Q15027 (ACAP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [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	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.8 Ref.9
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.9
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.
Sequence caution	The sequence BAA06418.2 differs from that shown. Reason: Erroneous initiation.

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	Nitration Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	positive regulation of GTPase activity Inferred from electronic annotation. Source: GOC 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 phospholipid binding Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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

485

1

Nitrated tyrosine Ref.6

Modified residue

554

1

Phosphoserine; by PKB Ref.5

Natural variations

Natural variant

68

1

R → C.
Corresponds to variant rs35933585 [ dbSNP | Ensembl ].

VAR_048328

Natural variant

114

1

K → R in a breast cancer sample; somatic mutation. Ref.10

VAR_036178

Natural variant

129

1

R → Q in a colorectal cancer sample; somatic mutation. Ref.10

VAR_036179

Natural variant

533

1

R → W.
Corresponds to variant rs35019942 [ dbSNP | Ensembl ].

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.7

Mutagenesis

448

1

R → Q: Loss of GAP activity. No effect on GULP1 binding or association with endosomal tubules when coexpressed with PIP5K1C. Ref.4 Ref.8

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 S-554, interaction with ITGB1 and ITGB1-dependent cell migration. Ref.5

Secondary structure

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740

Helix Strand Turn

Details...

Helix

407 – 412

6

Turn

415 – 418

4

Turn

421 – 423

3

Beta strand

430 – 432

3

Turn

433 – 436

4

Beta strand

437 – 439

3

Helix

441 – 450

10

Turn

452 – 454

3

Beta strand

457 – 459

3

Turn

460 – 462

3

Helix

467 – 475

9

Helix

478 – 485

8

Turn

486 – 493

8

Helix

503 – 514

12

Helix

571 – 578

8

Beta strand

580 – 582

3

Helix

585 – 593

9

Turn

603 – 606

4

Helix

610 – 616

7

Helix

620 – 628

9

Helix

643 – 650

8

Helix

653 – 661

9

Helix

676 – 682

7

Helix

686 – 696

11

Helix

713 – 720

8

Sequences

	Sequence		Length	Mass (Da)
	Q15027 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT SER-554, MUTAGENESIS OF SER-554 AND SER-724.
[6]	"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] [Europe PMC] [Abstract] Cited for: NITRATION [LARGE SCALE ANALYSIS] AT TYR-485, MASS SPECTROMETRY. Tissue: Pituitary adenoma.
[7]	"Cooperation of phosphoinositides and BAR domain proteins in endosomal tubulation." Shinozaki-Narikawa N., Kodama T., Shibasaki Y. Traffic 7:1539-1550(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PHOSPHOLIPIDS, MUTAGENESIS OF LYS-274.
[8]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH GULP AND ARF6, MUTAGENESIS OF ARG-448.
[9]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CLTC.
[10]	"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] [Europe PMC] [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. NM_014716.3.

UniGene

Hs.337242.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3JUE	X-ray	2.30	A/B	378-740	[»]
3T9K	X-ray	2.30	A/B	378-740	[»]
4F1P	X-ray	2.30	A/B	378-740	[»]

ProteinModelPortal

Q15027.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q15027. 6 interactions.

MINT

MINT-1446333.

STRING

9606.ENSP00000158762.

PTM databases

PhosphoSite

Q15027.

Polymorphism databases

DMDM

3183210.

Proteomic databases

PaxDb

Q15027.

PRIDE

Q15027.

Protocols and materials databases

DNASU

9744.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000158762; ENSP00000158762; ENSG00000072818.

GeneID

9744.

KEGG

hsa:9744.

UCSC

uc002ggd.2. human.

Organism-specific databases

CTD

9744.

GeneCards

GC17P007239.

HGNC

HGNC:16467. ACAP1.

HPA

HPA021127.

MIM

607763. gene.

neXtProt

NX_Q15027.

PharmGKB

PA26406.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5347.

HOGENOM

HOG000220815.

HOVERGEN

HBG050889.

InParanoid

Q15027.

KO

K12489.

OMA

HVVAQVQ.

OrthoDB

EOG4SQWW7.

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

Gene3D

1.20.1270.60. 1 hit.
1.25.40.20. 1 hit.
2.30.29.30. 1 hit.

InterPro

IPR027267. AH/BAR-dom.
IPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR001164. ArfGAP.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR000909. PLipase_C_PInositol-sp_X_dom.
[Graphical view]

Pfam

PF00023. Ank. 2 hits.
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]

SUPFAM

SSF48403. ANK. 1 hit.

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.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q15027.

GenomeRNAi

9744.

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:	May 1, 2013
This is version 126 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.