DNA-binding protein SMUBP-2 - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot P38935 (SMBP2_HUMAN)

Last modified July 7, 2009. Version 101. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    DNA-binding protein SMUBP-2
    EC=3.6.1.-
Alternative name(s):
    ATP-dependent helicase IGHMBP2
    Immunoglobulin mu-binding protein 2
    Glial factor 1
      Short name=GF-1

Gene names

Name:	IGHMBP2
Synonyms:	SMBP2, SMUBP2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	993 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Acts as a transcription regulator. Required for the transcriptional activation of the flounder liver-type antifreeze protein gene. Exhibited strong binding specificity to the enhancer element B of the flounder antifreeze protein gene intron. Binds to the insulin II gene RIPE3B enhancer region By similarity. DNA-binding protein specific to 5'-phosphorylated single-stranded guanine-rich sequence related to the immunoglobulin mu chain switch region. Preferentially binds to the 5'-GGGCT-3' motif. Stimulates the transcription of the human neurotropic virus JCV.
Subcellular location	Nucleus By similarity. Cytoplasm By similarity.
Tissue specificity	In all tissues examined.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.7
Involvement in disease	Defects in IGHMBP2 are the cause of distal hereditary motor neuronopathy type 6 (HMN6) [MIM:604320]; also known as spinal muscular atrophy distal autosomal recessive 1 (DSMA1) or spinal muscular atrophy with respiratory distress 1 (SMARD1). Distal hereditary motor neuronopathies constitute a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. The most prominent symptoms of HMN6 are severe respiratory distress resulting from diaphragmatic paralysis with eventration shown on chest x-ray and predominant involvement of the upper limbs and distal muscles. Ref.9 Ref.10 Ref.11
Sequence similarities	Belongs to the DNA2/NAM7 helicase family. Contains 1 AN1-type zinc finger. Contains 1 R3H domain.

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Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation Neurodegeneration
Domain	Zinc-finger
Ligand	ATP-binding DNA-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Activator Helicase Hydrolase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	DNA recombination Ref.1 Traceable author statement. Source: ProtInc DNA repair Traceable author statement. Source: ProtInc DNA replication Traceable author statement. Source: ProtInc cell death Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW DNA helicase activity Ref.1 Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: IntAct single-stranded DNA binding Ref.1 Traceable author statement. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
LSM8	O95777	1	EBI-372250,EBI-347779

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed Ref.3

Chain

2 – 993

992

DNA-binding protein SMUBP-2

PRO_0000080701

Regions

Domain

723 – 786

R3H

Nucleotide binding

214 – 221

ATP By similarity

DNA binding

638 – 785

148

SS DNA-binding By similarity

Zinc finger

894 – 940

AN1-type

Motif

864 – 868

Nuclear localization signal Potential

Compositional bias

251 – 426

176

Leu-rich

Compositional bias

795 – 859

Gln/Pro-rich

Compositional bias

864 – 870

Poly-Lys

Amino acid modifications

Modified residue

N-acetylalanine Ref.3

Modified residue

656

Phosphoserine Ref.7

Natural variations

Natural variant

A → T: dbSNP rs2228206.

VAR_055225

Natural variant

192

L → P in HMN6. Ref.10

VAR_022321

Natural variant

201

S → L: dbSNP rs560096. Ref.2

VAR_024242

Natural variant

213

H → R in HMN6. Ref.9

VAR_022322

Natural variant

221

T → A in HMN6. Ref.10

VAR_022323

Natural variant

241

C → R in HMN6. Ref.10

VAR_022324

Natural variant

275

I → V: dbSNP rs10896380.

VAR_024243

Natural variant

334

E → K in HMN6. Ref.10

VAR_022325

Natural variant

361

L → P in HMN6. Ref.10

VAR_022326

Natural variant

364

L → P in HMN6. Ref.10

VAR_022327

Natural variant

382

E → K in HMN6. Ref.10

VAR_022328

Natural variant

426

L → P in HMN6. Ref.10

VAR_022329

Natural variant

514

E → K in HMN6. Ref.9

VAR_022330

Natural variant

557

P → A: dbSNP rs7122089.

VAR_055226

Natural variant

565

D → N in HMN6. Ref.10

VAR_022331

Natural variant

572

Missing in HMN6. Ref.10

VAR_022332

Natural variant

577

L → P in HMN6. Ref.10

VAR_022333

Natural variant

580

V → I in HMN6. Ref.9

VAR_022334

Natural variant

583

N → I in HMN6. Ref.10

VAR_022335

Natural variant

586

G → C in HMN6. Ref.10

VAR_022336

Natural variant

603

R → H in HMN6. Ref.10

VAR_022337

Natural variant

637

R → C in HMN6. Ref.10

VAR_022338

Natural variant

671

T → A: dbSNP rs622082.

VAR_020147

Natural variant

694

R → W: dbSNP rs2236654.

VAR_021899

Natural variant

879

T → K in HMN6. dbSNP rs17612126.

VAR_022339

Natural variant

928

E → K: dbSNP rs2275996.

VAR_021900

Natural variant

974

D → E in HMN6. Ref.10

VAR_022340

Experimental info

Sequence conflict

292

I → N in AAA53082. Ref.1

Sequence conflict

461

L → V in AAA53082. Ref.1

Sequence conflict

491 – 494

VDTA → GGRV in AAA58611. Ref.6

Sequence conflict

863

E → K in AAA58611. Ref.6

Sequence conflict

866

K → T in AAA58611. Ref.6

Secondary structure

993

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P38935-1 [UniParc].

Last modified May 5, 2009. Version 2.
Checksum: AB9C106FCA03524F
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FASTA

993

109,123

        10         20         30         40         50         60 
MASAAVESFV TKQLDLLELE RDAEVEERRS WQENISLKEL QSRGVCLLKL QVSSQRTGLY 

        70         80         90        100        110        120 
GRLLVTFEPR RYGSAAALPS NSFTSGDIVG LYDAANEGSQ LATGILTRVT QKSVTVAFDE 

       130        140        150        160        170        180 
SHDFQLSLDR ENSYRLLKLA NDVTYRRLKK ALIALKKYHS GPASSLIEVL FGRSAPSPAS 

       190        200        210        220        230        240 
EIHPLTFFNT CLDTSQKEAV SFALSQKELA IIHGPPGTGK TTTVVEIILQ AVKQGLKVLC 

       250        260        270        280        290        300 
CAPSNIAVDN LVERLALCKQ RILRLGHPAR LLESIQQHSL DAVLARSDSA QIVADIRKDI 

       310        320        330        340        350        360 
DQVFVKNKKT QDKREKSNFR NEIKLLRKEL KEREEAAMLE SLTSANVVLA TNTGASADGP 

       370        380        390        400        410        420 
LKLLPESYFD VVVIDECAQA LEASCWIPLL KARKCILAGD HKQLPPTTVS HKAALAGLSL 

       430        440        450        460        470        480 
SLMERLAEEY GARVVRTLTV QYRMHQAIMR WASDTMYLGQ LTAHSSVARH LLRDLPGVAA 

       490        500        510        520        530        540 
TEETGVPLLL VDTAGCGLFE LEEEDEQSKG NPGEVRLVSL HIQALVDAGV PARDIAVVSP 

       550        560        570        580        590        600 
YNLQVDLLRQ SLVHRHPELE IKSVDGFQGR EKEAVILSFV RSNRKGEVGF LAEDRRINVA 

       610        620        630        640        650        660 
VTRARRHVAV ICDSRTVNNH AFLKTLVEYF TQHGEVRTAF EYLDDIVPEN YSHENSQGSS 

       670        680        690        700        710        720 
HAATKPQGPA TSTRTGSQRQ EGGQEAAAPA RQGRKKPAGK SLASEAPSQP SLNGGSPEGV 

       730        740        750        760        770        780 
ESQDGVDHFR AMIVEFMASK KMQLEFPPSL NSHDRLRVHQ IAEEHGLRHD SSGEGKRRFI 

       790        800        810        820        830        840 
TVSKRAPRPR AALGPPAGTG GPAPLQPVPP TPAQTEQPPR EQRGPDQPDL RTLHLERLQR 

       850        860        870        880        890        900 
VRSAQGQPAS KEQQASGQQK LPEKKKKKAK GHPATDLPTE EDFEALVSAA VKADNTCGFA 

       910        920        930        940        950        960 
KCTAGVTTLG QFCQLCSRRY CLSHHLPEIH GCGERARAHA RQRISREGVL YAGSGTKNGS 

       970        980        990 
LDPAKRAQLQ RRLDKKLSEL SNQRTSRRKE RGT

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human S mu bp-2, a DNA-binding protein specific to the single-stranded guanine-rich sequence related to the immunoglobulin mu chain switch region." Fukita Y., Mizuta T.-R., Shirozu M., Ozawa K., Shimizu A., Honjo T. J. Biol. Chem. 268:17463-17470(1993) [PubMed: 8349627] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-275.
[2]	"Smubp-2 represses the Epstein-Barr virus lytic switch promoter." Zhang Q., Wang Y.C., Montalvo E.A. Virology 255:160-170(1999) [PubMed: 10049831] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-201 AND VAL-275.
[3]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. Sakaki Y. Nature 440:497-500(2006) [PubMed: 16554811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT LEU-201.
[4]	"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] OF 1-868, VARIANT LEU-201. Tissue: Brain.
[5]	Bienvenut W.V., Boldt K., von Kriegsheim A.F., Kolch W. Submitted (JUL-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-12; 221-233 AND 824-831, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: Hepatoma.
[6]	"A recombinant cDNA derived from human brain encodes a DNA binding protein that stimulates transcription of the human neurotropic virus JCV." Kerr D., Khalili K. J. Biol. Chem. 266:15876-15881(1991) [PubMed: 1714899] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 491-866. Tissue: Brain.
[7]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-656, MASS SPECTROMETRY.
[8]	"Solution structure of the R3H domain from human Smubp-2." Liepinsh E., Leonchiks A., Sharipo A., Guignard L., Otting G. J. Mol. Biol. 326:217-223(2003) [PubMed: 12547203] [Abstract] Cited for: STRUCTURE BY NMR OF 709-794.
[9]	"Mutations in the gene encoding immunoglobulin mu-binding protein 2 cause spinal muscular atrophy with respiratory distress type 1." Grohmann K., Schuelke M., Diers A., Hoffmann K., Lucke B., Adams C., Bertini E., Leonhardt-Horti H., Muntoni F., Ouvrier R., Pfeufer A., Rossi R., Van Maldergem L., Wilmshurst J.M., Wienker T.F., Sendtner M., Rudnik-Schoeneborn S., Zerres K., Huebner C. Nat. Genet. 29:75-77(2001) [PubMed: 11528396] [Abstract] Cited for: VARIANTS HMN6 ARG-213; LYS-514 AND ILE-580.
[10]	"Infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1)." Grohmann K., Varon R., Stolz P., Schuelke M., Janetzki C., Bertini E., Bushby K., Muntoni F., Ouvrier R., Van Maldergem L., Goemans N.M.L.A., Lochmueller H., Eichholz S., Adams C., Bosch F., Grattan-Smith P., Navarro C., Neitzel H. Huebner C. Ann. Neurol. 54:719-724(2003) [PubMed: 14681881] [Abstract] Cited for: VARIANTS HMN6 PRO-192; ALA-221; ARG-241; LYS-334; PRO-361; PRO-364; LYS-382; PRO-426; ASN-565; LYS-572 DEL; PRO-577; ILE-583; CYS-586; HIS-603; CYS-637 AND GLU-974.
[11]	"A new mutation of IGHMBP2 gene in spinal muscular atrophy with respiratory distress type 1." Tachi N., Kikuchi S., Kozuka N., Nogami A. Pediatr. Neurol. 32:288-290(2005) [PubMed: 15797190] [Abstract] Cited for: VARIANT HMN6 LYS-879.
+	Additional computationally mapped references.

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Web resources

GeneReviews

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Cross-references

Sequence databases

L14754 mRNA. Translation: AAA53082.1.
L24544 Genomic DNA. Translation: AAA70430.1.
AP000808 Genomic DNA. No translation available.
BC025299 mRNA. Translation: AAH25299.1.
M64979 mRNA. Translation: AAA58611.1.

IPI

IPI00009379.

PIR

A47500.

RefSeq

NP_002171.2.

UniGene

Hs.503048

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MSZ	NMR	-	A	711-786	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P38935. 1 interaction.

PTM databases

PhosphoSite

P38935.

Proteomic databases

PRIDE

P38935.

Genome annotation databases

Ensembl

ENSG00000132740. Homo sapiens. [Contig view]

GeneID

3508.

Organism-specific databases

GeneCards

GC11P068427.

H-InvDB

HIX0009884.

HGNC

HGNC:5542. IGHMBP2.

MIM

600502. gene.
604320. phenotype.

Orphanet

98920. Spinal muscular atrophy with respiratory distress.

PharmGKB

PA29731.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P38935.

HOVERGEN

P38935.

Gene expression databases

ArrayExpress

P38935.

Bgee

P38935.

CleanEx

HS_IGHMBP2.

GermOnline

ENSG00000132740. Homo sapiens.

Family and domain databases

InterPro

IPR003593. ATPase_AAA+_core.
IPR014001. DEAD-like_N.
IPR004483. DNA_helicase_put.
IPR001374. R3H_ss_bd.
IPR000058. Znf_AN1.
[Graphical view]

Gene3D

G3DSA:4.10.1110.10. Znf_AN1. 1 hit.

Pfam

PF01424. R3H. 1 hit.
[Graphical view]

SMART

SM00382. AAA. 1 hit.
SM00487. DEXDc. 1 hit.
SM00393. R3H. 1 hit.
SM00154. ZnF_AN1. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00376. put_DNA_helic. 1 hit.

PROSITE

PS51061. R3H. 1 hit.
PS51039. ZF_AN1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

SOURCE

Search...

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Entry information

Entry name

SMBP2_HUMAN

Accession

Primary (citable) accession number: P38935
Secondary accession number(s): A0PJD2, Q00443, Q14177

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	May 5, 2009
Last modified:	July 7, 2009
This is version 101 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents