Q9BUL8 (PDC10_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Programmed cell death protein 10

Alternative name(s):
Cerebral cavernous malformations 3 protein
TF-1 cell apoptosis-related protein 15

Gene names

Name:	PDCD10
Synonyms:	CCM3, TFAR15

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	212 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Promotes cell proliferation. Modulates apoptotic pathways. Increases mitogen-activated protein kinase activity and MST4 activity. Important for cell migration, and for normal structure and assembly of the Golgi complex. Important for KDR/VEGFR2 signaling. Increases the stability of KDR/VEGFR2 and prevents its breakdown. Required for normal cardiovascular development. Required for normal angiogenesis, vasculogenesis and hematopoiesis during embryonic development By similarity. Ref.8 Ref.9 Ref.12
Subunit structure	Homodimer. Interacts (via C-terminus) with CCM2 and PXN. Interacts (via N-terminus) with MST4, STK24 and STK25. Interacts with GOLGA2. Identified in a complex with CCM1 and CCM2. Interacts with KDR/VEGFR2. Interaction with KDR/VEGFR2 is enhanced by stimulation with VEGFA By similarity. Ref.9 Ref.10 Ref.12 Ref.14
Subcellular location	Cytoplasm. Golgi apparatus membrane; Peripheral membrane protein; Cytoplasmic side. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Note: Partially co-localizes with endogenous PXN at the leading edges of migrating cells. Ref.9 Ref.12 Ref.14
Tissue specificity	Ubiquitous. Ref.8
Involvement in disease	Cerebral cavernous malformations 3 (CCM3) [MIM:603285]: A congenital vascular anomaly of the central nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. The lesions are characterized by grossly enlarged blood vessels consisting of a single layer of endothelium and without any intervening neural tissue, ranging in diameter from a few millimeters to several centimeters. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8
Sequence similarities	Belongs to the PDCD10 family.

Ontologies

Keywords
Biological process	Angiogenesis Apoptosis
Cellular component	Cell membrane Cytoplasm Golgi apparatus Membrane
Coding sequence diversity	Polymorphism
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of apoptotic process Inferred from direct assay Ref.9. Source: UniProtKB positive regulation of MAP kinase activity Inferred from direct assay Ref.9. Source: UniProtKB positive regulation of cell proliferation Inferred from direct assay Ref.9. Source: UniProtKB
Cellular_component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Inferred from direct assay Ref.9Ref.14. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CCM2	Q9BSQ5	4	EBI-740195,EBI-1573056
PTPN13	Q12923	3	EBI-740195,EBI-355227
STK24	Q9Y6E0	5	EBI-740195,EBI-740175
STK25	O00506	8	EBI-740195,EBI-618295
STRN	O43815	2	EBI-740195,EBI-1046642

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 212

212

Programmed cell death protein 10

PRO_0000187562

Amino acid modifications

Modified residue

179

1

N6-acetyllysine Ref.11

Natural variations

Natural variant

102

1

D → A. Ref.1
Corresponds to variant rs1129087 [ dbSNP | Ensembl ].

VAR_023578

Experimental info

Mutagenesis

132

1

K → D: Loss of interaction with CCM2 and PXN; when associated with D-139; D-172 and D-179. Ref.14

Mutagenesis

135

1

A → D: Loss of interaction with CCM2. Ref.14

Mutagenesis

139

1

K → D: Loss of interaction with CCM2 and PXN; when associated with D-132; D-172 and D-179. Ref.14

Mutagenesis

172

1

K → D: Loss of interaction with CCM2 and PXN; when associated with D-132; D-139 and D-179. Ref.14

Mutagenesis

175

1

S → D: Loss of interaction with CCM2. Ref.14

Mutagenesis

179

1

K → D: Loss of interaction with CCM2 and PXN; when associated with D-132; D-139 and D-172. Ref.14

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

212

Helix Strand Turn

Details...

