Reviewed, UniProtKB/Swiss-Prot Q99623 (PHB2_HUMAN)

Names and origin

Protein names

Recommended name:
    Prohibitin-2
Alternative name(s):
    B-cell receptor-associated protein BAP37
    Repressor of estrogen receptor activity
    D-prohibitin

Gene names

Name:	PHB2
Synonyms:	BAP, REA

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	299 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	Acts as a mediator of transcriptional repression by nuclear hormone receptors via recruitment of histone deacetylases By similarity. Functions as an estrogen receptor (ER)-selective coregulator that potentiates the inhibitory activities of antiestrogens and represses the activity of estrogens. Competes with NCOA1 for modulation of ER transcriptional activity. Probably involved in regulating mitochondrial respiration activity and in aging. Ref.8 Ref.2 UniProtKB O35129
Subunit structure	Interacts with PHB, ESR1, HDAC1 and HDAC5 By similarity. Ref.8 Ref.2 UniProtKB O35129
Subcellular location	Mitochondrion inner membrane By similarity. Cytoplasm By similarity. Nucleus By similarity. Note: Also cytoplasmic and nuclear By similarity.
Developmental stage	Levels of expression in fibroblasts decrease heterogeneously during cellular aging. Ref.8
Induction	Expression increases approximately 3-fold upon entry into G1 phase compared to other phases of the cell cycle. Also induced following inhibition of mitochondrial protein synthesis by thiamphenicol. Ref.8
Sequence similarities	Belongs to the prohibitin family.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Membrane Mitochondrion Mitochondrion inner membrane Nucleus
Domain	Coiled coil
Molecular function	Receptor Repressor
PTM	Acetylation Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	negative regulation of transcription Ref.2 Non-traceable author statement. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrial inner membrane Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	estrogen receptor binding Ref.2 Non-traceable author statement. Source: UniProtKB receptor activity Inferred from electronic annotation. Source: UniProtKB-KW specific transcriptional repressor activity Ref.2 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDC25B	P30305	1	EBI-358348,EBI-1051746
COPG	Q9Y678	1	EBI-358348,EBI-1049127
CTNNB1	P35222	1	EBI-358348,EBI-491549
DDX20	Q9UHI6	1	EBI-358348,EBI-347658
EPPK1	P58107	1	EBI-358348,EBI-297954
JUP	P14923	1	EBI-358348,EBI-702484
LGALS3BP	Q08380	1	EBI-358348,EBI-354956
MMS19	Q96T76	1	EBI-358348,EBI-1044169
NUP205	Q92621	1	EBI-358348,EBI-1045046
NUP93	Q8N1F7	1	EBI-358348,EBI-1042703
PDXDC1	Q6P996	1	EBI-358348,EBI-1049813
RIPK2	O43353	1	EBI-358348,EBI-358522
RUNX3	Q96QW2	1	EBI-358348,EBI-1046821
SERINC3	Q13530	1	EBI-358348,EBI-1045571
SIRT2	Q8IXJ6	1	EBI-358348,EBI-477232
TFE3	P19532	1	EBI-358348,EBI-1048957
TIMM50	Q3ZCQ8	1	EBI-358348,EBI-355175
UPF2	Q9HAU5	1	EBI-358348,EBI-372073
USP15	Q9Y4E8	1	EBI-358348,EBI-1043104

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.7
	Chain	2 – 299	298	Prohibitin-2		PRO_0000213884
Regions
	Region	19 – 49	31	Necessary for transcriptional repression Ref.2
	Region	150 – 174	25	Necessary for transcriptional repression Ref.2
	Coiled coil	190 – 238	49	Potential
Amino acid modifications
	Modified residue	2	1	N-acetylalanine Ref.7
	Modified residue	128	1	Phosphotyrosine Ref.9
	Modified residue	248	1	Phosphotyrosine Ref.10

