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Protein

Proliferation marker protein Ki-67

Gene

MKI67

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). Associates with the surface of the mitotic chromosome, the perichromosomal layer, and covers a substantial fraction of the chromosome surface (PubMed:27362226). Prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization (PubMed:24867636). It is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in maintaining mitotic chromosomes dispersed (Probable).By similarity3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi3034 – 3041ATPSequence analysis8

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • DNA binding Source: UniProtKB-KW
  • protein C-terminus binding Source: UniProtKB
  • RNA binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionDNA-binding
Biological processCell cycle
LigandATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Proliferation marker protein Ki-67Curated
Alternative name(s):
Antigen identified by monoclonal antibody Ki-671 Publication
Short name:
Antigen KI-67Curated
Short name:
Antigen Ki67Curated
Gene namesi
Name:MKI67Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000148773.12.
HGNCiHGNC:7107. MKI67.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Nucleus

Pathology & Biotechi

Biotechnological usei

Widely used as a marker to assess cell proliferation, as it is detected in the nucleus of proliferating cells only (PubMed:6339421, PubMed:21960707). In cancer research field for example, MKI67 is the most widely used marker for comparing proliferation between tumor samples (PubMed:21960707, PubMed:26680267).2 Publications1 Publication

Organism-specific databases

DisGeNETi4288.
OpenTargetsiENSG00000148773.
PharmGKBiPA30825.

Polymorphism and mutation databases

BioMutaiMKI67.
DMDMi118572663.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000843011 – 3256Proliferation marker protein Ki-67Add BLAST3256

