P07737 (PROF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Profilin-1

Alternative name(s):
Profilin I

Gene names

Name:

PFN1

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	140 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR. Ref.10
Subunit structure	Occurs in many kinds of cells as a complex with monomeric actin in a 1:1 ratio. Found in a complex with XPO6, Ran, ACTB and PFN1. Interacts with VASP. Interacts with HTT. Ref.10 Ref.20
Subcellular location	Cytoplasm › cytoskeleton.
Post-translational modification	Phosphorylation at Ser-138 reduces its affinity for G-actin and blocks its interaction with HTT, reducing its ability to inhibit androgen receptor (AR) and HTT aggregation.
Sequence similarities	Belongs to the profilin family.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton
Ligand	Actin-binding
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	actin cytoskeleton organization Inferred from electronic annotation. Source: InterPro platelet activation Traceable author statement. Source: Reactome platelet degranulation Traceable author statement. Source: Reactome
Cellular component	actin cytoskeleton Inferred from electronic annotation. Source: InterPro
Molecular function	actin binding Inferred from physical interaction Ref.20Ref.4. Source: UniProtKB proline-rich region binding Inferred from physical interaction Ref.20. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.3

Chain

2 – 140

139

Profilin-1

PRO_0000199571

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.3 Ref.11

Modified residue

85

1

Phosphoserine Ref.13

Modified residue

105

1

N6-acetyllysine Ref.7 Ref.14

Modified residue

108

1

N6-acetyllysine Ref.14

Modified residue

129

1

Phosphotyrosine Ref.6 Ref.8 Ref.12

Modified residue

138

1

Phosphoserine; by ROCK1 Ref.10

Cross-link

54

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.9

Secondary structure

1

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140

Helix Strand Turn

Details...

Helix

5 – 12

8

Beta strand

17 – 24

8

Beta strand

26 – 28

3

Beta strand

30 – 34

5

Helix

40 – 42

3

Helix

45 – 51

7

Helix

58 – 60

3

Beta strand

64 – 66

3

Beta strand

69 – 76

8

Beta strand

80 – 82

3

Beta strand

85 – 90

6

Beta strand

93 – 96

4

Beta strand

100 – 105

6

Beta strand

107 – 115

9

Helix

121 – 137

17

Sequences

	Sequence		Length	Mass (Da)
	P07737 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: F725119E55A289EB	FASTA	140	15,054
	10 20 30 40 50 60 MAGWNAYIDN LMADGTCQDA AIVGYKDSPS VWAAVPGKTF VNITPAEVGV LVGKDRSSFY 70 80 90 100 110 120 VNGLTLGGQK CSVIRDSLLQ DGEFSMDLRT KSTGGAPTFN VTVTKTDKTL VLLMGKEGVH 130 140 GGLINKKCYE MASHLRRSQY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human profilin. Molecular cloning, sequence comparison, and chromosomal analysis." Kwiatkowski D.J., Bruns G.A.P. J. Biol. Chem. 263:5910-5915(1988) [PubMed: 3356709] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"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]. Tissue: Colon, Lung, Pancreas and Placenta.
[3]	"The primary structure of human platelet profilin: reinvestigation of the calf spleen profilin sequence." Ampe C., Markey F., Lindberg U., Vandekerckhove J. FEBS Lett. 228:17-21(1988) [PubMed: 3342873] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-140, ACETYLATION AT ALA-2.
[4]	"Distinct biochemical characteristics of the two human profilin isoforms." Gieselmann R., Kwiatkowski D.J., Janmey P.A., Witke W. Eur. J. Biochem. 229:621-628(1995) [PubMed: 7758455] [Abstract] Cited for: CHARACTERIZATION.
[5]	"Exportin 6: a novel nuclear export receptor that is specific for profilin.actin complexes." Stueven T., Hartmann E., Goerlich D. EMBO J. 22:5928-5940(2003) [PubMed: 14592989] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH RAN; ACTB AND XPO6.
[6]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-129, MASS SPECTROMETRY.
[7]	"Substrate and functional diversity of lysine acetylation revealed by a proteomics survey." Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T., Kho Y., Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y. Mol. Cell 23:607-618(2006) [PubMed: 16916647] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-105, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-129, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[9]	"Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry." Meierhofer D., Wang X., Huang L., Kaiser P. J. Proteome Res. 7:4566-4576(2008) [PubMed: 18781797] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-54, MASS SPECTROMETRY.
[10]	"Phosphorylation of profilin by ROCK1 regulates polyglutamine aggregation." Shao J., Welch W.J., Diprospero N.A., Diamond M.I. Mol. Cell. Biol. 28:5196-5208(2008) [PubMed: 18573880] [Abstract] Cited for: FUNCTION, INTERACTION WITH HTT, PHOSPHORYLATION AT SER-138.
[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: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[12]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-129, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[13]	"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-85, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[14]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-105 AND LYS-108, MASS SPECTROMETRY.
[15]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]	"Characterization of the three-dimensional solution structure of human profilin: 1H, 13C, and 15N NMR assignments and global folding pattern." Metzler W.J., Constantine K.L., Friedrichs M.S., Bell A.J., Ernst E.G., Lavoie T.B., Mueller L. Biochemistry 32:13818-13829(1993) [PubMed: 8268157] [Abstract] Cited for: STRUCTURE BY NMR.
[17]	Fedorov A.A., Pollard T.D., Almo S.C. Submitted (APR-1996) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
[18]	"Structure of the profilin-poly-L-proline complex involved in morphogenesis and cytoskeletal regulation." Mahoney N.M., Janmey P.A., Almo S.C. Nat. Struct. Biol. 4:953-960(1997) [PubMed: 9360613] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF COMPLEX WITH POLY-PRO.
[19]	"Profilin binds proline-rich ligands in two distinct amide backbone orientations." Mahoney N.M., Rozwarski D.A., Fedorov E., Fedorov A.A., Almo S.C. Nat. Struct. Biol. 6:666-671(1999) [PubMed: 10404225] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF COMPLEX WITH POLY-PRO.
[20]	"Structural basis for the recruitment of profilin-actin complexes during filament elongation by Ena/VASP." Ferron F., Rebowski G., Lee S.H., Dominguez R. EMBO J. 26:4597-4606(2007) [PubMed: 17914456] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 2-140 IN COMPLEXES WITH VASP AND MONOMERIC ACTIN, INTERACTION WITH VASP.
[21]	"Modulation of actin structure and function by phosphorylation of Tyr-53 and profilin binding." Baek K., Liu X., Ferron F., Shu S., Korn E.D., Dominguez R. Proc. Natl. Acad. Sci. U.S.A. 105:11748-11753(2008) [PubMed: 18689676] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 2-140 IN COMPLEX WITH VASP AND ACTIN.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J03191 mRNA. Translation: AAA36486.1.
BC002475 mRNA. Translation: AAH02475.1.
BC006768 mRNA. Translation: AAH06768.1.
BC013439 mRNA. Translation: AAH13439.1.
BC015164 mRNA. Translation: AAH15164.1.
BC057828 mRNA. Translation: AAH57828.1.

IPI

IPI00216691.

PIR

A28622.

RefSeq

NP_005013.1. NM_005022.2.

UniGene

Hs.494691.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AWI	X-ray	2.20	A/B	3-140	[»]
1CF0	X-ray	2.20	A/B	3-140	[»]
1CJF	X-ray	2.30	A/B	2-140	[»]
1FIK	X-ray	2.30	A	2-139	[»]
1FIL	X-ray	2.00	A	2-139	[»]
1PFL	NMR	-	A	2-139	[»]
2PAV	X-ray	1.80	P	2-140	[»]
2PBD	X-ray	1.50	P	2-140	[»]
3CHW	X-ray	2.30	P	2-140	[»]

ProteinModelPortal

P07737.

SMR

P07737. Positions 2-140.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-30N.

IntAct

P07737. 20 interactions.

MINT

MINT-1372667.

STRING

P07737.

Protein family/group databases

Allergome

907. Hom s Profilin.

PTM databases

PhosphoSite

P07737.

Polymorphism databases

DMDM

130979.

2D gel databases

DOSAC-COBS-2DPAGE

P07737.

OGP

P07737.

REPRODUCTION-2DPAGE

IPI00216691.

UCD-2DPAGE

P07737.

Proteomic databases

PeptideAtlas

P07737.

PRIDE

P07737.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000225655; ENSP00000225655; ENSG00000108518.

GeneID

5216.

KEGG

hsa:5216.

UCSC

uc002gaa.1. human.

Organism-specific databases

CTD

5216.

GeneCards

GC17M004848.

H-InvDB

HIX0013456.

HGNC

HGNC:8881. PFN1.

HPA

CAB037140.

MIM

176610. gene.

neXtProt

NX_P07737.

PharmGKB

PA33219.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG16742.

HOGENOM

HBG506540.

HOVERGEN

HBG053683.

InParanoid

P07737.

OMA

HLRRAQY.

OrthoDB

EOG4SN1Q1.

PhylomeDB

P07737.

Enzyme and pathway databases

Reactome

REACT_111045. Developmental Biology.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

P07737.

Bgee

P07737.

CleanEx

HS_PFN1.

Genevestigator

P07737.

GermOnline

ENSG00000108518. Homo sapiens.

Family and domain databases

InterPro

IPR002097. Profilin.
IPR005454. Profilin_mammal.
[Graphical view]

KO

K05759.

Pfam

PF00235. Profilin. 1 hit.
[Graphical view]

PRINTS

PR01639. PROFILINMAML.

SMART

SM00392. PROF. 1 hit.
[Graphical view]

SUPFAM

SSF55770. Profilin. 1 hit.

PROSITE

PS00414. PROFILIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

20172.

PMAP-CutDB

P07737.

SOURCE

Search...

Entry information

Entry name

PROF1_HUMAN

Accession

Primary (citable) accession number: P07737

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 134 of the entry and version 2 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.