ID   INHA_HUMAN              Reviewed;         366 AA.
AC   P05111; A8K8H5;
DT   13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT   13-AUG-1987, sequence version 1.
DT   24-JAN-2024, entry version 209.
DE   RecName: Full=Inhibin alpha chain;
DE   Flags: Precursor;
GN   Name=INHA;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=3016724; DOI=10.1073/pnas.83.16.5849;
RA   Mayo K.E., Cerelli G.M., Spiess J., Rivier J., Rosenfeld M.G., Evans R.M.,
RA   Vale W.;
RT   "Inhibin A-subunit cDNAs from porcine ovary and human placenta.";
RL   Proc. Natl. Acad. Sci. U.S.A. 83:5849-5853(1986).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3758355; DOI=10.1016/0014-5793(86)81006-7;
RA   Stewart A.G., Milborrow H.M., Ring J.M., Crowther C.E., Forage R.G.;
RT   "Human inhibin genes. Genomic characterisation and sequencing.";
RL   FEBS Lett. 206:329-334(1986).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Testis;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
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   NUCLEOTIDE SEQUENCE [MRNA] OF 16-366.
RX   PubMed=3754442; DOI=10.1016/0006-291x(86)91021-1;
RA   Mason A.J., Niall H.D., Seeburg P.H.;
RT   "Structure of two human ovarian inhibins.";
RL   Biochem. Biophys. Res. Commun. 135:957-964(1986).
RN   [8]
RP   PARTIAL PROTEIN SEQUENCE, PROTEOLYTIC PROCESSING, GLYCOSYLATION AT ASN-268
RP   AND ASN-302, AND MUTAGENESIS.
RX   PubMed=8885240; DOI=10.1210/mend.10.9.8885240;
RA   Mason A.J., Farnworth P.G., Sullivan J.;
RT   "Characterization and determination of the biological activities of
RT   noncleavable high molecular weight forms of inhibin A and activin A.";
RL   Mol. Endocrinol. 10:1055-1065(1996).
RN   [9]
RP   TISSUE SPECIFICITY, AND INDUCTION.
RX   PubMed=9506758; DOI=10.1210/jcem.83.3.4640;
RA   Mellor S.L., Richards M.G., Pedersen J.S., Robertson D.M., Risbridger G.P.;
RT   "Loss of the expression and localization of inhibin alpha-subunit in high
RT   grade prostate cancer.";
RL   J. Clin. Endocrinol. Metab. 83:969-975(1998).
RN   [10]
RP   VARIANT THR-257.
RX   PubMed=11098038; DOI=10.1093/humrep/15.12.2644;
RA   Shelling A.N., Burton K.A., Chand A.L., van Ee C.C., France J.T.,
RA   Farquhar C.M., Milsom S.R., Love D.R., Gersak K., Aittomaki K.,
RA   Winship I.M.;
RT   "Inhibin: a candidate gene for premature ovarian failure.";
RL   Hum. Reprod. 15:2644-2649(2000).
RN   [11]
RP   VARIANT LEU-60, AND CHARACTERIZATION OF VARIANT LEU-60.
RX   PubMed=24302632; DOI=10.1002/humu.22489;
RA   Tournier I., Marlin R., Walton K., Charbonnier F., Coutant S., Thery J.C.,
RA   Charbonnier C., Spurrell C., Vezain M., Ippolito L., Bougeard G., Roman H.,
RA   Tinat J., Sabourin J.C., Stoppa-Lyonnet D., Caron O.,
RA   Bressac-de Paillerets B., Vaur D., King M.C., Harrison C., Frebourg T.;
RT   "Germline mutations of inhibins in early-onset ovarian epithelial tumors.";
RL   Hum. Mutat. 35:294-297(2014).
CC   -!- FUNCTION: Inhibins and activins inhibit and activate, respectively, the
CC       secretion of follitropin by the pituitary gland. Inhibins/activins are
CC       involved in regulating a number of diverse functions such as
CC       hypothalamic and pituitary hormone secretion, gonadal hormone
CC       secretion, germ cell development and maturation, erythroid
CC       differentiation, insulin secretion, nerve cell survival, embryonic
CC       axial development or bone growth, depending on their subunit
CC       composition. Inhibins appear to oppose the functions of activins.
