Reviewed, UniProtKB/Swiss-Prot Q15027 (ACAP1_HUMAN)

Names and origin

Protein names

Recommended name:
    Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 1
Alternative name(s):
    Centaurin-beta-1
      Short name=Cnt-b1

Gene names

Name:	ACAP1
Synonyms:	CENTB1, KIAA0050

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

General annotation (Comments)

Function	GTPase-activating protein (GAP) for ADP ribosylation factor 6 (ARF6) required for clathrin-dependent export of proteins from recycling endosomes to trans-Golgi network and cell surface. Ref.4 Ref.5 Ref.7 Ref.8
Enzyme regulation	GAP activity stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid. Ref.4
Subunit structure	Interacts with GTP-bound ARF6. Interacts with third cytoplasmic loop of SLC2A4/GLUT4. Interacts with CLTC. Interacts with GULP1. Forms a complex with GDP-bound ARF6 and GULP1. Ref.7 Ref.8 Ref.6
Tissue specificity	Highest level in lung and spleen. Low level in heart, kidney, liver and pancreas. Ref.4
Domain	PH domain binds phospholipids including phosphatidic acid, phosphatidylinositol 3-phosphate, phosphatidylinositol 3,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3). May mediate ACAP1-binding to PIP2 or PIP3 containing membranes.
Post-translational modification	Phosphorylation at Ser-554 by PKB is required for interaction with ITGB1, export of ITGB1 from recycling endosomes to the cell surface and ITGB1-dependent cell migration.
Miscellaneous	Cells overexpressing ACAP1 show an accumulation of ITGB1 in recycling endosomes and inhibition of stimulation-dependent cell migration. Cells with reduced levels of ACAP1 or AKT1 and AKT2 show inhibition of stimulation-dependent cell migration. Cells overexpressing ACAP1 and PIP5K1C show formation of tubular structures derived from endosomal membranes.
Sequence similarities	Contains 3 ANK repeats. Contains 1 Arf-GAP domain. Contains 1 BAR domain. Contains 1 PH domain.

Ontologies

Keywords
Biological process	Protein transport Transport
Coding sequence diversity	Polymorphism
Domain	ANK repeat Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	GTPase activation
PTM	Acetylation Nitration Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	intracellular signaling cascade Inferred from electronic annotation. Source: InterPro lipid metabolic process Inferred from electronic annotation. Source: InterPro protein transport Inferred from electronic annotation. Source: UniProtKB-KW regulation of ARF GTPase activity Inferred from electronic annotation. Source: InterPro
Molecular function	ARF GTPase activator activity Inferred from electronic annotation. Source: InterPro phospholipase C activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: IntAct zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ABL1	P00519	1	EBI-751746,EBI-375543
GRB2	P62993	1	EBI-751746,EBI-401755
NCK1	P16333	1	EBI-751746,EBI-389883
SRC	P12931	1	EBI-751746,EBI-621482

