PROF2_HUMAN
ID PROF2_HUMAN Reviewed; 140 AA.
AC P35080; B2R4C8; D3DNI4; Q4VBQ4; Q8WVF9; Q9HBK2;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 210.
DE RecName: Full=Profilin-2;
DE AltName: Full=Profilin II;
GN Name=PFN2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IIB).
RC TISSUE=Epithelium;
RX PubMed=8365484; DOI=10.1016/0014-5793(93)80262-s;
RA Honore B., Madsen P.S., Andersen A.H., Leffers H.;
RT "Cloning and expression of a novel human profilin variant, profilin II.";
RL FEBS Lett. 330:151-155(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IIA).
RC TISSUE=Brain;
RX PubMed=11027290; DOI=10.1128/mcb.20.21.8209-8219.2000;
RA Lambrechts A., Braun A., Jonckheere V., Aszodi A., Lanier L.M., Robbens J.,
RA Van Colen I., Vandekerckhove J., Faessler R., Ampe C.;
RT "Profilin II is alternatively spliced, resulting in profilin isoforms that
RT are differentially expressed and have distinct biochemical properties.";
RL Mol. Cell. Biol. 20:8209-8219(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS IIA AND IIB).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS IIA AND IIB).
RC TISSUE=Brain, Lung, and Spinal cord;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 30-69; 76-89; 92-105 AND 109-116, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [7]
RP INTERACTION WITH ACTIN.
RX PubMed=7758455; DOI=10.1111/j.1432-1033.1995.tb20506.x;
RA Gieselmann R., Kwiatkowski D.J., Janmey P.A., Witke W.;
RT "Distinct biochemical characteristics of the two human profilin isoforms.";
RL Eur. J. Biochem. 229:621-628(1995).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
RX PubMed=10600384; DOI=10.1006/jmbi.1999.3318;
RA Nodelman I.M., Bowman G.D., Lindberg U., Schutt C.E.;
RT "X-ray structure determination of human profilin II: a comparative
RT structural analysis of human profilins.";
RL J. Mol. Biol. 294:1271-1285(1999).
CC -!- FUNCTION: Binds to actin and affects the structure of the cytoskeleton.
CC At high concentrations, profilin prevents the polymerization of actin,
CC whereas it enhances it at low concentrations. By binding to PIP2, it
CC inhibits the formation of IP3 and DG.
CC -!- SUBUNIT: Occurs in many kinds of cells as a complex with monomeric
CC actin in a 1:1 ratio (PubMed:7758455). Interacts with PFN2 (By
CC similarity). {ECO:0000250|UniProtKB:Q9JJV2,
CC ECO:0000269|PubMed:7758455}.
CC -!- INTERACTION:
CC P35080; Q14789: GOLGB1; NbExp=2; IntAct=EBI-473138, EBI-709973;
CC P35080; P42858: HTT; NbExp=7; IntAct=EBI-473138, EBI-466029;
CC P35080; O08816: Wasl; Xeno; NbExp=3; IntAct=EBI-473138, EBI-6142604;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=IIa;
CC IsoId=P35080-1; Sequence=Displayed;
CC Name=IIb;
CC IsoId=P35080-2; Sequence=VSP_005217;
CC -!- TISSUE SPECIFICITY: Highly expressed in brain, skeletal muscle and
CC kidney and less strongly in heart, placenta, lung and liver.
CC -!- SIMILARITY: Belongs to the profilin family. {ECO:0000305}.
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DR EMBL; L10678; AAA03022.1; -; mRNA.
DR EMBL; AF228738; AAG24949.1; -; mRNA.
DR EMBL; AK311780; BAG34723.1; -; mRNA.
DR EMBL; AK311782; BAG34725.1; -; mRNA.
DR EMBL; CH471052; EAW78850.1; -; Genomic_DNA.
DR EMBL; BC002964; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; CH471052; EAW78852.1; -; Genomic_DNA.
DR EMBL; BC018049; AAH18049.1; -; mRNA.
DR EMBL; BC043646; AAH43646.1; -; mRNA.