CC   -!- SUBUNIT: Dimeric, linked by one or more disulfide bonds. Inhibin A is a
CC       dimer of alpha and beta-A. Inhibin B is a dimer of alpha and beta-B.
CC   -!- INTERACTION:
CC       P05111; Q8IUQ4: SIAH1; NbExp=3; IntAct=EBI-10194422, EBI-747107;
CC       P05111; Q8IUQ4-2: SIAH1; NbExp=3; IntAct=EBI-10194422, EBI-11522811;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Originally found in ovary (granulosa cells) and
CC       testis (Sertoli cells), but widely distributed in many tissues
CC       including brain and placenta. In adrenal cortex expression is limited
CC       to the zona reticularis and the innermost zona fasciculata in the
CC       normal gland, extending centripetally into the zona fasciculata in
CC       hyperplasia. Also found in adrenocortical tumors. Also expressed in
CC       prostate epithelium of benign prostatic hyperplasia, in regions of
CC       basal cell hyperplasia and in nonmalignant regions of high grade
CC       prostate cancer. Only circulating inhibin B is found in male, whereas
CC       circulating inhibins A and B are found in female.
CC       {ECO:0000269|PubMed:9506758}.
CC   -!- PTM: Proteolytic processing yields a number of bioactive forms. The
CC       20/23 kDa forms consist solely of the mature alpha chain, the 26/29 kDa
CC       forms consist of the most N-terminal propeptide linked through a
CC       disulfide bond to the mature alpha chain, the 50/53 kDa forms encompass
CC       the entire proprotein. Each type can be furthermore either mono- or
CC       diglycosylated, causing the mass difference.
CC       {ECO:0000269|PubMed:8885240}.
CC   -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Inhibin entry;
CC       URL="https://en.wikipedia.org/wiki/Inhibin";
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DR   EMBL; M13981; AAA59166.1; -; mRNA.
DR   EMBL; X04445; CAA28040.1; -; Genomic_DNA.
DR   EMBL; X04446; CAA28040.1; JOINED; Genomic_DNA.
DR   EMBL; BT006954; AAP35600.1; -; mRNA.
DR   EMBL; AK292340; BAF85029.1; -; mRNA.
DR   EMBL; CH471063; EAW70774.1; -; Genomic_DNA.
DR   EMBL; BC006391; AAH06391.1; -; mRNA.
DR   EMBL; M13144; AAA59167.1; -; mRNA.
DR   CCDS; CCDS2444.1; -.
DR   PIR; A23556; A24248.
DR   RefSeq; NP_002182.1; NM_002191.3.
DR   AlphaFoldDB; P05111; -.
DR   BioGRID; 109835; 52.
DR   DIP; DIP-5826N; -.
DR   ELM; P05111; -.
DR   IntAct; P05111; 5.
DR   STRING; 9606.ENSP00000243786; -.
DR   BindingDB; P05111; -.
DR   ChEMBL; CHEMBL5169109; -.
DR   GlyCosmos; P05111; 3 sites, No reported glycans.
DR   GlyGen; P05111; 3 sites.
DR   iPTMnet; P05111; -.
DR   PhosphoSitePlus; P05111; -.
DR   BioMuta; INHA; -.
DR   DMDM; 124274; -.
DR   MassIVE; P05111; -.
DR   PaxDb; 9606-ENSP00000243786; -.
DR   PeptideAtlas; P05111; -.
DR   ProteomicsDB; 51796; -.
DR   Antibodypedia; 4368; 941 antibodies from 43 providers.
DR   DNASU; 3623; -.
DR   Ensembl; ENST00000243786.3; ENSP00000243786.2; ENSG00000123999.5.
DR   GeneID; 3623; -.
DR   KEGG; hsa:3623; -.
DR   MANE-Select; ENST00000243786.3; ENSP00000243786.2; NM_002191.4; NP_002182.1.
DR   UCSC; uc002vmk.3; human.
DR   AGR; HGNC:6065; -.
DR   CTD; 3623; -.
DR   DisGeNET; 3623; -.
DR   GeneCards; INHA; -.
DR   HGNC; HGNC:6065; INHA.
DR   HPA; ENSG00000123999; Group enriched (adrenal gland, ovary, testis).
DR   MIM; 147380; gene.
DR   neXtProt; NX_P05111; -.
DR   OpenTargets; ENSG00000123999; -.
DR   Orphanet; 619; NON RARE IN EUROPE: Primary ovarian failure.
DR   PharmGKB; PA29876; -.
DR   VEuPathDB; HostDB:ENSG00000123999; -.
DR   eggNOG; KOG3900; Eukaryota.
DR   GeneTree; ENSGT00390000005935; -.
DR   HOGENOM; CLU_064515_0_0_1; -.
DR   InParanoid; P05111; -.
DR   OMA; PEHWTVF; -.
DR   OrthoDB; 5344254at2759; -.
DR   PhylomeDB; P05111; -.
DR   TreeFam; TF331531; -.
DR   PathwayCommons; P05111; -.
DR   Reactome; R-HSA-1502540; Signaling by Activin.
DR   Reactome; R-HSA-201451; Signaling by BMP.
DR   Reactome; R-HSA-209822; Glycoprotein hormones.
DR   SignaLink; P05111; -.
DR   SIGNOR; P05111; -.
DR   BioGRID-ORCS; 3623; 12 hits in 1156 CRISPR screens.
DR   GeneWiki; INHA; -.
DR   GenomeRNAi; 3623; -.
DR   Pharos; P05111; Tbio.
DR   PRO; PR:P05111; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; P05111; Protein.
DR   Bgee; ENSG00000123999; Expressed in adrenal tissue and 96 other cell types or tissues.
DR   GO; GO:0005576; C:extracellular region; TAS:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0043512; C:inhibin A complex; IDA:HGNC-UCL.
DR   GO; GO:0043513; C:inhibin B complex; IEA:Ensembl.
DR   GO; GO:0034673; C:inhibin-betaglycan-ActRII complex; IDA:BHF-UCL.
DR   GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR   GO; GO:0001917; C:photoreceptor inner segment; IEA:Ensembl.
DR   GO; GO:0001750; C:photoreceptor outer segment; IEA:Ensembl.
DR   GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR   GO; GO:0008083; F:growth factor activity; TAS:UniProtKB.
DR   GO; GO:0005179; F:hormone activity; TAS:UniProtKB.
DR   GO; GO:0034711; F:inhibin binding; IEA:Ensembl.
DR   GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR   GO; GO:0005102; F:signaling receptor binding; IPI:HGNC-UCL.
DR   GO; GO:0030154; P:cell differentiation; TAS:UniProtKB.
DR   GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:UniProtKB.
DR   GO; GO:0007267; P:cell-cell signaling; TAS:UniProtKB.
DR   GO; GO:0030218; P:erythrocyte differentiation; NAS:UniProtKB.
DR   GO; GO:0042541; P:hemoglobin biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR   GO; GO:0045578; P:negative regulation of B cell differentiation; TAS:UniProtKB.
DR   GO; GO:0045786; P:negative regulation of cell cycle; TAS:UniProtKB.
DR   GO; GO:0046882; P:negative regulation of follicle-stimulating hormone secretion; NAS:UniProtKB.
DR   GO; GO:0045650; P:negative regulation of macrophage differentiation; TAS:UniProtKB.
DR   GO; GO:0042326; P:negative regulation of phosphorylation; TAS:UniProtKB.
DR   GO; GO:0032689; P:negative regulation of type II interferon production; TAS:UniProtKB.
DR   GO; GO:0001541; P:ovarian follicle development; NAS:UniProtKB.
DR   GO; GO:0046881; P:positive regulation of follicle-stimulating hormone secretion; TAS:UniProtKB.
DR   GO; GO:0051726; P:regulation of cell cycle; IDA:HGNC-UCL.
DR   GO; GO:0042127; P:regulation of cell population proliferation; IDA:HGNC-UCL.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
DR   Gene3D; 2.10.90.10; Cystine-knot cytokines; 1.
DR   InterPro; IPR029034; Cystine-knot_cytokine.
DR   InterPro; IPR017175; Inhibin_asu.
DR   InterPro; IPR001839; TGF-b_C.
DR   InterPro; IPR015615; TGF-beta-rel.
DR   InterPro; IPR017948; TGFb_CS.
DR   PANTHER; PTHR11848:SF117; INHIBIN ALPHA CHAIN; 1.
DR   PANTHER; PTHR11848; TGF-BETA FAMILY; 1.
DR   Pfam; PF00019; TGF_beta; 1.
DR   PIRSF; PIRSF037328; Inhibin_alpha_subunit; 1.
DR   PRINTS; PR00669; INHIBINA.