Helix

17 – 19

3

Helix

20 – 24

5

Helix

26 – 36

11

Helix

38 – 54

17

Helix

58 – 68

11

Helix

70 – 83

14

Helix

84 – 86

3

Turn

89 – 91

3

Helix

98 – 115

18

Helix

117 – 120

4

Beta strand

121 – 123

3

Helix

124 – 151

28

Helix

154 – 156

3

Helix

157 – 184

28

Helix

187 – 210

24

Sequences

	Sequence		Length	Mass (Da)
	Q9BUL8 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 5AA613F71FAAEF56	FASTA	212	24,702
	10 20 30 40 50 60 MRMTMEEMKN EAETTSMVSM PLYAVMYPVF NELERVNLSA AQTLRAAFIK AEKENPGLTQ 70 80 90 100 110 120 DIIMKILEKK SVEVNFTESL LRMAADDVEE YMIERPEPEF QDLNEKARAL KQILSKIPDE 130 140 150 160 170 180 INDRVRFLQT IKDIASAIKE LLDTVNNVFK KYQYQNRRAL EHQKKEFVKY SKSFSDTLKT 190 200 210 YFKDGKAINV FVSANRLIHQ TNLILQTFKT VA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning and expression of an apoptosis-related gene, human TFAR-15 gene." Wang Y.G., Liu H.T., Ma D.L., Zhang Y.M. Sci. China, Ser. C, Life Sci. 42:323-329(1999) Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ALA-102.
[2]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"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].
[4]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., 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., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin and Urinary bladder.
[7]	Bienvenut W.V., Claeys D. Submitted (NOV-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 36-45 AND 117-124, MASS SPECTROMETRY. Tissue: Platelet.
[8]	"Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations." Bergametti F., Denier C., Labauge P., Arnoult M., Boetto S., Clanet M., Coubes P., Echenne B., Ibrahim R., Irthum B., Jacquet G., Lonjon M., Moreau J.J., Neau J.P., Parker F., Tremoulet M., Tournier-Lasserve E. Am. J. Hum. Genet. 76:42-51(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, INVOLVEMENT IN CCM3.
[9]	"PDCD10 interacts with Ste20-related kinase MST4 to promote cell growth and transformation via modulation of the ERK pathway." Ma X., Zhao H., Shan J., Long F., Chen Y., Chen Y., Zhang Y., Han X., Ma D. Mol. Biol. Cell 18:1965-1978(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MST4, FUNCTION, SUBCELLULAR LOCATION.
[10]	"Functional analyses of human and zebrafish 18-amino acid in-frame deletion pave the way for domain mapping of the cerebral cavernous malformation 3 protein." Voss K., Stahl S., Hogan B.M., Reinders J., Schleider E., Schulte-Merker S., Felbor U. Hum. Mutat. 30:1003-1011(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH STK25; CCM2 AND MST4, IDENTIFICATION IN A COMPLEX WITH CCM1 AND CCM2.
[11]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-179, MASS SPECTROMETRY.
[12]	"CCM3/PDCD10 stabilizes GCKIII proteins to promote Golgi assembly and cell orientation." Fidalgo M., Fraile M., Pires A., Force T., Pombo C., Zalvide J. J. Cell Sci. 123:1274-1284(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH GOLGA2; MST4; STK24 AND STK25, SUBCELLULAR LOCATION.
[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]	"Crystal structure of CCM3, a cerebral cavernous malformation protein critical for vascular integrity." Li X., Zhang R., Zhang H., He Y., Ji W., Min W., Boggon T.J. J. Biol. Chem. 285:24099-24107(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), SUBUNIT, INTERACTION WITH CCM2 AND PXN, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-132; ALA-135; LYS-139; LYS-172; SER-175 AND LYS-179.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF022385 mRNA. Translation: AAB72225.1.
CR457107 mRNA. Translation: CAG33388.1.
AK291130 mRNA. Translation: BAF83819.1.
AC079822 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW78574.1.
CH471052 Genomic DNA. Translation: EAW78575.1.
CH471052 Genomic DNA. Translation: EAW78576.1.
CH471052 Genomic DNA. Translation: EAW78577.1.
CH471052 Genomic DNA. Translation: EAW78578.1.
CH471052 Genomic DNA. Translation: EAW78580.1.
CH471052 Genomic DNA. Translation: EAW78581.1.
BC002506 mRNA. Translation: AAH02506.1.
BC016353 mRNA. Translation: AAH16353.1.

IPI

IPI00298558.

RefSeq

NP_009148.2. NM_007217.3.
NP_665858.1. NM_145859.1.
NP_665859.1. NM_145860.1.

UniGene

Hs.478150.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3AJM	X-ray	2.30	A/B	8-212	[»]
3L8I	X-ray	2.50	A/B/C/D	1-212	[»]
3L8J	X-ray	3.05	A	14-212	[»]
3RQE	X-ray	2.80	A/B/C/D	1-212	[»]
3RQF	X-ray	2.70	A/B/C/D	1-212	[»]
3RQG	X-ray	2.50	A/B/C/D	1-212	[»]

ProteinModelPortal

Q9BUL8.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9BUL8. 25 interactions.

MINT

MINT-5003501.

STRING

9606.ENSP00000338141.

PTM databases

PhosphoSite

Q9BUL8.

Polymorphism databases

DMDM

74733232.

2D gel databases

OGP

Q9BUL8.

Proteomic databases

PaxDb

Q9BUL8.

PRIDE

Q9BUL8.

Protocols and materials databases

DNASU

11235.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000392750; ENSP00000376506; ENSG00000114209.
ENST00000461494; ENSP00000420021; ENSG00000114209.
ENST00000470131; ENSP00000417202; ENSG00000114209.
ENST00000473645; ENSP00000418317; ENSG00000114209.
ENST00000497056; ENSP00000420553; ENSG00000114209.

GeneID

11235.

KEGG

hsa:11235.

UCSC

uc003fex.3. human.

Organism-specific databases

CTD

11235.

GeneCards

GC03M167381.

HGNC

HGNC:8761. PDCD10.

HPA

HPA027095.

MIM

603285. phenotype.
609118. gene.

neXtProt

NX_Q9BUL8.

Orphanet

221061. Hereditary cerebral cavernous malformation.

PharmGKB

PA33111.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG275788.

HOGENOM

HOG000007888.

HOVERGEN

HBG052811.

InParanoid

Q9BUL8.

OMA

KREFVKY.

OrthoDB

EOG41ZFBT.

PhylomeDB

Q9BUL8.

Gene expression databases

ArrayExpress

Q9BUL8.

Bgee

Q9BUL8.

CleanEx

HS_PDCD10.

Genevestigator

Q9BUL8.

GermOnline

ENSG00000114209. Homo sapiens.

Family and domain databases

InterPro

IPR009652. DUF1241.
[Graphical view]

PANTHER

PTHR13250. PTHR13250. 1 hit.

Pfam

PF06840. DUF1241. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

PDCD10. human.

EvolutionaryTrace

Q9BUL8.

GenomeRNAi

11235.

NextBio

42758.

SOURCE

Search...

Entry information

Entry name

PDC10_HUMAN

Accession

Primary (citable) accession number: Q9BUL8
Secondary accession number(s): A8K515, D3DNN5, O14811

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2005
Last sequence update:	June 1, 2001
Last modified:	May 1, 2013
This is version 96 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.