MIS_MOUSE
ID MIS_MOUSE Reviewed; 554 AA.
AC P27106; A7E2R1; Q5EC55;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 2.
DT 03-AUG-2022, entry version 124.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RC STRAIN=129; TISSUE=Testis;
RX PubMed=1782869; DOI=10.1242/dev.113.2.613;
RA Muensterberg A., Lovell-Badge R.;
RT "Expression of the mouse anti-Mullerian hormone gene suggests a role in
RT both male and female sexual differentiation.";
RL Development 113:613-624(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129;
RA Dresser D.W., Jamin S., Atkins C.J., Guerrier D.;
RT "A GNRP-like gene shares a bidirectional promoter with SAP62 immediately
RT upstream of AMH.";
RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Johnson J.M., Altuntas C.Z., Tuohy V.K.;
RT "Immunogenicity of anti-Mullerian hormone.";
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-42.
RC STRAIN=129;
RX PubMed=8541848; DOI=10.1093/hmg/4.9.1613;
RA Dresser D.W., Hacker A., Lovell-Badge R., Guerrier D.;
RT "The genes for a spliceosome protein (SAP62) and the anti-Mullerian hormone
RT (AMH) are contiguous.";
RL Hum. Mol. Genet. 4:1613-1618(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [6]
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 [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=7954809; DOI=10.1016/0092-8674(94)90251-8;
RA Behringer R.R., Finegold M.J., Cate R.L.;
RT "Muellerian-inhibiting substance function during mammalian sexual
RT development.";
RL Cell 79:415-425(1994).
RN [8]
RP FUNCTION.
RX PubMed=9435237; DOI=10.1073/pnas.95.2.594;
RA Racine C., Rey R., Forest M.G., Louis F., Ferre A., Huhtaniemi I.,
RA Josso N., di Clemente N.;
RT "Receptors for anti-muellerian hormone on Leydig cells are responsible for
RT its effects on steroidogenesis and cell differentiation.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:594-599(1998).
RN [9]
RP FUNCTION.
RX PubMed=11606457; DOI=10.1210/endo.142.11.8486;
RA Durlinger A.L., Gruijters M.J., Kramer P., Karels B., Kumar T.R.,
RA Matzuk M.M., Rose U.M., de Jong F.H., Uilenbroek J.T., Grootegoed J.A.,
RA Themmen A.P.;
RT "Anti-Muellerian hormone attenuates the effects of FSH on follicle
RT development in the mouse ovary.";
RL Endocrinology 142:4891-4899(2001).
RN [10]
RP FUNCTION.
RX PubMed=11861535; DOI=10.1210/endo.143.3.8691;
RA Durlinger A.L., Gruijters M.J., Kramer P., Karels B., Ingraham H.A.,
RA Nachtigal M.W., Uilenbroek J.T., Grootegoed J.A., Themmen A.P.;
RT "Anti-Muellerian hormone inhibits initiation of primordial follicle growth
RT in the mouse ovary.";
RL Endocrinology 143:1076-1084(2002).
CC -!- FUNCTION: Plays an important role in several reproductive functions,
CC including Muellerian duct regression during male fetal sexua,l
CC differentiation and in the adult plays a role in Leydig cell
CC differentiation and function (PubMed:1782869, PubMed:9435237). In
CC female acts as a negative regulator of the primordial to primary
CC follicle transition and decreases FSH sensitivity of growing follicles
CC (PubMed:11861535, PubMed:11606457). Binds to its sole type II receptor,
CC AMHR2 that recruits type I receptors ACVR1 and BMPR1A which
CC subsequently activates the Smad pathway (By similarity).
CC {ECO:0000250|UniProtKB:P03971, ECO:0000269|PubMed:11606457,
CC ECO:0000269|PubMed:11861535, ECO:0000269|PubMed:1782869,
CC ECO:0000269|PubMed:9435237}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000250|UniProtKB:P03971}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P03971}.
CC -!- TISSUE SPECIFICITY: Expressed in Sertoli cells of fetal testes, and in
CC testes just after birth, but absent in adult testes. In female, AMH is
CC expressed after birth in the granulosa cells of the follicle.
CC {ECO:0000269|PubMed:1782869}.
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 AMHRII induces dissociation of the pro-region from the
CC mature C-terminal dimer. The N-terminal portion of the protein, despite
CC having no intrinsic activity, has the role of amplifying the activity
CC of the C-terminus. {ECO:0000250|UniProtKB:P03971}.
CC -!- DISRUPTION PHENOTYPE: Homozygous null mutant males have a complete male
CC reproductive tract and functional sperm, but also uterus and oviducts
CC (PubMed:7954809). Most are infertile due to female organs blocking
CC sperm transfer. Females are fertile with enlarged ovaries and atypical
CC follicles (PubMed:7954809). Furthemore in the absence of AMH, follicle
CC growth is more sensitive to stimulation by FSH (PubMed:11606457).
CC {ECO:0000269|PubMed:11606457, ECO:0000269|PubMed:7954809}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
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DR EMBL; X63240; CAA44912.1; -; Genomic_DNA.
DR EMBL; X83733; CAC10450.1; -; Genomic_DNA.
DR EMBL; AY911505; AAW84293.1; -; mRNA.
DR EMBL; GL456156; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC150477; AAI50478.1; -; mRNA.
DR PIR; S20100; S20100.
DR RefSeq; NP_031471.2; NM_007445.2.