DR   SMART; SM00204; TGFB; 1.
DR   SUPFAM; SSF57501; Cystine-knot cytokines; 1.
DR   PROSITE; PS00250; TGF_BETA_1; 1.
DR   PROSITE; PS51362; TGF_BETA_2; 1.
DR   Genevisible; P05111; HS.
PE   1: Evidence at protein level;
KW   Cleavage on pair of basic residues; Direct protein sequencing;
KW   Disulfide bond; Glycoprotein; Growth factor; Hormone; Reference proteome;
KW   Secreted; Signal.
FT   SIGNAL          1..18
FT   PROPEP          19..61
FT                   /id="PRO_0000033685"
FT   PROPEP          62..232
FT                   /note="Inhibin alpha N-terminal region"
FT                   /id="PRO_0000033686"
FT   CHAIN           233..366
FT                   /note="Inhibin alpha chain"
FT                   /id="PRO_0000033687"
FT   SITE            61..62
FT                   /note="Cleavage"
FT   SITE            232..233
FT                   /note="Cleavage"
FT   CARBOHYD        146
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        268
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:8885240"
FT   CARBOHYD        302
FT                   /note="N-linked (GlcNAc...) asparagine; partial"
FT                   /evidence="ECO:0000269|PubMed:8885240"
FT   DISULFID        262..328
FT                   /evidence="ECO:0000250"
FT   DISULFID        291..363
FT                   /evidence="ECO:0000250"
FT   DISULFID        295..365
FT                   /evidence="ECO:0000250"
FT   DISULFID        327
FT                   /note="Interchain"
FT                   /evidence="ECO:0000250"
FT   VARIANT         60
FT                   /note="R -> L (found in a patient with early-onset
FT                   epithelial ovarian tumor; uncertain significance; alters
FT                   the ratio of secreted activins and ihibins)"
FT                   /evidence="ECO:0000269|PubMed:24302632"
FT                   /id="VAR_072639"
FT   VARIANT         227
FT                   /note="G -> R (in dbSNP:rs12720061)"
FT                   /id="VAR_034016"
FT   VARIANT         257
FT                   /note="A -> T (may play a role in premature ovarian
FT                   failure; dbSNP:rs12720062)"
FT                   /evidence="ECO:0000269|PubMed:11098038"
FT                   /id="VAR_015110"
FT   MUTAGEN         56..57
FT                   /note="RR->AA: Loss of cleavage; when associated with
FT                   60-AA-61."
FT                   /evidence="ECO:0000269|PubMed:8885240"
FT   MUTAGEN         60..61
FT                   /note="RR->AA: Loss of cleavage; when associated with
FT                   55-AA-56."
FT                   /evidence="ECO:0000269|PubMed:8885240"
FT   MUTAGEN         231..232
FT                   /note="RR->EA: Loss of cleavage."
FT                   /evidence="ECO:0000269|PubMed:8885240"
FT   MUTAGEN         268
FT                   /note="N->Q: Loss of glycosylation."
FT                   /evidence="ECO:0000269|PubMed:8885240"
FT   MUTAGEN         302
FT                   /note="N->Q: Loss of glycosylation."
FT                   /evidence="ECO:0000269|PubMed:8885240"
FT   CONFLICT        17
FT                   /note="H -> V (in Ref. 7)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        19
FT                   /note="C -> S (in Ref. 7)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   366 AA;  39670 MW;  0E03D2AB12BF8E57 CRC64;
     MVLHLLLFLL LTPQGGHSCQ GLELARELVL AKVRALFLDA LGPPAVTREG GDPGVRRLPR
     RHALGGFTHR GSEPEEEEDV SQAILFPATD ASCEDKSAAR GLAQEAEEGL FRYMFRPSQH
     TRSRQVTSAQ LWFHTGLDRQ GTAASNSSEP LLGLLALSPG GPVAVPMSLG HAPPHWAVLH
     LATSALSLLT HPVLVLLLRC PLCTCSARPE ATPFLVAHTR TRPPSGGERA RRSTPLMSWP
     WSPSALRLLQ RPPEEPAAHA NCHRVALNIS FQELGWERWI VYPPSFIFHY CHGGCGLHIP
     PNLSLPVPGA PPTPAQPYSL LPGAQPCCAA LPGTMRPLHV RTTSDGGYSF KYETVPNLLT
     QHCACI
//