DR EMBL; BC095444; AAH95444.1; -; mRNA.
DR CCDS; CCDS3148.1; -. [P35080-1]
DR CCDS; CCDS46934.1; -. [P35080-2]
DR PIR; S36804; S36804.
DR RefSeq; NP_002619.1; NM_002628.4. [P35080-2]
DR RefSeq; NP_444252.1; NM_053024.3. [P35080-1]
DR PDB; 1D1J; X-ray; 2.20 A; A/B/C/D=2-138.
DR PDBsum; 1D1J; -.
DR AlphaFoldDB; P35080; -.
DR BMRB; P35080; -.
DR SMR; P35080; -.
DR BioGRID; 111238; 97.
DR CORUM; P35080; -.
DR IntAct; P35080; 52.
DR MINT; P35080; -.
DR STRING; 9606.ENSP00000239940; -.
DR DrugBank; DB02580; Pentaglyme.
DR DrugBank; DB02078; Triglyme.
DR GlyGen; P35080; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P35080; -.
DR MetOSite; P35080; -.
DR PhosphoSitePlus; P35080; -.
DR SwissPalm; P35080; -.
DR BioMuta; PFN2; -.
DR DMDM; 20178322; -.
DR REPRODUCTION-2DPAGE; P35080; -.
DR EPD; P35080; -.
DR jPOST; P35080; -.
DR MassIVE; P35080; -.
DR MaxQB; P35080; -.
DR PaxDb; P35080; -.
DR PeptideAtlas; P35080; -.
DR PRIDE; P35080; -.
DR ProteomicsDB; 54978; -. [P35080-1]
DR ProteomicsDB; 54979; -. [P35080-2]
DR Antibodypedia; 33583; 265 antibodies from 31 providers.
DR DNASU; 5217; -.
DR Ensembl; ENST00000239940.12; ENSP00000239940.7; ENSG00000070087.15. [P35080-1]
DR Ensembl; ENST00000452853.6; ENSP00000410464.2; ENSG00000070087.15. [P35080-2]
DR GeneID; 5217; -.
DR KEGG; hsa:5217; -.
DR MANE-Select; ENST00000239940.12; ENSP00000239940.7; NM_053024.4; NP_444252.1.
DR UCSC; uc003ext.3; human. [P35080-1]
DR CTD; 5217; -.
DR DisGeNET; 5217; -.
DR GeneCards; PFN2; -.
DR HGNC; HGNC:8882; PFN2.
DR HPA; ENSG00000070087; Low tissue specificity.
DR MIM; 176590; gene.
DR neXtProt; NX_P35080; -.
DR OpenTargets; ENSG00000070087; -.
DR PharmGKB; PA33220; -.
DR VEuPathDB; HostDB:ENSG00000070087; -.
DR eggNOG; KOG1755; Eukaryota.
DR GeneTree; ENSGT00940000153664; -.
DR InParanoid; P35080; -.
DR OMA; FFHMCSV; -.
DR OrthoDB; 1428600at2759; -.
DR PhylomeDB; P35080; -.
DR TreeFam; TF331744; -.
DR PathwayCommons; P35080; -.
DR Reactome; R-HSA-376176; Signaling by ROBO receptors.
DR Reactome; R-HSA-5663220; RHO GTPases Activate Formins.
DR SignaLink; P35080; -.
DR BioGRID-ORCS; 5217; 7 hits in 1075 CRISPR screens.
DR ChiTaRS; PFN2; human.
DR EvolutionaryTrace; P35080; -.
DR GeneWiki; PFN2; -.
DR GenomeRNAi; 5217; -.
DR Pharos; P35080; Tbio.
DR PRO; PR:P35080; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P35080; protein.
DR Bgee; ENSG00000070087; Expressed in frontal pole and 212 other tissues.
DR ExpressionAtlas; P35080; baseline and differential.
DR Genevisible; P35080; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0098794; C:postsynapse; IEA:Ensembl.
DR GO; GO:0098793; C:presynapse; IEA:Ensembl.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IEA:Ensembl.
