Protein

Runt-related transcription factor 2

Gene

RUNX2

Organism

Homo sapiens (Human)

Status

Reviewed-Annotation score: -Experimental evidence at protein levelⁱ

Functionⁱ

Transcription factor involved in osteoblastic differentiation and skeletal morphogenesis. Essential for the maturation of osteoblasts and both intramembranous and endochondral ossification. CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, osteocalcin, osteopontin, bone sialoprotein, alpha 1(I) collagen, LCK, IL-3 and GM-CSF promoters. In osteoblasts, supports transcription activation: synergizes with SPEN/MINT to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Inhibits KAT6B-dependent transcriptional activation.By similarity1 Publication

GO - Molecular functionⁱ

ATP binding Source: InterPro
bHLH transcription factor binding Source: Ensembl
chromatin binding Source: Ensembl
protein domain specific binding Source: Ensembl
repressing transcription factor binding Source: Ensembl
RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: Ensembl
RNA polymerase II core promoter sequence-specific DNA binding Source: Ensembl
RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: GO_Central
transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: Ensembl
transcription factor activity, sequence-specific DNA binding
Source: ProtInc
Non-traceable author statementⁱ
- 9182765

Complete GO annotation...

GO - Biological processⁱ

BMP signaling pathway Source: BHF-UCL
cell maturation Source: Ensembl
cellular response to BMP stimulus Source: BHF-UCL
chondrocyte development Source: Ensembl
chondrocyte differentiation Source: GO_Central
embryonic cranial skeleton morphogenesis Source: Ensembl
embryonic forelimb morphogenesis Source: Ensembl
endochondral ossification Source: Ensembl
hemopoiesis Source: GO_Central
negative regulation of smoothened signaling pathway Source: Ensembl
negative regulation of transcription, DNA-templated
Source: UniProtKB
Inferred from direct assayⁱ
- 11965546
neuron differentiation Source: GO_Central
odontogenesis of dentin-containing tooth Source: Ensembl
ossification
Source: UniProtKB
Traceable author statementⁱ
- 12217689
osteoblast development Source: Ensembl
osteoblast differentiation
Source: UniProtKB
Inferred from expression patternⁱ
- 20128911
osteoblast fate commitment Source: Ensembl
positive regulation of cell proliferation Source: Ensembl
positive regulation of chondrocyte differentiation Source: Ensembl
positive regulation of osteoblast differentiation Source: Ensembl
positive regulation of transcription, DNA-templated
Source: UniProtKB
Inferred from direct assayⁱ
- 11965546
positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus Source: BHF-UCL
regulation of cell differentiation Source: GO_Central
regulation of fibroblast growth factor receptor signaling pathway Source: Ensembl
regulation of odontogenesis of dentin-containing tooth Source: Ensembl
regulation of transcription from RNA polymerase II promoter Source: GO_Central
stem cell differentiation Source: Ensembl
T cell differentiation Source: Ensembl

Complete GO annotation...

Keywordsⁱ

Molecular function	DNA-binding
Biological process	Transcription, Transcription regulation

Enzyme and pathway databases

Reactomeⁱ	R-HSA-2032785. YAP1- and WWTR1 (TAZ)-stimulated gene expression.
SignaLinkⁱ	Q13950.
SIGNORⁱ	Q13950.

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Runt-related transcription factor 2 Alternative name(s): Acute myeloid leukemia 3 protein Core-binding factor subunit alpha-1 Short name: CBF-alpha-1 Oncogene AML-3 Osteoblast-specific transcription factor 2 Short name: OSF-2 Polyomavirus enhancer-binding protein 2 alpha A subunit Short name: PEA2-alpha A Short name: PEBP2-alpha A SL3-3 enhancer factor 1 alpha A subunit SL3/AKV core-binding factor alpha A subunit
Gene namesⁱ	Name:RUNX2 Synonyms:AML3, CBFA1, OSF2, PEBP2A
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 6

Organism-specific databases

Human Gene Nomenclature Database More...HGNCⁱ	HGNC:10472. RUNX2.

HGNCⁱ

HGNC:10472. RUNX2.

Subcellular locationⁱ

Nucleus

GO - Cellular componentⁱ

cytoplasm Source: Ensembl
nuclear chromatin Source: BHF-UCL
nucleoplasm Source: HPA
nucleus Source: GO_Central
transcription factor complex Source: Ensembl

Complete GO annotation...

Keywords - Cellular componentⁱ

Nucleus

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Cleidocranial dysplasia (CLCD)14 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionAutosomal dominant skeletal disorder with high penetrance and variable expressivity. It is due to defective endochondral and intramembranous bone formation. Typical features include hypoplasia/aplasia of clavicles, patent fontanelles, wormian bones (additional cranial plates caused by abnormal ossification of the calvaria), supernumerary teeth, short stature, and other skeletal changes. In some cases defects in RUNX2 are exclusively associated with dental anomalies.

Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly (MDMHB)1 Publication

The disease is caused by mutations affecting the gene represented in this entry. Analysis for copy-number variations revealed that a 105 kb duplication within RUNX2 segregated with the MDMHB phenotype in a region with maximum linkage. Real-time PCR for copy-number variation in genomic DNA in eight samples, as well as sequence analysis of fibroblast cDNA from one subject with MDMHB confirmed that affected family members were heterozygous for the presence of an intragenic duplication encompassing exons 3 to 5 of RUNX2. These three exons code for the Q/A domain and the functionally essential DNA-binding Runt domain of RUNX2. The RUNX2 duplication found in individuals with MDMHB leads to a gain of function (PubMed:23290074).1 Publication

Disease descriptionAn autosomal dominant bone dysplasia characterized by metaphyseal flaring of long bones, enlargement of the medial halves of the clavicles, maxillary hypoplasia, variable brachydactyly, and dystrophic teeth.

Mutagenesis

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Mutagenesisⁱ	451	S → A: Reduced DNA-binding and impaired phosphorylation. 1 Publication		1

Keywords - Diseaseⁱ

Disease mutation

Organism-specific databases

DisGeNET More...DisGeNETⁱ	860.
MalaCards human disease database More...MalaCardsⁱ	RUNX2.
MIMⁱ	119600. phenotype. 156510. phenotype.
Open Targets More...OpenTargetsⁱ	ENSG00000124813.
Orphanetⁱ	1452. Cleidocranial dysplasia. 2504. Metaphyseal dysplasia - maxillary hypoplasia - brachydacty.
PharmGKBⁱ	PA34885.

Polymorphism and mutation databases

BioMutaⁱ	RUNX2.
DMDMⁱ	17368460.

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000174659	1 – 521	Runt-related transcription factor 2Add BLAST		521

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	267	Asymmetric dimethylarginineBy similarity	1
Modified residueⁱ	451	Phosphoserine; by CDK11 Publication	1
Isoform 3 (identifier: Q13950-3)
Modified residueⁱ	340	PhosphoserineCombined sources	1

Post-translational modificationⁱ

Phosphorylated; probably by MAP kinases (MAPK). Phosphorylation by HIPK3 is required for the SPEN/MINT and FGF2 transactivation during osteoblastic differentiation (By similarity). Phosphorylation at Ser-451 by CDK1 promotes endothelial cell proliferation required for tumor angiogenesis probably by facilitating cell cycle progression. Isoform 3 is phosphorylated on Ser-340.By similarity1 Publication

Keywords - PTMⁱ

Methylation, Phosphoprotein

Proteomic databases

EPDⁱ	Q13950.
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	Q13950.
PaxDbⁱ	Q13950.
PeptideAtlas More...PeptideAtlasⁱ	Q13950.
PRIDEⁱ	Q13950.

PTM databases

iPTMnetⁱ	Q13950.
PhosphoSitePlusⁱ	Q13950.
SwissPalmⁱ	Q13950.

Expressionⁱ

Tissue specificityⁱ

Specifically expressed in osteoblasts.

Gene expression databases

Bgeeⁱ	ENSG00000124813.
CleanExⁱ	HS_RUNX2.
ExpressionAtlasⁱ	Q13950. baseline and differential.
Genevisibleⁱ	Q13950. HS.

Organism-specific databases

Human Protein Atlas More...HPAⁱ	CAB008374. CAB062561. CAB068226. HPA022040.

HPAⁱ

CAB008374.
CAB062561.
CAB068226.
HPA022040.

Interactionⁱ

Subunit structureⁱ

Heterodimer of an alpha and a beta subunit. The alpha subunit binds DNA as a monomer and through the Runt domain. DNA-binding is increased by heterodimerization. Interacts with XRCC6 (Ku70) and XRCC5 (Ku80). Interacts with HIVEP3. Interacts with IFI204. Interaction with SATB2; the interaction results in enhanced DNA binding and transactivation by these transcription factors. Binds to HIPK3. Interacts (isoform 3) with DDX5. Interacts with FOXO1 (via a C-terminal region); the interaction inhibits RUNX2 transcriptional activity towards BGLAP. This interaction is prevented on insulin or IGF1 stimulation as FOXO1 is exported from the nucleus (By similarity). Interacts with CCNB1, KAT6A and KAT6B. Interacts with FOXP3. Interacts with TMEM119 (By similarity).By similarity4 Publications

Binary interactionsⁱ

With	Entry	#Exp.	IntAct
PIN1	Q13526	7	EBI-976402,EBI-714158
SMAD6	O43541	3	EBI-976402,EBI-976374
TP73	O15350	3	EBI-976402,EBI-389606

Show more details

GO - Molecular functionⁱ

bHLH transcription factor binding Source: Ensembl
protein domain specific binding Source: Ensembl
repressing transcription factor binding Source: Ensembl

Complete GO annotation...

Protein-protein interaction databases

BioGridⁱ	107308. 45 interactors.
Database of interacting proteins More...DIPⁱ	DIP-36707N.
IntActⁱ	Q13950. 6 interactors.
Molecular INTeraction database More...MINTⁱ	MINT-219985.
STRINGⁱ	9606.ENSP00000360493.

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q13950.
SMRⁱ	Q13950.
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	101 – 229	RuntPROSITE-ProRule annotationAdd BLAST		129

Region

Feature key	Position(s)	DescriptionActions	Length
Regionⁱ	242 – 258	Required for interaction with FOXO1By similarityAdd BLAST	17
Regionⁱ	336 – 439	Interaction with KAT6ABy similarityAdd BLAST	104
Regionⁱ	374 – 468	Interaction with KAT6B1 PublicationAdd BLAST	95

Compositional bias

Feature key	Position(s)	DescriptionActions	Length
Compositional biasⁱ	49 – 71	Poly-GlnAdd BLAST	23
Compositional biasⁱ	73 – 89	Poly-AlaAdd BLAST	17
Compositional biasⁱ	237 – 521	Pro/Ser/Thr-richAdd BLAST	285

Domainⁱ

A proline/serine/threonine rich region at the C-terminus is necessary for transcriptional activation of target genes and contains the phosphorylation sites.

Phylogenomic databases

eggNOGⁱ	KOG3982. Eukaryota. ENOG4111J4Y. LUCA.
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00390000016964.
HOGENOMⁱ	HOG000045616.
HOVERGENⁱ	HBG060268.
InParanoidⁱ	Q13950.
KEGG Orthology (KO) More...KOⁱ	K09278.
OMAⁱ	SDPRQFT.
PhylomeDBⁱ	Q13950.
TreeFamⁱ	TF321496.

Family and domain databases

Gene3Dⁱ	2.60.40.720. 1 hit. 4.10.770.10. 1 hit.
InterProⁱ	View protein in InterPro IPR000040. AML1_Runt. IPR008967. p53-like_TF_DNA-bd. IPR012346. p53/RUNT-type_TF_DNA-bd. IPR013524. Runt_dom. IPR027384. Runx_central_dom. IPR013711. RunxI_C_dom. IPR016554. TF_Runt-rel_RUNX.
PANTHERⁱ	PTHR11950. PTHR11950. 1 hit.
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00853. Runt. 1 hit. PF08504. RunxI. 1 hit.
PIRSFⁱ	PIRSF009374. TF_Runt-rel_RUNX. 1 hit.
PRINTSⁱ	PR00967. ONCOGENEAML1.
SUPFAMⁱ	SSF49417. SSF49417. 1 hit.
PROSITEⁱ	View protein in PROSITE PS51062. RUNT. 1 hit.

Sequences (3)ⁱ

Sequence statusⁱ: Complete.

This entry describes 3 isoformsⁱ produced by alternative splicing. Align Add to basket Added to basket

Isoform 1 (identifier: Q13950-1) [UniParc]FASTA Add to basket

Also known as: Cbfa1a

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
MASNSLFSTV TPCQQNFFWD PSTSRRFSPP SSSLQPGKMS DVSPVVAAQQ 
        60         70         80         90        100
QQQQQQQQQQ QQQQQQQQQQ QEAAAAAAAA AAAAAAAAAV PRLRPPHDNR 
       110        120        130        140        150
TMVEIIADHP AELVRTDSPN FLCSVLPSHW RCNKTLPVAF KVVALGEVPD 
       160        170        180        190        200
GTVVTVMAGN DENYSAELRN ASAVMKNQVA RFNDLRFVGR SGRGKSFTLT 
       210        220        230        240        250
ITVFTNPPQV ATYHRAIKVT VDGPREPRRH RQKLDDSKPS LFSDRLSDLG 
       260        270        280        290        300
RIPHPSMRVG VPPQNPRPSL NSAPSPFNPQ GQSQITDPRQ AQSSPPWSYD 
       310        320        330        340        350
QSYPSYLSQM TSPSIHSTTP LSSTRGTGLP AITDVPRRIS DDDTATSDFC 
       360        370        380        390        400
LWPSTLSKKS QAGASELGPF SDPRQFPSIS SLTESRFSNP RMHYPATFTY 
       410        420        430        440        450
TPPVTSGMSL GMSATTHYHT YLPPPYPGSS QSQSGPFQTS STPYLYYGTS 
       460        470        480        490        500
SGSYQFPMVP GGDRSPSRML PPCTTTSNGS TLLNPNLPNQ NDGVDADGSH 
       510        520 
SSSPTVLNSS GRMDESVWRP Y

Length:521

Mass (Da):56,648

Last modified:November 2, 2001 - v2

Checksum:ⁱ44C4F3867D6F3EB1

Isoform 2 (identifier: Q13950-2) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
1-19: MASNSLFSTVTPCQQNFFW → MRIPV

« Hide

        10         20         30         40         50
MRIPVDPSTS RRFSPPSSSL QPGKMSDVSP VVAAQQQQQQ QQQQQQQQQQ 
        60         70         80         90        100
QQQQQQQEAA AAAAAAAAAA AAAAAVPRLR PPHDNRTMVE IIADHPAELV 
       110        120        130        140        150
RTDSPNFLCS VLPSHWRCNK TLPVAFKVVA LGEVPDGTVV TVMAGNDENY 
       160        170        180        190        200
SAELRNASAV MKNQVARFND LRFVGRSGRG KSFTLTITVF TNPPQVATYH 
       210        220        230        240        250
RAIKVTVDGP REPRRHRQKL DDSKPSLFSD RLSDLGRIPH PSMRVGVPPQ 
       260        270        280        290        300
NPRPSLNSAP SPFNPQGQSQ ITDPRQAQSS PPWSYDQSYP SYLSQMTSPS 
       310        320        330        340        350
IHSTTPLSST RGTGLPAITD VPRRISDDDT ATSDFCLWPS TLSKKSQAGA 
       360        370        380        390        400
SELGPFSDPR QFPSISSLTE SRFSNPRMHY PATFTYTPPV TSGMSLGMSA 
       410        420        430        440        450
TTHYHTYLPP PYPGSSQSQS GPFQTSSTPY LYYGTSSGSY QFPMVPGGDR 
       460        470        480        490        500
SPSRMLPPCT TTSNGSTLLN PNLPNQNDGV DADGSHSSSP TVLNSSGRMD 

ESVWRPY

Show »

Length:507

Mass (Da):55,054

Checksum:ⁱ7228C267328DE1DC

Isoform 3 (identifier: Q13950-3) [UniParc]FASTA Add to basket

Also known as: Cbfa1b

The sequence of this isoform differs from the canonical sequence as follows:
341-362: Missing.

« Hide

        10         20         30         40         50
MASNSLFSTV TPCQQNFFWD PSTSRRFSPP SSSLQPGKMS DVSPVVAAQQ 
        60         70         80         90        100
QQQQQQQQQQ QQQQQQQQQQ QEAAAAAAAA AAAAAAAAAV PRLRPPHDNR 
       110        120        130        140        150
TMVEIIADHP AELVRTDSPN FLCSVLPSHW RCNKTLPVAF KVVALGEVPD 
       160        170        180        190        200
GTVVTVMAGN DENYSAELRN ASAVMKNQVA RFNDLRFVGR SGRGKSFTLT 
       210        220        230        240        250
ITVFTNPPQV ATYHRAIKVT VDGPREPRRH RQKLDDSKPS LFSDRLSDLG 
       260        270        280        290        300
RIPHPSMRVG VPPQNPRPSL NSAPSPFNPQ GQSQITDPRQ AQSSPPWSYD 
       310        320        330        340        350
QSYPSYLSQM TSPSIHSTTP LSSTRGTGLP AITDVPRRIS GASELGPFSD 
       360        370        380        390        400
PRQFPSISSL TESRFSNPRM HYPATFTYTP PVTSGMSLGM SATTHYHTYL 
       410        420        430        440        450
PPPYPGSSQS QSGPFQTSST PYLYYGTSSG SYQFPMVPGG DRSPSRMLPP 
       460        470        480        490 
CTTTSNGSTL LNPNLPNQND GVDADGSHSS SPTVLNSSGR MDESVWRPY

Show »

Length:499

Mass (Da):54,249

Checksum:ⁱ4BA956230C96EB2E

Experimental Info

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Sequence conflictⁱ	16	N → S in AAC77441 (PubMed:9651525).Curated		1

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_064081	53	Q → L in CLCD. 1 Publication	1
Natural variantⁱVAR_012131	78 – 83	Missing 1 Publication	6
Natural variantⁱVAR_012130	84	A → AAAAAAAAAAA in CLCD; the patient also shows brachydactyly of hands and feet. 1 Publication	1
Natural variantⁱVAR_012132	113	L → R in CLCD. 1 Publication	1
Natural variantⁱVAR_064082	118	S → N in CLCD. 1 Publication	1
Natural variantⁱVAR_012133	118	S → R in CLCD. 1 Publication	1
Natural variantⁱVAR_012134	121	F → C in CLCD. 1 Publication	1
Natural variantⁱVAR_012135	123	C → R in CLCD. 1 Publication	1
Natural variantⁱVAR_064083	131	R → C in CLCD. 1 Publication	1
Natural variantⁱVAR_064084	131	R → G in CLCD. 1 Publication	1
Natural variantⁱVAR_064085	131	R → S in CLCD. 1 Publication	1
Natural variantⁱVAR_012136	133	Missing in CLCD. 1 Publication	1
Natural variantⁱVAR_064086	136	L → P in CLCD. 1 Publication	1
Natural variantⁱVAR_064087	156	V → D in CLCD. 1 Publication	1
Natural variantⁱVAR_064088	156	V → G in CLCD. 1 Publication	1
Natural variantⁱVAR_064089	169	R → P in CLCD. 2 PublicationsCorresponds to variant dbSNP:rs104893995Ensembl.	1
Natural variantⁱVAR_012137	169	R → Q in CLCD. 1 PublicationCorresponds to variant dbSNP:rs104893995Ensembl.	1
Natural variantⁱVAR_064090	175	M → K in CLCD. 1 Publication	1
Natural variantⁱVAR_012138	175	M → R in CLCD; abolishes DNA binding. 2 PublicationsCorresponds to variant dbSNP:rs104893989Ensembl.	1
Natural variantⁱVAR_064091	175	M → V in CLCD. 1 PublicationCorresponds to variant dbSNP:rs201647225Ensembl.	1
Natural variantⁱVAR_064092	187	F → S in CLCD. 1 Publication	1
Natural variantⁱVAR_012139	190	R → Q in CLCD; abolishes DNA binding. 1 Publication	1
Natural variantⁱVAR_012140	190	R → W in CLCD; has severely impaired DNA binding and transactivation. 3 Publications	1
Natural variantⁱVAR_012141	191	S → N in CLCD; abolishes DNA binding. 2 PublicationsCorresponds to variant dbSNP:rs104893990Ensembl.	1
Natural variantⁱVAR_012142	193	R → C in CLCD. 1 Publication	1
Natural variantⁱVAR_064093	193	R → Q in CLCD. 1 Publication	1
Natural variantⁱVAR_012143	197	F → S in CLCD; retains heterodimerization activity together with a trace potential for DNA binding; retains a low but still substantial transactivation activity. 2 Publications	1
Natural variantⁱVAR_012144	199	L → F in CLCD; abolishes DNA binding. 1 Publication	1
Natural variantⁱVAR_012145	200	T → A in CLCD; mild; associated also with isolated dental anomalies; normal DNA binding. 1 PublicationCorresponds to variant dbSNP:rs104893993Ensembl.	1
Natural variantⁱVAR_064094	200	T → I in CLCD. 1 Publication	1
Natural variantⁱVAR_064095	201	I → K in CLCD. 1 Publication	1
Natural variantⁱVAR_012146	205	T → R in CLCD. 1 Publication	1
Natural variantⁱVAR_064096	209	Q → H in CLCD. 1 Publication	1
Natural variantⁱVAR_012147	209	Q → R in CLCD. 1 Publication	1
Natural variantⁱVAR_064097	211	A → P in CLCD. 1 Publication	1
Natural variantⁱVAR_064098	218	K → E in CLCD. 1 Publication	1
Natural variantⁱVAR_064099	218	K → N in CLCD; has severely impaired DNA binding and transactivation. 1 PublicationCorresponds to variant dbSNP:rs752933596Ensembl.	1
Natural variantⁱVAR_064100	218	K → Q in CLCD. 1 Publication	1
Natural variantⁱVAR_064101	220	T → I in CLCD; has severely impaired DNA binding and transactivation. 1 Publication	1
Natural variantⁱVAR_064102	225	R → L in CLCD. 1 Publication	1
Natural variantⁱVAR_012148	225	R → Q in CLCD; interferes with nuclear localization; abolishes DNA binding. 5 PublicationsCorresponds to variant dbSNP:rs104893991Ensembl.	1
Natural variantⁱVAR_012149	225	R → W in CLCD; interferes with nuclear localization; has severely impaired DNA binding and transactivation. 4 PublicationsCorresponds to variant dbSNP:rs104893992Ensembl.	1
Natural variantⁱVAR_064103	228	R → G in CLCD. 1 Publication	1
Natural variantⁱVAR_064104	233	K → R in CLCD. 1 Publication	1
Natural variantⁱVAR_064105	287	D → N in CLCD. 1 Publication	1
Natural variantⁱVAR_064106	362	A → V in CLCD. 1 Publication	1
Natural variantⁱVAR_064107	420	T → I in CLCD. 1 Publication	1
Natural variantⁱVAR_064108	420	T → N in CLCD. 1 Publication	1
Natural variantⁱVAR_012150	511	G → S in CLCD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs11498198Ensembl.	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Alternative sequenceⁱVSP_005937	1 – 19	MASNS…QNFFW → MRIPV in isoform 2. CuratedAdd BLAST		19
Alternative sequenceⁱVSP_005938	341 – 362	Missing in isoform 3. 1 PublicationAdd BLAST		22

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AF001450 AF001449 Genomic DNA. Translation: AAB65159.2. AF001450 AF001449 Genomic DNA. Translation: AAB65158.1. AL161907, AL096865, AL358135 Genomic DNA. Translation: CAI19638.1. AL161907, AL096865, AL358135 Genomic DNA. Translation: CAI19639.1. AL358135, AL096865, AL161907 Genomic DNA. Translation: CAI13528.1. AL358135, AL096865, AL161907 Genomic DNA. Translation: CAI13531.1. AL096865, AL161907, AL358135 Genomic DNA. Translation: CAI19925.1. AL096865, AL161907, AL358135 Genomic DNA. Translation: CAI19931.1. AF053952 mRNA. Translation: AAC78624.1. AF053949 Genomic DNA. Translation: AAC77441.1. L40992 mRNA. Translation: AAA89072.1.
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS43467.2. [Q13950-1] CCDS43468.2. [Q13950-3]
NCBI Reference Sequences More...RefSeqⁱ	NP_001015051.3. NM_001015051.3. [Q13950-3] NP_001019801.3. NM_001024630.3. [Q13950-1]
UniGeneⁱ	Hs.535845.

Genome annotation databases

Ensemblⁱ	ENST00000359524; ENSP00000352514; ENSG00000124813. [Q13950-2] ENST00000371432; ENSP00000360486; ENSG00000124813. [Q13950-3] ENST00000371436; ENSP00000360491; ENSG00000124813. [Q13950-3] ENST00000371438; ENSP00000360493; ENSG00000124813. [Q13950-1] ENST00000465038; ENSP00000420707; ENSG00000124813. [Q13950-1]
GeneIDⁱ	860.
KEGGⁱ	hsa:860.
UCSC genome browser More...UCSCⁱ	uc003oxt.5. human. [Q13950-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing, Polymorphism

Similar proteinsⁱ

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:

100%	UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%	UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%	UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

The DNASU plasmid repository More...DNASUⁱ	860.
Structural Biology Knowledgebase	Search...

CTDⁱ	860.
DisGeNET More...DisGeNETⁱ	860.
GeneCardsⁱ	RUNX2.
GeneReviewsⁱ	RUNX2.
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:10472. RUNX2.
Human Protein Atlas More...HPAⁱ	CAB008374. CAB062561. CAB068226. HPA022040.
MalaCards human disease database More...MalaCardsⁱ	RUNX2.
MIMⁱ	119600. phenotype. 156510. phenotype. 600211. gene.
neXtProtⁱ	NX_Q13950.
Open Targets More...OpenTargetsⁱ	ENSG00000124813.
Orphanetⁱ	1452. Cleidocranial dysplasia. 2504. Metaphyseal dysplasia - maxillary hypoplasia - brachydacty.
PharmGKBⁱ	PA34885.
GenAtlas: human gene database More...GenAtlasⁱ	Search...

ChiTaRSⁱ	RUNX2. human.
GeneWikiⁱ	RUNX2.
GenomeRNAiⁱ	860.
Protein Ontology More...PROⁱ	PR:Q13950.
SOURCEⁱ	Search...

Entry informationⁱ

Entry nameⁱ	RUNX2_HUMAN
Accessionⁱ	Q13950Primary (citable) accession number: Q13950 Secondary accession number(s): O14614, O14615, O95181
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	November 2, 2001
	Last sequence update:	November 2, 2001
	Last modified:	June 7, 2017
	This is version 175 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	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.

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Documents

Human chromosome 6
Human chromosome 6: entries, gene names and cross-references to MIM
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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UniProtKB - Q13950 (RUNX2_HUMAN)

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Runt-related transcription factor 2

RUNX2

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

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<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

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<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

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<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including length and molecular weight.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3)i

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<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

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<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

GO - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequences (3)ⁱ

Cross-referencesⁱ

Web resourcesⁱ

Entry informationⁱ

Miscellaneousⁱ