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Q15027 (ACAP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length740 AA.
Sequence statusComplete.
Protein existenceEvidence 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. Required for regulated export of ITGB1 from recycling endosomes to the cell surface and ITGB1-dependent cell migration. Ref.4 Ref.5 Ref.8 Ref.9 Ref.10

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. Interacts with ITGB1; required for ITGB1 recycling. Ref.5 Ref.7 Ref.8 Ref.9 Ref.10

Subcellular location

Recycling endosome membrane; Peripheral membrane protein; Cytoplasmic side Ref.5.

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. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processProtein transport
Transport
   Cellular componentEndosome
Membrane
   Coding sequence diversityPolymorphism
   DomainANK repeat
Repeat
Zinc-finger
   LigandMetal-binding
Zinc
   Molecular functionGTPase activation
   PTMNitration
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processprotein transport

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of ARF GTPase activity

Inferred from electronic annotation. Source: InterPro

   Cellular_componentrecycling endosome membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionARF GTPase activator activity

Inferred from electronic annotation. Source: InterPro

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 740740Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 1
PRO_0000074209

Regions

Domain1 – 226226BAR
Domain265 – 36096PH
Domain405 – 527123Arf-GAP
Repeat606 – 63530ANK 1
Repeat639 – 66830ANK 2
Repeat672 – 70231ANK 3
Zinc finger420 – 44324C4-type
Region1 – 382382Required for formation of endosomal tubules when overexpressed with PIP5K1C
Region405 – 740336Required for interaction with GULP1
Region525 – 56642Prevents interaction with ITGB1 when S-554 is not phosphorylated

Amino acid modifications

Modified residue4851Nitrated tyrosine Ref.6
Modified residue5541Phosphoserine; by PKB Ref.5

Natural variations

Natural variant681R → C.
Corresponds to variant rs35933585 [ dbSNP | Ensembl ].
VAR_048328
Natural variant1141K → R in a breast cancer sample; somatic mutation. Ref.11
VAR_036178
Natural variant1291R → Q in a colorectal cancer sample; somatic mutation. Ref.11
VAR_036179
Natural variant5331R → W.
Corresponds to variant rs35019942 [ dbSNP | Ensembl ].
VAR_048329

Experimental info

Mutagenesis141S → A: No effect on interaction with ITGB1. Ref.5
Mutagenesis291S → A: No effect on interaction with ITGB1. Ref.5
Mutagenesis2741K → N: Loss of binding to PIP2 and PIP3. Loss of association with endosomal tubules when coexpressed with PIP5K1C. Ref.7
Mutagenesis2771S → A: No effect on interaction with ITGB1. Ref.5
Mutagenesis2891T → A: No effect on interaction with ITGB1. Ref.5
Mutagenesis3581S → A: No effect on interaction with ITGB1. Ref.5
Mutagenesis3891T → A: No effect on interaction with ITGB1. Ref.5
Mutagenesis4481R → Q: Loss of GAP activity. No effect on GULP1 binding or association with endosomal tubules when coexpressed with PIP5K1C. Ref.4 Ref.8
Mutagenesis4611T → A: No effect on interaction with ITGB1. Ref.5
Mutagenesis5541S → A: Loss of phosphorylation by PKB, interaction with ITGB1 and ITGB1-dependent cell migration. Ref.5 Ref.10
Mutagenesis5541S → D: Enhances interaction with ITGB1. Ref.5 Ref.10
Mutagenesis5681S → A: No effect on interaction with ITGB1. Ref.5
Mutagenesis7111T → A: No effect on interaction with ITGB1. Ref.5
Mutagenesis7121Y → F: No effect on interaction with ITGB1. Ref.5
Mutagenesis7241S → A: Loss of phosphorylation at S-554, interaction with ITGB1 and ITGB1-dependent cell migration. Ref.5
Mutagenesis7241S → D: Enhances interaction with ITGB1. Ref.5

Secondary structure

............................................... 740
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q15027 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 64891DA3CE00189C

FASTA74081,536
        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 

« Hide

References

« Hide '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, IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH ITGB1, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-14; SER-29; SER-277; THR-289; SER-358; THR-389; THR-461; SER-554; SER-568; THR-711; TYR-712 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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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]"Mechanistic insights into regulated cargo binding by ACAP1 protein."
Bai M., Pang X., Lou J., Zhou Q., Zhang K., Ma J., Li J., Sun F., Hsu V.W.
J. Biol. Chem. 287:28675-28685(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 378-740 WILD TYPE AND MUTANT ASP-554 IN COMPLEX WITH ITGB1 PEPTIDE AND ZINC IONS, FUNCTION, INTERACTION WITH ITGB1, MUTAGENESIS OF SER-554.
[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. expand/collapse author list , 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.
RefSeqNP_055531.1. NM_014716.3.
UniGeneHs.337242.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3JUEX-ray2.30A/B378-740[»]
3T9KX-ray2.30A/B378-740[»]
4F1PX-ray2.30A/B378-740[»]
ProteinModelPortalQ15027.
SMRQ15027. Positions 4-361, 405-723.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115092. 3 interactions.
IntActQ15027. 6 interactions.
MINTMINT-1446333.
STRING9606.ENSP00000158762.

PTM databases

PhosphoSiteQ15027.

Polymorphism databases

DMDM3183210.

Proteomic databases

PaxDbQ15027.
PRIDEQ15027.

Protocols and materials databases

DNASU9744.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000158762; ENSP00000158762; ENSG00000072818.
GeneID9744.
KEGGhsa:9744.
UCSCuc002ggd.2. human.

Organism-specific databases

CTD9744.
GeneCardsGC17P007239.
HGNCHGNC:16467. ACAP1.
HPAHPA021127.
MIM607763. gene.
neXtProtNX_Q15027.
PharmGKBPA26406.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5347.
HOGENOMHOG000220815.
HOVERGENHBG050889.
InParanoidQ15027.
KOK12489.
OMAHVVAQVQ.
OrthoDBEOG7PVWNT.
PhylomeDBQ15027.
TreeFamTF318315.

Enzyme and pathway databases

SignaLinkQ15027.

Gene expression databases

ArrayExpressQ15027.
BgeeQ15027.
CleanExHS_ACAP1.
GenevestigatorQ15027.

Family and domain databases

Gene3D1.20.1270.60. 1 hit.
1.25.40.20. 1 hit.
2.30.29.30. 1 hit.
InterProIPR027267. 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]
PfamPF00023. Ank. 2 hits.
PF01412. ArfGap. 1 hit.
PF00169. PH. 1 hit.
[Graphical view]
PRINTSPR00405. REVINTRACTNG.
SMARTSM00248. ANK. 3 hits.
SM00105. ArfGap. 1 hit.
SM00233. PH. 1 hit.
[Graphical view]
SUPFAMSSF48403. SSF48403. 1 hit.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 2 hits.
PS50115. ARFGAP. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ15027.
GeneWikiCENTB1.
GenomeRNAi9744.
NextBio36666.
PROQ15027.
SOURCESearch...

Entry information

Entry nameACAP1_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 135 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM