Q8C0D7 (ING4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Inhibitor of growth protein 4

Alternative name(s):
p29ING4

Gene names

Name:

Ing4

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	249 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of the HBO1 complex which has a histone H4-specific acetyltransferase activity, a reduced activity toward histone H3 and is responsible for the bulk of histone H4 acetylation in vivo. Through chromatin acetylation it may function in DNA replication. May inhibit tumor progression by modulating the transcriptional output of signaling pathways which regulate cell proliferation. Can suppress brain tumor angiogenesis through transcriptional repression of RELA/NFKB3 target genes when complexed with RELA. May also specifically suppress loss of contact inhibition elicited by activated oncogenes such as MYC. Represses hypoxia inducible factor's (HIF) activity by interacting with HIF prolyl hydroxylase 2 (EGLN1) By similarity.
Subunit structure	Homodimer. Interacts with H3K4me3 and to a lesser extent with H3K4me2, the interaction augments HBO1 acetylation activity on H3 tails. Component of the HBO1 complex composed at least of ING4 or ING5, KAT7/HBO1, MEAF6, and one of PHF15, PHF16 and PHF17. Interacts with EP300, RELA and TP53; these interactions may be indirect. Interacts with EGLN1 By similarity.
Subcellular location	Nucleus By similarity.
Domain	The PHD-type zinc finger mediates the binding to H3K4me3 By similarity. The N-terminal coiled-coil domain mediates homodimerization By similarity.
Post-translational modification	Citrullination by PADI4 within the nuclear localization signal disrupts the interaction with p53 and increases susceptibility to degradation By similarity.
Sequence similarities	Belongs to the ING family. Contains 1 PHD-type zinc finger.
Sequence caution	The sequence BAC25009.1 differs from that shown. Reason: Frameshift at positions 226, 232, 239, 246 and 249.

Ontologies

Keywords
Biological process	Cell cycle
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Disease	Tumor suppressor
Domain	Coiled coil Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Chromatin regulator
PTM	Acetylation Citrullination Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator Inferred from sequence or structural similarity. Source: UniProtKB DNA replication Inferred from sequence or structural similarity. Source: UniProtKB apoptotic process Inferred from electronic annotation. Source: Compara cell cycle arrest Inferred from electronic annotation. Source: Compara histone H3 acetylation Inferred from sequence or structural similarity. Source: UniProtKB histone H4-K12 acetylation Inferred from sequence or structural similarity. Source: UniProtKB histone H4-K5 acetylation Inferred from sequence or structural similarity. Source: UniProtKB histone H4-K8 acetylation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of growth Inferred from electronic annotation. Source: Compara negative regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: Compara positive regulation of apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	histone acetyltransferase complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	transcription coactivator activity Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8C0D7-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8C0D7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     131-131: K → S
     132-132: Missing.

Note: May be due to a competing donor splice site.

Isoform 3 (identifier: Q8C0D7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     131-131: K → S
     132-132: Missing.
     217-228: CSIEWFHFACVG → VRTVSSGLGEEL
     229-249: Missing.

Note: May be due to intron retention.

Isoform 4 (identifier: Q8C0D7-4)

The sequence of this isoform differs from the canonical sequence as follows:
     131-131: K → S
     132-132: Missing.
     168-249: Missing.

Note: May be due to intron retention.

Isoform 5 (identifier: Q8C0D7-5)

The sequence of this isoform differs from the canonical sequence as follows:
     127-130: Missing.
     170-172: EYG → MER
     173-249: Missing.

Note: May be due to a competing acceptor splice site.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 249

249

Inhibitor of growth protein 4

PRO_0000212669

Regions

Zinc finger

196 – 245

50

PHD-type

Coiled coil

25 – 118

94

Potential

Motif

127 – 148

22

Bipartite nuclear localization signal By similarity

Sites

Binding site

198

1

Histone H3K4me3 By similarity

Binding site

209

1

Histone H3K4me3 By similarity

Binding site

213

1

Histone H3K4me3 By similarity

Binding site

221

1

Histone H3K4me3 By similarity

Amino acid modifications

Modified residue

112

1

N6-acetyllysine By similarity

Modified residue

127

1

N6-acetyllysine By similarity

Modified residue

129

1

N6-acetyllysine By similarity

Modified residue

133

1

Citrulline

Modified residue

146

1

N6-acetyllysine By similarity

Modified residue

148

1

N6-acetyllysine By similarity

Modified residue

150

1

Phosphoserine Ref.4

Modified residue

156

1

N6-acetyllysine By similarity

Modified residue

166

1

Citrulline

Natural variations

Alternative sequence

127 – 130

4

Missing in isoform 5.

VSP_012520

Alternative sequence

131

1

K → S in isoform 2, isoform 3 and isoform 4.

VSP_012521

Alternative sequence

132

1

Missing in isoform 2, isoform 3 and isoform 4.

VSP_012522

Alternative sequence

168 – 249

82

Missing in isoform 4.

VSP_012523

Alternative sequence

170 – 172

3

EYG → MER in isoform 5.

VSP_012524

Alternative sequence

173 – 249

77

Missing in isoform 5.

VSP_012525

Alternative sequence

217 – 228

12

CSIEW…FACVG → VRTVSSGLGEEL in isoform 3.

VSP_012526

Alternative sequence

229 – 249

21

Missing in isoform 3.

VSP_012527

Experimental info

Sequence conflict

105

1

A → S in BAC27489. Ref.2

Sequence conflict

179

1

G → S in BAC27489. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

249

Helix Strand Turn

Details...

Beta strand

207 – 210

4

Turn

224 – 228

5

Turn

240 – 242

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 4, 2005. Version 2. Checksum: 6C5C5582A249E412	FASTA	249	28,528
	10 20 30 40 50 60 MAAGMYLEHY LDSIENLPFE LQRNFQLMRD LDQRTEDLKA EIDKLATEYM SSARSLSSEE 70 80 90 100 110 120 KLALLRQIQE AYGKCKEFGD DKVQLAMQTY EMVDKHIRRL DTDLARFEAD LKEKQIESSD 130 140 150 160 170 180 YDSSSSKGKK KGRTQKEKKA ARARSKGKNS DEEAPKAAQK KLKLVRTSPE YGMPSVTFGS 190 200 210 220 230 240 VHPSDVLDMP VDPNEPTYCL CHQVSYGEMI GCDNPDCSIE WFHFACVGLT TKPRGKWFCP RCSQERKKK
	Isoform 2 [UniParc]. Checksum: E3DAE9EB05C71924	FASTA	248	28,430
	10 20 30 40 50 60 MAAGMYLEHY LDSIENLPFE LQRNFQLMRD LDQRTEDLKA EIDKLATEYM SSARSLSSEE 70 80 90 100 110 120 KLALLRQIQE AYGKCKEFGD DKVQLAMQTY EMVDKHIRRL DTDLARFEAD LKEKQIESSD 130 140 150 160 170 180 YDSSSSKGKK SRTQKEKKAA RARSKGKNSD EEAPKAAQKK LKLVRTSPEY GMPSVTFGSV 190 200 210 220 230 240 HPSDVLDMPV DPNEPTYCLC HQVSYGEMIG CDNPDCSIEW FHFACVGLTT KPRGKWFCPR CSQERKKK
	Isoform 3 [UniParc]. Checksum: CDAC78AF142ACED3	FASTA	227	25,718
	10 20 30 40 50 60 MAAGMYLEHY LDSIENLPFE LQRNFQLMRD LDQRTEDLKA EIDKLATEYM SSARSLSSEE 70 80 90 100 110 120 KLALLRQIQE AYGKCKEFGD DKVQLAMQTY EMVDKHIRRL DTDLARFEAD LKEKQIESSD 130 140 150 160 170 180 YDSSSSKGKK SRTQKEKKAA RARSKGKNSD EEAPKAAQKK LKLVRTSPEY GMPSVTFGSV 190 200 210 220 HPSDVLDMPV DPNEPTYCLC HQVSYGEMIG CDNPDVRTVS SGLGEEL
	Isoform 4 [UniParc]. Checksum: C1F7459388A4FACD	FASTA	166	19,176
	10 20 30 40 50 60 MAAGMYLEHY LDSIENLPFE LQRNFQLMRD LDQRTEDLKA EIDKLATEYM SSARSLSSEE 70 80 90 100 110 120 KLALLRQIQE AYGKCKEFGD DKVQLAMQTY EMVDKHIRRL DTDLARFEAD LKEKQIESSD 130 140 150 160 YDSSSSKGKK SRTQKEKKAA RARSKGKNSD EEAPKAAQKK LKLVRT
	Isoform 5 [UniParc]. Checksum: 1B865B7AB7E683A8	FASTA	168	19,433
	10 20 30 40 50 60 MAAGMYLEHY LDSIENLPFE LQRNFQLMRD LDQRTEDLKA EIDKLATEYM SSARSLSSEE 70 80 90 100 110 120 KLALLRQIQE AYGKCKEFGD DKVQLAMQTY EMVDKHIRRL DTDLARFEAD LKEKQIESSD 130 140 150 160 YDSSSSKGRT QKEKKAARAR SKGKNSDEEA PKAAQKKLKL VRTSPMER

