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Q9UQ13 (SHOC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Leucine-rich repeat protein SHOC-2
Alternative name(s):
Protein soc-2 homolog
Protein sur-8 homolog
Gene names
Name:SHOC2
Synonyms:KIAA0862
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length582 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Regulatory subunit of protein phosphatase 1 (PP1c) that acts as a M-Ras/MRAS effector and participates in MAPK pathway activation. Upon M-Ras/MRAS activation, targets PP1c to specifically dephosphorylate the 'Ser-259' inhibitory site of RAF1 kinase and stimulate RAF1 activity at specialized signaling complexes. Ref.8 Ref.10

Subunit structure

Interacts with M-Ras/MRAS, and RAF1. Forms a multiprotein complex with Ras (M-Ras/MRAS), Raf (RAF1) and protein phosphatase 1 (PPP1CA, PPP1CB and PPP1CC). Interacts with ERBB2IP; disrupts the interaction with RAF1 and Ras, leading to prevent activation of the Ras signaling pathway. Specifically binds K-Ras/KRAS, M-Ras/MRAS and N-Ras/NRAS but not H-Ras/HRAS. Ref.1 Ref.9 Ref.10

Subcellular location

Cytoplasm. Nucleus. Note: Translocates from cytoplasm to nucleus upon growth factor stimulation. Ref.12

Involvement in disease

Noonan syndrome-like disorder with loose anagen hair (NSLH) [MIM:607721]: A syndrome characterized by Noonan dysmorphic features such as macrocephaly, high forehead, hypertelorism, palpebral ptosis, low-set and posteriorly rotated ears, short and webbed neck, pectus anomalies, in association with pluckable, sparse, thin and slow-growing hair.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12

Sequence similarities

Belongs to the SHOC2 family.

Contains 20 LRR (leucine-rich) repeats.

Sequence caution

The sequence BAA74885.2 differs from that shown. Reason: Erroneous initiation.

The sequence BAG52235.1 differs from that shown. Reason: Erroneous initiation.

The sequence CAH72813.1 differs from that shown. Reason: Erroneous gene model prediction.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UQ13-1)

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: Q9UQ13-2)

The sequence of this isoform differs from the canonical sequence as follows:
     234-279: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 582582Leucine-rich repeat protein SHOC-2
PRO_0000097737

Regions

Repeat101 – 12222LRR 1
Repeat124 – 14522LRR 2
Repeat147 – 16923LRR 3
Repeat170 – 19122LRR 4
Repeat193 – 21422LRR 5
Repeat216 – 23722LRR 6
Repeat239 – 26022LRR 7
Repeat262 – 28322LRR 8
Repeat285 – 30723LRR 9
Repeat308 – 32922LRR 10
Repeat332 – 35322LRR 11
Repeat356 – 37722LRR 12
Repeat380 – 40021LRR 13
Repeat403 – 42422LRR 14
Repeat426 – 44823LRR 15
Repeat449 – 47022LRR 16
Repeat472 – 49423LRR 17
Repeat495 – 51622LRR 18
Repeat518 – 54023LRR 19
Repeat542 – 56322LRR 20

Natural variations

Alternative sequence234 – 27946Missing in isoform 2.
VSP_038188
Natural variant21S → G in NSLH; creates a N-myristoylation site, resulting in myristoylation of the protein and aberrant targeting to the plasma membrane. Ref.12
VAR_060199

Experimental info

Sequence conflict4751K → E in BAF85522. Ref.4
Sequence conflict5351F → L in BAA74885. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 20, 2001. Version 2.
Checksum: F3F828646642A855

FASTA58264,888
        10         20         30         40         50         60 
MSSSLGKEKD SKEKDPKVPS AKEREKEAKA SGGFGKESKE KEPKTKGKDA KDGKKDSSAA 

        70         80         90        100        110        120 
QPGVAFSVDN TIKRPNPAPG TRKKSSNAEV IKELNKCREE NSMRLDLSKR SIHILPSSIK 

       130        140        150        160        170        180 
ELTQLTELYL YSNKLQSLPA EVGCLVNLMT LALSENSLTS LPDSLDNLKK LRMLDLRHNK 

       190        200        210        220        230        240 
LREIPSVVYR LDSLTTLYLR FNRITTVEKD IKNLSKLSML SIRENKIKQL PAEIGELCNL 

       250        260        270        280        290        300 
ITLDVAHNQL EHLPKEIGNC TQITNLDLQH NELLDLPDTI GNLSSLSRLG LRYNRLSAIP 

       310        320        330        340        350        360 
RSLAKCSALE ELNLENNNIS TLPESLLSSL VKLNSLTLAR NCFQLYPVGG PSQFSTIYSL 

       370        380        390        400        410        420 
NMEHNRINKI PFGIFSRAKV LSKLNMKDNQ LTSLPLDFGT WTSMVELNLA TNQLTKIPED 

       430        440        450        460        470        480 
VSGLVSLEVL ILSNNLLKKL PHGLGNLRKL RELDLEENKL ESLPNEIAYL KDLQKLVLTN 

       490        500        510        520        530        540 
NQLTTLPRGI GHLTNLTHLG LGENLLTHLP EEIGTLENLE ELYLNDNPNL HSLPFELALC 

       550        560        570        580 
SKLSIMSIEN CPLSHLPPQI VAGGPSFIIQ FLKMQGPYRA MV 

« Hide

Isoform 2 [UniParc].

Checksum: 7F662A1A4580F3B7
Show »

FASTA53659,743

References

« Hide 'large scale' references
[1]"SUR-8, a conserved Ras-binding protein with leucine-rich repeats, positively regulates Ras-mediated signaling in C. elegans."
Sieburth D.S., Sun Q., Han M.
Cell 94:119-130(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH KRAS AND NRAS.
[2]"Soc-2 encodes a leucine-rich repeat protein implicated in fibroblast growth factor receptor signaling."
Selfors L.M., Schutzman J.L., Borland C.Z., Stern M.J.
Proc. Natl. Acad. Sci. U.S.A. 95:6903-6908(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain.
[3]"Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 5:355-364(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[4]"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. expand/collapse author list , 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 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 165-582 (ISOFORM 2).
Tissue: Amygdala and Trachea.
[5]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]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. expand/collapse author list , 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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).
Tissue: Testis.
[8]"The leucine-rich repeat protein SUR-8 enhances MAP kinase activation and forms a complex with Ras and Raf."
Li W., Han M., Guan K.-L.
Genes Dev. 14:895-900(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Erbin inhibits RAF activation by disrupting the sur-8-Ras-Raf complex."
Dai P., Xiong W.C., Mei L.
J. Biol. Chem. 281:927-933(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ERBB2IP.
[10]"A phosphatase holoenzyme comprised of Shoc2/Sur8 and the catalytic subunit of PP1 functions as an M-Ras effector to modulate Raf activity."
Rodriguez-Viciana P., Oses-Prieto J., Burlingame A., Fried M., McCormick F.
Mol. Cell 22:217-230(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MRAS AND RAF1, IDENTIFICATION IN A COMPLEX WITH PP1CA; PPP1CB; PPP1CC; RAF1 AND MRAS.
[11]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Mutation of SHOC2 promotes aberrant protein N-myristoylation and causes Noonan-like syndrome with loose anagen hair."
Cordeddu V., Di Schiavi E., Pennacchio L.A., Ma'ayan A., Sarkozy A., Fodale V., Cecchetti S., Cardinale A., Martin J., Schackwitz W., Lipzen A., Zampino G., Mazzanti L., Digilio M.C., Martinelli S., Flex E., Lepri F., Bartholdi D. expand/collapse author list , Kutsche K., Ferrero G.B., Anichini C., Selicorni A., Rossi C., Tenconi R., Zenker M., Merlo D., Dallapiccola B., Iyengar R., Bazzicalupo P., Gelb B.D., Tartaglia M.
Nat. Genet. 41:1022-1026(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NSLH GLY-2, CHARACTERIZATION OF VARIANT NSLH GLY-2, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Web resources

Protein Spotlight

The matchmaker - Issue 121 of September 2010

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF068920 mRNA. Translation: AAC39856.1.
AF054828 mRNA. Translation: AAC25698.1.
AB020669 mRNA. Translation: BAA74885.2. Different initiation.
AK090820 mRNA. Translation: BAG52235.1. Different initiation.
AK292833 mRNA. Translation: BAF85522.1.
AL158163 Genomic DNA. Translation: CAH72812.1.
AL158163 Genomic DNA. Translation: CAH72813.1. Sequence problems.
CH471066 Genomic DNA. Translation: EAW49548.1.
BC050445 mRNA. Translation: AAH50445.1.
CCDSCCDS58095.1. [Q9UQ13-2]
CCDS7568.1. [Q9UQ13-1]
RefSeqNP_001255968.1. NM_001269039.1. [Q9UQ13-2]
NP_031399.2. NM_007373.3. [Q9UQ13-1]
UniGeneHs.104315.

3D structure databases

ProteinModelPortalQ9UQ13.
SMRQ9UQ13. Positions 73-576.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113729. 8 interactions.
IntActQ9UQ13. 6 interactions.
MINTMINT-131517.
STRING9606.ENSP00000358464.

PTM databases

PhosphoSiteQ9UQ13.

Polymorphism databases

DMDM14423936.

Proteomic databases

MaxQBQ9UQ13.
PaxDbQ9UQ13.
PeptideAtlasQ9UQ13.
PRIDEQ9UQ13.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265277; ENSP00000265277; ENSG00000108061. [Q9UQ13-2]
ENST00000369452; ENSP00000358464; ENSG00000108061. [Q9UQ13-1]
GeneID8036.
KEGGhsa:8036.
UCSCuc001kzl.4. human. [Q9UQ13-1]
uc001kzn.3. human. [Q9UQ13-2]

Organism-specific databases

CTD8036.
GeneCardsGC10P112679.
HGNCHGNC:15454. SHOC2.
HPAHPA009164.
MIM602775. gene.
607721. phenotype.
neXtProtNX_Q9UQ13.
Orphanet2701. Noonan syndrome-like disorder with loose anagen hair.
PharmGKBPA37960.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG4886.
HOGENOMHOG000116557.
HOVERGENHBG055661.
InParanoidQ9UQ13.
OMAHGIGNLR.
OrthoDBEOG773XFV.
PhylomeDBQ9UQ13.
TreeFamTF315742.

Enzyme and pathway databases

SignaLinkQ9UQ13.

Gene expression databases

BgeeQ9UQ13.
CleanExHS_SHOC2.
GenevestigatorQ9UQ13.

Family and domain databases

InterProIPR001611. Leu-rich_rpt.
IPR025875. Leu-rich_rpt_4.
IPR003591. Leu-rich_rpt_typical-subtyp.
[Graphical view]
PfamPF12799. LRR_4. 1 hit.
PF13504. LRR_7. 1 hit.
PF13855. LRR_8. 4 hits.
[Graphical view]
SMARTSM00369. LRR_TYP. 1 hit.
[Graphical view]
PROSITEPS51450. LRR. 17 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSHOC2. human.
GeneWikiSHOC2.
GenomeRNAi8036.
NextBio30623.
PROQ9UQ13.
SOURCESearch...

Entry information

Entry nameSHOC2_HUMAN
AccessionPrimary (citable) accession number: Q9UQ13
Secondary accession number(s): A8K9W8 expand/collapse secondary AC list , B3KR23, O76063, Q5VZS8, Q5VZS9
Entry history
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: June 20, 2001
Last modified: July 9, 2014
This is version 130 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM