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Reviewed, UniProtKB/Swiss-Prot P38935 (SMBP2_HUMAN)

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

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length993 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

LSM8O957771EBI-372250,EBI-347779

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.3
Chain2 – 993992DNA-binding protein SMUBP-2
PRO_0000080701

Regions

Domain723 – 78664R3H
Nucleotide binding214 – 2218ATP By similarity
DNA binding638 – 785148SS DNA-binding By similarity
Zinc finger894 – 94047AN1-type
Motif864 – 8685Nuclear localization signal Potential
Compositional bias251 – 426176Leu-rich
Compositional bias795 – 85965Gln/Pro-rich
Compositional bias864 – 8707Poly-Lys

Amino acid modifications

Modified residue21N-acetylalanine Ref.3
Modified residue6561Phosphoserine Ref.7

Natural variations

Natural variant751A → T: dbSNP rs2228206.
VAR_055225
Natural variant1921L → P in HMN6. Ref.10
VAR_022321
Natural variant2011S → L: dbSNP rs560096. Ref.2
VAR_024242
Natural variant2131H → R in HMN6. Ref.9
VAR_022322
Natural variant2211T → A in HMN6. Ref.10
VAR_022323
Natural variant2411C → R in HMN6. Ref.10
VAR_022324
Natural variant2751I → V: dbSNP rs10896380.
VAR_024243
Natural variant3341E → K in HMN6. Ref.10
VAR_022325
Natural variant3611L → P in HMN6. Ref.10
VAR_022326
Natural variant3641L → P in HMN6. Ref.10
VAR_022327
Natural variant3821E → K in HMN6. Ref.10
VAR_022328
Natural variant4261L → P in HMN6. Ref.10
VAR_022329
Natural variant5141E → K in HMN6. Ref.9
VAR_022330
Natural variant5571P → A: dbSNP rs7122089.
VAR_055226
Natural variant5651D → N in HMN6. Ref.10
VAR_022331
Natural variant5721Missing in HMN6. Ref.10
VAR_022332
Natural variant5771L → P in HMN6. Ref.10
VAR_022333
Natural variant5801V → I in HMN6. Ref.9
VAR_022334
Natural variant5831N → I in HMN6. Ref.10
VAR_022335
Natural variant5861G → C in HMN6. Ref.10
VAR_022336
Natural variant6031R → H in HMN6. Ref.10
VAR_022337
Natural variant6371R → C in HMN6. Ref.10
VAR_022338
Natural variant6711T → A: dbSNP rs622082.
VAR_020147
Natural variant6941R → W: dbSNP rs2236654.
VAR_021899
Natural variant8791T → K in HMN6. dbSNP rs17612126.
VAR_022339
Natural variant9281E → K: dbSNP rs2275996.
VAR_021900
Natural variant9741D → E in HMN6. Ref.10
VAR_022340

Experimental info

Sequence conflict2921I → N in AAA53082. Ref.1
Sequence conflict4611L → V in AAA53082. Ref.1
Sequence conflict491 – 4944VDTA → GGRV in AAA58611. Ref.6
Sequence conflict8631E → K in AAA58611. Ref.6
Sequence conflict8661K → T in AAA58611. Ref.6

Secondary structure

............. 993
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P38935-1 [UniParc].

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

FASTA993109,123
        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 

« Hide

References

« Hide '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. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., 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. expand/collapse author list , Polster T., Topaloglu H., Steglich C., Guenther U.P., Zerres K., Rudnik-Schoeneborn S., 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.

Web resources

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.
IPIIPI00009379.
PIRA47500.
RefSeqNP_002171.2.
UniGeneHs.503048

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1MSZNMR-A711-786[»]
ModBaseSearch...

Protein-protein interaction databases

IntActP38935. 1 interaction.

PTM databases

PhosphoSiteP38935.

Proteomic databases

PRIDEP38935.

Genome annotation databases

EnsemblENSG00000132740. Homo sapiens. [Contig view]
GeneID3508.

Organism-specific databases

GeneCardsGC11P068427.
H-InvDBHIX0009884.
HGNCHGNC:5542. IGHMBP2.
MIM600502. gene.
604320. phenotype.
Orphanet98920. Spinal muscular atrophy with respiratory distress.
PharmGKBPA29731.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP38935.
HOVERGENP38935.

Gene expression databases

ArrayExpressP38935.
BgeeP38935.
CleanExHS_IGHMBP2.
GermOnlineENSG00000132740. Homo sapiens.

Family and domain databases

InterProIPR003593. ATPase_AAA+_core.
IPR014001. DEAD-like_N.
IPR004483. DNA_helicase_put.
IPR001374. R3H_ss_bd.
IPR000058. Znf_AN1.
[Graphical view]
Gene3DG3DSA:4.10.1110.10. Znf_AN1. 1 hit.
PfamPF01424. R3H. 1 hit.
[Graphical view]
SMARTSM00382. AAA. 1 hit.
SM00487. DEXDc. 1 hit.
SM00393. R3H. 1 hit.
SM00154. ZnF_AN1. 1 hit.
[Graphical view]
TIGRFAMsTIGR00376. put_DNA_helic. 1 hit.
PROSITEPS51061. R3H. 1 hit.
PS51039. ZF_AN1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

SOURCESearch...

Entry information

Entry nameSMBP2_HUMAN
AccessionPrimary (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 statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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 · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents