P81274 (GPSM2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
G-protein-signaling modulator 2

Alternative name(s):
Mosaic protein LGN

Gene names

Name:	GPSM2
Synonyms:	LGN

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

General annotation (Comments)

Function	Plays an important role in spindle pole orientation. Interacts and contributes to the functional activity of G(i) alpha proteins. Acts to stabilize the apical complex during neuroblast divisions. Ref.8
Subunit structure	Interacts with LLGL2. Interacts with INSC/inscuteable and probably with F2RL2. Ref.8 Ref.9
Subcellular location	Cytoplasm. Cytoplasm › cell cortex. Note: Localizes in the cytoplasm in the interphase and at cell periphery in the metaphase. Ref.8
Tissue specificity	Ubiquitously expressed.
Involvement in disease	Chudley-McCullough syndrome (CMCS) [MIM:604213]: An autosomal recessive neurologic disorder characterized by early-onset sensorineural deafness and specific brain anomalies on MRI, including hypoplasia of the corpus callosum, enlarged cysterna magna with mild focal cerebellar dysplasia, and nodular heterotopia. Some patients have hydrocephalus. Psychomotor development is normal. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.13
Miscellaneous	Dysfunction of LGN is associated with the phenotype of multiple micronuclei due to chromosomal mis-segregation and defect in cell division through mis-localization of mitotic splindle regulator protein NuMA.
Sequence similarities	Belongs to the GPSM family. Contains 4 GoLoco domains. Contains 8 TPR repeats.
Caution	It is uncertain whether Met-1 or Met-8 is the initiator. Mutations in GPSM2 have been identified in people with profound congenital non-syndromic deafness designated as DFNB82 (Ref.11). Subsequent brain imaging of these individuals has revealed frontal polymicrogyria, abnormal corpus callosum, and gray matter heterotopia, consistent with a diagnosis of Chudley-McCullough syndrome (Ref.13).
Sequence caution	The sequence AAB40385.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAH27732.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Cellular component	Cytoplasm
Disease	Deafness
Domain	Repeat TPR repeat
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway Traceable author statement Ref.1. Source: ProtInc establishment of mitotic spindle orientation Inferred from electronic annotation. Source: Compara lung epithelial cell differentiation Inferred from electronic annotation. Source: Compara regulation of G-protein coupled receptor protein signaling pathway Inferred from electronic annotation. Source: InterPro
Cellular_component	apical part of cell Inferred from electronic annotation. Source: Compara cell cortex Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA
Molecular_function	GDP-dissociation inhibitor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		7	EBI-618655,EBI-618655
GNAI1	P63096	3	EBI-618655,EBI-618639
NUMA1	Q14980	6	EBI-618655,EBI-521611

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 684

684

G-protein-signaling modulator 2

PRO_0000106358

Regions

Repeat

24 – 57

34

TPR 1

Repeat

62 – 95

34

TPR 2

Repeat

102 – 135

34

TPR 3

Repeat

142 – 184

43

TPR 4

Repeat

202 – 235

34

TPR 5

Repeat

242 – 275

34

TPR 6

Repeat

282 – 315

34

TPR 7

Repeat

322 – 355

34

TPR 8

Domain

489 – 511

23

GoLoco 1

Domain

544 – 566

23

GoLoco 2

Domain

594 – 616

23

GoLoco 3

Domain

628 – 650

23

GoLoco 4

Amino acid modifications

Modified residue

132

1

Phosphoserine; by PKG Potential

Modified residue

352

1

Phosphoserine; by PKG Potential

Modified residue

408

1

Phosphoserine Ref.12

Modified residue

483

1

Phosphoserine Ref.10

Modified residue

486

1

Phosphothreonine Ref.10

Modified residue

501

1

Phosphoserine; by PKC Potential

Modified residue

541

1

Phosphoserine Ref.10

Modified residue

565

1

Phosphoserine Ref.12

Modified residue

607

1

Phosphoserine; by PKG Potential

Experimental info

Sequence conflict

400

1

R → L in AAB40385. Ref.1

Secondary structure

1

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684

Helix Strand Turn

Details...

Helix

24 – 36

13

Helix

40 – 53

14

Helix

58 – 74

17

Helix

78 – 94

17

Helix

98 – 114

17

Helix

118 – 135

18

Helix

138 – 157

20

Helix

172 – 194

23

Helix

198 – 215

18

Helix

218 – 234

17

Helix

238 – 254

17

Helix

258 – 274

17

Helix

278 – 294

17

Helix

298 – 314

17

Helix

318 – 335

18

Helix

338 – 354

17

Helix

358 – 376

19

Sequences

	Sequence		Length	Mass (Da)
	P81274 [UniParc]. Last modified April 20, 2010. Version 3. Checksum: D007A4765F57CB90	FASTA	684	76,662
	10 20 30 40 50 60 MEENLISMRE DHSFHVRYRM EASCLELALE GERLCKSGDC RAGVSFFEAA VQVGTEDLKT 70 80 90 100 110 120 LSAIYSQLGN AYFYLHDYAK ALEYHHHDLT LARTIGDQLG EAKASGNLGN TLKVLGNFDE 130 140 150 160 170 180 AIVCCQRHLD ISRELNDKVG EARALYNLGN VYHAKGKSFG CPGPQDVGEF PEEVRDALQA 190 200 210 220 230 240 AVDFYEENLS LVTALGDRAA QGRAFGNLGN THYLLGNFRD AVIAHEQRLL IAKEFGDKAA 250 260 270 280 290 300 ERRAYSNLGN AYIFLGEFET ASEYYKKTLL LARQLKDRAV EAQSCYSLGN TYTLLQDYEK 310 320 330 340 350 360 AIDYHLKHLA IAQELNDRIG EGRACWSLGN AYTALGNHDQ AMHFAEKHLE ISREVGDKSG 370 380 390 400 410 420 ELTARLNLSD LQMVLGLSYS TNNSIMSENT EIDSSLNGVR PKLGRRHSME NMELMKLTPE 430 440 450 460 470 480 KVQNWNSEIL AKQKPLIAKP SAKLLFVNRL KGKKYKTNSS TKVLQDASNS IDHRIPNSQR 490 500 510 520 530 540 KISADTIGDE GFFDLLSRFQ SNRMDDQRCC LQEKNCHTAS TTTSSTPPKM MLKTSSVPVV 550 560 570 580 590 600 SPNTDEFLDL LASSQSRRLD DQRASFSNLP GLRLTQNSQS VLSHLMTNDN KEADEDFFDI 610 620 630 640 650 660 LVKCQGSRLD DQRCAPPPAT TKGPTVPDED FFSLILRSQG KRMDEQRVLL QRDQNRDTDF 670 680 GLKDFLQNNA LLEFKNSGKK SADH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and cDNA cloning of a novel human mosaic protein, LGN, based on interaction with G alpha i2." Mochizuki N., Cho G., Wen B., Insel P.A. Gene 181:39-43(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: B-cell.
[2]	"Involvement of C0671 overexpression in breast cancer cell growth." Katagiri T., Fukukawa C., Nakamura Y. Submitted (JUL-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases 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]. Tissue: Muscle.
[6]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." Puhl H.L. III, Ikeda S.R., Aronstam R.S. Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 8-684. Tissue: Brain.
[7]	"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] OF 8-684.
[8]	"Direct binding of Lgl2 to LGN during mitosis and its requirement for normal cell division." Yasumi M., Sakisaka T., Hoshino T., Kimura T., Sakamoto Y., Yamanaka T., Ohno S., Takai Y. J. Biol. Chem. 280:6761-6765(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH LLGL2, SUBCELLULAR LOCATION. Tissue: Brain.
[9]	"Two forms of human Inscuteable-related protein that links Par3 to the Pins homologues LGN and AGS3." Izaki T., Kamakura S., Kohjima M., Sumimoto H. Biochem. Biophys. Res. Commun. 341:1001-1006(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH INSC.
[10]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-483; THR-486 AND SER-541, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Whole exome sequencing and homozygosity mapping identify mutation in the cell polarity protein GPSM2 as the cause of nonsyndromic hearing loss DFNB82." Walsh T., Shahin H., Elkan-Miller T., Lee M.K., Thornton A.M., Roeb W., Abu Rayyan A., Loulus S., Avraham K.B., King M.C., Kanaan M. Am. J. Hum. Genet. 87:90-94(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN CMCS.
[12]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-408 AND SER-565, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"GPSM2 mutations cause the brain malformations and hearing loss in Chudley-McCullough syndrome." Doherty D., Chudley A.E., Coghlan G., Ishak G.E., Innes A.M., Lemire E.G., Rogers R.C., Mhanni A.A., Phelps I.G., Jones S.J., Zhan S.H., Fejes A.P., Shahin H., Kanaan M., Akay H., Tekin M., Triggs-Raine B., Zelinski T. Am. J. Hum. Genet. 90:1088-1093(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN CMCS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U54999 mRNA. Translation: AAB40385.1. Different initiation.
AB445462 mRNA. Translation: BAH84760.1.
AL449266 Genomic DNA. Translation: CAI14361.1.
CH471122 Genomic DNA. Translation: EAW56340.1.
BC027732 mRNA. Translation: AAH27732.1. Different initiation.
AY136740 mRNA. Translation: AAN01266.1.
CR456786 mRNA. Translation: CAG33067.1.

IPI

IPI00642575.

PIR

G02540. JC5334.

RefSeq

NP_037428.3. NM_013296.4.

UniGene

Hs.584901.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3SF4	X-ray	2.60	A/B/C	20-421	[»]

ProteinModelPortal

P81274.

SMR

P81274. Positions 20-381.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-399N.

IntAct

P81274. 3 interactions.

MINT

MINT-3023522.

STRING

9606.ENSP00000264126.

PTM databases

PhosphoSite

P81274.

Polymorphism databases

DMDM

294862507.

Proteomic databases

PaxDb

P81274.

PRIDE

P81274.

Protocols and materials databases

DNASU

29899.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000264126; ENSP00000264126; ENSG00000121957.
ENST00000406462; ENSP00000385510; ENSG00000121957.

GeneID

29899.

KEGG

hsa:29899.

UCSC

uc010ovc.2. human.

Organism-specific databases

CTD

29899.

GeneCards

GC01P109417.

HGNC

HGNC:29501. GPSM2.

HPA

CAB018962.
HPA007327.
HPA008408.

MIM

604213. phenotype.
609245. gene.

neXtProt

NX_P81274.

Orphanet

90636. Autosomal recessive nonsyndromic sensorineural deafness type DFNB.

PharmGKB

PA134993615.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0457.

HOGENOM

HOG000231543.

HOVERGEN

HBG051823.

InParanoid

P81274.

KO

K15837.

OMA

EYYEANL.

OrthoDB

EOG4SXNC5.

Gene expression databases

ArrayExpress

P81274.

Bgee

P81274.

CleanEx

HS_GPSM2.

Genevestigator

P81274.

GermOnline

ENSG00000121957. Homo sapiens.

Family and domain databases

Gene3D

1.25.40.10. 2 hits.

InterPro

IPR024807. G_prot_signal_mod_2.
IPR003109. GoLoco_motif.
IPR001440. TPR-1.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical.
IPR019734. TPR_repeat.
[Graphical view]

PANTHER

PTHR10098:SF39. PTHR10098:SF39. 1 hit.

Pfam

PF02188. GoLoco. 4 hits.
PF00515. TPR_1. 5 hits.
PF13176. TPR_7. 1 hit.
[Graphical view]

SMART

SM00390. GoLoco. 4 hits.
SM00028. TPR. 6 hits.
[Graphical view]

PROSITE

PS50877. GOLOCO. 4 hits.
PS50005. TPR. 6 hits.
PS50293. TPR_REGION. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

29899.

NextBio

52462.

SOURCE

Search...

Entry information

Entry name

GPSM2_HUMAN

Accession

Primary (citable) accession number: P81274
Secondary accession number(s): Q5T1N8, Q6IBL7, Q8N0Z5

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	April 20, 2010
Last modified:	May 1, 2013
This is version 137 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.