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei125PhosphoserineCombined sources1
Modified residuei128PhosphoserineCombined sources1
Modified residuei166PhosphoserineBy similarity1
Cross-linki245Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei264PhosphoserineCombined sources1
Modified residuei296PhosphoserineBy similarity1
Modified residuei308PhosphoserineCombined sources1
Modified residuei328PhosphothreonineCombined sources1
Modified residuei347PhosphothreonineCombined sources1
Modified residuei352PhosphoserineCombined sources1
Modified residuei357PhosphoserineCombined sources1
Modified residuei374PhosphoserineBy similarity1
Modified residuei401PhosphothreonineCombined sources1
Modified residuei411PhosphoserineCombined sources1
Modified residuei538PhosphoserineCombined sources1
Modified residuei543PhosphothreonineCombined sources1
Modified residuei579PhosphoserineCombined sources1
Modified residuei584PhosphoserineCombined sources1
Modified residuei648PhosphoserineCombined sources1
Modified residuei761PhosphothreonineCombined sources1
Modified residuei859PhosphoserineCombined sources1
Modified residuei1017PhosphothreonineCombined sources1
Cross-linki1022Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki1035Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei1071PhosphoserineCombined sources1
Modified residuei1091PhosphothreonineCombined sources1
Cross-linki1093Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)Combined sources
Cross-linki1093Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei1098PhosphoserineCombined sources1
Modified residuei1111PhosphothreonineCombined sources1
Modified residuei1131PhosphoserineCombined sources1
Modified residuei1139PhosphothreonineCombined sources1
Modified residuei1142PhosphoserineCombined sources1
Modified residuei1167PhosphothreonineCombined sources1
Modified residuei1169PhosphoserineBy similarity1
Modified residuei1176PhosphothreonineCombined sources1
Cross-linki1185Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki1188Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei1193PhosphothreonineCombined sources1
Modified residuei1207PhosphoserineCombined sources1
Modified residuei1233PhosphothreonineCombined sources1
Modified residuei1253PhosphoserineCombined sources1
Modified residuei1256PhosphoserineCombined sources1
Modified residuei1261PhosphothreonineCombined sources1
Modified residuei1298PhosphothreonineCombined sources1
Modified residuei1315PhosphothreonineCombined sources1
Modified residuei1327PhosphothreonineCombined sources1
Modified residuei1329PhosphoserineCombined sources1
Modified residuei1335PhosphothreonineCombined sources1
Cross-linki1337Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei1355PhosphothreonineCombined sources1
Modified residuei1376PhosphoserineCombined sources1
Modified residuei1383PhosphothreonineCombined sources1
Modified residuei1386PhosphoserineBy similarity1
Modified residuei1420PhosphothreonineBy similarity1
Modified residuei1437PhosphothreonineBy similarity1
Modified residuei1496PhosphoserineCombined sources1
Modified residuei1503PhosphothreonineCombined sources1
Modified residuei1506PhosphoserineCombined sources1
Modified residuei1540PhosphothreonineCombined sources1
Modified residuei1552PhosphotyrosineCombined sources1
Modified residuei1557PhosphothreonineCombined sources1
Modified residuei1569PhosphothreonineCombined sources1
Modified residuei1571PhosphoserineCombined sources1
Modified residuei1617PhosphoserineBy similarity1
Modified residuei1639N6-acetyllysineCombined sources1
Cross-linki1643Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei1679PhosphoserineCombined sources1
Modified residuei1689PhosphoserineCombined sources1
Cross-linki1703Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei1719PhosphothreonineCombined sources1
Modified residuei1721PhosphoserineCombined sources1
Modified residuei1740PhosphoserineCombined sources1
Modified residuei1747PhosphothreonineCombined sources1
Modified residuei1764PhosphothreonineCombined sources1
Modified residuei1784PhosphothreonineCombined sources1
Modified residuei1801PhosphothreonineCombined sources1
Modified residuei1815PhosphoserineCombined sources1
Modified residuei1841PhosphothreonineCombined sources1
Modified residuei1861PhosphoserineCombined sources1
Modified residuei1864PhosphoserineCombined sources1
Modified residuei1869PhosphothreonineCombined sources1
Modified residuei1897PhosphothreonineCombined sources1
Modified residuei1906PhosphothreonineBy similarity1
Modified residuei1923PhosphothreonineCombined sources1
Modified residuei1937PhosphoserineCombined sources1
Modified residuei1963PhosphothreonineCombined sources1
Modified residuei1983PhosphoserineCombined sources1
Modified residuei2005N6-acetyllysineCombined sources1
Cross-linki2009Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)Combined sources
Cross-linki2009Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei2028PhosphothreonineBy similarity1
Modified residuei2065PhosphothreonineCombined sources1
Cross-linki2067Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)Combined sources
Cross-linki2067Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei2072PhosphoserineCombined sources1
Modified residuei2085PhosphothreonineCombined sources1
Modified residuei2105PhosphoserineCombined sources1
Modified residuei2113PhosphothreonineCombined sources1
Modified residuei2116PhosphoserineBy similarity1
Modified residuei2135PhosphoserineCombined sources1
Modified residuei2146PhosphothreonineBy similarity1
Modified residuei2163PhosphothreonineBy similarity1
Modified residuei2203PhosphothreonineCombined sources1
Modified residuei2223PhosphoserineCombined sources1
Modified residuei2231PhosphothreonineCombined sources1
Modified residuei2233PhosphothreonineCombined sources1
Modified residuei2239PhosphoserineCombined sources1
Modified residuei2259PhosphothreonineBy similarity1
Modified residuei2261PhosphoserineBy similarity1
Modified residuei2268PhosphothreonineCombined sources1
Modified residuei2285PhosphothreonineCombined sources1
Modified residuei2325PhosphothreonineCombined sources1
Modified residuei2328PhosphothreonineCombined sources1
Modified residuei2333PhosphothreonineCombined sources1
Modified residuei2344PhosphoserineCombined sources1
Modified residuei2352PhosphothreonineCombined sources1
Modified residuei2389PhosphothreonineCombined sources1
Modified residuei2395PhosphoserineCombined sources1
Modified residuei2406PhosphothreonineCombined sources1
Modified residuei2420PhosphoserineCombined sources1
Modified residuei2426PhosphothreonineCombined sources1
Modified residuei2446PhosphothreonineCombined sources1
Modified residuei2466PhosphoserineCombined sources1
Cross-linki2492Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)Combined sources
Modified residuei2505PhosphoserineCombined sources1
Modified residuei2528PhosphoserineCombined sources1
Modified residuei2588PhosphoserineCombined sources1
Cross-linki2613Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)Combined sources
Cross-linki2613Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei2638PhosphoserineCombined sources1
Modified residuei2708PhosphoserineCombined sources1
Cross-linki2734Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)Combined sources
Cross-linki2734Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei2827PhosphoserineCombined sources1
Modified residuei2828PhosphoserineCombined sources1
Modified residuei2838PhosphoserineBy similarity1
Cross-linki2852Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)Combined sources
Cross-linki2852Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki2967Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei2986N6-acetyllysineBy similarity1
Modified residuei3041PhosphoserineCombined sources1
Modified residuei3128PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated. Hyperphosphorylated in mitosis (PubMed:10502411, PubMed:10653604). Hyperphosphorylated form does not bind DNA.2 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP46013.
MaxQBiP46013.
PaxDbiP46013.
PeptideAtlasiP46013.
PRIDEiP46013.

PTM databases

iPTMnetiP46013.
PhosphoSitePlusiP46013.
SwissPalmiP46013.

Expressioni

Developmental stagei

Expression occurs preferentially during late G1, S, G2 and M phases of the cell cycle, while in cells in G0 phase the antigen cannot be detected (at protein level) (PubMed:6206131). Present at highest level in G2 phase and during mitosis (at protein level). In interphase, forms fiber-like structures in fibrillarin-deficient regions surrounding nucleoli (PubMed:2674163, PubMed:8799815).3 Publications

Gene expression databases

BgeeiENSG00000148773.
CleanExiHS_MKI67.
GenevisibleiP46013. HS.

Organism-specific databases

HPAiCAB000058.
CAB068198.
HPA000451.
HPA001164.

Interactioni

Subunit structurei

Interacts with KIF15 (PubMed:10878014). Interacts (via the FHA domain) with NIFK (PubMed:11342549, PubMed:14659764, PubMed:16244663). Interacts with PPP1CC (PubMed:24867636). Part of a complex composed at least of ASCL2, EMSY, HCFC1, HSPA8, CCAR2, MATR3, MKI67, RBBP5, TUBB2A, WDR5 and ZNF335; this complex may have a histone H3-specific methyltransferase activity (PubMed:19131338, PubMed:23178126).7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
KIF15Q9NS874EBI-876367,EBI-712159

GO - Molecular functioni

  • protein C-terminus binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110434. 53 interactors.
DIPiDIP-28132N.
IntActiP46013. 44 interactors.
MINTiMINT-137995.
STRINGi9606.ENSP00000357643.

Structurei

Secondary structure

13256
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi5 – 12Combined sources8
Beta strandi15 – 21Combined sources7
Beta strandi24 – 32Combined sources9
Beta strandi35 – 38Combined sources4
Beta strandi49 – 53Combined sources5
Beta strandi58 – 60Combined sources3
Beta strandi65 – 67Combined sources3
Beta strandi80 – 82Combined sources3
Beta strandi86 – 89Combined sources4
Beta strandi94 – 99Combined sources6
Beta strandi515 – 517Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1R21NMR-A1-120[»]
2AFFNMR-A1-120[»]
5J28X-ray2.00C/D496-536[»]
ProteinModelPortaliP46013.
SMRiP46013.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP46013.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 76FHAPROSITE-ProRule annotationAdd BLAST50
Domaini502 – 549PP1-bindingSequence analysisAdd BLAST48
Repeati1001 – 1112K167R 1Sequence analysisAdd BLAST112
Repeati1123 – 1234K167R 2Sequence analysisAdd BLAST112
Repeati1245 – 1356K167R 3Sequence analysisAdd BLAST112
Repeati1367 – 1477K167R 4Sequence analysisAdd BLAST111
Repeati1488 – 1597K167R 5Sequence analysisAdd BLAST110
Repeati1609 – 1720K167R 6Sequence analysisAdd BLAST112
Repeati1731 – 1842K167R 7Sequence analysisAdd BLAST112
Repeati1854 – 1964K167R 8Sequence analysisAdd BLAST111
Repeati1975 – 2086K167R 9Sequence analysisAdd BLAST112
Repeati2097 – 2204K167R 10Sequence analysisAdd BLAST108
Repeati2215 – 2326K167R 11Sequence analysisAdd BLAST112
Repeati2336 – 2447K167R 12Sequence analysisAdd BLAST112
Repeati2458 – 2569K167R 13Sequence analysisAdd BLAST112
Repeati2700 – 2805K167R 15Sequence analysisAdd BLAST106
Repeati2819 – 2928K167R 16Sequence analysisAdd BLAST110

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1000 – 292816 X 122 AA approximate repeats1 PublicationAdd BLAST1929

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410JR7C. Eukaryota.
ENOG410ZXYW. LUCA.
GeneTreeiENSGT00530000064425.
HOGENOMiHOG000113223.
HOVERGENiHBG006213.
InParanoidiP46013.
KOiK17582.
OMAiQTPKEKA.
OrthoDBiEOG091G005S.
PhylomeDBiP46013.
TreeFamiTF336000.

Family and domain databases

InterProiView protein in InterPro
IPR000253. FHA_dom.
IPR012568. K167R.
IPR029334. PP1-bd.
IPR008984. SMAD_FHA_domain.
PfamiView protein in Pfam
PF00498. FHA. 1 hit.
PF08065. K167R. 16 hits.
PF15276. PP1_bind. 1 hit.
SMARTiView protein in SMART
SM00240. FHA. 1 hit.
SM01295. K167R. 16 hits.
SUPFAMiSSF49879. SSF49879. 1 hit.
PROSITEiView protein in PROSITE
PS50006. FHA_DOMAIN. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Long (identifier: P46013-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MWPTRRLVTI KRSGVDGPHF PLSLSTCLFG RGIECDIRIQ LPVVSKQHCK
60 70 80 90 100
IEIHEQEAIL HNFSSTNPTQ VNGSVIDEPV RLKHGDVITI IDRSFRYENE
110 120 130 140 150
SLQNGRKSTE FPRKIREQEP ARRVSRSSFS SDPDEKAQDS KAYSKITEGK
160 170 180 190 200
VSGNPQVHIK NVKEDSTADD SKDSVAQGTT NVHSSEHAGR NGRNAADPIS
210 220 230 240 250
GDFKEISSVK LVSRYGELKS VPTTQCLDNS KKNESPFWKL YESVKKELDV
260 270 280 290 300
KSQKENVLQY CRKSGLQTDY ATEKESADGL QGETQLLVSR KSRPKSGGSG
310 320 330 340 350
HAVAEPASPE QELDQNKGKG RDVESVQTPS KAVGASFPLY EPAKMKTPVQ
360 370 380 390 400
YSQQQNSPQK HKNKDLYTTG RRESVNLGKS EGFKAGDKTL TPRKLSTRNR
410 420 430 440 450
TPAKVEDAAD SATKPENLSS KTRGSIPTDV EVLPTETEIH NEPFLTLWLT
460 470 480 490 500
QVERKIQKDS LSKPEKLGTT AGQMCSGLPG LSSVDINNFG DSINESEGIP
510 520 530 540 550
LKRRRVSFGG HLRPELFDEN LPPNTPLKRG EAPTKRKSLV MHTPPVLKKI
560 570 580 590 600
IKEQPQPSGK QESGSEIHVE VKAQSLVISP PAPSPRKTPV ASDQRRRSCK
610 620 630 640 650
TAPASSSKSQ TEVPKRGGRK SGNLPSKRVS ISRSQHDILQ MICSKRRSGA
660 670 680 690 700
SEANLIVAKS WADVVKLGAK QTQTKVIKHG PQRSMNKRQR RPATPKKPVG
710 720 730 740 750
EVHSQFSTGH ANSPCTIIIG KAHTEKVHVP ARPYRVLNNF ISNQKMDFKE
760 770 780 790 800
DLSGIAEMFK TPVKEQPQLT STCHIAISNS ENLLGKQFQG TDSGEEPLLP
810 820 830 840 850
TSESFGGNVF FSAQNAAKQP SDKCSASPPL RRQCIRENGN VAKTPRNTYK
860 870 880 890 900
MTSLETKTSD TETEPSKTVS TANRSGRSTE FRNIQKLPVE SKSEETNTEI
910 920 930 940 950
VECILKRGQK ATLLQQRREG EMKEIERPFE TYKENIELKE NDEKMKAMKR
960 970 980 990 1000
SRTWGQKCAP MSDLTDLKSL PDTELMKDTA RGQNLLQTQD HAKAPKSEKG
1010 1020 1030 1040 1050
KITKMPCQSL QPEPINTPTH TKQQLKASLG KVGVKEELLA VGKFTRTSGE
1060 1070 1080 1090 1100
TTHTHREPAG DGKSIRTFKE SPKQILDPAA RVTGMKKWPR TPKEEAQSLE
1110 1120 1130 1140 1150
DLAGFKELFQ TPGPSEESMT DEKTTKIACK SPPPESVDTP TSTKQWPKRS
1160 1170 1180 1190 1200
LRKADVEEEF LALRKLTPSA GKAM