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 740	740	Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 1		PRO_0000074209
Regions
	Domain	1 – 226	226	BAR
	Domain	265 – 360	96	PH
	Domain	405 – 527	123	Arf-GAP
	Repeat	606 – 635	30	ANK 1
	Repeat	639 – 668	30	ANK 2
	Repeat	672 – 702	31	ANK 3
	Zinc finger	420 – 443	24	C4-type
	Region	1 – 382	382	Required for formation of endosomal tubules when overexpressed with PIP5K1C
	Region	405 – 740	336	Required for interaction with GULP1
Amino acid modifications
	Modified residue	274	1	N6-acetyllysine Ref.10
	Modified residue	485	1	Nitrated tyrosine Ref.9
	Modified residue	554	1	Phosphoserine; by PKB Ref.5
Natural variations
	Natural variant	68	1	R → C: dbSNP rs35933585.		VAR_048328
	Natural variant	114	1	K → R in a breast cancer sample; somatic mutation. Ref.11		VAR_036178
	Natural variant	129	1	R → Q in a colorectal cancer sample; somatic mutation. Ref.11		VAR_036179
	Natural variant	533	1	R → W: dbSNP rs35019942.		VAR_048329
Experimental info
	Mutagenesis	274	1	K → N: Loss of binding to PIP2 and PIP3. Loss of association with endosomal tubules when coexpressed with PIP5K1C. Ref.6
	Mutagenesis	448	1	R → Q: Loss of GAP acitivity. No effect on GULP1 binding or association with endosomal tubules when coexpressed with PIP5K1C. Ref.4 Ref.7
	Mutagenesis	554	1	S → A: Loss of phosphorylation by PKB, interaction with ITGB1 and ITGB1-dependent cell migration. Ref.5
	Mutagenesis	724	1	S → A: Loss of phosphorylation at Ser-554, interaction with ITGB1 and ITGB1-dependent cell migration. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Q15027-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 64891DA3CE00189C	FASTA	740	81,536
	10 20 30 40 50 60 MTVKLDFEEC LKDSPRFRAS IELVEAEVSE LETRLEKLLK LGTGLLESGR HYLAASRAFV 70 80 90 100 110 120 VGICDLARLG PPEPMMAECL EKFTVSLNHK LDSHAELLDA TQHTLQQQIQ TLVKEGLRGF 130 140 150 160 170 180 REARRDFWRG AESLEAALTH NAEVPRRRAQ EAEEAGAALR TARAGYRGRA LDYALQINVI 190 200 210 220 230 240 EDKRKFDIME FVLRLVEAQA THFQQGHEEL SRLSQYRKEL GAQLHQLVLN SAREKRDMEQ 250 260 270 280 290 300 RHVLLKQKEL GGEEPEPSLR EGPGGLVMEG HLFKRASNAF KTWSRRWFTI QSNQLVYQKK 310 320 330 340 350 360 YKDPVTVVVD DLRLCTVKLC PDSERRFCFE VVSTSKSCLL QADSERLLQL WVSAVQSSIA 370 380 390 400 410 420 SAFSQARLDD SPRGPGQGSG HLAIGSAATL GSGGMARGRE PGGVGHVVAQ VQSVDGNAQC 430 440 450 460 470 480 CDCREPAPEW ASINLGVTLC IQCSGIHRSL GVHFSKVRSL TLDSWEPELV KLMCELGNVI 490 500 510 520 530 540 INQIYEARVE AMAVKKPGPS CSRQEKEAWI HAKYVEKKFL TKLPEIRGRR GGRGRPRGQP 550 560 570 580 590 600 PVPPKPSIRP RPGSLRSKPE PPSEDLGSLH PGALLFRASG HPPSLPTMAD ALAHGADVNW 610 620 630 640 650 660 VNGGQDNATP LIQATAANSL LACEFLLQNG ANVNQADSAG RGPLHHATIL GHTGLACLFL 670 680 690 700 710 720 KRGADLGARD SEGRDPLTIA METANADIVT LLRLAKMREA EAAQGQAGDE TYLDIFRDFS 730 740 LMASDDPEKL SRRSHDLHTL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1." Nomura N., Nagase T., Miyajima N., Sazuka T., Tanaka A., Sato S., Seki N., Kawarabayasi Y., Ishikawa K., Tabata S. DNA Res. 1:223-229(1994) [PubMed: 7584044] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Bone marrow.
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"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]. Tissue: Lymph.
[4]	"ACAPs are arf6 GTPase-activating proteins that function in the cell periphery." Jackson T.R., Brown F.D., Nie Z., Miura K., Foroni L., Sun J., Hsu V.W., Donaldson J.G., Randazzo P.A. J. Cell Biol. 151:627-638(2000) [PubMed: 11062263] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, TISSUE SPECIFICITY, MUTAGENESIS OF ARG-448.
[5]	"Phosphorylation of ACAP1 by Akt regulates the stimulation-dependent recycling of integrin beta1 to control cell migration." Li J., Ballif B.A., Powelka A.M., Dai J., Gygi S.P., Hsu V.W. Dev. Cell 9:663-673(2005) [PubMed: 16256741] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT SER-554, MUTAGENESIS OF SER-554 AND SER-724.
[6]	"Cooperation of phosphoinositides and BAR domain proteins in endosomal tubulation." Shinozaki-Narikawa N., Kodama T., Shibasaki Y. Traffic 7:1539-1550(2006) [PubMed: 17010122] [Abstract] Cited for: INTERACTION WITH PHOSPHOLIPIDS, MUTAGENESIS OF LYS-274.
[7]	"Regulation of Arf6 and ACAP1 signaling by the PTB-domain-containing adaptor protein GULP." Ma Z., Nie Z., Luo R., Casanova J.E., Ravichandran K.S. Curr. Biol. 17:722-727(2007) [PubMed: 17398097] [Abstract] Cited for: FUNCTION, INTERACTION WITH GULP AND ARF6, MUTAGENESIS OF ARG-448.
[8]	"An ACAP1-containing clathrin coat complex for endocytic recycling." Li J., Peters P.J., Bai M., Dai J., Bos E., Kirchhausen T., Kandror K.V., Hsu V.W. J. Cell Biol. 178:453-464(2007) [PubMed: 17664335] [Abstract] Cited for: FUNCTION, INTERACTION WITH CLTC.
[9]	"Nitroproteins from a human pituitary adenoma tissue discovered with a nitrotyrosine affinity column and tandem mass spectrometry." Zhan X., Desiderio D.M. Anal. Biochem. 354:279-289(2006) [PubMed: 16777052] [Abstract] Cited for: NITRATION [LARGE SCALE ANALYSIS] AT TYR-485, MASS SPECTROMETRY. Tissue: Pituitary adenoma.
[10]	"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-274, MASS SPECTROMETRY.
[11]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] ARG-114 AND GLN-129.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D30758 mRNA. Translation: BAA06418.2. Different initiation. BT009788 mRNA. Translation: AAP88790.1. BC018543 mRNA. Translation: AAH18543.1.
IPI	IPI00014199.
RefSeq	NP_055531.1.
UniGene	Hs.337242
3D structure databases
SMR	Q15027. Positions 4-357, 406-698.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q15027. 5 interactions.
STRING	Q15027.
PTM databases
PhosphoSite	Q15027.
Proteomic databases
PRIDE	Q15027.
Genome annotation databases
Ensembl	ENST00000158762; ENSP00000158762; ENSG00000072818; Homo sapiens. [Genome view]
GeneID	9744.
KEGG	hsa:9744.
UCSC	uc002ggd.1. human.
Organism-specific databases
CTD	9744.
GeneCards	GC17P007181.
H-InvDB	HIX0013106. HIX0059754.
HGNC	HGNC:16467. ACAP1.
MIM	607763. gene.
PharmGKB	PA26406.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG314594.
HOVERGEN	Q15027.
InParanoid	Q15027.
OMA	ALTHNAE.
OrthoDB	EOG9CVJSW.
PhylomeDB	Q15027.
Enzyme and pathway databases
Pathway_Interaction_DB	arf6cyclingpathway. Arf6 signaling events. arf6_traffickingpathway. Arf6 trafficking events.
Gene expression databases
ArrayExpress	Q15027.
Bgee	Q15027.
CleanEx	HS_ACAP1.
Genevestigator	Q15027.
GermOnline	ENSG00000072818. Homo sapiens.
Family and domain databases
InterPro	IPR002110. Ankyrin_rpt. IPR020683. Ankyrin_rpt-contain_dom. IPR001164. ArfGAP. IPR011993. PH_type. IPR001849. Pleckstrin_homology. IPR000909. PLipase_C_PInositol-sp_X_dom. [Graphical view]
Gene3D	G3DSA:1.25.40.20. ANK. 1 hit. G3DSA:2.30.29.30. PH_type. 1 hit.
Pfam	PF01412. ArfGap. 1 hit. PF00169. PH. 1 hit. [Graphical view]
PRINTS	PR00405. REVINTRACTNG.
SMART	SM00248. ANK. 3 hits. SM00105. ArfGap. 1 hit. SM00233. PH. 1 hit. [Graphical view]
PROSITE	PS50297. ANK_REP_REGION. 1 hit. PS50088. ANK_REPEAT. 2 hits. PS50115. ARFGAP. 1 hit. PS51021. BAR. False negative. PS50003. PH_DOMAIN. 1 hit. PS50007. PIPLC_X_DOMAIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	36666.
SOURCE	Search...

Entry information

Entry name

ACAP1_HUMAN

Accession

Primary (citable) accession number: Q15027
Secondary accession number(s): Q53XN9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	November 1, 1996
Last modified:	January 19, 2010
This is version 92 of the entry and version 1 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.