P57075 (UBS3A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquitin-associated and SH3 domain-containing protein A

Alternative name(s):
Cbl-interacting protein 4
Short name=CLIP4
Suppressor of T-cell receptor signaling 2
Short name=STS-2
T-cell ubiquitin ligand 1
Short name=TULA-1

Gene names

Name:	UBASH3A
Synonyms:	STS2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	661 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Interferes with CBL-mediated down-regulation and degradation of receptor-type tyrosine kinases. Promotes accumulation of activated target receptors, such as T-cell receptors, EGFR and PDGFRB, on the cell surface. Exhibits negligigle protein tyrosine phosphatase activity at neutral pH. May act as a dominant-negative regulator of UBASH3B-dependent dephosphorylation. May inhibit dynamin-dependent endocytic pathways by functionally sequestering dynamin via its SH3 domain. Ref.5 Ref.6 Ref.7
Subunit structure	Homodimer or homooligomer. Interacts with CBL. Part of a complex containing CBL and activated EGFR. Interacts with ubiquitin and with mono-ubiquitinated proteins. Interacts with dynamin. Ref.2 Ref.5 Ref.6
Subcellular location	Cytoplasm. Nucleus Ref.2 Ref.5.
Tissue specificity	Highest expression of UBASH3A in tissues belonging to the immune system, including spleen, peripheral blood leukocytes, thymus and bone marrow. Ref.1 Ref.2
Sequence similarities	Contains 1 SH3 domain. Contains 1 UBA domain.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	SH3 domain
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Cellular component	cytosol Inferred from direct assay. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P57075-1)

Also known as: Long;

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: P57075-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     185-223: GTSVSRFWIFSQVPGHGPNLRLSNLTRASFVSHYILQKY → D

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 661

661

Ubiquitin-associated and SH3 domain-containing protein A

PRO_0000210994

Regions

Domain

15 – 60

46

UBA

Domain

276 – 340

65

SH3

Region

395 – 661

267

Phosphatase-like

Natural variations

Alternative sequence

185 – 223

39

GTSVS…ILQKY → D in isoform 2.

VSP_006703

Natural variant

18

1

S → G. Ref.4
Corresponds to variant rs2277798 [ dbSNP | Ensembl ].

VAR_026971

Natural variant

28

1

L → F. Ref.4
Corresponds to variant rs2277800 [ dbSNP | Ensembl ].

VAR_026972

Natural variant

286

1

Q → R.
Corresponds to variant rs13048049 [ dbSNP | Ensembl ].

VAR_026973

Natural variant

324

1

R → L.
Corresponds to variant rs13048049 [ dbSNP | Ensembl ].

VAR_061921

Natural variant

324

1

R → Q.
Corresponds to variant rs13048049 [ dbSNP | Ensembl ].

VAR_061922

Natural variant

466

1

D → E.
Corresponds to variant rs17114930 [ dbSNP | Ensembl ].

VAR_052675

Experimental info

Mutagenesis

317

1

W → A: Loss of interaction with CBL. Ref.5 Ref.6

Mutagenesis

317

1

W → L: Abolishes binding to dynamin. Ref.5 Ref.6

Sequence conflict

64

1

P → H in AAH69511. Ref.4

Sequence conflict

229

1

C → Y in AAH69511. Ref.4

Sequence conflict

283

1

A → V in AAH69483. Ref.4

Sequence conflict

393

1

V → I in AAH69511. Ref.4

Sequence conflict

651

1

A → V in AAH69511. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

661

Helix Strand Turn

Details...

