P08476 (INHBA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Inhibin beta A chain

Alternative name(s):
Activin beta-A chain
Erythroid differentiation protein
Short name=EDF

Gene names

Name:

INHBA

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	426 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	Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythroid differentiation, insulin secretion, nerve cell survival, embryonic axial development or bone growth, depending on their subunit composition. Inhibins appear to oppose the functions of activins.
Subunit structure	Dimeric, linked by one or more disulfide bonds. Inhibin A is a dimer of alpha and beta-A. Inhibin B is a dimer of alpha and beta-B. Activin A is a homodimer of beta-A. Activin B is a homodimer of beta-B. Activin AB is a dimer of beta-A and beta-B. Interacts with FST and FSTL3. Ref.8
Subcellular location	Secreted.
Sequence similarities	Belongs to the TGF-beta family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Growth factor Hormone
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G1/S transition of mitotic cell cycle Inferred from direct assay PubMed 9884026. Source: HGNC cell cycle arrest Inferred from direct assay PubMed 9884026. Source: HGNC cell surface receptor signaling pathway Traceable author statement PubMed 12456957. Source: UniProtKB cellular response to cholesterol Inferred from electronic annotation. Source: Compara cellular response to follicle-stimulating hormone stimulus Inferred from electronic annotation. Source: Compara defense response Traceable author statement PubMed 12456957. Source: UniProtKB erythrocyte differentiation Non-traceable author statement PubMed 1310063. Source: UniProtKB eyelid development in camera-type eye Inferred from sequence or structural similarity. Source: UniProtKB growth Inferred from electronic annotation. Source: InterPro hair follicle development Inferred from genetic interaction PubMed 10932194. Source: UniProtKB hematopoietic progenitor cell differentiation Inferred from direct assay PubMed 15451575. Source: UniProtKB hemoglobin biosynthetic process Inferred from direct assay PubMed 1310063. Source: UniProtKB induction of apoptosis Inferred from direct assay PubMed 8267637. Source: UniProtKB male gonad development Inferred from genetic interaction PubMed 10932194. Source: UniProtKB mesodermal cell differentiation Inferred from electronic annotation. Source: Compara negative regulation of B cell differentiation Traceable author statement PubMed 12456957. Source: UniProtKB negative regulation of cell growth Inferred from direct assay PubMed 20573232. Source: UniProtKB negative regulation of cell proliferation Inferred from direct assay PubMed 11948405. Source: UniProtKB negative regulation of follicle-stimulating hormone secretion Non-traceable author statement Ref.2. Source: UniProtKB negative regulation of interferon-gamma biosynthetic process Traceable author statement PubMed 12456957. Source: UniProtKB negative regulation of macrophage differentiation Traceable author statement PubMed 12456957. Source: UniProtKB negative regulation of phosphorylation Traceable author statement PubMed 12456957. Source: UniProtKB nervous system development Non-traceable author statement PubMed 10320815. Source: UniProtKB odontogenesis Inferred from genetic interaction PubMed 10932194. Source: UniProtKB ovarian follicle development Inferred from genetic interaction PubMed 10932194. Source: UniProtKB palate development Inferred from genetic interaction PubMed 10932194. Source: UniProtKB positive regulation of erythrocyte differentiation Inferred from direct assay PubMed 9032295. Source: HGNC positive regulation of follicle-stimulating hormone secretion Traceable author statement PubMed 12456957. Source: UniProtKB positive regulation of ovulation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of pathway-restricted SMAD protein phosphorylation Inferred from direct assay PubMed 19736306. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 12702211PubMed 21281489. Source: UniProtKB progesterone secretion Inferred from genetic interaction PubMed 10932194. Source: UniProtKB regulation of activin receptor signaling pathway Inferred from direct assay PubMed 9884026. Source: HGNC response to drug Inferred from direct assay PubMed 20573232. Source: UniProtKB
Cellular_component	activin A complex Inferred from direct assay PubMed 7890768. Source: HGNC inhibin A complex Inferred from direct assay PubMed 7890768. Source: HGNC
Molecular_function	cytokine activity Inferred from direct assay PubMed 9884026. Source: HGNC growth factor activity Traceable author statement PubMed 12324653. Source: UniProtKB hormone activity Traceable author statement PubMed 12456957. Source: UniProtKB peptide hormone binding Inferred from physical interaction PubMed 16198295. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

By similarity

Propeptide

21 – 310

290

PRO_0000033708

Chain

311 – 426

116

Inhibin beta A chain

PRO_0000033709

Amino acid modifications

Glycosylation

165

1

N-linked (GlcNAc...) Potential

Disulfide bond

314 ↔ 322

Ref.10

Disulfide bond

321 ↔ 391

Ref.10

Disulfide bond

350 ↔ 423

Ref.10

Disulfide bond

354 ↔ 425

Ref.10

Disulfide bond

390

Interchain Ref.10

Natural variations

Natural variant

299

1

Q → P.
Corresponds to variant rs41294833 [ dbSNP | Ensembl ].

VAR_052566

Experimental info

Sequence conflict

377 – 379

3

RMR → AC in CAA51163. Ref.7

Secondary structure

1

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.

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426

Helix Strand Turn

Details...

Beta strand

321 – 324

4

Beta strand

327 – 329

3

Helix

330 – 333

4

Turn

336 – 338

3

Beta strand

339 – 341

3

Beta strand

343 – 346

4

Beta strand

349 – 352

4

Helix

356 – 358

3

Beta strand

362 – 364

3

Helix

368 – 375

8

Turn

378 – 380

3

Turn

382 – 386

5

Beta strand

391 – 404

14

Turn

406 – 408

3

Beta strand

410 – 425

16

Sequences

	Sequence		Length	Mass (Da)
	P08476 [UniParc]. Last modified July 1, 1989. Version 2. Checksum: 201CDEDF99CB6919	FASTA	426	47,442
	10 20 30 40 50 60 MPLLWLRGFL LASCWIIVRS SPTPGSEGHS AAPDCPSCAL AALPKDVPNS QPEMVEAVKK 70 80 90 100 110 120 HILNMLHLKK RPDVTQPVPK AALLNAIRKL HVGKVGENGY VEIEDDIGRR AEMNELMEQT 130 140 150 160 170 180 SEIITFAESG TARKTLHFEI SKEGSDLSVV ERAEVWLFLK VPKANRTRTK VTIRLFQQQK 190 200 210 220 230 240 HPQGSLDTGE EAEEVGLKGE RSELLLSEKV VDARKSTWHV FPVSSSIQRL LDQGKSSLDV 250 260 270 280 290 300 RIACEQCQES GASLVLLGKK KKKEEEGEGK KKGGGEGGAG ADEEKEQSHR PFLMLQARQS 310 320 330 340 350 360 EDHPHRRRRR GLECDGKVNI CCKKQFFVSF KDIGWNDWII APSGYHANYC EGECPSHIAG 370 380 390 400 410 420 TSGSSLSFHS TVINHYRMRG HSPFANLKSC CVPTKLRPMS MLYYDDGQNI IKKDIQNMIV EECGCS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure of two human ovarian inhibins." Mason A.J., Niall H.D., Seeburg P.H. Biochem. Biophys. Res. Commun. 135:957-964(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Erythroid differentiation factor is encoded by the same mRNA as that of the inhibin beta A chain." Murata M., Eto Y., Shibai H., Sakai M., Muramatsu M. Proc. Natl. Acad. Sci. U.S.A. 85:2434-2438(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Structure and sequence analysis of the human activin beta A subunit gene." Tanimoto K., Handa S.I., Ueno N., Murakami K., Fukamizu A. DNA Seq. 2:103-110(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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]. Tissue: Eye.
[6]	"Human inhibin genes. Genomic characterisation and sequencing." Stewart A.G., Milborrow H.M., Ring J.M., Crowther C.E., Forage R.G. FEBS Lett. 206:329-334(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 311-426.
[7]	Berg H., Walter M., Northemann W. Submitted (MAY-1993) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE OF 311-426. Tissue: Testis.
[8]	"Differential binding and neutralization of activins A and B by follistatin and follistatin like-3 (FSTL-3/FSRP/FLRG)." Schneyer A., Schoen A., Quigg A., Sidis Y. Endocrinology 144:1671-1674(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FST AND FSTL3.
[9]	"Structures of an ActRIIB:activin A complex reveal a novel binding mode for TGF-beta ligand:receptor interactions." Thompson T.B., Woodruff T.K., Jardetzky T.S. EMBO J. 22:1555-1566(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.05 ANGSTROMS) IN COMPLEX WITH RAT ACTRIIB EXTRACELLULAR DOMAIN.
[10]	"The structure of FSTL3.activin A complex. Differential binding of N-terminal domains influences follistatin-type antagonist specificity." Stamler R., Keutmann H.T., Sidis Y., Kattamuri C., Schneyer A., Thompson T.B. J. Biol. Chem. 283:32831-32838(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.48 ANGSTROMS) OF 311-426 IN COMPLEX WITH FSTL3, DISULFIDE BONDS.
+	Additional computationally mapped references.

Web resources

Wikipedia

Activin entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M13436 mRNA. Translation: AAA59168.1.
X04447 Genomic DNA. Translation: CAA28041.1.
X57578, X57579 Genomic DNA. Translation: CAA40805.1.
X57579 Genomic DNA. Translation: CAA40806.1.
AC005027 Genomic DNA. Translation: AAQ96861.1.
BC007858 mRNA. Translation: AAH07858.1.
J03634 mRNA. Translation: AAA35787.1.
X72498 mRNA. Translation: CAA51163.1.

IPI

IPI00028670.

PIR

B24248. S30488.

RefSeq

NP_002183.1. NM_002192.2.

UniGene

Hs.583348.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NYS	X-ray	3.05	B/D	311-426	[»]
1NYU	X-ray	3.10	B/D	311-426	[»]
1S4Y	X-ray	2.30	B/D	311-426	[»]
2ARP	X-ray	2.00	A	311-426	[»]
2ARV	X-ray	2.00	A/B	311-426	[»]
2B0U	X-ray	2.80	A/B	311-426	[»]
2P6A	X-ray	3.40	A/B	311-426	[»]
3B4V	X-ray	2.48	A/B/E/F	311-426	[»]

ProteinModelPortal

P08476.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5824N.

MINT

MINT-1786936.

STRING

9606.ENSP00000242208.

PTM databases

PhosphoSite

P08476.

Polymorphism databases

DMDM

124279.

Proteomic databases

PaxDb

P08476.

PRIDE

P08476.

Protocols and materials databases

DNASU

3624.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000242208; ENSP00000242208; ENSG00000122641.
ENST00000442711; ENSP00000397197; ENSG00000122641.

GeneID

3624.

KEGG

hsa:3624.

UCSC

uc003thq.3. human.

Organism-specific databases

CTD

3624.

GeneCards

GC07M041724.

HGNC

HGNC:6066. INHBA.

HPA

HPA020031.

MIM

147290. gene.

neXtProt

NX_P08476.

PharmGKB

PA29877.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG312557.

HOGENOM

HOG000220890.

HOVERGEN

HBG105613.

InParanoid

P08476.

KO

K04667.

OMA

RKSTWHI.

OrthoDB

EOG4C87T4.

PhylomeDB

P08476.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P08476.

Bgee

P08476.

CleanEx

HS_INHBA.

Genevestigator

P08476.

GermOnline

ENSG00000122641. Homo sapiens.

Family and domain databases

InterPro

IPR000491. Inhibin_betaA.
IPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]

PANTHER

PTHR11848. PTHR11848. 1 hit.

Pfam

PF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
[Graphical view]

PRINTS

PR00670. INHIBINBA.

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

EvolutionaryTrace

P08476.

GenomeRNAi

3624.

NextBio

14181.

SOURCE

Search...

Entry information

Entry name

INHBA_HUMAN

Accession

Primary (citable) accession number: P08476
Secondary accession number(s): Q14599

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	July 1, 1989
Last modified:	May 1, 2013
This is version 155 of the entry and version 2 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.