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Muellerian-inhibiting factor (Anti-Muellerian hormone) (AMH) (Muellerian-inhibiting substance) (MIS)

 MIS_HUMAN               Reviewed;         560 AA.
P03971; O75246; Q6GTN3;
23-OCT-1986, integrated into UniProtKB/Swiss-Prot.
30-NOV-2010, sequence version 3.
08-MAY-2019, entry version 186.
RecName: Full=Muellerian-inhibiting factor;
AltName: Full=Anti-Muellerian hormone;
Short=AMH;
AltName: Full=Muellerian-inhibiting substance;
Short=MIS;
Flags: Precursor;
Name=AMH; Synonyms=MIF;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-49 AND ALA-515.
PubMed=3754790; DOI=10.1016/0092-8674(86)90783-X;
Cate R.L., Mattaliano R.J., Hession C., Tizard R., Farber N.M.,
Cheung A., Ninfa E.G., Frey A.Z., Gash D.J., Chow E.P., Fisher R.A.,
Bertonis J.M., Torres G., Wallner B.P., Ramachandran K.L., Ragin R.C.,
Manganaro T.F., McLaughlin D.T., Donahoe P.K.;
"Isolation of the bovine and human genes for Mullerian inhibiting
substance and expression of the human gene in animal cells.";
Cell 45:685-698(1986).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15057824; DOI=10.1038/nature02399;
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
Rubin E.M., Lucas S.M.;
"The DNA sequence and biology of human chromosome 19.";
Nature 428:529-535(2004).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-515.
TISSUE=Brain;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[4]
VARIANT ARG-325.
PubMed=1483695; DOI=10.1007/BF00220465;
Carre-Eusebe D., Imbeaud S., Harbison M., New M.I., Josso N.,
Picard J.-Y.;
"Variants of the anti-Mullerian hormone gene in a compound
heterozygote with the persistent Mullerian duct syndrome and his
family.";
Hum. Genet. 90:389-394(1992).
[5]
VARIANTS PMDS1 GLY-12; PRO-70; VAL-101; TRP-123; CYS-167; CYS-194 AND
ALA-477.
PubMed=8162013; DOI=10.1093/hmg/3.1.125;
Imbeaud S., Carre-Eusebe D., Rey R., Belville C., Josso N.,
Picard J.-Y.;
"Molecular genetics of the persistent Mullerian duct syndrome: a study
of 19 families.";
Hum. Mol. Genet. 3:125-131(1994).
[6]
VARIANTS PMDS1 GLN-506 AND TYR-525.
PubMed=8872466; DOI=10.1093/hmg/5.9.1269;
Imbeaud S., Belville C., Messika-Zeitoun L., Rey R., di Clemente N.,
Josso N., Picard J.-Y.;
"A 27 base-pair deletion of the anti-Muellerian type II receptor gene
is the most common cause of the persistent Muellerian duct syndrome.";
Hum. Mol. Genet. 5:1269-1277(1996).
-!- FUNCTION: This glycoprotein, produced by the Sertoli cells of the
testis, causes regression of the Muellerian duct. It is also able
to inhibit the growth of tumors derived from tissues of Muellerian
duct origin.
-!- SUBUNIT: Homodimer; disulfide-linked.
-!- SUBCELLULAR LOCATION: Secreted.
-!- DISEASE: Persistent Muellerian duct syndrome 1 (PMDS1)
[MIM:261550]: A form of male pseudohermaphroditism characterized
by a failure of Muellerian duct regression in otherwise normal
males. {ECO:0000269|PubMed:8162013, ECO:0000269|PubMed:8872466}.
Note=The disease is caused by mutations affecting the gene
represented in this entry.
-!- MISCELLANEOUS: Although it does not compete with EGF for receptor
binding sites, MIS can inhibit the autophosphorylation of the EGF
receptor in vitro.
-!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
-!- WEB RESOURCE: Name=Wikipedia; Note=Anti-Mullerian hormone entry;
URL="https://en.wikipedia.org/wiki/Anti-m%C3%BCllerian_hormone";
-----------------------------------------------------------------------
Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
Distributed under the Creative Commons Attribution (CC BY 4.0) License
-----------------------------------------------------------------------
EMBL; K03474; AAA98805.1; -; Genomic_DNA.
EMBL; AC005263; AAC25614.1; -; Genomic_DNA.
EMBL; BC049194; AAH49194.1; -; mRNA.
CCDS; CCDS12085.1; -.
PIR; A01397; WFHUM.
RefSeq; NP_000470.2; NM_000479.4.
SMR; P03971; -.
BioGrid; 106765; 5.
IntAct; P03971; 4.
STRING; 9606.ENSP00000221496; -.
iPTMnet; P03971; -.
PhosphoSitePlus; P03971; -.
BioMuta; AMH; -.
DMDM; 313104218; -.
MaxQB; P03971; -.
PaxDb; P03971; -.
PeptideAtlas; P03971; -.
PRIDE; P03971; -.
ProteomicsDB; 51624; -.
DNASU; 268; -.
Ensembl; ENST00000221496; ENSP00000221496; ENSG00000104899.
GeneID; 268; -.
KEGG; hsa:268; -.
UCSC; uc002lvh.3; human.
CTD; 268; -.
DisGeNET; 268; -.
GeneCards; AMH; -.
HGNC; HGNC:464; AMH.
HPA; HPA066973; -.
MalaCards; AMH; -.
MIM; 261550; phenotype.
MIM; 600957; gene.
neXtProt; NX_P03971; -.
OpenTargets; ENSG00000104899; -.
Orphanet; 2856; Persistent Muellerian duct syndrome.
PharmGKB; PA24769; -.
eggNOG; KOG3900; Eukaryota.
eggNOG; ENOG410XT8Z; LUCA.
GeneTree; ENSGT00390000006337; -.
HOGENOM; HOG000113593; -.
InParanoid; P03971; -.
KO; K04665; -.
OMA; DPAPLHD; -.
OrthoDB; 516965at2759; -.
PhylomeDB; P03971; -.
TreeFam; TF335595; -.
Reactome; R-HSA-201451; Signaling by BMP.
SignaLink; P03971; -.
SIGNOR; P03971; -.
GenomeRNAi; 268; -.
PRO; PR:P03971; -.
Proteomes; UP000005640; Chromosome 19.
Bgee; ENSG00000104899; Expressed in 89 organ(s), highest expression level in cerebellar hemisphere.
Genevisible; P03971; HS.
GO; GO:0005576; C:extracellular region; TAS:Reactome.
GO; GO:0005615; C:extracellular space; IBA:GO_Central.
GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
GO; GO:0005179; F:hormone activity; TAS:ProtInc.
GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB.
GO; GO:0005160; F:transforming growth factor beta receptor binding; IEA:Ensembl.
GO; GO:0007568; P:aging; IEA:Ensembl.
GO; GO:0030509; P:BMP signaling pathway; TAS:Reactome.
GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
GO; GO:0007506; P:gonadal mesoderm development; IEA:UniProtKB-KW.
GO; GO:0001880; P:Mullerian duct regression; IDA:UniProtKB.
GO; GO:2000355; P:negative regulation of ovarian follicle development; IEA:Ensembl.
GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IEA:Ensembl.
GO; GO:0001546; P:preantral ovarian follicle growth; IEA:Ensembl.
GO; GO:0042493; P:response to drug; IEA:Ensembl.
GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
GO; GO:0007530; P:sex determination; TAS:ProtInc.
GO; GO:0007548; P:sex differentiation; TAS:UniProtKB.
GO; GO:0001655; P:urogenital system development; IBA:GO_Central.
Gene3D; 2.10.90.10; -; 1.
InterPro; IPR006799; AMH_N.
InterPro; IPR029034; Cystine-knot_cytokine.
InterPro; IPR021203; Muellerian-inhibiting_factor.
InterPro; IPR001839; TGF-b_C.
InterPro; IPR017948; TGFb_CS.
PANTHER; PTHR15009; PTHR15009; 1.
Pfam; PF04709; AMH_N; 1.
Pfam; PF00019; TGF_beta; 1.
PIRSF; PIRSF037270; Muellerian-inhibiting_factor; 1.
SMART; SM00204; TGFB; 1.
SUPFAM; SSF57501; SSF57501; 1.
PROSITE; PS00250; TGF_BETA_1; 1.
PROSITE; PS51362; TGF_BETA_2; 1.
1: Evidence at protein level;
Complete proteome; Differentiation; Disease mutation; Disulfide bond;
Glycoprotein; Gonadal differentiation; Growth factor; Polymorphism;
Pseudohermaphroditism; Reference proteome; Secreted; Signal.
SIGNAL 1 18 {ECO:0000255}.
PROPEP 19 25 {ECO:0000255}.
/FTId=PRO_0000033746.
CHAIN 26 560 Muellerian-inhibiting factor.
/FTId=PRO_0000033747.
CARBOHYD 64 64 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 329 329 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 462 526 {ECO:0000250}.
DISULFID 488 557 {ECO:0000250}.
DISULFID 492 559 {ECO:0000250}.
DISULFID 525 525 Interchain. {ECO:0000250}.
VARIANT 12 12 V -> G (in PMDS1; dbSNP:rs149082963).
{ECO:0000269|PubMed:8162013}.
/FTId=VAR_007483.
VARIANT 49 49 S -> I (in dbSNP:rs10407022).
{ECO:0000269|PubMed:3754790}.
/FTId=VAR_007484.
VARIANT 70 70 L -> P (in PMDS1).
{ECO:0000269|PubMed:8162013}.
/FTId=VAR_007485.
VARIANT 101 101 G -> V (in PMDS1).
{ECO:0000269|PubMed:8162013}.
/FTId=VAR_007486.
VARIANT 123 123 R -> W (in PMDS1; dbSNP:rs569914235).
{ECO:0000269|PubMed:8162013}.
/FTId=VAR_007487.
VARIANT 167 167 Y -> C (in PMDS1; dbSNP:rs371874189).
{ECO:0000269|PubMed:8162013}.
/FTId=VAR_007488.
VARIANT 185 185 Q -> E (in dbSNP:rs200523942).
/FTId=VAR_007489.
VARIANT 194 194 R -> C (in PMDS1; dbSNP:rs777003373).
{ECO:0000269|PubMed:8162013}.
/FTId=VAR_007490.
VARIANT 325 325 Q -> R (in dbSNP:rs140765565).
{ECO:0000269|PubMed:1483695}.
/FTId=VAR_007491.
VARIANT 477 477 V -> A (in PMDS1; dbSNP:rs1358787117).
{ECO:0000269|PubMed:8162013}.
/FTId=VAR_007492.
VARIANT 506 506 H -> Q (in PMDS1; dbSNP:rs138571039).
{ECO:0000269|PubMed:8872466}.
/FTId=VAR_031027.
VARIANT 515 515 V -> A (in dbSNP:rs10417628).
{ECO:0000269|PubMed:15489334,
ECO:0000269|PubMed:3754790}.
/FTId=VAR_065100.
VARIANT 525 525 C -> Y (in PMDS1).
{ECO:0000269|PubMed:8872466}.
/FTId=VAR_031028.
SEQUENCE 560 AA; 59195 MW; D05DCEE4FEDF94C2 CRC64;
MRDLPLTSLA LVLSALGALL GTEALRAEEP AVGTSGLIFR EDLDWPPGSP QEPLCLVALG
GDSNGSSSPL RVVGALSAYE QAFLGAVQRA RWGPRDLATF GVCNTGDRQA ALPSLRRLGA
WLRDPGGQRL VVLHLEEVTW EPTPSLRFQE PPPGGAGPPE LALLVLYPGP GPEVTVTRAG
LPGAQSLCPS RDTRYLVLAV DRPAGAWRGS GLALTLQPRG EDSRLSTARL QALLFGDDHR
CFTRMTPALL LLPRSEPAPL PAHGQLDTVP FPPPRPSAEL EESPPSADPF LETLTRLVRA
LRVPPARASA PRLALDPDAL AGFPQGLVNL SDPAALERLL DGEEPLLLLL RPTAATTGDP
APLHDPTSAP WATALARRVA AELQAAAAEL RSLPGLPPAT APLLARLLAL CPGGPGGLGD
PLRALLLLKA LQGLRVEWRG RDPRGPGRAQ RSAGATAADG PCALRELSVD LRAERSVLIP
ETYQANNCQG VCGWPQSDRN PRYGNHVVLL LKMQVRGAAL ARPPCCVPTA YAGKLLISLS
EERISAHHVP NMVATECGCR


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Pathways :
WP1981: Thyroxine (thyroid hormone) production
WP2355: Corticotropin-releasing hormone
WP1065: Endochondral Ossification
WP1206: Signaling of Hepatocyte Growth Factor Receptor
WP444: Signaling of Hepatocyte Growth Factor Receptor
WP828: Endochondral Ossification
WP1308: Endochondral Ossification
WP1789: Binding of RNA by Insulin-like Growth Factor-2 mRNA Binding Proteins (IGF2BPs/IMPs/VICKZs)
WP947: Endochondral Ossification
WP1963: The effect of Glucocorticoids on target gene expression
WP1046: Signaling of Hepatocyte Growth Factor Receptor
WP2148: Brain derived neurotrophic factor
WP313: Signaling of Hepatocyte Growth Factor Receptor
WP1181: Endochondral Ossification
WP1270: Endochondral Ossification
WP810: Signaling of Hepatocyte Growth Factor Receptor
WP94: Signaling of Hepatocyte Growth Factor Receptor
WP1531: Vitamin D synthesis
WP193: Signaling of Hepatocyte Growth Factor Receptor
WP1983: Splicing factor NOVA regulated synpatic proteins
WP272: Blood Clotting Cascade
WP1162: Signaling of Hepatocyte Growth Factor Receptor
WP1235: Signaling of Hepatocyte Growth Factor Receptor
WP474: Endochondral Ossification
WP927: Signaling of Hepatocyte Growth Factor Receptor

Related Genes :
[NR5A1 AD4BP FTZF1 SF1] Steroidogenic factor 1 (SF-1) (STF-1) (hSF-1) (Adrenal 4-binding protein) (Fushi tarazu factor homolog 1) (Nuclear receptor subfamily 5 group A member 1) (Steroid hormone receptor Ad4BP)
[MIF GLIF MMIF] Macrophage migration inhibitory factor (MIF) (EC 5.3.2.1) (Glycosylation-inhibiting factor) (GIF) (L-dopachrome isomerase) (L-dopachrome tautomerase) (EC 5.3.3.12) (Phenylpyruvate tautomerase)
[Mif] Macrophage migration inhibitory factor (MIF) (EC 5.3.2.1) (Delayed early response protein 6) (DER6) (Glycosylation-inhibiting factor) (GIF) (L-dopachrome isomerase) (L-dopachrome tautomerase) (EC 5.3.3.12) (Phenylpyruvate tautomerase)
[SST] Somatostatin (Growth hormone release-inhibiting factor) [Cleaved into: Somatostatin-28; Somatostatin-14 (SST-14); Neuronostatin (NST)]
[HIF1AN FIH1] Hypoxia-inducible factor 1-alpha inhibitor (EC 1.14.11.30) (EC 1.14.11.n4) (Factor inhibiting HIF-1) (FIH-1) (Hypoxia-inducible factor asparagine hydroxylase)
[GNAI1] Guanine nucleotide-binding protein G(i) subunit alpha-1 (Adenylate cyclase-inhibiting G alpha protein)
[SRY TDF] Sex-determining region Y protein (Testis-determining factor)
[FADD MORT1 GIG3] FAS-associated death domain protein (FAS-associating death domain-containing protein) (Growth-inhibiting gene 3 protein) (Mediator of receptor induced toxicity) (Protein FADD)
[ACTA2 ACTSA ACTVS GIG46] Actin, aortic smooth muscle (Alpha-actin-2) (Cell growth-inhibiting gene 46 protein) [Cleaved into: Actin, aortic smooth muscle, intermediate form]
[SERPINA3 AACT GIG24 GIG25] Alpha-1-antichymotrypsin (ACT) (Cell growth-inhibiting gene 24/25 protein) (Serpin A3) [Cleaved into: Alpha-1-antichymotrypsin His-Pro-less]
[PER3 GIG13] Period circadian protein homolog 3 (hPER3) (Cell growth-inhibiting gene 13 protein) (Circadian clock protein PERIOD 3)
[MIF] Macrophage migration inhibitory factor (MIF) (EC 5.3.2.1) (Glycosylation-inhibiting factor) (GIF) (L-dopachrome isomerase) (L-dopachrome tautomerase) (EC 5.3.3.12) (Phenylpyruvate tautomerase)
[Sst Smst] Somatostatin (somatotropin release-inhibiting factor) (SRIF) [Cleaved into: Antrin; Somatostatin-28; Somatostatin-14; Neuronostatin (NST)]
[PGIP2] Polygalacturonase inhibitor 2 (Polygalacturonase-inhibiting protein 2) (PGIP-2)
[] Molt-inhibiting hormone (MIH)
[GNAI2 GNAI2B] Guanine nucleotide-binding protein G(i) subunit alpha-2 (Adenylate cyclase-inhibiting G alpha protein)
[FOLH1 FOLH NAALAD1 PSM PSMA GIG27] Glutamate carboxypeptidase 2 (EC 3.4.17.21) (Cell growth-inhibiting gene 27 protein) (Folate hydrolase 1) (Folylpoly-gamma-glutamate carboxypeptidase) (FGCP) (Glutamate carboxypeptidase II) (GCPII) (Membrane glutamate carboxypeptidase) (mGCP) (N-acetylated-alpha-linked acidic dipeptidase I) (NAALADase I) (Prostate-specific membrane antigen) (PSM) (PSMA) (Pteroylpoly-gamma-glutamate carboxypeptidase)
[SAP18 GIG38] Histone deacetylase complex subunit SAP18 (18 kDa Sin3-associated polypeptide) (2HOR0202) (Cell growth-inhibiting gene 38 protein) (Sin3-associated polypeptide p18)
[Gnai2 Gnai-2] Guanine nucleotide-binding protein G(i) subunit alpha-2 (Adenylate cyclase-inhibiting G alpha protein)
[Gnai2 Gnai-2] Guanine nucleotide-binding protein G(i) subunit alpha-2 (Adenylate cyclase-inhibiting G alpha protein)
[GNAI1] Guanine nucleotide-binding protein G(i) subunit alpha-1 (Adenylate cyclase-inhibiting G alpha protein)
[HAO2 HAOX2 GIG16] Hydroxyacid oxidase 2 (HAOX2) (EC 1.1.3.15) ((S)-2-hydroxy-acid oxidase, peroxisomal) (Cell growth-inhibiting gene 16 protein) (Long chain alpha-hydroxy acid oxidase) (Long-chain L-2-hydroxy acid oxidase)
[RPL35A GIG33] 60S ribosomal protein L35a (Cell growth-inhibiting gene 33 protein) (Large ribosomal subunit protein eL33)
[GNAI2] Guanine nucleotide-binding protein G(i) subunit alpha-2 (Adenylate cyclase-inhibiting G alpha protein)
[LTF GIG12 LF] Lactotransferrin (Lactoferrin) (EC 3.4.21.-) (Growth-inhibiting protein 12) (Talalactoferrin) [Cleaved into: Lactoferricin-H (Lfcin-H); Kaliocin-1; Lactoferroxin-A; Lactoferroxin-B; Lactoferroxin-C]
[] Crustacean hyperglycemic hormones isoform A [Cleaved into: CHH precursor-related peptide A (CPRP-A); Crustacean hyperglycemic hormone A (CHH-A) (Molt-inhibiting hormone) (MIH)]
[WNT4 UNQ426/PRO864] Protein Wnt-4
[SERPING1 C1IN C1NH] Plasma protease C1 inhibitor (C1 Inh) (C1Inh) (C1 esterase inhibitor) (C1-inhibiting factor) (Serpin G1)
[DNAJC15 DNAJD1 GIG22 HSD18] DnaJ homolog subfamily C member 15 (Cell growth-inhibiting gene 22 protein) (Methylation-controlled J protein) (MCJ)
[rsrA SCO5217] Anti-sigma factor RsrA (Regulator of SigR) (Sigma-R anti-sigma factor RsrA)

Bibliography :
[29947765] Expression of Müllerian-Inhibiting Substance/Anti-Müllerian Hormone Type II Receptor in the Human Theca Cells.
[28643088] Potential therapeutic applications of human anti-Müllerian hormone (AMH) analogues in reproductive medicine.
[28599968] The possible role of AMH in shortening the gubernacular cord in testicular descent: A reappraisal of the evidence.
[27103037] A PCR assay detects a male-specific duplicated copy of Anti-Müllerian hormone (amh) in the lingcod (Ophiodon elongatus).
[27042447] Chemotherapy: Impact on Anti-Müllerian Hormone Levels in Breast Carcinoma.
[25264524] Müllerian inhibiting substance/anti-Müllerian hormone: A novel treatment for gynecologic tumors.
[22962306] The Müllerian inhibiting substance type 2 receptor suppresses tumorigenesis in testes with sustained β-catenin signaling.
[22131240] Anti-mullerian hormone as a predictive factor in assisted reproductive technique of polycystic ovary syndrome patients.
[21573503] Identification of characteristic molecular signature of Müllerian inhibiting substance in human HPV-related cervical cancer cells.
[21490063] β-Catenin is essential for Müllerian duct regression during male sexual differentiation.