DR GO; GO:0003779; F:actin binding; IBA:GO_Central.
DR GO; GO:0003785; F:actin monomer binding; IPI:UniProtKB.
DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:GO_Central.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; IEA:InterPro.
DR GO; GO:0098885; P:modification of postsynaptic actin cytoskeleton; IEA:Ensembl.
DR GO; GO:0030837; P:negative regulation of actin filament polymerization; IDA:UniProtKB.
DR GO; GO:0010633; P:negative regulation of epithelial cell migration; IMP:UniProtKB.
DR GO; GO:1900028; P:negative regulation of ruffle assembly; IMP:UniProtKB.
DR GO; GO:0032233; P:positive regulation of actin filament bundle assembly; IMP:UniProtKB.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IGI:UniProtKB.
DR GO; GO:0032781; P:positive regulation of ATP-dependent activity; IDA:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IMP:UniProtKB.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IMP:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB.
DR GO; GO:0030833; P:regulation of actin filament polymerization; IBA:GO_Central.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IEA:Ensembl.
DR CDD; cd00148; PROF; 1.
DR InterPro; IPR005455; PFN.
DR InterPro; IPR029891; PFN2.
DR InterPro; IPR036140; PFN_sf.
DR InterPro; IPR005454; Profilin1/2/3_vertebrate.
DR InterPro; IPR027310; Profilin_CS.
DR PANTHER; PTHR13936:SF15; PTHR13936:SF15; 1.
DR Pfam; PF00235; Profilin; 1.
DR PRINTS; PR00392; PROFILIN.
DR PRINTS; PR01639; PROFILINMAML.
DR SMART; SM00392; PROF; 1.
DR SUPFAM; SSF55770; SSF55770; 1.
DR PROSITE; PS00414; PROFILIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Actin-binding; Alternative splicing; Cytoplasm;
KW Cytoskeleton; Direct protein sequencing; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22223895"
FT CHAIN 2..140
FT /note="Profilin-2"
FT /id="PRO_0000199575"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22223895"
FT VAR_SEQ 109..140
FT /note="VLVFVMGKEGVHGGGLNKKAYSMAKYLRDSGF -> ALVIVMGKEGVHGGTL
FT NKKAYELALYLRRSDV (in isoform IIb)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:8365484"
FT /id="VSP_005217"
FT CONFLICT 65
FT /note="T -> A (in Ref. 5; AAH18049)"
FT /evidence="ECO:0000305"
FT HELIX 5..11
FT /evidence="ECO:0007829|PDB:1D1J"
FT STRAND 17..24
FT /evidence="ECO:0007829|PDB:1D1J"
FT STRAND 26..28
FT /evidence="ECO:0007829|PDB:1D1J"
FT STRAND 30..34
FT /evidence="ECO:0007829|PDB:1D1J"
FT HELIX 40..42
FT /evidence="ECO:0007829|PDB:1D1J"
FT HELIX 45..52
FT /evidence="ECO:0007829|PDB:1D1J"
FT HELIX 58..62
FT /evidence="ECO:0007829|PDB:1D1J"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:1D1J"
FT STRAND 69..80
FT /evidence="ECO:0007829|PDB:1D1J"
FT STRAND 85..90
FT /evidence="ECO:0007829|PDB:1D1J"
FT STRAND 93..95
FT /evidence="ECO:0007829|PDB:1D1J"
FT STRAND 100..105
FT /evidence="ECO:0007829|PDB:1D1J"
FT STRAND 107..115
FT /evidence="ECO:0007829|PDB:1D1J"
FT HELIX 121..137
FT /evidence="ECO:0007829|PDB:1D1J"
SQ SEQUENCE 140 AA; 15046 MW; F43884E1427C9A99 CRC64;
MAGWQSYVDN LMCDGCCQEA AIVGYCDAKY VWAATAGGVF QSITPIEIDM IVGKDREGFF
TNGLTLGAKK CSVIRDSLYV DGDCTMDIRT KSQGGEPTYN VAVGRAGRVL VFVMGKEGVH
GGGLNKKAYS MAKYLRDSGF
