Reviewed, UniProtKB/Swiss-Prot Q8N556 (AFAP1_HUMAN)

Names and origin

Protein names

Recommended name:
    Actin filament-associated protein 1
Alternative name(s):
    110 kDa actin filament-associated protein
    AFAP-110

Gene names

Name:	AFAP1
Synonyms:	AFAP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	730 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Can cross-link actin filaments into both network and bundle structures By similarity. May modulate changes in actin filament integrity and induce lamellipodia formation. May function as an adapter molecule that links other proteins, such as SRC and PKC to the actin cytoskeleton. Seems to play a role in the development and progression of prostate adenocarcinoma by regulating cell-matrix adhesions and migration in the cancer cells.
Subunit structure	Monomer and homomultimer. Interacts via its C-terminus with F-actin; probably involving AFAP1 multimers By similarity. Interacts with activated SRC SH3-SH2 domains. Interacts via its PH 1 domain with PRKCA, PRKCB and PRKCI By similarity.
Subcellular location	Cytoplasm › cytoskeleton. Note= Localizes with stress fibers in quiescent cells, concentrated in cell motility structures such as lamellipodia, filopodia and membrane ruffles upon their induction.
Tissue specificity	Low expression in normal breast epithelial cell line MCF-10A and in tumorigenic breast cancer cell lines MCF-7, T-47D, and ZR75-1. Highly expressed in the invasive breast cancer cell lines MDA-MB-231 and MDA-MB-435.
Post-translational modification	Phosphorylated on tyrosine residues by SRC.
Involvement in disease	Overexpressed in prostate carcinoma, expression levels positively correlate with aggressiveness of the disease.
Miscellaneous	Knockdown in MDA-MB-231 cells resulted in loss of actin stress fibers, decreased adhesion and spreading on fibronectin.
Sequence similarities	Contains 2 PH domains.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton
Coding sequence diversity	Polymorphism
Domain	Coiled coil Repeat
Ligand	Actin-binding
PTM	Phosphoprotein
Gene Ontology (GO)
None. [Check GOA]

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 730	730	Actin filament-associated protein 1
Regions
	Domain	153 – 249	97	PH 1
	Domain	347 – 441	95	PH 2
	Region	594 – 637	44	Interaction with F-actin By similarity
	Coiled coil	557 – 648	92	Potential
	Motif	71 – 74	4	SH3-binding By similarity
	Motif	94 – 97	4	SH2-binding 1 By similarity
	Motif	451 – 456	6	SH2-binding 2 By similarity
	Compositional bias	60 – 106	47	Pro-rich
Amino acid modifications
	Modified residue	282	1	Phosphoserine
	Modified residue	336	1	Phosphoserine
	Modified residue	337	1	Phosphothreonine
	Modified residue	341	1	Phosphothreonine
	Modified residue	342	1	Phosphoserine
	Modified residue	343	1	Phosphoserine
	Modified residue	665	1	Phosphoserine
	Modified residue	668	1	Phosphoserine
Natural variations
	Natural variant	403	1	S → C: dbSNP rs28406288.
	Natural variant	518	1	V → M: dbSNP rs41264705.
Experimental info
	Mutagenesis	71	1	P → A: Decreased tyrosine phosphorylation
	Mutagenesis	77	1	P → A: No effect on tyrosine phosphorylation
	Mutagenesis	93	1	Y → F: Reduces phosphorylation and phosphorylation of SRC at Y-416; when associated with F-94; F-125; F-451 and F-453
	Mutagenesis	94	1	Y → F: Reduces phosphorylation and phosphorylation of SRC at Y-416; when associated with F-93; F-125; F-451 and F-453
	Mutagenesis	125	1	Y → F: Reduces phosphorylation and phosphorylation of SRC at Y-416; when associated with F-93; F-94; F-451 and F-453
	Mutagenesis	451	1	Y → F: Reduces phosphorylation and phosphorylation of SRC at Y-416; when associated with F-93; F-94; F-125 and F-453
	Mutagenesis	453	1	Y → F: Reduces phosphorylation and phosphorylation of SRC at Y-416; when associated with F-93; F-94; F-125 and F-451
	Sequence conflict	197	1	P → L in AAG17055. Ref.1
	Sequence conflict	223	1	G → D in AAG17055. Ref.1
	Sequence conflict	238	1	E → G in AAG17055. Ref.1
	Sequence conflict	465	1	T → A in BAF83496. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q8N556-1 [UniParc]. Last modified February 5, 2008. Version 2. Checksum: 4E916BB4F82F5547	FASTA	730	80,725
	10 20 30 40 50 60 MEELIVELRL FLELLDHEYL TSTVREKKAV ITNILLRIQS SKGFDVKDHA QKQETANSLP 70 80 90 100 110 120 APPQMPLPEI PQPWLPPDSG PPPLPTSSLP EGYYEEAVPL SPGKAPEYIT SNYDSDAMSS 130 140 150 160 170 180 SYESYDEEEE DGKGKKTRHQ WPSEEASMDL VKDAKICAFL LRKKRFGQWT KLLCVIKDTK 190 200 210 220 230 240 LLCYKSSKDQ QPQMELPLQG CNITYIPKDS KKKKHELKIT QQGTDPLVLA VQSKEQAEQW 250 260 270 280 290 300 LKVIKEAYSG CSGPVDSECP PPPSSPVHKA ELEKKLSSER PSSDGEGVVE NGITTCNGKE 310 320 330 340 350 360 QVKRKKSSKS EAKGTVSKVT GKKITKIISL GKKKPSTDEQ TSSAEEDVPT CGYLNVLSNS 370 380 390 400 410 420 RWRERWCRVK DNKLIFHKDR TDLKTHIVSI PLRGCEVIPG LDSKHPLTFR LLRNGQEVAV 430 440 450 460 470 480 LEASSSEDMG RWIGILLAET GSSTDPEALH YDYIDVEMSA SVIQTAKQTF CFMNRRVISA 490 500 510 520 530 540 NPYLGGTSNG YAHPSGTALH YDDVPCINGS LKGKKPPVAS NGVTGKGKTL SSQPKKADPA 550 560 570 580 590 600 AVVKRTGSNA AQYKYGKNRV EADAKRLQTK EEELLKRKEA LRNRLAQLRK ERKDLRAAIE 610 620 630 640 650 660 VNAGRKPQAI LEEKLKQLEE ECRQKEAERV SLELELTEVK ESLKKALAGG VTLGLAIEPK 670 680 690 700 710 720 SGTSSPQSPV FRHRTLENSP ISSCDTSDTE GPVPVNSAAV LKKSQAAPGS SPCRGHVLRK 730 AKEWELKNGT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Conversion of mechanical force into biochemical signaling." Han B., Bai X.H., Lodyga M., Xu J., Yang B.B., Keshavjee S., Post M., Liu M. J. Biol. Chem. 279:54793-54801(2004) [PubMed: 15485829] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SRC, PHOSPHORYLATION BY SRC, MUTAGENESIS OF PRO-71; PRO-77; TYR-93; TYR-94; TYR-125; TYR-451 AND TYR-453. Tissue: Lung.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney.
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT CYS-403. Tissue: Brain.
[4]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 93-730, VARIANT MET-518. Tissue: Brain.
[5]	"AFAP-110 is required for actin stress fiber formation and cell adhesion in MDA-MB-231 breast cancer cells." Dorfleutner A., Stehlik C., Zhang J., Gallick G.E., Flynn D.C. J. Cell. Physiol. 213:740-749(2007) [PubMed: 17520695] [Abstract] Cited for: TISSUE SPECIFICITY, KNOCKDOWN IN MDA-MB-231 CELLS.
[6]	"AFAP-110 is overexpressed in prostate cancer and contributes to tumorigenic growth by regulating focal contacts." Zhang J., Park S.I., Artime M.C., Summy J.M., Shah A.N., Bomser J.A., Dorfleutner A., Flynn D.C., Gallick G.E. J. Clin. Invest. 117:2962-2973(2007) [PubMed: 17885682] [Abstract] Cited for: ROLE IN PROSTATE CANCER.
[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: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-282; SER-336; THR-337; THR-341; SER-342 AND SER-343, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"Phosphoproteome analysis of the human mitotic spindle." Nousiainen M., Sillje H.H.W., Sauer G., Nigg E.A., Koerner R. Proc. Natl. Acad. Sci. U.S.A. 103:5391-5396(2006) [PubMed: 16565220] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-665 AND SER-668, MASS SPECTROMETRY. Tissue: Epithelium.
[9]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-668, MASS SPECTROMETRY.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF188700 mRNA. Translation: AAG17055.1. AK290807 mRNA. Translation: BAF83496.1. BC032777 mRNA. Translation: AAH32777.1. AB209676 mRNA. Translation: BAD92913.1.
RefSeq	NP_067651.2. NP_940997.1.
UniGene	Hs.529369
3D structure databases
ModBase	Search...
PTM databases
PhosphoSite	Q8N556.
Genome annotation databases
Ensembl	ENSG00000196526. Homo sapiens. [Contig view]
GeneID	60312.
KEGG	hsa:60312.
Organism-specific databases
HGNC	HGNC:24017. AFAP1.
HPA	HPA015642.
MIM	608252. gene.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	Q8N556.
HOVERGEN	Q8N556.
Gene expression databases
ArrayExpress	Q8N556.
CleanEx	HS_AFAP1.
Family and domain databases
InterPro	IPR001849. PH. IPR011993. PH_type. [Graphical view]
Gene3D	G3DSA:2.30.29.30. PH_type. 2 hits.
Pfam	PF00169. PH. 2 hits. [Graphical view]
SMART	SM00233. PH. 2 hits. [Graphical view]
PROSITE	PS50003. PH_DOMAIN. 2 hits. [Graphical view]
ProDom	Q8N556. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
Other Resources
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

AFAP1_HUMAN

Accession

Primary (citable) accession number: Q8N556
Secondary accession number(s): A8K442, Q59EY5, Q9HBY1

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 5, 2008
Last sequence update:	February 5, 2008
Last modified:	July 22, 2008
This is version 35 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)