Reviewed, UniProtKB/Swiss-Prot O75689 (ADAP1_HUMAN)

Names and origin

Protein names

Recommended name:
    Arf-GAP with dual PH domain-containing protein 1
Alternative name(s):
    Centaurin-alpha-1
    Putative MAPK-activating protein PM25

Gene names

Name:	ADAP1
Synonyms:	CENTA1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	374 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	GTPase-activating protein for the ADP ribosylation factor family Probable. Binds phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3) and inositol 1,3,4,5-tetrakisphosphate (InsP4). Ref.1 Ref.2
Subunit structure	Interacts with PRKCA, PRKCI and PRKCZ. Interacts with the N-terminal region of PRKD1. Ref.8
Subcellular location	Nucleus. Cytoplasm. Note: Recruited to the plasma membrane upon epidermal growth factor-dependent activation of phosphatidylinositol 4,5-diphosphate (PtdInsP2) 3-kinase. Ref.1 Ref.2
Tissue specificity	Expressed at highest levels in brain and at lower levels in peripheral blood leukocytes. Ref.1
Post-translational modification	Phosphorylated by PRKCA, PRKCI, PRKCZ and PRKD1 in vitro. Ref.8
Sequence similarities	Contains 1 Arf-GAP domain. Contains 2 PH domains.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	GTPase activation
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	cell surface receptor linked signal transduction Ref.2 Traceable author statement. Source: ProtInc regulation of ARF GTPase activity Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Ref.1 Ref.2 Inferred from direct assay. Source: UniProtKB nucleus Ref.1 Ref.2 Inferred from direct assay. Source: UniProtKB plasma membrane Ref.1 Ref.2 Inferred from direct assay. Source: UniProtKB
Molecular function	ARF GTPase activator activity Ref.1 Ref.2 Inferred from direct assay. Source: UniProtKB inositol 1,3,4,5 tetrakisphosphate binding Traceable author statement. Source: UniProtKB protein binding Ref.8 Inferred from physical interaction. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 374

374

Arf-GAP with dual PH domain-containing protein 1

PRO_0000074205

Regions

Domain

7 – 126

120

Arf-GAP

Domain

129 – 230

102

PH 1

Domain

252 – 356

105

PH 2

Zinc finger

21 – 44

24

C4-type

Amino acid modifications

Modified residue

87

1

Phosphoserine; by PKC Ref.8

Modified residue

272

1

N6-acetyllysine Ref.9

Modified residue

276

1

Phosphothreonine; by PKC Ref.8

Natural variations

Natural variant

241

1

G → S: dbSNP rs10256887. Ref.2 Ref.3 Ref.4 Ref.7

VAR_047470

Experimental info

Mutagenesis

21

1

C → A: Loss of GTPase-activating activity. Ref.1 Ref.2

Mutagenesis

24

1

C → A: Loss of GTPase-activating activity. Ref.1 Ref.2

Mutagenesis

149

1

R → C: 40-45% reduction in PtdInsP2 3-kinase dependent membrane localization. Almost complete loss of PtdInsP2 3-kinase dependent membrane localization; when associated with C-273. Ref.1 Ref.2

Mutagenesis

273

1

R → C: 70% reduction in PtdInsP2 3-kinase dependent membrane localization. Almost complete loss of PtdInsP2 3-kinase dependent membrane localization; when associated with C-149. Ref.1 Ref.2

Secondary structure

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374

Helix Strand Turn

Details...

Helix

4 – 13

10

Beta strand

31 – 34

4

Turn

42 – 44

3

Helix

48 – 50

3

Turn

52 – 54

3

Beta strand

57 – 59

3

Turn

60 – 62

3

Helix

67 – 75

9

Helix

79 – 85

7

Turn

86 – 88

3

Helix

102 – 113

12

Turn

117 – 119

3

Helix

121 – 124

4

Helix

125 – 128

4

Beta strand

136 – 138

3

Beta strand

147 – 149

3

Beta strand

151 – 153

3

Beta strand

160 – 162

3

Beta strand

165 – 167

3

Beta strand

172 – 175

4

Helix

177 – 179

3

Beta strand

181 – 183

3

Turn

186 – 188

3

Beta strand

196 – 201

6

Beta strand

204 – 211

8

Helix

217 – 236

20

Helix

242 – 245

4

Helix

246 – 248

3

Beta strand

259 – 261

3

Beta strand

271 – 278

8

Beta strand

281 – 287

7

Beta strand

307 – 309

3

Beta strand

325 – 328

4

Beta strand

333 – 340

8

Helix

341 – 356

16

Sequences

	Sequence		Length	Mass (Da)
	O75689-1 [UniParc]. Last modified November 25, 2008. Version 2. Checksum: 38547281FB09D9B9	FASTA	374	43,395
	10 20 30 40 50 60 MAKERRRAVL ELLQRPGNAR CADCGAPDPD WASYTLGVFI CLSCSGIHRN IPQVSKVKSV 70 80 90 100 110 120 RLDAWEEAQV EFMASHGNDA ARARFESKVP SFYYRPTPSD CQLLREQWIR AKYERQEFIY 130 140 150 160 170 180 PEKQEPYSAG YREGFLWKRG RDNGQFLSRK FVLTEREGAL KYFNRNDAKE PKAVMKIEHL 190 200 210 220 230 240 NATFQPAKIG HPHGLQVTYL KDNSTRNIFI YHEDGKEIVD WFNALRAARF HYLQVAFPGA 250 260 270 280 290 300 GDADLVPKLS RNYLKEGYME KTGPKQTEGF RKRWFTMDDR RLMYFKDPLD AFARGEVFIG 310 320 330 340 350 360 SKESGYTVLH GFPPSTQGHH WPHGITIVTP DRKFLFACET ESDQREWVAA FQKAVDRPML 370 PQEYAVEAHF KHKP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and functional characterization of a human homologue of centaurin-alpha." Venkateswarlu K., Cullen P.J. Biochem. Biophys. Res. Commun. 262:237-244(1999) [PubMed: 10448098] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF ARG-149 AND ARG-273. Tissue: Blood.
[2]	"Identification of centaurin-alpha1 as a potential in vivo phosphatidylinositol 3,4,5-trisphosphate-binding protein that is functionally homologous to the yeast ADP-ribosylation factor (ARF) GTPase-activating protein, Gcs1." Venkateswarlu K., Oatey P.B., Tavare J.M., Jackson T.R., Cullen P.J. Biochem. J. 340:359-363(1999) [PubMed: 10333475] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-21; CYS-24; ARG-149 AND ARG-273, VARIANT SER-241. Tissue: Peripheral blood.
[3]	"Molecular identification of a high-affinity Ins(1,3,4,5)tetrakisphosphate/phosphatidylinositol(3,4, 5)trisphosphate binding protein from human brain, p42IP4." Horstmeyer A., Reiser G. Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-241. Tissue: Brain.
[4]	"Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways." Matsuda A., Suzuki Y., Honda G., Muramatsu S., Matsuzaki O., Nagano Y., Doi T., Shimotohno K., Harada T., Nishida E., Hayashi H., Sugano S. Oncogene 22:3307-3318(2003) [PubMed: 12761501] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-241. Tissue: Lung fibroblast.
[5]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed: 12690205] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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].
[7]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-241. Tissue: Brain.
[8]	"Centaurin-alpha(1) associates with and is phosphorylated by isoforms of protein kinase C." Zemlickova E., Dubois T., Kerai P., Clokie S., Cronshaw A.D., Wakefield R.I.D., Johannes F.-J., Aitken A. Biochem. Biophys. Res. Commun. 307:459-465(2003) [PubMed: 12893243] [Abstract] Cited for: INTERACTION WITH PRKCA; PRKCI; PRKCZ AND PRKD1, PHOSPHORYLATION AT SER-87 AND THR-276.
[9]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-272, MASS SPECTROMETRY.
[10]	"Crystal structure of full length centaurin alpha-1." Structural genomics consortium (SGC) Submitted (DEC-2008) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 3-370.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AJ006422 mRNA. Translation: CAA07024.1.
AF082324 mRNA. Translation: AAD11414.1.
AB097049 mRNA. Translation: BAC77402.1.
CH236965 Genomic DNA. Translation: EAL23709.1.
CH471144 Genomic DNA. Translation: EAW87183.1.
BC033747 mRNA. Translation: AAH33747.1.

IPI

IPI00009992.

PIR

JC7091.

RefSeq

NP_006860.1.

UniGene

Hs.644629

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3FEH	X-ray	1.90	A	3-370	[»]
3FM8	X-ray	2.30	C/D	1-374	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

O75689. 2 interactions.

STRING

O75689.

PTM databases

PhosphoSite

O75689.

Genome annotation databases

Ensembl

ENST00000265846; ENSP00000265846; ENSG00000105963; Homo sapiens. [Genome view]

GeneID

11033.

KEGG

hsa:11033.

UCSC

uc003sjo.2. human.

Organism-specific databases

CTD

11033.

GeneCards

GC07M000905.

HGNC

HGNC:16486. ADAP1.

HPA

HPA007033.
HPA012049.

MIM

608114. gene.

PharmGKB

PA26404.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

O75689.

HOVERGEN

O75689.

Enzyme and pathway databases

Pathway_Interaction_DB

arf6cyclingpathway. Arf6 signaling events.
pi3kcipathway. Class I PI3K signaling events.

Gene expression databases

ArrayExpress

O75689.

Bgee

O75689.

CleanEx

HS_ADAP1.

Genevestigator

O75689.

GermOnline

ENSG00000105963. Homo sapiens.

Family and domain databases

InterPro

IPR001164. ArfGAP.
IPR011993. PH_type.
IPR001849. Pleckstrin_homology.
[Graphical view]

Gene3D

G3DSA:2.30.29.30. PH_type. 2 hits.

Pfam

PF01412. ArfGap. 1 hit.
PF00169. PH. 1 hit.
[Graphical view]

PRINTS

PR00405. REVINTRACTNG.

SMART

SM00105. ArfGap. 1 hit.
SM00233. PH. 2 hits.
[Graphical view]

PROSITE

PS50115. ARFGAP. 1 hit.
PS50003. PH_DOMAIN. 2 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

41926.

SOURCE

Search...

Entry information

Entry name

ADAP1_HUMAN

Accession

Primary (citable) accession number: O75689
Secondary accession number(s): A4D2Q2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 5, 2005
Last sequence update:	November 25, 2008
Last modified:	November 24, 2009
This is version 77 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.