Q9UBW5 (BIN2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Bridging integrator 2

Alternative name(s):
Breast cancer-associated protein 1

Gene names

Name:	BIN2
Synonyms:	BRAP1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	565 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Promotes cell motility and migration, probably via its interaction with the cell membrane and with podosome proteins that mediate interaction with the cytoskeleton. Modulates membrane curvature and mediates membrane tubulation. Plays a role in podosome formation. Inhibits phagocytosis. Ref.8
Subunit structure	Homodimer. Interacts with BIN1. Interacts with ARHGEF6 (via SH3 domain), ARHGEF7 (via SH3 domain), SH3GL1, SH3GL2 and SH3GL3. Identified in a complex with ARHGEF6 and GIT2. Ref.1 Ref.8
Subcellular location	Cytoplasm. Cell projection › podosome membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasm › cell cortex. Cell projection › phagocytic cup. Note: Associates with membranes enriched in phosphoinositides. Detected in the actin-rich cell cortex at the leading edge of migrating cells. Detected at podosomes, at an actin-rich ring-like structure. Ref.1 Ref.8
Tissue specificity	Detected in natural killer cells (at protein level). Highest level expression seen in spleen and peripheral blood leukocytes and is also expressed at high levels in thymus, colon and placenta, suggesting preferential expression in hematopoietic tissues. Ref.1 Ref.8
Induction	Up-regulated during monocytic differentiation. Ref.1
Domain	The BAR domain mediates dimerization and interaction with membranes enriched in phosphatidylinositides. Ref.8
Sequence similarities	Contains 1 BAR domain.
Sequence caution	The sequence BAA91376.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence BAA91376.1 differs from that shown. Reason: Frameshift at position 156.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Cell projection Cytoplasm Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell chemotaxis Inferred from mutant phenotype Ref.8. Source: UniProtKB membrane tubulation Inferred from direct assay Ref.8. Source: UniProtKB phagocytosis, engulfment Inferred from mutant phenotype Ref.8. Source: UniProtKB podosome assembly Inferred from mutant phenotype Ref.8. Source: UniProtKB
Cellular_component	cell cortex Inferred from electronic annotation. Source: UniProtKB-SubCell cell junction Inferred from electronic annotation. Source: UniProtKB-KW cell projection Inferred from electronic annotation. Source: UniProtKB-KW phagocytic cup Inferred from electronic annotation. Source: UniProtKB-SubCell podosome Inferred from direct assay Ref.8. Source: UniProtKB
Molecular_function	phospholipid binding Inferred from direct assay Ref.8. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BIN1	O00499	2	EBI-2042570,EBI-719094

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UBW5-1)

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: Q9UBW5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     105-136: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 565

565

Bridging integrator 2

PRO_0000256140

Regions

Domain

28 – 244

217

BAR

Coiled coil

304 – 329

26

Potential

Compositional bias

253 – 256

4

Poly-Ser

Compositional bias

413 – 479

67

Pro-rich

Amino acid modifications

Modified residue

273

1

Phosphoserine Ref.7

Modified residue

357

1

Phosphoserine Ref.7

Modified residue

436

1

Phosphoserine Ref.7

Modified residue

438

1

Phosphothreonine Ref.7

Modified residue

444

1

Phosphoserine Ref.7

Modified residue

447

1

Phosphoserine Ref.7

Modified residue

458

1

Phosphoserine Ref.7

Natural variations

Alternative sequence

105 – 136

32

Missing in isoform 2.

VSP_021328

Natural variant

48

1

S → N. Ref.2
Corresponds to variant rs7312857 [ dbSNP | Ensembl ].

VAR_028883

Natural variant

529

1

N → D. Ref.1 Ref.2 Ref.3 Ref.5
Corresponds to variant rs7954976 [ dbSNP | Ensembl ].

VAR_028884

Experimental info

Mutagenesis

13

1

F → A: Strongly reduces binding to membranes. Ref.8

Mutagenesis

21

1

F → A: Strongly reduces binding to membranes. Ref.8

Mutagenesis

81

1

V → R: Abolishes dimerization and membrane binding; when associated with E-214. Ref.8

Mutagenesis

214

1

S → E: Abolishes dimerization and membrane binding; when associated with R-81. Ref.8

Sequence conflict

163

1

Missing in AAD54227. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

565

Helix Strand Turn

Details...

Helix

16 – 31

16

Helix

41 – 88

48

Helix

96 – 120

25

Helix

122 – 130

9

Helix

132 – 160

29

Beta strand

161 – 164

4

Helix

167 – 200

34

Helix

202 – 241

40

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 3, 2007. Version 3. Checksum: B1D1FB89A97E9E43	FASTA	565	61,874
	10 20 30 40 50 60 MAEGKAGGAA GLFAKQVQKK FSRAQEKVLQ KLGKAVETKD ERFEQSASNF YQQQAEGHKL 70 80 90 100 110 120 YKDLKNFLSA VKVMHESSKR VSETLQEIYS SEWDGHEELK AIVWNNDLLW EDYEEKLADQ 130 140 150 160 170 180 AVRTMEIYVA QFSEIKERIA KRGRKLVDYD SARHHLEAVQ NAKKKDEAKT AKAEEEFNKA 190 200 210 220 230 240 QTVFEDLNQE LLEELPILYN SRIGCYVTIF QNISNLRDVF YREMSKLNHN LYEVMSKLEK 250 260 270 280 290 300 QHSNKVFVVK GLSSSSRRSL VISPPVRTAT VSSPLTSPTS PSTLSLKSES ESVSATEDLA 310 320 330 340 350 360 PDAAQGEDNS EIKELLEEEE IEKEGSEASS SEEDEPLPAC NGPAQAQPSP TTERAKSQEE 370 380 390 400 410 420 VLPSSTTPSP GGALSPSGQP SSSATEVVLR TRTASEGSEQ PKKRASIQRT SAPPSRPPPP 430 440 450 460 470 480 RATASPRPSS GNIPSSPTAS GGGSPTSPRA SLGTGTASPR TSLEVSPNPE PPEKPVRTPE 490 500 510 520 530 540 AKENENIHNQ NPEELCTSPT LMTSQVASEP GEAKKMEDKE KDNKLISANS SEGQDQLQVS 550 560 MVPENNNLTA PEPQEEVSTS ENPQL
	Isoform 2 [UniParc]. Checksum: E549F6F418F01E02	FASTA	533	58,030
	10 20 30 40 50 60 MAEGKAGGAA GLFAKQVQKK FSRAQEKVLQ KLGKAVETKD ERFEQSASNF YQQQAEGHKL 70 80 90 100 110 120 YKDLKNFLSA VKVMHESSKR VSETLQEIYS SEWDGHEELK AIVWERIAKR GRKLVDYDSA 130 140 150 160 170 180 RHHLEAVQNA KKKDEAKTAK AEEEFNKAQT VFEDLNQELL EELPILYNSR IGCYVTIFQN 190 200 210 220 230 240 ISNLRDVFYR EMSKLNHNLY EVMSKLEKQH SNKVFVVKGL SSSSRRSLVI SPPVRTATVS 250 260 270 280 290 300 SPLTSPTSPS TLSLKSESES VSATEDLAPD AAQGEDNSEI KELLEEEEIE KEGSEASSSE 310 320 330 340 350 360 EDEPLPACNG PAQAQPSPTT ERAKSQEEVL PSSTTPSPGG ALSPSGQPSS SATEVVLRTR 370 380 390 400 410 420 TASEGSEQPK KRASIQRTSA PPSRPPPPRA TASPRPSSGN IPSSPTASGG GSPTSPRASL 430 440 450 460 470 480 GTGTASPRTS LEVSPNPEPP EKPVRTPEAK ENENIHNQNP EELCTSPTLM TSQVASEPGE 490 500 510 520 530 AKKMEDKEKD NKLISANSSE GQDQLQVSMV PENNNLTAPE PQEEVSTSEN PQL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Bin2, a functionally nonredundant member of the BAR adaptor gene family." Ge K., Prendergast G.C. Genomics 67:210-220(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ASP-529, INDUCTION, INTERACTION WITH BIN2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]	"Genomic structure and chromosome location of the BRAP1 gene." Miki Y., Saito H. Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), VARIANTS ASN-48 AND ASP-529. Tissue: Mammary gland.
[3]	"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. , 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] (ISOFORM 2), VARIANT ASP-529. Tissue: Colon.
[4]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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 ASP-529. Tissue: Ovary.
[6]	"Phosphorylation analysis of primary human T lymphocytes using sequential IMAC and titanium oxide enrichment." Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J. J. Proteome Res. 7:5167-5176(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: T-cell.
[7]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-273; SER-357; SER-436; THR-438; SER-444; SER-447 AND SER-458, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[8]	"Bin2 is a membrane sculpting N-BAR protein that influences leucocyte podosomes, motility and phagocytosis." Sanchez-Barrena M.J., Vallis Y., Clatworthy M.R., Doherty G.J., Veprintsev D.B., Evans P.R., McMahon H.T. PLoS ONE 7:E52401-E52401(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.53 ANGSTROMS) OF 1-238, FUNCTION, DOMAIN, SUBUNIT, INTERACTION WITH ARHGEF6; ARHGEF7; SH3GL1; SH3GL2; SH3GL3, IDENTIFICATION IN A COMPLEX WITH GIT2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF PHE-13; PHE-21; VAL-81 AND SER-214.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF146531 mRNA. Translation: AAD54227.1.
AB032698 mRNA. Translation: BAA88108.1.
AB032710 Genomic DNA. Translation: BAA88125.1.
AK000783 mRNA. Translation: BAA91376.1. Sequence problems.
AC046135 Genomic DNA. No translation available.
BC047686 mRNA. Translation: AAH47686.1.

IPI

IPI00550792.
IPI00795778.

RefSeq

NP_057377.2. NM_016293.2.

UniGene

Hs.14770.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4AVM	X-ray	1.91	A	11-245	[»]
4I1Q	X-ray	2.53	A/B	20-238	[»]

ProteinModelPortal

Q9UBW5.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UBW5. 3 interactions.

STRING

9606.ENSP00000267012.

PTM databases

PhosphoSite

Q9UBW5.

Polymorphism databases

DMDM

143811367.

2D gel databases

OGP

Q9UBW5.

Proteomic databases

PaxDb

Q9UBW5.

PRIDE

Q9UBW5.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000267012; ENSP00000267012; ENSG00000110934.
ENST00000452142; ENSP00000410217; ENSG00000110934.

GeneID

51411.

KEGG

hsa:51411.

UCSC

uc001ryg.3. human.
uc009zlz.3. human.

Organism-specific databases

CTD

51411.

GeneCards

GC12M051697.

H-InvDB

HIX0201823.

HGNC

HGNC:1053. BIN2.

HPA

HPA038666.
HPA038667.

MIM

605936. gene.

neXtProt

NX_Q9UBW5.

PharmGKB

PA25356.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG264615.

HOGENOM

HOG000252987.

HOVERGEN

HBG004224.

InParanoid

Q9UBW5.

OMA

RFEQSAS.

OrthoDB

EOG45HRXJ.

PhylomeDB

Q9UBW5.

Gene expression databases

ArrayExpress

Q9UBW5.

Bgee

Q9UBW5.

CleanEx

HS_BIN2.

Genevestigator

Q9UBW5.

GermOnline

ENSG00000110934. Homo sapiens.

Family and domain databases

Gene3D

1.20.1270.60. 1 hit.

InterPro

IPR027267. AH/BAR-dom.
IPR003005. Amphiphysin.
IPR004148. BAR_dom.
[Graphical view]

Pfam

PF03114. BAR. 1 hit.
[Graphical view]

PRINTS

PR01251. AMPHIPHYSIN.

SMART

SM00721. BAR. 1 hit.
[Graphical view]

PROSITE

PS51021. BAR. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

BIN2. human.

GenomeRNAi

51411.

NextBio

54957.

SOURCE

Search...

Entry information

Entry name

BIN2_HUMAN

Accession

Primary (citable) accession number: Q9UBW5
Secondary accession number(s): Q86VV0, Q9NWK4, Q9UKN4

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2006
Last sequence update:	April 3, 2007
Last modified:	May 1, 2013
This is version 84 of the entry and version 3 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.