P03971 (MIS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Muellerian-inhibiting factor

Alternative name(s):
Anti-Muellerian hormone
Short name=AMH
Muellerian-inhibiting substance
Short name=MIS

Gene names

Name:	AMH
Synonyms:	MIF

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	560 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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 structure	Homodimer; disulfide-linked.
Subcellular location	Secreted.
Involvement in 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Ref.6
Miscellaneous	Although it does not compete with EGF for receptor binding sites, MIS can inhibit the autophosphorylation of the EGF receptor in vitro.
Sequence similarities	Belongs to the TGF-beta family.

Ontologies

Keywords
Biological process	Differentiation Gonadal differentiation
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation Pseudohermaphroditism
Domain	Signal
Molecular function	Growth factor
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Mullerian duct regression Inferred from direct assay PubMed 14695376. Source: UniProtKB aging Inferred from electronic annotation. Source: Compara cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW cell-cell signaling Traceable author statement Ref.1. Source: ProtInc gonadal mesoderm development Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of NF-kappaB transcription factor activity Inferred from electronic annotation. Source: Compara positive regulation of gene expression Inferred from mutant phenotype PubMed 14695376. Source: UniProtKB preantral ovarian follicle growth Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to organic cyclic compound Inferred from electronic annotation. Source: Compara sex determination Traceable author statement Ref.1. Source: ProtInc urogenital system development Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from electronic annotation. Source: Compara extracellular space Traceable author statement Ref.1. Source: ProtInc
Molecular_function	hormone activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Potential
	Propeptide	19 – 25	7	Potential		PRO_0000033746
	Chain	26 – 560	535	Muellerian-inhibiting factor		PRO_0000033747
Amino acid modifications
	Glycosylation	64	1	N-linked (GlcNAc...) Potential
	Glycosylation	329	1	N-linked (GlcNAc...) Potential
	Disulfide bond	462 ↔ 526		By similarity
	Disulfide bond	488 ↔ 557		By similarity
	Disulfide bond	492 ↔ 559		By similarity
	Disulfide bond	525		Interchain By similarity
Natural variations
	Natural variant	12	1	V → G in PMDS1. Ref.5		VAR_007483
	Natural variant	49	1	S → I. Ref.1 Corresponds to variant rs10407022 [ dbSNP | Ensembl ].		VAR_007484
	Natural variant	70	1	L → P in PMDS1. Ref.5		VAR_007485
	Natural variant	101	1	G → V in PMDS1. Ref.5		VAR_007486
	Natural variant	123	1	R → W in PMDS1. Ref.5		VAR_007487
	Natural variant	167	1	Y → C in PMDS1. Ref.5		VAR_007488
	Natural variant	185	1	Q → E.		VAR_007489
	Natural variant	194	1	R → C in PMDS1. Ref.5		VAR_007490
	Natural variant	325	1	Q → R. Ref.4		VAR_007491
	Natural variant	477	1	V → A in PMDS1. Ref.5		VAR_007492
	Natural variant	506	1	H → Q in PMDS1. Ref.6		VAR_031027
	Natural variant	515	1	V → A. Ref.1 Ref.3 Corresponds to variant rs10417628 [ dbSNP | Ensembl ].		VAR_065100
	Natural variant	525	1	C → Y in PMDS1. Ref.6		VAR_031028

Sequences

	Sequence		Length	Mass (Da)
	P03971 [UniParc]. Last modified November 30, 2010. Version 3. Checksum: D05DCEE4FEDF94C2	FASTA	560	59,195
	10 20 30 40 50 60 MRDLPLTSLA LVLSALGALL GTEALRAEEP AVGTSGLIFR EDLDWPPGSP QEPLCLVALG 70 80 90 100 110 120 GDSNGSSSPL RVVGALSAYE QAFLGAVQRA RWGPRDLATF GVCNTGDRQA ALPSLRRLGA 130 140 150 160 170 180 WLRDPGGQRL VVLHLEEVTW EPTPSLRFQE PPPGGAGPPE LALLVLYPGP GPEVTVTRAG 190 200 210 220 230 240 LPGAQSLCPS RDTRYLVLAV DRPAGAWRGS GLALTLQPRG EDSRLSTARL QALLFGDDHR 250 260 270 280 290 300 CFTRMTPALL LLPRSEPAPL PAHGQLDTVP FPPPRPSAEL EESPPSADPF LETLTRLVRA 310 320 330 340 350 360 LRVPPARASA PRLALDPDAL AGFPQGLVNL SDPAALERLL DGEEPLLLLL RPTAATTGDP 370 380 390 400 410 420 APLHDPTSAP WATALARRVA AELQAAAAEL RSLPGLPPAT APLLARLLAL CPGGPGGLGD 430 440 450 460 470 480 PLRALLLLKA LQGLRVEWRG RDPRGPGRAQ RSAGATAADG PCALRELSVD LRAERSVLIP 490 500 510 520 530 540 ETYQANNCQG VCGWPQSDRN PRYGNHVVLL LKMQVRGAAL ARPPCCVPTA YAGKLLISLS 550 560 EERISAHHVP NMVATECGCR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of the bovine and human genes for Mullerian inhibiting substance and expression of the human gene in animal cells." 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. Cell 45:685-698(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-49 AND ALA-515.
[2]	"The DNA sequence and biology of human chromosome 19." 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. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-515. Tissue: Brain.
[4]	"Variants of the anti-Mullerian hormone gene in a compound heterozygote with the persistent Mullerian duct syndrome and his family." Carre-Eusebe D., Imbeaud S., Harbison M., New M.I., Josso N., Picard J.-Y. Hum. Genet. 90:389-394(1992) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ARG-325.
[5]	"Molecular genetics of the persistent Mullerian duct syndrome: a study of 19 families." Imbeaud S., Carre-Eusebe D., Rey R., Belville C., Josso N., Picard J.-Y. Hum. Mol. Genet. 3:125-131(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PMDS1 GLY-12; PRO-70; VAL-101; TRP-123; CYS-167; CYS-194 AND ALA-477.
[6]	"A 27 base-pair deletion of the anti-Muellerian type II receptor gene is the most common cause of the persistent Muellerian duct syndrome." Imbeaud S., Belville C., Messika-Zeitoun L., Rey R., di Clemente N., Josso N., Picard J.-Y. Hum. Mol. Genet. 5:1269-1277(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PMDS1 GLN-506 AND TYR-525.
+	Additional computationally mapped references.

Web resources

Wikipedia

Anti-Mullerian hormone entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	K03474 Genomic DNA. Translation: AAA98805.1. AC005263 Genomic DNA. Translation: AAC25614.1. BC049194 mRNA. Translation: AAH49194.1.
IPI	IPI00008577.
PIR	WFHUM. A01397.
RefSeq	NP_000470.2. NM_000479.3.
UniGene	Hs.112432.
3D structure databases
ProteinModelPortal	P03971.
SMR	P03971. Positions 459-560.
ModBase	Search...
Protein-protein interaction databases
IntAct	P03971. 3 interactions.
STRING	9606.ENSP00000221496.
PTM databases
PhosphoSite	P03971.
Polymorphism databases
DMDM	160332382.
Proteomic databases
PaxDb	P03971.
PRIDE	P03971.
Protocols and materials databases
DNASU	268.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000221496; ENSP00000221496; ENSG00000104899.
GeneID	268.
KEGG	hsa:268.
UCSC	uc002lvh.2. human.
Organism-specific databases
CTD	268.
GeneCards	GC19P002251.
HGNC	HGNC:464. AMH.
HPA	CAB031933.
MIM	261550. phenotype. 600957. gene.
neXtProt	NX_P03971.
Orphanet	2856. Persistent Mullerian duct syndrome.
PharmGKB	PA24769.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG290074.
HOGENOM	HOG000113593.
HOVERGEN	HBG006358.
InParanoid	P03971.
KO	K04665.
OMA	QRARWGP.
OrthoDB	EOG4HT8TF.
PhylomeDB	P03971.
Gene expression databases
Bgee	P03971.
CleanEx	HS_AMH. HS_MIF.
Genevestigator	P03971.
GermOnline	ENSG00000104899. Homo sapiens.
Family and domain databases
InterPro	IPR006799. AMH_N. IPR021203. Muellerian-inhibiting_factor. IPR001839. TGF-b_C. IPR017948. TGFb_CS. [Graphical view]
PANTHER	PTHR15009. PTHR15009. 1 hit.
Pfam	PF04709. AMH_N. 1 hit. PF00019. TGF_beta. 1 hit. [Graphical view]
PIRSF	PIRSF037270. Muellerian-inhibiting_factor. 1 hit.
SMART	SM00204. TGFB. 1 hit. [Graphical view]
PROSITE	PS00250. TGF_BETA_1. 1 hit. PS51362. TGF_BETA_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	268.
NextBio	1053.
SOURCE	Search...

Entry information

Entry name

MIS_HUMAN

Accession

Primary (citable) accession number: P03971
Secondary accession number(s): O75246, Q6GTN3

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 23, 1986
Last sequence update:	November 30, 2010
Last modified:	May 1, 2013
This is version 140 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.