Sequences

	Sequence		Length	Mass (Da)
	Q99623-1 [UniParc]. Last modified July 1, 1997. Version 2. Checksum: A887CC982BF85C80	FASTA	299	33,296
	10 20 30 40 50 60 MAQNLKDLAG RLPAGPRGMG TALKLLLGAG AVAYGVRESV FTVEGGHRAI FFNRIGGVQQ 70 80 90 100 110 120 DTILAEGLHF RIPWFQYPII YDIRARPRKI SSPTGSKDLQ MVNISLRVLS RPNAQELPSM 130 140 150 160 170 180 YQRLGLDYEE RVLPSIVNEV LKSVVAKFNA SQLITQRAQV SLLIRRELTE RAKDFSLILD 190 200 210 220 230 240 DVAITELSFS REYTAAVEAK QVAQQEAQRA QFLVEKAKQE QRQKIVQAEG EAEAAKMLGE 250 260 270 280 290 ALSKNPGYIK LRKIRAAQNI SKTIATSQNR IYLTADNLVL NLQDESFTRG SDSLIKGKK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Large-scale sequencing in human chromosome 12p13: experimental and computational gene structure determination." Ansari-Lari M.A., Shen Y., Muzny D.M., Lee W., Gibbs R.A. Genome Res. 7:268-280(1997) [PubMed: 9074930] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]	"An estrogen receptor-selective coregulator that potentiates the effectiveness of antiestrogens and represses the activity of estrogens." Montano M.M., Ekena K., Delage-Mourroux R., Chang W., Martini P., Katzenellenbogen B.S. Proc. Natl. Acad. Sci. U.S.A. 96:6947-6952(1999) [PubMed: 10359819] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH ESR1. Tissue: Mammary cancer.
[3]	"Identification of a novel D-prohibitin from dendritic cells." Zhang W., Wan T., Chen T., Cao X. Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Dendritic cell.
[4]	"Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning." Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M. , Zhou J., Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L. Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000) [PubMed: 10931946] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Hypothalamus.
[5]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed: 16541075] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta and Skin.
[7]	Bienvenut W.V., Lilla S., Zebisch A., Kolch W. Submitted (MAR-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-11; 108-131; 148-157; 172-191; 210-216; 225-236 AND 271-289, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: Colon carcinoma.
[8]	"Mammalian prohibitin proteins respond to mitochondrial stress and decrease during cellular senescence." Coates P.J., Nenutil R., McGregor A., Picksley S.M., Crouch D.H., Hall P.A., Wright E.G. Exp. Cell Res. 265:262-273(2001) [PubMed: 11302691] [Abstract] Cited for: FUNCTION, INTERACTION WITH PHB, DEVELOPMENTAL STAGE, INDUCTION.
[9]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-128, MASS SPECTROMETRY.
[10]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-248, MASS SPECTROMETRY.
[11]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U47924 Genomic DNA. Translation: AAB51324.1. U72511 mRNA. Translation: AAC51639.1. AF150962 mRNA. Translation: AAD38042.1. AF178980 mRNA. Translation: AAF44345.1. AF126021 mRNA. Translation: AAF17231.1. BC014766 mRNA. Translation: AAH14766.1. BC110322 mRNA. Translation: AAI10323.1.
IPI	IPI00027252.
RefSeq	NP_001138303.1. NP_009204.1.
UniGene	Hs.504620
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q99623. 43 interactions.
PTM databases
PhosphoSite	Q99623.
2-D gel databases
OGP	Q99623.
Proteomic databases
PeptideAtlas	Q99623.
PRIDE	Q99623.
Genome annotation databases
Ensembl	ENSG00000215021. Homo sapiens. [Contig view]
GeneID	11331.
KEGG	hsa:11331.
Organism-specific databases
GeneCards	GC12M006945.
H-InvDB	HIX0010380.
HGNC	HGNC:30306. PHB2.
HPA	CAB014889.
MIM	610704. gene.
PharmGKB	PA27825.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q99623.
Gene expression databases
Bgee	Q99623.
CleanEx	HS_PHB2.
Family and domain databases
InterPro	IPR001107. Band_7. IPR000163. Prohibitin. [Graphical view]
PANTHER	PTHR23222. Prohibitin. 1 hit.
Pfam	PF01145. Band_7. 1 hit. [Graphical view]
PRINTS	PR00679. PROHIBITIN.
SMART	SM00244. PHB. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	43043.
SOURCE	Search...

Entry information

Entry name

PHB2_HUMAN

Accession

Primary (citable) accession number: Q99623
Secondary accession number(s): Q2YDA4, Q7KYU3, Q92978

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 27, 2005
Last sequence update:	July 1, 1997
Last modified:	June 16, 2009
This is version 74 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)