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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: Annotation score: 5 out of 5-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

Enzyme 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

Complete GO annotation...

Keywordsi

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000072818-MONOMER.
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

HGNCiHGNC:16467. ACAP1.

Subcellular locationi

  • Recycling endosome membrane 1 Publication; Peripheral membrane protein 1 Publication; Cytoplasmic side 1 Publication

GO - Cellular componenti

  • membrane Source: UniProtKB
  • recycling endosome membrane Source: UniProtKB-SubCell

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.

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.
CleanExiHS_ACAP1.
ExpressionAtlasiQ15027. baseline and differential.
GenevisibleiQ15027. HS.

Organism-specific databases

HPAiHPA021127.

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. 7 interactors.
IntActiQ15027. 8 interactors.
MINTiMINT-1446333.
STRINGi9606.ENSP00000158762.

Structurei

Secondary structure

1740
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi1 – 4Combined sources4
Helixi7 – 12Combined sources6
Helixi15 – 68Combined sources54
Beta strandi69 – 71Combined sources3
Helixi74 – 113Combined sources40
Helixi115 – 117Combined sources3
Helixi118 – 143Combined sources26
Helixi149 – 212Combined sources64
Helixi214 – 248Combined sources35
Beta strandi258 – 260Combined sources3
Beta strandi263 – 265Combined sources3
Beta strandi267 – 275Combined sources9
Turni277 – 279Combined sources3
Beta strandi283 – 291Combined sources9
Beta strandi294 – 303Combined sources10
Beta strandi306 – 310Combined sources5
Helixi312 – 314Combined sources3
Beta strandi315 – 319Combined sources5
Beta strandi323 – 325Combined sources3
Beta strandi328 – 335Combined sources8
Beta strandi337 – 341Combined sources5
Helixi345 – 361Combined sources17
Helixi407 – 412Combined sources6
Turni415 – 418Combined sources4
Turni421 – 423Combined sources3
Beta strandi430 – 432Combined sources3
Turni433 – 436Combined sources4
Beta strandi437 – 439Combined sources3
Helixi441 – 450Combined sources10
Turni452 – 454Combined sources3
Beta strandi457 – 459Combined sources3
Turni460 – 462Combined sources3
Helixi467 – 475Combined sources9
Helixi478 – 485Combined sources8
Turni486 – 493Combined sources8
Helixi503 – 514Combined sources12
Helixi571 – 578Combined sources8
Beta strandi580 – 582Combined sources3
Helixi585 – 593Combined sources9
Turni603 – 606Combined sources4
Helixi610 – 616Combined sources7
Helixi620 – 628Combined sources9
Helixi643 – 650Combined sources8
Helixi653 – 661Combined sources9
Helixi676 – 682Combined sources7
Helixi686 – 696Combined sources11
Helixi713 – 720Combined sources8

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...

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

Sequence similaritiesi

Contains 3 ANK repeats.PROSITE-ProRule annotation
Contains 1 Arf-GAP domain.PROSITE-ProRule annotation
Contains 1 BAR domain.Curated
Contains 1 PH domain.PROSITE-ProRule annotation

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.
OMAiSHNAEVP.
OrthoDBiEOG091G029F.
PhylomeDBiQ15027.
TreeFamiTF318315.

Family and domain databases

Gene3Di1.20.1270.60. 1 hit.
1.25.40.20. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR027267. AH/BAR-dom.
IPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR001164. ArfGAP.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR000909. PLipase_C_PInositol-sp_X_dom.
[Graphical view]
PfamiPF12796. Ank_2. 1 hit.
PF01412. ArfGap. 1 hit.
PF00169. PH. 1 hit.
[Graphical view]
PRINTSiPR00405. REVINTRACTNG.
SMARTiSM00248. ANK. 3 hits.
SM00105. ArfGap. 1 hit.
SM00233. PH. 1 hit.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 2 hits.
PS50115. ARFGAP. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

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. Corresponds to variant dbSNP:rs7598550541 PublicationEnsembl.1
Natural variantiVAR_036179129R → Q in a colorectal cancer sample; somatic mutation. Corresponds to variant dbSNP:rs7547402251 PublicationEnsembl.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

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. 7 interactors.
IntActiQ15027. 8 interactors.
MINTiMINT-1446333.
STRINGi9606.ENSP00000158762.

PTM databases

iPTMnetiQ15027.
PhosphoSitePlusiQ15027.

Polymorphism and mutation databases

BioMutaiACAP1.
DMDMi3183210.

Proteomic databases

EPDiQ15027.
MaxQBiQ15027.
PaxDbiQ15027.
PeptideAtlasiQ15027.
PRIDEiQ15027.

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.
GeneCardsiACAP1.
HGNCiHGNC:16467. ACAP1.
HPAiHPA021127.
MIMi607763. gene.
neXtProtiNX_Q15027.
OpenTargetsiENSG00000072818.
PharmGKBiPA26406.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000072818-MONOMER.
SignaLinkiQ15027.
SIGNORiQ15027.

Miscellaneous databases

EvolutionaryTraceiQ15027.
GeneWikiiCENTB1.
GenomeRNAii9744.
PROiQ15027.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000072818.
CleanExiHS_ACAP1.
ExpressionAtlasiQ15027. baseline and differential.
GenevisibleiQ15027. HS.

Family and domain databases

Gene3Di1.20.1270.60. 1 hit.
1.25.40.20. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR027267. AH/BAR-dom.
IPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR001164. ArfGAP.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR000909. PLipase_C_PInositol-sp_X_dom.
[Graphical view]
PfamiPF12796. Ank_2. 1 hit.
PF01412. ArfGap. 1 hit.
PF00169. PH. 1 hit.
[Graphical view]
PRINTSiPR00405. REVINTRACTNG.
SMARTiSM00248. ANK. 3 hits.
SM00105. ArfGap. 1 hit.
SM00233. PH. 1 hit.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 2 hits.
PS50115. ARFGAP. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]
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: November 30, 2016
This is version 161 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

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.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.