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O43150

- ASAP2_HUMAN

UniProt

O43150 - ASAP2_HUMAN

Protein

Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 2

Gene

ASAP2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 138 (01 Oct 2014)
      Sequence version 3 (29 Mar 2004)
      Previous versions | rss
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    Functioni

    Activates the small GTPases ARF1, ARF5 and ARF6. Regulates the formation of post-Golgi vesicles and modulates constitutive secretion. Modulates phagocytosis mediated by Fc gamma receptor and ARF6. Modulates PXN recruitment to focal contacts and cell migration.3 Publications

    GO - Molecular functioni

    1. ARF GTPase activator activity Source: InterPro
    2. enzyme activator activity Source: ProtInc
    3. protein binding Source: UniProtKB
    4. zinc ion binding Source: InterPro

    GO - Biological processi

    1. positive regulation of catalytic activity Source: GOC
    2. regulation of ARF GTPase activity Source: InterPro

    Keywords - Molecular functioni

    GTPase activation

    Keywords - Ligandi

    Metal-binding, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 2
    Alternative name(s):
    Development and differentiation-enhancing factor 2
    Paxillin-associated protein with ARF GAP activity 3
    Short name:
    PAG3
    Pyk2 C-terminus-associated protein
    Short name:
    PAP
    Gene namesi
    Name:ASAP2
    Synonyms:DDEF2, KIAA0400
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:2721. ASAP2.

    Subcellular locationi

    GO - Cellular componenti

    1. Golgi cisterna membrane Source: UniProtKB-SubCell
    2. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Golgi apparatus, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi436 – 4361C → A: Loss of Arf-GAP activity. 1 Publication

    Organism-specific databases

    PharmGKBiPA164716118.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 10061006Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 2PRO_0000074198Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei701 – 7011Phosphoserine5 Publications
    Modified residuei822 – 8221Phosphoserine2 Publications
    Modified residuei903 – 9031Phosphothreonine2 Publications

    Post-translational modificationi

    Phosphorylated on tyrosine residues by SRC and PTK2B.6 Publications

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiO43150.
    PaxDbiO43150.
    PRIDEiO43150.

    PTM databases

    PhosphoSiteiO43150.

    Expressioni

    Tissue specificityi

    Detected in heart, brain, placenta, kidney, monocytes and pancreas.1 Publication

    Inductioni

    Up-regulated during monocytic maturation.

    Gene expression databases

    ArrayExpressiO43150.
    BgeeiO43150.
    CleanExiHS_ASAP2.
    GenevestigatoriO43150.

    Organism-specific databases

    HPAiCAB018615.

    Interactioni

    Subunit structurei

    Binds PXN, ARF1, ARF5, ARF6, PTK2B and SRC.

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    apcP700394EBI-310968,EBI-8069633From a different organism.
    GRB2P629933EBI-310968,EBI-401755
    PLCG1P191743EBI-310968,EBI-79387
    UBCP0CG482EBI-310968,EBI-3390054

    Protein-protein interaction databases

    BioGridi114378. 15 interactions.
    IntActiO43150. 13 interactions.
    MINTiMINT-243403.
    STRINGi9606.ENSP00000281419.

    Structurei

    3D structure databases

    ProteinModelPortaliO43150.
    SMRiO43150. Positions 30-406, 419-694, 947-1006.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini305 – 39793PHPROSITE-ProRule annotationAdd
    BLAST
    Domaini421 – 543123Arf-GAPPROSITE-ProRule annotationAdd
    BLAST
    Repeati584 – 61633ANK 1Add
    BLAST
    Repeati620 – 64930ANK 2Add
    BLAST
    Domaini944 – 100663SH3PROSITE-ProRule annotationAdd
    BLAST

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili256 – 28328Sequence AnalysisAdd
    BLAST
    Coiled coili729 – 75224Sequence AnalysisAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi771 – 936166Pro-richAdd
    BLAST

    Domaini

    The conserved Arg-464 in the Arf-GAP domain probably becomes part of the active site of bound small GTPases and is necessary for GTP hydrolysis.

    Sequence similaritiesi

    Contains 2 ANK repeats.PROSITE-ProRule annotation
    Contains 1 Arf-GAP domain.PROSITE-ProRule annotation
    Contains 1 PH domain.PROSITE-ProRule annotation
    Contains 1 SH3 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    ANK repeat, Coiled coil, Repeat, SH3 domain

    Phylogenomic databases

    eggNOGiCOG5347.
    HOGENOMiHOG000230570.
    HOVERGENiHBG051327.
    InParanoidiO43150.
    KOiK12488.
    OMAiYQLGSNQ.
    OrthoDBiEOG7WQ7RJ.
    PhylomeDBiO43150.
    TreeFamiTF325156.

    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.
    IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR001452. SH3_domain.
    [Graphical view]
    PfamiPF00023. Ank. 1 hit.
    PF01412. ArfGap. 1 hit.
    PF00169. PH. 1 hit.
    PF14604. SH3_9. 1 hit.
    [Graphical view]
    PRINTSiPR00405. REVINTRACTNG.
    SMARTiSM00248. ANK. 3 hits.
    SM00105. ArfGap. 1 hit.
    SM00233. PH. 1 hit.
    SM00326. SH3. 1 hit.
    [Graphical view]
    SUPFAMiSSF48403. SSF48403. 1 hit.
    SSF50044. SSF50044. 1 hit.
    PROSITEiPS50297. ANK_REP_REGION. 1 hit.
    PS50088. ANK_REPEAT. 1 hit.
    PS50115. ARFGAP. 1 hit.
    PS50003. PH_DOMAIN. 1 hit.
    PS50002. SH3. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O43150-1) [UniParc]FASTAAdd to Basket

    Also known as: PAPalpha

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MPDQISVSEF VAETHEDYKA PTASSFTTRT AQCRNTVAAI EEALDVDRMV     50
    LYKMKKSVKA INSSGLAHVE NEEQYTQALE KFGGNCVCRD DPDLGSAFLK 100
    FSVFTKELTA LFKNLIQNMN NIISFPLDSL LKGDLKGVKG DLKKPFDKAW 150
    KDYETKITKI EKEKKEHAKL HGMIRTEISG AEIAEEMEKE RRFFQLQMCE 200
    YLLKVNEIKI KKGVDLLQNL IKYFHAQCNF FQDGLKAVES LKPSIETLST 250
    DLHTIKQAQD EERRQLIQLR DILKSALQVE QKEDSQIRQS TAYSLHQPQG 300
    NKEHGTERNG SLYKKSDGIR KVWQKRKCSV KNGFLTISHG TANRPPAKLN 350
    LLTCQVKTNP EEKKCFDLIS HDRTYHFQAE DEQECQIWMS VLQNSKEEAL 400
    NNAFKGDDNT GENNIVQELT KEIISEVQRM TGNDVCCDCG APDPTWLSTN 450
    LGILTCIECS GIHRELGVHY SRMQSLTLDV LGTSELLLAK NIGNAGFNEI 500
    MECCLPAEDS VKPNPGSDMN ARKDYITAKY IERRYARKKH ADNAAKLHSL 550
    CEAVKTRDIF GLLQAYADGV DLTEKIPLAN GHEPDETALH LAVRSVDRTS 600
    LHIVDFLVQN SGNLDKQTGK GSTALHYCCL TDNAECLKLL LRGKASIEIA 650
    NESGETPLDI AKRLKHEHCE ELLTQALSGR FNSHVHVEYE WRLLHEDLDE 700
    SDDDMDEKLQ PSPNRREDRP ISFYQLGSNQ LQSNAVSLAR DAANLAKEKQ 750
    RAFMPSILQN ETYGALLSGS PPPAQPAAPS TTSAPPLPPR NVGKVQTASS 800
    ANTLWKTNSV SVDGGSRQRS SSDPPAVHPP LPPLRVTSTN PLTPTPPPPV 850
    AKTPSVMEAL SQPSKPAPPG ISQIRPPPLP PQPPSRLPQK KPAPGADKST 900
    PLTNKGQPRG PVDLSATEAL GPLSNAMVLQ PPAPMPRKSQ ATKLKPKRVK 950
    ALYNCVADNP DELTFSEGDV IIVDGEEDQE WWIGHIDGDP GRKGAFPVSF 1000
    VHFIAD 1006
    Length:1,006
    Mass (Da):111,651
    Last modified:March 29, 2004 - v3
    Checksum:i6A213517DCD99E1B
    GO
    Isoform 2 (identifier: O43150-2) [UniParc]FASTAAdd to Basket

    Also known as: PAPbeta

    The sequence of this isoform differs from the canonical sequence as follows:
         795-840: VQTASSANTLWKTNSVSVDGGSRQRSSSDPPAVHPPLPPLRVTSTN → D

    Show »
    Length:961
    Mass (Da):106,982
    Checksum:i7C8DF5590A4FB792
    GO

    Sequence cautioni

    The sequence BAA23696.2 differs from that shown. Reason: Erroneous initiation.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti86 – 861C → R in AAH63308. (PubMed:15489334)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti748 – 7481E → D.1 Publication
    Corresponds to variant rs2715860 [ dbSNP | Ensembl ].
    VAR_020307

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei795 – 84046VQTAS…VTSTN → D in isoform 2. 1 PublicationVSP_009722Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB007860 mRNA. Translation: BAA23696.2. Different initiation.
    CH471053 Genomic DNA. Translation: EAX01004.1.
    CH471053 Genomic DNA. Translation: EAX01006.1.
    BC063308 mRNA. Translation: AAH63308.1.
    CCDSiCCDS1661.1. [O43150-1]
    CCDS46224.1. [O43150-2]
    PIRiT00050.
    RefSeqiNP_001128663.1. NM_001135191.1. [O43150-2]
    NP_003878.1. NM_003887.2. [O43150-1]
    UniGeneiHs.555902.

    Genome annotation databases

    EnsembliENST00000281419; ENSP00000281419; ENSG00000151693. [O43150-1]
    ENST00000315273; ENSP00000316404; ENSG00000151693. [O43150-2]
    GeneIDi8853.
    KEGGihsa:8853.
    UCSCiuc002qzh.2. human. [O43150-1]
    uc002qzi.2. human. [O43150-2]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB007860 mRNA. Translation: BAA23696.2 . Different initiation.
    CH471053 Genomic DNA. Translation: EAX01004.1 .
    CH471053 Genomic DNA. Translation: EAX01006.1 .
    BC063308 mRNA. Translation: AAH63308.1 .
    CCDSi CCDS1661.1. [O43150-1 ]
    CCDS46224.1. [O43150-2 ]
    PIRi T00050.
    RefSeqi NP_001128663.1. NM_001135191.1. [O43150-2 ]
    NP_003878.1. NM_003887.2. [O43150-1 ]
    UniGenei Hs.555902.

    3D structure databases

    ProteinModelPortali O43150.
    SMRi O43150. Positions 30-406, 419-694, 947-1006.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114378. 15 interactions.
    IntActi O43150. 13 interactions.
    MINTi MINT-243403.
    STRINGi 9606.ENSP00000281419.

    PTM databases

    PhosphoSitei O43150.

    Proteomic databases

    MaxQBi O43150.
    PaxDbi O43150.
    PRIDEi O43150.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000281419 ; ENSP00000281419 ; ENSG00000151693 . [O43150-1 ]
    ENST00000315273 ; ENSP00000316404 ; ENSG00000151693 . [O43150-2 ]
    GeneIDi 8853.
    KEGGi hsa:8853.
    UCSCi uc002qzh.2. human. [O43150-1 ]
    uc002qzi.2. human. [O43150-2 ]

    Organism-specific databases

    CTDi 8853.
    GeneCardsi GC02P009346.
    HGNCi HGNC:2721. ASAP2.
    HPAi CAB018615.
    MIMi 603817. gene.
    neXtProti NX_O43150.
    PharmGKBi PA164716118.
    HUGEi Search...
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5347.
    HOGENOMi HOG000230570.
    HOVERGENi HBG051327.
    InParanoidi O43150.
    KOi K12488.
    OMAi YQLGSNQ.
    OrthoDBi EOG7WQ7RJ.
    PhylomeDBi O43150.
    TreeFami TF325156.

    Miscellaneous databases

    ChiTaRSi ASAP2. human.
    GeneWikii DDEF2.
    GenomeRNAii 8853.
    NextBioi 33237.
    PROi O43150.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O43150.
    Bgeei O43150.
    CleanExi HS_ASAP2.
    Genevestigatori O43150.

    Family and domain databases

    Gene3Di 1.20.1270.60. 1 hit.
    1.25.40.20. 1 hit.
    2.30.29.30. 1 hit.
    InterProi IPR027267. AH/BAR-dom.
    IPR002110. Ankyrin_rpt.
    IPR020683. Ankyrin_rpt-contain_dom.
    IPR001164. ArfGAP.
    IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR001452. SH3_domain.
    [Graphical view ]
    Pfami PF00023. Ank. 1 hit.
    PF01412. ArfGap. 1 hit.
    PF00169. PH. 1 hit.
    PF14604. SH3_9. 1 hit.
    [Graphical view ]
    PRINTSi PR00405. REVINTRACTNG.
    SMARTi SM00248. ANK. 3 hits.
    SM00105. ArfGap. 1 hit.
    SM00233. PH. 1 hit.
    SM00326. SH3. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48403. SSF48403. 1 hit.
    SSF50044. SSF50044. 1 hit.
    PROSITEi PS50297. ANK_REP_REGION. 1 hit.
    PS50088. ANK_REPEAT. 1 hit.
    PS50115. ARFGAP. 1 hit.
    PS50003. PH_DOMAIN. 1 hit.
    PS50002. SH3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro."
      Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
      DNA Res. 4:307-313(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Brain.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    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] (ISOFORM 2), VARIANT ASP-748.
      Tissue: Placenta.
    4. "Identification of a new Pyk2 target protein with Arf-GAP activity."
      Andreev J., Simon J.-P., Sabatini D.D., Kam J., Plowman G., Randazzo P.A., Schlessinger J.
      Mol. Cell. Biol. 19:2338-2350(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PHOSPHORYLATION, INTERACTION WITH ARF1; ARF5; ARF6; PTK2B AND SRC, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ALTERNATIVE SPLICING.
    5. "A new paxillin-binding protein, PAG3/Papalpha/KIAA0400, bearing an ADP-ribosylation factor GTPase-activating protein activity, is involved in paxillin recruitment to focal adhesions and cell migration."
      Kondo A., Hashimoto S., Yano H., Nagayama K., Mazaki Y., Sabe H.
      Mol. Biol. Cell 11:1315-1327(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF CYS-436, SUBCELLULAR LOCATION, INTERACTION WITH PXN.
    6. "PAG3/Papalpha/KIAA0400, a GTPase-activating protein for ADP-ribosylation factor (ARF), regulates ARF6 in Fcgamma receptor-mediated phagocytosis of macrophages."
      Uchida H., Kondo A., Yoshimura Y., Mazaki Y., Sabe H.
      J. Exp. Med. 193:955-966(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ARF6 AND ACTIN FILAMENTS.
    7. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
      Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
      Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-701, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    8. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-701, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Platelet.
    9. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-822, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    10. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-701, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    11. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
      Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
      Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-701 AND THR-903, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiASAP2_HUMAN
    AccessioniPrimary (citable) accession number: O43150
    Secondary accession number(s): D6W4Y8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 29, 2004
    Last sequence update: March 29, 2004
    Last modified: October 1, 2014
    This is version 138 of the entry and version 3 of the sequence. [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

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3