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Q8N556 (AFAP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 86. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

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

Protein attributes

Sequence length730 AA.
Sequence statusComplete.
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. Ref.1 Ref.8

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. Ref.1

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 ZR-75-1. Highly expressed in the invasive breast cancer cell lines MDA-MB-231 and MDA-MB-435. Overexpressed in prostate carcinoma. Ref.7 Ref.8

Post-translational modification

Phosphorylated on tyrosine residues by SRC. Ref.1

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 diversityAlternative splicing
Polymorphism
   DomainCoiled coil
Repeat
   LigandActin-binding
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-KW

cytoskeleton

Inferred from electronic annotation. Source: UniProtKB-SubCell

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8N556-1)

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: Q8N556-2)

The sequence of this isoform differs from the canonical sequence as follows:
     510-510: S → SWEPEDGFPA...GRASLGLNSQ
Note: No experimental confirmation available.

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 residue11N-acetylmethionine Ref.12
Modified residue2821Phosphoserine Ref.9
Modified residue2831Phosphoserine Ref.9
Modified residue5481Phosphoserine Ref.10
Modified residue6641Phosphoserine Ref.9
Modified residue6651Phosphoserine Ref.9
Modified residue6681Phosphoserine Ref.9 Ref.10 Ref.11
Modified residue6791Phosphoserine Ref.9
Modified residue6871Phosphoserine Ref.9

Natural variations

Alternative sequence5101S → SWEPEDGFPASCSRGLGEEV LYDNAGLYDNLPPPHIFARY SPADRKASRLSADKLSSNHY KYPASAQSVTNTSSVGRASL GLNSQ in isoform 2.
VSP_044838
Natural variant4031S → C. Ref.2 Ref.4
Corresponds to variant rs28406288 [ dbSNP | Ensembl ].
VAR_038578
Natural variant5181V → M. Ref.5
Corresponds to variant rs41264705 [ dbSNP | Ensembl ].
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
Isoform 2:
Sequence conflict5611A → V in BAG60004. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 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

Isoform 2 [UniParc].

Checksum: B066A95292C261FC
Show »

FASTA81489,795

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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT CYS-403.
Tissue: Brain and Kidney.
[3]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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 1), VARIANT CYS-403.
Tissue: Brain.
[5]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 (ISOFORM 1), VARIANT MET-518.
Tissue: Brain.
[6]"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"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] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, KNOCKDOWN IN MDA-MB-231 CELLS.
[8]"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] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, POSSIBLE FUNCTION IN PROSTATE CANCER PROGRESSION.
[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-282; SER-283; SER-664; SER-665; SER-668; SER-679 AND SER-687, 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-548 AND SER-668, 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-668, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF188700 mRNA. Translation: AAG17055.1.
AK290807 mRNA. Translation: BAF83496.1.
AK297631 mRNA. Translation: BAG60004.1.
AC004169 Genomic DNA. No translation available.
AC097381 Genomic DNA. No translation available.
AC112254 Genomic DNA. No translation available.
AC141931 Genomic DNA. No translation available.
AC144451 Genomic DNA. No translation available.
BC032777 mRNA. Translation: AAH32777.1.
AB209676 mRNA. Translation: BAD92913.1.
RefSeqNP_001128119.1. NM_001134647.1.
NP_940997.1. NM_198595.2.
UniGeneHs.529369.

3D structure databases

ProteinModelPortalQ8N556.
SMRQ8N556. Positions 150-249, 342-437.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121895. 8 interactions.
IntActQ8N556. 1 interaction.
STRING9606.ENSP00000410689.

PTM databases

PhosphoSiteQ8N556.

Polymorphism databases

DMDM166919564.

Proteomic databases

PaxDbQ8N556.
PRIDEQ8N556.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000358461; ENSP00000351245; ENSG00000196526. [Q8N556-1]
ENST00000360265; ENSP00000353402; ENSG00000196526. [Q8N556-1]
ENST00000382543; ENSP00000371983; ENSG00000196526. [Q8N556-2]
ENST00000420658; ENSP00000410689; ENSG00000196526. [Q8N556-2]
GeneID60312.
KEGGhsa:60312.
UCSCuc003gkg.1. human. [Q8N556-1]
uc011bwk.1. human.

Organism-specific databases

CTD60312.
GeneCardsGC04M007682.
H-InvDBHIX0031430.
HGNCHGNC:24017. AFAP1.
HPACAB024712.
HPA015642.
MIM608252. gene.
neXtProtNX_Q8N556.
PharmGKBPA162375733.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG48103.
HOGENOMHOG000033832.
HOVERGENHBG106875.
InParanoidQ8N556.
OMAAGRKTQV.
OrthoDBEOG7KQ217.
PhylomeDBQ8N556.

Gene expression databases

BgeeQ8N556.
CleanExHS_AFAP1.
GenevestigatorQ8N556.

Family and domain databases

Gene3D2.30.29.30. 2 hits.
InterProIPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
[Graphical view]
PfamPF00169. PH. 2 hits.
[Graphical view]
SMARTSM00233. PH. 2 hits.
[Graphical view]
PROSITEPS50003. PH_DOMAIN. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSAFAP1. human.
GeneWikiAFAP1.
GenomeRNAi60312.
NextBio65281.
PROQ8N556.
SOURCESearch...

Entry information

Entry nameAFAP1_HUMAN
AccessionPrimary (citable) accession number: Q8N556
Secondary accession number(s): A8K442 expand/collapse secondary AC list , B4DMU2, E9PDT7, Q59EY5, Q9HBY1
Entry history
Integrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: February 5, 2008
Last modified: April 16, 2014
This is version 86 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM