O43150 (ASAP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	ASAP2
Synonyms:	DDEF2, KIAA0400

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	1006 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.4 Ref.5 Ref.6
Subunit structure	Binds PXN, ARF1, ARF5, ARF6, PTK2B and SRC.
Subcellular location	Cytoplasm. Golgi apparatus › Golgi stack membrane; Peripheral membrane protein. Cell membrane; Peripheral membrane protein. Note: Colocalizes with F-actin and ARF6 in phagocytic cups. Ref.4 Ref.5 Ref.6
Tissue specificity	Detected in heart, brain, placenta, kidney, monocytes and pancreas. Ref.4
Induction	Up-regulated during monocytic maturation.
Domain	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.
Post-translational modification	Phosphorylated on tyrosine residues by SRC and PTK2B. Ref.4
Sequence similarities	Contains 2 ANK repeats. Contains 1 Arf-GAP domain. Contains 1 PH domain. Contains 1 SH3 domain.
Sequence caution	The sequence BAA23696.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	ANK repeat Coiled coil Repeat SH3 domain
Ligand	Metal-binding Zinc
Molecular function	GTPase activation
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	positive regulation of GTPase activity Inferred from electronic annotation. Source: GOC regulation of ARF GTPase activity Inferred from electronic annotation. Source: InterPro
Cellular_component	Golgi cisterna membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ARF GTPase activator activity Inferred from electronic annotation. Source: InterPro enzyme activator activity Traceable author statement PubMed 9819391. Source: ProtInc phospholipid binding Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GRB2	P62993	3	EBI-310968,EBI-401755
PLCG1	P19174	3	EBI-310968,EBI-79387

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O43150-1)

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.

Isoform 2 (identifier: O43150-2)

Also known as: PAPbeta;

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1006	1006	Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 2		PRO_0000074198
Regions
	Domain	305 – 397	93	PH
	Domain	421 – 543	123	Arf-GAP
	Repeat	584 – 616	33	ANK 1
	Repeat	620 – 649	30	ANK 2
	Domain	944 – 1006	63	SH3
	Coiled coil	256 – 283	28	Potential
	Coiled coil	729 – 752	24	Potential
	Compositional bias	771 – 936	166	Pro-rich
Amino acid modifications
	Modified residue	701	1	Phosphoserine Ref.7 Ref.8 Ref.10 Ref.11
	Modified residue	822	1	Phosphoserine Ref.9
	Modified residue	903	1	Phosphothreonine Ref.11
Natural variations
	Alternative sequence	795 – 840	46	VQTAS…VTSTN → D in isoform 2.		VSP_009722
	Natural variant	748	1	E → D. Ref.3 Corresponds to variant rs2715860 [ dbSNP | Ensembl ].		VAR_020307
Experimental info
	Mutagenesis	436	1	C → A: Loss of Arf-GAP activity. Ref.5
	Sequence conflict	86	1	C → R in AAH63308. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (PAPalpha) [UniParc]. Last modified March 29, 2004. Version 3. Checksum: 6A213517DCD99E1B	FASTA	1,006	111,651
	10 20 30 40 50 60 MPDQISVSEF VAETHEDYKA PTASSFTTRT AQCRNTVAAI EEALDVDRMV LYKMKKSVKA 70 80 90 100 110 120 INSSGLAHVE NEEQYTQALE KFGGNCVCRD DPDLGSAFLK FSVFTKELTA LFKNLIQNMN 130 140 150 160 170 180 NIISFPLDSL LKGDLKGVKG DLKKPFDKAW KDYETKITKI EKEKKEHAKL HGMIRTEISG 190 200 210 220 230 240 AEIAEEMEKE RRFFQLQMCE YLLKVNEIKI KKGVDLLQNL IKYFHAQCNF FQDGLKAVES 250 260 270 280 290 300 LKPSIETLST DLHTIKQAQD EERRQLIQLR DILKSALQVE QKEDSQIRQS TAYSLHQPQG 310 320 330 340 350 360 NKEHGTERNG SLYKKSDGIR KVWQKRKCSV KNGFLTISHG TANRPPAKLN LLTCQVKTNP 370 380 390 400 410 420 EEKKCFDLIS HDRTYHFQAE DEQECQIWMS VLQNSKEEAL NNAFKGDDNT GENNIVQELT 430 440 450 460 470 480 KEIISEVQRM TGNDVCCDCG APDPTWLSTN LGILTCIECS GIHRELGVHY SRMQSLTLDV 490 500 510 520 530 540 LGTSELLLAK NIGNAGFNEI MECCLPAEDS VKPNPGSDMN ARKDYITAKY IERRYARKKH 550 560 570 580 590 600 ADNAAKLHSL CEAVKTRDIF GLLQAYADGV DLTEKIPLAN GHEPDETALH LAVRSVDRTS 610 620 630 640 650 660 LHIVDFLVQN SGNLDKQTGK GSTALHYCCL TDNAECLKLL LRGKASIEIA NESGETPLDI 670 680 690 700 710 720 AKRLKHEHCE ELLTQALSGR FNSHVHVEYE WRLLHEDLDE SDDDMDEKLQ PSPNRREDRP 730 740 750 760 770 780 ISFYQLGSNQ LQSNAVSLAR DAANLAKEKQ RAFMPSILQN ETYGALLSGS PPPAQPAAPS 790 800 810 820 830 840 TTSAPPLPPR NVGKVQTASS ANTLWKTNSV SVDGGSRQRS SSDPPAVHPP LPPLRVTSTN 850 860 870 880 890 900 PLTPTPPPPV AKTPSVMEAL SQPSKPAPPG ISQIRPPPLP PQPPSRLPQK KPAPGADKST 910 920 930 940 950 960 PLTNKGQPRG PVDLSATEAL GPLSNAMVLQ PPAPMPRKSQ ATKLKPKRVK ALYNCVADNP 970 980 990 1000 DELTFSEGDV IIVDGEEDQE WWIGHIDGDP GRKGAFPVSF VHFIAD
	Isoform 2 (PAPbeta) [UniParc]. Checksum: 7C8DF5590A4FB792	FASTA	961	106,982
	10 20 30 40 50 60 MPDQISVSEF VAETHEDYKA PTASSFTTRT AQCRNTVAAI EEALDVDRMV LYKMKKSVKA 70 80 90 100 110 120 INSSGLAHVE NEEQYTQALE KFGGNCVCRD DPDLGSAFLK FSVFTKELTA LFKNLIQNMN 130 140 150 160 170 180 NIISFPLDSL LKGDLKGVKG DLKKPFDKAW KDYETKITKI EKEKKEHAKL HGMIRTEISG 190 200 210 220 230 240 AEIAEEMEKE RRFFQLQMCE YLLKVNEIKI KKGVDLLQNL IKYFHAQCNF FQDGLKAVES 250 260 270 280 290 300 LKPSIETLST DLHTIKQAQD EERRQLIQLR DILKSALQVE QKEDSQIRQS TAYSLHQPQG 310 320 330 340 350 360 NKEHGTERNG SLYKKSDGIR KVWQKRKCSV KNGFLTISHG TANRPPAKLN LLTCQVKTNP 370 380 390 400 410 420 EEKKCFDLIS HDRTYHFQAE DEQECQIWMS VLQNSKEEAL NNAFKGDDNT GENNIVQELT 430 440 450 460 470 480 KEIISEVQRM TGNDVCCDCG APDPTWLSTN LGILTCIECS GIHRELGVHY SRMQSLTLDV 490 500 510 520 530 540 LGTSELLLAK NIGNAGFNEI MECCLPAEDS VKPNPGSDMN ARKDYITAKY IERRYARKKH 550 560 570 580 590 600 ADNAAKLHSL CEAVKTRDIF GLLQAYADGV DLTEKIPLAN GHEPDETALH LAVRSVDRTS 610 620 630 640 650 660 LHIVDFLVQN SGNLDKQTGK GSTALHYCCL TDNAECLKLL LRGKASIEIA NESGETPLDI 670 680 690 700 710 720 AKRLKHEHCE ELLTQALSGR FNSHVHVEYE WRLLHEDLDE SDDDMDEKLQ PSPNRREDRP 730 740 750 760 770 780 ISFYQLGSNQ LQSNAVSLAR DAANLAKEKQ RAFMPSILQN ETYGALLSGS PPPAQPAAPS 790 800 810 820 830 840 TTSAPPLPPR NVGKDPLTPT PPPPVAKTPS VMEALSQPSK PAPPGISQIR PPPLPPQPPS 850 860 870 880 890 900 RLPQKKPAPG ADKSTPLTNK GQPRGPVDLS ATEALGPLSN AMVLQPPAPM PRKSQATKLK 910 920 930 940 950 960 PKRVKALYNC VADNPDELTF SEGDVIIVDG EEDQEWWIGH IDGDPGRKGA FPVSFVHFIA D

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases 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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-701, MASS SPECTROMETRY. Tissue: Platelet.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-822, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB007860 mRNA. Translation: BAA23696.2. Different initiation. CH471053 Genomic DNA. Translation: EAX01004.1. CH471053 Genomic DNA. Translation: EAX01006.1. BC063308 mRNA. Translation: AAH63308.1.
IPI	IPI00022058. IPI00409613.
PIR	T00050.
RefSeq	NP_001128663.1. NM_001135191.1. NP_003878.1. NM_003887.2.
UniGene	Hs.555902.
3D structure databases
ProteinModelPortal	O43150.
ModBase	Search...
Protein-protein interaction databases
IntAct	O43150. 9 interactions.
MINT	MINT-243403.
STRING	9606.ENSP00000281419.
PTM databases
PhosphoSite	O43150.
Proteomic databases
PaxDb	O43150.
PRIDE	O43150.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000281419; ENSP00000281419; ENSG00000151693. ENST00000315273; ENSP00000316404; ENSG00000151693.
GeneID	8853.
KEGG	hsa:8853.
UCSC	uc002qzh.2. human. uc002qzi.2. human.
Organism-specific databases
CTD	8853.
GeneCards	GC02P009346.
HGNC	HGNC:2721. ASAP2.
HPA	CAB018615.
MIM	603817. gene.
neXtProt	NX_O43150.
PharmGKB	PA164716118.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5347.
HOGENOM	HOG000230570.
HOVERGEN	HBG051327.
InParanoid	O43150.
KO	K12488.
OMA	YQLGSNQ.
OrthoDB	EOG4VHK5P.
PhylomeDB	O43150.
Enzyme and pathway databases
Pathway_Interaction_DB	arf6_traffickingpathway. Arf6 trafficking events.
Gene expression databases
ArrayExpress	O43150.
Bgee	O43150.
CleanEx	HS_ASAP2.
Genevestigator	O43150.
GermOnline	ENSG00000151693. 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. IPR001452. SH3_domain. [Graphical view]
Pfam	PF00023. Ank. 1 hit. PF01412. ArfGap. 1 hit. PF00169. PH. 1 hit. PF00018. SH3_1. 1 hit. [Graphical view]
PRINTS	PR00405. REVINTRACTNG.
SMART	SM00248. ANK. 3 hits. SM00105. ArfGap. 1 hit. SM00233. PH. 1 hit. SM00326. SH3. 1 hit. [Graphical view]
SUPFAM	SSF48403. ANK. 1 hit. SSF50044. SH3. 1 hit.
PROSITE	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]
ProtoNet	Search...
Other
ChiTaRS	ASAP2. human.
GenomeRNAi	8853.
NextBio	33237.
SOURCE	Search...

Entry information

Entry name

ASAP2_HUMAN

Accession

Primary (citable) accession number: O43150
Secondary accession number(s): D6W4Y8

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 29, 2004
Last sequence update:	March 29, 2004
Last modified:	May 1, 2013
This is version 125 of the entry and version 3 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.