Q76I76 (SSH2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein phosphatase Slingshot homolog 2
EC=3.1.3.16
EC=3.1.3.48

Alternative name(s):
SSH-like protein 2
Short name=SSH-2L
Short name=hSSH-2L

Gene names

Name:	SSH2
Synonyms:	KIAA1725, SSH2L

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	1423 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Protein phosphatase which regulates actin filament dynamics. Dephosphorylates and activates the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly. Inhibitory phosphorylation of cofilin is mediated by LIMK1, which may also be dephosphorylated and inactivated by this protein. Ref.1
Catalytic activity	Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. A phosphoprotein + H2O = a protein + phosphate.
Subunit structure	Interacts with filamentous actin. Ref.1
Subcellular location	Cytoplasm › cytoskeleton.
Miscellaneous	Tyrosine phosphatase activity has not been demonstrated for this protein to date.
Sequence similarities	Belongs to the protein-tyrosine phosphatase family. Contains 1 tyrosine-protein phosphatase domain.
Sequence caution	The sequence AAH11636.2 differs from that shown. Reason: Erroneous initiation. The sequence AAL92027.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Actin-binding
Molecular function	Hydrolase Protein phosphatase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	actin cytoskeleton organization Inferred from mutant phenotype Ref.1. Source: UniProtKB peptidyl-tyrosine dephosphorylation Inferred from electronic annotation. Source: GOC regulation of actin polymerization or depolymerization Inferred from Biological aspect of Ancestor. Source: RefGenome regulation of axonogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome regulation of lamellipodium assembly Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular_component	cytoplasm Inferred from Biological aspect of Ancestor. Source: RefGenome cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	DNA binding Inferred from electronic annotation. Source: InterPro actin binding Inferred from direct assay Ref.1. Source: UniProtKB protein tyrosine phosphatase activity Inferred from electronic annotation. Source: EC protein tyrosine/serine/threonine phosphatase activity Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q76I76-1)

Also known as: L;

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: Q76I76-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: MALVTVQRSP...EEECRSQPRS → MTLSTLARKR...VISQNAINQL
     179-195: SALQSLHKACEVARAHN → VDRDSRNKHCYVLLVEE
     196-1423: Missing.

Isoform 3 (identifier: Q76I76-3)

Also known as: A;

The sequence of this isoform differs from the canonical sequence as follows:
     179-195: SALQSLHKACEVARAHN → VDRDSRNKHCYVLLVEE
     196-1423: Missing.

Isoform 4 (identifier: Q76I76-4)

The sequence of this isoform differs from the canonical sequence as follows:
     449-449: S → R
     450-1423: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1423

1423

Protein phosphatase Slingshot homolog 2

PRO_0000094843

Regions

Domain

307 – 447

141

Tyrosine-protein phosphatase

Sites

Active site

392

1

Phosphocysteine intermediate Ref.9

Amino acid modifications

Modified residue

36

1

Phosphoserine Ref.6

Modified residue

487

1

Phosphoserine Ref.7

Modified residue

1422

1

Phosphothreonine Ref.6 Ref.7

Natural variations

Alternative sequence

1 – 36

36

MALVT…SQPRS → MTLSTLARKRKAPLACTCSL GGPDMIPYFSANAVISQNAI NQL in isoform 2.

VSP_016321

Alternative sequence

179 – 195

17

SALQS…ARAHN → VDRDSRNKHCYVLLVEE in isoform 2 and isoform 3.

VSP_016322

Alternative sequence

196 – 1423

1228

Missing in isoform 2 and isoform 3.

VSP_016323

Alternative sequence

449

1

S → R in isoform 4.

VSP_016324

Alternative sequence

450 – 1423

974

Missing in isoform 4.

VSP_016325

Natural variant

743

1

S → L.
Corresponds to variant rs2289629 [ dbSNP | Ensembl ].

VAR_051758

Natural variant

763

1

V → A.
Corresponds to variant rs6505140 [ dbSNP | Ensembl ].

VAR_051759

Natural variant

1300

1

H → Q.
Corresponds to variant rs8080046 [ dbSNP | Ensembl ].

VAR_051760

Experimental info

Mutagenesis

392

1

C → S: Abrogates phosphatase activity. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

1423

Helix Strand Turn

Details...

Beta strand

309 – 312

4

Beta strand

315 – 318

4

Helix

320 – 323

4

Helix

326 – 331

6

Beta strand

334 – 339

6

Beta strand

342 – 344

3

Beta strand

352 – 356

5

Helix

368 – 370

3

Helix

371 – 383

13

Beta strand

387 – 391

5

Beta strand

393 – 397

5

Helix

398 – 411

14

Helix

415 – 425

11

Helix

433 – 447

15

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (L) [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 23D0B59C97D6BE38	FASTA	1,423	158,216
	10 20 30 40 50 60 MALVTVQRSP TPSTTSSPCA SEADSGEEEC RSQPRSISES FLTVKGAALF LPRGNGSSTP 70 80 90 100 110 120 RISHRRNKHA GDLQQHLQAM FILLRPEDNI RLAVRLESTY QNRTRYMVVV STNGRQDTEE 130 140 150 160 170 180 SIVLGMDFSS NDSSTCTMGL VLPLWSDTLI HLDGDGGFSV STDNRVHIFK PVSVQAMWSA 190 200 210 220 230 240 LQSLHKACEV ARAHNYYPGS LFLTWVSYYE SHINSDQSSV NEWNAMQDVQ SHRPDSPALF 250 260 270 280 290 300 TDIPTERERT ERLIKTKLRE IMMQKDLENI TSKEIRTELE MQMVCNLREF KEFIDNEMIV 310 320 330 340 350 360 ILGQMDSPTQ IFEHVFLGSE WNASNLEDLQ NRGVRYILNV TREIDNFFPG VFEYHNIRVY 370 380 390 400 410 420 DEEATDLLAY WNDTYKFISK AKKHGSKCLV HCKMGVSRSA STVIAYAMKE YGWNLDRAYD 430 440 450 460 470 480 YVKERRTVTK PNPSFMRQLE EYQGILLASK QRHNKLWRSH SDSDLSDHHE PICKPGLELN 490 500 510 520 530 540 KKDITTSADQ IAEVKTMESH PPIPPVFVEH MVPQDANQKG LCTKERMICL EFTSREFHAG 550 560 570 580 590 600 QIEDELNLND INGCSSGCCL NESKFPLDNC HASKALIQPG HVPEMANKFP DLTVEDLETD 610 620 630 640 650 660 ALKADMNVHL LPMEELTSPL KDPPMSPDPE SPSPQPSCQT EISDFSTDRI DFFSALEKFV 670 680 690 700 710 720 ELSQETRSRS FSHSRMEELG GGRNESCRLS VVEVAPSKVT ADDQRSSSLS NTPHASEESS 730 740 750 760 770 780 MDEEQSKAIS ELVSPDIFMQ SHSENAISVK EIVTEIESIS QGVGQIQLKG DILPNPCHTP 790 800 810 820 830 840 KKNSIHELLL ERAQTPENKP GHMEQDEDSC TAQPELAKDS GMCNPEGCLT THSSIADLEE 850 860 870 880 890 900 GEPAEGEQEL QGSGMHPGAK WYPGSVRRAT LEFEERLRQE QEHHGAAPTC TSLSTRKNSK 910 920 930 940 950 960 NDSSVADLAP KGKSDEAPPE HSFVLKEPEM SKGKGKYSGS EAGSLSHSEQ NATVPAPRVL 970 980 990 1000 1010 1020 EFDHLPDPQE GPGSDTGTQQ EGVLKDLRTV IPYQESETQA VPLPLPKRVE IIEYTHIVTS 1030 1040 1050 1060 1070 1080 PNHTGPGSEI ATSEKSGEQG LRKVNMEKSV TVLCTLDENL NRTLDPNQVS LHPQVLPLPH 1090 1100 1110 1120 1130 1140 SSSPEHNRPT DHPTSILSSP EDRGSSLSTA LETAAPFVSH TTHLLSASLD YLHPQTMVHL 1150 1160 1170 1180 1190 1200 EGFTEQSSTT DEPSAEQVSW EESQESPLSS GSEVPYKDSQ LSSADLSLIS KLGDNTGELQ 1210 1220 1230 1240 1250 1260 EKMDPLPVAC RLPHSSSSEN IKSLSHSPGV VKERAKEIES RVVFQAGLTK PSQMRRSASL 1270 1280 1290 1300 1310 1320 AKLGYLDLCK DCLPEREPAS CESPHLKLLQ PFLRTDSGMH AMEDQESLEN PGAPHNPEPT 1330 1340 1350 1360 1370 1380 KSFVEQLTTT ECIVQSKPVE RPLVQYAKEF GSSQQYLLPR AGLELTSSEG GLPVLQTQGL 1390 1400 1410 1420 QCACPAPGLA VAPRQQHGRT HPLRRLKKAN DKKRTTNPFY NTM
	Isoform 2 [UniParc]. Checksum: 027BBBE4C2D6FE7B	FASTA	202	22,470
	10 20 30 40 50 60 MTLSTLARKR KAPLACTCSL GGPDMIPYFS ANAVISQNAI NQLISESFLT VKGAALFLPR 70 80 90 100 110 120 GNGSSTPRIS HRRNKHAGDL QQHLQAMFIL LRPEDNIRLA VRLESTYQNR TRYMVVVSTN 130 140 150 160 170 180 GRQDTEESIV LGMDFSSNDS STCTMGLVLP LWSDTLIHLD GDGGFSVSTD NRVHIFKPVS 190 200 VQAMWVDRDS RNKHCYVLLV EE
	Isoform 3 (A) [UniParc]. Checksum: 21EB60284CB3E961	FASTA	195	21,685
	10 20 30 40 50 60 MALVTVQRSP TPSTTSSPCA SEADSGEEEC RSQPRSISES FLTVKGAALF LPRGNGSSTP 70 80 90 100 110 120 RISHRRNKHA GDLQQHLQAM FILLRPEDNI RLAVRLESTY QNRTRYMVVV STNGRQDTEE 130 140 150 160 170 180 SIVLGMDFSS NDSSTCTMGL VLPLWSDTLI HLDGDGGFSV STDNRVHIFK PVSVQAMWVD 190 RDSRNKHCYV LLVEE
	Isoform 4 [UniParc]. Checksum: AFD156098A92A04D	FASTA	449	51,492
	10 20 30 40 50 60 MALVTVQRSP TPSTTSSPCA SEADSGEEEC RSQPRSISES FLTVKGAALF LPRGNGSSTP 70 80 90 100 110 120 RISHRRNKHA GDLQQHLQAM FILLRPEDNI RLAVRLESTY QNRTRYMVVV STNGRQDTEE 130 140 150 160 170 180 SIVLGMDFSS NDSSTCTMGL VLPLWSDTLI HLDGDGGFSV STDNRVHIFK PVSVQAMWSA 190 200 210 220 230 240 LQSLHKACEV ARAHNYYPGS LFLTWVSYYE SHINSDQSSV NEWNAMQDVQ SHRPDSPALF 250 260 270 280 290 300 TDIPTERERT ERLIKTKLRE IMMQKDLENI TSKEIRTELE MQMVCNLREF KEFIDNEMIV 310 320 330 340 350 360 ILGQMDSPTQ IFEHVFLGSE WNASNLEDLQ NRGVRYILNV TREIDNFFPG VFEYHNIRVY 370 380 390 400 410 420 DEEATDLLAY WNDTYKFISK AKKHGSKCLV HCKMGVSRSA STVIAYAMKE YGWNLDRAYD 430 440 YVKERRTVTK PNPSFMRQLE EYQGILLAR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Control of actin reorganization by Slingshot, a family of phosphatases that dephosphorylate ADF/cofilin." Niwa R., Nagata-Ohashi K., Takeichi M., Mizuno K., Uemura T. Cell 108:233-246(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), FUNCTION, INTERACTION WITH ACTIN, MUTAGENESIS OF CYS-392.
[2]	"Differential activities, subcellular distribution and tissue expression patterns of three members of Slingshot family phosphatases that dephosphorylate cofilin." Ohta Y., Kousaka K., Nagata-Ohashi K., Ohashi K., Muramoto A., Shima Y., Niwa R., Uemura T., Mizuno K. Genes Cells 8:811-824(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"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] (ISOFORMS 2 AND 3). Tissue: Brain and Lung.
[4]	"Identification of genes expressed during myocardial development." Chan S.Y., Chan A.K.W., Cheung B.P.K., Liang Y., Leung M.P. Chin. Med. J. 116:1329-1332(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 282-409 (ISOFORMS 1/4).
[5]	"Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O. DNA Res. 7:347-355(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 382-1423 (ISOFORM 1). Tissue: Brain.
[6]	"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-36 AND THR-1422, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-487 AND THR-1422, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[8]	"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[9]	"Crystal structure of human slingshot phosphatase 2." Jung S.K., Jeong D.G., Yoon T.S., Kim J.H., Ryu S.E., Kim S.J. Proteins 68:408-412(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 305-448, ACTIVE SITE.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB072358 mRNA. Translation: BAB84117.1.
AB072359 mRNA. Translation: BAB84118.1.
AB099290 mRNA. Translation: BAC97813.1.
BC008941 mRNA. Translation: AAH08941.1.
BC011636 mRNA. Translation: AAH11636.2. Different initiation.
BC068223 mRNA. Translation: AAH68223.1.
AF484838 mRNA. Translation: AAL92027.1. Different initiation.
AB051512 mRNA. Translation: BAB21816.1.

IPI

IPI00061728.
IPI00383249.
IPI00655806.
IPI01009829.

RefSeq

NP_203747.2. NM_033389.2.

UniGene

Hs.654754.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2NT2	X-ray	2.10	A/B/C	305-448	[»]

ProteinModelPortal

Q76I76.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000269033.

PTM databases

PhosphoSite

Q76I76.

Polymorphism databases

DMDM

74749833.

Proteomic databases

PaxDb

Q76I76.

PRIDE

Q76I76.

Protocols and materials databases

DNASU

85464.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000269033; ENSP00000269033; ENSG00000141298.

GeneID

85464.

KEGG

hsa:85464.

UCSC

uc002heo.1. human.
uc002hep.1. human.
uc002heq.3. human.
uc002her.3. human.

Organism-specific databases

CTD

85464.

GeneCards

GC17M027952.

HGNC

HGNC:30580. SSH2.

HPA

CAB017189.

MIM

606779. gene.

neXtProt

NX_Q76I76.

PharmGKB

PA134861867.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2453.

HOVERGEN

HBG094002.

InParanoid

Q76I76.

KO

K05766.

OrthoDB

EOG4ZGPBG.

PhylomeDB

Q76I76.

Gene expression databases

ArrayExpress

Q76I76.

Bgee

Q76I76.

CleanEx

HS_SSH2.

Genevestigator

Q76I76.

GermOnline

ENSG00000141298. Homo sapiens.

Family and domain databases

Gene3D

1.10.10.60. 1 hit.

InterPro

IPR014876. DEK_C.
IPR000340. Dual-sp_phosphatase_cat-dom.
IPR020422. Dual-sp_phosphatase_subgr_cat.
IPR024950. DUSP.
IPR009057. Homeodomain-like.
IPR000387. Tyr/Dual-sp_Pase.
IPR016130. Tyr_Pase_AS.
[Graphical view]

PANTHER

PTHR10159. PTHR10159. 1 hit.

Pfam

PF08766. DEK_C. 1 hit.
PF00782. DSPc. 1 hit.
[Graphical view]

SMART

SM00195. DSPc. 1 hit.
[Graphical view]

PROSITE

PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50054. TYR_PHOSPHATASE_DUAL. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

SSH2. human.

EvolutionaryTrace

Q76I76.

GenomeRNAi

85464.

NextBio

76121.

SOURCE

Search...

Entry information

Entry name

SSH2_HUMAN

Accession

Primary (citable) accession number: Q76I76
Secondary accession number(s): Q8TDB5 , Q8WYL1, Q8WYL2, Q96F40, Q96H36, Q9C0D8

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 22, 2005
Last sequence update:	July 5, 2004
Last modified:	May 1, 2013
This is version 93 of the entry and version 1 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.