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of mouse ING1 homolog splicing variants." Ha S., Lee S., Choi Y. Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3; 4 AND 5). Strain: ICR.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Kidney, Pancreas, Testis and Tongue.
[3]	"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] (ISOFORM 2). Strain: FVB/N. Tissue: Mammary tumor.
[4]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-150, MASS SPECTROMETRY. Tissue: Melanoma.
[5]	"Solution structure of PHD domain in ING1-like protein BAC25079." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2004) to the PDB data bank Cited for: STRUCTURE BY NMR OF 168-245.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY035880 mRNA. Translation: AAK63168.1.
AY035881 mRNA. Translation: AAK63169.1.
AY036107 mRNA. Translation: AAK64509.1.
AK002821 mRNA. Translation: BAC25009.1. Frameshift.
AK009267 mRNA. Translation: BAB26183.1.
AK031633 mRNA. Translation: BAC27489.1.
AK050522 mRNA. Translation: BAC34304.1.
BC009127 mRNA. Translation: AAH09127.1.

IPI

IPI00187468.
IPI00336376.
IPI00515302.
IPI00515461.
IPI00515729.

RefSeq

NP_579923.1. NM_133345.2.

UniGene

Mm.262547.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WEN	NMR	-	A	188-244	[»]
1WEU	NMR	-	A	168-244	[»]

ProteinModelPortal

Q8C0D7.

SMR

Q8C0D7. Positions 4-105, 169-245.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q8C0D7. 3 interactions.

PTM databases

PhosphoSite

Q8C0D7.

Proteomic databases

PRIDE

Q8C0D7.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000032480; ENSMUSP00000032480; ENSMUSG00000030330.
ENSMUST00000112417; ENSMUSP00000108036; ENSMUSG00000030330.
ENSMUST00000140131; ENSMUSP00000121519; ENSMUSG00000030330.
ENSMUST00000140883; ENSMUSP00000118561; ENSMUSG00000030330.
ENSMUST00000151125; ENSMUSP00000119709; ENSMUSG00000030330.

GeneID

28019.

KEGG

mmu:28019.

UCSC

uc009dtd.1. mouse.
uc009dtf.1. mouse.

Organism-specific databases

CTD

51147.

MGI

MGI:107307. Ing4.

Phylogenomic databases

eggNOG

COG5034.

GeneTree

ENSGT00550000074538.

HOGENOM

HOG000239724.

HOVERGEN

HBG006607.

InParanoid

Q8C0D7.

KO

K11346.

OMA

QIESTDY.

OrthoDB

EOG40CHHT.

Gene expression databases

Bgee

Q8C0D7.

CleanEx

MM_ING4.

Genevestigator

Q8C0D7.

GermOnline

ENSMUSG00000030330. Mus musculus.

Family and domain databases

Gene3D

3.30.40.10. 1 hit.

InterPro

IPR024610. ING_N.
IPR019786. Zinc_finger_PHD-type_CS.
IPR011011. Znf_FYVE_PHD.
IPR001965. Znf_PHD.
IPR019787. Znf_PHD-finger.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]

Pfam

PF12998. ING. 1 hit.
PF00628. PHD. 1 hit.
[Graphical view]

SMART

SM00249. PHD. 1 hit.
[Graphical view]

SUPFAM

SSF57903. FYVE_PHD_ZnF. 1 hit.

PROSITE

PS01359. ZF_PHD_1. 1 hit.
PS50016. ZF_PHD_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q8C0D7.

NextBio

306534.

SOURCE

Search...

Entry information

Entry name

ING4_MOUSE

Accession

Primary (citable) accession number: Q8C0D7
Secondary accession number(s): Q8C1S7 , Q8K3Q5, Q8K3Q6, Q8K3Q7, Q9D7F9

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 4, 2005
Last sequence update:	January 4, 2005
Last modified:	April 3, 2013
This is version 99 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program