INHA_HUMAN
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 03-AUG-2022, entry version 201.
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 GlyGen; P05111; 3 sites.
DR iPTMnet; P05111; -.
DR PhosphoSitePlus; P05111; -.
DR BioMuta; INHA; -.
DR DMDM; 124274; -.
DR MassIVE; P05111; -.
DR PaxDb; P05111; -.
DR PeptideAtlas; P05111; -.
DR PRIDE; P05111; -.
DR ProteomicsDB; 51796; -.
DR Antibodypedia; 4368; 819 antibodies from 42 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 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; TYVFRPS; -.
DR OrthoDB; 1177863at2759; -.
DR PhylomeDB; P05111; -.
DR TreeFam; TF331531; -.
DR PathwayCommons; P05111; -.
DR Reactome; R-HSA-209822; Glycoprotein hormones.
DR SignaLink; P05111; -.
DR SIGNOR; P05111; -.
DR BioGRID-ORCS; 3623; 8 hits in 1078 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 94 other tissues.
DR Genevisible; P05111; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
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:0032689; P:negative regulation of interferon-gamma production; TAS: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:0001541; P:ovarian follicle development; NAS:UniProtKB.
DR GO; GO:0046881; P:positive regulation of follicle-stimulating hormone secretion; TAS:UniProtKB.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IBA:GO_Central.
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 GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR Gene3D; 2.10.90.10; -; 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; PTHR11848; 1.
DR PANTHER; PTHR11848:SF117; PTHR11848:SF117; 1.
DR Pfam; PF00019; TGF_beta; 1.
DR PIRSF; PIRSF037328; Inhibin_alpha_subunit; 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 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; unknown pathological
FT significance; alters the ratio of secreted activins and
FT 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 60-
FT AA-61."
FT /evidence="ECO:0000269|PubMed:8885240"
FT MUTAGEN 60..61
FT /note="RR->AA: Loss of cleavage; when associated with 55-
FT 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