DR AlphaFoldDB; P27106; -.
DR STRING; 10090.ENSMUSP00000043153; -.
DR GlyGen; P27106; 3 sites.
DR iPTMnet; P27106; -.
DR PhosphoSitePlus; P27106; -.
DR PaxDb; P27106; -.
DR PRIDE; P27106; -.
DR ProteomicsDB; 290084; -.
DR ProteomicsDB; 332474; -.
DR Antibodypedia; 22968; 548 antibodies from 32 providers.
DR DNASU; 11705; -.
DR GeneID; 11705; -.
DR KEGG; mmu:11705; -.
DR UCSC; uc007get.1; mouse.
DR CTD; 268; -.
DR MGI; MGI:88006; Amh.
DR VEuPathDB; HostDB:ENSMUSG00000035262; -.
DR eggNOG; KOG3900; Eukaryota.
DR HOGENOM; CLU_025681_1_0_1; -.
DR InParanoid; P27106; -.
DR OMA; DPAPLHD; -.
DR OrthoDB; 516965at2759; -.
DR PhylomeDB; P27106; -.
DR TreeFam; TF335595; -.
DR Reactome; R-MMU-201451; Signaling by BMP.
DR BioGRID-ORCS; 11705; 2 hits in 73 CRISPR screens.
DR PRO; PR:P27106; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; P27106; protein.
DR Bgee; ENSMUSG00000035262; Expressed in seminiferous tubule epithelium and 29 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0005160; F:transforming growth factor beta receptor binding; ISO:MGI.
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; IMP:UniProtKB.
DR GO; GO:0001880; P:Mullerian duct regression; ISS:UniProtKB.
DR GO; GO:2000355; P:negative regulation of ovarian follicle development; IMP:UniProtKB.
DR GO; GO:0001541; P:ovarian follicle development; IMP:UniProtKB.
DR GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:0001546; P:preantral ovarian follicle growth; ISO:MGI.
DR GO; GO:0007530; P:sex determination; IMP:UniProtKB.
DR GO; GO:0001655; P:urogenital system development; ISO: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..24
FT /evidence="ECO:0000255"
FT PROPEP 25..446
FT /evidence="ECO:0000250|UniProtKB:P03971"
FT /id="PRO_0000033748"
FT CHAIN 447..554
FT /note="Muellerian-inhibiting factor"
FT /id="PRO_0000033749"
FT SITE 446..447
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:P03971"
FT CARBOHYD 62
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 326
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 410
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 456..520
FT /evidence="ECO:0000250|UniProtKB:P03971"
FT DISULFID 482..551
FT /evidence="ECO:0000250|UniProtKB:P03971"
FT DISULFID 486..553
FT /evidence="ECO:0000250|UniProtKB:P03971"
FT DISULFID 519
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P03971"
FT CONFLICT 101
FT /note="C -> S (in Ref. 1; CAA44912 and 2; CAC10450)"
FT CONFLICT 165
FT /note="P -> S (in Ref. 1; CAA44912 and 2; CAC10450)"
FT CONFLICT 207
FT /note="S -> F (in Ref. 1; CAA44912 and 2; CAC10450)"
FT CONFLICT 350
FT /note="A -> T (in Ref. 1; CAA44912 and 2; CAC10450)"
FT CONFLICT 358..359
FT /note="MP -> IR (in Ref. 1; CAA44912 and 2; CAC10450)"
FT CONFLICT 445..452
FT /note="GRSAGTGT -> RAQRGDKGQ (in Ref. 1; CAA44912 and 2;
FT CAC10450)"
FT /evidence="ECO:0000305"
FT CONFLICT 487
FT /note="A -> R (in Ref. 1; CAA44912 and 2; CAC10450)"
FT CONFLICT 541
FT /note="H -> D (in Ref. 1; CAA44912 and 2; CAC10450)"
FT CONFLICT 554
FT /note="V -> R (in Ref. 1; CAA44912 and 2; CAC10450)"
SQ SEQUENCE 554 AA; 59244 MW; 5746431AB00D0C98 CRC64;
MQGPHLSPLV LLLATMGAVL QPEAVENLAT NTRGLIFLED ELWPPSSPPE PLCLVTVRGE
GNTSRASLRV VGGLNSYEYA FLEAVQESRW GPQDLATFGV CSTDSQATLP ALQRLGAWLG
ETGEQQLLVL HLAEVIWEPE LLLKFQEPPP GGASRWEQAL LVLYPGPGPQ VTVTGTGLRG
TQNLCPTRDT RYLVLTVDFP AGAWSGSGLI LTLQPSREGA TLSIDQLQAF LFGSDSRCFT
RMTPTLVVLP PAEPSPQPAH GQLDTMPFPQ PGLSLEPEAL PHSADPFLET LTRLVRALRG
PLTQASNTQL ALDPGALASF PQGLVNLSDP AALGRLLDWE EPLLLLLSPA AATEREPMPL
HGPASAPWAA GLQRRVAVEL QAAASELRDL PGLPPTAPPL LARLLALCPN DSRSSGDPLR
ALLLLKALQG LRAEWHGREG RGRTGRSAGT GTDGPCALRE LSVDLRAERS VLIPETYQAN
NCQGACAWPQ SDRNPRYGNH VVLLLKMQAR GAALGRLPCC VPTAYAGKLL ISLSEERISA
HHVPNMVATE CGCV