Helix

25 – 30

6

Helix

35 – 45

11

Helix

50 – 60

11

Beta strand

61 – 63

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) [UniParc]. Last modified December 1, 2000. Version 1. Checksum: 60DA2E0B8CE4ABFC	FASTA	661	74,123
	10 20 30 40 50 60 MAAGETQLYA KVSNKLKSRS SPSLLEPLLA MGFPVHTALK ALAATGRKTA EEALAWLHDH 70 80 90 100 110 120 CNDPSLDDPI PQEYALFLCP TGPLLEKLQE FWRESKRQCA KNRAHEVFPH VTLCDFFTCE 130 140 150 160 170 180 DQKVECLYEA LKRAGDRLLG SFPTAVPLAL HSSISYLGFF VSGSPADVIR EFAMTFATEA 190 200 210 220 230 240 SLLAGTSVSR FWIFSQVPGH GPNLRLSNLT RASFVSHYIL QKYCSVKPCT KQLHLTLAHK 250 260 270 280 290 300 FYPHHQRTLE QLARAIPLGH SCQWTAALYS RDMRFVHYQT LRALFQYKPQ NVDELTLSPG 310 320 330 340 350 360 DYIFVDPTQQ DEASEGWVIG ISQRTGCRGF LPENYTDRAS ESDTWVKHRM YTFSLATDLN 370 380 390 400 410 420 SRKDGEASSR CSGEFLPQTA RSLSSLQALQ ATVARKSVLV VRHGERVDQI FGKAWLQQCS 430 440 450 460 470 480 TPDGKYYRPD LNFPCSLPRR SRGIKDFEND PPLSSCGIFQ SRIAGDALLD SGIRISSVFA 490 500 510 520 530 540 SPALRCVQTA KLILEELKLE KKIKIRVEPG IFEWTKWEAG KTTPTLMSLE ELKEANFNID 550 560 570 580 590 600 TDYRPAFPLS ALMPAESYQE YMDRCTASMV QIVNTCPQDT GVILIVSHGS TLDSCTRPLL 610 620 630 640 650 660 GLPPRECGDF AQLVRKIPSL GMCFCEENKE EGKWELVNPP VKTLTHGANA AFNWRNWISG N
	Isoform 2 (Short) [UniParc]. Checksum: E5AA549B7D3C915E	FASTA	623	69,791
	10 20 30 40 50 60 MAAGETQLYA KVSNKLKSRS SPSLLEPLLA MGFPVHTALK ALAATGRKTA EEALAWLHDH 70 80 90 100 110 120 CNDPSLDDPI PQEYALFLCP TGPLLEKLQE FWRESKRQCA KNRAHEVFPH VTLCDFFTCE 130 140 150 160 170 180 DQKVECLYEA LKRAGDRLLG SFPTAVPLAL HSSISYLGFF VSGSPADVIR EFAMTFATEA 190 200 210 220 230 240 SLLADCSVKP CTKQLHLTLA HKFYPHHQRT LEQLARAIPL GHSCQWTAAL YSRDMRFVHY 250 260 270 280 290 300 QTLRALFQYK PQNVDELTLS PGDYIFVDPT QQDEASEGWV IGISQRTGCR GFLPENYTDR 310 320 330 340 350 360 ASESDTWVKH RMYTFSLATD LNSRKDGEAS SRCSGEFLPQ TARSLSSLQA LQATVARKSV 370 380 390 400 410 420 LVVRHGERVD QIFGKAWLQQ CSTPDGKYYR PDLNFPCSLP RRSRGIKDFE NDPPLSSCGI 430 440 450 460 470 480 FQSRIAGDAL LDSGIRISSV FASPALRCVQ TAKLILEELK LEKKIKIRVE PGIFEWTKWE 490 500 510 520 530 540 AGKTTPTLMS LEELKEANFN IDTDYRPAFP LSALMPAESY QEYMDRCTAS MVQIVNTCPQ 550 560 570 580 590 600 DTGVILIVSH GSTLDSCTRP LLGLPPRECG DFAQLVRKIP SLGMCFCEEN KEEGKWELVN 610 620 PPVKTLTHGA NAAFNWRNWI SGN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of the UBASH3A gene on 21q22.3 encoding a potential nuclear protein with a novel combination of domains." Wattenhofer M., Shibuya K., Kudoh J., Lyle R., Michaud J., Rossier C., Kawasaki K., Asakawa S., Minoshima S., Berry A., Bonne-Tamir B., Shimizu N., Antonarakis S.E., Scott H.S. Hum. Genet. 108:140-147(2001) [PubMed: 11281453] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY. Tissue: Placenta.
[2]	"TULA: an SH3- and UBA-containing protein that binds to c-Cbl and ubiquitin." Feshchenko E.A., Smirnova E.V., Swaminathan G., Teckchandani A.M., Agrawal R., Band H., Zhang X., Annan R.S., Carr S.A., Tsygankov A.Y. Oncogene 23:4690-4706(2004) [PubMed: 15107835] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), MASS SPECTROMETRY, INTERACTION WITH CBL AND UBIQUITIN, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Leukemia.
[3]	"The DNA sequence of human chromosome 21." Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A. , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L. Nature 405:311-319(2000) [PubMed: 10830953] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] (ISOFORMS 1 AND 2), VARIANTS GLY-18 AND PHE-28.
[5]	"Suppressors of T-cell receptor signaling Sts-1 and Sts-2 bind to Cbl and inhibit endocytosis of receptor tyrosine kinases." Kowanetz K., Crosetto N., Haglund K., Schmidt M.H., Heldin C.-H., Dikic I. J. Biol. Chem. 279:32786-32795(2004) [PubMed: 15159412] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF TRP-317, SUBUNIT, INTERACTION WITH CBL AND UBIQUITIN, IDENTIFICATION IN A COMPLEX WITH EGFR, SUBCELLULAR LOCATION.
[6]	"The Cbl-interacting protein TULA inhibits dynamin-dependent endocytosis." Bertelsen V., Breen K., Sandvig K., Stang E., Madshus I.H. Exp. Cell Res. 313:1696-1709(2007) [PubMed: 17382318] [Abstract] Cited for: FUNCTION, INTERACTION WITH DYNAMIN, MUTAGENESIS OF TRP-317.
[7]	"TULA proteins regulate activity of the protein tyrosine kinase Syk." Agrawal R., Carpino N., Tsygankov A. J. Cell. Biochem. 104:953-964(2008) [PubMed: 18189269] [Abstract] Cited for: FUNCTION, LACK OF PROTEIN PHOSPHATASE ACTIVITY.
[8]	"Solution structure of the UBA domain of human UBASH3A protein." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 20-70.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ277750 mRNA. Translation: CAB91543.1.
AF520809 mRNA. Translation: AAP80731.1.
AF521702 mRNA. Translation: AAP80738.1.
AP001746 Genomic DNA. No translation available.
BC069357 mRNA. Translation: AAH69357.1.
BC069483 mRNA. Translation: AAH69483.1.
BC069511 mRNA. Translation: AAH69511.1.

IPI

IPI00025707.
IPI00215661.

RefSeq

NP_001001895.1. NM_001001895.2.
NP_001230396.1. NM_001243467.1.
NP_061834.1. NM_018961.3.

UniGene

Hs.473912.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CRN	NMR	-	A	20-70	[»]

ProteinModelPortal

P57075.

SMR

P57075. Positions 24-70, 269-350, 395-659.

ModBase

Search...

Protein-protein interaction databases

IntAct

P57075. 1 interaction.

MINT

MINT-5208648.

STRING

P57075.

PTM databases

PhosphoSite

P57075.

Polymorphism databases

DMDM

10720330.

Proteomic databases

PRIDE

P57075.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000319294; ENSP00000317327; ENSG00000160185.

GeneID

53347.

KEGG

hsa:53347.

UCSC

uc002zbe.1. human.
uc002zbf.1. human.

Organism-specific databases

CTD

53347.

GeneCards

GC21P043824.

H-InvDB

HIX0016140.

HGNC

HGNC:12462. UBASH3A.

MIM

605736. gene.

neXtProt

NX_P57075.

PharmGKB

PA37112.

GenAtlas

Search...

Phylogenomic databases

GeneTree

ENSGT00390000018249.

HOGENOM

HBG402867.

HOVERGEN

HBG018025.

InParanoid

P57075.

OMA

VIREFAM.

PhylomeDB

P57075.

Gene expression databases

ArrayExpress

P57075.

Bgee

P57075.

CleanEx

HS_UBASH3A.

Genevestigator

P57075.

GermOnline

ENSG00000160185. Homo sapiens.

Family and domain databases

InterPro

IPR013078. His_Pase_superF_clade-1.
IPR001452. SH3_domain.
IPR009060. UBA-like.
IPR015940. UBA/transl_elong_EF1B_N_euk.
[Graphical view]

Pfam

PF00300. His_Phos_1. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]

SMART

SM00326. SH3. 1 hit.
[Graphical view]

SUPFAM

SSF50044. SH3. 1 hit.
SSF46934. UBA_like. 1 hit.

PROSITE

PS50002. SH3. 1 hit.
PS50030. UBA. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

55998.

SOURCE

Search...

Entry information

Entry name

UBS3A_HUMAN

Accession

Primary (citable) accession number: P57075
Secondary accession number(s): Q6HA34 , Q6HA35, Q6ISI6, Q6ISK3, Q6ISS9

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	December 1, 2000
Last modified:	January 25, 2012
This is version 99 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.