BFSP2_HUMAN
ID BFSP2_HUMAN Reviewed; 415 AA.
AC Q13515; Q14D32; Q9HBW5;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Phakinin {ECO:0000303|PubMed:28935373};
DE AltName: Full=49 kDa cytoskeletal protein;
DE AltName: Full=Beaded filament structural protein 2 {ECO:0000303|PubMed:10729115};
DE AltName: Full=Lens fiber cell beaded filament protein CP 47 {ECO:0000303|PubMed:28935373};
DE Short=CP47 {ECO:0000303|PubMed:28935373};
DE AltName: Full=Lens fiber cell beaded filament protein CP 49 {ECO:0000303|PubMed:8636093};
DE Short=CP49 {ECO:0000303|PubMed:8636093};
DE AltName: Full=Lens intermediate filament-like light {ECO:0000303|PubMed:10729115};
DE Short=LIFL-L {ECO:0000303|PubMed:10729115};
GN Name=BFSP2;
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].
RC TISSUE=Lens;
RX PubMed=8636093; DOI=10.1074/jbc.271.12.6729;
RA Hess J.F., Casselman J.T., FitzGerald P.G.;
RT "Gene structure and cDNA sequence identify the beaded filament protein CP49
RT as a highly divergent type I intermediate filament protein.";
RL J. Biol. Chem. 271:6729-6735(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 164-415, AND VARIANT CTRCT12 GLU-233
RP DEL.
RX PubMed=10739768; DOI=10.1086/302872;
RA Jakobs P.M., Hess J.F., FitzGerald P.G., Kramer P., Weleber R.G., Litt M.;
RT "Autosomal-dominant congenital cataract associated with a deletion mutation
RT in the human beaded filament protein gene BFSP2.";
RL Am. J. Hum. Genet. 66:1432-1436(2000).
RN [4]
RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH BFSP1 AND CRYAA.
RX PubMed=28935373; DOI=10.1016/j.bbrc.2017.09.088;
RA Chaves J.M., Gupta R., Srivastava K., Srivastava O.;
RT "Human alpha A-crystallin missing N-terminal domain poorly complexes with
RT filensin and phakinin.";
RL Biochem. Biophys. Res. Commun. 494:402-408(2017).
RN [5]
RP VARIANT CTRCT12 TRP-287.
RX PubMed=10729115; DOI=10.1086/302871;
RA Conley Y.P., Erturk D., Keverline A., Mah T.S., Keravala A., Barnes L.R.,
RA Bruchis A., Hess J.F., FitzGerald P.G., Weeks D.E., Ferrell R.E.,
RA Gorin M.B.;
RT "A juvenile-onset, progressive cataract locus on chromosome 3q21-q22 is
RT associated with a missense mutation in the beaded filament structural
RT protein-2.";
RL Am. J. Hum. Genet. 66:1426-1431(2000).
RN [6]
RP VARIANT CTRCT12 GLU-233 DEL.
RX PubMed=15570218;
RA Zhang Q., Guo X., Xiao X., Yi J., Jia X., Hejtmancik J.F.;
RT "Clinical description and genome wide linkage study of Y-sutural cataract
RT and myopia in a Chinese family.";
RL Mol. Vis. 10:890-900(2004).
RN [7]
RP VARIANT CTRCT12 GLU-233 DEL.
RX PubMed=17200662;
RA Zhang L., Gao L., Li Z., Qin W., Gao W., Cui X., Feng G., Fu S., He L.,
RA Liu P.;
RT "Progressive sutural cataract associated with a BFSP2 mutation in a Chinese
RT family.";
RL Mol. Vis. 12:1626-1631(2006).
RN [8]
RP VARIANT CTRCT12 GLU-233 DEL.
RX PubMed=17982427;
RA Cui X., Gao L., Jin Y., Zhang Y., Bai J., Feng G., Gao W., Liu P., He L.,
RA Fu S.;
RT "The E233del mutation in BFSP2 causes a progressive autosomal dominant
RT congenital cataract in a Chinese family.";
RL Mol. Vis. 13:2023-2029(2007).
RN [9]
RP VARIANT CTRCT12 GLU-379.
RX PubMed=28839118; DOI=10.1534/g3.117.300109;
RA Javadiyan S., Craig J.E., Souzeau E., Sharma S., Lower K.M., Mackey D.A.,
RA Staffieri S.E., Elder J.E., Taranath D., Straga T., Black J., Pater J.,
RA Casey T., Hewitt A.W., Burdon K.P.;
RT "High-Throughput Genetic Screening of 51 Pediatric Cataract Genes
RT Identifies Causative Mutations in Inherited Pediatric Cataract in South
RT Eastern Australia.";
RL G3 (Bethesda) 7:3257-3268(2017).
RN [10]
RP VARIANT CTRCT12 GLU-233 DEL.
RX PubMed=29914532; DOI=10.1186/s13023-018-0828-0;
RA Li J., Leng Y., Han S., Yan L., Lu C., Luo Y., Zhang X., Cao L.;
RT "Clinical and genetic characteristics of Chinese patients with familial or
RT sporadic pediatric cataract.";
RL Orphanet J. Rare Dis. 13:94-94(2018).
CC -!- FUNCTION: Required for the correct formation of lens intermediate
CC filaments as part of a complex composed of BFSP1, BFSP2 and CRYAA
CC (PubMed:28935373). Plays a role in maintenance of retinal lens optical
CC clarity (By similarity). {ECO:0000250|UniProtKB:Q6NVD9,
CC ECO:0000269|PubMed:28935373}.
CC -!- SUBUNIT: Part of a complex required for lens intermediate filament
CC formation composed of BFSP1, BFSP2 and CRYAA (PubMed:28935373). Found
CC in a complex composed of PPL (via C-terminal linker domain), BFSP1 and
CC BFSP2 in the retinal lens (By similarity). Within the complex interacts
CC with PPL (via C-terminal linker domain) and with BFSP1 (By similarity).
CC Identified in a complex that contains VIM, EZR, AHNAK, BFSP1, BFSP2,
CC ANK2, PLEC, PRX and spectrin (By similarity). Interacts with LGSN (By
CC similarity). Interacts with VIM (By similarity).
CC {ECO:0000250|UniProtKB:Q6NVD9, ECO:0000269|PubMed:28935373}.
CC -!- INTERACTION:
CC Q13515; Q9P2A4: ABI3; NbExp=5; IntAct=EBI-10229433, EBI-742038;
CC Q13515; Q9Y2J4: AMOTL2; NbExp=3; IntAct=EBI-10229433, EBI-746752;
CC Q13515; Q7Z3H0-1: ANKRD33; NbExp=3; IntAct=EBI-10229433, EBI-16746154;
CC Q13515; P18848: ATF4; NbExp=11; IntAct=EBI-10229433, EBI-492498;
CC Q13515; Q00994: BEX3; NbExp=3; IntAct=EBI-10229433, EBI-741753;
CC Q13515; Q5H9J7: BEX5; NbExp=3; IntAct=EBI-10229433, EBI-10243741;
CC Q13515; Q12934-2: BFSP1; NbExp=5; IntAct=EBI-10229433, EBI-12123320;
CC Q13515; Q6AI39: BICRAL; NbExp=3; IntAct=EBI-10229433, EBI-1012434;
CC Q13515; Q6QNY1: BLOC1S2; NbExp=3; IntAct=EBI-10229433, EBI-465872;
CC Q13515; Q6ZUJ4: C3orf62; NbExp=3; IntAct=EBI-10229433, EBI-2837036;
CC Q13515; Q8TC20-4: CAGE1; NbExp=3; IntAct=EBI-10229433, EBI-11522698;
CC Q13515; Q9P1Z2: CALCOCO1; NbExp=3; IntAct=EBI-10229433, EBI-749920;
CC Q13515; Q494R4-2: CCDC153; NbExp=3; IntAct=EBI-10229433, EBI-11974185;
CC Q13515; G5E9W6: CCDC183; NbExp=3; IntAct=EBI-10229433, EBI-17212717;
CC Q13515; Q9BXL8: CDCA4; NbExp=3; IntAct=EBI-10229433, EBI-1773949;
CC Q13515; Q86X02: CDR2L; NbExp=4; IntAct=EBI-10229433, EBI-11063830;
CC Q13515; Q9C0F1: CEP44; NbExp=3; IntAct=EBI-10229433, EBI-744115;
CC Q13515; Q96MT8-3: CEP63; NbExp=3; IntAct=EBI-10229433, EBI-11522539;
CC Q13515; Q7L5N1: COPS6; NbExp=3; IntAct=EBI-10229433, EBI-486838;
CC Q13515; Q8WUE5: CT55; NbExp=3; IntAct=EBI-10229433, EBI-6873363;
CC Q13515; Q9NRI5-2: DISC1; NbExp=3; IntAct=EBI-10229433, EBI-11988027;
CC Q13515; Q9NPF5: DMAP1; NbExp=5; IntAct=EBI-10229433, EBI-399105;
CC Q13515; Q9BQ95: ECSIT; NbExp=3; IntAct=EBI-10229433, EBI-712452;
CC Q13515; Q96CS2: HAUS1; NbExp=5; IntAct=EBI-10229433, EBI-2514791;
CC Q13515; O14964: HGS; NbExp=3; IntAct=EBI-10229433, EBI-740220;
CC Q13515; P02533: KRT14; NbExp=3; IntAct=EBI-10229433, EBI-702178;
CC Q13515; Q2M2I5: KRT24; NbExp=3; IntAct=EBI-10229433, EBI-2952736;
CC Q13515; Q7Z3Y8: KRT27; NbExp=3; IntAct=EBI-10229433, EBI-3044087;
CC Q13515; Q15323: KRT31; NbExp=3; IntAct=EBI-10229433, EBI-948001;
CC Q13515; O76014: KRT37; NbExp=3; IntAct=EBI-10229433, EBI-1045716;
CC Q13515; P43360: MAGEA6; NbExp=3; IntAct=EBI-10229433, EBI-1045155;
CC Q13515; Q9NS73-5: MBIP; NbExp=6; IntAct=EBI-10229433, EBI-10182361;
CC Q13515; P59942: MCCD1; NbExp=3; IntAct=EBI-10229433, EBI-11987923;
CC Q13515; P15173: MYOG; NbExp=3; IntAct=EBI-10229433, EBI-3906629;
CC Q13515; O43482: OIP5; NbExp=3; IntAct=EBI-10229433, EBI-536879;
CC Q13515; P40425: PBX2; NbExp=3; IntAct=EBI-10229433, EBI-348489;
CC Q13515; Q9BYU1: PBX4; NbExp=3; IntAct=EBI-10229433, EBI-10302990;
CC Q13515; P78424: POU6F2; NbExp=3; IntAct=EBI-10229433, EBI-12029004;
CC Q13515; Q96KQ4: PPP1R13B; NbExp=3; IntAct=EBI-10229433, EBI-1105153;
CC Q13515; P62195: PSMC5; NbExp=3; IntAct=EBI-10229433, EBI-357745;
CC Q13515; Q6NUQ1: RINT1; NbExp=3; IntAct=EBI-10229433, EBI-726876;
CC Q13515; Q5GAN6: RNASE10; NbExp=3; IntAct=EBI-10229433, EBI-12423312;
CC Q13515; Q86UD0: SAPCD2; NbExp=3; IntAct=EBI-10229433, EBI-2561646;
CC Q13515; Q9UIL1-3: SCOC; NbExp=3; IntAct=EBI-10229433, EBI-10692913;
CC Q13515; Q9UJW9: SERTAD3; NbExp=3; IntAct=EBI-10229433, EBI-748621;
CC Q13515; O75971-2: SNAPC5; NbExp=3; IntAct=EBI-10229433, EBI-12004298;
CC Q13515; O95295: SNAPIN; NbExp=3; IntAct=EBI-10229433, EBI-296723;
CC Q13515; Q9UMX1: SUFU; NbExp=4; IntAct=EBI-10229433, EBI-740595;
CC Q13515; Q8N0S2: SYCE1; NbExp=11; IntAct=EBI-10229433, EBI-6872807;
CC Q13515; Q96RU7: TRIB3; NbExp=3; IntAct=EBI-10229433, EBI-492476;
CC Q13515; Q8N6Y0: USHBP1; NbExp=6; IntAct=EBI-10229433, EBI-739895;
CC Q13515; Q70EL1-9: USP54; NbExp=3; IntAct=EBI-10229433, EBI-11975223;
CC Q13515; Q9Y3C0: WASHC3; NbExp=3; IntAct=EBI-10229433, EBI-712969;
CC Q13515; Q6P1L6: ZNF343; NbExp=3; IntAct=EBI-10229433, EBI-10252492;
CC Q13515; Q6ZNG0: ZNF620; NbExp=3; IntAct=EBI-10229433, EBI-4395669;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q28177};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:Q28177}; Cytoplasmic
CC side {ECO:0000250|UniProtKB:Q28177}. Cytoplasm
CC {ECO:0000250|UniProtKB:D3ZER2}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q28177}. Cytoplasm, cell cortex
CC {ECO:0000250|UniProtKB:Q28177}. Note=Expressed primarily at the plasma
CC membrane in peripheral lens fiber cells, however also localizes to the
CC cytoplasm in mature lens fiber cells. {ECO:0000250|UniProtKB:Q28177}.
CC -!- TISSUE SPECIFICITY: Lens.
CC -!- DISEASE: Cataract 12, multiple types (CTRCT12) [MIM:611597]: An
CC opacification of the crystalline lens of the eye that frequently
CC results in visual impairment or blindness. Opacities vary in
CC morphology, are often confined to a portion of the lens, and may be
CC static or progressive. In general, the more posteriorly located and
CC dense an opacity, the greater the impact on visual function. The
CC opacities can be nuclear, sutural, stellate cortical, lamellar,
CC cortical, nuclear embryonic, Y-sutural, punctate cortical, congenital
CC or with juvenile- and adult-onset. {ECO:0000269|PubMed:10729115,
CC ECO:0000269|PubMed:10739768, ECO:0000269|PubMed:15570218,
CC ECO:0000269|PubMed:17200662, ECO:0000269|PubMed:17982427,
CC ECO:0000269|PubMed:28839118, ECO:0000269|PubMed:29914532}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the intermediate filament family.
CC {ECO:0000255|PROSITE-ProRule:PRU01188}.
CC -!- WEB RESOURCE: Name=Human Intermediate Filament Mutation Database;
CC URL="http://www.interfil.org";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U48224; AAC50414.1; -; mRNA.
DR EMBL; BC113518; AAI13519.1; -; mRNA.
DR EMBL; BC113520; AAI13521.1; -; mRNA.
DR EMBL; AF195044; AAG30728.1; -; Genomic_DNA.
DR CCDS; CCDS33859.1; -.
DR RefSeq; NP_003562.1; NM_003571.3.
DR RefSeq; XP_016862804.1; XM_017007315.1.
DR AlphaFoldDB; Q13515; -.
DR SMR; Q13515; -.
DR BioGRID; 114005; 67.
DR IntAct; Q13515; 63.
DR STRING; 9606.ENSP00000304987; -.
DR iPTMnet; Q13515; -.
DR PhosphoSitePlus; Q13515; -.
DR BioMuta; BFSP2; -.
DR DMDM; 17366451; -.
DR EPD; Q13515; -.
DR MassIVE; Q13515; -.
DR MaxQB; Q13515; -.
DR PaxDb; Q13515; -.
DR PeptideAtlas; Q13515; -.
DR PRIDE; Q13515; -.
DR ProteomicsDB; 59513; -.
DR Antibodypedia; 33369; 172 antibodies from 19 providers.
DR DNASU; 8419; -.
DR Ensembl; ENST00000302334.3; ENSP00000304987.2; ENSG00000170819.5.
DR GeneID; 8419; -.
DR KEGG; hsa:8419; -.
DR MANE-Select; ENST00000302334.3; ENSP00000304987.2; NM_003571.4; NP_003562.1.
DR UCSC; uc003epn.3; human.
DR CTD; 8419; -.
DR DisGeNET; 8419; -.
DR GeneCards; BFSP2; -.
DR HGNC; HGNC:1041; BFSP2.
DR HPA; ENSG00000170819; Not detected.
DR MalaCards; BFSP2; -.
DR MIM; 603212; gene.
DR MIM; 611597; phenotype.
DR neXtProt; NX_Q13515; -.
DR OpenTargets; ENSG00000170819; -.
DR Orphanet; 441452; Early-onset lamellar cataract.
DR Orphanet; 98985; Early-onset sutural cataract.
DR Orphanet; 98984; Pulverulent cataract.
DR PharmGKB; PA25344; -.
DR VEuPathDB; HostDB:ENSG00000170819; -.
DR eggNOG; ENOG502QTD1; Eukaryota.
DR GeneTree; ENSGT00940000159820; -.
DR HOGENOM; CLU_012560_0_0_1; -.
DR InParanoid; Q13515; -.
DR OMA; ETIRIQW; -.
DR OrthoDB; 803338at2759; -.
DR PhylomeDB; Q13515; -.
DR TreeFam; TF332742; -.
DR PathwayCommons; Q13515; -.
DR SignaLink; Q13515; -.
DR BioGRID-ORCS; 8419; 10 hits in 1072 CRISPR screens.
DR GeneWiki; BFSP2; -.
DR GenomeRNAi; 8419; -.
DR Pharos; Q13515; Tbio.
DR PRO; PR:Q13515; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q13515; protein.
DR Bgee; ENSG00000170819; Expressed in lens of camera-type eye and 91 other tissues.
DR Genevisible; Q13515; HS.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0005882; C:intermediate filament; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc.
DR GO; GO:0005212; F:structural constituent of eye lens; IEA:UniProtKB-KW.
DR GO; GO:0048469; P:cell maturation; IEA:Ensembl.
DR GO; GO:0045109; P:intermediate filament organization; ISS:UniProtKB.
DR GO; GO:0070307; P:lens fiber cell development; IEA:Ensembl.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR InterPro; IPR039008; IF_rod_dom.
DR InterPro; IPR002957; Keratin_I.
DR InterPro; IPR027694; Phakinin.
DR PANTHER; PTHR23239; PTHR23239; 1.
DR PANTHER; PTHR23239:SF32; PTHR23239:SF32; 1.
DR Pfam; PF00038; Filament; 1.
DR PRINTS; PR01248; TYPE1KERATIN.
DR SMART; SM01391; Filament; 1.
DR PROSITE; PS51842; IF_ROD_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cataract; Cell membrane; Coiled coil; Cytoplasm; Cytoskeleton;
KW Disease variant; Eye lens protein; Intermediate filament; Membrane;
KW Phosphoprotein; Reference proteome; Repeat; Sensory transduction; Vision.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q28177"
FT CHAIN 2..415
FT /note="Phakinin"
FT /evidence="ECO:0000305"
FT /id="PRO_0000063851"
FT DOMAIN 104..415
FT /note="IF rod"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01188"
FT REGION 1..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..114
FT /note="Head"
FT REGION 396..415
FT /note="Tail"
FT COILED 115..144
FT /evidence="ECO:0000255"
FT COILED 199..253
FT /evidence="ECO:0000255"
FT COILED 309..400
FT /evidence="ECO:0000255"
FT COMPBIAS 9..45
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q28177"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q28177"
FT MOD_RES 32
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q28177"
FT MOD_RES 35
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q28177"
FT MOD_RES 90
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q28177"
FT VARIANT 233
FT /note="Missing (in CTRCT12; dbSNP:rs121908938)"
FT /evidence="ECO:0000269|PubMed:10739768,
FT ECO:0000269|PubMed:15570218, ECO:0000269|PubMed:17200662,
FT ECO:0000269|PubMed:17982427, ECO:0000269|PubMed:29914532"
FT /id="VAR_012163"
FT VARIANT 287
FT /note="R -> W (in CTRCT12; dbSNP:rs104893685)"
FT /evidence="ECO:0000269|PubMed:10729115"
FT /id="VAR_012164"
FT VARIANT 379
FT /note="A -> E (in CTRCT12; unknown pathological
FT significance; dbSNP:rs774824478)"
FT /evidence="ECO:0000269|PubMed:28839118"
FT /id="VAR_084817"
SQ SEQUENCE 415 AA; 45880 MW; 4CB899386D443FEA CRC64;
MSERRVVVDL PTSASSSMPL QRRRASFRGP RSSSSLESPP ASRTNAMSGL VRAPGVYVGT
APSGCIGGLG ARVTRRALGI SSVFLQGLRS SGLATVPAPG LERDHGAVED LGGCLVEYMA
KVHALEQVSQ ELETQLRMHL ESKATRSGNW GALRASWASS CQQVGEAVLE NARLMLQTET
IQAGADDFKE RYENEQPFRK AAEEEINSLY KVIDEANLTK MDLESQIESL KEELGSLSRN
YEEDVKLLHK QLAGCELEQM DAPIGTGLDD ILETIRIQWE RDVEKNRVEA GALLQAKQQA
EVAHMSQTQE EKLAAALRVE LHNTSCQVQS LQAETESLRA LKRGLENTLH DAKHWHDMEL
QNLGAVVGRL EAELREIRAE AEQQQQERAH LLARKCQLQK DVASYHALLD REESG
