD.
DR GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:RGD.
DR GO; GO:0001546; P:preantral ovarian follicle growth; IDA:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0007530; P:sex determination; ISO:RGD.
DR GO; GO:0001655; P:urogenital system development; IDA:MGI.
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 2: Evidence at transcript level;
KW Differentiation; Disulfide bond; Glycoprotein; Gonadal differentiation;
KW Growth factor; Reference proteome; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..445
FT /evidence="ECO:0000250|UniProtKB:P03971"
FT /id="PRO_0000033752"
FT CHAIN 446..553
FT /note="Muellerian-inhibiting factor"
FT /id="PRO_0000033753"
FT SITE 445..446
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:P03971"
FT CARBOHYD 325
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 409
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 455..519
FT /evidence="ECO:0000250|UniProtKB:P03971"
FT DISULFID 481..550
FT /evidence="ECO:0000250|UniProtKB:P03971"
FT DISULFID 485..552
FT /evidence="ECO:0000250|UniProtKB:P03971"
FT DISULFID 518
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P03971"
SQ SEQUENCE 553 AA; 58889 MW; 75DAF3949A038A69 CRC64;
MQGPHLSLLL LLLATMGAVL QADTVEELTN TRGLIFLEDG VWPPSSPPEP LCLVAVRGEG
DTSKASLTVV GGLHSYEHAF LEAVQESRWG PQDLATFGVC STDSQTTLPA LQRLGAWLGE
TGEQQLLVLH LAEVIWEPQL LLKFQEPPPG GASRWEQALL VLYPGPGPQV TVTGAGLQGT
QSLCPTRDTR YLVLTVHFPA GAWSGSGLAL TLQPSKEGAT LTIAQLQAFL FGSDSRCFTR
MTPTLVLLPP TGPTPQPAHG QLDTVPFPQP GLSLEPEDLP HSADPFLETL TRLVRALRGP
LTRASNTRLA LDPGALASFP QGLVNLSDPV ALGRLLDGEE PLLLLLSPAA ATVGEPMRLH
SPTSAPWAAG LARRVAVELQ AAASELRDLP GLPPTAPPLL SRLLALCPND SRSAGDPLRA
LLLLKALQGL RAEWRGREGR GRAGRSKGTG TDGLCALREL SVDLRAERSV LIPETYQANN
CQGACAWPQS DRNPRYGNHV VLLLKMQARG AALGRLPCCV PTAYTGKLLI SLSEEHISAH
HVPNMVATEC GCR
