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Protein

Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 1

Gene

ACAP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.5 Publications

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.

Activity regulationi

GAP activity stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri420 – 443C4-typePROSITE-ProRule annotationAdd BLAST24

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionGTPase activation
Biological processProtein transport, Transport
LigandMetal-binding, Zinc

Enzyme and pathway databases

SignaLinkiQ15027
SIGNORiQ15027

Names & Taxonomyi

Protein namesi
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 namesi
Name:ACAP1
Synonyms:CENTB1, KIAA0050
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000072818.11
HGNCiHGNC:16467 ACAP1
MIMi607763 gene
neXtProtiNX_Q15027

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi14S → A: No effect on interaction with ITGB1. 1 Publication1
Mutagenesisi29S → A: No effect on interaction with ITGB1. 1 Publication1
Mutagenesisi274K → N: Loss of binding to PIP2 and PIP3. Loss of association with endosomal tubules when coexpressed with PIP5K1C. 1 Publication1
Mutagenesisi277S → A: No effect on interaction with ITGB1. 1 Publication1
Mutagenesisi280F → A: Reduced membrane binding and ability to induce liposome tubulation. 1 Publication1
Mutagenesisi280F → E: Almost abolishes membrane binding. 1 Publication1
Mutagenesisi280F → W: Preserves membrane binding and ability to tubulate liposomes. 1 Publication1
Mutagenesisi289T → A: No effect on interaction with ITGB1. 1 Publication1
Mutagenesisi358S → A: No effect on interaction with ITGB1. 1 Publication1
Mutagenesisi389T → A: No effect on interaction with ITGB1. 1 Publication1
Mutagenesisi448R → Q: Loss of GAP activity. No effect on GULP1 binding or association with endosomal tubules when coexpressed with PIP5K1C. 2 Publications1
Mutagenesisi461T → A: No effect on interaction with ITGB1. 1 Publication1
Mutagenesisi554S → A: Loss of phosphorylation by PKB, interaction with ITGB1 and ITGB1-dependent cell migration. 2 Publications1
Mutagenesisi554S → D: Enhances interaction with ITGB1. 2 Publications1
Mutagenesisi568S → A: No effect on interaction with ITGB1. 1 Publication1
Mutagenesisi711T → A: No effect on interaction with ITGB1. 1 Publication1
Mutagenesisi712Y → F: No effect on interaction with ITGB1. 1 Publication1
Mutagenesisi724S → A: Loss of phosphorylation at S-554, interaction with ITGB1 and ITGB1-dependent cell migration. 1 Publication1
Mutagenesisi724S → D: Enhances interaction with ITGB1. 1 Publication1

Organism-specific databases

DisGeNETi9744
OpenTargetsiENSG00000072818
PharmGKBiPA26406

Polymorphism and mutation databases

BioMutaiACAP1
DMDMi3183210

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000742091 – 740Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 1Add BLAST740

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei485Nitrated tyrosineCombined sources1
Modified residuei554Phosphoserine; by PKB1 Publication1

Post-translational modificationi

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.1 Publication

Keywords - PTMi

Nitration, Phosphoprotein

Proteomic databases

EPDiQ15027
MaxQBiQ15027
PaxDbiQ15027
PeptideAtlasiQ15027
PRIDEiQ15027
ProteomicsDBi60378

PTM databases

iPTMnetiQ15027
PhosphoSitePlusiQ15027

Expressioni

Tissue specificityi

Highest level in lung and spleen. Low level in heart, kidney, liver and pancreas.1 Publication

Gene expression databases

BgeeiENSG00000072818 Expressed in 208 organ(s), highest expression level in testis
CleanExiHS_ACAP1
ExpressionAtlasiQ15027 baseline and differential
GenevisibleiQ15027 HS

Organism-specific databases

HPAiHPA075570

Interactioni

Subunit structurei

Banana-shaped homodimer laterally assembling into tetramers, the tetramers further pack helically onto the membrane. 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.6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GRB2P629933EBI-751746,EBI-401755

Protein-protein interaction databases

BioGridi115092, 8 interactors
CORUMiQ15027
IntActiQ15027, 10 interactors
STRINGi9606.ENSP00000158762

Structurei

Secondary structure

1740
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ15027
SMRiQ15027
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ15027

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 226BARAdd BLAST226
Domaini265 – 360PHPROSITE-ProRule annotationAdd BLAST96
Domaini405 – 527Arf-GAPPROSITE-ProRule annotationAdd BLAST123
Repeati606 – 635ANK 1Add BLAST30
Repeati639 – 668ANK 2Add BLAST30
Repeati672 – 702ANK 3Add BLAST31

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 382Required for formation of endosomal tubules when overexpressed with PIP5K1CAdd BLAST382
Regioni405 – 740Required for interaction with GULP1Add BLAST336
Regioni525 – 566Prevents interaction with ITGB1 when S-554 is not phosphorylatedAdd BLAST42

Domaini

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. Only one PH domain of one ACAP1 dimer inserts into the membrane, while the other PH domain acts primaryly to interact with adjacent ACAP1 dimers.1 Publication
The BAR domain mediates homodimerization, it can neither bind membrane nor impart curvature, but instead requires the neighboring PH domain to achieve these functions.1 Publication

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri420 – 443C4-typePROSITE-ProRule annotationAdd BLAST24

Keywords - Domaini

ANK repeat, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG0521 Eukaryota
COG5347 LUCA
GeneTreeiENSGT00760000118874
HOGENOMiHOG000220815
HOVERGENiHBG050889
InParanoidiQ15027
KOiK12489
OMAiGPPEPMM
OrthoDBiEOG091G029F
PhylomeDBiQ15027
TreeFamiTF318315

Family and domain databases

CDDicd00204 ANK, 1 hit
Gene3Di1.20.1270.60, 1 hit
1.25.40.20, 1 hit
2.30.29.30, 1 hit
3.30.40.160, 1 hit
InterProiView protein in InterPro
IPR027267 AH/BAR_dom_sf
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
IPR037278 ARFGAP/RecO
IPR001164 ArfGAP_dom
IPR038508 ArfGAP_dom_sf
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR000909 PLipase_C_PInositol-sp_X_dom
PfamiView protein in Pfam
PF12796 Ank_2, 1 hit
PF01412 ArfGap, 1 hit
PF00169 PH, 1 hit
PRINTSiPR00405 REVINTRACTNG
SMARTiView protein in SMART
SM00248 ANK, 3 hits
SM00105 ArfGap, 1 hit
SM00233 PH, 1 hit
SUPFAMiSSF103657 SSF103657, 1 hit
SSF48403 SSF48403, 1 hit
SSF57863 SSF57863, 1 hit
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 2 hits
PS50115 ARFGAP, 1 hit
PS50003 PH_DOMAIN, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.iShow all

Q15027-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MTVKLDFEEC LKDSPRFRAS IELVEAEVSE LETRLEKLLK LGTGLLESGR
60 70 80 90 100
HYLAASRAFV VGICDLARLG PPEPMMAECL EKFTVSLNHK LDSHAELLDA
110 120 130 140 150
TQHTLQQQIQ TLVKEGLRGF REARRDFWRG AESLEAALTH NAEVPRRRAQ
160 170 180 190 200
EAEEAGAALR TARAGYRGRA LDYALQINVI EDKRKFDIME FVLRLVEAQA
210 220 230 240 250
THFQQGHEEL SRLSQYRKEL GAQLHQLVLN SAREKRDMEQ RHVLLKQKEL
260 270 280 290 300
GGEEPEPSLR EGPGGLVMEG HLFKRASNAF KTWSRRWFTI QSNQLVYQKK
310 320 330 340 350
YKDPVTVVVD DLRLCTVKLC PDSERRFCFE VVSTSKSCLL QADSERLLQL
360 370 380 390 400
WVSAVQSSIA SAFSQARLDD SPRGPGQGSG HLAIGSAATL GSGGMARGRE
410 420 430 440 450
PGGVGHVVAQ VQSVDGNAQC CDCREPAPEW ASINLGVTLC IQCSGIHRSL
460 470 480 490 500
GVHFSKVRSL TLDSWEPELV KLMCELGNVI INQIYEARVE AMAVKKPGPS
510 520 530 540 550
CSRQEKEAWI HAKYVEKKFL TKLPEIRGRR GGRGRPRGQP PVPPKPSIRP
560 570 580 590 600
RPGSLRSKPE PPSEDLGSLH PGALLFRASG HPPSLPTMAD ALAHGADVNW
610 620 630 640 650
VNGGQDNATP LIQATAANSL LACEFLLQNG ANVNQADSAG RGPLHHATIL
660 670 680 690 700
GHTGLACLFL KRGADLGARD SEGRDPLTIA METANADIVT LLRLAKMREA
710 720 730 740
EAAQGQAGDE TYLDIFRDFS LMASDDPEKL SRRSHDLHTL
Length:740
Mass (Da):81,536
Last modified:November 1, 1996 - v1
Checksum:i64891DA3CE00189C
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
I3L268I3L268_HUMAN
Arf-GAP with coiled-coil, ANK repea...
ACAP1
101Annotation score:
I3L0K9I3L0K9_HUMAN
Arf-GAP with coiled-coil, ANK repea...
ACAP1
148Annotation score:

Sequence cautioni

The sequence BAA06418 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04832868R → C. Corresponds to variant dbSNP:rs35933585Ensembl.1
Natural variantiVAR_036178114K → R in a breast cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs759855054Ensembl.1
Natural variantiVAR_036179129R → Q in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs754740225Ensembl.1
Natural variantiVAR_048329533R → W. Corresponds to variant dbSNP:rs35019942Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D30758 mRNA Translation: BAA06418.2 Different initiation.
BT009788 mRNA Translation: AAP88790.1
BC018543 mRNA Translation: AAH18543.1
CCDSiCCDS11101.1
RefSeqiNP_055531.1, NM_014716.3
UniGeneiHs.337242

Genome annotation databases

EnsembliENST00000158762; ENSP00000158762; ENSG00000072818
GeneIDi9744
KEGGihsa:9744
UCSCiuc002ggd.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D30758 mRNA Translation: BAA06418.2 Different initiation.
BT009788 mRNA Translation: AAP88790.1
BC018543 mRNA Translation: AAH18543.1
CCDSiCCDS11101.1
RefSeqiNP_055531.1, NM_014716.3
UniGeneiHs.337242

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3JUEX-ray2.30A/B378-740[»]
3T9KX-ray2.30A/B378-740[»]
4CKGelectron microscopy12.00A/B/C/D1-377[»]
4CKHelectron microscopy14.00A/B/C/D1-377[»]
4F1PX-ray2.30A/B378-740[»]
4NSWX-ray2.20A/B1-377[»]
ProteinModelPortaliQ15027
SMRiQ15027
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115092, 8 interactors
CORUMiQ15027
IntActiQ15027, 10 interactors
STRINGi9606.ENSP00000158762

PTM databases

iPTMnetiQ15027
PhosphoSitePlusiQ15027

Polymorphism and mutation databases

BioMutaiACAP1
DMDMi3183210

Proteomic databases

EPDiQ15027
MaxQBiQ15027
PaxDbiQ15027
PeptideAtlasiQ15027
PRIDEiQ15027
ProteomicsDBi60378

Protocols and materials databases

DNASUi9744
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000158762; ENSP00000158762; ENSG00000072818
GeneIDi9744
KEGGihsa:9744
UCSCiuc002ggd.3 human

Organism-specific databases

CTDi9744
DisGeNETi9744
EuPathDBiHostDB:ENSG00000072818.11
GeneCardsiACAP1
HGNCiHGNC:16467 ACAP1
HPAiHPA075570
MIMi607763 gene
neXtProtiNX_Q15027
OpenTargetsiENSG00000072818
PharmGKBiPA26406
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0521 Eukaryota
COG5347 LUCA
GeneTreeiENSGT00760000118874
HOGENOMiHOG000220815
HOVERGENiHBG050889
InParanoidiQ15027
KOiK12489
OMAiGPPEPMM
OrthoDBiEOG091G029F
PhylomeDBiQ15027
TreeFamiTF318315

Enzyme and pathway databases

SignaLinkiQ15027
SIGNORiQ15027

Miscellaneous databases

EvolutionaryTraceiQ15027
GeneWikiiCENTB1
GenomeRNAii9744
PROiPR:Q15027
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000072818 Expressed in 208 organ(s), highest expression level in testis
CleanExiHS_ACAP1
ExpressionAtlasiQ15027 baseline and differential
GenevisibleiQ15027 HS

Family and domain databases

CDDicd00204 ANK, 1 hit
Gene3Di1.20.1270.60, 1 hit
1.25.40.20, 1 hit
2.30.29.30, 1 hit
3.30.40.160, 1 hit
InterProiView protein in InterPro
IPR027267 AH/BAR_dom_sf
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
IPR037278 ARFGAP/RecO
IPR001164 ArfGAP_dom
IPR038508 ArfGAP_dom_sf
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR000909 PLipase_C_PInositol-sp_X_dom
PfamiView protein in Pfam
PF12796 Ank_2, 1 hit
PF01412 ArfGap, 1 hit
PF00169 PH, 1 hit
PRINTSiPR00405 REVINTRACTNG
SMARTiView protein in SMART
SM00248 ANK, 3 hits
SM00105 ArfGap, 1 hit
SM00233 PH, 1 hit
SUPFAMiSSF103657 SSF103657, 1 hit
SSF48403 SSF48403, 1 hit
SSF57863 SSF57863, 1 hit
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 2 hits
PS50115 ARFGAP, 1 hit
PS50003 PH_DOMAIN, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiACAP1_HUMAN
AccessioniPrimary (citable) accession number: Q15027
Secondary accession number(s): Q53XN9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: September 12, 2018
This is version 175 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health

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