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Reviewed, UniProtKB/Swiss-Prot Q8N556 (AFAP1_HUMAN)

Last modified December 15, 2009. Version 50. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Actin filament-associated protein 1
Alternative name(s):
    110 kDa actin filament-associated protein
    AFAP-110
Gene names
Name: AFAP1
Synonyms: AFAP
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length730 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence 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

Cytoplasmcytoskeleton. Note: Localizes with stress fibers in quiescent cells, concentrated in cell motility structures such as lamellipodia, filopodia and membrane ruffles upon their induction. Ref.1

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. Ref.5

Post-translational modification

Phosphorylated on tyrosine residues by SRC. Ref.1 Ref.7 Ref.8 Ref.9 Ref.10

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 componentCytoplasm
Cytoskeleton
   Coding sequence diversityPolymorphism
   DomainCoiled coil
Repeat
   LigandActin-binding
   PTMPhosphoprotein
   Technical termComplete proteome
Gene Ontology (GO)
   Cellular componentcytoplasm

Inferred from direct assay. Source: HPA

cytoskeleton

Inferred from direct assay. Source: HPA

focal adhesion

Inferred from direct assay. Source: HPA

   Molecular functionactin binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 730730Actin filament-associated protein 1
PRO_0000317658

Regions

Domain153 – 24997PH 1
Domain347 – 44195PH 2
Region594 – 63744Interaction with F-actin By similarity
Coiled coil557 – 64892 Potential
Motif71 – 744SH3-binding By similarity
Motif94 – 974SH2-binding 1 By similarity
Motif451 – 4566SH2-binding 2 By similarity
Compositional bias60 – 10647Pro-rich

Amino acid modifications

Modified residue2771Phosphoserine Ref.10
Modified residue2781Phosphoserine Ref.10
Modified residue2821Phosphoserine Ref.7 Ref.10
Modified residue2831Phosphoserine Ref.10
Modified residue3361Phosphoserine Ref.7
Modified residue3371Phosphothreonine Ref.7
Modified residue3411Phosphothreonine Ref.7
Modified residue3421Phosphoserine Ref.7
Modified residue3431Phosphoserine Ref.7
Modified residue5461Phosphothreonine By similarity
Modified residue6631Phosphothreonine Ref.10
Modified residue6641Phosphoserine Ref.10
Modified residue6651Phosphoserine Ref.8 Ref.10
Modified residue6681Phosphoserine Ref.8 Ref.9 Ref.10
Modified residue6791Phosphoserine Ref.10
Modified residue6861Phosphothreonine Ref.10
Modified residue6871Phosphoserine Ref.10

Natural variations

Natural variant4031S → C: dbSNP rs28406288. Ref.3
VAR_038578
Natural variant5181V → M: dbSNP rs41264705. Ref.4
VAR_038579

Experimental info

Mutagenesis711P → A: Decreased tyrosine phosphorylation. Ref.1
Mutagenesis771P → A: No effect on tyrosine phosphorylation. Ref.1
Mutagenesis931Y → F: Reduces phosphorylation and phosphorylation of SRC at Y-416; when associated with F-94; F-125; F-451 and F-453. Ref.1
Mutagenesis941Y → F: Reduces phosphorylation and phosphorylation of SRC at Y-416; when associated with F-93; F-125; F-451 and F-453. Ref.1
Mutagenesis1251Y → F: Reduces phosphorylation and phosphorylation of SRC at Y-416; when associated with F-93; F-94; F-451 and F-453. Ref.1
Mutagenesis4511Y → F: Reduces phosphorylation and phosphorylation of SRC at Y-416; when associated with F-93; F-94; F-125 and F-453. Ref.1
Mutagenesis4531Y → F: Reduces phosphorylation and phosphorylation of SRC at Y-416; when associated with F-93; F-94; F-125 and F-451. Ref.1
Sequence conflict1971P → L in AAG17055. Ref.1
Sequence conflict2231G → D in AAG17055. Ref.1
Sequence conflict2381E → G in AAG17055. Ref.1
Sequence conflict4651T → A in BAF83496. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q8N556-1 [UniParc].

Last modified February 5, 2008. Version 2.
Checksum: 4E916BB4F82F5547

FASTA73080,725
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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.
[10]"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: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-277; SER-278; SER-282; SER-283; THR-663; SER-664; SER-665; SER-668; SER-679; THR-686 AND SER-687, MASS SPECTROMETRY.
[11]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-664; SER-668 AND SER-687, MASS SPECTROMETRY.
[12]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-668, MASS SPECTROMETRY.
Tissue: T-cell.

Cross-references

Sequence databases

AF188700 mRNA. Translation: AAG17055.1.
AK290807 mRNA. Translation: BAF83496.1.
BC032777 mRNA. Translation: AAH32777.1.
AB209676 mRNA. Translation: BAD92913.1.
IPIIPI00398154.
RefSeqNP_001128119.1.
NP_940997.1.
UniGeneHs.529369

3D structure databases

HSSPHSSP built from PDB template 2COF based on UniProtKB Q8N4X5.
ModBaseSearch...

Protein-protein interaction databases

STRINGQ8N556.

PTM databases

PhosphoSiteQ8N556.

Proteomic databases

PRIDEQ8N556.

Genome annotation databases

EnsemblENST00000358461; ENSP00000351245; ENSG00000196526; Homo sapiens. [Genome view]
ENST00000360265; ENSP00000353402; ENSG00000196526; Homo sapiens. [Genome view]
GeneID60312.
KEGGhsa:60312.
UCSCuc003gkf.1. human.

Organism-specific databases

CTD60312.
GeneCardsGC04M007811.
HGNCHGNC:24017. AFAP1.
HPAHPA015642.
MIM608252. gene.
GenAtlasSearch...

Phylogenomic databases

HOVERGENQ8N556.
InParanoidQ8N556.
OrthoDBEOG941SX9.

Gene expression databases

ArrayExpressQ8N556.
BgeeQ8N556.
CleanExHS_AFAP1.
GenevestigatorQ8N556.

Family and domain databases

InterProIPR011993. PH_type.
IPR001849. Pleckstrin_homology.
[Graphical view]
Gene3DG3DSA:2.30.29.30. PH_type. 2 hits.
PfamPF00169. PH. 2 hits.
[Graphical view]
SMARTSM00233. PH. 2 hits.
[Graphical view]
PROSITEPS50003. PH_DOMAIN. 2 hits.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio65281.
SOURCESearch...

Entry information

Entry nameAFAP1_HUMAN
AccessionPrimary (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: December 15, 2009
This is version 50 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

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List of human entries with polymorphisms or disease mutations

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Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents