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 13-OCT-2009, entry version 110. DE RecName: Full=Inhibin alpha chain; DE Flags: Precursor; GN Name=INHA; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=86287350; PubMed=3016724; DOI=10.1073/pnas.83.16.5849; RA Mayo K.E., Cerelli G.M., Spiess J., Rivier J., Rosenfeld M.G., RA Evans R.M., 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 MEDLINE=87005283; 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 RT 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 16-366. RX MEDLINE=86186863; 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 RP ASN-268 AND ASN-302, AND MUTAGENESIS. RX MEDLINE=97039688; PubMed=8885240; DOI=10.1210/me.10.9.1055; 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 MEDLINE=98165602; PubMed=9506758; DOI=10.1210/jc.83.3.969; RA Mellor S.L., Richards M.G., Pedersen J.S., Robertson D.M., RA Risbridger G.P.; RT "Loss of the expression and localization of inhibin alpha-subunit in RT high grade prostate cancer."; RL J. Clin. Endocrinol. Metab. 83:969-975(1998). RN [10] RP VARIANT THR-257. RX MEDLINE=20551311; 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). CC -!- FUNCTION: Inhibins and activins inhibit and activate, CC respectively, the secretion of follitropin by the pituitary gland. CC Inhibins/activins are involved in regulating a number of diverse CC functions such as hypothalamic and pituitary hormone secretion, CC gonadal hormone secretion, germ cell development and maturation, CC erythroid differentiation, insulin secretion, nerve cell survival, CC embryonic axial development or bone growth, depending on their CC subunit composition. Inhibins appear to oppose the functions of CC activins. CC -!- SUBUNIT: Dimeric, linked by one or more disulfide bonds. Inhibin A CC is a dimer of alpha and beta-A. Inhibin B is a dimer of alpha and CC beta-B. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- TISSUE SPECIFICITY: Originally found in ovary (granulosa cells) CC and testis (Sertoli cells), but widely distributed in many tissues CC including brain and placenta. In adrenal cortex expression is CC limited to the zona reticularis and the innermost zona fasciculata CC in the normal gland, extending centripetally into the zona CC fasciculata in hyperplasia. Also found in adrenocortical tumors. CC Also expressed in prostate epithelium of benign prostatic CC hyperplasia, in regions of basal cell hyperplasia and in CC nonmalignant regions of high grade prostate cancer. Only CC circulating inhibin B is found in male, whereas circulating CC inhibins A and B are found in female. CC -!- PTM: Proteolytic processing yields a number of bioactive forms. CC The 20/23 kDa forms consist solely of the mature alpha chain, the CC 26/29 kDa forms consist of the most N-terminal propeptide linked CC through a disulfide bond to the mature alpha chain, the 50/53 kDa CC forms encompass the entire proprotein. Each type can be CC furthermore either mono- or diglycosylated, causing the mass CC difference. CC -!- SIMILARITY: Belongs to the TGF-beta family. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Inhibin entry; CC URL="http://en.wikipedia.org/wiki/Inhibin"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 IPI; IPI00007080; -. DR PIR; A23556; A24248. DR RefSeq; NP_002182.1; -. DR UniGene; Hs.407506; -. DR DIP; DIP:5826N; -. DR STRING; P05111; -. DR PhosphoSite; P05111; -. DR PRIDE; P05111; -. DR Ensembl; ENST00000243786; ENSP00000243786; ENSG00000123999; Homo sapiens. DR GeneID; 3623; -. DR KEGG; hsa:3623; -. DR UCSC; uc002vmk.1; human. DR CTD; 3623; -. DR GeneCards; GC02P220145; -. DR H-InvDB; HIX0002871; -. DR HGNC; HGNC:6065; INHA. DR HPA; CAB000047; -. DR HPA; HPA019141; -. DR MIM; 147380; gene. DR PharmGKB; PA29876; -. DR HOGENOM; P05111; -. DR HOVERGEN; P05111; -. DR OMA; P05111; YSFKYET. DR NextBio; 14177; -. DR ArrayExpress; P05111; -. DR Bgee; P05111; -. DR CleanEx; HS_INHA; -. DR Genevestigator; P05111; -. DR GermOnline; ENSG00000123999; Homo sapiens. DR GO; GO:0043512; C:inhibin A complex; IDA:HGNC. DR GO; GO:0034673; C:inhibin-betaglycan-ActRII complex; IDA:UniProtKB. DR GO; GO:0005125; F:cytokine activity; TAS:UniProtKB. DR GO; GO:0008083; F:growth factor activity; TAS:UniProtKB. DR GO; GO:0005179; F:hormone activity; TAS:UniProtKB. DR GO; GO:0004871; F:signal transducer activity; IDA:UniProtKB. DR GO; GO:0007050; P:cell cycle arrest; TAS:UniProtKB. DR GO; GO:0007166; P:cell surface receptor linked signal transdu...; 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:0006917; P:induction of apoptosis; IDA:UniProtKB. 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...; NAS:UniProtKB. DR GO; GO:0045077; P:negative regulation of interferon-gamma bio...; TAS:UniProtKB. DR GO; GO:0045650; P:negative regulation of macrophage different...; TAS:UniProtKB. DR GO; GO:0042326; P:negative regulation of phosphorylation; TAS:UniProtKB. DR GO; GO:0007399; P:nervous system development; NAS:UniProtKB. DR GO; GO:0001541; P:ovarian follicle development; NAS:UniProtKB. DR GO; GO:0046881; P:positive regulation of follicle-stimulating...; TAS:UniProtKB. DR GO; GO:0042127; P:regulation of cell proliferation; IDA:HGNC. DR GO; GO:0009605; P:response to external stimulus; TAS:UniProtKB. DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc. DR InterPro; IPR002405; Inhibin_asu. DR InterPro; IPR017175; Inhibin_asu_subgr. DR InterPro; IPR001839; TGFb. DR InterPro; IPR017948; TGFb_CS. DR InterPro; IPR015615; TGFbeta. DR PANTHER; PTHR11848; TGFbeta; 1. DR Pfam; PF00019; TGF_beta; 1. DR PIRSF; PIRSF037328; Inhibin_alpha_subunit; 1. DR PRINTS; PR00669; INHIBINA. DR ProDom; PD000357; TGFb; 1. DR SMART; SM00204; TGFB; 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; Complete proteome; KW Direct protein sequencing; Disulfide bond; Glycoprotein; KW Growth factor; Hormone; Polymorphism; Secreted; Signal. FT SIGNAL 1 18 FT PROPEP 19 61 FT /FTId=PRO_0000033685. FT PROPEP 62 232 Inhibin alpha N-terminal region. FT /FTId=PRO_0000033686. FT CHAIN 233 366 Inhibin alpha chain. FT /FTId=PRO_0000033687. FT SITE 61 62 Cleavage. FT SITE 232 233 Cleavage. FT CARBOHYD 146 146 N-linked (GlcNAc...) (Potential). FT CARBOHYD 268 268 N-linked (GlcNAc...). FT CARBOHYD 302 302 N-linked (GlcNAc...); partial. FT DISULFID 262 328 By similarity. FT DISULFID 291 363 By similarity. FT DISULFID 295 365 By similarity. FT DISULFID 327 327 Interchain (By similarity). FT VARIANT 227 227 G -> R (in dbSNP:rs12720061). FT /FTId=VAR_034016. FT VARIANT 257 257 A -> T (either a rare polymorphism or may FT play a role in premature ovarian failure; FT dbSNP:rs12720062). FT /FTId=VAR_015110. FT MUTAGEN 56 57 RR->AA: Loss of cleavage; when associated FT with 60-AA-61. FT MUTAGEN 60 61 RR->AA: Loss of cleavage; when associated FT with 55-AA-56. FT MUTAGEN 231 232 RR->EA: Loss of cleavage. FT MUTAGEN 268 268 N->Q: Loss of glycosylation. FT MUTAGEN 302 302 N->Q: Loss of glycosylation. FT CONFLICT 17 17 H -> V (in Ref. 7). FT CONFLICT 19 19 C -> S (in Ref. 7). 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 //