Q9BYG3 (MK67I_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
MKI67 FHA domain-interacting nucleolar phosphoprotein

Alternative name(s):
Nucleolar phosphoprotein Nopp34
Nucleolar protein interacting with the FHA domain of pKI-67
Short name=hNIFK

Gene names

Name:	MKI67IP
Synonyms:	NIFK, NOPP34

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	293 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)

Subunit structure	Binds to the FHA domain of MKI67; this interaction is enhanced in mitosis. Ref.1 Ref.8
Subcellular location	Nucleus › nucleolus. Chromosome. Note: Localizes to mitotic chromosomes in conjunction with MKI67. Ref.1 Ref.7
Post-translational modification	Sequentially phosphorylated on Thr-238, Thr-234 and Ser-230. Thr-234 is phosphorylated only when Thr-238 is phosphorylated. Likewise, phosphorylation at Ser-230 requires that Thr-234 and Thr-238 are phosphorylated. Phosphorylation enhances MKI67 binding. Ref.1 Ref.8 Ref.15
Sequence similarities	Contains 1 RRM (RNA recognition motif) domain.

Ontologies

Keywords
Cellular component	Chromosome Nucleus
Coding sequence diversity	Polymorphism
Ligand	RNA-binding
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of phosphatase activity Inferred from direct assay PubMed 19389623. Source: UniProtKB protein complex assembly Non-traceable author statement Ref.1. Source: UniProtKB rRNA metabolic process Non-traceable author statement Ref.1. Source: UniProtKB rRNA transcription Non-traceable author statement Ref.1. Source: UniProtKB
Cellular_component	condensed nuclear chromosome Inferred from direct assay Ref.1. Source: UniProtKB cytoplasm Inferred from direct assay Ref.1. Source: UniProtKB nucleolus Inferred from direct assay Ref.1. Source: UniProtKB nucleoplasm Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	RNA binding Inferred from direct assay Ref.1. Source: UniProtKB nucleotide binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.6

Chain

2 – 293

292

MKI67 FHA domain-interacting nucleolar phosphoprotein

PRO_0000081629

Regions

Domain

45 – 123

79

RRM

Region

226 – 269

44

Interaction with MKI67

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.6

Modified residue

218

1

Phosphoserine Ref.12 Ref.14

Modified residue

223

1

Phosphothreonine Ref.9 Ref.12 Ref.14

Modified residue

230

1

Phosphoserine Ref.15

Modified residue

234

1

Phosphothreonine Ref.8 Ref.10 Ref.15

Modified residue

238

1

Phosphothreonine Ref.10 Ref.15

Modified residue

247

1

Phosphoserine Ref.14

Modified residue

279

1

Phosphothreonine Ref.10

Natural variations

Natural variant

144

1

P → Q. Ref.5
Corresponds to variant rs17852212 [ dbSNP | Ensembl ].

VAR_027182

Experimental info

Mutagenesis

230

1

S → A: Loss of phosphorylation site. Ref.15

Mutagenesis

234

1

T → A: Loss of phosphorylation site. Abrogates interaction with MKI67. Ref.1 Ref.15

Mutagenesis

235

1

P → A: Reduces phosphorylation at T-234. Ref.15

Mutagenesis

238

1

T → A: Loss of phosphorylation site. Abrogates interaction with MKI67. Ref.1 Ref.15

Mutagenesis

239

1

P → A: Reduces phosphorylation at T-234 and T-238. Ref.15

Secondary structure

1

.

.

.

.

.

.

.

293

Helix Strand Turn

Details...

Helix

239 – 251

13

Helix

254 – 257

4

Beta strand

260 – 265

6

Sequences

	Sequence		Length	Mass (Da)
	Q9BYG3 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 9D288ECF2B4CE119	FASTA	293	34,222
	10 20 30 40 50 60 MATFSGPAGP ILSLNPQEDV EFQKEVAQVR KRITQRKKQE QLTPGVVYVR HLPNLLDETQ 70 80 90 100 110 120 IFSYFSQFGT VTRFRLSRSK RTGNSKGYAF VEFESEDVAK IVAETMNNYL FGERLLECHF 130 140 150 160 170 180 MPPEKVHKEL FKDWNIPFKQ PSYPSVKRYN RNRTLTQKLR MEERFKKKER LLRKKLAKKG 190 200 210 220 230 240 IDYDFPSLIL QKTESISKTN RQTSTKGQVL RKKKKKVSGT LDTPEKTVDS QGPTPVCTPT 250 260 270 280 290 FLERRKSQVA ELNDDDKDDE IVFKQPISCV KEEIQETQTP THSRKKRRRS SNQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel nucleolar protein, NIFK, interacts with the forkhead associated domain of Ki-67 antigen in mitosis." Takagi M., Sueishi M., Saiwaki T., Kametaka A., Yoneda Y. J. Biol. Chem. 276:25386-25391(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH MKI67, MUTAGENESIS OF THR-234 AND THR-238, SUBCELLULAR LOCATION, PHOSPHORYLATION.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skeletal muscle.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases 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], VARIANT GLN-144. Tissue: Brain, Lung and Placenta.
[6]	Bienvenut W.V., Waridel P., Quadroni M. Submitted (MAR-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-24; 87-114; 180-192; 227-244 AND 272-284, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"Functional proteomic analysis of human nucleolus." Scherl A., Coute Y., Deon C., Calle A., Kindbeiter K., Sanchez J.-C., Greco A., Hochstrasser D.F., Diaz J.-J. Mol. Biol. Cell 13:4100-4109(2002) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[8]	"Structure of human Ki67 FHA domain and its binding to a phosphoprotein fragment from hNIFK reveal unique recognition sites and new views to the structural basis of FHA domain functions." Li H., Byeon I.-J., Ju Y., Tsai M.-D. J. Mol. Biol. 335:371-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-234, INTERACTION WITH MKI67.
[9]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-223, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-234; THR-238 AND THR-279, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[12]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218 AND THR-223, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218; THR-223 AND SER-247, MASS SPECTROMETRY.
[15]	"Sequential phosphorylation and multisite interactions characterize specific target recognition by the FHA domain of Ki67." Byeon I.-J., Li H., Song H., Gronenborn A.M., Tsai M.-D. Nat. Struct. Mol. Biol. 12:987-993(2005) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 226-269 IN COMPLEX WITH MKI67, MASS SPECTROMETRY, MUTAGENESIS OF SER-230; THR-234; PRO-235; THR-238 AND PRO-239, PHOSPHORYLATION AT SER-230; THR-234 AND THR-238.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB044971 mRNA. Translation: BAB41210.1.
AK291903 mRNA. Translation: BAF84592.1.
AC018737 Genomic DNA. Translation: AAY14830.1.
CH471103 Genomic DNA. Translation: EAW95261.1.
BC012457 mRNA. Translation: AAH12457.1.
BC022990 mRNA. Translation: AAH22990.1.
BC024238 mRNA. Translation: AAH24238.1.

IPI

IPI00154590.

RefSeq

NP_115766.3. NM_032390.4.

UniGene

Hs.367842.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2AFF	NMR	-	B	226-269	[»]

ProteinModelPortal

Q9BYG3.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-28134N.

IntAct

Q9BYG3. 5 interactions.

MINT

MINT-1031770.

STRING

9606.ENSP00000285814.

PTM databases

PhosphoSite

Q9BYG3.

Polymorphism databases

DMDM

71151919.

2D gel databases

SWISS-2DPAGE

Q9BYG3.

Proteomic databases

PaxDb

Q9BYG3.

PeptideAtlas

Q9BYG3.

PRIDE

Q9BYG3.

Protocols and materials databases

DNASU

84365.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000285814; ENSP00000285814; ENSG00000155438.

GeneID

84365.

KEGG

hsa:84365.

UCSC

uc002tnk.3. human.

Organism-specific databases

CTD

84365.

GeneCards

GC02M122484.

HGNC

HGNC:17838. MKI67IP.

HPA

CAB015382.

MIM

611970. gene.

neXtProt

NX_Q9BYG3.

PharmGKB

PA38470.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG244773.

HOGENOM

HOG000242795.

HOVERGEN

HBG057796.

InParanoid

Q9BYG3.

KO

K14838.

OMA

QVRKRIT.

OrthoDB

EOG4MKNGX.

PhylomeDB

Q9BYG3.

Gene expression databases

ArrayExpress

Q9BYG3.

Bgee

Q9BYG3.

CleanEx

HS_MKI67IP.

Genevestigator

Q9BYG3.

GermOnline

ENSG00000155438. Homo sapiens.

Family and domain databases

Gene3D

3.30.70.330. 1 hit.

InterPro

IPR021043. hNIFK_FHA_Ki67_binding.
IPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view]

Pfam

PF12196. hNIFK_binding. 1 hit.
PF00076. RRM_1. 1 hit.
[Graphical view]

SMART

SM00360. RRM. 1 hit.
[Graphical view]

PROSITE

PS50102. RRM. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9BYG3.

GenomeRNAi

84365.

NextBio

74141.

SOURCE

Search...

Entry information

Entry name

MK67I_HUMAN

Accession

Primary (citable) accession number: Q9BYG3
Secondary accession number(s): A8K788, Q8TB66, Q96ED4

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2005
Last sequence update:	June 1, 2001
Last modified:	May 1, 2013
This is version 108 of the entry and version 1 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.