Q9UQ13 (SHOC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Leucine-rich repeat protein SHOC-2

Alternative name(s):
Protein soc-2 homolog
Protein sur-8 homolog

Gene names

Name:	SHOC2
Synonyms:	KIAA0862

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	582 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Domain	Leucine-rich repeat Repeat
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Ras protein signal transduction Non-traceable author statement Ref.1. Source: UniProtKB fibroblast growth factor receptor signaling pathway Non-traceable author statement Ref.2. Source: UniProtKB positive regulation of Ras protein signal transduction Inferred from mutant phenotype Ref.10Ref.12. Source: UniProtKB
Cellular_component	nucleus Inferred from direct assay Ref.12. Source: UniProtKB protein phosphatase type 1 complex Inferred from direct assay Ref.10. Source: UniProtKB
Molecular_function	protein phosphatase binding Inferred from direct assay Ref.10. Source: UniProtKB protein phosphatase regulator activity Traceable author statement Ref.10. Source: UniProtKB
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 582	582	Leucine-rich repeat protein SHOC-2		PRO_0000097737
Regions
	Repeat	101 – 122	22	LRR 1
	Repeat	124 – 145	22	LRR 2
	Repeat	147 – 169	23	LRR 3
	Repeat	170 – 191	22	LRR 4
	Repeat	193 – 214	22	LRR 5
	Repeat	216 – 237	22	LRR 6
	Repeat	239 – 260	22	LRR 7
	Repeat	262 – 283	22	LRR 8
	Repeat	285 – 307	23	LRR 9
	Repeat	308 – 329	22	LRR 10
	Repeat	332 – 353	22	LRR 11
	Repeat	356 – 377	22	LRR 12
	Repeat	380 – 400	21	LRR 13
	Repeat	403 – 424	22	LRR 14
	Repeat	426 – 448	23	LRR 15
	Repeat	449 – 470	22	LRR 16
	Repeat	472 – 494	23	LRR 17
	Repeat	495 – 516	22	LRR 18
	Repeat	518 – 540	23	LRR 19
	Repeat	542 – 563	22	LRR 20
Natural variations
	Alternative sequence	234 – 279	46	Missing in isoform 2.		VSP_038188
	Natural variant	2	1	S → 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 conflict	475	1	K → E in BAF85522. Ref.4
	Sequence conflict	535	1	F → L in BAA74885. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 20, 2001. Version 2. Checksum: F3F828646642A855	FASTA	582	64,888
	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
	Isoform 2 [UniParc]. Checksum: 7F662A1A4580F3B7	FASTA	536	59,743
	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 PAEIGNLSSL 250 260 270 280 290 300 SRLGLRYNRL SAIPRSLAKC SALEELNLEN NNISTLPESL LSSLVKLNSL TLARNCFQLY 310 320 330 340 350 360 PVGGPSQFST IYSLNMEHNR INKIPFGIFS RAKVLSKLNM KDNQLTSLPL DFGTWTSMVE 370 380 390 400 410 420 LNLATNQLTK IPEDVSGLVS LEVLILSNNL LKKLPHGLGN LRKLRELDLE ENKLESLPNE 430 440 450 460 470 480 IAYLKDLQKL VLTNNQLTTL PRGIGHLTNL THLGLGENLL THLPEEIGTL ENLEELYLND 490 500 510 520 530 NPNLHSLPFE LALCSKLSIM SIENCPLSHL PPQIVAGGPS FIIQFLKMQG PYRAMV

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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. , 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.
IPI	IPI00298928. IPI00479890.
RefSeq	NP_001255968.1. NM_001269039.1. NP_031399.2. NM_007373.3.
UniGene	Hs.104315.
3D structure databases
ProteinModelPortal	Q9UQ13.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UQ13. 3 interactions.
MINT	MINT-131517.
STRING	9606.ENSP00000358464.
PTM databases
PhosphoSite	Q9UQ13.
Polymorphism databases
DMDM	14423936.
Proteomic databases
PaxDb	Q9UQ13.
PeptideAtlas	Q9UQ13.
PRIDE	Q9UQ13.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000265277; ENSP00000265277; ENSG00000108061. ENST00000369452; ENSP00000358464; ENSG00000108061. ENST00000451838; ENSP00000408275; ENSG00000108061.
GeneID	8036.
KEGG	hsa:8036.
UCSC	uc001kzl.4. human. uc001kzn.3. human.
Organism-specific databases
CTD	8036.
GeneCards	GC10P112679.
HGNC	HGNC:15454. SHOC2.
HPA	HPA009164.
MIM	602775. gene. 607721. phenotype.
neXtProt	NX_Q9UQ13.
Orphanet	2701. Noonan-like syndrome with loose anagen hair.
PharmGKB	PA37960.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG4886.
HOGENOM	HOG000116557.
HOVERGEN	HBG055661.
InParanoid	Q9UQ13.
OMA	LPHGIGN.
OrthoDB	EOG408N7W.
PhylomeDB	Q9UQ13.
Enzyme and pathway databases
SignaLink	Q9UQ13.
Gene expression databases
Bgee	Q9UQ13.
CleanEx	HS_SHOC2.
Genevestigator	Q9UQ13.
GermOnline	ENSG00000108061. Homo sapiens.
Family and domain databases
InterPro	IPR001611. Leu-rich_rpt. IPR025875. Leu-rich_rpt_4. IPR003591. Leu-rich_rpt_typical-subtyp. IPR027036. SHOC2. [Graphical view]
PANTHER	PTHR23155:SF38. PTHR23155:SF38. 1 hit.
Pfam	PF00560. LRR_1. 1 hit. PF12799. LRR_4. 2 hits. [Graphical view]
SMART	SM00369. LRR_TYP. 1 hit. [Graphical view]
PROSITE	PS51450. LRR. 17 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SHOC2. human.
GenomeRNAi	8036.
NextBio	30623.
SOURCE	Search...

Entry information

Entry name

SHOC2_HUMAN

Accession

Primary (citable) accession number: Q9UQ13
Secondary accession number(s): A8K9W8 , B3KR23, O76063, Q5VZS8, Q5VZS9

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2001
Last sequence update:	June 20, 2001
Last modified:	May 29, 2013
This is version 118 of the entry and version 2 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.