O75531 (BAF_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Barrier-to-autointegration factor

Alternative name(s):
Breakpoint cluster region protein 1

Gene names

Name:	BANF1
Synonyms:	BAF, BCRG1

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	89 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays fundamental roles in nuclear assembly, chromatin organization, gene expression and gonad development. May potently compress chromatin structure and be involved in membrane recruitment and chromatin decondensation during nuclear assembly. Contains 2 non-specific dsDNA-binding sites which may promote DNA cross-bridging. Exploited by retroviruses for inhibiting self-destructing autointegration of retroviral DNA, thereby promoting integration of viral DNA into the host chromosome. EMD and BAF are cooperative cofactors of HIV-1 infection. Association of EMD with the viral DNA requires the presence of BAF and viral integrase. The association of viral DNA with chromatin requires the presence of BAF and EMD. Ref.6 Ref.9 Ref.17
Subunit structure	Homodimer. Heterodimerizes with BAFL. Binds non-specifically to double-stranded DNA, and is found as a hexamer or dodecamer upon DNA binding. Binds to LEM domain-containing nuclear proteins such as LEMD3/MAN1, TMPO/LAP2 and EMD (emerin). Interacts with CRX and LMNA (lamin-A). Binds linker histone H1.1 and core histones H3 with in vitro affinities of 500-900 and 100-200 nM. Interacts with HIV-1 pre-integration complex in cytoplasm by binding to viral matrix protein and Gag polyprotein. Ref.7 Ref.8 Ref.10 Ref.11 Ref.12 Ref.13 Ref.15
Subcellular location	Nucleus. Cytoplasm. Chromosome. Note: Significantly enriched at the nuclear inner membrane, diffusely throughout the nucleus during interphase and concentrated at the chromosomes during the M-phase. May be included in HIV-1 virions via its interaction with viral GAG polyprotein. The phosphorylated form (by VRK1) shows a cytoplasmic localization. Ref.16
Tissue specificity	Widely expressed. Expressed in colon, brain, heart, kidney, liver, lung, ovary, pancreas, placenta, prostate, skeletal muscle, small intestine, spleen and testis. Not detected in thymus and peripheral blood leukocytes.
Domain	Has a helix-hairpin-helix (HhH) structural motif conserved among proteins that bind non-specifically to DNA. LEM domain proteins bind centrally on the BAF dimer, whereas DNA binds to the left and right sides.
Post-translational modification	Ser-4 is the major site of phosphorylation as compared to Thr-2 and Thr-3. Phosphorylation on Thr-2; Thr-3 and Ser-4 disrupts its ability to bind DNA and reduces its ability to bind LEM domain-containing proteins. Non phosphorylated BAF seems to enhance binding between EMD and LMNA. Ref.14 Ref.16
Involvement in disease	Defects in BANF1 are the cause of Nestor-Guillermo progeria syndrome (NGPS) [MIM:614008]. NGPS is an atypical progeroid syndrome characterized by normal development in the first years of life, later followed by the emergence of generalized lipoatrophy, severe osteoporosis, and marked osteolysis. The atrophic facial subcutaneous fat pad and the marked osteolysis of the maxilla and mandible result in a typical pseudosenile facial appearance with micrognatia, prominent subcutaneous venous patterning, a convex nasal ridge, and proptosis. Cognitive development is completely normal. Patients do not have cardiovascular dysfunction, atherosclerosis, or metabolic anomalies. Ref.21
Sequence similarities	Belongs to the BAF family.
Sequence caution	The sequence AAC08964.1 differs from that shown. Reason: Frameshift at position 87.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Chromosome Cytoplasm Nucleus
Disease	Disease mutation
Ligand	DNA-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	initiation of viral infection Traceable author statement. Source: Reactome interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW provirus integration Traceable author statement. Source: Reactome response to virus Traceable author statement. Source: ProtInc
Cellular component	chromosome Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome
Molecular function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 89

89

Barrier-to-autointegration factor

PRO_0000221026

Amino acid modifications

Modified residue

2

1

Phosphothreonine; by VRK1 and VRK2 Ref.16

Modified residue

3

1

Phosphothreonine; by VRK1 and VRK2 Ref.16

Modified residue

4

1

Phosphoserine; by VRK1 and VRK2 Ref.14 Ref.16

Natural variations

Natural variant

12

1

A → T in NGPS; shows a dramatic reduction in BANF1 protein levels indicating that the mutation impairs protein stability. Ref.21

VAR_065954

Experimental info

Mutagenesis

4

1

S → A: Complete loss of phosphorylation. Ref.14

Mutagenesis

4

1

S → E: Complete loss of phosphorylation and mislocalization of EMD in nucleus. Ref.14

Mutagenesis

6

1

K → A: Complete loss of LEMD3/MAN1 and histone H1/H3 binding. Ref.6 Ref.9 Ref.12 Ref.13

Mutagenesis

6

1

K → E: Complete loss of dsDNA and LEMD3/MAN1 binding. Ref.6 Ref.9 Ref.12 Ref.13

Mutagenesis

8

1

R → A: Enhances histone H1/H3 binding. Ref.12 Ref.13

Mutagenesis

8

1

R → E: Complete loss of LEMD3/MAN1 binding. Ref.12 Ref.13

Mutagenesis

9

1

D → A: Reduces binding to dsDNA, LEMD3/MAN1 and histone H1/H3. Ref.9 Ref.12 Ref.13

Mutagenesis

14

1

P → A: No effect on LEMD3/MAN1 and enhances histone H1/H3 binding. Ref.6 Ref.12 Ref.13

Mutagenesis

18

1

K → A: No effect on histone H1/H3 binding. Ref.6 Ref.13

Mutagenesis

25

1

G → E: Complete loss of dsDNA, EMD, histone H1/H3 and LEMD3/MAN1 binding. Ref.9 Ref.12 Ref.13

Mutagenesis

25

1

G → Q: Complete loss of EMD binding and reduces dsDNA binding. Ref.9 Ref.12 Ref.13

Mutagenesis

26

1

I → A: Reduces histone H1/H3 and LEMD3/MAN1 binding. Fails to promote HIV-1 genome integration. Ref.6 Ref.12 Ref.13

Mutagenesis

26

1

I → K: Fails to promote HIV-1 genome integration. Ref.6 Ref.12 Ref.13

Mutagenesis

27

1

G → E: Fails to bind dsDNA. Ref.9

Mutagenesis

27

1

G → Q: Reduces binding to dsDNA. Ref.9

Mutagenesis

29

1

V → A: No effect on histone H1/H3 binding. Ref.13

Mutagenesis

32

1

K → E: No effect on histone H1/H3 binding. Ref.13

Mutagenesis

33

1

K → E: No effect on histone H1/H3 binding. Ref.13

Mutagenesis

37

1

R → A: No effect on histone H1/H3 binding. Ref.12 Ref.13

Mutagenesis

37

1

R → E: Reduces LEMD3/MAN1 binding. Ref.12 Ref.13

Mutagenesis

41

1

K → A: No effect on histone H1/H3 and LEMD3/MAN1 binding. Ref.6 Ref.12 Ref.13

Mutagenesis

41

1

K → E: Reduces histone H1/H3 binding. Ref.6 Ref.12 Ref.13

Mutagenesis

46

1

L → E: Complete loss of dsDNA, histone H1/H3 and LEMD3/MAN1 binding. Ref.9 Ref.12 Ref.13

Mutagenesis

47

1

G → E: Complete loss of EMD, histone H1/h3 and LEMD3/MAN1 binding. Ref.9 Ref.12 Ref.13

Mutagenesis

50

1

L → A: Reduces LEMD3/MAN1 binding. No effect on Histone H1/H3 binding. Ref.6 Ref.12 Ref.13

Mutagenesis

50

1

L → K: Fails to promote HIV-1 genome integration. Ref.6 Ref.12 Ref.13

Mutagenesis

51

1

V → E: Complete loss of EMD, and histone H1/H3 binding. Reduces dsDNA and LEMD3/MAN1 binding. Ref.9 Ref.12 Ref.13

Mutagenesis

53

1

K → A: No effect on LEMD3/MAN1 binding. Enhances histone H1/H3 binding. Ref.6 Ref.9 Ref.12 Ref.13

Mutagenesis

53

1

K → E: Complete loss of EMD binding. Reduces LEMD3/MAN1 binding. Enhances histone H1/H3 binding. Ref.6 Ref.9 Ref.12 Ref.13

Mutagenesis

54

1

K → A: Reduces LEMD3/MAN1 binding. No effect on histone H1/H3 binding. Ref.6 Ref.9 Ref.12 Ref.13

Mutagenesis

54

1

K → E: Reduces binding to dsDNA. Ref.6 Ref.9 Ref.12 Ref.13

Mutagenesis

60

1

R → E: No effect on histone H1/H3 binding. Ref.13

Mutagenesis

62

1

W → A: Complete loss of LEMD3/MAN1 binding. Enhances histone H1/H3 binding. Ref.6 Ref.12 Ref.13

Mutagenesis

64

1

K → E: Enhances histone H1/H3 binding. Ref.13

Mutagenesis

75

1

R → E: Reduces binding to dsDNA. No effect on histone H1/H3 binding. Ref.9 Ref.13

Mutagenesis

80

1

C → A: No effect on histone H1/H3 and LEMD3/MAN1 binding. Ref.6 Ref.12 Ref.13

Mutagenesis

82

1

R → E: No effect on histone H1/H3 binding. Ref.13

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

89

Helix Strand Turn

Details...

Helix

5 – 11

7

Helix

20 – 22

3

Helix

28 – 36

9

Helix

42 – 51

10

Turn

52 – 54

3

Helix

56 – 67

12

Helix

71 – 88

18

Sequences

	Sequence		Length	Mass (Da)
	O75531 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 9A2180A2D284F5D0	FASTA	89	10,059
	10 20 30 40 50 60 MTTSQKHRDF VAEPMGEKPV GSLAGIGEVL GKKLEERGFD KAYVVLGQFL VLKKDEDLFR 70 80 EWLKDTCGAN AKQSRDCFGC LREWCDAFL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A previously unidentified host protein protects retroviral DNA from autointegration." Lee M.S., Craigie R. Proc. Natl. Acad. Sci. U.S.A. 95:1528-1533(1998) [PubMed: 9465049] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Genomic and functional map of the chromosome 14 t(12;14) breakpoint cluster region in uterine leiomyoma." Lynch R.A., Piper M., Bankier A., Bhugra B., Surti U., Liu J., Buckler A., Dear P.H., Menon A.G. Genomics 52:17-26(1998) [PubMed: 9740667] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Uterus.
[3]	"Human BAF homolog gene." Zhang J., Liu T., Ye M., Zhang Q., Fu G., Zhou J., Wu J., Shen Y., Yu M., Chen S., Mao M., Chen Z. Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[6]	"Both the structure and DNA binding function of the barrier-to-autointegration factor contribute to reconstitution of HIV type 1 integration in vitro." Harris D., Engelman A. J. Biol. Chem. 275:39671-39677(2000) [PubMed: 11005805] [Abstract] Cited for: FUNCTION IN HIV-1 INTEGRATION, MUTAGENESIS OF LYS-6; PRO-14; LYS-18; ILE-26; LYS-41; LEU-50; LYS-53; LYS-54; TRP-62 AND CYS-80.
[7]	"Barrier-to-autointegration factor (BAF) bridges DNA in a discrete, higher-order nucleoprotein complex." Zheng R., Ghirlando R., Lee M.S., Mizuuchi K., Krause M., Craigie R. Proc. Natl. Acad. Sci. U.S.A. 97:8997-9002(2000) [PubMed: 10908652] [Abstract] Cited for: MULTIMERIZATION.
[8]	"BAF is required for emerin assembly into the reforming nuclear envelope." Haraguchi T., Koujin T., Segura-Totten M., Lee K.K., Matsuoka Y., Yoneda Y., Wilson K.L., Hiraoka Y. J. Cell Sci. 114:4575-4585(2001) [PubMed: 11792822] [Abstract] Cited for: INTERACTION WITH EMD.
[9]	"Barrier-to-autointegration factor: major roles in chromatin decondensation and nuclear assembly." Segura-Totten M., Kowalski A.K., Craigie R., Wilson K.L. J. Cell Biol. 158:475-485(2002) [PubMed: 12163470] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF LYS-6; ASP-9; GLY-25; GLY-27; LEU-46; GLY-47; VAL-51; LYS-53; LYS-54 AND ARG-75.
[10]	"The barrier-to-autointegration factor is a component of functional human immunodeficiency virus type 1 preintegration complexes." Lin C.W., Engelman A. J. Virol. 77:5030-5036(2003) [PubMed: 12663813] [Abstract] Cited for: INTERACTION WITH HIV-1 PRE-INTEGRATION COMPLEX.
[11]	"Barrier-to-autointegration factor BAF binds p55 Gag and matrix and is a host component of human immunodeficiency virus type 1 virions." Mansharamani M., Graham D.R., Monie D., Lee K.K., Hildreth J.E., Siliciano R.F., Wilson K.L. J. Virol. 77:13084-13092(2003) [PubMed: 14645565] [Abstract] Cited for: INTERACTION WITH HIV-1 MATRIX PROTEIN.
[12]	"Direct binding of nuclear membrane protein MAN1 to emerin in vitro and two modes of binding to barrier-to-autointegration factor." Mansharamani M., Wilson K.L. J. Biol. Chem. 280:13863-13870(2005) [PubMed: 15681850] [Abstract] Cited for: INTERACTION WITH LEMD3/MAN1, MUTAGENESIS OF LYS-6; ARG-8; ASP-9; PRO-14; GLY-25; ILE-26; ARG-37; LYS-41; LEU-46; GLY-47; LEU-50; VAL-51; LYS-53; LYS-54; TRP-62 AND CYS-80.
[13]	"Binding of barrier to autointegration factor (BAF) to histone H3 and selected linker histones including H1.1." de Oca R.M., Lee K.K., Wilson K.L. J. Biol. Chem. 280:42252-42262(2005) [PubMed: 16203725] [Abstract] Cited for: INTERACTION WITH HISTONE H1/H3, MUTAGENESIS OF LYS-6; ARG-8; ASP-9; PRO-14; LYS-18; GLY-25; ILE-26; VAL-29; LYS-32; LYS-33; ARG-37; LYS-41; LEU-46; GLY-47; LEU-50; VAL-51; LYS-53; LYS-54; ARG-60; TRP-62; LYS-64; ARG-75; CYS-80 AND ARG-82.
[14]	"Barrier-to-autointegration factor phosphorylation on Ser-4 regulates emerin binding to lamin A in vitro and emerin localization in vivo." Bengtsson L., Wilson K.L. Mol. Biol. Cell 17:1154-1163(2006) [PubMed: 16371512] [Abstract] Cited for: PHOSPHORYLATION AT SER-4, MUTAGENESIS OF SER-4.
[15]	"Barrier-to-autointegration factor-like (BAF-L): a proposed regulator of BAF." Tifft K.E., Segura-Totten M., Lee K.K., Wilson K.L. Exp. Cell Res. 312:478-487(2006) [PubMed: 16337940] [Abstract] Cited for: INTERACTION WITH BAFL.
[16]	"The vaccinia-related kinases phosphorylate the N' terminus of BAF, regulating its interaction with DNA and its retention in the nucleus." Nichols R.J., Wiebe M.S., Traktman P. Mol. Biol. Cell 17:2451-2464(2006) [PubMed: 16495336] [Abstract] Cited for: PHOSPHORYLATION AT THR-2; THR-3 AND SER-4, SUBCELLULAR LOCATION.
[17]	"The inner-nuclear-envelope protein emerin regulates HIV-1 infectivity." Jacque J.-M., Stevenson M. Nature 441:641-645(2006) [PubMed: 16680152] [Abstract] Cited for: FUNCTION.
[18]	"BAF: roles in chromatin, nuclear structure and retrovirus integration." Segura-Totten M., Wilson K.L. Trends Cell Biol. 14:261-266(2004) [PubMed: 15130582] [Abstract] Cited for: REVIEW.
[19]	"Solution structure of the cellular factor BAF responsible for protecting retroviral DNA from autointegration." Cai M., Huang Y., Zheng R., Wei S.Q., Ghirlando R., Lee M.S., Craigie R., Gronenborn A.M., Clore G.M. Nat. Struct. Biol. 5:903-909(1998) [PubMed: 9783751] [Abstract] Cited for: STRUCTURE BY NMR.
[20]	"Structural basis of DNA bridging by barrier-to-autointegration factor." Umland T.C., Wei S.-Q., Craigie R., Davies D.R. Biochemistry 39:9130-9138(2000) [PubMed: 10924106] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF HOMODIMER.
[21]	"Exome sequencing and functional analysis identifies BANF1 mutation as the cause of a hereditary progeroid syndrome." Puente X.S., Quesada V., Osorio F.G., Cabanillas R., Cadinanos J., Fraile J.M., Ordonez G.R., Puente D.A., Gutierrez-Fernandez A., Fanjul-Fernandez M., Levy N., Freije J.M., Lopez-Otin C. Am. J. Hum. Genet. 88:650-656(2011) [PubMed: 21549337] [Abstract] Cited for: VARIANT NGPS THR-12.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF070447 mRNA. Translation: AAC23575.1.
AF044773 mRNA. Translation: AAC08964.1. Frameshift.
AF068235 mRNA. Translation: AAD15901.1.
CR542140 mRNA. Translation: CAG46937.1.
BC005942 mRNA. Translation: AAH05942.1.
BC107702 mRNA. Translation: AAI07703.1.

IPI

IPI00026087.

RefSeq

NP_001137457.1. NM_001143985.1.
NP_003851.1. NM_003860.3.

UniGene

Hs.433759.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CI4	X-ray	1.90	A/B	1-89	[»]
1QCK	NMR	-	A/B	1-89	[»]
2BZF	X-ray	2.87	A	1-89	[»]
2EZX	NMR	-	A/B	1-89	[»]
2EZY	NMR	-	A/B	1-89	[»]
2EZZ	NMR	-	A/B	1-89	[»]
2ODG	NMR	-	A/B	1-89	[»]

ProteinModelPortal

O75531.

SMR

O75531. Positions 1-89.

ModBase

Search...

Protein-protein interaction databases

IntAct

O75531. 1 interaction.

STRING

O75531.

PTM databases

PhosphoSite

O75531.

Proteomic databases

PeptideAtlas

O75531.

PRIDE

O75531.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000312175; ENSP00000310275; ENSG00000175334.
ENST00000445560; ENSP00000416128; ENSG00000175334.

GeneID

8815.

KEGG

hsa:8815.

UCSC

uc001ogo.1. human.

Organism-specific databases

CTD

8815.

GeneCards

GC11P065769.

H-InvDB

HIX0009819.

HGNC

HGNC:17397. BANF1.

HPA

CAB032896.

MIM

603811. gene.
614008. phenotype.

neXtProt

NX_O75531.

PharmGKB

PA134903639.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG20642.

GeneTree

ENSGT00390000018613.

HOGENOM

HBG381393.

HOVERGEN

HBG029345.

InParanoid

O75531.

OMA

NFVAEPM.

OrthoDB

EOG4SN1Q8.

PhylomeDB

O75531.

Enzyme and pathway databases

Reactome

REACT_6185. HIV Infection.

Gene expression databases

ArrayExpress

O75531.

Bgee

O75531.

CleanEx

HS_BANF1.

Genevestigator

O75531.

GermOnline

ENSG00000175334. Homo sapiens.

Family and domain databases

InterPro

IPR004122. BAF_prot.
[Graphical view]

Gene3D

G3DSA:1.10.150.40. BAF_prot. 1 hit.

PANTHER

PTHR12912. BAF_prot. 1 hit.

Pfam

PF02961. BAF. 1 hit.
[Graphical view]

ProDom

PD019964. PD019964. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM01023. BAF. 1 hit.
[Graphical view]

SUPFAM

SSF47798. BAF_prot. 1 hit.

ProtoNet

Search...

Other

NextBio

33066.

SOURCE

Search...

Entry information

Entry name

BAF_HUMAN

Accession

Primary (citable) accession number: O75531
Secondary accession number(s): O60558, Q6FGG7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	November 1, 1998
Last modified:	January 25, 2012
This is version 108 of the entry and version 1 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.